Estimating dose—response relationships for vitamin D with coronary heart disease, stroke, and all-cause mortality: observational and revised Mendelian randomization analyses

Background Randomised trials of vitamin D supplementation for cardiovascular disease and all-cause mortality have generally reported null findings. However, generalisability of results to individuals with low vitamin D status is unclear. We aimed to characterise dose-response relationships between 25-hydroxyvitamin D (25[OH]D) concentrations and risk of coronary heart disease, stroke, and all-cause mortality in observational and Mendelian randomisation frameworks. Methods Observational analyses were undertaken using data from 33 prospective studies comprising 500 962 individuals with no known history of coronary heart disease or stroke at baseline. Mendelian randomisation analyses were performed in four population-based cohort studies (UK Biobank, EPIC-CVD, and two Copenhagen population-based studies) comprising 386 406 middle-aged individuals of European ancestries, including 33 546 people who developed coronary heart disease, 18 166 people who had a stroke, and 27 885 people who died. Primary outcomes were coronary heart disease, defined as fatal ischaemic heart disease (International Classification of Diseases 10th revision code I20-I25) or non-fatal myocardial infarction (I21-I23); stroke, defined as any cerebrovascular disease (I60-I69); and all-cause mortality. Findings Observational analyses suggested inverse associations between incident coronary heart disease, stroke, and all-cause mortality outcomes with 25(OH)D concentration at low 25(OH)D concentrations. In population-wide genetic analyses, there were no associations of genetically predicted 25(OH)D with coronary heart disease (odds ratio [OR] per 10 nmol/L higher genetically-predicted 25(OH)D concentration 0·98, 95% CI 0·95–1·01), stroke (1·01, [0·97–1·05]), or all-cause mortality (0·99, 0·95–1·02). Null findings were also observed in genetic analyses for cause-specific mortality outcomes, and in stratified genetic analyses for all outcomes at all observed levels of 25(OH)D concentrations. Interpretation Stratified Mendelian randomisation analyses suggest a lack of causal relationship for 25(OH)D concentrations with both cardiovascular and mortality outcomes for individuals at all levels of 25(OH)D. Our findings suggest that substantial reductions in mortality and cardiovascular morbidity due to long-term low-dose vitamin D supplementation are unlikely even if targeted at individuals with low vitamin D status

Extraction of β-Glucan from Oat Bran in Laboratory Scale

Effects of various enzymes and extraction conditions on yield and molecular weight of beta-glucans extracted from two batches of commercial oat bran produced in Sweden are reported. Hot-water extraction with a thermostable alpha-amylase resulted in an extraction yield of approximate to 76% of the beta-glucans, while the high peak molecular weight was maintained (1.6 x 10(6)). A subsequent protein hydrolysis significantly reduced the peak molecular weight of beta-glucans (by pancreatin to 908 x 10(3) and by papain to 56 x 10(3)). These results suggest that the protein hydrolyzing enzymes may not be pure enough for purifying beta-glucans. The isolation scheme consisted of removal of lipids with ethanol extraction, enzymatic digestion of starch with alpha-amylase, enzymatic digestion of protein using protease, centrifugation to remove insoluble material, removal of low molecular weight components using dialysis, precipitation of beta-glucans with ethanol, and air-drying

Extracellular matrix reinforced bioinks for 3D bioprinting human tissue

Recent advances in 3D bioprinting allow for generating intricate structures with dimensions relevant for human tissue, but suitable bioinks for producing translationally relevant tissue with complex geometries remain unidentified. Here, a tissue‐specific hybrid bioink is described, composed of a natural polymer, alginate, reinforced with extracellular matrix derived from decellularized tissue (rECM). rECM has rheological and gelation properties beneficial for 3D bioprinting while retaining biologically inductive properties supporting tissue maturation ex vivo and in vivo. These bioinks are shear thinning, resist cell sedimentation, improve viability of multiple cell types, and enhance mechanical stability in hydrogels derived from them. 3D printed constructs generated from rECM bioinks suppress the foreign body response, are pro‐angiogenic and support recipient‐derived de novo blood vessel formation across the entire graft thickness in a murine model of transplant immunosuppression. Their proof‐of‐principle for generating human tissue is demonstrated by 3D bioprinting human airways composed of regionally specified primary human airway epithelial progenitor and smooth muscle cells. Airway lumens remained patent with viable cells for one month in vitro with evidence of differentiation into mature epithelial cell types found in native human airways. rECM bioinks are a promising new approach for generating functional human tissue using 3D bioprinting

'The body gets used to them': patients' interpretations of antibiotic resistance and the implications for containment strategies.

Item does not contain fulltextBACKGROUND: Interventions promoting evidence based antibiotic prescribing and use frequently build on the concept of antibiotic resistance but patients and clinicians may not share the same assumptions about its meaning. OBJECTIVE: To explore patients' interpretations of 'antibiotic resistance' and to consider the implications for strategies to contain antibiotic resistance. DESIGN: Multi country qualitative interview study. PARTICIPANTS: One hundred and twenty-one adult patients from primary care research networks based in nine European countries who had recently consulted a primary care clinician with symptoms of Lower Respiratory Tract Infection (LRTI). APPROACH: Semi-structured interviews with patients following their consultation and subjected to a five-stage analytic framework approach (familiarization, developing a thematic framework from the interview questions and the themes emerging from the data, indexing, charting, and mapping to search for interpretations in the data), with local network facilitators commenting on preliminary reports. RESULTS: The dominant theme was antibiotic resistance as a property of a 'resistant human body', where the barrier to antibiotic effectiveness was individual loss of responsiveness. Less commonly, patients correctly conceptualized antibiotic resistance as a property of bacteria. Nevertheless, the over-use of antibiotics was a strong central concept in almost all patients' explanations, whether they viewed resistance as located in either the body or in bacteria. CONCLUSIONS: Most patients were aware of the link between antibiotic use and antibiotic resistance. The identification of the misinterpretation of antibiotic resistance as a property of the human body rather than bacterial cells could inform clearer clinician-patient discussions and public health interventions through emphasising the transferability of resistance, and the societal contribution individuals can make through more appropriate antibiotic prescribing and use.1 juli 201

Multiple Effects of Changes in Arctic Snow Cover

Snow cover plays a major role in the climate, hydrological and ecological systems of the Arctic and other regions through its influence on the surface energy balance (e.g. reflectivity), water balance (e.g. water storage and release), thermal regimes (e.g. insulation), vegetation and trace gas fluxes. Feedbacks to the climate system have global consequences. The livelihoods and well-being of Arctic residents and many services for the wider population depend on snow conditions so changes have important consequences. Already, changing snow conditions, particularly reduced summer soil moisture, winter thaw events and rain-on-snow conditions have negatively affected commercial forestry, reindeer herding, some wild animal populations and vegetation. Reductions in snow cover are also adversely impacting indigenous peoples' access to traditional foods with negative impacts on human health and well-being. However, there are likely to be some benefits from a changing Arctic snow regime such as more even run-off from melting snow that favours hydropower operations