OnabotulinumtoxinA 100U provides significant improvements in overactive bladder symptoms in patients with urinary incontinence regardless of the number of anticholinergic therapies used or reason for inadequate management of overactive bladder

INTRODUCTION: A prespecified pooled analysis of two placebo-controlled, phase 3 trials evaluated whether the number of prior anticholinergics used or reason for their discontinuation affected the treatment response to onabotulinumtoxinA 100U in overactive bladder (OAB) patients with urinary incontinence (UI). METHODS: Patients with symptoms of OAB received intradetrusor injections of onabotulinumtoxinA 100U or placebo, sparing the trigone. Change from baseline at week 12 in UI episodes/day, proportion of patients reporting a positive response (‘greatly improved’ or ‘improved’) on the treatment benefit scale (TBS), micturition and urgency were evaluated by number of prior anticholinergics (1, 2 or ≥ 3) and reason for their discontinuation (insufficient efficacy or side effects). Adverse events (AE) were assessed. RESULTS: Patients had taken an average of 2.4 anticholinergics before study enrolment. OnabotulinumtoxinA reduced UI episodes/day from baseline vs. placebo, regardless of the number of prior anticholinergics (−2.82 vs. −1.52 for one prior anticholinergic; −2.58 vs. −0.58 for two prior anticholinergics; and −2.92 vs. −0.73 for three or more prior anticholinergics; all p < 0.001). The proportion of TBS responders was higher with onabotulinumtoxinA vs. placebo (69.0% vs. 37.2% for one prior anticholinergic; 58.8% vs. 24.8% for two prior anticholinergics and 56.4% vs. 22.5% for three or more prior anticholinergics; all p < 0.001). Similar results were observed regardless of the reason for discontinuation. OnabotulinumtoxinA reduced the episodes of urgency and frequency of micturition vs. placebo in all groups. AEs were well tolerated, with a comparable incidence in all groups. CONCLUSION: In patients with symptoms of OAB who were inadequately managed by one or more anticholinergics, onabotulinumtoxinA 100U provided significant and similar treatment benefit and safety profile regardless of the number of prior anticholinergics used or reason for inadequate management of OAB. ClinicalTrials.gov: NCT00910845, NCT00910520

Effects of hydrogen on the morphology and electrical properties of GaN grown by plasma-assisted molecular-beam epitaxy

We study the effect of introducing hydrogen gas through the rf-plasma source during plasma-assisted molecular-beam epitaxy of GaN(0001). The well-known smooth-to-rough transition that occurs for this surface as a function of decreasing Ga flux in the absence of H is found to persist even with H present, although the critical Ga flux for this transition increases. Under Ga-rich conditions, the presence of hydrogen is found to induce step bunching (facetting) on the surface. Conductive atomic force microscopy reveals that leakage current through dislocation cores is significantly reduced when hydrogen is present during the growth

Microbial diversity and community structure across environmental gradients in Bransfield Strait, Western Antarctic Peninsula

© The Author(s), 2014. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Frontiers in Microbiology 5 (2014): 647, doi:10.3389/fmicb.2014.00647.The Southern Ocean is currently subject to intense investigations, mainly related to its importance for global biogeochemical cycles and its alarming rate of warming in response to climate change. Microbes play an essential role in the functioning of this ecosystem and are the main drivers of the biogeochemical cycling of elements. Yet, the diversity and abundance of microorganisms in this system remain poorly studied, in particular with regards to changes along environmental gradients. Here, we used amplicon sequencing of 16S rRNA gene tags using primers covering both Bacteria and Archaea to assess the composition and diversity of the microbial communities from four sampling depths (surface, the maximum and minimum of the oxygen concentration, and near the seafloor) at 10 oceanographic stations located in Bransfield Strait [northwest of the Antarctic Peninsula (AP)] and near the sea ice edge (north of the AP). Samples collected near the seafloor and at the oxygen minimum exhibited a higher diversity than those from the surface and oxygen maximum for both bacterial and archaeal communities. The main taxonomic groups identified below 100 m were Thaumarchaeota, Euryarchaeota and Proteobacteria (Gamma-, Delta-, Beta-, and Alphaproteobacteria), whereas in the mixed layer above 100 m Bacteroidetes and Proteobacteria (mainly Alpha- and Gammaproteobacteria) were found to be dominant. A combination of environmental factors seems to influence the microbial community composition. Our results help to understand how the dynamic seascape of the Southern Ocean shapes the microbial community composition and set a baseline for upcoming studies to evaluate the response of this ecosystem to future changes.This work was supported by the Brazilian National Counsel of Technological and Scientific Development (Polar Canion CNPq 556848/2009-8, ProOasis CNPq 565040/2010-3, Interbiota CNPq 407889/2013-2 and INCT-MAR-COI). Alex Enrich-Prast received a CNPq Productivity fellowship. Camila N. Signori was supported by a WHOI Mary Sears Visitor Award (for the microbial community analyses) and by the Brazilian Federal Agency for Support and Evaluation of Graduate Education (CAPES) for the “Doctorate Sandwich” scholarship (n. 18835/12-0)

Genus-specific carbon fixation activity measurements reveal distinct responses to oxygen among hydrothermal vent campylobacteria

Author Posting. © American Society for Microbiology, 2022. This article is posted here by permission of American Society for Microbiology for personal use, not for redistribution. The definitive version was published in Applied and Environmental Microbiology 88(2),(2022): e02083-21, https://doi.org/10.1128/AEM.02083-21.Molecular surveys of low temperature deep-sea hydrothermal vent fluids have shown that Campylobacteria (previously Epsilonproteobacteria) often dominate the microbial community and that three genera, Arcobacter, Sulfurimonas, and Sulfurovum, frequently coexist. In this study, we used replicated radiocarbon incubations of deep-sea hydrothermal fluids to investigate activity of each genus under three experimental conditions. To quantify genus-specific radiocarbon incorporation, we used newly designed oligonucleotide probes for Arcobacter, Sulfurimonas, and Sulfurovum to quantify their activity using catalyzed-reporter deposition fluorescence in situ hybridization (CARD-FISH) combined with fluorescence-activated cell sorting. All three genera actively fixed CO2 in short-term (∼ 20 h) incubations, but responded differently to the additions of nitrate and oxygen. Oxygen additions had the largest effect on community composition, and caused a pronounced shift in community composition at the amplicon sequence variant (ASV) level after only 20 h of incubation. The effect of oxygen on carbon fixation rates appeared to depend on the initial starting community. The presented results support the hypothesis that these chemoautotrophic genera possess functionally redundant core metabolic capabilities, but also reveal finer-scale differences in growth likely reflecting adaptation of physiologically-distinct phylotypes to varying oxygen concentrations in situ. Overall, our study provides new insights into how oxygen controls community composition and total chemoautotrophic activity, and underscores how quickly deep-sea vent microbial communities respond to disturbances.This research was funded by the U.S. National Science Foundation grants OCE-1131095 (S.M.S.) and OCE-1136727 (S.M.S., J.S.S.). Further support was provided by the WHOI Investment in Science Fund (S.M.S.). Funding for J.M. was further provided by doctoral fellowships from the Natural Sciences and Engineering Research Council of Canada (PGSD3-430487-2013, PGSM-405117-2011) and the National Aeronautics and Space Administration Earth Systems Science Fellowship (PLANET14F-0075), an award from the Canadian Meteorological and Oceanographic Society, and the WHOI Academic Programs Office

Targeted metabolomics reveals proline as a major osmolyte in the chemolithoautotroph Sulfurimonas denitrificans

© The Author(s), 2018. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in MicrobiologyOpen 7 (2018): e00586, doi:10.1002/mbo3.586.Chemoautotrophic bacteria belonging to the genus Sulfurimonas in the class Campylobacteria are widespread in many marine environments characterized by redox interfaces, yet little is known about their physiological adaptations to different environmental conditions. Here, we used liquid chromatography coupled with tandem mass spectrometry (LC-MS/ MS) in a targeted metabolomics approach to study the adaptations of Sulfurimonas denitrificans to varying salt concentrations that are found in its natural habitat of tidal mudflats. Proline was identified as one of the most abundant internal metabolites and its concentration showed a strong positive correlation with ionic strength, suggesting that it acts as an important osmolyte in S. denitrificans. 2,3-dihydroxypropane- 1- sulfonate was also positively correlated with ionic strength, indicating it might play a previously unrecognized role in osmoregulation. Furthermore, the detection of metabolites from the reductive tricarboxylic acid cycle at high internal concentrations reinforces the importance of this pathway for carbon fixation in Campylobacteria and as a hub for biosynthesis. As the first report of metabolomic data for an campylobacterial chemolithoautotroph, this study provides data that will be useful to understand the adaptations of Campylobacteria to their natural habitat at redox interfaces.NSF, Grant/Award Number: OCE- 1136727 and OCE-1154320; Woods Hole Oceanographic Institution; U.S. Geological Surve

Primary productivity below the seafloor at deep-sea hot springs

© The Author(s), 2018. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Proceedings of the National Academy of Sciences.of the United States of America 115 (2018): 6756–6761, doi:10.1073/pnas.1804351115.The existence of a chemosynthetic subseafloor biosphere was immediately recognized when deep-sea hot springs were discovered in 1977. However, quantifying how much new carbon is fixed in this environment has remained elusive. In this study, we incubated natural subseafloor communities under in situ pressure/temperature and measured their chemosynthetic growth efficiency and metabolic rates. Combining these data with fluid flux and in situ chemical measurements, we derived empirical constraints on chemosynthetic activity in the natural environment. Our study shows subseafloor microorganisms are highly productive (up to 1.4 Tg C produced yearly), fast-growing (turning over every 17–41 hours), and physiologically diverse. These estimates place deep-sea hot springs in a quantitative framework and allow us to assess their importance for global biogeochemical cycles.This research was funded by a grant of the Dimensions of Biodiversity program of the US National Science Foundation (NSF-OCE-1136727 to S.M.S. and J.S.S.). Funding for J.M. was further provided by doctoral fellowships from the Natural Sciences and Engineering Research Council of Canada (PGSD3-430487-2013, PGSM-405117-2011) and the National Aeronautics and Space Administration Earth Systems Science Fellowship (PLANET14F-0075), an award from the Canadian Meteorological and Oceanographic Society, and the WHOI Academic Programs Office

A biophysical model of prokaryotic diversity in geothermal hot springs

Recent field investigations of photosynthetic bacteria living in geothermal hot spring environments have revealed surprisingly complex ecosystems, with an unexpected level of genetic diversity. One case of particular interest involves the distribution along hot spring thermal gradients of genetically distinct bacterial strains that differ in their preferred temperatures for reproduction and photosynthesis. In such systems, a single variable, temperature, defines the relevant environmental variation. In spite of this, each region along the thermal gradient exhibits multiple strains of photosynthetic bacteria adapted to several distinct thermal optima, rather than the expected single thermal strain adapted to the local environmental temperature. Here we analyze microbiology data from several ecological studies to show that the thermal distribution field data exhibit several universal features independent of location and specific bacterial strain. These include the distribution of optimal temperatures of different thermal strains and the functional dependence of the net population density on temperature. Further, we present a simple population dynamics model of these systems that is highly constrained by biophysical data and by physical features of the environment. This model can explain in detail the observed diversity of different strains of the photosynthetic bacteria. It also reproduces the observed thermal population distributions, as well as certain features of population dynamics observed in laboratory studies of the same organisms

Single cell genomics-based analysis of gene content and expression of prophages in a diffuse-flow deep-sea hydrothermal system

© The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Labonte, J. M., Pachiadaki, M., Fergusson, E., McNichol, J., Grosche, A., Gulmann, L. K., Vetriani, C., Sievert, S. M., & Stepanauskas, R. Single cell genomics-based analysis of gene content and expression of prophages in a diffuse-flow deep-sea hydrothermal system. Frontiers in Microbiology, 10, (2019): 1262, doi:10.3389/fmicb.2019.01262.Phage–host interactions likely play a major role in the composition and functioning of many microbiomes, yet remain poorly understood. Here, we employed single cell genomics to investigate phage–host interactions in a diffuse-flow, low-temperature hydrothermal vent that may be reflective of a broadly distributed biosphere in the subseafloor. We identified putative prophages in 13 of 126 sequenced single amplified genomes (SAGs), with no evidence for lytic infections, which is in stark contrast to findings in the surface ocean. Most were distantly related to known prophages, while their hosts included bacterial phyla Campylobacterota, Bacteroidetes, Chlorobi, Proteobacteria, Lentisphaerae, Spirochaetes, and Thermotogae. Our results suggest the predominance of lysogeny over lytic interaction in diffuse-flow, deep-sea hydrothermal vents, despite the high activity of the dominant Campylobacteria that would favor lytic infections. We show that some of the identified lysogens have co-evolved with their host over geological time scales and that their genes are transcribed in the environment. Functional annotations of lysogeny-related genes suggest involvement in horizontal gene transfer enabling host’s protection against toxic metals and antibacterial compounds.This work was supported by the U.S. National Science Foundation’s Dimensions of Biodiversity Program [OCE-1136488 (to RS), OCE-1136727 (to SMS) and OCE-1136451 (to CV)], as well as DEB-1441717 and OCE-1335810 (to RS), and the DOE JGI CSP project 1477

Fatal septicemia in a patient with cerebral lymphoma and an Amplatzer septal occluder: a case report

<p>Abstract</p> <p>Introduction</p> <p>The Amplatzer septal occluder is frequently used for percutaneous closure of an atrial septal defect. Complications include thrombosis and embolism, dislocation, cardiac perforation, and, rarely, infection. We report the case of a patient who had survived an occluder-related thromboembolism two years previously.</p> <p>Case presentation</p> <p>A 72-year-old Caucasian woman had received a septal occluder because of an atrial septal defect seven years ago. Two years ago, she underwent chemotherapy of a non-Hodgkin lymphoma, developed atrial fibrillation, and experienced a left-sided occluder thrombosis with stroke and peripheral embolism. Now, she presented with cerebral lymphoma, received glucocorticoids, and subsequently developed skin lesions. Swabs from the lesions and blood cultures were positive for methicillin-resistant <it>Staphylococcus aureus </it>and <it>Pseudomonas aeruginosa</it>. Endocarditis, however, was considered only two months later and echocardiography suggested aortic valve endocarditis. Despite antibiotic therapy, she died three days later because of septicemia, and no post-mortem investigation was carried out. It remains uncertain whether the septal occluder was endothelialized or infected and whether explantation might have changed the outcome.</p> <p>Conclusions</p> <p>If infections occur in patients with a septal occluder, endocarditis should be considered and echocardiography should be performed early. To prevent a fatal outcome, explantation of the septal occluder should be considered, especially in patients with problems that suggest delayed endothelialization. Post-mortem investigations, including bacteriologic studies, should be carried out in patients with a septal occluder in order to assess the focal and global long-term effects of these devices.</p

The accident insurance as a promising direction for insurance in Russia

Статья посвящена анализу состояния рынка услуг страхования от несчастных случаев. Актуальность исследования определяется тем, что страхование является неотъемлемым атрибутом цивилизованного общества, позволяющим сохранить обеспеченность доходами при неблагоприятных ситуациях. По статистике в России уровень травматизма и непредвиденных обстоятельств весьма велик. Люди традиционно уделяют мало внимания формированию резервов на случай временной или постоянной нетрудоспособности. Цель работы: рассмотреть систему страхования от несчастных случаев. Методы исследования: метод сопоставления, необходимый для выявления главных тенденций на рынке страховых услуг; аналитический метод, позволяющий понять, какие проблемы характерны для этого вида страхования; статистический метод, выявляющий масштабы страхования от несчастных случаев. Результаты: раскрывается сущность и виды страхования от несчастных случаев.The article is devoted to analysis of service market of accident insurance. The relevant of the study is determined by the fact that insurance is an integral attribute of a civilized society that allows you to save security income in adverse situations. According to statistics, in Russia the level of injury and unforeseen circumstances is very great. People traditionally pay little attention to formation of reserves in case of temporary or permanent incapacity for work. The main aim of the study is to consider the system of the accident insurance. Methods: the matching method required to identify the main trends in the insurance market; the analytical technique which allows understanding the typical problems for this type of insurance; the statistical method allows us to identify the extent of accident insurance. Results. The paper reveals the essence and types of accident insurance and considers the model events when the insurance company indemnifies for the damage. The causes of the demand for this type of insurance in Russia are identified. Based on the statistical data the author has determined the proportion of the accident insured people