Metformin reduces airway glucose permeability and hyperglycaemia-induced Staphylococcus aureus load independently of effects on blood glucose

Background Diabetes is a risk factor for respiratory infection, and hyperglycaemia is associated with increased glucose in airway surface liquid and risk of Staphylococcus aureus infection. Objectives To investigate whether elevation of basolateral/blood glucose concentration promotes airway Staphylococcus aureus growth and whether pretreatment with the antidiabetic drug metformin affects this relationship. Methods Human airway epithelial cells grown at air–liquid interface (±18 h pre-treatment, 30 μM–1 mM metformin) were inoculated with 5×105 colony-forming units (CFU)/cm2 S aureus 8325-4 or JE2 or Pseudomonas aeruginosa PA01 on the apical surface and incubated for 7 h. Wild-type C57BL/6 or db/db (leptin receptor-deficient) mice, 6–10 weeks old, were treated with intraperitoneal phosphate-buffered saline or 40 mg/kg metformin for 2 days before intranasal inoculation with 1×107 CFU S aureus. Mice were culled 24 h after infection and bronchoalveolar lavage fluid collected. Results Apical S aureus growth increased with basolateral glucose concentration in an in vitro airway epithelia–bacteria co-culture model. S aureus reduced transepithelial electrical resistance (RT) and increased paracellular glucose flux. Metformin inhibited the glucose-induced growth of S aureus, increased RT and decreased glucose flux. Diabetic (db/db) mice infected with S aureus exhibited a higher bacterial load in their airways than control mice after 2 days and metformin treatment reversed this effect. Metformin did not decrease blood glucose but reduced paracellular flux across ex vivo murine tracheas. Conclusions Hyperglycaemia promotes respiratory S aureus infection, and metformin modifies glucose flux across the airway epithelium to limit hyperglycaemia-induced bacterial growth. Metformin might, therefore, be of additional benefit in the prevention and treatment of respiratory infection

Elevated Paracellular Glucose Flux across Cystic Fibrosis Airway Epithelial Monolayers Is an Important Factor for Pseudomonas aeruginosa Growth.

People with cystic fibrosis (CF) who develop related diabetes (CFRD) have accelerated pulmonary decline, increased infection with antibiotic-resistant Pseudomonas aeruginosa and increased pulmonary exacerbations. We have previously shown that glucose concentrations are elevated in airway surface liquid (ASL) of people with CF, particularly in those with CFRD. We therefore explored the hypotheses that glucose homeostasis is altered in CF airway epithelia and that elevation of glucose flux into ASL drives increased bacterial growth, with an effect over and above other cystic fibrosis transmembrane conductance regulator (CFTR)-related ASL abnormalities. The aim of this study was to compare the mechanisms governing airway glucose homeostasis in CF and non-CF primary human bronchial epithelial (HBE) monolayers, under normal conditions and in the presence of Ps. aeruginosa filtrate. HBE-bacterial co-cultures were performed in the presence of 5 mM or 15 mM basolateral glucose to investigate how changes in blood glucose, such as those seen in CFRD, affects luminal Ps. aeruginosa growth. Calu-3 cell monolayers were used to evaluate the potential importance of glucose on Ps. aeruginosa growth, in comparison to other hallmarks of the CF ASL, namely mucus hyperviscosity and impaired CFTR-dependent fluid secretions. We show that elevation of basolateral glucose promotes the apical growth of Ps. aeruginosa on CF airway epithelial monolayers more than non-CF monolayers. Ps. aeruginosa secretions elicited more glucose flux across CF airway epithelial monolayers compared to non-CF monolayers which we propose increases glucose availability in ASL for bacterial growth. In addition, elevating basolateral glucose increased Ps. aeruginosa growth over and above any CFTR-dependent effects and the presence or absence of mucus in Calu-3 airway epithelia-bacteria co-cultures. Together these studies highlight the importance of glucose as an additional factor in promoting Ps. aeruginosa growth and respiratory infection in CF disease

Circulating 250HD, dietary vitamin D, PTH, and calcium associations with incident cardiovascular disease and mortality: The MIDSPAN Family Study

<p>Context: Observational studies relating circulating 25-hydroxyvitamin D (25OHD) and dietary vitamin D intake to cardiovascular disease (CVD) have reported conflicting results.</p> <p>Objective: Our objective was to investigate the association of 25OHD, dietary vitamin D, PTH, and adjusted calcium with CVD and mortality in a Scottish cohort.</p> <p>Design and Setting: TheMIDSPAN Family Study is a prospective study of 1040 men and 1298 women from the West of Scotland recruited in 1996 and followed up for a median 14.4 yr. Participants: Locally resident adult offspring of a general population cohort were recruited from 1972–1976.</p> <p>Main Outcome Measures: CVD events (n = 416) and all-cause mortality (n=100) were evaluated.</p> <p>Results: 25OHD was measured using liquid chromatography-tandem mass spectrometry in available plasma (n=2081). Median plasma 25OHD was 18.6 ng/ml, and median vitamin D intake was 3.2 µ g/d (128 IU/d). Vitamin D deficiency (25OHD<15 ng/ml) was present in 689 participants (33.1%). There was no evidence that dietary vitamin D intake, PTH, or adjusted calcium were associated with CVD events or with mortality. Vitamin D deficiency was not associated with CVD (fully adjusted hazard ratio=1.00; 95% confidence interval=0.77–1.31). Results were similar after excluding patients who reported an activity-limiting longstanding illness at baseline (18.8%) and those taking any vitamin supplements (21.7%). However, there was some evidence vitamin D deficiency was associated with all-cause mortality (fully adjusted hazard ratio=2.02; 95% confidence interval=1.17–3.51).</p> <p>Conclusion: Vitamin D deficiency was not associated with risk of CVD in this cohort with very low 25OHD. Future trials of vitamin D supplementation in middle-aged cohorts should be powered to detect differences inmortality outcomes as well as CVD.(J Clin EndocrinolMetab97: 0000 –0000, 2012)</p&gt

Developing an intervention to facilitate family communication about inherited genetic conditions, and training genetic counsellors in its delivery.

Many families experience difficulty in talking about an inherited genetic condition that affects one or more of them. There have now been a number of studies identifying the issues in detail, however few have developed interventions to assist families. The SPRinG collaborative have used the UK Medical Research Council's guidance on Developing and Evaluating Complex Interventions, to work with families and genetic counsellors (GCs) to co-design a psycho-educational intervention to facilitate family communication and promote better coping and adaptation to living with an inherited genetic condition for parents and their children (<18 years). The intervention is modelled on multi-family discussion groups (MFDGs) used in psychiatric settings. The MFDG was developed and tested over three phases. First focus groups with parents, young people, children and health professionals discussed whether MFDG was acceptable and proposed a suitable design. Using evidence and focus group data, the intervention and a training manual were developed and three GCs were trained in its delivery. Finally, a prototype MFDG was led by a family therapist and co-facilitated by the three GCs. Data analysis showed that families attending the focus groups and intervention thought MFDG highly beneficial, and the pilot sessions had a significant impact on their family' functioning. We also demonstrated that it is possible to train GCs to deliver the MFDG intervention. Further studies are now required to test the feasibility of undertaking a definitive randomised controlled trial to evaluate its effectiveness in improving family outcomes before implementing into genetic counselling practice.The National Institute of Health Research funded the study but any views expressed do not necessarily reflect those of the Authority. Funded by NIHR reference number: RP-DG-1211-10015

The Grizzly, February 17, 1989

Malicious Arson Attempt Suspected In Fire • Board of Dirs. Calls for Big, but Beneficial Bucks • Letter: Let\u27s Keep Campbell! • WVOU Far From FM Waves • Glastnost Russian Roulette? • Freeman Displays Her Patchwork • Grim: No Meal Like a Home Meal • Drug Awareness a Downer • Title in Sight • Wrestlers Cruising at Unprecedented 21-2 • \u27Nasts O.K. • Intro. to Judaism Offered • Women\u27s Indoor Crushes \u27Em • Men\u27s Track \u27Sloshing\u27 Along • Aquabears Paddlin\u27 Wellhttps://digitalcommons.ursinus.edu/grizzlynews/1229/thumbnail.jp

Bicycle Friendly Community Assessment Spring 2015

Completed by Cal Poly, San Luis Obispo City & Regional Planning students enrolled in a bicycle and pedestrian planning course (CRP 425), under the direction of Dr. William Riggs this report was designed to gather data in advance of the City of San Luis Obispo\u27s application to be a Bicycle Friendly Community. The report focuses on the key certification areas of Engineering, Education, Encouragement, Evaluation/Planning and Enforcement providing documentation for the City\u27s eventual application

Quality standards for the management of alcohol-related liver disease: consensus recommendations from the British Association for the Study of the Liver and British Society of Gastroenterology ARLD special interest group

Objective Alcohol-related liver disease (ALD) is the most common cause of liver-related ill health and liver-related deaths in the UK, and deaths from ALD have doubled in the last decade. The management of ALD requires treatment of both liver disease and alcohol use; this necessitates effective and constructive multidisciplinary working. To support this, we have developed quality standard recommendations for the management of ALD, based on evidence and consensus expert opinion, with the aim of improving patient care.Design A multidisciplinary group of experts from the British Association for the Study of the Liver and British Society of Gastroenterology ALD Special Interest Group developed the quality standards, with input from the British Liver Trust and patient representatives.Results The standards cover three broad themes: the recognition and diagnosis of people with ALD in primary care and the liver outpatient clinic; the management of acutely decompensated ALD including acute alcohol-related hepatitis and the posthospital care of people with advanced liver disease due to ALD. Draft quality standards were initially developed by smaller working groups and then an anonymous modified Delphi voting process was conducted by the entire group to assess the level of agreement with each statement. Statements were included when agreement was 85% or greater. Twenty-four quality standards were produced from this process which support best practice. From the final list of statements, a smaller number of auditable key performance indicators were selected to allow services to benchmark their practice and an audit tool provided.Conclusion It is hoped that services will review their practice against these recommendations and key performance indicators and institute service development where needed to improve the care of patients with ALD

Volatile metal emissions from volcanic degassing and lava–seawater interactions at Kīlauea Volcano, Hawai’i

Funder: EPSRC-CASE studentshipFunder: NERC studentshipFunder: Leverhulme Trust; doi: https://doi.org/10.13039/501100000275Funder: NERC-CASE studentshipFunder: Rolex InstituteAbstract: Volcanoes represent one of the largest natural sources of metals to the Earth’s surface. Emissions of these metals can have important impacts on the biosphere as pollutants or nutrients. Here we use ground- and drone-based direct measurements to compare the gas and particulate chemistry of the magmatic and lava–seawater interaction (laze) plumes from the 2018 eruption of Kīlauea, Hawai’i. We find that the magmatic plume contains abundant volatile metals and metalloids whereas the laze plume is further enriched in copper and seawater components, like chlorine, with volatile metals also elevated above seawater concentrations. Speciation modelling of magmatic gas mixtures highlights the importance of the S2− ligand in highly volatile metal/metalloid degassing at the magmatic vent. In contrast, volatile metal enrichments in the laze plume can be explained by affinity for chloride complexation during late-stage degassing of distal lavas, which is potentially facilitated by the HCl gas formed as seawater boils