The oral mucosal and salivary microbial community of Behçet's syndrome and recurrent aphthous stomatitis.

This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License, permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.Behçet's syndrome (BS) is a multisystem immune-related disease of unknown etiology. Recurrent aphthous stomatitis (RAS) is characterized by the presence of idiopathic oral ulceration without extraoral manifestation. The interplay between the oral microbial communities and the immune response could play an important role in the etiology and pathogenesis of both BS and RAS

Regulation of prophage induction and lysogenization by phage communication systems.

This is the final version. Available on open access from Elsevier via the DOI in this recordData and code availability: Data have been deposited at the Dryad data repository and are publicly available as of the date of publication. DOIs are listed in the Key resources table.Many viruses cause both lytic infections, where they release viral particles, and dormant infections, where they await future opportunities to reactivate.1 The benefits of each transmission mode depend on the density of susceptible hosts in the environment.2-4 Some viruses infecting bacteria use molecular signaling to respond plastically to changes in host availability.5 These viruses produce a signal during lytic infection and regulate, based on the signal concentration in the environment, the probability with which they switch to causing dormant infections.5,6 We present an analytical framework to examine the adaptive significance of plasticity in viral life-history traits in fluctuating environments. Our model generalizes and extends previous theory7 and predicts that host density fluctuations should select for plasticity in entering lysogeny as well as virus reactivation once signal concentrations decline. Using Bacillus subtilis and its phage phi3T, we experimentally confirm the prediction that phages use signal to make informed decisions over prophage induction. We also demonstrate that lysogens produce signaling molecules and that signal is degraded by hosts in a density-dependent manner. Declining signal concentrations therefore potentially indicate the presence of uninfected hosts and trigger prophage induction. Finally, we find that conflict over the responses of lysogenization and reactivation to signal is resolved through the evolution of different response thresholds for each trait. Collectively, these findings deepen our understanding of the ways viruses use molecular communication to regulate their infection strategies, which can be leveraged to manipulate host and phage population dynamics in natural environments.European Union Horizon 2020Natural Environment Research Council (NERC)AN

Microdissection: A method developed to investigate mechanisms involved in transmissible spongiform encephalopathy pathogenesis

BACKGROUND: The transmissible spongiform encephalopathies (TSEs) are a group of neurodegenerative diseases affecting both human and animals. The neuroanatomical changes which occur in the central nervous system (CNS) of TSE infected animals include vacuolation, gliosis, neuronal loss and the deposition of a disease specific protein, PrP(Sc). Experimental murine models of scrapie, a TSE of sheep, have revealed that pathology may be confined to specific brain areas with targeting of particular neuronal subsets depending on route of injection and scrapie isolate. To assess the biochemical changes which are taking place in these targeted areas it was necessary to develop a reliable sampling procedure (microdissection) which could be used for a variety of tests such as western blotting and magnetic resonance spectroscopy. METHODS: The method described is for the microdissection of murine brains. To assess the usefulness of this dissection technique for producing similar sample types for analysis by various down-stream biochemical techniques, the areas dissected were analysed for PrP(Sc )by western blotting and compared to immunocytochemical (ICC) techniques. RESULTS: Results show that the method generates samples yielding a consistent protein content which can be analysed for PrP(Sc). The areas in which PrP(Sc )is found by western blotting compares well with localisation visualised by immunocytochemistry. CONCLUSION: The microdisssection method described can be used to generate samples suitable for a range of biochemical techniques. Using these samples a range of assays can be carried out which will help to elucidate the molecular and cellular mechanisms underlying TSE pathogenesis. The method would also be useful for any study requiring the investigation of discrete areas within the murine brain

Better assessment of physical function: item improvement is neglected but essential

INTRODUCTION: Physical function is a key component of patient-reported outcome (PRO) assessment in rheumatology. Modern psychometric methods, such as Item Response Theory (IRT) and Computerized Adaptive Testing, can materially improve measurement precision at the item level. We present the qualitative and quantitative item-evaluation process for developing the Patient Reported Outcomes Measurement Information System (PROMIS) Physical Function item bank. METHODS: The process was stepwise: we searched extensively to identify extant Physical Function items and then classified and selectively reduced the item pool. We evaluated retained items for content, clarity, relevance and comprehension, reading level, and translation ease by experts and patient surveys, focus groups, and cognitive interviews. We then assessed items by using classic test theory and IRT, used confirmatory factor analyses to estimate item parameters, and graded response modeling for parameter estimation. We retained the 20 Legacy (original) Health Assessment Questionnaire Disability Index (HAQ-DI) and the 10 SF-36\u27s PF-10 items for comparison. Subjects were from rheumatoid arthritis, osteoarthritis, and healthy aging cohorts (n = 1,100) and a national Internet sample of 21,133 subjects. RESULTS: We identified 1,860 items. After qualitative and quantitative evaluation, 124 newly developed PROMIS items composed the PROMIS item bank, which included revised Legacy items with good fit that met IRT model assumptions. Results showed that the clearest and best-understood items were simple, in the present tense, and straightforward. Basic tasks (like dressing) were more relevant and important versus complex ones (like dancing). Revised HAQ-DI and PF-10 items with five response options had higher item-information content than did comparable original Legacy items with fewer response options. IRT analyses showed that the Physical Function domain satisfied general criteria for unidimensionality with one-, two-, three-, and four-factor models having comparable model fits. Correlations between factors in the test data sets were \u3e 0.90. CONCLUSIONS: Item improvement must underlie attempts to improve outcome assessment. The clear, personally important and relevant, ability-framed items in the PROMIS Physical Function item bank perform well in PRO assessment. They will benefit from further study and application in a wider variety of rheumatic diseases in diverse clinical groups, including those at the extremes of physical functioning, and in different administration modes

Use of the novel hemostatic textile Stasilon® to arrest refractory retroperitoneal hemorrhage: a case report

<p>Abstract</p> <p>Introduction</p> <p>Stasilon^®is a novel hemostatic woven textile composed of allergen-free fibers of continuous filament fiberglass and bamboo yarn. The development of this product resulted from controlled <it>in vitro </it>thrombogenic analysis of an array of potentially hemostatic textile materials and it has been cleared for both external and internal use by the United States Food and Drug Administration for the arrest of hemorrhage. The goal of the study was to assess the hemostatic and adhesive properties of Stasilon^®in the setting of life-threatening refractory hemorrhage.</p> <p>Case presentation</p> <p>A 39-year-old Caucasian man presented with severe necrotic pancreatitis that failed multiple aggressive attempts to control associated bleeding with electrocautery, suture ligation, and sequential anatomic packing with cotton-based sponges. Subsequent retroperitoneal packing with Stasilon^®produced a non-adherent wound-dressing interface and resulted in the achievement of persistent hemostasis in the operative field.</p> <p>Conclusion</p> <p>In our patient, Stasilon^®was demonstrated to be effective in the arrest of refractory hemorrhage.</p

Gestational diabetes and pregnancy outcomes - a systematic review of the World Health Organization (WHO) and the International Association of Diabetes in Pregnancy Study Groups (IADPSG) diagnostic criteria

<p>Abstract</p> <p>Background</p> <p>Two criteria based on a 2 h 75 g OGTT are being used for the diagnosis of gestational diabetes (GDM), those recommended over the years by the World Health Organization (WHO), and those recently recommended by the International Association for Diabetes in Pregnancy Study Group (IADPSG), the latter generated in the HAPO study and based on pregnancy outcomes. Our aim is to systematically review the evidence for the associations between GDM (according to these criteria) and adverse outcomes.</p> <p>Methods</p> <p>We searched relevant studies in MEDLINE, EMBASE, LILACS, the Cochrane Library, CINHAL, WHO-Afro library, IMSEAR, EMCAT, IMEMR and WPRIM. We included cohort studies permitting the evaluation of GDM diagnosed by WHO and or IADPSG criteria against adverse maternal and perinatal outcomes in untreated women. Only studies with universal application of a 75 g OGTT were included. Relative risks (RRs) and their 95% confidence intervals (CI) were obtained for each study. We combined study results using a random-effects model. Inconsistency across studies was defined by an inconsistency index (I²) > 50%.</p> <p>Results</p> <p>Data were extracted from eight studies, totaling 44,829 women. Greater risk of adverse outcomes was observed for both diagnostic criteria. When using the WHO criteria, consistent associations were seen for macrosomia (RR = 1.81; 95%CI 1.47-2.22; p < 0.001); large for gestational age (RR = 1.53; 95%CI 1.39-1.69; p < 0.001); perinatal mortality (RR = 1.55; 95% CI 0.88-2.73; p = 0.13); preeclampsia (RR = 1.69; 95%CI 1.31-2.18; p < 0.001); and cesarean delivery (RR = 1.37;95%CI 1.24-1.51; p < 0.001). Less data were available for the IADPSG criteria, and associations were inconsistent across studies (I²≥ 73%). Magnitudes of RRs and their 95%CIs were 1.73 (1.28-2.35; p = 0.001) for large for gestational age; 1.71 (1.38-2.13; p < 0.001) for preeclampsia; and 1.23 (1.01-1.51; p = 0.04) for cesarean delivery. Excluding either the HAPO or the EBDG studies minimally altered these associations, but the RRs seen for the IADPSG criteria were reduced after excluding HAPO.</p> <p>Conclusions</p> <p>The WHO and the IADPSG criteria for GDM identified women at a small increased risk for adverse pregnancy outcomes. Associations were of similar magnitude for both criteria. However, high inconsistency was seen for those with the IADPSG criteria. Full evaluation of the latter in settings other than HAPO requires additional studies.</p

Intellectual Property in Medical Imaging and Informatics: The Independent Inventor’s Perspective

While innovation and new product development is traditionally thought of as the exclusive domain of industry and academia, a large number of innovations in medicine and information technology have come from independent inventors, which account for almost 30% of new patents issued in the U.S. today. A large number of economic, political, and legal challenges exist within the current marketplace that serves as relative impediments to independent invention. This article explores the existing challenges facing the independent inventor and offers a number of recommendations and resources to facilitate independent inventors in their quest for innovation and entrepreneurship. The concept of “outsourcing innovation” is discussed as an alternative to the existing model of industry sponsored research and development (R&D), with the goal of combining the unique attributes and strengths of independent inventors and industry sponsors

In Situ Ambient Pressure X-ray Photoelectron Spectroscopy Studies of Lithium-Oxygen Redox Reactions

The lack of fundamental understanding of the oxygen reduction and oxygen evolution in nonaqueous electrolytes significantly hinders the development of rechargeable lithium-air batteries. Here we employ a solid-state Li4+xTi5O12/LiPON/LixV2O5 cell and examine in situ the chemistry of Li-O2 reaction products on LixV2O5 as a function of applied voltage under ultra high vacuum (UHV) and at 500 mtorr of oxygen pressure using ambient pressure X-ray photoelectron spectroscopy (APXPS). Under UHV, lithium intercalated into LixV2O5 while molecular oxygen was reduced to form lithium peroxide on LixV2O5 in the presence of oxygen upon discharge. Interestingly, the oxidation of Li2O2 began at much lower overpotentials (~240 mV) than the charge overpotentials of conventional Li-O2 cells with aprotic electrolytes (~1000 mV). Our study provides the first evidence of reversible lithium peroxide formation and decomposition in situ on an oxide surface using a solid-state cell, and new insights into the reaction mechanism of Li-O2 chemistry.National Science Foundation (U.S.) (Materials Research Science and Engineering Center (MRSEC) Program, Award DMR-0819762)United States. Dept. of Energy (Assistant Secretary for Energy Efficiency and Renewable Energy, Office of FreedomCAR and Vehicle Technologies of the U. S. Department of Energy under contract no. DE-AC03-76SF00098)Lawrence Berkeley National LaboratoryUnited States. Dept. of Energy (Office of Basic Energy Sciences, Materials Sciences and Engineering

Genetic Tests for Ecological and Allopatric Speciation in Anoles on an Island Archipelago

From Darwin's study of the Galapagos and Wallace's study of Indonesia, islands have played an important role in evolutionary investigations, and radiations within archipelagos are readily interpreted as supporting the conventional view of allopatric speciation. Even during the ongoing paradigm shift towards other modes of speciation, island radiations, such as the Lesser Antillean anoles, are thought to exemplify this process. Geological and molecular phylogenetic evidence show that, in this archipelago, Martinique anoles provide several examples of secondary contact of island species. Four precursor island species, with up to 8 mybp divergence, met when their islands coalesced to form the current island of Martinique. Moreover, adjacent anole populations also show marked adaptation to distinct habitat zonation, allowing both allopatric and ecological speciation to be tested in this system. We take advantage of this opportunity of replicated island coalescence and independent ecological adaptation to carry out an extensive population genetic study of hypervariable neutral nuclear markers to show that even after these very substantial periods of spatial isolation these putative allospecies show less reproductive isolation than conspecific populations in adjacent habitats in all three cases of subsequent island coalescence. The degree of genetic interchange shows that while there is always a significant genetic signature of past allopatry, and this may be quite strong if the selection regime allows, there is no case of complete allopatric speciation, in spite of the strong primae facie case for it. Importantly there is greater genetic isolation across the xeric/rainforest ecotone than is associated with any secondary contact. This rejects the development of reproductive isolation in allopatric divergence, but supports the potential for ecological speciation, even though full speciation has not been achieved in this case. It also explains the paucity of anole species in the Lesser Antilles compared to the Greater Antilles

Of Mice and ‘Convicts’: Origin of the Australian House Mouse, Mus musculus

The house mouse, Mus musculus, is one of the most ubiquitous invasive species worldwide and in Australia is particularly common and widespread, but where it originally came from is still unknown. Here we investigated this origin through a phylogeographic analysis of mitochondrial DNA sequences (D-loop) comparing mouse populations from Australia with those from the likely regional source area in Western Europe. Our results agree with human historical associations, showing a strong link between Australia and the British Isles. This outcome is of intrinsic and applied interest and helps to validate the colonization history of mice as a proxy for human settlement history