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a theoretical framework based on our results and recent literature to explain how B. subtilis manages biofilm-bound Fe and Fe uptake in response to environmental Fe availability. These results provide important insights into the management of biofilm-bound and environmental Fe by B. subtilis in response to Fe stress.Class IIa bacteriocin antimicrobial peptides (AMPs) are a compelling alternative to current antimicrobials because of potential specific activity toward antibiotic-resistant bacteria, including vancomycin-resistant enterococci. Engineering of these molecules would be enhanced by a better understanding of AMP sequence-activity relationships to improve efficacy in vivo and limit effects of off-target activity. Toward this goal, we experimentally evaluated 210 natural and variant class IIa bacteriocins for antimicrobial activity against six strains of enterococci. Inhibitory activity was ridge regressed to AMP sequence to predict performance, achieving an area under the curve of 0.70 and demonstrating the potential of statistical models for identifying and designing AMPs. Active AMPs were individually produced and evaluated against eight enterococcus strains and four Listeria strains to elucidate trends in susceptibility. It was determined that the mannose phosphotransferase system (manPTS) sequence is informatih targeting of the mannose phosphotransferase system (manPTS) of a subset of Gram-positive bacteria, although factors affecting this mechanism are not entirely understood. Peptides identified from genomic data, as well as variants of previously characterized AMPs, can offer insight into how peptide sequence affects activity and selectivity. The experimental methods presented here identify promising potent and selective bacteriocins for further evaluation, highlight the potential of simple computational modeling for prediction of AMP performance, and demonstrate that factors beyond manPTS sequence affect bacterial susceptibility to class IIa bacteriocins.

Low back pain, and especially non-specific low back pain, is a common cause of presentation to the emergency department (ED). Although these patients typically report relatively high pain intensity, the clinical course of their pain and disability remains unclear. Our objective was to review the literature and describe the clinical course of non-specific low back pain after an ED visit.

Electronic searches were conducted using MEDLINE, CINAHL and EMBASE from inception to March 2019. We screened for cohort studies or randomised trials investigating pain or disability in patients with non-specific low back pain presenting to EDs. We excluded studies that enrolled participants with minimal pain or disability scores at baseline. Two reviewers independently screened the full texts, extracted the data and assessed risk of bias and quality of evidence. Estimates of pain and disability were converted to a common 0-100 scale. We estimated pooled means and 95% CIs of pain and disability as a function of time since cate patients so they can have realistic expectations of their recovery.The gastrointestinal tract is often considered as a key organ involved in the digestion of food and providing nutrients to the body for proper maintenance. However, this system is composed of organs that are extremely complex. Among the different parts, the intestine is viewed as an incredible surface of contact with the environment and is colonised by hundreds of trillions of gut microbes. The role of the gut barrier has been studied for decades, but the exact mechanisms involved in the protection of the gut barrier are various and complementary. Among them, the integrity of the mucus barrier is one of the first lines of protection of the gastrointestinal tract. In the past, this 'slimy' partner was mostly considered a simple lubricant for facilitating the progression of the food bolus and the stools in the gut. Since then, different researchers have made important progress, and currently, the regulation of this mucus barrier is gaining increasing attention from the scientific community. Among the factors influencing the mucus barrier, the microbiome plays a major role in driving mucus changes. Additionally, our dietary habits (ie, high-fat diet, low-fibre/high-fibre diet, food additives, pre- probiotics) influence the mucus at different levels. Given that the mucus layer has been linked with the appearance of diseases, proper knowledge is highly warranted. Here, we debate different aspects of the mucus layer by focusing on its chemical composition, regulation of synthesis and degradation by the microbiota as well as some characteristics of the mucus layer in both physiological and pathological situations.The clinical false negative rate of reverse transcriptase polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 on a single upper respiratory tract sample was calculated using convalescent antibody testing as a comparator. The sensitivity in symptomatic individuals was 86.2% (25/29). Of the missed cases, one (3.5%) was detected by repeat RT-PCR, one by CT thorax and two (7.1%) by convalescent antibody. The clinical false negative rate of a single RT-PCR on an upper respiratory tract sample of 14% in symptomatic patients is reassuring when compared to early reports. This report supports a strategy of combining repeat swabbing, use of acute and convalescent antibody testing and CT thorax for COVID-19 diagnosis.The logistical challenges of rapidly and accurately identifying those patients who needed to shield during the COVID-19 pandemic were unprecedented. We report our experiences of meeting this challenge for >9,000 patients with rheumatic and musculoskeletal disease at our centre, incorporating an element of guided patient self-stratification. Our results indicate that patients are able to stratify their own risk accurately using the BSR COVID-19 risk stratification guidance.Modern antiretroviral therapies (ART) have decreased the prevalence of HIV-associated nephropathy (HIVAN). Nonetheless, we continue to see children and adolescents with HIVAN all over the world. Furthermore, once HIVAN is established in children, it is difficult to revert its long-term progression, and we need better animal models of childhood HIVAN to test new treatments. To define whether the HIV-1 trans-activator (Tat) gene precipitates HIVAN in young mice, and to develop an inducible mouse model of childhood HIVAN, an HIV-Tat gene cloned from a child with HIVAN was used to generate recombinant adenoviral vectors (rAd-Tat). rAd-Tat and LacZ control vectors (2×109) were expressed in the kidney of newborn wild-type and HIV-transgenic (Tg26) FVB/N mice without significant proteinuria (n=5; 8 per group). Mice were sacrificed 7 and 35 days later to assess their renal outcome, the expression of HIV-genes and growth factors, and markers of cell growth and differentiation by RT-qPCR, immunohistochemistry and/or western blots. HIV-Tat induced the expression of HIV-1 genes and heparin-binding growth factors in the kidney of HIV-Tg26 mice, and precipitated HIVAN in the first month of life. No significant renal changes were detected in wild-type mice infected with rAd-Tat vectors, suggesting that HIV-Tat alone does not induce renal disease. This new mouse model of childhood HIVAN highlights the critical role that HIV-Tat plays in the pathogenesis of HIVAN, and could be used to study the pathogenesis and treatment of HIVAN in children and adolescents.Globally, unintentional injuries contribute significantly to disability and death. Prevention efforts have traditionally focused on individual injury mechanisms and their specific risk factors, which has resulted in slow progress in reducing the burden. The Sustainable Development Goals (SDGs) represent a global agenda for promoting human prosperity while respecting planetary boundaries. While injury prevention is currently only recognised in the SDG agenda via two road safety targets, the relevance of the SDGs for injury prevention is much broader. In this State of the Art Review, we illustrate how unintentional injury prevention efforts can be advanced substantially within a broad range of SDG goals and advocate for the integration of safety considerations across all sectors and stakeholders. This review uncovers injury prevention opportunities within broader global priorities such as urbanisation, population shifts, water safeguarding and corporate social responsibility. We demonstrate the relevance of injury prevention efforts to the SDG agenda beyond the health goal (SDG 3) and the two specific road safety targets (SDG 3.6 and SDG 11.2), highlighting 13 additional SDGs of relevance. We argue that all involved in injury prevention are at a critical juncture where we can continue with the status quo and expect to see more of the same, or mobilise the global community in an 'Injury Prevention in All Policies' approach.Collectively, the epidemic increases in the United States of opioid-related deaths and suicides during the first two decades of the 21st century have exposed shortcomings in current forensic and epidemiological approaches for determining and codifying manner of death-a vital function fulfilled by medical examiners, coroners and nosologists-the foundation for the National Violent Death Reporting System (NVDRS), an incident-based surveillance system providing individual-level information on decedent characteristics, manner, cause and circumstances of suicide, homicide and other violent injury deaths. Drug intoxication deaths are generally classified as 'accidents' or unintentional, a fundamental mischaracterisation; most arose from repetitive self-harm behaviours related to substance acquisition and misuse. Moreover, given the burden of affirmative evidence required to determine suicide, many of these 'accidents' likely reflected unrecognised intentional acts-that is, suicides. Addition of a simple checkbox for self-injury mortality on the death certificate would enrich the National Death Index and NVDRS, and in turn, inform prevention and clinical research, and enhance the evaluation of prevention programmes and therapeutic regimens.

Health and job satisfaction are key independent determinants of ability to work to older ages. We investigated the interaction of these two important factors on health-related job loss (HRJL) over 2 years of follow-up comparing male and female older workers.

A population sample of adults aged 50-64 years, recruited from 24 English general practices in the Health and Employment After Fifty (HEAF) study, completed questionnaires at baseline with follow-ups at 12 and 24 months. Multiple-record Cox proportional hazards models were performed to explore the main effects of, and potential interactions between, job satisfaction and self-rated health (SRH) as predictors of time to first HRJL.

Of the initial 8134 participants, 5143 were ever in work in the study period. Among men, 5.7% and 14.3% reported job dissatisfaction (those in good and poor SRH, respectively), while among women these percentages were 4.6 and 12.9. HRJL was reported by 106 men and 176 women. Men in good health dissatisfied with their job had a sixfold (HR=6.4; 95% CI 3.3 to 12.4) increased risk of HRJL compared with men satisfied with their job (significant multiplicative interaction). Women dissatisfied with their job were more likely to have an HRJL within 2 years of follow-up irrespective of their SRH.

SRH and job dissatisfaction have important individual effects on the risk of stopping work for health among older workers. These findings point to the importance of job satisfaction in reducing health-related exit from paid work among older workers.

SRH and job dissatisfaction have important individual effects on the risk of stopping work for health among older workers. These findings point to the importance of job satisfaction in reducing health-related exit from paid work among older workers.

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