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This review discusses the current state of the viral metabolism field and gaps in knowledge that will be important for future studies to investigate. We discuss metabolic rewiring caused by viruses, the influence of oncogenic viruses on host cell metabolism, and the use of viruses as guides to identify critical metabolic nodes for cancer anabolism. We also discuss the need for more mechanistic studies identifying viral proteins responsible for metabolic hijacking and for in vivo studies of viral-induced metabolic rewiring. Improved technologies for detailed metabolic measurements and genetic manipulation will lead to important discoveries over the next decade.

Retention in opioid substitution (OST) treatment is associated with substantial reductions in all cause and overdose mortality. This systematic review aims to identify both protective factors supporting retention in OST, and risk factors for treatment dropout. A systematic search was performed using MEDLINE, Embase, PsycInfo, CINAHL and Web of Science (January 2001 to October 2019). Randomised controlled trials (RCTs) and observational cohort studies reporting on retention rates and factors associated with retention in OST were included. Factors associated with treatment retention and dropout were explored according to the Maudsley Addiction Profile. A narrative synthesis is provided. 67 studies were included in this review (4 RCTs and 63 observational cohort studies; N = 294,592), all assessing factors associated with retention in OST or treatment dropout. The median retention rate across observational studies was approximately 57% at 12 months, which fell to 38.4% at three years. Studies included were heterogeneous in nature with respect to treatment setting, type of OST, risk factor assessment, ascertainment of outcome and duration of follow-up. While the presence of such methodological heterogeneity makes it difficult to synthesise results, there is limited evidence to support the influence of a number of factors on retention, including age, substance use, OST drug dose, legal issues, and attitudes to OST. Younger age, substance use particularly cocaine and heroin use, lower doses of methadone, criminal activity/incarceration, and negative attitudes to MMT appear to be associated with reduced retention in OST. A consensus definition of retention is required to allow for comparability across future studies.

Microbial amplicon sequencing studies are an important tool in biological and biomedical research. Widespread 16S rRNA gene microbial surveys have shed light on the structure of many ecosystems inhabited by bacteria, including the human body. However, specialized software and algorithms are needed to convert raw sequencing data into biologically meaningful information (i.e. tables of bacterial counts). While different bioinformatic pipelines are available in a rapidly changing and improving field, users are often unaware of limitations and biases associated with individual pipelines and there is a lack of agreement regarding best practices. Here, we compared six bioinformatic pipelines for the analysis of amplicon sequence data: three OTU-level flows (QIIME-uclust, MOTHUR, and USEARCH-UPARSE) and three ASV-level (DADA2, Qiime2-Deblur, and USEARCH-UNOISE3). We tested workflows with different quality control options, clustering algorithms, and cutoff parameters on a mock community as well as on a large (N = 2170) recently published fecal sample dataset from the multi-ethnic HELIUS study. We assessed the sensitivity, specificity, and degree of consensus of the different outputs. DADA2 offered the best sensitivity, at the expense of decreased specificity compared to USEARCH-UNOISE3 and Qiime2-Deblur. USEARCH-UNOISE3 showed the best balance between resolution and specificity. OTU-level USEARCH-UPARSE and MOTHUR performed well, but with lower specificity than ASV-level pipelines. QIIME-uclust produced large number of spurious OTUs as well as inflated alpha-diversity measures and should be avoided in future studies. This study provides guidance for researchers using amplicon sequencing to gain biological insights.

Attention to women's and girls' menstrual needs is critical for global health and gender equality. The importance of this neglected experience has been elucidated by a growing body of qualitative research, which we systematically reviewed and synthesised. We undertook systematic searching to identify qualitative studies of women's and girls' experiences of menstruation in low- and middle-income countries (LMICs). Of 6,892 citations screened, 76 studies reported in 87 citations were included. Studies captured the experiences of over 6,000 participants from 35 countries. This included 45 studies from sub-Saharan Africa (with the greatest number of studies from Kenya [n = 7], Uganda [n = 6], and Ethiopia [n = 5]), 21 from South Asia (including India [n = 12] and Nepal [n = 5]), 8 from East Asia and the Pacific, 5 from Latin America and the Caribbean, 5 from the Middle East and North Africa, and 1 study from Europe and Central Asia. Through synthesis, we identified overarching themes and their relationships to develop a directional model of menstrual experience. This model maps distal and proximal antecedents of menstrual experience through to the impacts of this experience on health and well-being. The sociocultural context, including menstrual stigma and gender norms, influenced experiences by limiting knowledge about menstruation, limiting social support, and shaping internalised and externally enforced behavioural expectations. Resource limitations underlay inadequate physical infrastructure to support menstruation, as well as an economic environment restricting access to affordable menstrual materials. Menstrual experience included multiple themes: menstrual practices, perceptions of practices and environments, confidence, shame and distress, and containment of bleeding and odour. These components of experience were interlinked and contributed to negative impacts on women's and girls' lives. Impacts included harms to physical and psychological health as well as education and social engagement. Our review is limited by the available studies. Study quality was varied, with 18 studies rated as high, 35 medium, and 23 low trustworthiness. Sampling and analysis tended to be untrustworthy in lower-quality studies. Studies focused on the experiences of adolescent girls were most strongly represented, and we achieved early saturation for this group. Reflecting the focus of menstrual health research globally, there was an absence of studies focused on adult women and those from certain geographical areas. Through synthesis of extant qualitative studies of menstrual experience, we highlight consistent challenges and developed an integrated model of menstrual experience. This model hypothesises directional pathways that could be tested by future studies and may serve as a framework for program and policy development by highlighting critical antecedents and pathways through which interventions could improve women's and girls' health and well-being. The review protocol registration is PROSPERO: CRD42018089581.

The incidence of heatstroke has been increasing in Japan, and future climate change is likely to increase heatstroke risk. We therefore developed a method to quantify the spatial distribution of outdoor heatstroke risk and predicted future changes in this risk considering the predicted climate change in Sendai, Japan. Heatstroke risk was quantified by assessing hazard, vulnerability and exposure. Daily maximum wet-bulb globe temperature (WBGT) was selected as the hazard index. The distribution of WBGT was predicted by mesoscale meteorological simulations using the Weather Research and Forecasting (WRF) model. The relationship between daily maximum WBGT and the daily incidence rate was approximated by analyzing emergency transport data. This relationship was selected as the vulnerability index. Using the hazard and vulnerability indices, a spatial distribution of the monthly incidence rate was obtained. Finally, the total number of heatstroke patients per month was estimated by multiplying the monthly incidence rate by the population density. The outdoor heatstroke risk for August was then estimated for current (2000s) and near-future (2030s) climatic conditions in Sendai. WBGT at coastal areas in the 2030s increased owing to increases in humidity, while WBGT at inland areas increased owing to increases in air temperature. This increase in WBGT drove increases in heatstroke risk.

Background The use of computers/TV has become increasingly common worldwide after entering the twenty-first century and depression represents a growing public health burden. Understanding the association between screen time-based sedentary behavior (ST-SB) and the risk of depression is important to the development of prevention and intervention strategies. Methods We searched the electronic databases of Medline, Embase and the Cochrane Library. The odds ratio (OR) with corresponding 95% confidence intervals (CIs) was adopted as the pooled measurement. Subgroup analyses were investigated by stratified meta-analyses based on age, gender and reference group (reference category of screen time, e.g. 2 h/day, 4 h/day). Results There were 12 cross-sectional studies and 7 longitudinal studies met the inclusion criteria. Overall, the pooled OR was 1.28 with high heterogeneity (I 2  = 89%). Compared to those who reported less SB, persons reporting more SB had a significantly higher risk of depression. When the gender was stratified, the pooled OR was 1.18 in female groups while no significant association was observed in males. Among the 19 studies, 5 studies used a reference group with ST = 2 h/days (pooled OR = 1.46), 9 studies used ≥4 h as a reference group (pooled OR = 1.38), 2 studies used 1 h as a reference group (pooled OR = 1.07) and for the remaining 3 studies, hours of ST were calculated as a continuous variable (pooled OR = 1.04). Conclusions ST-SB is associated with depression risk and the effects vary in different populations. In addition, valid objective measures of SB should be developed in future studies.

Abstract Adipose tissue is present in close proximity to various organs in the human body. One prominent example is fat contained in the mesentery that is contiguous with all abdominal digestive organs including the intestine. Despite the fact that mesenteric fat-wrapping around the inflamed gut (so called “creeping fat”) was described as a characteristic feature of Crohn’s disease (CD) in the early 1930s, the functional implications of creeping fat have received only recent attention. As a potent producer of fatty acids, cytokines, growth factors, and adipokines, creeping fat plays an important role in regulation of immunity and inflammation. Increasing evidence points to a link between creeping fat and intestinal inflammation in CD, where histopathologic evaluation shows a significant association between creeping fat and connective tissue changes in the bowel wall, such as muscular hypertrophy, fibrosis, and stricture formation. In addition, emerging mechanistic data indicate a link between creeping fat, muscularis propria hyperplasia, and stricturing disease. Information on fat–mesenchymal interactions in other organs could provide clues to fill the fundamental knowledge gap on the role of distinct components of creeping fat in intestinal fibrosis and stricture formation. Future studies will provide important new information that in turn could lead to novel therapeutic agents aimed at prevention or treatment of CD-associated fibrosis and stricture formation.

Background Microorganisms in biogas reactors are essential for degradation of organic matter and methane production. However, a comprehensive genome-centric comparison, including relevant metadata for each sample, is still needed to identify the globally distributed biogas community members and serve as a reliable repository. Results Here, 134 publicly available metagenomes derived from different biogas reactors were used to recover 1635 metagenome-assembled genomes (MAGs) representing different biogas bacterial and archaeal species. All genomes were estimated to be > 50% complete and nearly half ≥ 90% complete with ≤ 5% contamination. In most samples, specialized microbial communities were established, while only a few taxa were widespread among the different reactor systems. Metabolic reconstruction of the MAGs enabled the prediction of functional traits related to biomass degradation and methane production from waste biomass. An extensive evaluation of the replication index provided an estimation of the growth dynamics for microbes involved in different steps of the food chain. Conclusions The outcome of this study highlights a high flexibility of the biogas microbiome, allowing it to modify its composition and to adapt to the environmental conditions, including temperatures and a wide range of substrates. Our findings enhance our mechanistic understanding of the AD microbiome and substantially extend the existing repository of genomes. The established database represents a relevant resource for future studies related to this engineered ecosystem.

The glycocalyx is a gel-like layer covering the luminal surface of vascular endothelial cells. It is comprised of membrane-attached proteoglycans, glycosaminoglycan chains, glycoproteins, and adherent plasma proteins. The glycocalyx maintains homeostasis of the vasculature, including controlling vascular permeability and microvascular tone, preventing microvascular thrombosis, and regulating leukocyte adhesion. During sepsis, the glycocalyx is degraded via inflammatory mechanisms such as metalloproteinases, heparanase, and hyaluronidase. These sheddases are activated by reactive oxygen species and pro-inflammatory cytokines such as tumor necrosis factor alpha and interleukin-1beta. Inflammation-mediated glycocalyx degradation leads to vascular hyper-permeability, unregulated vasodilation, microvessel thrombosis, and augmented leukocyte adhesion. Clinical studies have demonstrated the correlation between blood levels of glycocalyx components with organ dysfunction, severity, and mortality in sepsis. Fluid resuscitation therapy is an essential part of sepsis treatment, but overaggressive fluid therapy practices (leading to hypervolemia) may augment glycocalyx degradation. Conversely, fresh frozen plasma and albumin administration may attenuate glycocalyx degradation. The beneficial and harmful effects of fluid and plasma infusion on glycocalyx integrity in sepsis are not well understood; future studies are warranted. In this review, we first analyze the underlying mechanisms of glycocalyx degradation in sepsis. Second, we demonstrate how the blood and urine levels of glycocalyx components are associated with patient outcomes. Third, we show beneficial and harmful effects of fluid therapy on the glycocalyx status during sepsis. Finally, we address the concept of glycocalyx degradation as a therapeutic target.

Accurate and systematic transcriptome-wide detection of 5-methylcytosine (m5C) has proved challenging, and there are conflicting views about the prevalence of this modification in mRNAs. Here we report an experimental and computational framework that robustly identified mRNA m5C sites and determined sequence motifs and structural features associated with the modification using a set of high-confidence sites. We developed a quantitative atlas of RNA m5C sites in human and mouse tissues based on our framework. In a given tissue, we typically identified several hundred exonic m5C sites. About 62–70% of the sites had low methylation levels (<20% methylation), while 8–10% of the sites were moderately or highly methylated (>40% methylation). Cross-species analysis revealed that species, rather than tissue type, was the primary determinant of methylation levels, indicating strong cis-directed regulation of RNA methylation. Combined, these data provide a valuable resource for identifying the regulation and functions of RNA methylation.A quantitative atlas of RNA m5C sites in human and mouse tissues based on a new discovery pipeline allows the identification of sequence motifs and structural features associated with the modification and provides a resource for future studies.