scholarly journals Exploratory extracellular vesicle-bound miRNA profiling to identify candidate biomarkers of chronic alcohol drinking in non-human primates

2021 ◽  
Author(s):  
Sloan A. Lewis ◽  
Brianna Doratt ◽  
Suhas Sureshchandra ◽  
Tianyu Pan ◽  
Steven W. Gonzalez ◽  
...  

Background: Long-term alcohol drinking is associated with numerous health complications including susceptibility to infection, cancer, and organ damage. However, due to the complex nature of human drinking behavior, it is challenging to determine whether alcohol use should be considered a risk factor during diagnosis and treatment. We lack reliable biomarkers of alcohol use that could be used to determine drinking behavior prior to signs of overt organ damage. Recently, extracellular vesicle-bound microRNA (EV-miRNA) have been discovered to be consistent biomarkers of conditions including cancer and liver disease. Methods: In this study, we profiled the plasma EV-miRNA content by miRNA-Seq from 80 non-human primates after 12 months of voluntary ethanol drinking. Results: We identified a list of up- and downregulated EV-miRNA candidate biomarkers of both heavy drinking as well as those positively correlated with ethanol dose. We further overexpressed these candidate miRNA in control primary peripheral immune cells to assess potential functional mechanisms of these EV-miRNA. We identified that overexpression of miR-155, miR-154, miR-34c, miR-450a, and miR-204 led to increased inflammatory TNFA; or IL-6 production in PBMC after stimulation. Conclusion: This exploratory study identified several EV-miRNA that could serve as biomarkers of long-term alcohol drinking as well as provided a mechanism for alcohol-induced peripheral inflammation.

2007 ◽  
Vol 27 (13) ◽  
pp. 3593-3602 ◽  
Author(s):  
J. Wang ◽  
S. Carnicella ◽  
K. Phamluong ◽  
J. Jeanblanc ◽  
J. A. Ronesi ◽  
...  

2017 ◽  
Vol 72 (1) ◽  
pp. 61-67 ◽  
Author(s):  
Jenni Ervasti ◽  
Mika Kivimäki ◽  
Jaana Pentti ◽  
Jaana I Halonen ◽  
Jussi Vahtera ◽  
...  

BackgroundWe investigated whether changes in alcohol use predict changes in the risk of sickness absence in a case-crossover design.MethodsFinnish public sector employees were surveyed in 2000, 2004 and 2008 on alcohol use and covariates. Heavy drinking was defined as either a weekly intake that exceeded recommendations (12 units for women; 23 for men) or having an extreme drinking session. The responses were linked to national sickness absence registers. We analysed the within-person relative risk of change in the risk of sickness absence in relation to change in drinking. Case period refers to being sickness absent within 1 year of the survey and control period refers to not being sickness absent within 1 year of the survey.ResultsPeriods of heavy drinking were associated with increased odds of self-certified short-term (1–3 days) sickness absence (multivariable-adjusted OR 1.21, 95% CI 1.07 to 1.38 for all participants; 1.62, 95% CI 1.19 to 2.21 for men and 1.15, 95% CI 1.00 to 1.33 for women). A higher risk of short-term sickness absence was also observed after increase in drinking (OR=1.27, 95% CI 1.07 to 1.52) and a lower risk was observed after decrease in drinking (OR=0.83, 95% CI 0.69 to 1.00). Both increase (OR=1.38, 95% CI 1.21 to 1.57) and decrease (OR=1.27, 95% CI 1.19 to 1.43) in drinking were associated with increased risk of long-term (>9 days) medically certified all-cause sickness absence.ConclusionIncrease in drinking was related to increases in short-term and long-term sickness absences. Men and employees with a low socioeconomic position in particular seemed to be at risk.


10.2196/13765 ◽  
2019 ◽  
Vol 7 (11) ◽  
pp. e13765 ◽  
Author(s):  
Daniel J Fridberg ◽  
James Faria ◽  
Dingcai Cao ◽  
Andrea C King

Background Binge drinking, defined as consuming five or more standard alcoholic drinks for men (four for women) within a 2-hour period, is common among young adults and is associated with significant alcohol-related morbidity and mortality. To date, most research on this problem in young adults has relied upon retrospective questionnaires or costly laboratory-based procedures. Smartphone-based ecological momentary assessment (EMA) may address these limitations by allowing researchers to measure alcohol use and related consequences in real time and in drinkers’ natural environments. To date, however, relatively less research has systematically examined the utility of this approach in a sample of young adults targeting real-world heavy drinking episodes specifically. Objective This study aimed to evaluate the feasibility, acceptability, and safety of a smartphone-based EMA method targeting binge drinking and related outcomes in heavy drinking young adults during real-world drinking occasions. Methods Young adult binge drinkers in the smartphone group (N=83; mean 25.4 (SD 2.6) years; 58% (48/83) male; bingeing on 23.2% (6.5/28) days in the past month) completed baseline measures of alcohol use and drinking-related consequences, followed by up to two smartphone-based EMA sessions of typical drinking behavior and related outcomes in their natural environments. They also completed next-day and two-week follow-up surveys further assessing alcohol use and related consequences during the EMA sessions and two weeks after study participation, respectively. A separate demographic- and drinking-matched safety comparison group (N=25) completed the baseline and two-week follow-up surveys but did not complete EMA of real-world drinking behavior. Results Most participants (71%, 59/83) in the smartphone group engaged in binge drinking during at least one 3-hour EMA session, consuming 7.3 (SD 3.0) standard alcoholic drinks. They completed 87.2% (507/581) system-initiated EMA prompts during the real-world drinking episode, supporting the feasibility of this approach. The procedure was acceptable, as evidenced by high participant ratings for overall satisfaction with the EMA software and study procedures and low ratings for intrusiveness of the mobile surveys. Regarding safety, participants endorsed few drinking-related consequences during or after the real-world drinking episode, with no adverse or serious adverse events reported. There were no differences between the groups in terms of changes in drinking behavior or consequences from baseline to two-week follow-up. Conclusions This study provided preliminary support for the feasibility, acceptability, and safety of a smartphone-based EMA of real-time alcohol use and related outcomes in young adult heavy drinkers. The results suggest that young adults can use smartphones to safely monitor drinking even during very heavy drinking episodes. Smartphone-based EMA has strong potential to inform future research on the epidemiology of and intervention for alcohol use disorder by providing researchers with an efficient and inexpensive way to capture large amounts of data on real-world drinking behavior and consequences.


2019 ◽  
Author(s):  
Daniel J Fridberg ◽  
James Faria ◽  
Dingcai Cao ◽  
Andrea C King

BACKGROUND Binge drinking, defined as consuming five or more standard alcoholic drinks for men (four for women) within a 2-hour period, is common among young adults and is associated with significant alcohol-related morbidity and mortality. To date, most research on this problem in young adults has relied upon retrospective questionnaires or costly laboratory-based procedures. Smartphone-based ecological momentary assessment (EMA) may address these limitations by allowing researchers to measure alcohol use and related consequences in real time and in drinkers’ natural environments. To date, however, relatively less research has systematically examined the utility of this approach in a sample of young adults targeting real-world heavy drinking episodes specifically. OBJECTIVE This study aimed to evaluate the feasibility, acceptability, and safety of a smartphone-based EMA method targeting binge drinking and related outcomes in heavy drinking young adults during real-world drinking occasions. METHODS Young adult binge drinkers in the smartphone group (N=83; mean 25.4 (SD 2.6) years; 58% (48/83) male; bingeing on 23.2% (6.5/28) days in the past month) completed baseline measures of alcohol use and drinking-related consequences, followed by up to two smartphone-based EMA sessions of typical drinking behavior and related outcomes in their natural environments. They also completed next-day and two-week follow-up surveys further assessing alcohol use and related consequences during the EMA sessions and two weeks after study participation, respectively. A separate demographic- and drinking-matched safety comparison group (N=25) completed the baseline and two-week follow-up surveys but did not complete EMA of real-world drinking behavior. RESULTS Most participants (71%, 59/83) in the smartphone group engaged in binge drinking during at least one 3-hour EMA session, consuming 7.3 (SD 3.0) standard alcoholic drinks. They completed 87.2% (507/581) system-initiated EMA prompts during the real-world drinking episode, supporting the feasibility of this approach. The procedure was acceptable, as evidenced by high participant ratings for overall satisfaction with the EMA software and study procedures and low ratings for intrusiveness of the mobile surveys. Regarding safety, participants endorsed few drinking-related consequences during or after the real-world drinking episode, with no adverse or serious adverse events reported. There were no differences between the groups in terms of changes in drinking behavior or consequences from baseline to two-week follow-up. CONCLUSIONS This study provided preliminary support for the feasibility, acceptability, and safety of a smartphone-based EMA of real-time alcohol use and related outcomes in young adult heavy drinkers. The results suggest that young adults can use smartphones to safely monitor drinking even during very heavy drinking episodes. Smartphone-based EMA has strong potential to inform future research on the epidemiology of and intervention for alcohol use disorder by providing researchers with an efficient and inexpensive way to capture large amounts of data on real-world drinking behavior and consequences.


2020 ◽  
Vol 1 (2) ◽  
pp. 11-15
Author(s):  
Yury P. Sivolap ◽  

The increase in alcohol use during the COVID-19 pandemic is one of the major global health problems. Alcohol abuse is caused by many causes, including the stress associated with the pandemic. The problem of alcohol abuse is getting worse by the difficult access of patients to medical care, and lockdown, including a restrained sale of alcohol, can lead to numerous cases of severe alcohol withdrawal, alcohol psychosis and suicide. Excessive alcohol consumption reduces the immune system, increases susceptibility to infection, including SARS-CoV-2, and contributes to the severe course of COVID-19, increasing the likelihood of complications and death. It is assumed that alcohol abuse during the pandemic will have long-term adverse consequences in the form of significant deterioration of public health, an increase in the number of patients with alcohol dependence and alcoholic liver disease, and an excessive burden on global health. Experts justify the need to apply special programs to help people with alcohol use disorders during the pandemic and develop a set of preventive measures to prevent the adverse long-term consequences of excessive alcohol use.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 406-406
Author(s):  
Angela Curl ◽  
Jennifer Bulanda ◽  
Amy Restorick Roberts

Abstract Supportive marital relationships may reduce partners’ problematic health behaviors, whereas unhappy relationships may lack efficacious spousal monitoring of health and increase the likelihood of using maladaptive coping strategies, such as heavy alcohol use, to deal with relationship problems. We used pooled data from the 2014 and 2016 waves of the Health and Retirement Study to examine how both partners’ perceptions of marital quality were associated with heavy drinking. Our analytic sample included married couples in which both spouses were over age 50, completed the leave-behind psychosocial questionnaire, and provided non-missing data on marital quality and alcohol use (n=2,095 couples). Measures included both positive and negative dimensions of marital quality and controls for sociodemographic, economic, health, household and marital characteristics. Using Proc Glimmix, we estimated a dual-intercept Actor-Partner Interdependence Model (APIM), in which separate equations were computed simultaneously for husbands and wives. For husbands, higher negative marital quality was associated with an increase in the odds of their own heavy drinking (OR=1.27), but there was no significant association between wives’ marital quality and husbands’ heavy drinking behavior. For wives, marital quality was not significantly associated with their own heavy drinking, but husbands’ higher ratings of both negative and positive marital quality increased the risk of wives’ heavy drinking (OR=1.60 and OR=1.75, respectively). Results suggest that marital quality is associated with heavy drinking in later life: self-ratings of marital quality matter for men, whereas spousal perceptions of marital quality are more important for women.


1988 ◽  
Vol 18 (3) ◽  
pp. 235-242 ◽  
Author(s):  
Sehwan Kim

This study reports short- and long-term outcome evaluation results of an alcohol education prevention program entitled “Here's Looking at You (HLAY)” as implemented by one of the largest school districts in the nation during 1982–1987. Since the adoption of this program as a demonstration project by the National Institute on Alcohol Abuse and Alcoholism, the program has become one of the most widely known alcohol education or prevention programs in the nation. In 1982, the program was adopted by the Charlotte-Mecklenburg Schools (CMS) and has been under continuous replication. On the basis of the most recent replication of the HLAY during the spring semester 1987 and on the basis of the CMS system-wide student drug survey in 1986, the program has been evaluated using the following criterion variables: knowledge gain; three subdimensions on the general attitude about alcohol, i.e., undifferentiated-primitive attitude, reward-associated attitude, and health-related attitude; intentions about future alcohol use; and the actual drinking behavior. On a short-term basis, 1) there has been a knowledge gain about alcohol and alcoholism on the part of the HLAY recipients between the pre and post tests of the Alcohol Education Evaluation Instrument (AEEI). However, this gain in the HLAY group was less than the knowledge gain observed among control group student; 2) in comparison to the students in the control group, there has been a positive attitudinal net gain among the HLAY recipients along the undifferentiated-primitive attitude about alcohol; 3) however, the HLAY was not able to impact upon the reward-associated attitude, health-related attitude, the intentions about future alcohol use, and the actual drinking behavior. On a long-term basis, the actual alcohol drinking pattern of the HLAY recipients was indistinguishable from those students who had not been exposed to the program.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Daria Piacentino ◽  
Silvia Grant-Beurmann ◽  
Carlotta Vizioli ◽  
Xiaobai Li ◽  
Catherine F. Moore ◽  
...  

AbstractA relationship between the gut microbiome and alcohol use disorder has been suggested. Excessive alcohol use produces changes in the fecal microbiome and metabolome in both rodents and humans. Yet, these changes can be observed only in a subgroup of the studied populations, and reversal does not always occur after abstinence. We aimed to analyze fecal microbial composition and function in a translationally relevant baboon model of chronic heavy drinking that also meets binge criteria (drinking too much, too fast, and too often), i.e., alcohol ~1 g/kg and blood alcohol levels (BALs) ≥ 0.08 g/dL in a 2-hour period, daily, for years. We compared three groups of male baboons (Papio anubis): L = Long-term alcohol drinking group (12.1 years); S = Short-term alcohol drinking group (2.7 years); and C = Control group, drinking a non-alcoholic reinforcer (Tang®) (8.2 years). Fecal collection took place during 3 days of Drinking (D), followed by a short period (3 days) of Abstinence (A). Fecal microbial alpha- and beta-diversity were significantly lower in L vs. S and C (p’s < 0.05). Members of the commensal families Lachnospiraceae and Prevotellaceae showed a relative decrease, whereas the opportunistic pathogen Streptococcus genus showed a relative increase in L vs. S and C (p’s < 0.05). Microbiota-related metabolites of aromatic amino acids, tricarboxylic acid cycle, and pentose increased in L vs. S and C (FDR-corrected p < 0.01), with the latter two suggesting high energy metabolism and enhanced glycolysis in the gut lumen in response to alcohol. Consistent with the long-term alcohol exposure, mucosal damage and oxidative stress markers (N-acetylated amino acids, 2-hydroxybutyrate, and metabolites of the methionine cycle) increased in L vs. S and C (FDR-corrected p < 0.01). Overall, S showed few differences vs. C, possibly due to the long-term, chronic alcohol exposure needed to alter the normal gut microbiota. In the three groups, the fecal microbiome barely differed between conditions D and A, whereas the metabolome shifted in the transition from condition D to A. In conclusion, changes in the fecal microbiome and metabolome occur after significant long-term excessive drinking and are only partially affected by acute forced abstinence from alcohol. These results provide novel information on the relationship between the fecal microbiome and metabolome in a controlled experimental setting and using a unique non-human primate model of chronic excessive alcohol drinking.


F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 298 ◽  
Author(s):  
Lara Hwa ◽  
Joyce Besheer ◽  
Thomas Kash

Glutamate signaling in the brain is one of the most studied targets in the alcohol research field. Here, we report the current understanding of how the excitatory neurotransmitter glutamate, its receptors, and its transporters are involved in low, episodic, and heavy alcohol use. Specific animal behavior protocols can be used to assess these different drinking levels, including two-bottle choice, operant self-administration, drinking in the dark, the alcohol deprivation effect, intermittent access to alcohol, and chronic intermittent ethanol vapor inhalation. Importantly, these methods are not limited to a specific category, since they can be interchanged to assess different states in the development from low to heavy drinking. We encourage a circuit-based perspective beyond the classic mesolimbic-centric view, as multiple structures are dynamically engaged during the transition from positive- to negative-related reinforcement to drive alcohol drinking. During this shift from lower-level alcohol drinking to heavy alcohol use, there appears to be a shift from metabotropic glutamate receptor-dependent behaviors to N-methyl-D-aspartate receptor-related processes. Despite high efficacy of the glutamate-related pharmaceutical acamprosate in animal models of drinking, it is ineffective as treatment in the clinic. Therefore, research needs to focus on other promising glutamatergic compounds to reduce heavy drinking or mediate withdrawal symptoms or both.


2020 ◽  
Author(s):  
Frank R Wendt ◽  
Antonella De Lillo ◽  
Gita A Pathak ◽  
Flavio De Angelis ◽  
Renato Polimanti ◽  
...  

AbstractTo distinguish correlation from causation, we performed in-silico analyses of three COVID-19 outcomes (N>1,000,000). We show genetic correlation and putative causality with depressive symptoms, metformin use, and alcohol use. COVID-19 risk loci associated with several hematologic biomarkers. Comprehensive findings inform genetic contributions to COVID-19 epidemiology, molecular mechanisms, and risk factors.


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