Alcohol abuse suppresses the immune responses of alveolar macrophages (AMs) and increases the risk of a respiratory infection via chronic oxidative stress and depletion of critical antioxidants within alveolar cells and the alveolar lining fluid. Although alcohol-induced mitochondrial oxidative stress has been demonstrated, the oxidation of the mitochondrial thioredoxin redox circuit in response to alcohol has not been examined. In vitro ethanol exposure of a mouse AM cell line and AMs from ethanol-fed mice demonstrated NADPH depletion concomitant with oxidation of mitochondrial glutathione and oxidation of the thioredoxin redox circuit system including thioredoxin 2 (Trx2) and thioredoxin 2 reductase (Trx2R). Mitochondrial peroxiredoxins (Prdx's), which are critical for the reduction of the thioredoxin circuit, were irreversibly hyperoxidized to an inactive form. Ethanol also decreased the mRNAs for Trx2, Trx2R, Prdx3, and Prdx5 plus the mitochondrial thiol-disulfide proteins glutaredoxin 2, glutathione reductase, and glutathione peroxidase 2. Thus, the mitochondrial thioredoxin circuit was highly oxidized by ethanol, thereby compromising the mitochondrial antioxidant capacity and ability to detoxify mitochondrial reactive oxygen species. Oxidation of the mitochondrial thioredoxin redox circuit would further compromise the transient oxidation of thiol groups within specific proteins, the basis of redox signaling, and the processes by which cells respond to oxidants. Impaired mitochondria can then jeopardize cellular function of AMs, such as phagocytosis, which may explain the increased risk of respiratory infection in subjects with an alcohol use disorder.
Objectives: Fetal alcohol spectrum disorders are more common in disadvantaged populations. Environmental factors, like suboptimal nutrition, may potentiate the developmental effects of prenatal alcohol exposure. To evaluate the impact of micronutrients, including choline, on reduction of effects of exposure, we examined timing and dose of alcohol and effects of nutritional supplementation at two OMNI-Net sites in Western Ukraine that included high and low risk individuals. Methods: Alcohol-using and nondrinking women were randomized to one of three multivitamin/mineral supplement groups: none, multivitamins/minerals (MVM), and multivitamin/minerals plus choline. Children (N = 367) were tested at 6 months with the Bayley Scales of Infant Development (2nd ED) yielding standard scores for Mental Development Index (MDI), Psychomotor Development Index (PDI) and Behavior. Results: Generalized linear modeling was used: (1) for factorial analysis of effects of alcohol group, multivitamin/minerals, and choline supplementation; and (2) to examine the relationship between amount and timing of alcohol (ounces of absolute alcohol/day [ozAA/day] peri-conception and on average in the second trimester) and MVM supplementation on developmental outcomes while controlling sex, social class, and smoking. MDI was significantly impacted by peri-conceptual alcohol dose ($$\upchi_{(1)}^{2} = 8.54$$χ(1)2=8.54, p < .001) with more alcohol associated with lower scores and males more negatively affected than females ($$\upchi_{(3)}^{2} = 11.04$$χ(3)2=11.04, p < .002). Micronutrient supplementation had a protective effect; those receiving supplements performed better ($$\upchi_{(1)}^{2} = 8.03$$χ(1)2=8.03, p < .005). The PDI motor scores did not differ by group but were affected by peri-conceptual alcohol dose ($$\upchi_{(1)}^{2} = 4.17$$χ(1)2=4.17, p < .04). Conclusions for Practice: Multivitamin/mineral supplementation can reduce the negative impact of alcohol use during pregnancy on specific developmental outcomes.
by
Mohammad H. Forouzanfar;
Ashkan Afshin;
Lily T. Alexander;
H. Ross Anderson;
Zulfiqar A. Bhutta;
Rahul Gupta;
Yang Liu;
Michael Phillips;
Edgar P. Simard;
K.M. Venkat Narayan
Background The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation.
Background: We hypothesized that maternal alcohol use occurs in pregnancies that end prematurely and that in utero alcohol exposure is associated with an increased risk of morbidities of premature newborns.
Methods: In an observational study of mothers who delivered very low birth weight newborns (VLBW) ≤1,500 g, maternal alcohol use was determined via a standardized administered questionnaire. We compared the effect of maternal drinking on the odds of developing late-onset sepsis (LOS), bronchopulmonary dysplasia (BPD), death, BPD or Death days on oxygen or any morbidity (either LOS, BPD or death). The effect of drinking amounts (light versus heavy) was also evaluated.
Results: A total of 129 subjects who delivered 143 VLBW newborns were enrolled. Approximately 1 in 3 (34%) subjects reported drinking alcohol during the first trimester ("exposed"). Within the exposed group, 15% reported drinking ≥7. drinks/week ("heavy") and 85% of the subjects reported drinking < 7. drinks/week ("light"). When controlling for maternal age, drug or tobacco use during pregnancy and neonatal gestational age, any drinking increased the odds of BPD or Death and any morbidity. Furthermore, light or heavy drinking increased the odds of BPD or Death and any morbidity, whereas heavy drinking increased the odds of LOS.
Conclusions: In utero alcohol exposure during the first trimester occurred in 34% of VLBW newborns. Maternal drinking in the first trimester was associated with significantly increased odds of neonatal morbidity. Further studies are warranted to determine the full effect of . in utero alcohol exposure on the adverse outcomes of VLBW premature newborns.
Objectives: Tobacco exposure is an established risk factor for pancreatic cancer and chronic pancreatitis; however, its role in pancreatic insufficiency is not clear. Methods: This controlled, cross-sectional study examined smokers and nonsmokers with no history of pancreatic disease. Histories and validated inventories of alcohol and tobacco use were obtained, and pancreatic insufficiency was assessed using the fecal elastase-1 assay. Results: Of 7854 patients approached, 226 were interviewed and 200 enrolled. The rates of pancreatic insufficiency [18% (18/100)] and severe pancreatic insufficiency [10% (10/100)] were significantly higher in smokers than in controls [6% (6/100), P = 0.009 and 1% (1/100), P = 0.010, respectively]. On multivariate logistic regression, the risk of pancreatic insufficiency in smokers was significantly increased [odds ratio, 4.34 (1.37-13.75); P = 0.012], controlling for alcohol use and relevant covariates. Tobacco exposure was associated with the highest odds ratio for pancreatic insufficiency. Alcohol consumption was strongly associated with tobacco exposure (P < 0.001), but not with pancreatic insufficiency by multivariate analysis (P = 0.792). Conclusions: This study suggests that tobacco exposure is independently associated with pancreatic exocrine insufficiency in patients without a prior diagnosis of pancreatic disease. Tobacco exposure seems to have greater detrimental effects on pancreatic function than alcohol in this population.
by
Owen Middleton;
Daniel Atherton;
Elizabeth Bundock;
Elizabeth Donner;
Daniel Friedman;
Dale Hesdorffer;
Heather Jarrell;
Aileen McCrillis;
Othon J. Mena;
Mitchel Morey;
David Thurman;
Niu Tian;
Torbjorn Tomson;
Zian Tseng;
Steven White;
Cyndi Wright;
Orrin Devinsky
Sudden unexpected death of an individual with epilepsy can pose a challenge to death investigators, as most deaths are unwitnessed, and the individual is commonly found dead in bed. Anatomic findings (eg, tongue/lip bite) are commonly absent and of varying specificity, thereby limiting the evidence to implicate epilepsy as a cause of or contributor to death. Thus it is likely that death certificates significantly underrepresent the true number of deaths in which epilepsy was a factor. To address this, members of the National Association of Medical Examiners, North American SUDEP Registry, Epilepsy Foundation SUDEP Institute, American Epilepsy Society, and the Centers for Disease Control and Prevention constituted an expert panel to generate evidence-based recommendations for the practice of death investigation and autopsy, toxicological analysis, interpretation of autopsy and toxicology findings, and death certification to improve the precision of death certificate data available for public health surveillance of epilepsy-related deaths. The recommendations provided in this paper are intended to assist medical examiners, coroners, and death investigators when a sudden unexpected death in a person with epilepsy is encountered.
Background:
Energy drinks (ED) are caffeine- and sugar-rich beverages with other ingredients that are marketed for their energy-boosting and performance-enhancing effects. The consumption of these drinks, with and without alcohol, is dramatically increasing worldwide, despite the reported side effects and potential harms to consumers. Few studies, to date, have explored the perceptions and experiences of young adults towards these beverages.
Objective:
The present study aimed to explore the consumption patterns and correlates of ED consumption, as well as the perceptions and experiences of university students in Lebanon towards these beverages.
Methods:
A sequential explanatory mixed-methods approach was adopted. Data collection was conducted in two private universities in Beirut, Lebanon. A self-administered 36-item quantitative survey was first used to explore the prevalence and correlates of ED consumption among a convenience sample of university students (n = 226). The survey included questions related to socio-demographic characteristics, anthropometric measurements, and other lifestyle behaviors, including physical activity of university students. The subsequent qualitative phase consisted of focus group discussions (FGD) conducted to further examine the perceptions and experiences of university students towards ED. Descriptive statistics and logistic regression analyses were conducted using survey data, whereas the transcribed FGD were analyzed thematically.
Results:
A total of 226 university students completed the survey. Results showed that 45% of survey respondents consumed ED at least once in their life (ever consumers), among which 30% reported consumption of ED mixed with alcohol (AmED). Adjusting for socio-demographic and anthropometric characteristics, coffee and sports drinks consumption were significantly associated with ED (OR = 2.45, 95% CI = 1.20, 5.00, and OR = 4.88, 95%CI = 2.41, 9.88, respectively). In addition, physically active participants were 1.89 times (95%CI = 1.01, 3.51) more likely to consume ED compared to their inactive counterparts. During the qualitative phase, a total of six FGD were conducted with 29 university students, who reported consuming ED at least once per month. Three main themes were derived reflecting individual-, interpersonal/social- and environmental-level factors affecting ED consumption among university students. These themes were further supported by eight subthemes, including: perceived benefits of ED, experienced side effects, misinformation about content of ED, peer pressure and social image, as well as affordability and accessibility of ED.
Conclusion:
Findings highlight the need for public health policies and programs to curb the growing public health phenomenon of ED consumption amongst university students. Such programs should consider the multi-level factors affecting ED consumption at the individual, interpersonal/social, and environmental levels, including educational campaigns on ED potential harms, regulating ED content and labeling, as well as restricting sales and marketing of these beverages, especially among young consumers.
by
Paulius V. Kuprys;
Hidekazu Tsukamoto;
Bin Gao;
Lin Jia;
Jacob McGowan;
Craig Coopersmith;
Maria Camargo Moreno;
Holly Hulsebus;
Avtar S. Meena;
Flavia M. Souza-Smith;
Philip Roper;
Michelle T. Foster;
S. Vamsee Raju;
S. Alex Marshall;
Mayumi Fujita;
Brenda J. Curtis;
Todd A. Wyatt;
Pranoti Mandrekar;
Elizabeth J. Kovacs;
Mashkoor A. Choudhry
On January 26, 2018, the 23rd annual Alcohol and Immunology Research Interest Group (AIRIG) meeting was held at the University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado. The meeting consisted of plenary sessions with oral presentations and a poster presentation session. There were four plenary sessions that covered a wide range of topics relating to alcohol use: Alcohol and Liver Disease; Alcohol, Inflammation and Immune Response; Alcohol and Organ Injury; Heath Consequences and Alcohol Drinking. The meeting provided a forum for the presentation and discussion of novel research findings regarding alcohol use and immunology.
Objective: To investigate associations of a oxidative balance score (OBS) with blood levels of total cholesterol, low-density lipoprotein-(LDL)-cholesterol, high-density lipoprotein-(HDL) cholesterol and triglycerides, and biomarkers of inflammation (serum C-reactive protein [CRP], albumin and venous total white blood cell [WBC] counts) among 19,825 participants in a nationwide study.
Methods: Using cross-sectional data 14 dietary and lifestyle components were incorporated into the OBS and the resulting score (range 3–26) was then divided into five equal intervals. Multivariable-adjusted odds ratios (ORs) for abnormal biomarker levels and 95% confidence intervals (CIs) were calculated using logistic regression models.
Results: The ORs (95% CIs) comparing those in the highest relative to those in the lowest OBS equal interval categories were 0.50 (0.38–0.66) for CRP, 0.50 (0.36–0.71) for the total WBC count, and 0.75 (0.58–0.98) for LDL-cholesterol; all three p-values for trend were <0.001. The OBS-HDL-cholesterol association was statistically significantly inverse among females, but not among males. The OBS was not associated with serum albumin or triglycerides.
Conclusion: Our findings suggest that an OBS may be associated with some, but not all, circulating lipids/lipoproteins and biomarkers of inflammation.
by
Weihong Tang;
Lu Yao;
Nicholas S. Roetker;
Alvaro Alonso;
Pamela L. Lutsey;
Carol C. Steenson;
Frank A. Lederle;
David W. Hunter;
Lindsay G.S. Bengtson;
Weihua Guan;
Emil Missov;
Aaron R. Folsom
Objective - Abdominal aortic aneurysm (AAA) is an important vascular disease in older adults, but data on lifetime risk of AAA are sparse. We examined lifetime risk of AAA in a community-based cohort and prospectively assessed the association between midlife cardiovascular risk factors and AAAs. Approach and Results - In ARIC study (Atherosclerosis Risk in Communities), 15 792 participants were recruited at visit 1 in 1987 to 1989 and followed up through 2013. Longitudinal smoking status was defined using smoking behavior ascertained from visit 1 (1987-1989) to visit 4 (1996-1998). We followed up participants for incident, clinical AAAs using hospital discharge diagnoses, Medicare outpatient diagnoses, or death certificates through 2011 and identified 590 incident AAAs. An abdominal ultrasound was conducted in 2011 to 2013 in 5911 surviving participants, and 75 asymptomatic AAAs were identified. We estimated the lifetime risk of AAA from the index age 45 years through 85 years of age. At age 45, the lifetime risk for AAA was 5.6% (95% confidence interval, 4.8-6.1) and was higher in men (8.2%) and current smokers (10.5%). Smokers who quit smoking between visit 1 and visit 4 had a 29% lower AAA lifetime risk compared with continuous smokers but had a higher risk than pre-visit 1 quitters. The lifetime risk of rupture or medical intervention was 1.6% (95% confidence interval, 1.2-1.8). Smoking, white race, male sex, greater height, and greater low-density lipoprotein or total cholesterol were associated with an increased risk of clinical AAA and asymptomatic AAA. Conclusions - At least 1 in 9 middle-aged current smokers developed AAA in their lifetime. Smoking cessation reduced the lifetime risk of AAA.