Cardioviruses comprise a genus of picornaviruses that cause severe illnesses in rodents, but little is known about the prevalence, diversity, or spectrum of disease of such agents among humans. A ...single cardiovirus isolate, Saffold virus, was cultured in 1981 in stool from an infant with fever. Here, we describe the identification of a group of human cardioviruses that have been cloned directly from patient specimens, the first of which was detected using a pan-viral microarray in respiratory secretions from a child with influenza-like illness. Phylogenetic analysis of the nearly complete viral genome (7961 bp) revealed that this virus belongs to the Theiler's murine encephalomyelitis virus (TMEV) subgroup of cardioviruses and is most closely related to Saffold virus. Subsequent screening by RT-PCR of 719 additional respiratory specimens 637 (89%) from patients with acute respiratory illness and 400 cerebrospinal fluid specimens from patients with neurological disease (aseptic meningitis, encephalitis, and multiple sclerosis) revealed no evidence of cardiovirus infection. However, screening of 751 stool specimens from 498 individuals in a gastroenteritis cohort resulted in the detection of 6 additional cardioviruses (1.2%). Although all 8 human cardioviruses (including Saffold virus) clustered together by phylogenetic analysis, significant sequence diversity was observed in the VP1 gene (66.9%-100% pairwise amino acid identities). These findings suggest that there exists a diverse group of novel human Theiler's murine encephalomyelitis virus-like cardioviruses that hitherto have gone largely undetected, are found primarily in the gastrointestinal tract, can be shed asymptomatically, and have potential links to enteric and extraintestinal disease.
Abstract To determine if West Nile virus (WNV) infection of insect cells induces a protective RNAi response, Drosophila melanogaster S2 and Aedes albopictus C6/36 cells were infected with WNV, and ...the production of WNV-homologous small RNAs was assayed as an indicator of RNAi induction. A distinct population of ~ 25 nt WNV-homologous small RNAs was detected in infected S2 cells but not C6/36 cells. RNAi knockdown of Argonaute 2 in S2 cells resulted in slightly increased susceptibility to WNV infection, suggesting that some WNV-homologous small RNAs produced in infected S2 cells are functional small interfering RNAs. WNV was shown to infect adult D. melanogaster , and adult flies containing mutations in each of four different RNAi genes ( Argonaute 2 , spindle-E , piwi , and Dicer-2 ) were significantly more susceptible to WNV infection than wildtype flies. These results combined with the analysis of WNV infection of S2 and C6/36 cells support the conclusion that WNV infection of D. melanogaster , but perhaps not Ae. albopictus , induces a protective RNAi response.
Brachytherapy is integral to vaginal cancer treatment and is typically delivered using an intracavitary single-channel vaginal cylinder (SCVC) or an interstitial brachytherapy (ISBT) applicator. ...Multi-channel vaginal cylinder (MCVC) applicators allow for improved organ-at-risk (OAR) sparing compared to SCVC while maintaining target coverage. We present clinical outcomes of patients treated with image-based high dose-rate (HDR) brachytherapy using a MCVC.
Sixty patients with vaginal cancer (27% primary vaginal and 73% recurrence from other primaries) were treated with combination external beam radiotherapy (EBRT) and image-based HDR brachytherapy utilizing a MCVC if residual disease thickness was 7 mm or less after EBRT. All pts received 3D image-based BT to a total equivalent dose of 70–80 Gy.
The median high-risk clinical target volume was 24.4 cm3 (interquartile range IQR, 14.1), with a median dose to 90% of 77.2 Gy (IQR, 2.8). After a median follow-up of 45 months (range, 11–78), the 4-year local-regional control, distant control, DFS, and OS rates were 92.6%, 76.1%, 64.0%, and 67.2%, respectively. The 4-year LRC rates were similar between the primary vaginal (92%) and recurrent (93%) groups (p = 0.290). Pts with lymph node positive disease had a lower rate of distant control at 4 years (22.7% vs. 89.0%, p < 0.001). There were no Grade 3 or higher acute complications. The 4-year rate of late Grade 3 or higher toxicity was 2.7%.
Clinical outcomes of pts with primary and recurrent vaginal cancer treated definitively in a systematic manner with combination EBRT with image-guided HDR BT utilizing a MCVC applicator demonstrate high rates of local control and low rates of severe morbidity. The MCVC technique allows interstitial implantation to be avoided in select pts with ≤7 mm residual disease thickness following EBRT while maintaining excellent clinical outcomes with extended 4-year follow-up in this rare malignancy.
•Treatment of vaginal cancers with multi-channel cylinder produced high local control.•There were no severe acute complications and only 3% severe late morbidity.•Interstitial implantation can be avoided in select patients with good outcomes.
Plants and fungi use light and other signals to regulate development, growth, and metabolism. The fruiting bodies of the fungus Phycomyces blakesleeanus are single cells that react to environmental ...cues, including light, but the mechanisms are largely unknown 1. The related fungus Mucor circinelloides is an opportunistic human pathogen that changes its mode of growth upon receipt of signals from the environment to facilitate pathogenesis 2. Understanding how these organisms respond to environmental cues should provide insights into the mechanisms of sensory perception and signal transduction by a single eukaryotic cell, and their role in pathogenesis. We sequenced the genomes of P. blakesleeanus and M. circinelloides and show that they have been shaped by an extensive genome duplication or, most likely, a whole-genome duplication (WGD), which is rarely observed in fungi 3–6. We show that the genome duplication has expanded gene families, including those involved in signal transduction, and that duplicated genes have specialized, as evidenced by differences in their regulation by light. The transcriptional response to light varies with the developmental stage and is still observed in a photoreceptor mutant of P. blakesleeanus. A phototropic mutant of P. blakesleeanus with a heterozygous mutation in the photoreceptor gene madA demonstrates that photosensor dosage is important for the magnitude of signal transduction. We conclude that the genome duplication provided the means to improve signal transduction for enhanced perception of environmental signals. Our results will help to understand the role of genome dynamics in the evolution of sensory perception in eukaryotes.
•We sequenced the genomes of fungi Mucor circinelloides and Phycomyces blakesleeanus•Extensive genomic duplications increased the number of genes for signal transduction•After duplication, genes specialized their transcriptional regulation by light•Genome duplications provided new components to improve sensory perception in fungi
Fungi use light and other signals to regulate development, but the mechanisms and origin are largely unknown. Corrochano et al. have found that a group of fungi has acquired new components for signal transduction pathways after extensive genomic duplication. The expanded gene repertoire allows an enhanced perception of environmental signals.
Glycopyrronium tosylate (GT) is a topical anticholinergic developed for once-daily treatment of primary axillary hyperhidrosis.
Assess the efficacy and safety of GT for primary axillary ...hyperhidrosis.
ATMOS-1 and ATMOS-2 were replicate randomized, double-blind, vehicle-controlled, 4-week phase 3 trials. Patients were randomized 2:1 to GT 3.75% or vehicle applied once daily to each axilla for 4 weeks. Coprimary endpoints were responder rate (≥4-point improvement from baseline) on item 2 (severity of sweating) of the Axillary Sweating Daily Diary (ASDD), which is a newly developed patient-reported outcome measure, and absolute change from baseline in axillary gravimetric sweat production at week 4. Safety evaluation included treatment-emergent adverse events.
Pooled data, which are consistent with the individual trial results, show that significantly more GT-treated patients achieved an ASDD-Item 2 response than did those treated with vehicle (59.5% vs 27.6%), and they had reduced sweat production from baseline (–107.6 mg/5 min vs –92.1 mg/5 min) at week 4 (P < .001 for both coprimary end points). Most treatment-emergent adverse events were mild or moderate and infrequently led to discontinuation.
Short trial duration and inherent challenges in gravimetrically assessing sweat production.
GT applied topically on a daily basis over 4 weeks reduced the severity of sweating as measured by ASDD-Item 2, reduced sweat production as measured gravimetrically, and was generally well tolerated in patients with primary axillary hyperhidrosis.
The first International Peat Congress (IPC) held in the tropics – in Kuching (Malaysia) – brought together over 1000 international peatland scientists and industrial partners from across the world ...(“International Peat Congress with over 1000 participants!,” 2016). The congress covered all aspects of peatland ecosystems and their management, with a strong focus on the environmental, societal and economic challenges associated with contemporary large-scale agricultural conversion of tropical peat.
The two single-pass, externally seeded free-electron lasers (FELs) of the FERMI user facility are designed around Apple-II-type undulators that can operate at arbitrary polarization in the vacuum ...ultraviolet-to-soft x-ray spectral range. Furthermore, within each FEL tuning range, any output wavelength and polarization can be set in less than a minute of routine operations. We report the first demonstration of the full output polarization capabilities of FERMI FEL-1 in a campaign of experiments where the wavelength and nominal polarization are set to a series of representative values, and the polarization of the emitted intense pulses is thoroughly characterized by three independent instruments and methods, expressly developed for the task. The measured radiation polarization is consistently >90% and is not significantly spoiled by the transport optics; differing, relative transport losses for horizontal and vertical polarization become more prominent at longer wavelengths and lead to a non-negligible ellipticity for an originally circularly polarized state. The results from the different polarimeter setups validate each other, allow a cross-calibration of the instruments, and constitute a benchmark for user experiments.
We report constraints on nonstandard neutrino interactions (NSI) from the observation of atmospheric neutrinos with IceCube, limiting all individual coupling strengths from a single dataset. ...Furthermore, IceCube is the first experiment to constrain flavor-violating and nonuniversal couplings simultaneously. Hypothetical NSI are generically expected to arise due to the exchange of a new heavy mediator particle. Neutrinos propagating in matter scatter off fermions in the forward direction with negligible momentum transfer. Hence the study of the matter effect on neutrinos propagating in the Earth is sensitive to NSI independently of the energy scale of new physics. We present constraints on NSI obtained with an all-flavor event sample of atmospheric neutrinos based on three years of IceCube DeepCore data. The analysis uses neutrinos arriving from all directions, with reconstructed energies between 5.6 GeV and 100 GeV. We report constraints on the individual NSI coupling strengths considered singly, allowing for complex phases in the case of flavor-violating couplings. This demonstrates that IceCube is sensitive to the full NSI flavor structure at a level competitive with limits from the global analysis of all other experiments. In addition, we investigate a generalized matter potential, whose overall scale and flavor structure are also constrained.
The Sun provides an excellent target for studying spin-dependent dark matter-proton scattering due to its high matter density and abundant hydrogen content. Dark matter particles from the Galactic ...halo can elastically interact with Solar nuclei, resulting in their capture and thermalization in the Sun. The captured dark matter can annihilate into Standard Model particles including an observable flux of neutrinos. Here, we present the results of a search for low-energy (<500 GeV) neutrinos correlated with the direction of the Sun using 7 years of IceCube data. This work utilizes, for the first time, new optimized cuts to extend IceCube's sensitivity to dark matter mass down to 5 GeV. We find no significant detection of neutrinos from the Sun. Our observations exclude capture by spin-dependent dark matter-proton scattering with cross section down to a few times 10-41 cm2, assuming there is equilibrium with annihilation into neutrinos/antineutrinos for dark matter masses between 5 GeV and 100 GeV. These are the strongest constraints at GeV energies for dark matter annihilation directly to neutrinos.
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