Serum Bovine Immunoglobulins Improve Inflammation and Gut Barrier Function in Persons with HIV and Enteropathy on Suppressive ART.

BackgroundSystemic inflammation persists in chronic HIV infection and is associated with increased rates of non-AIDS events such as cardiovascular and liver disease. Increased gut permeability and systemic exposure to microbial products are key drivers of this inflammation. Serum-derived bovine immunoglobulin/protein isolate (SBI) supports gut healing in other conditions such as inflammatory bowel disease.MethodsIn this randomized, double-blind study, participants receiving suppressive antiretroviral therapy (ART) with chronic diarrhea received placebo or SBI at 2.5 g BID or 5 g BID for 4 weeks, followed by a 20-week placebo-free extension phase with SBI at either 2.5 or 5 g BID. Intestinal fatty acid binding protein (I-FABP), zonulin, flagellin, lipopolysaccharide (LPS) and LPS-binding protein, and inflammatory markers were measured by ELISA or multiplex assays. Non-parametric tests were used for analysis.ResultsOne hundred three participants completed the study. By week 24 SBI significantly decreased circulating levels of I-FABP (-0.35 ng/μL, P=0.002) and zonulin (-4.90 ng/μL, P=0.003), suggesting improvement in gut damage, and interleukin-6 (IL-6) (-0.40 pg/μL, P=0.002), reflecting improvement in systemic inflammation. In participants with the lowest quartile of CD4+ T-cell counts at baseline (189-418 cells/μL), CD4+ T-cell counts increased significantly (26 cells/μL; P=0.002).ConclusionsOral SBI may decrease inflammation and warrants further exploration as a potential strategy to improve gut integrity and decrease systemic inflammation among persons receiving prolonged suppressive ART

Malnutrition defined by GLIM criteria identifies a higher incidence of malnutrition and is associated with pulmonary complications after oesophagogastric cancer surgery, compared to ICD-10-defined malnutrition

Background & Objectives Low muscle mass, measured using computed tomography (CT), is associated with poor surgical outcomes. We aimed to include CT-muscle mass in malnutrition diagnosis using the Global Leadership Initiative on Malnutrition (GLIM) criteria, compare it to the International Classification of Diseases 10th Revision (ICD-10) criteria, and assess the impact on postoperative outcomes after oesophagogastric (OG) cancer surgery. Methods One hundred and eight patients who underwent radical OG cancer surgery and had preoperative abdominal CT imaging were included. GLIM and ICD-10 malnutrition data were assessed against complication and survival outcomes. Low CT-muscle mass was determined using predefined cut-points. Results GLIM-defined malnutrition prevalence was significantly higher than ICD-10-malnutrition (72.2% vs. 40.7%, p < 0.001). Of the 78 patients with GLIM-defined malnutrition, low muscle mass (84.6%) was the predominant phenotypic criterion. GLIM-defined malnutrition was associated with pneumonia (26.9% vs. 6.7%, p = 0.010) and pleural effusions (12.8% vs. 0%, p = 0.029). Postoperative complications did not correlate with ICD-10 malnutrition. Severe GLIM (HR: 2.51, p = 0.014) and ICD-10 (HR: 2.15, p = 0.039) malnutrition were independently associated with poorer 5-year survival. Conclusions GLIM criteria appear to identify more malnourished patients and more closely relate to surgical risk than ICD-10 malnutrition, likely due to incorporating objective muscle mass assessment

Rifaximin Treatment in Hepatic Encephalopathy

Background Hepatic encephalopathy is a chronically debilitating complication of hepatic cirrhosis. The efficacy of rifaximin, a minimally absorbed antibiotic, is well documented in the treatment of acute hepatic encephalopathy, but its efficacy for prevention of the disease has not been established. Methods In this randomized, double-blind, placebo-controlled trial, we randomly assigned 299 patients who were in remission from recurrent hepatic encephalopathy resulting from chronic liver disease to receive either rifaximin, at a dose of 550 mg twice daily (140 patients), or placebo (159 patients) for 6 months. The primary efficacy end point was the time to the first breakthrough episode of hepatic encephalopathy. The key secondary end point was the time to the first hospitalization involving hepatic encephalopathy. Results Rifaximin significantly reduced the risk of an episode of hepatic encephalopathy, as compared with placebo, over a 6-month period (hazard ratio with rifaximin, 0.42; 95% confidence interval [CI], 0.28 to 0.64; P Conclusions Over a 6-month period, treatment with rifaximin maintained remission from hepatic encephalopathy more effectively than did placebo. Rifaximin treatment also significantly reduced the risk of hospitalization involving hepatic encephalopathy. (ClinicalTrials.gov number, NCT00298038.

Young people’s experiences of COVID-19 messaging at the start of the UK lockdown:Lessons for positive engagement and information sharing

BACKGROUND: To reduce COVID-19 infection rates during the initial stages of the pandemic, the UK Government mandated a strict period of restriction on freedom of movement or 'lockdown'. For young people, closure of schools and higher education institutions and social distancing rules may have been particularly challenging, coming at a critical time in their lives for social and emotional development. This study explored young people's experiences of the UK Government's initial response to the pandemic and related government messaging.METHODS: This qualitative study combines data from research groups at the University of Southampton, University of Edinburgh and University College London. Thirty-six online focus group discussions (FGDs) were conducted with 150 young people (Southampton: n = 69; FGD = 7; Edinburgh: n = 41; FGD = 5; UCL: n = 40; FGD = 24). Thematic analysis was conducted to explore how young people viewed the government's response and messaging and to develop recommendations for how to best involve young people in addressing similar crises in the future. RESULTS: The abrupt onset of lockdown left young people shocked, confused and feeling ignored by government and media messaging. Despite this, they were motivated to adhere to government advice by the hope that life might soon return to normal. They felt a responsibility to help with the pandemic response, and wanted to be productive with their time, but saw few opportunities to volunteer.CONCLUSIONS: Young people want to be listened to and feel they have a part to play in responding to a national crisis such as the COVID-19 epidemic. To reduce the likelihood of disenfranchising the next generation, Government and the media should focus on developing messaging that reflects young people's values and concerns and to provide opportunities for young people to become involved in responses to future crises

Rifaximin Therapy for Patients with Irritable Bowel Syndrome without Constipation

BACKGROUND Evidence suggests that gut flora may play an important role in the pathophysiology of the irritable bowel syndrome (IBS). We evaluated rifaximin, a minimally absorbed antibiotic, as treatment for IBS. METHODS In two identically designed, phase 3, double-blind, placebo-controlled trials (TARGET 1 and TARGET 2), patients who had IBS without constipation were randomly assigned to either rifaximin at a dose of 550 mg or placebo, three times daily for 2 weeks, and were followed for an additional 10 weeks. The primary end point, the proportion of patients who had adequate relief of global IBS symptoms, and the key secondary end point, the proportion of patients who had adequate relief of IBS-related bloating, were assessed weekly. Adequate relief was defined as self-reported relief of symptoms for at least 2 of the first 4 weeks after treatment. Other secondary end points included the percentage of patients who had a response to treatment as assessed by daily self-ratings of global IBS symptoms and individual symptoms of bloating, abdominal pain, and stool consistency during the 4 weeks after treatment and during the entire 3 months of the study. RESULTS Significantly more patients in the rifaximin group than in the placebo group had adequate relief of global IBS symptoms during the first 4 weeks after treatment (40.8% vs. 31.2%, P=0.01, in TARGET 1; 40.6% vs. 32.2%, P=0.03, in TARGET 2; 40.7% vs. 31.7%, P<0.001, in the two studies combined). Similarly, more patients in the rifaximin group than in the placebo group had adequate relief of bloating (39.5% vs. 28.7%, P=0.005, in TARGET 1; 41.0% vs. 31.9%, P=0.02, in TARGET 2; 40.2% vs. 30.3%, P<0.001, in the two studies combined). In addition, significantly more patients in the rifaximin group had a response to treatment as assessed by daily ratings of IBS symptoms, bloating, abdominal pain, and stool consistency. The incidence of adverse events was similar in the two groups. CONCLUSIONS Among patients who had IBS without constipation, treatment with rifaximin for 2 weeks provided significant relief of IBS symptoms, bloating, abdominal pain, and loose or watery stools. (Funded by Salix Pharmaceuticals; ClinicalTrials.gov numbers, NCT00731679 and NCT00724126.)

Can biodiversity of preexisting and created salt marshes match across scales? An assessment from microbes to predators

Coastal wetlands are rapidly disappearing worldwide due to a variety of processes, including climate change and flood control. The rate of loss in the Mississippi River Delta is among the highest in the world and billions of dollars have been allocated to build and restore coastal wetlands. A key question guiding assessment is whether created coastal salt marshes have similar biodiversity to preexisting, reference marshes. However, the numerous biodiversity metrics used to make these determinations are typically scale dependent and often conflicting. Here, we applied ecological theory to compare the diversity of different assemblages (surface and below-surface soil microbes, plants, macroinfauna, spiders, and on-marsh and off-marsh nekton) between two created marshes (4–6 years old) and four reference marshes. We also quantified the scale-dependent effects of species abundance distribution, aggregation, and density on richness differences and explored differences in species composition. Total, between-sample, and within-sample diversity (γ, β, and α, respectively) were not consistently lower at created marshes. Richness decomposition varied greatly among assemblages and marshes (e.g., soil microbes showed high equitability and α diversity, but plant diversity was restricted to a few dominant species with high aggregation). However, species abundance distribution, aggregation, and density patterns were not directly associated with differences between created and reference marshes. One exception was considerably lower density for macroinfauna at one of the created marshes, which was drier because of being at a higher elevation and having coarser substrate compared with the other marshes. The community compositions of created marshes were more dissimilar than reference marshes for microbe and macroinfauna assemblages. However, differences were small, particularly for microbes. Together, our results suggest generally similar taxonomic diversity and composition between created and reference marshes. This provides support for the creation of marsh habitat as tools for the maintenance and restoration of coastal biodiversity. However, caution is needed when creating marshes because specific building and restoration plans may lead to different colonization patterns

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Global Change Could Amplify Fire Effects on Soil Greenhouse Gas Emissions

Background: Little is known about the combined impacts of global environmental changes and ecological disturbances on ecosystem functioning, even though such combined impacts might play critical roles in shaping ecosystem processes that can in turn feed back to climate change, such as soil emissions of greenhouse gases.[br/] Methodology/Principal Findings: We took advantage of an accidental, low-severity wildfire that burned part of a long-term global change experiment to investigate the interactive effects of a fire disturbance and increases in CO(2) concentration, precipitation and nitrogen supply on soil nitrous oxide (N(2)O) emissions in a grassland ecosystem. We examined the responses of soil N(2)O emissions, as well as the responses of the two main microbial processes contributing to soil N(2)O production - nitrification and denitrification - and of their main drivers. We show that the fire disturbance greatly increased soil N(2)O emissions over a three-year period, and that elevated CO(2) and enhanced nitrogen supply amplified fire effects on soil N(2)O emissions: emissions increased by a factor of two with fire alone and by a factor of six under the combined influence of fire, elevated CO(2) and nitrogen. We also provide evidence that this response was caused by increased microbial denitrification, resulting from increased soil moisture and soil carbon and nitrogen availability in the burned and fertilized plots. [br/] Conclusions/Significance: Our results indicate that the combined effects of fire and global environmental changes can exceed their effects in isolation, thereby creating unexpected feedbacks to soil greenhouse gas emissions. These findings highlight the need to further explore the impacts of ecological disturbances on ecosystem functioning in the context of global change if we wish to be able to model future soil greenhouse gas emissions with greater confidence

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London