Influence of Peri-duodenal Non-constrictive Cuff on the Body Weight of Rats

Background Weight loss has been found to improve or re- solve cardiovascular comorbidities. There is a significant need for reversible device approaches to weight loss. Methods Non-constrictive cuff (NCC) is made of implantable silicone rubber with an internal diameter greater than the duodenum. Ten or 11 NCC were individually mounted along the duodenum from the pyloric sphincter toward the distal duodenum to cover ~22 mm in the length. Twelve Wistar rats were implanted with NCC, and six served as sham, and both groups were observed over 4 months. Six rats with implant had their NCC removed and were observed for additional 4weeks. Results The food intake decreased from 40.1 to 28.1 g/day after 4 months of NCC implant. The body weight gain decreased from 1.76 to 0.46 g/day after 4 months of NCC implant. The fasting glucose decreased from 87.7 to 75.3 mg/ dl at terminal day. The duodenal muscle layer covered by the NCC increased from 0.133 to 0.334 mm. After 4 weeks of NCC removal, the food intake, body weight gain, and fasting glucose recovered to 36.2, 2.51 g/day, and 83.9 mg/dl. The duodenal muscle layer covered by the NCC decreased to 0.217 mm. Conclusion The NCC implant placed on the proximal duode- num is safe in rats for a 4-month period. The efficacy of the NCC implant is significant for decrease in food intake, body weight gain, and fasting glucose in a normal rat model. The removal of NCC implant confirmed a cause-effect relation with food intake and hence body weight

Distension-Induced Gastric Contraction is Attenuated in an Experimental Model of Gastric Restraint

Background Gastric distension has important implications for motility and satiety. The hypothesis of this study was that distension affects the amplitude and duration of gastric contraction and that these parameters are largely mediated by efferent vagus stimulation. Methods A novel isovolumic myograph was introduced to test these hypotheses. The isovolumic myograph isolates the stomach and records the pressure generated by the gastric contraction under isovolumic conditions. Accordingly, the phasic changes of gastric contractility can be documented. A group of 12 rats were used under in vivo conditions and isolated ex vivo conditions and with two different gastric restraints (small and large) to determine the effect of degree of restraint. Results The comparison of the in vivo and ex vivo contractility provided information on the efferent vagus mediation of gastric contraction, i.e., the in vivo amplitude and duration reached maximum of 12.6±2.7 mmHg and 19.8±5.6 s in contrast to maximum of 5.7±0.9 mmHg and 7.3±1.3 s in ex vivo amplitude and duration, respectively. The comparison of gastric restraint and control groups highlights the role of distension on in vivo gastric contractility. The limitation of gastric distension by restraint drastically reduced the maximal amplitude to below 2.9±0.2 mmHg. Conclusions The results show that distension-induced gastric contractility is regulated by both central nervous system and local mechanisms with the former being more substantial. Furthermore, the gastric restraint significantly attenuates gastric contractility (decreased amplitude and shortened duration of contraction) which is mediated by the efferent vagus activation. These findings have important implications for gastric motility and physiology and may improve our understanding of satiety

Influence of dietary protein on glomerular filtration before and after bariatric surgery: a cohort study

BACKGROUND: Obesity-associated elevations in glomerular filtration rate (GFR) are common and may play a role in the development of kidney disease, so identifying the underlying mechanism is important. We therefore studied whether reductions in dietary protein intake, which is known to modulate GFR, explain why GFR decreases after bariatric surgery-induced weight loss. STUDY DESIGN: Cohort study with participants as their own controls. SETTING & PARTICIPANTS: 8 severely obese patients with normal kidney function were recruited from bariatric surgery centers in Indianapolis, IN. All participants were placed on a fixed-protein (50-g/d) diet for 1 week before and after a minimum of a 20-kg weight loss by bariatric surgery and were followed up closely by dieticians for adherence. PREDICTOR: Ad lib versus low-protein diet before versus after bariatric surgery. OUTCOME: Measured GFR, using repeated-measures analysis, was used to estimate the independent effects of diet and surgery. MEASUREMENT: GFR was measured using plasma iohexol clearance. RESULTS: A median of 32.9 (range, 19.5-54.4)kg was lost between the first presurgery visit and first postsurgery visit. Dietetic evaluations and urinary urea excretion confirmed that patients generally adhered to the study diet. GFRs on an ad lib diet were significantly higher before compared to after surgery (GFR medians were 144 (range, 114-178) and 107 (range, 85-147) mL/min, respectively; P=0.01). Although bariatric surgery (-26mL/min; P=0.005) and dietary sodium intake (+7.5mL/min per 100mg of dietary sodium; P=0.001) both influenced GFR, consuming a low-protein diet did not (P=0.7). LIMITATIONS: Small sample size; mostly white women; possible lack of generalizability. CONCLUSIONS: The decrease in GFR observed after bariatric surgery is explained at least in part by the effects of surgery and/or dietary sodium intake, but not by low dietary protein consumption

Predicting the glomerular filtration rate in bariatric surgery patients

BACKGROUND/AIMS: Identifying the best method to estimate the glomerular filtration rate (GFR) in bariatric surgery patients has important implications for the clinical care of obese patients and research into the impact of obesity and weight reduction on kidney health. We therefore performed such an analysis in patients before and after surgical weight loss. METHODS: Fasting measured GFR (mGFR) by plasma iohexol clearance before and after bariatric surgery was obtained in 36 severely obese individuals. Estimated GFR was calculated using the Modification of Diet in Renal Disease equation, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation using serum creatinine only, the CKD-EPI equation using serum cystatin C only and a recently derived equation that uses both serum creatinine and cystatin C (CKD-EPIcreat-cystC) and then compared to mGFR. RESULTS: Participants were primarily middle-aged white females with a mean baseline body mass index of 46 ± 9, serum creatinine of 0.81 ± 0.24 mg/dl and mGFR of 117 ± 40 ml/min. mGFR had a stronger linear relationship with inverse cystatin C before (r = 0.28, p = 0.09) and after (r = 0.38, p = 0.02) surgery compared to the inverse of creatinine (before: r = 0.26, p = 0.13; after: r = 0.11, p = 0.51). mGFR fell by 17 ± 35 ml/min (p = 0.007) following surgery. The CKD-EPIcreat-cystC was unquestionably the best overall performing estimating equation before and after surgery, revealing very little bias and a capacity to estimate mGFR within 30% of its true value over 80% of the time. This was true whether or not mGFR was indexed for body surface area. CONCLUSIONS: In severely obese bariatric surgery patients with normal kidney function, cystatin C is more strongly associated with mGFR than is serum creatinine. The CKD-EPIcreat-cystC equation best predicted mGFR both before and after surgery

Metabolic improvements following Roux-en-Y surgery assessed by solid meal test in subjects with short duration type 2 diabetes

BACKGROUND: Glucose homeostasis improves within days following Roux-en-Y gastric bypass (RYGB) surgery. The dynamic metabolic response to caloric intake following RYGB has been assessed using liquid mixed meal tolerance tests (MMTT). Few studies have evaluated the glycemic and hormonal response to a solid mixed meal in subjects with diabetes prior to, and within the first month following RYGB. METHODS: Seventeen women with type 2 diabetes of less than 5 years duration participated. Fasting measures of glucose homeostasis, lipids and gut hormones were obtained pre- and post-surgery. MMTT utilizing a solid 4 oz chocolate pudding performed pre-, 2 and 4 weeks post-surgery. Metabolic response to 4 and 2 oz MMTT assessed in five diabetic subjects not undergoing surgery. RESULTS: Significant reductions in fasting glucose and insulin at 3 days, and in fasting betatrophin, triglycerides and total cholesterol at 2 weeks post-surgery. Hepatic insulin clearance was greater at 3 days post-surgery. Subjects exhibited less hunger and greater feelings of fullness and satisfaction during the MMTT while consuming 52.9 ± 6.5% and 51.0 ± 6.5% of the meal at 2 and 4 weeks post-surgery respectively. At 2 weeks post-surgery, glucose and insulin response to MMTT were improved, with greater GLP-1 and PYY secretion. Improved response to solid MMTT not replicated by consumption of smaller pudding volume in diabetic non-surgical subjects. CONCLUSIONS: With a test meal of size and composition representative of the routine diet of post-RYGB subjects, improved glycemic and gut hormone responses occur which cannot be replicated by reducing the size of the MMTT in diabetic subjects not undergoing surgery

Quantifying risks and interventions that have affected the burden of diarrhoea among children younger than 5 years : an analysis of the Global Burden of Disease Study 2017

Background Many countries have shown marked declines in diarrhoea! disease mortality among children younger than 5 years. With this analysis, we provide updated results on diarrhoeal disease mortality among children younger than 5 years from the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) and use the study's comparative risk assessment to quantify trends and effects of risk factors, interventions, and broader sociodemographic development on mortality changes in 195 countries and territories from 1990 to 2017. Methods This analysis for GBD 2017 had three main components. Diarrhoea mortality was modelled using vital registration data, demographic surveillance data, and verbal autopsy data in a predictive, Bayesian, ensemble modelling tool; and the attribution of risk factors and interventions for diarrhoea were modelled in a counterfactual framework that combines modelled population-level prevalence of the exposure to each risk or intervention with the relative risk of diarrhoea given exposure to that factor. We assessed the relative and absolute change in diarrhoea mortality rate between 1990 and 2017, and used the change in risk factor exposure and sociodemographic status to explain differences in the trends of diarrhoea mortality among children younger than 5 years. Findings Diarrhoea was responsible for an estimated 533 768 deaths (95% uncertainty interval 477 162-593 145) among children younger than 5 years globally in 2017, a rate of 78.4 deaths (70.1-87.1) per 100 000 children. The diarrhoea mortality rate ranged between countries by over 685 deaths per 100 000 children. Diarrhoea mortality per 100 000 globally decreased by 69.6% (63.1-74.6) between 1990 and 2017. Among the risk factors considered in this study, those responsible for the largest declines in the diarrhoea mortality rate were reduction in exposure to unsafe sanitation (13.3% decrease, 11.2-15.5), childhood wasting (9.9% decrease, 9.6-10.2), and low use of oral rehydration solution (6.9% decrease, 4-8-8-4). Interpretation Diarrhoea mortality has declined substantially since 1990, although there are variations by country. Improvements in sociodemographic indicators might explain some of these trends, but changes in exposure to risk factors-particularly unsafe sanitation, childhood growth failure, and low use of oral rehydration solution-appear to be related to the relative and absolute rates of decline in diarrhoea mortality. Although the most effective interventions might vary by country or region, identifying and scaling up the interventions aimed at preventing and protecting against diarrhoea that have already reduced diarrhoea mortality could further avert many thousands of deaths due to this illness

Quantifying risks and interventions that have affected the burden of lower respiratory infections among children younger than 5 years : an analysis for the Global Burden of Disease Study 2017

Background Despite large reductions in under-5 lower respiratory infection (LRI) mortality in many locations, the pace of progress for LRIs has generally lagged behind that of other childhood infectious diseases. To better inform programmes and policies focused on preventing and treating LRIs, we assessed the contributions and patterns of risk factor attribution, intervention coverage, and sociodemographic development in 195 countries and territories by drawing from the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) LRI estimates. Methods We used four strategies to model LRI burden: the mortality due to LRIs was modelled using vital registration data, demographic surveillance data, and verbal autopsy data in a predictive ensemble modelling tool; the incidence of LRIs was modelled using population representative surveys, health-care utilisation data, and scientific literature in a compartmental meta-regression tool; the attribution of risk factors for LRI mortality was modelled in a counterfactual framework; and trends in LRI mortality were analysed applying changes in exposure to risk factors over time. In GBD, infectious disease mortality, including that due to LRI, is among HIV-negative individuals. We categorised locations based on their burden in 1990 to make comparisons in the changing burden between 1990 and 2017 and evaluate the relative percent change in mortality rate, incidence, and risk factor exposure to explain differences in the health loss associated with LRIs among children younger than 5 years. Findings In 2017, LRIs caused 808 920 deaths (95% uncertainty interval 747 286-873 591) in children younger than 5 years. Since 1990, there has been a substantial decrease in the number of deaths (from 2 337 538 to 808 920 deaths; 65.4% decrease, 61.5-68.5) and in mortality rate (from 362.7 deaths [3304-392.0] per 100 000 children to 118.9 deaths [109.8-128.3] per 100 000 children; 67.2% decrease, 63.5-70.1). LRI incidence dedined globally (32.4% decrease, 27.2-37.5). The percent change in under-5 mortality rate and incidence has varied across locations. Among the risk factors assessed in this study, those responsible for the greatest decrease in under-5 LRI mortality between 1990 and 2017 were increased coverage of vaccination against Haemophilus influenza type b (11.4% decrease, 0.0-24.5), increased pneumococcal vaccine coverage (6.3% decrease, 6.1-6.3), and reductions in household air pollution (8.4%, 6 8-9.2). Interpretation Our findings show that there have been substantial but uneven declines in LRI mortality among countries between 1990 and 2017. Although improvements in indicators of sociodemographic development could explain some of these trends, changes in exposure to modifiable risk factors are related to the rates of decline in LRI mortality. No single intervention would universally accelerate reductions in health loss associated with LRIs in all settings, but emphasising the most dominant risk factors, particularly in countries with high case fatality, can contribute to the reduction of preventable deaths

Quantifying risks and interventions that have affected the burden of diarrhoea among children younger than 5 years : an analysis of the Global Burden of Disease Study 2017

Background Many countries have shown marked declines in diarrhoea! disease mortality among children younger than 5 years. With this analysis, we provide updated results on diarrhoeal disease mortality among children younger than 5 years from the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) and use the study's comparative risk assessment to quantify trends and effects of risk factors, interventions, and broader sociodemographic development on mortality changes in 195 countries and territories from 1990 to 2017. Methods This analysis for GBD 2017 had three main components. Diarrhoea mortality was modelled using vital registration data, demographic surveillance data, and verbal autopsy data in a predictive, Bayesian, ensemble modelling tool; and the attribution of risk factors and interventions for diarrhoea were modelled in a counterfactual framework that combines modelled population-level prevalence of the exposure to each risk or intervention with the relative risk of diarrhoea given exposure to that factor. We assessed the relative and absolute change in diarrhoea mortality rate between 1990 and 2017, and used the change in risk factor exposure and sociodemographic status to explain differences in the trends of diarrhoea mortality among children younger than 5 years. Findings Diarrhoea was responsible for an estimated 533 768 deaths (95% uncertainty interval 477 162-593 145) among children younger than 5 years globally in 2017, a rate of 78.4 deaths (70.1-87.1) per 100 000 children. The diarrhoea mortality rate ranged between countries by over 685 deaths per 100 000 children. Diarrhoea mortality per 100 000 globally decreased by 69.6% (63.1-74.6) between 1990 and 2017. Among the risk factors considered in this study, those responsible for the largest declines in the diarrhoea mortality rate were reduction in exposure to unsafe sanitation (13.3% decrease, 11.2-15.5), childhood wasting (9.9% decrease, 9.6-10.2), and low use of oral rehydration solution (6.9% decrease, 4-8-8-4). Interpretation Diarrhoea mortality has declined substantially since 1990, although there are variations by country. Improvements in sociodemographic indicators might explain some of these trends, but changes in exposure to risk factors-particularly unsafe sanitation, childhood growth failure, and low use of oral rehydration solution-appear to be related to the relative and absolute rates of decline in diarrhoea mortality. Although the most effective interventions might vary by country or region, identifying and scaling up the interventions aimed at preventing and protecting against diarrhoea that have already reduced diarrhoea mortality could further avert many thousands of deaths due to this illness. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd.Peer reviewe

Mapping disparities in education across low- and middle-income countries

Analyses of the proportions of individuals who have completed key levels of schooling across all low- and middle-income countries from 2000 to 2017 reveal inequalities across countries as well as within populations. Educational attainment is an important social determinant of maternal, newborn, and child health(1-3). As a tool for promoting gender equity, it has gained increasing traction in popular media, international aid strategies, and global agenda-setting(4-6). The global health agenda is increasingly focused on evidence of precision public health, which illustrates the subnational distribution of disease and illness(7,8); however, an agenda focused on future equity must integrate comparable evidence on the distribution of social determinants of health(9-11). Here we expand on the available precision SDG evidence by estimating the subnational distribution of educational attainment, including the proportions of individuals who have completed key levels of schooling, across all low- and middle-income countries from 2000 to 2017. Previous analyses have focused on geographical disparities in average attainment across Africa or for specific countries, but-to our knowledge-no analysis has examined the subnational proportions of individuals who completed specific levels of education across all low- and middle-income countries(12-14). By geolocating subnational data for more than 184 million person-years across 528 data sources, we precisely identify inequalities across geography as well as within populations.Peer reviewe