Explore the vast range of titles available.

Increased sedentariness has been linked to the growing prevalence of obesity in children, but some longitudinal studies suggest that sedentariness may be a consequence rather than a cause of increased adiposity. We used Mendelian randomization to examine the causal relations between body mass index (BMI) and objectively assessed sedentary time and physical activity in 3-8 year-old children from one Finnish and two Danish cohorts [NTOTAL =679]. A genetic risk score (GRS) comprised of 15 independent genetic variants associated with childhood BMI was used as the instrumental variable to test causal effects of BMI on sedentary time, total physical activity, and moderate-to-vigorous physical activity (MVPA). In fixed effects meta-analyses, the GRS was associated with 0.05 SD/allele increase in sedentary time (P=0.019), but there was no significant association with total physical activity (beta=0.011 SD/allele, P=0.58) or MVPA (beta=0.001 SD/allele, P=0.96), adjusting for age, sex, monitor wear-time and first three genome-wide principal components. In two-stage least squares regression analyses, each genetically instrumented one unit increase in BMI z-score increased sedentary time by 0.47 SD (P=0.072). Childhood BMI may have a causal influence on sedentary time but not on total physical activity or MVPA in young children. Our results provide important insights into the regulation of movement behaviour in childhood.

Fetal intrauterine growth is influenced by complex interactions between the maternal genes, environment and fetal genes. The aim of this study was to assess the effect of GWAS-identified genetic variants associated with birth weight on intrauterine fetal growth in 665 children. Fetal growth was estimated by two-dimensional ultrasound scans at 20, 25 and 32 weeks of gestation and growth trajectories were modeled using mixed linear regression. A genetic risk score (GRS) of birth weight-raising variants was associated with intrauterine growth showing an attenuating effect on the unconditional daily reduction in proportional weight gain of 8.92 × 10 −6 percentage points/allele/day (p = 2.0 × 10 −4 ), corresponding to a mean difference of 410 g at 40 weeks of gestation between a child with lowest and highest GRS. Eight variants were independently associated with intrauterine growth throughout the pregnancy, while four variants were associated with fetal growth in the periods 20–25 or 25–32 weeks of gestation, indicating that some variants may act in specific time windows during pregnancy. Four of the intrauterine growth variants were associated with type 2 diabetes, hypertension or BMI in the UK Biobank, which may provide basis for further understanding of the link between intrauterine growth and later risk of metabolic disease.

The TCF7L2 rs7903146 T-allele shows the strongest association with type 2 diabetes (T2D) among common gene variants. The aim of this study was to assess circulating levels of metabolites following a meal test in individuals carrying the high risk rs790346 TT genotype (cases) and low-risk CC genotype (controls). Sixty-two men were recruited based on TCF7L2 genotype, 31 were TT carriers and 31 were age- and BMI-matched CC carriers. All participants consumed a test meal after 12 hours of fasting. Metabolites were measured using proton nuclear magnetic resonance (NMR) spectroscopy. Metabolomic profiling of TCF7L2 carriers were performed for 141 lipid estimates. TT carriers had lower fasting levels of L-VLDL-L (total lipids in large very low density lipoproteins, p = 0.045), L-VLDL-CE (cholesterol esters in large VLDL, p = 0.03), and L-VLDL-C (total cholesterol in large VLDL, p = 0.045) compared to CC carriers. Additionally, TT carriers had lower postprandial levels of total triglycerides (TG) (q = 0.03), VLDL-TG (q = 0.05, including medium, small and extra small, q = 0.048, q = 0.0009, q = 0.04, respectively), HDL-TG (triglycerides in high density lipoproteins q = 0.037) and S-HDL-TG (q = 0.00003). In conclusion, TT carriers show altered postprandial triglyceride response, mainly influencing VLDL and HDL subclasses suggesting a genotype-mediated effect on hepatic lipid regulation.

Summary Background Dislipidaemia and increased levels of apolipoprotein B (apoB) in individuals with obesity are risk factors for development of cardiovascular disease (CVD). The aim of this study was to investigate the effect of weight loss and weight maintenance with and without liraglutide treatment on plasma lipid profiles and apoB. Methods Fifty‐eight individuals with obesity (body mass index 34.5 ± 3.0 kg/m2 [mean ± SD]) were included in this study. After 8 weeks on a very low‐calorie diet (800 kcal/day), participants were randomized to weight maintenance with meal replacements with or without liraglutide (1.2 mg daily) for 1 year. Plasma samples from before and after weight loss and after 1 year of weight maintenance were subjected to nuclear magnetic resonance‐based lipidomics analysis. Results After an 8‐week low‐calorie diet, study participants lost 12.0 ± 2.9 kg (mean ± SD) of their body weight, which was reflected in their lipid profiles (80 out of 124 lipids changed significantly), including reduced levels of apoB, total cholesterol, free cholesterol, remnant cholesterol, triglycerides, low‐density lipoprotein and very low‐density lipoprotein subclasses. After 1 year of maintained weight loss, the majority of the lipids had returned to pre‐weight loss levels even though weight loss was successfully maintained in both groups. Interestingly, apoB levels remained low in the liraglutide treated group (apoB change: 0.03 ± 0.02 mmol/L, p = 0.4) in contrast to an increase in the control group (apoB change: 0.06 ± 0.07 mmol/L, p = 0.02). Conclusion An 8‐week low‐calorie diet, in individuals with obesity, reduced plasma levels of lipids and the atherogenic marker apoB. After 1 year of weight maintenance, only study participants treated with liraglutide maintained reduced levels of apoB, despite similar body weight maintenance. Treatment with liraglutide may therefore reduce apoB levels and thus reflect lower CVD risk. Including apoB measurements in clinical practice when monitoring patients with dislipidemia or CVD might prove to be useful.

Aging in place can be a challenge for seniors living in cities, where the infrastructure and associated services are typically designed for the working population to enhance efficiency and productivity. Through surveying community-dwelling seniors, we ask these research questions: How is the neighborhood environment related to the physical and mental health of seniors living in Hong Kong, Singapore, and Tokyo? How can we make cities more age-friendly to encourage aging in place? To answer these research questions, both observational and questionnaire surveys are used. Characteristics of the local neighborhood are captured by individual-based and general local characteristics. Multilevel analysis is used to disentangle the effects of factors operating at different spatial scales. A total of 687 seniors aged sixty-five and older living in Hong Kong, Singapore, and Tokyo in eleven residential neighborhood districts were recruited through local senior community centers. Based on the final models, 17.53 percent and 8.24 percent of the variance in the physical and mental health scores is across general neighborhoods, respectively, and the remaining is at the individual level, including individual-based neighborhood factors. Biological factors are not the most important. Instead, having a normal range of weight and the proper use of a walking aid can allow seniors, even of the oldest-old group of eighty-five and older, to be more active. Policy-wise, neighborhood factors should be carefully planned to promote seniors' health directly through enhancing walkability and fostering supportive peer groups and indirectly through encouraging a more active lifestyle. Promoting a walkable urban environment should be a priority area for supporting aging in place in cities.

Sponsorship promotes female entry and advancement through the surgical field, and can mitigate gender inequities that persist in the surgical field. 35 women in surgery, including 14 surgeons, 11 residents, and 10 fourth-year medical students, were interviewed from July 30, 2021 to August 18, 2021 at a single institution. All participants had provided or received sponsorship. Main themes included: (1) Evolving needs of sponsorship, (2) Decreased Access to Sponsorship as Career Level Advances, (3) Evolving importance of sponsorship, (4) Perceived limitations of receiving sponsorship, and (5) Perceived limitations of providing sponsorship. Faculty members most frequently reported barriers to both receiving and providing sponsorship. The lack of sponsorship for female faculty limits their ability to rise to organizational leadership, and consequently, their ability to sponsor others. Increasing access to sponsorship for female surgeons can help to bridge the gender gap in the surgical field. •Sponsorship plays a pivotal role for female career advancement within the surgical field.•There is decreased access to sponsorship for women in surgery as career level advances.•Female faculty reports lower levels of sponsorship than younger female surgical trainees.•Limited sponsorship for female faculty restricts their ability to sponsor others.•Appropriate sponsorship for women in surgery can improve gender equity in the surgical field.

Background Geriatric depression is a growing public health issue worldwide. This study aims at identifying the relevant neighbourhood attributes, separate from the individual-level characteristics, that are related to the onset of depressive disorders among the geriatric population. Methods This study adopts a structural equation modelling (SEM) approach to understand the effect of the neighbourhood environment on geriatric depression, as identified by data collected from community-dwelling elderly living in Hong Kong and Singapore. Using network buffers as the unit of analysis, different features of the neighbourhood environment are captured and analysed. SEM also examines the strength and direction of the relationships using different parameters at both the individual and neighbourhood levels, as well as the prevalence of depressive symptoms among the elderly. Results The total sample size is 347, with 173 and 174 elderly people in Hong Kong and Singapore respectively. The results show that in addition to one’s physical health status, both objective and subjective neighbourhood factors including the size of parks, land use mix, walkability, and connectivity are all statistically significant influential factors in geriatric depression. In particular, enhancing walkability and providing more parks at the neighbourhood level can bring mental health benefits. Conclusions Public health policy initiatives aimed at tackling geriatric depression can be achieved by adopting a holistic and integrative approach to better prepare the neighbourhood environment in an ageing society.

The effect of horticultural therapy (HT) on immune and endocrine biomarkers remains largely unknown. We designed a waitlist-control randomized controlled trial to investigate the effectiveness of HT in improving mental well-being and modulating biomarker levels. A total of 59 older adults was recruited, with 29 randomly assigned to the HT intervention and 30 to the waitlist control group. The participants attended weekly intervention sessions for the first 3 months and monthly sessions for the subsequent 3 months. Biological and psychosocial data were collected. Biomarkers included IL-1β, IL-6, sgp-130, CXCL12/SDF-1α, CCL-5/RANTES, BDNF (brain-derived neurotrophic factor), hs-CRP, cortisol and DHEA (dehydroepiandrosterone). Psychosocial measures examined cognitive functions, depression, anxiety, psychological well-being, social connectedness and satisfaction with life. A significant reduction in plasma IL-6 level (p = 0.02) was observed in the HT intervention group. For the waitlist control group, significant reductions in plasma CXCL12 (SDF-1α) (p = 0.003), CXCL5 (RANTES) (p = 0.05) and BDNF (p = 0.003) were observed. A significant improvement in social connectedness was also observed in the HT group (p = 0.01). Conclusion: HT, in reducing plasma IL-6, may prevent inflammatory disorders and through maintaining plasma CXCL12 (SDF-1α), may maintain hematopoietic support to the brain. HT may be applied in communal gardening to enhance the well-being of older adults.

This study assessed the clinical and economic burden of geographic atrophy (GA) using real-world data from elderly patients with Medicare Advantage plans in the United States. A retrospective cohort design of patients with GA only, GA + visual impairment (GA + VI), GA + blindness (GA + B), and patients without GA were identified using administrative healthcare claims data from Optum Clinformatics Data Mart. Inverse probability of treatment weighting controlled for confounding when comparing patients with GA only vs without GA, GA + VI vs GA only, and GA + B vs GA only. Endpoints included all-cause and ophthalmic condition-related healthcare resource utilization (HRU), injurious falls, and healthcare costs. HRU and injurious falls were assessed per-person-per-year and per 100 person-years, respectively. Cohorts were compared using rate ratios, 95% confidence intervals (CIs), and p-values from weighted Poisson regression models. Healthcare costs were evaluated per-person-per-year using mean cost differences, 95% CIs, and p-values from weighted linear regression. The study included 18,119 patients with GA only, 2,285 with GA + VI, 1,716 with GA + B, and 72,476 patients without GA. Higher rates of all-cause hospitalizations (RR [95% CI]: 1.08 [1.03, 1.12]), outpatient visits (1.08 [1.05, 1.10]), other visits (1.14 [1.08, 1.21]), and falls with head injuries (1.24 [1.05, 1.45]) were observed in patients with GA vs without GA (P<0.05). GA was associated with higher annual all-cause total healthcare costs, spending an average of $1,171 more after adjustment (P<0.05). Progression to GA + VI and GA + B was associated with a more pronounced burden. The clinical and economic burden of GA is substantial and escalates as the disease advances. These findings suggest early intervention aimed at slowing GA progression may help to mitigate the healthcare burden associated with advancement of GA to visual impairment and blindness.

Background Rett syndrome (RTT) is a neurodevelopmental disorder that almost exclusively affects females and is associated with high clinical burden. However, literature characterizing the real-world journey of patients with RTT is limited. This study provided an overview of the epidemiology, patient characteristics, clinical manifestations, healthcare resource utilization (HRU), costs, and treatment patterns of patients with RTT in the US. Methods IQVIA™ Medical Claims Data and Longitudinal Prescription Data (11/01/2016–10/31/2019) were used to identify female patients with RTT, with the first observed diagnosis defined as the index date. Annual incidence and prevalence of RTT were assessed over the entire study period; clinical manifestations, all-cause and RTT-related HRU and costs, and treatment patterns were evaluated during the observation period—from the index date to end of clinical activity or end of data availability, whichever occurred first. Results were further stratified into pediatric (< 18 years) and adult (≥ 18 years) subgroups. Results In 2019, prevalence and incidence of RTT was 0.32 and 0.23 per 10,000 enrollees, respectively. Among 5,940 female patients (pediatric: 3,078; adult: 2,862) with mean observation period of 2.04 years, the most prevalent clinical manifestations were neurological disorders (72.8%), gastrointestinal/nutritional disorders (41.9%), and orthopedic disorders (34.6%). The incidence rate of all-cause HRU was 44.43 visits per-patient-per-year and RTT-related HRU comprised 47% of all-cause HRU. Mean all-cause healthcare costs were $40,326 per-patient-per-year, with medical costs driven by home/hospice care visits, therapeutic services, outpatient visits, and inpatient visits. RTT-related healthcare costs comprised 45% of all-cause healthcare costs. The most prevalent supportive therapy and pharmacologic agent were feeding assistance (37.9%) and antiepileptic drugs (54.8%), respectively. Trends were similar by subgroup; although, rates of HRU were generally higher among pediatric patients relative to adult patients (all-cause: 52.43 and 35.86, respectively), which translated into higher mean healthcare costs (all-cause: $45,718 and $34,548, respectively). Conclusions Patients with RTT have substantial disease burden, including prevalent clinical manifestations, high rates of HRU and annual healthcare costs, and reliance on pharmacologic and supportive therapies. These findings underscore the unmet need for effective therapies to target the multifactorial manifestations of RTT.