Genetic Associations of Type 2 Diabetes with Islet Amyloid Polypeptide Processing and Degrading Pathways in Asian Populations

10.1371/journal.pone.0062378PLoS ONE86

Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population.

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (Pinteraction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications

Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (P interaction  = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications

Sleep and Obesity

Rising global prevalence and incidence of obesity lead to increased cardiovascular-renal complications and cancers. Epidemiological studies reported a worldwide trend towards suboptimal sleep duration and poor sleep quality in parallel with this obesity epidemic. From rodents and human models, it is highly plausible that abnormalities in sleep, both quantity and quality, impact negatively on energy metabolism. While excess dietary intake and physical inactivity are the known drivers of the obesity epidemic, promotion of healthy sleep habits has emerged as a new target to combat obesity. In this light, present review focuses on the existing literature examining the relationship between sleep physiology and energy homeostasis. Notably, sleep dysregulation perturbs the metabolic milieu via alterations in hormones such as leptin and ghrelin, eating behavior, neuroendocrine and autonomic nervous systems. In addition, shift work and trans-meridian air travel may exert a negative influence on the hypothalamic-pituitary-adrenal axis and trigger circadian misalignment, leading to impaired glucose tolerance and increased fat accumulation. Amassing evidence has also suggested that uncoupling of the circadian clock can increase the risk of adverse metabolic health. Given the importance of sleep in maintaining energy homeostasis and that it is potentially modifiable, promoting good sleep hygiene may create new avenues for obesity prevention and treatment

Unplanned Admission After Day-case Haemorrhoidectomy: A Retrospective Study

To identify the risk factors associated with unplanned admission after day-case haemorrhoidectomy. Methods: This was a retrospective review of the outcomes of patients who underwent elective, intended day-case haemorrhoidectomy in a surgical institution between January 2005 and December 2009. Data were generated from a computerized database. Information on patient demographics, type of surgery, mode of anaesthesia, operative time, operation end time, and perioperative drugs were collected and analysed. Unplanned admission was carefully recorded. Results: In a 5-year period, 243 patients underwent intended day-case haemorrhoidectomy. Of these, 43 (17.7%) had unplanned admission, with acute urinary retention as the most common cause (n = 30). Using univariate analysis, male gender, the use of spinal anaesthesia, and a late operation end time of after 2 PM were found to be positive risk factors associated with unplanned admission, whereas the use of single-dose dexamethasone during induction was identified as having a negative effect on unplanned admission. However, multivariate analysis showed that only male gender, the use of spinal anaesthesia, and a late operation end time of after 2 PM were independent risk factors. Conclusion: Good operation listing and the use of general anaesthesia are recommended in the practice of day-case haemorrhoidectomy

The effect of weekend and holiday sleep compensation on childhood overweight and obesity

OBJECTIVES: A growing trend in childhood sleep habits is to compensate for the weekday sleep deficit by longer weekend and holiday sleep duration. We aimed to investigate the effect of weekend/holiday sleep compensation in relation to childhood overweight and obesity. METHODS: This is a community-based cross-sectional study with 5159 children (49.6% boys), mean age of 9.25 years (SD: 1.78), from 13 primary schools in Hong Kong. Data on sleep patterns, lifestyle, body weight, and height of children were obtained from questionnaires. Sleep durations during weekdays, weekends, and holidays were predictor variables. BMI z scores and obesity/overweight status were the outcome measures. RESULTS: Children slept significantly longer during holidays (mean [SD]: 10.20 (0.92) hours) and weekends (school terms) (10.07 [0.93] hours) than during school weekdays (9.18 [0.95] hours). Children with shorter sleep duration had higher BMI z scores regardless of the sleep parameters used in the analysis. Among children who slept <8 hours during weekdays, those children who did not compensate for their sleep deficit during weekends or holidays had significantly increased risk of overweight/obesity compared with those children with sleep compensation (odds ratios: 2.59 [95% confidence interval: 1.22-5.48] and 2.32 [95% confidence interval: 1.00 -5.53], respectively). CONCLUSIONS: There was a prominent difference in sleep duration between weekdays and weekends/holidays among school children. Short sleep duration was associated with higher BMI, but compensation of sleep during weekends/holidays may partly ameliorate the risk of childhood overweight/obesity. Further prospective and interventional study is needed to delineate the risk-benefit effect of these increasingly common sleep habits among children and adolescents. Copyright © 2009 by the American Academy of Pediatrics.Link_to_subscribed_fulltex

Restless legs symptoms in adolescents: Epidemiology, heritability, and pubertal effects

Aims: We aimed to determine the prevalence, pubertal effect, familial aggregation, and heritability of restless legs (RLS) symptoms in Chinese adolescents. In addition, the correlates and consequences of RLS symptoms were examined. Methods: This was a population-based family study that involved 1549 adolescents (probands), their parents and siblings. RLS symptoms were assessed by a single question measuring the core features of RLS. Subjects with RLS symptoms for at least once per week were considered as abnormal. Impairment of daytime functions, behavioral problems, health status, and lifestyle practice were also documented. Results: The prevalence of RLS symptoms was 2.8% in adolescents and 7.4% in their parents with female preponderance. Gender difference of RLS symptoms emerged in mid-pubertal adolescents (Tanner stage 3 or above). RLS symptoms were closely associated with various sleep problems (range of ORs=2.24 to 32.5, p<0.05), except habitual snoring. They were also independently associated with impairment of daytime functions, poor general health and frequent temper outbursts but not caffeine or alcohol intake or cigarette smoking after adjustment for age, sex, and other comorbid sleep problems. RLS symptoms presented with a modest familial aggregation and heritability (h2±SE=0.17±0.04, p<0.001).Interpretation. RLS symptoms are common in Chinese adolescents with significant health repercussions. Puberty plays a critical role in the emergence of gender difference of RLS symptoms, which are accounted for by both genetic and environmental factors. © 2013 Elsevier Inc.Link_to_subscribed_fulltex

Generation of a Bag1 homozygous knockout mouse embryonic stem cell line using CRISPR/Cas9

Bag1 transcribes a multifunctional protein that participates in many important biological processes such as cell apoptosis, proliferation, differentiation and embryo development. Despite numerous published studies, the role of Bag1 in the context of embryonic stem (ES) cells, has not been explored. To investigate the function of Bag1 in ES cells, we generated mutant Bag1−/− ES cells using the CRISPR/Cas9 system. We established that the Bag1 double knockout ES cell line maintained their pluripotency, possessed a normal karyotype and the ability to differentiate into all three germ layers

基础胰岛素治疗2型糖尿病的有效性、安全性、初始最佳剂量和最佳维持剂量范围:一项meta分析的系统综述

Abstract Aims To investigate the effectiveness, safety, optimal starting dose, optimal maintenance dose range, and target fasting plasma glucose of five basal insulins in insulin‐naïve patients with type 2 diabetes mellitus. Methods MEDLINE, EMBASE, Web of Science, and the Cochrane Library were searched from January 2000 to February 2022. The Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines were followed and the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach was adopted. The registration ID is CRD42022319078 in PROSPERO. Results Among 11 163 citations retrieved, 35 publications met the planned criteria. From meta‐analyses and network meta‐analyses, we found that when injecting basal insulin regimens at bedtime, the optimal choice in order of most to least effective might be glargine U‐300 or degludec U‐100, glargine U‐100 or detemir, followed by neutral protamine hagedorn (NPH). Injecting glargine U‐100 in the morning may be more effective (ie, more patients archiving glycated hemoglobin < 7.0%) and lead to fewer hypoglycemic events than injecting it at bedtime. The optimal starting dose for the initiation of any basal insulins can be 0.10–0.20 U/kg/day. There is no eligible evidence to investigate the optimal maintenance dose for basal insulins. Conclusions The five basal insulins are effective for the target population. Glargine U‐300, degludec U‐100, glargine U‐100, and detemir lead to fewer hypoglycemic events than NPH without compromising glycemic control