Fit for Life: Educating About a Healthy Lifestyle in Omaha Elementary Schools

Background: The prevalence of childhood obesity is increasing across the country. Health education at a young age is critical for children to establish healthy habits. The Fit for Life program is put together by Creighton medical students to inspire elementary students to lead a healthy lifestyle. The curriculum integrates physical exercise, real organ demonstrations, emotional wellness exercises, and nutritious meal building to model and encourage healthy habits. Methods: Over four weeks, medical students taught the 4th and 5th graders of two Omaha schools over live video while they followed along with hands-on activities. Before and after the program, students’ height and weight were measured to calculate BMI, and the students completed pre- and post-program quizzes. Paired t-tests were performed to analyze differences in student BMIs and quiz scores. Pre-program quiz scores of students who completed two consecutive years were compared using paired t-tests. Results: Student BMIs before and after the program showed no significant changes (p = 0.479, n = 45) however, quiz scores significantly improved after the program (p \u3c 0.001, n = 44). Self-reported survey responses after the program demonstrate increased motivation for a healthy lifestyle as well as improved understanding of the importance of sleep, exercise, reduced screen time, and healthy eating. Those who completed the program for two consecutive years had significantly higher pre-program quiz scores the second year (p \u3c 0.05, n = 18). Conclusion: Our study found a significant increase in pre- and post-program assessment scores which suggest improvement in student perspective and knowledge of healthy habits. Similarly, students who completed the program for two consecutive years demonstrated an increase in pre-program quiz scores suggesting retention of health knowledge. While there was no significant difference in pre- and post-program BMIs, results may be limited by the duration of the study, given that changes in weight are often insubstantial in the short-term.https://digitalcommons.unmc.edu/chri_forum/1006/thumbnail.jp

A genome-wide association study identifies protein quantitative trait loci (pQTLs)

There is considerable evidence that human genetic variation influences gene expression. Genome-wide studies have revealed that mRNA levels are associated with genetic variation in or close to the gene coding for those mRNA transcripts - cis effects, and elsewhere in the genome - trans effects. The role of genetic variation in determining protein levels has not been systematically assessed. Using a genome-wide association approach we show that common genetic variation influences levels of clinically relevant proteins in human serum and plasma. We evaluated the role of 496,032 polymorphisms on levels of 42 proteins measured in 1200 fasting individuals from the population based InCHIANTI study. Proteins included insulin, several interleukins, adipokines, chemokines, and liver function markers that are implicated in many common diseases including metabolic, inflammatory, and infectious conditions. We identified eight Cis effects, including variants in or near the IL6R (p = 1.8×10 -57), CCL4L1 (p = 3.9×10-21), IL18 (p = 6.8×10-13), LPA (p = 4.4×10-10), GGT1 (p = 1.5×10-7), SHBG (p = 3.1×10-7), CRP (p = 6.4×10-6) and IL1RN (p = 7.3×10-6) genes, all associated with their respective protein products with effect sizes ranging from 0.19 to 0.69 standard deviations per allele. Mechanisms implicated include altered rates of cleavage of bound to unbound soluble receptor (IL6R), altered secretion rates of different sized proteins (LPA), variation in gene copy number (CCL4L1) and altered transcription (GGT1). We identified one novel trans effect that was an association between ABO blood group and tumour necrosis factor alpha (TNF-alpha) levels (p = 6.8×10-40), but this finding was not present when TNF-alpha was measured using a different assay , or in a second study, suggesting an assay-specific association. Our results show that protein levels share some of the features of the genetics of gene expression. These include the presence of strong genetic effects in cis locations. The identification of protein quantitative trait loci (pQTLs) may be a powerful complementary method of improving our understanding of disease pathways. © 2008 Melzer et al

Hypothermia and Fever After Organophosphorus Poisoning in Humans—A Prospective Case Series

There have been many animal studies on the effects of organophosphorus pesticide (OP) poisoning on thermoregulation with inconsistent results. There have been no prospective human studies. Our aim was to document the changes in body temperature with OP poisoning. A prospective study was conducted in a rural hospital in Polonnaruwa, Sri Lanka. We collected data on sequential patients with OP poisoning and analyzed 12 patients selected from 53 presentations who had overt signs and symptoms of OP poisoning and who had not received atropine prior to arrival. All patients subsequently received specific management with atropine and/or pralidoxime and general supportive care. Tympanic temperature, ambient temperature, heart rate, and clinical examination and interventions were recorded prospectively throughout their hospitalization. Initial hypothermia as low as 32°C was observed in untreated patients. Tympanic temperature increased over time from an early hypothermia (<35°C in 6/12 patients) to later fever (7/12 patients >38°C at some later point). While some of the late high temperatures occurred in the setting of marked tachycardia, it was also apparent that in some cases fever was not accompanied by tachycardia, making excessive atropine or severe infection an unlikely explanation for all the fevers. In humans, OP poisoning causes an initial hypothermia, and this is followed by a period of normal to high body temperature. Atropine and respiratory complications may contribute to fever but do not account for all cases

AVURT: aspirin versus placebo for the treatment of venous leg ulcers a Phase II pilot randomised controlled trial

Background Venous leg ulcers (VLUs) are the most common cause of leg ulceration, affecting 1 in 100 adults. VLUs may take many months to heal (25% fail to heal). Estimated prevalence is between 1% and 3% of the elderly population. Compression is the mainstay of treatment and few additional therapies exist to improve healing. Two previous trials have indicated that low-dose aspirin, as an adjunct to standard care, may improve healing time, but these trials were insufficiently robust. Aspirin is an inexpensive, widely used medication but its safety and efficacy in the treatment of VLUs remains to be established. Objectives Primary objective – to assess the effects of 300 mg of aspirin (daily) versus placebo on the time to healing of the reference VLU. Secondary objectives – to assess the feasibility of leading into a larger pragmatic Phase III trial and the safety of aspirin in this population. Design A multicentred, pilot, Phase II randomised double-blind, parallel-group, placebo-controlled efficacy trial. Setting Community leg ulcer clinics or services, hospital outpatient clinics, leg ulcer clinics, tissue viability clinics and wound clinics in England, Wales and Scotland. Participants Patients aged ≥ 18 years with a chronic VLU (i.e. the VLU is > 6 weeks in duration or the patient has a history of VLU) and who are not regularly taking aspirin. Interventions 300 mg of daily oral aspirin versus placebo. All patients were offered care in accordance with Scottish Intercollegiate Guidelines Network (SIGN) guidance with multicomponent compression therapy aiming to deliver 40 mmHg at the ankle when possible. Randomisation Participants were allocated in a 1 : 1 (aspirin : placebo) ratio by the Research Pharmacy, St George’s University Hospitals NHS Foundation Trust, using a randomisation schedule generated in advance by the investigational medicinal product manufacturer. Randomisation was stratified according to ulcer size (≤ 5cm2 or > 5cm2). Main outcome measure The primary outcome was time to healing of the largest eligible ulcer (reference ulcer). Feasibility results – recruitment 27 patients were recruited from eight sites over a period of 8 months. The target of 100 patients was not achieved and two sites did not recruit. Barriers to recruitment included a short recruitment window and a large proportion of participants failing to meet the eligibility criteria. Results The average age of the 27 randomised participants (placebo, n = 13; aspirin, n = 14) was 62 years (standard deviation 13 years), and two-thirds were male (n = 18). Participants had their reference ulcer for a median of 15 months, and the median size of ulcer was 17.1 cm2. There was no evidence of a difference in time to healing of the reference ulcer between groups in an adjusted analysis for log-ulcer area and duration (hazard ratio 0.58, 95% confidence interval 0.18 to 1.85; p = 0.357). One expected, related serious adverse event was recorded for a participant in the aspirin group. Limitations The trial under-recruited because many patients did not meet the eligibility criteria. Conclusions There was no evidence that aspirin was efficacious in hastening the healing of chronic VLUs. It can be concluded that a larger Phase III (effectiveness) trial would not be feasible. Trial registration Clinical Trials.gov NCT02333123; European Clinical Trials Database (EudraCT) 2014-003979-39. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 55. See the NIHR Journals Library website for further project information

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication