Current inpatient treatment options for COVID-19:an update

In dit overzichtsartikel geven wij een update van de adviezen voor de medicamenteuze behandeling van covid-19 in de tweede lijn.Deze adviezen zijn opgesteld door de Stichting Werkgroep Antibioticabeleid (SWAB) in samenwerking met onder andere de Federatie Medisch Specialisten (FMS).Zowel opties voor behandeling in het ziekenhuis als opties voor behandeling in de ambulante setting worden besproken.De behandeling omvat zowel anti-inflammatoire als antivirale therapie.In this article we provide an overview of the current treatment recommendations for COVID-19. These recommendations are made by the SWAB (StichtingWerkgroepAntibioticabeleid), in cooperation with the FMS (FederatieMedischSpecialisten (online: swab.nl/nl/covid-19.). Treatment options for patients in both ambulatory care and admitted to the hospital are listed. These treatment options include both antiinflammatory and antiviral therapy.</p

The reaction coordinate mapping in quantum thermodynamics

We present an overview of the reaction coordinate approach to handling strong system-reservoir interactions in quantum thermodynamics. This technique is based on incorporating a collective degree of freedom of the reservoir (the reaction coordinate) into an enlarged system Hamiltonian (the supersystem), which is then treated explicitly. The remaining residual reservoir degrees of freedom are traced out in the usual perturbative manner. The resulting description accurately accounts for strong system-reservoir coupling and/or non-Markovian effects over a wide range of parameters, including regimes in which there is a substantial generation of system-reservoir correlations. We discuss applications to both discrete stroke and continuously operating heat engines, as well as perspectives for additional developments. In particular, we find narrow regimes where strong coupling is not detrimental to the performance of continuously operating heat engines.Comment: 17 pages, 2 tables, 7 figures. As a chapter of: F. Binder, L. A. Correa, C. Gogolin, J. Anders, and G. Adesso (eds.), "Thermodynamics in the quantum regime - Recent Progress and Outlook", (Springer International Publishing

High-resolution spatial patterns and drivers of terrestrial ecosystem carbon dioxide, methane, and nitrous oxide fluxes in the tundra

Arctic terrestrial greenhouse gas (GHG) fluxes of carbon dioxide (CO2), methane (CH4), and nitrous oxide (N2O) play an important role in the global GHG budget. However, these GHG fluxes are rarely studied simultaneously, and our understanding of the conditions controlling them across spatial gradients is limited. Here, we explore the magnitudes and drivers of GHG fluxes across fine-scale terrestrial gradients during the peak growing season (July) in sub-Arctic Finland. We measured chamber-derived GHG fluxes and soil temperature, soil moisture, soil organic carbon and nitrogen stocks, soil pH, soil carbon-to-nitrogen (C/N) ratio, soil dissolved organic carbon content, vascular plant biomass, and vegetation type from 101 plots scattered across a heterogeneous tundra landscape (5 km2). We used these field data together with high-resolution remote sensing data to develop machine learning models for predicting (i.e., upscaling) daytime GHG fluxes across the landscape at 2 m resolution. Our results show that this region was on average a daytime net GHG sink during the growing season. Although our results suggest that this sink was driven by CO2 uptake, it also revealed small but widespread CH4 uptake in upland vegetation types, almost surpassing the high wetland CH4 emissions at the landscape scale. Average N2O fluxes were negligible. CO2 fluxes were controlled primarily by annual average soil temperature and biomass (both increase net sink) and vegetation type, CH4 fluxes by soil moisture (increases net emissions) and vegetation type, and N2O fluxes by soil C/N (lower C/N increases net source). These results demonstrate the potential of high spatial resolution modeling of GHG fluxes in the Arctic. They also reveal the dominant role of CO2 fluxes across the tundra landscape but suggest that CH4 uptake in dry upland soils might play a significant role in the regional GHG budget.</p

Molecular, microbiological and clinical characterization of Clostridium difficile isolates from tertiary care hospitals in Colombia

In Colombia, the epidemiology and circulating genotypes of Clostridium difficile have not yet been described. Therefore, we molecularly characterized clinical isolates of C.difficile from patients with suspicion of C.difficile infection (CDI) in three tertiary care hospitals. C.difficile was isolated from stool samples by culture, the presence of A/B toxins were detected by enzyme immunoassay, cytotoxicity was tested by cell culture and the antimicrobial susceptibility determined. After DNA extraction, tcdA, tcdB and binary toxin (CDTa/CDTb) genes were detected by PCR, and PCR-ribotyping performed. From a total of 913 stool samples collected during 2013–2014, 775 were included in the study. The frequency of A/B toxins-positive samples was 9.7% (75/775). A total of 143 isolates of C.difficile were recovered from culture, 110 (76.9%) produced cytotoxic effect in cell culture, 100 (69.9%) were tcdA+/tcdB+, 11 (7.7%) tcdA-/tcdB+, 32 (22.4%) tcdA-/tcdB- and 25 (17.5%) CDTa+/CDTb+. From 37 ribotypes identified, ribotypes 591 (20%), 106 (9%) and 002 (7.9%) were the most prevalent; only one isolate corresponded to ribotype 027, four to ribotype 078 and four were new ribotypes (794,795, 804,805). All isolates were susceptible to vancomycin and metronidazole, while 85% and 7.7% were resistant to clindamycin and moxifloxacin, respectively. By multivariate analysis, significant risk factors associated to CDI were, staying in orthopedic service, exposure to third-generation cephalosporins and staying in an ICU before CDI symptoms; moreover, steroids showed to be a protector factor. These results revealed new C. difficile ribotypes and a high diversity profile circulating in Colombia different from those reported in America and European countries

Clostridium difficile infection.

Infection of the colon with the Gram-positive bacterium Clostridium difficile is potentially life threatening, especially in elderly people and in patients who have dysbiosis of the gut microbiota following antimicrobial drug exposure. C. difficile is the leading cause of health-care-associated infective diarrhoea. The life cycle of C. difficile is influenced by antimicrobial agents, the host immune system, and the host microbiota and its associated metabolites. The primary mediators of inflammation in C. difficile infection (CDI) are large clostridial toxins, toxin A (TcdA) and toxin B (TcdB), and, in some bacterial strains, the binary toxin CDT. The toxins trigger a complex cascade of host cellular responses to cause diarrhoea, inflammation and tissue necrosis - the major symptoms of CDI. The factors responsible for the epidemic of some C. difficile strains are poorly understood. Recurrent infections are common and can be debilitating. Toxin detection for diagnosis is important for accurate epidemiological study, and for optimal management and prevention strategies. Infections are commonly treated with specific antimicrobial agents, but faecal microbiota transplants have shown promise for recurrent infections. Future biotherapies for C. difficile infections are likely to involve defined combinations of key gut microbiota

Comparative genomic analysis of toxin-negative strains of Clostridium difficile from humans and animals with symptoms of gastrointestinal disease

Background: Clostridium difficile infections (CDI) are a significant health problem to humans and food animals. Clostridial toxins ToxA and ToxB encoded by genes tcdA and tcdB are located on a pathogenicity locus known as the PaLoc and are the major virulence factors of C. difficile. While toxin-negative strains of C. difficile are often isolated from faeces of animals and patients suffering from CDI, they are not considered to play a role in disease. Toxin-negative strains of C. difficile have been used successfully to treat recurring CDI but their propensity to acquire the PaLoc via lateral gene transfer and express clinically relevant levels of toxins has reinforced the need to characterise them genetically. In addition, further studies that examine the pathogenic potential of toxin-negative strains of C. difficile and the frequency by which toxin-negative strains may acquire the PaLoc are needed. Results: We undertook a comparative genomic analysis of five Australian toxin-negative isolates of C. difficile that lack tcdA, tcdB and both binary toxin genes cdtA and cdtB that were recovered from humans and farm animals with symptoms of gastrointestinal disease. Our analyses show that the five C. difficile isolates cluster closely with virulent toxigenic strains of C. difficile belonging to the same sequence type (ST) and have virulence gene profiles akin to those in toxigenic strains. Furthermore, phage acquisition appears to have played a key role in the evolution of C. difficile. Conclusions: Our results are consistent with the C. difficile global population structure comprising six clades each containing both toxin-positive and toxin-negative strains. Our data also suggests that toxin-negative strains of C. difficile encode a repertoire of putative virulence factors that are similar to those found in toxigenic strains of C. difficile, raising the possibility that acquisition of PaLoc by toxin-negative strains poses a threat to human health. Studies in appropriate animal models are needed to examine the pathogenic potential of toxin-negative strains of C. difficile and to determine the frequency by which toxin-negative strains may acquire the PaLoc