Effects of two fractions of swietenia macrophylla and catechin on muscle damage induced by bothrops venom and PLA(2)

Plant natural products can attenuate the myonecrosis caused by Bothrops snake venom and their phospholipases A(2) (PLA(2)). In this study, we evaluated the effects of two fractions (F4 and F6) from Swietenia macrophylla and purified catechin on the muscle damage caused by a myotoxic PLA(2) from Colombian Bothrops asper venom (BaColPLA(2)) in mice and by Bothrops marmoratus venom from Brazil in mouse phrenic nerve-diaphragm muscle (PND) preparations in vitro. Male mice were injected with PLA(2) (50 mu g) in the absence or presence of F4, F6, and catechin, in the gastrocnemius muscle and then killed 3, 7, 14, and 28 h later for histopathological analysis of myonecrosis, leukocyte infiltration, and the presence of collagen. Fractions F4 and F6 (500 mu g) and catechin (90 mu g) significantly reduced the extent of necrosis at all-time intervals. These two fractions and catechin also attenuated the leukocyte infiltration on day 3, as did catechin on day 14. There was medium-to-moderate collagen deposition in all groups up to day 7, but greater deposition on days 14 and 28 in the presence of F6 and catechin. Bothrops marmoratus venom (100 mu g/mL) caused slight (25%) muscle facilitation after 10 min and weak neuromuscular blockade (64% decrease in contractile activity after a 120-min incubation). Pre-incubation of venom with F4 or F6 abolished the facilitation, whereas catechin, which was itself facilitatory, did not. All three fractions attenuated the venom-induced decrease in muscle contractions. These findings indicate that fractions and catechin from S. macrophylla can reduce the muscle damage caused by Bothrops venom and PLA(2). These fractions or their components could be useful for treating venom-induced local damage11

Gene co-expression architecture in peripheral blood in a cohort of remitted first-episode schizophrenia patients

A better understanding of schizophrenia subtypes is necessary to stratify the patients according to clinical attributes. To explore the genomic architecture of schizophrenia symptomatology, we analyzed blood co-expression modules and their association with clinical data from patients in remission after a first episode of schizophrenia. In total, 91 participants of the 2EPS project were included. Gene expression was assessed using the Clariom S Human Array. Weighted-gene co-expression network analysis (WGCNA) was applied to identify modules of co-expressed genes and to test its correlation with global functioning, clinical symptomatology, and premorbid adjustment. Among the 25 modules identified, six modules were significantly correlated with clinical data. These modules could be clustered in two groups according to their correlation with clinical data. Hub genes in each group showing overlap with risk genes for schizophrenia were enriched in biological processes related to metabolic processes, regulation of gene expression, cellular localization and protein transport, immune processes, and neurotrophin pathways. Our results indicate that modules with significant associations with clinical data showed overlap with gene sets previously identified in differential gene-expression analysis in brain, indicating that peripheral tissues could reveal pathogenic mechanisms. Hub genes involved in these modules revealed multiple signaling pathways previously related to schizophrenia, which may represent the complex interplay in the pathological mechanisms behind the disease. These genes could represent potential targets for the development of peripheral biomarkers underlying illness traits in clinical remission stages after a first episode of schizophrenia

Comparison of seven prognostic tools to identify low-risk pulmonary embolism in patients aged <50 years

publishersversionPeer reviewe

The Global Alliance for Infections in Surgery : defining a model for antimicrobial stewardship-results from an international cross-sectional survey

Background: Antimicrobial Stewardship Programs (ASPs) have been promoted to optimize antimicrobial usage and patient outcomes, and to reduce the emergence of antimicrobial-resistant organisms. However, the best strategies for an ASP are not definitively established and are likely to vary based on local culture, policy, and routine clinical practice, and probably limited resources in middle-income countries. The aim of this study is to evaluate structures and resources of antimicrobial stewardship teams (ASTs) in surgical departments from different regions of the world. Methods: A cross-sectional web-based survey was conducted in 2016 on 173 physicians who participated in the AGORA (Antimicrobials: A Global Alliance for Optimizing their Rational Use in Intra-Abdominal Infections) project and on 658 international experts in the fields of ASPs, infection control, and infections in surgery. Results: The response rate was 19.4%. One hundred fifty-six (98.7%) participants stated their hospital had a multidisciplinary AST. The median number of physicians working inside the team was five [interquartile range 4-6]. An infectious disease specialist, a microbiologist and an infection control specialist were, respectively, present in 80.1, 76.3, and 67.9% of the ASTs. A surgeon was a component in 59.0% of cases and was significantly more likely to be present in university hospitals (89.5%, p <0.05) compared to community teaching (83.3%) and community hospitals (66.7%). Protocols for pre-operative prophylaxis and for antimicrobial treatment of surgical infections were respectively implemented in 96.2 and 82.3% of the hospitals. The majority of the surgical departments implemented both persuasive and restrictive interventions (72.8%). The most common types of interventions in surgical departments were dissemination of educational materials (62.5%), expert approval (61.0%), audit and feedback (55.1%), educational outreach (53.7%), and compulsory order forms (51.5%). Conclusion: The survey showed a heterogeneous organization of ASPs worldwide, demonstrating the necessity of a multidisciplinary and collaborative approach in the battle against antimicrobial resistance in surgical infections, and the importance of educational efforts towards this goal.Peer reviewe

The energy spectrum of cosmic rays beyond the turn-down around 10^17 eV as measured with the surface detector of the Pierre Auger Observatory

We present a measurement of the cosmic-ray spectrum above 100&nbsp;PeV using the part of the surface detector of the Pierre Auger Observatory that has a spacing of 750&nbsp;m. An inflection of the spectrum is observed, confirming the presence of the so-called second-knee feature. The spectrum is then combined with that of the 1500&nbsp;m array to produce a single measurement of the flux, linking this spectral feature with the three additional breaks at the highest energies. The combined spectrum, with an energy scale set calorimetrically via fluorescence telescopes and using a single detector type, results in the most statistically and systematically precise measurement of spectral breaks yet obtained. These measurements are critical for furthering our understanding of the highest energy cosmic rays

Status and performance of the underground muon detector of the Pierre Auger Observatory

The Auger Muons and Infill for the Ground Array (AMIGA) is an enhancement of the Pierre Auger Observatory, whose purpose is to lower the energy threshold of the observatory down to 1016.5 eV, and to measure the muonic content of air showers directly. These measurements will significantly contribute to the determination of primary particle masses in the range between the second knee and the ankle, to the study of hadronic interaction models with air showers, and, in turn, to the understanding of the muon puzzle. The underground muon detector of AMIGA is concomitant to two triangular grids of water-Cherenkov stations with spacings of 433 and 750 m; each grid position is equipped with a 30 m2 plastic scintillator buried at 2.3 m depth. After the engineering array completion in early 2018 and general improvements to the design, the production phase commenced. In this work, we report on the status of the underground muon detector, the progress of its deployment, and the performance achieved after two years of operation. The detector construction is foreseen to finish by mid-2022

Performance of the 433 m surface array of the Pierre Auger Observatory

The Pierre Auger Observatory, located in western Argentina, is the world’s largest cosmic-ray observatory. While it was originally built to study the cosmic-ray flux above 1018.5 eV, several enhancements have reduced this energy threshold. One such enhancement is a surface array composed of a triangular grid of 19 water-Cherenkov detectors separated by 433 m (SD-433) to explore the energies down to about 1016 eV. We are developing two research lines employing the SD-433. Firstly, we will measure the energy spectrum in a region where previous experiments have shown evidence of the second knee. Secondly, we will search for ultra-high energy photons to study PeV cosmic-ray sources residing in the Galactic center. In this work, we introduce the SD-433 and we show that it is fully efficient above 5×1016 eV for hadronic primaries with θ &lt; 45°. Using seven years of data, we present the parametrization of the lateral distribution function of measured signals. Finally, we show that an angular resolution of 1.8° (0.5°) can be attained at the lowest (highest) primary energies. Our study lays the goundmark for measurements in the energy range above 1016 eV by utilizing the SD-433 and thus expanding the scientific output of the Auger surface detector