Bacteriophage are abundant at sites of bacterial infection, but their effects on mammalian hosts are unclear. We have identified pathogenic roles for filamentous Pf bacteriophage produced by
(
) in ...suppression of immunity against bacterial infection. Pf promote
wound infection in mice and are associated with chronic human
wound infections. Murine and human leukocytes endocytose Pf, and internalization of this single-stranded DNA virus results in phage RNA production. This triggers Toll-like receptor 3 (TLR3)- and TIR domain-containing adapter-inducing interferon-β (TRIF)-dependent type I interferon production, inhibition of tumor necrosis factor (TNF), and the suppression of phagocytosis. Conversely, immunization of mice against Pf prevents
wound infection. Thus, Pf triggers maladaptive innate viral pattern-recognition responses, which impair bacterial clearance. Vaccination against phage virions represents a potential strategy to prevent bacterial infection.
Type III interferons have been touted as promising therapeutics in outpatients with coronavirus disease 2019 (COVID-19). We conducted a randomized, single-blind, placebo-controlled trial ...(NCT04331899) in 120 outpatients with mild to moderate COVID-19 to determine whether a single, 180 mcg subcutaneous dose of Peginterferon Lambda-1a (Lambda) within 72 hours of diagnosis could shorten the duration of viral shedding (primary endpoint) or symptoms (secondary endpoint). In both the 60 patients receiving Lambda and 60 receiving placebo, the median time to cessation of viral shedding was 7 days (hazard ratio HR = 0.81; 95% confidence interval CI 0.56 to 1.19). Symptoms resolved in 8 and 9 days in Lambda and placebo, respectively, and symptom duration did not differ significantly between groups (HR 0.94; 95% CI 0.64 to 1.39). Both Lambda and placebo were well-tolerated, though liver transaminase elevations were more common in the Lambda vs. placebo arm (15/60 vs 5/60; p = 0.027). In this study, a single dose of subcutaneous Peginterferon Lambda-1a neither shortened the duration of SARS-CoV-2 viral shedding nor improved symptoms in outpatients with uncomplicated COVID-19.
Current sanitation systems are inherently limited in their ability to address the new challenges for (waste)water management that arise from the rising demand to restore resource cycles. These ...challenges include removal of micropollutants, water (re)use, and nutrient recovery. New opportunities to address these challenges arise from new sanitation, a system innovation that combines elements of source separation, local treatment and reuse, and less use of water. New sanitation is applied, but not yet widespread, in several residential areas in Europe. Implementation is hindered by the lack of insight into the general public's willingness to engage in new sanitation, and the resulting uncertainty about this among decision makers and other stakeholders in wastewater management. Using value-belief-norm theory as a conceptual lens, this paper addresses the individual motivations (pro-environmental personal norms) and personal drivers (benefits) and barriers (risks) for acceptance of new sanitation by the Dutch general public. The results of an online survey (N = 338) indicated that both pro-environmental personal norms and risk and benefit perceptions predict consumers' willingness to accept new sanitation. More specifically, they showed that consumer acceptance is driven by perceived risks relating to the housing market and the need to change behavior, but also by environmental benefits. Overall, new sanitation was favorably evaluated by respondents: 64% indicated that they would likely use new sanitation if they were owner-occupiers. The results of this explorative study are discussed in light of the development of novel sanitation systems that are sensitive to perceptions of end-users and other key stakeholders.
•64% of end-users indicated that they would likely use new sanitation.•Perceived benefits/risks and pro-environmental personal norms drive user acceptance.•Property value and environment are significant factors for benefit perceptions.•Only potential behavior change contributed significantly to risk perceptions.•Risk & benefit perception improved VBN theory: from 30% to 50% explained variance.
Chromosomal copy number variation (CCNV) plays a key role in evolution and health of eukaryotes. The unicellular yeast
is an important model for studying the generation, physiological impact, and ...evolutionary significance of CCNV. Fundamental studies of this yeast have contributed to an extensive set of methods for analyzing and introducing CCNV. Moreover, these studies provided insight into the balance between negative and positive impacts of CCNV in evolutionary contexts. A growing body of evidence indicates that CCNV not only frequently occurs in industrial strains of
yeasts but also is a key contributor to the diversity of industrially relevant traits. This notion is further supported by the frequent involvement of CCNV in industrially relevant traits acquired during evolutionary engineering. This review describes recent developments in genome sequencing and genome editing techniques and discusses how these offer opportunities to unravel contributions of CCNV in industrial
s strains as well as to rationally engineer yeast chromosomal copy numbers and karyotypes.
The review discusses the recent literature on plaque angiogenesis and its relation to inflammation and plaque destabilization. Furthermore, it discusses how plaque angiogenesis can be used to monitor ...atherosclerosis and serve as a therapeutic target.
Histopathologic studies have shown a clear relationship between plaque angiogenesis, intraplaque hemorrhage (IPH), plaque vulnerability, and cardiovascular events. Hypoxia is a main driver of plaque angiogenesis and the mechanism behind angiogenesis is only partly known. IPH, as the result of immature neovessels, is associated with increased influx of inflammatory cells in the plaques. Experimental models displaying certain features of human atherosclerosis such as plaque angiogenesis or IPH are developed and can contribute to unraveling the mechanism behind plaque vulnerability. New imaging techniques are established, with which plaque angiogenesis and vulnerability can be detected. Furthermore, antiangiogenic therapies in atherosclerosis gain much attention.
Plaque angiogenesis, IPH, and inflammation contribute to plaque vulnerability. Histopathologic and imaging studies together with specific experimental studies have provided insights in plaque angiogenesis and plaque vulnerability. However, more extensive knowledge on the underlying mechanism is required for establishing new therapies for patients at risk.
Increasing rates of infection by antibiotic resistant bacteria have led to a resurgence of interest in bacteriophage (phage) therapy. Several phage therapy studies in animals and humans have been ...completed over the last two decades. We conducted a systematic review of safety and toxicity data associated with phage therapy in both animals and humans reported in English language publications from 2008–2021. Overall, 69 publications met our eligibility criteria including 20 animal studies, 35 clinical case reports or case series, and 14 clinical trials. After summarizing safety and toxicity data from these publications, we discuss potential approaches to optimize safety and toxicity monitoring with the therapeutic use of phage moving forward. In our systematic review of the literature, we found some adverse events associated with phage therapy, but serious events were extremely rare. Comprehensive and standardized reporting of potential toxicities associated with phage therapy has generally been lacking in the published literature. Structured safety and tolerability endpoints are necessary when phages are administered as anti-infective therapeutics.
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