Loss of sucrase-isomaltase function increases acetate levels and improves metabolic health in Greenlandic cohorts

Background & Aims The sucrase-isomaltase (SI) c.273_274delAG loss-of-function variant is common in Arctic populations and causes congenital sucrase-isomaltase deficiency, which is an inability to break down and absorb sucrose and isomaltose. Children with this condition experience gastrointestinal symptoms when dietary sucrose is introduced. We aimed to describe the health of adults with sucrase-isomaltase deficiency. Methods The association between c.273_274delAG and phenotypes related to metabolic health was assessed in 2 cohorts of Greenlandic adults (n = 4922 and n = 1629). A sucrase-isomaltase knockout (Sis-KO) mouse model was used to further elucidate the findings. Results Homozygous carriers of the variant had a markedly healthier metabolic profile than the remaining population, including lower body mass index (β [standard error], –2.0 [0.5] kg/m2; P = 3.1 × 10–5), body weight (–4.8 [1.4] kg; P = 5.1 × 10–4), fat percentage (–3.3% [1.0%]; P = 3.7 × 10–4), fasting triglyceride (–0.27 [0.07] mmol/L; P = 2.3 × 10–6), and remnant cholesterol (–0.11 [0.03] mmol/L; P = 4.2 × 10–5). Further analyses suggested that this was likely mediated partly by higher circulating levels of acetate observed in homozygous carriers (β [standard error], 0.056 [0.002] mmol/L; P = 2.1 × 10–26), and partly by reduced sucrose uptake, but not lower caloric intake. These findings were verified in Sis-KO mice, which, compared with wild-type mice, were leaner on a sucrose-containing diet, despite similar caloric intake, had significantly higher plasma acetate levels in response to a sucrose gavage, and had lower plasma glucose level in response to a sucrose-tolerance test. Conclusions These results suggest that sucrase-isomaltase constitutes a promising drug target for improvement of metabolic health, and that the health benefits are mediated by reduced dietary sucrose uptake and possibly also by higher levels of circulating acetate

Opposing effects of dietary n-3 and n-6 fatty acids on mammary carcinogenesis: The Singapore Chinese Health Study

10.1038/sj.bjc.6601340British Journal of Cancer8991686-1692BJCA

Sensing of Fatty Acids for Octanoylation of Ghrelin Involves a Gustatory G-Protein

Ghrelin is an important regulator of energy--and glucose homeostasis. The octanoylation at Ser(3) is essential for ghrelin's biological effects but the mechanisms involved in the octanoylation are unknown. We investigated whether the gustatory G-protein, α-gustducin, and the free fatty acid receptors GPR40 and GPR120 are involved in the fatty acid sensing mechanisms of the ghrelin cell.Wild-type (WT) and α-gustducin knockout (gust(-/-)) mice were fed a glyceryl trioctanoate-enriched diet (OD) during 2 weeks. Ghrelin levels and gastric emptying were determined. Co-localization between GPR40, GPR120 and ghrelin or α-gustducin/α-transducin was investigated by immunofluorescence staining. The role of GPR120 in the effect of medium and long chain fatty acids on the release of ghrelin was studied in the ghrelinoma cell line, MGN3-1. The effect of the GPR40 agonist, MEDICA16, and the GPR120 agonist, grifolic acid, on ghrelin release was studied both in vitro and in vivo.Feeding an OD specifically increased octanoyl ghrelin levels in the stomach of WT mice but not of gust(-/-) mice. Gastric emptying was accelerated in WT but not in gust(-/-) mice. GPR40 was colocalized with desoctanoyl but not with octanoyl ghrelin, α-gustducin or α-transducin positive cells in the stomach. GPR120 only colocalized with ghrelin in the duodenum. Addition of octanoic acid or α-linolenic acid to MGN3-1 cells increased and decreased octanoyl ghrelin levels, respectively. Both effects could not be blocked by GPR120 siRNA. MEDICA16 and grifolic acid did not affect ghrelin secretion in vitro but oral administration of grifolic acid increased plasma ghrelin levels.This study provides the first evidence that α-gustducin is involved in the octanoylation of ghrelin and shows that the ghrelin cell can sense long- and medium-chain fatty acids directly. GPR120 but not GPR40 may play a role in the lipid sensing cascade of the ghrelin cell

Cost-effectiveness of In-home Automated External Defibrillators for Individuals at Increased Risk of Sudden Cardiac Death

In-home automated external defibrillators (AEDs) are increasingly recommended as a means for improving survival of cardiac arrests that occur at home. The current study was conducted to explore the relationship between individuals' risk of cardiac arrest and cost-effectiveness of in-home AED deployment. Design : Markov decision model employing a societal perspective. Patients : Four hypothetical cohorts of American adults 60 years of age at progressively greater risk for sudden cardiac death (SCD): 1) all adults (annual probability of SCD 0.4%); 2) adults with multiple SCD risk factors (probability 2%); 3) adults with previous myocardial infarction (probability 4%); and 4) adults with ischemic cardiomyopathy unable to receive an implantable defibrillator (probability 6%). Intervention : Strategy 1: individuals suffering an in-home cardiac arrest were treated with emergency medical services equipped with AEDs (EMS-D). Strategy 2: individuals suffering an in-home cardiac arrest received initial treatment with an in-home AED, followed by EMS. Results : Assuming cardiac arrest survival rates of 15% with EMS-D and 30% with AEDs, the cost per quality-adjusted life-year gained (QALY) of providing in-home AEDs to all adults 60 years of age is $216,000. Costs of providing in-home AEDs to adults with multiple risk factors (2$132,000, $104,000, and$88,000, respectively. Conclusions : The cost-effectiveness of in-home AEDs is intimately linked to individuals' risk of SCD. However, providing in-home AEDs to all adults over age 60 appears relatively expensive.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72168/1/j.1525-1497.2005.40247.x.pd

Reexamining age, race, site, and thermometer type as variables affecting temperature measurement in adults – A comparison study

BACKGROUND: As a result of the recent international vigilance regarding disease assessment, accurate measurement of body temperature has become increasingly important. Yet, trusted low-tech, portable mercury glass thermometers are no longer available. Thus, comparing accuracy of mercury-free thermometers with mercury devices is essential. Study purposes were 1) to examine age, race, site as variables affecting temperature measurement in adults, and 2) to compare clinical accuracy of low-tech Galinstan-in-glass device to mercury-in-glass at oral, axillary, groin, and rectal sites in adults. METHODS: Setting 176 bed accredited healthcare facility, rural northwest US Participants Convenience sample (N = 120) of hospitalized persons ≥ 18 years old. Instruments Temperatures (°F) measured at oral, skin (simultaneous), immediately followed by rectal sites with four each mercury-glass (BD) and Galinstan-glass (Geratherm) thermometers; 10 minute dwell times. RESULTS: Participants averaged 61.6 years (SD 17.9), 188 pounds (SD 55.3); 61% female; race: 85% White, 8.3% Native Am., 4.2% Hispanic, 1.7 % Asian, 0.8% Black. For both mercury and Galinstan-glass thermometers, within-subject temperature readings were highest rectally; followed by oral, then skin sites. Galinstan assessments demonstrated rectal sites 0.91°F > oral and ≅ 1.3°F > skin sites. Devices strongly correlated between and across sites. Site difference scores between devices showed greatest variability at skin sites; least at rectal site. 95% confidence intervals of difference scores by site (°F): oral (0.142 – 0.265), axilla (0.167 – 0.339), groin (0.037 – 0.321), and rectal (-0.111 – 0.111). Race correlated with age, temperature readings each site and device. CONCLUSION: Temperature readings varied by age, race. Mercury readings correlated with Galinstan thermometer readings at all sites. Site mean differences between devices were considered clinically insignificant. Still considered the gold standard, mercury-glass thermometers may no longer be available worldwide. Therefore, mercury-free, environmentally safe low-tech Galinstan-in-glass may be an appropriate replacement. This is especially important as we face new, internationally transmitted diseases

Smoking prevalence and attributable disease burden in 195 countries and territories, 1990-2015 : a systematic analysis from the Global Burden of Disease Study 2015

Background The scale-up of tobacco control, especially after the adoption of the Framework Convention for Tobacco Control, is a major public health success story. Nonetheless, smoking remains a leading risk for early death and disability worldwide, and therefore continues to require sustained political commitment. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) offers a robust platform through which global, regional, and national progress toward achieving smoking-related targets can be assessed. Methods We synthesised 2818 data sources with spatiotemporal Gaussian process regression and produced estimates of daily smoking prevalence by sex, age group, and year for 195 countries and territories from 1990 to 2015. We analysed 38 risk-outcome pairs to generate estimates of smoking-attributable mortality and disease burden, as measured by disability-adjusted life-years (DALYs). We then performed a cohort analysis of smoking prevalence by birth-year cohort to better understand temporal age patterns in smoking. We also did a decomposition analysis, in which we parsed out changes in all-cause smoking-attributable DALYs due to changes in population growth, population ageing, smoking prevalence, and risk-deleted DALY rates. Finally, we explored results by level of development using the Socio-demographic Index (SDI). Findings Worldwide, the age-standardised prevalence of daily smoking was 25.0% (95% uncertainty interval [UI] 24.2-25.7) for men and 5.4% (5.1-5.7) for women, representing 28.4% (25.8-31.1) and 34.4% (29.4-38.6) reductions, respectively, since 1990. A greater percentage of countries and territories achieved significant annualised rates of decline in smoking prevalence from 1990 to 2005 than in between 2005 and 2015; however, only four countries had significant annualised increases in smoking prevalence between 2005 and 2015 (Congo [Brazzaville] and Azerbaijan for men and Kuwait and Timor-Leste for women). In 2015, 11.5% of global deaths (6.4 million [95% UI 5.7-7.0 million]) were attributable to smoking worldwide, of which 52.2% took place in four countries (China, India, the USA, and Russia). Smoking was ranked among the five leading risk factors by DALYs in 109 countries and territories in 2015, rising from 88 geographies in 1990. In terms of birth cohorts, male smoking prevalence followed similar age patterns across levels of SDI, whereas much more heterogeneity was found in age patterns for female smokers by level of development. While smoking prevalence and risk-deleted DALY rates mostly decreased by sex and SDI quintile, population growth, population ageing, or a combination of both, drove rises in overall smoking-attributable DALYs in low-SDI to middle-SDI geographies between 2005 and 2015. Interpretation The pace of progress in reducing smoking prevalence has been heterogeneous across geographies, development status, and sex, and as highlighted by more recent trends, maintaining past rates of decline should not be taken for granted, especially in women and in low-SDI to middle-SDI countries. Beyond the effect of the tobacco industry and societal mores, a crucial challenge facing tobacco control initiatives is that demographic forces are poised to heighten smoking's global toll, unless progress in preventing initiation and promoting cessation can be substantially accelerated. Greater success in tobacco control is possible but requires effective, comprehensive, and adequately implemented and enforced policies, which might in turn require global and national levels of political commitment beyond what has been achieved during the past 25 years.Peer reviewe

Five insights from the Global Burden of Disease Study 2019

The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides a rules-based synthesis of the available evidence on levels and trends in health outcomes, a diverse set of risk factors, and health system responses. GBD 2019 covered 204 countries and territories, as well as first administrative level disaggregations for 22 countries, from 1990 to 2019. Because GBD is highly standardised and comprehensive, spanning both fatal and non-fatal outcomes, and uses a mutually exclusive and collectively exhaustive list of hierarchical disease and injury causes, the study provides a powerful basis for detailed and broad insights on global health trends and emerging challenges. GBD 2019 incorporates data from 281 586 sources and provides more than 3.5 billion estimates of health outcome and health system measures of interest for global, national, and subnational policy dialogue. All GBD estimates are publicly available and adhere to the Guidelines on Accurate and Transparent Health Estimate Reporting. From this vast amount of information, five key insights that are important for health, social, and economic development strategies have been distilled. These insights are subject to the many limitations outlined in each of the component GBD capstone papers.Peer reviewe