Pathogen- and Host-Directed Antileishmanial Effects Mediated by Polyhexanide (PHMB)

BACKGROUND:Cutaneous leishmaniasis (CL) is a neglected tropical disease caused by protozoan parasites of the genus Leishmania. CL causes enormous suffering in many countries worldwide. There is no licensed vaccine against CL, and the chemotherapy options show limited efficacy and high toxicity. Localization of the parasites inside host cells is a barrier to most standard chemo- and immune-based interventions. Hence, novel drugs, which are safe, effective and readily accessible to third-world countries and/or drug delivery technologies for effective CL treatments are desperately needed. METHODOLOGY/PRINCIPAL FINDINGS:Here we evaluated the antileishmanial properties and delivery potential of polyhexamethylene biguanide (PHMB; polyhexanide), a widely used antimicrobial and wound antiseptic, in the Leishmania model. PHMB showed an inherent antileishmanial activity at submicromolar concentrations. Our data revealed that PHMB kills Leishmania major (L. major) via a dual mechanism involving disruption of membrane integrity and selective chromosome condensation and damage. PHMB's DNA binding and host cell entry properties were further exploited to improve the delivery and immunomodulatory activities of unmethylated cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODN). PHMB spontaneously bound CpG ODN, forming stable nanopolyplexes that enhanced uptake of CpG ODN, potentiated antimicrobial killing and reduced host cell toxicity of PHMB. CONCLUSIONS:Given its low cost and long history of safe topical use, PHMB holds promise as a drug for CL therapy and delivery vehicle for nucleic acid immunomodulators

European association for the study of obesity position statement on the global COVID-19 pandemic

COVID-19, the infectious disease caused by the coronavirus SARS-CoV-2, was declared a pandemic by the World Health Organization on March 12, 2020. The European Association for the Study of Obesity (EASO), as a scientific and medical society dedicated to the promotion of health and well-being, is greatly concerned about this global health challenge and its significant impacts on individuals, families, communities, health systems, nations, and wider society

A genomic catalog of Earth’s microbiomes

The reconstruction of bacterial and archaeal genomes from shotgun metagenomes has enabled insights into the ecology and evolution of environmental and host-associated microbiomes. Here we applied this approach to >10,000 metagenomes collected from diverse habitats covering all of Earth’s continents and oceans, including metagenomes from human and animal hosts, engineered environments, and natural and agricultural soils, to capture extant microbial, metabolic and functional potential. This comprehensive catalog includes 52,515 metagenome-assembled genomes representing 12,556 novel candidate species-level operational taxonomic units spanning 135 phyla. The catalog expands the known phylogenetic diversity of bacteria and archaea by 44% and is broadly available for streamlined comparative analyses, interactive exploration, metabolic modeling and bulk download. We demonstrate the utility of this collection for understanding secondary-metabolite biosynthetic potential and for resolving thousands of new host linkages to uncultivated viruses. This resource underscores the value of genome-centric approaches for revealing genomic properties of uncultivated microorganisms that affect ecosystem processes

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Keys to success of a community of clinical practice in primary care : a qualitative evaluation of the ECOPIH project

The current reality of primary care (PC) makes it essential to have telemedicine systems available to facilitate communication between care levels. Communities of practice have great potential in terms of care and education, and that is why the Online Communication Tool between Primary and Hospital Care was created. This tool enables PC and non-GP specialist care (SC) professionals to raise clinical cases for consultation and to share information. The objective of this article is to explore healthcare professionals' views on communities of clinical practice (CoCPs) and the changes that need to be made in an uncontrolled real-life setting after more than two years of use. A descriptive-interpretative qualitative study was conducted on a total of 29 healthcare professionals who were users and non-users of a CoCP using 2 focus groups, 3 triangular groups and 5 individual interviews. There were 18 women, 21 physicians and 8 nurses. Of the interviewees, 21 were PC professionals, 24 were users of a CoCP and 7 held managerial positions. For a system of communication between PC and SC to become a tool that is habitually used and very useful, the interviewees considered that it would have to be able to find quick, effective solutions to the queries raised, based on up-to-date information that is directly applicable to daily clinical practice. Contact should be virtual - and probably collaborative - via a platform integrated into their habitual workstations and led by PC professionals. Organisational changes should be implemented to enable users to have more time in their working day to spend on the tool, and professionals should have a proactive attitude in order to make the most if its potential. It is also important to make certain technological changes, basically aimed at improving the tool's accessibility, by integrating it into habitual clinical workstations. The collaborative tool that provides reliable, up-to-date information that is highly transferrable to clinical practice is valued for its effectiveness, efficiency and educational capacity. In order to make the most of its potential in terms of care and education, organisational changes and techniques are required to foster greater use. The online version of this article (10.1186/s12875-018-0739-0) contains supplementary material, which is available to authorized users

WSES guidelines for management of Clostridium difficile infection in surgical patients

In the last two decades there have been dramatic changes in the epidemiology of Clostridium difficile infection (CDI), with increases in incidence and severity of disease in many countries worldwide. The incidence of CDI has also increased in surgical patients. Optimization of management of C difficile, has therefore become increasingly urgent. An international multidisciplinary panel of experts prepared evidenced-based World Society of Emergency Surgery (WSES) guidelines for management of CDI in surgical patients.Peer reviewe

Reservoir Water-Level Drawdowns Accelerate and Amplify Methane Emission

Water-level fluctuations due to reservoir management could substantially affect the timing and magnitude of reservoir methane (CH4) fluxes to the atmosphere. However, effects of such fluctuations on CH4 emissions have received limited attention. Here we examine CH4 emission dynamics in six Pacific Northwest U.S. reservoirs of varying trophic status, morphometry, and management regimes. In these systems, we show that water-level drawdowns can, at least temporarily, greatly increase per-area reservoir CH4 fluxes to the atmosphere, and can account for more than 90% of annual reservoir CH4 flux in a period of just a few weeks. Reservoirs with higher epilimnetic [chlorophyll a] experienced larger increases in CH4 emission in response to drawdown (R2 = 0.84, p < 0.01), suggesting that eutrophication magnifies the effect of drawdown on CH4 emission. We show that drawdowns as small as 0.5 m can stimulate ebullition events. Given that drawdown events of this magnitude are quite common in reservoirs, our results suggest that this process must be considered in sampling strategies designed to characterize total CH4 fluxes from reservoirs. The extent to which (and the mechanisms by which) drawdowns short-circuit connections between methanogenesis and methanotrophy, thereby increasing net CH4 fluxes to the atmosphere, should be a focus of future work

European association for the study of obesity position statement on the global COVID-19 pandemic

COVID-19, the infectious disease caused by the coronavirus SARS-CoV-2, was declared a pandemic by the World Health Organization on March 12, 2020. The European Association for the Study of Obesity (EASO), as a scientific and medical society dedicated to the promotion of health and well-being, is greatly concerned about this global health challenge and its significant impacts on individuals, families, communities, health systems, nations, and wider society