Increased Alcohol Intake Research Articles

Metabolic Dysfunction-Associated Steatotic Liver Disease and Metabolic Dysfunction-Associated Steatotic Liver Disease with Increased Alcohol Intake Increase the Risk of Developing Hepatocellular Carcinoma and Incident or Decompensated Cirrhosis: A Korean Nationwide Study

Introduction: This study aimed to investigate the liver-related outcomes of newly suggested metabolic dysfunction-associated steatotic liver disease (MASLD) and MASLD with increased alcohol intake (MetALD), as well as alcohol-associated liver disease (ALD). Methods: From a National Health Insurance Service Health Screening Cohort, we included 369,094 participants who underwent health checkups between 2009 and 2010 in South Korea. Steatotic liver disease (SLD) was defined as a fatty liver index ≥60. The risk of primary liver cancer (PLCa), hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), incident cirrhosis, and decompensated cirrhosis was compared with no SLD. The subdistribution hazard ratio (SHR) was calculated using the Fine-Gray model regarding competing risks. Results: A total of 3,232 participants (0.9%) developed PLCa during the median follow-up of 3,227,176 person-years: 0.5% with no SLD, 1.1% with MASLD, 1.3% with MetALD, and 1.9% with ALD. Competing risk analysis revealed that compared with no SLD, MASLD (SHR: 1.65; 95% CI: 1.44−1.88), MetALD (SHR: 1.87; 95% CI: 1.52−2.29), and ALD (SHR: 1.86; 95% CI: 1.39−2.49) were associated with an increased risk of PLCa. MASLD (SHR: 1.96; 95% CI: 1.67−2.31), MetALD (SHR: 2.23; 95% CI: 1.75−2.84), and ALD (SHR: 2.34; 95% CI: 1.67−3.29) were associated with a higher risk of HCC. No significant difference was observed in the risk of iCCA. The risk of incident cirrhosis and decompensated cirrhosis increased in the order of no SLD, MASLD, MetALD, and ALD. Conclusion: MASLD, MetALD, and ALD have an increased risk of PLCa, HCC, incident cirrhosis, and decompensated cirrhosis but not iCCA. These findings may serve as a robust ground for the prognostic value of the newly suggested MASLD and MetALD.

2 The Longitudinal Relationship Between Concussion History, Years of Football Participation, and Alcohol Use Among Former National Football League (NFL) Players: an NFL-LONG Study

Objective:It has been posited that alcohol use may confound the association between greater concussion history and poorer neurobehavioral functioning. However, while greater alcohol use is positively correlated with neurobehavioral difficulties, the association between alcohol use and concussion history is not well understood. Therefore, this study investigated the cross-sectional and longitudinal associations between cumulative concussion history, years of contact sport participation, and health-related/psychological factors with alcohol use in former professional football players across multiple decades.Participants and Methods:Former professional American football players completed general health questionnaires in 2001 and 2019, including demographic information, football history, concussion/medical history, and health-related/psychological functioning. Alcohol use frequency and amount was reported for three timepoints: during professional career (collected retrospectively in 2001), 2001, and 2019. During professional career and 2001 alcohol use frequency included none, 1-2, 3-4, 5-7 days/week, while amount included none, 12, 3-5, 6-7, 8+ drinks/occasion. For 2019, frequency included never, monthly or less, 2-4 times/month, 2-3 times/week, >4 times/week, while amount included none, 1-2, 3-4, 5-6, 7-9, 10+ drinks/occasion. Scores on a screening measure for Alcohol Use Disorder (CAGE) were also available at during professional career and 2001 timepoints. Concussion history was recorded in 2001 and binned into five groups: 0, 1-2, 3-5, 6-9, 10+. Depression and pain interference were assessed via PROMIS measures at all timepoints. Sleep disturbance was assessed in 2001 via separate instrument and with PROMIS Sleep Disturbance in 2019. Spearman’s rho correlations tested associations between concussion history and years of sport participation with alcohol use across timepoints, and whether poor health functioning (depression, pain interference, sleep disturbance) in 2001 and 2019 were associated with alcohol use both within and between timepoints.Results:Among the 351 participants (Mage=47.86[SD=10.18] in 2001), there were no significant associations between concussion history or years of contact sport participation with CAGE scores or alcohol use frequency/amount during professional career, 2001, or 2019 (rhos=-.072-.067, ps>.05). In 2001, greater depressive symptomology and sleep disturbance were related to higher CAGE scores (rho=.209, p<.001; rho=.176, p<.001, respectively), while greater depressive symptomology, pain interference, and sleep disturbance were related to higher alcohol use frequency (rho=.176, p=.002; rho=.109, p=.045; rho=.132, p=.013, respectively) and amount/occasion (rho=.215, p<.001; rho=.127, p=.020; rho=.153, p=.004, respectively). In 2019, depressive symptomology, pain interference, and sleep disturbance were not related to alcohol use (rhos=-.047-.087, ps>.05). Between timepoints, more sleep disturbance in 2001 was associated with higher alcohol amount/occasion in 2019 (rho=.115, p=.036).Conclusions:Increased alcohol intake has been theorized to be a consequence of greater concussion history, and as such, thought to confound associations between concussion history and neurobehavioral function later in life. Our findings indicate concussion history and years of contact sport participation were not significantly associated with alcohol use cross-sectionally or longitudinally, regardless of alcohol use characterization. While higher levels of depression, pain interference, and sleep disturbance in 2001 were related to greater alcohol use in 2001, they were not associated cross-sectionally in 2019. Results support the need to concurrently address health-related and psychological factors in the implementation of alcohol use interventions for former NFL players, particularly earlier in the sport discontinuation timeline.

Prevalence, distribution, and hepatic fibrosis burden of the different subtypes of steatotic liver disease in primary care settings.

In relation to the new umbrella terminology for steatotic liver disease (SLD), we aimed to elucidate the prevalence, distribution, and clinical characteristics of the SLD subgroups in the primary care setting. We retrospectively collected data from 2535 individuals who underwent magnetic resonance elastography and MRI proton density fat fraction during health checkups in 5 primary care health promotion clinics. We evaluated the presence of cardiometabolic risk factors according to predefined criteria and divided all the participants according to the new SLD classification. The prevalence of SLD was 39.13% in the total cohort, and 95.77% of the SLD cases had metabolic dysfunction (one or more cardiometabolic risk factors). The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) was 29.51%, with those of metabolic dysfunction and alcohol associated steatotic liver disease (MetALD) and alcohol-associated liver disease (ALD) at 7.89% and 0.39%, respectively. According to the old criteria, the prevalence of NAFLD was 29.11%, and 95.80% of the NAFLD cases fulfilled the new criteria for MASLD. The distribution of SLD subtypes was highest for MASLD, at 75.40%, followed by MetALD at 20.06%, cryptogenic SLD at 3.33%, and ALD at 1.01%. The MetALD group had a significantly higher mean magnetic resonance elastography than the MASLD or ALD group. Almost all the patients with NAFLD met the new criteria for MASLD. The fibrosis burden of the MetALD group was higher than those of the MASLD and ALD groups.

Metabolic dysfunction-associated steatotic liver disease and risk of cardiovascular disease

ObjectiveWe explored clinical implications of the new definition of metabolic dysfunction-associated steatotic liver disease (MASLD) by assessing its prevalence and associated cardiovascular disease (CVD) risk.DesignFrom nationwide health screening data, we...

Metabolic dysfunction-associated steatotic liver disease increases the risk of incident cardiovascular disease: a nationwide cohort study

The various subcategories under the overarching term of steatotic liver disease (SLD) have been recently proposed by the nomenclature consensus group and endorsed by international academic liver societies. Our aim was to investigate the association between each subtype of SLD and incident cardiovascular disease (CVD) in a nationwide Korean cohort. From a nationwide health screening database from Korea, 351,068 individuals aged 47-86 years between January 1, 2009 and December 31, 2010 were included and followed until December 31, 2019 for a median of 9.0 years. Individuals were categorised into no SLD, metabolic dysfunction-associated steatotic liver disease (MASLD), MASLD with increased alcohol intake (MetALD), and alcohol-related liver disease (ALD). Hepatic steatosis was defined as fatty liver index ≥60. The primary outcome was a composite CVD, which includes non-fatal and fatal myocardial infarction and stroke. The subdistribution hazard ratio (SHR) was calculated using the Fine-Gray model with treating non-CVD-related death as a competing risk. There were 199,817 male (56.9%) and 151,251 female (43.1%) with a median age of 55 years (interquartile range, 50-61). The prevalence of no SLD, MASLD, MetALD, and ALD was 44.3%, 47.2%, 6.4%, and 2.1%, respectively; and the incidence rate of CVD in each subcategory was 6.2, 8.5, 8.5, and 9.6 per 1000 person-years, respectively. MASLD (SHR, 1.19; 95% confidence interval [CI], 1.15-1.24), MetALD (SHR, 1.28; 95% CI, 1.20-1.36), and ALD (SHR, 1.29; 95% CI, 1.18-1.41) increased the risk of CVD compared to no SLD, which increment was in consecutive order (Ptrend < 0.001). Individuals with MASLD, MetALD, or ALD are at an increased risk of developing incident CVD. Higher risk of CVD observed in MetALD compared to MASLD suggests the additive impact of alcohol consumption in conjunction with cardiometabolic risk factors on CVD development. These findings support and validate the utility of the new consensus criteria for SLD in predicting CVD. The National Research Foundation of Korea and the Korea Centers for Disease Control and Prevention.

Secondary risk reduction service acceptability amongst Irish breast cancer survivors and clinicians

Abstract Background Many patients (&amp;gt;75%) diagnosed with breast cancer in Ireland today will be cured and are at risk of dying from other cancers and non-communicable diseases. Breast cancer diagnosis provides a pivotal time point for education on modifiable risk factors and engagement with secondary risk reduction services. Our study set out to establish the level of awareness and acceptability of these areas, respectively. Methods A survey was developed for breast cancer survivors and oncology clinicians using previously validated questionnaires; the ‘Mitchelstown Cohort Survey’ and the ‘International Physical Activity Questionnaire'. IBM SPSS software (Version 28.0) was used for data analysis. Results Between September and December 2021, 322 patients and 29 clinicians attending the South Infirmary Victoria and Cork University Hospitals, completed the survey. Over 80% of patients and clinicians were aware of modifiable cancer risk factors. Only 1 in 5 clinicians had training in secondary risk reduction however 90% were willing to refer to services. Education had an impact on the likelihood of patient engagement with weight management, dietary, and exercise education (Pearson chi-squared test; p = 0.009, 0.039, 0.139 respectively). Patients who smoked, had increased alcohol intake, or gained weight since diagnosis were more likely to engage with services (p = &amp;lt;0.001, p = &amp;lt;0.001, p = 0.015 respectively). Patients who made changes to activity levels since diagnosis were more likely to engage with exercise education (p = 0.015). Conclusions This study identified that over 4 in 5 breast cancer survivors and oncology clinicians were aware of the importance of modifiable lifestyle risk factors. While 9 in 10 clinicians were willing to refer to secondary prevention services if available, the likelihood of patient engagement was associated with their at-risk behaviours and education level. Our study highlights the challenges of implementing health promotion programs in this cohort. Key messages • High level of intended engagement with secondary risk reduction services amongst breast cancer survivors and oncology clinicians. • Likelihood of patient engagement was associated with their at-risk behaviours and education level.

Functional Variation in the FAAH Gene Is Directly Associated with Subjective Well-Being and Indirectly Associated with Problematic Alcohol Use.

Fatty acid amide hydrolase (FAAH) is an enzyme that degrades anandamide, an endocannabinoid that modulates mesolimbic dopamine release and, consequently, influences states of well-being. Despite these known interactions, the specific role of FAAH in subjective well-being remains underexplored. Since well-being is a dynamic trait that can fluctuate over time, we hypothesized that we could provide deeper insights into the link between FAAH and well-being using longitudinal data. To this end, we analyzed well-being data collected three years apart using the WHO (Ten) Well-Being Index and genotyped a functional polymorphism in the FAAH gene (rs324420, Pro129Thr) in a sample of 2822 individuals. We found that the A-allele of rs324420, which results in reduced FAAH activity and elevated anandamide levels, was associated with lower well-being scores at both time points (Wave I, B: -0.52, p = 0.007; Wave II, B: -0.41, p = 0.03, adjusted for age and sex). A subsequent phenome-wide association study (PheWAS) affirmed our well-being findings in the UK Biobank (N = 126,132, alternative C-allele associated with elevated happiness, p = 0.008) and revealed an additional association with alcohol dependence. In our cohort, using lagged longitudinal mediation analyses, we uncovered evidence of an indirect association between rs324420 and problematic alcohol use (AUDIT-P) through the pathway of lower well-being (indirect effect Boot: 0.015, 95% CI [0.003, 0.030], adjusted for AUDIT in Wave I). We propose that chronically elevated anandamide levels might influence disruptions in the endocannabinoid system-a biological contributor to well-being-which could, in turn, contribute to increased alcohol intake, though multiple factors may be at play. Further genetic studies and mediation analyses are needed to validate and extend these findings.

National prevalence estimates for steatotic liver disease and subclassifications using consensus nomenclature.

The multisociety consensus nomenclature has renamed NAFLD to steatotic liver disease (SLD) with various subclassifications. There is a paucity of data regarding how the new nomenclature modifies our understanding of disease prevalence and patient phenotypes. Using the National Health and Nutrition Examination Survey from January 2017 to March 2020, we included all participants aged 18 years or above with complete vibration-controlled transient elastography measures. SLD and its subclassifications [metabolic dysfunction-associated SLD (MASLD), MASLD + increased alcohol intake (MetALD), alcohol-associated liver disease (ALD), etiology-specific/cryptogenic] were defined according to consensus nomenclature. National SLD prevalence and subclassifications were estimated, and among key subgroups [age, sex, race/ethnicity, advanced liver fibrosis (liver stiffness measurement [LSM] ≥11.7 kPa)]. Among 7367 participants, 2549 had SLD (mean age 51 y, 57.7% male, 63.2% non-Hispanic White). The estimated prevalence of SLD was 34.2% (95% CI 31.9%-36.5%): MASLD 31.3% (29.2%-33.4%), MetALD 2% (1.6%-2.9%), ALD 0.7% (0.5-0.9%), etiology-specific/cryptogenic 0.03% (0.01%-0.08%). In exploratory analyses, participants classified as non-SLD with (vs. without) advanced fibrosis had a higher mean number of metabolic risk factors [2.7 (2.3-3.1) vs. 2.0 (1.9-2.0)] and a higher proportion with average alcohol use ≥20 g/d (women)/≥30 g/d (men) [20.9% (6.2%-51.3%) vs. 7.2% (6.1%-8.4%)]. In another exploratory analysis, increasing quantities of alcohol use remaining below the threshold for MASLD + increased alcohol intake were associated with advanced liver fibrosis in men, but not women. There was 99% overlap in cases of NAFLD and MASLD. Our findings highlight the utility of the new consensus nomenclature to address deficiencies present with the old nomenclature, and identify areas that require research to further refine classifications of SLD.

Patients’ Perspectives on Dietary Patterns and Eating Behaviors During Weight Regain After Gastric Bypass Surgery

PurposeFood quality, energy intake, and various eating-related problems have been highlighted as some of the components influencing weight after bariatric surgery. This study aimed to increase our knowledge of patients’ perspectives on dietary patterns and eating behaviors during weight regain after bariatric surgery.Materials and MethodsWe recruited 4 men and 12 women with obesity and the experience of weight regain after bariatric surgery at an obesity clinic in Stockholm, Sweden. Data were collected during 2018–2019. We conducted a qualitative study, carried out individual semi-structured interviews, and analyzed the recorded and transcribed interview data with thematic analysis.ResultsParticipants had regained 12 to 71% from their lowest weight after gastric bypass surgery performed 3 to 15 years before. They perceived their dietary challenges as overwhelming and had not expected weight management, meal patterns, increasing portion sizes, and appealing energy-dense foods to be problematic after surgery. In addition, difficulties with disordered eating patterns, emotional eating, and increased alcohol intake further contributed to the weight management hurdles. Insufficient nutritional knowledge and lack of support limited participants’ ability to avoid weight regain, leading to restrictive eating and dieting without sustained weight loss.ConclusionEating behavior and dietary factors such as lack of nutritional knowledge, emotional eating, or disorganized meal patterns contribute to difficulties with weight management after gastric bypass surgery. Improved counseling may help patients prepare for possible weight regain and remaining challenges with food and eating. The results highlight the importance of regular medical nutrition therapy after gastric bypass surgery.Graphical

Dose-dependent Association of Alcohol Consumption With Obesity and Type 2 Diabetes: Mendelian Randomization Analyses.

Effects of modest alcohol consumption remain controversial. Mendelian randomization (MR) can help to mitigate biases due to confounding and reverse causation in observational studies, and evaluate the potential causal role of alcohol consumption. This work aimed to evaluate dose-dependent effect of alcohol consumption on obesity and type 2 diabetes. Assessing 408 540 participants of European ancestry in the UK Biobank, we first tested the association between self-reported alcohol intake frequency and 10 anthropometric measurements, obesity, and type 2 diabetes. We then conducted MR analyses both in the overall population and in subpopulations stratified by alcohol intake frequency. Among individuals having more than 14 drinks per week, a 1-drink-per-week increase in genetically predicted alcohol intake frequency was associated with a 0.36-kg increase in fat mass (SD = 0.03 kg), a 1.08-fold increased odds of obesity (95% CI, 1.06-1.10), and a 1.10-fold increased odds of type 2 diabetes (95% CI, 1.06-1.13). These associations were stronger in women than in men. Furthermore, no evidence was found supporting the association between genetically increased alcohol intake frequency and improved health outcomes among individuals having 7 or fewer drinks per week, as MR estimates largely overlapped with the null. These results withstood multiple sensitivity analyses assessing the validity of MR assumptions. As opposed to observational associations, MR results suggest there may not be protective effects of modest alcohol consumption on obesity traits and type 2 diabetes. Heavy alcohol consumption could lead to increased measures of obesity as well as increased risk of type 2 diabetes.

Prior experience with flavored alcohol increases preference for flavored alcohol but flavor does not influence binge-like drinking behavior in mice

BackgroundBinge drinking can lead to various negative consequences and in non-experimental settings, alcohol usually contains flavoring, which may promote increased binge drinking. Preclinical models of binge-like drinking have been well established, however, the influence of flavor on alcohol preference and binge-like drinking has not been fully explored. MethodsMale and female C57BL/6 J mice were tested via two-bottle choice with alcohol flavored with different concentrations of unsweetened Cherry flavor Kool-Aid and water. Next, mice were tested for preference for flavored alcohol over plain alcohol. Consumption of flavored alcohol versus water was examined over 48 h. Binge-like drinking with flavored alcohol was validated via drinking in the dark (DID). A separate cohort of mice underwent chronic DID for 6 weeks with either flavored or plain alcohol. After chronic DID, mice were then tested for preference for flavored versus plain alcohol and then alcohol consumption despite adverse effects was examined using the quinine adulteration test. ResultsThe 0.1% Kool-Aid concentration was chosen to use for further testing based on intake. Mice preferred Kool-Aid flavored alcohol over plain alcohol after the concentration test, but mice with no prior exposure to plain or flavored alcohol preferred plain over flavored alcohol. Throughout all initial testing, female mice showed increased alcohol intake compared to male mice. Both male and female mice showed binge-like drinking of flavored alcohol, with females having higher intake and blood alcohol levels. Kool-Aid flavor did not increase alcohol intake during chronic binge-like drinking. Previous exposure to flavored alcohol during DID increased the preference for flavored alcohol over plain alcohol but did not influence alcohol consumption despite adverse effects. ConclusionThe present study indicates that prior experience with flavored alcohol increases preference and intake, suggesting an effect of learned safety from neophobia. However, flavor does not impact binge-like alcohol consumption or alcohol drinking despite negative consequences. Additionally, the current study shows that female mice will consume more flavored alcohol than males, similar to findings from other alcohol studies.

#6758 THE CASUAL ASSOCIATION OF ALCOHOL CONSUMPTION AND CHRONIC KIDNEY DISEASE: A MENDELIAN RANDOMIZATION STUDY

Abstract Background and Aims Many previous views believed that alcohol intake increases the risk of chronic kidney disease progression. Even in the previous KDIGO guidelines, alcohol restriction was included in the guidelines. However, in recent years, some research contradicted these views and removed alcohol restriction from the KDIGO guidelines. The causal relationship between alcohol intake and the risk of progression of chronic kidney disease was explored using the methods of Mendelian randomized studies. Method Using data from a large sample of genome-wide association studies, the Society for Genome-wide Association Analysis and Sequencing of alcohol and nicotine consumption or use (GSCAN) database (1.2 million individuals) was used to identify independent genetic loci strongly associated with alcohol consumption. Then select the corresponding genetic loci in the CKDgen consortium database (one million individuals) as instrumental variables. One is not to use “MR-PRESSO” package for analysis. Then, two sample Mendelian random methods, such as inverse variance weighting method, approximate maximum method, MR-Egger regression method, weighted median method and weighted model method, are adopted. The other one is to use “MR-PRESSO” bag to detect whether there are outlier points, remove them, and then use the inverse variance weighting method of quantity sample Mendelian random method. The causal relationship between alcohol intake and chronic kidney disease was reflected by the change in eGFR value with increased unit alcohol intake. Results A total of 44 single nucleotide polymorphisms (SNPS) were screened as instrumental variables. Without the use of “MR-PRESSO” package, the results obtained by using inverse variance weighting method, approximate maximum method and MR-Egger regression method were not statistically significant. The weighted median method showed that alcohol intake increased by one unit per week. The glomerular filtration rate (eGFR) was increased by 0.015ml/min (95%CI 0.005-0.026,P = 0.004). Weighted model results showed that an increase of one unit per week in alcohol intake was associated with an increase of 0.017ml/min in estimated glomerular filtration rate (eGFR) (95%CI 0.005-0.026, P = 0.002). The MR-Egger regression result showed that the genetic pleiotropy did not bias the result (intercept = 0.009,P = 0.507). However, with the removal of six outliers using MR-PRESSO, the inverse variance weighting method showed that an increase of one unit of alcohol intake per week increased the estimated glomerular filtration rate (eGFR) by 0.014ml/min (95%CI 0.010-0.020, P = 0.004). Conclusion This study provides an association between alcohol intake and progression of chronic kidney disease. Overall, increased alcohol intake is protective against progression of chronic kidney disease. Clinically, alcohol intake is associated with many diseases. Although this study concluded that alcohol has a protective effect on the progression of chronic kidney disease, whether increasing alcohol intake can protect kidney function needs to be treated with caution. In addition, the long-term effects of alcohol intake on the progression of chronic kidney disease also need to be studied.

The Psychosocial Impact of COVID-19 on an Adult Indian Population.

Coronavirus disease (COVID-19) was a pandemic with many physical, psychological, and socioeconomic effects. COVID-19 caused a global increase in anxiety and depression because of its novelty, high infectivity, varied presentation, and unpredictable mortality. In the face of collapsing healthcare facilities, monetary setbacks, and loneliness because of lockdowns, people were anxious, and this was compounded by media sensationalism. We aimed to study the psychosocial impact of COVID-19 on the adult Indian population. An online survey using SurveyMonkey was floated through WhatsApp messages in April 2020, using the 'chain-referral sampling' method. Responses from individuals >18 years were included, and questions included age, sex, occupation, demographics, and socioeconomic conditions. The prevalence of anxiety and depression was assessed using the Generalized Anxiety Disorder (GAD-7) and the Patient Health Questionnaire (PHQ-9) scales. Data was analyzed using IBM SPSS software, and predictors of anxiety and depression were assessed. A total of 2640 responses from individuals between 18 years and81 years were analyzed, of which 39% were from females and 85% from those <50 years of age. There were students (15.6%), teachers (10.7%), healthcare workers (16.8%), homemakers (9%), and daily wage laborers (4.1%), among others. Nearly 80% lived in cities, 55% had salaried jobs, 37% were working from home, 22% were temporarily unemployed, 10% were feeling work stress, 11% had increased alcohol intake, and 7.5% saw an increase in domestic violence. The income of 50% was adversely affected. Nearly 50% of our respondents had some symptoms of anxiety, and 23% had significant anxiety (GAD ≥5). The presence of anxiety was significantly higher in females, younger adults, city dwellers, healthcare workers, unemployed people, individuals living away from home, those without fixed salaries,those with work stress, and in people whose incomes had been adversely affected by the pandemic. On logistic regression analysis, female sex, younger age, unemployment, lack of salaried jobs, work stress, being a healthcare worker, and media reports were independent predictors of anxiety. About 60% of our respondents had some symptoms of depression, with 26% having significant depression (PHQ-9 ≥5). The presence of depression was significantly higher in females, younger adults, city dwellers, unemployed people, individuals living away from home without fixed salaries, andpeople with work stress. On logistic regression analysis, younger age, female sex, unemployment, lack of salaried jobs, work stress, and media reports were independent predictors of depression. Among our respondents, 70% used the time during the lockdown to study, 77% caught up with their families, and 56% reconnected with hobbies. Nearly 88% of our respondents had adjusted to their changing circumstances, helped by their religious beliefs and faith, the support of family and friends, good government measures, and the assurance of healthcare. Significant anxiety and depression were seen in 23% and 26% of respondents, respectively. Being a healthcare worker was an independent predictor of anxiety. Female sex, younger age, unemployment, work stress, and sensational media reports were independent predictors of both anxiety and depression.

Physical activity reduces alcohol consumption induced by reward downshift.

Increased voluntary consumption of alcohol and other anxiolytics has been demonstrated in animals after experiencing frustrative reward devaluation (downshift) or omission. These results have been interpreted in terms of emotional self-medication. In the present study, we analyzed whether voluntary physical activity reduces alcohol intake induced by reward downshift. Sixty-four male Wistar rats were divided into eight groups (n = 8). Thirty-two (downshifted) animals received 32% sucrose during 10 preshift sessions (5 min), followed by 4% sucrose during five postshift sessions, whereas 32 (unshifted) controls were always exposed to 4% sucrose. Immediately after each consummatory session, animals were exposed to a 2-hr two-bottle preference test involving 32% alcohol versus water or water versus water. Half of the animals had also access to a wheel for voluntary running during the preference test. The results showed lower sucrose consumption in downshifted groups compared with unshifted controls (the frustrative reward downshift effect). Reward downshift significantly increased alcohol intake, this effect being absent in downshifted animals with access to the wheel. These findings suggest that physical exercise could be useful to prevent alcohol self-medication induced by frustrative nonreward. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Influence of alcohol on newly developed metabolic dysfunction-associated fatty liver disease in both sexes: A longitudinal study

The influence of changes in alcohol consumption on newly developed metabolic dysfunction-associated fatty liver disease (MAFLD) is unclear. We investigated the influence of alcohol consumption on newly developed MAFLD in both sexes. This observational cohort study included 4071 patients who underwent more than two health check-ups between 2015 and 2020 over an interval of more than a year. Generalised estimating equations were used for analyses. At baseline, the rates of drinking and MAFLD between men and women were 72.5% versus 41.7% and 42.2% versus 22.1%, respectively. At the most recent stage, the rates of an increase in alcohol consumption for men and women were 13.3% and 8.7%, respectively, and 311/1192 (26.1%) men and 155/1566 (9.9%) women had newly developed MAFLD. The odds ratio (OR) for drinking in patients with newly developed MAFLD was 0.863 (men) (95% confidence interval [CI], 0.676-1.102, p=0.237) and 1.041 (women) (95% CI, 0.753-1.439, p=0.808); the OR for women who drank 140-279.9g/week was 2.135 (95% CI, 1.158-3.939, p<0.05) and that for all drinking categories among women was >1. Several non-invasive fibrosis scores were significantly associated with the quantity of alcohol consumption in patients with newly developed MAFLD (p<0.005). Alcohol consumption had no significant protective effect against newly developed MAFLD in both sexes, regardless of quantity. Conversely, alcohol consumption ≥140g/week was a risk factor for newly developed MAFLD in women. The development of liver fibrosis with increased alcohol intake should be considered in patients with MAFLD.

Life in lockdown: a qualitative study exploring the experience of living through the initial COVID-19 lockdown in the UK and its impact on diet, physical activity and mental health

BackgroundIn response to the COVID-19 pandemic, the UK imposed a national lockdown prompting change to daily routines. Among behaviours impacted by the lockdown, diet and physical activity may be particularly important due to their association with mental health and physical health. The aim of this study was to explore people’s experiences of how lockdown impacted their physical activity, dietary behaviours and mental health, with a view to informing public health promotion.MethodsThis phenomenological qualitative study used semi-structured telephone interviews. Interviews were audio-recorded and transcribed verbatim. Thematic analysis was conducted, guided by the Framework Approach.ResultsForty participants (28 female) completed an interview (mean duration: 36 min) between May and July 2020. The overarching themes identified were (i) Disruption (loss of routines, social interaction and cues to physical activity) and (ii) Adaptation (structuring the day, accessing the outdoor environment, finding new ways for social support). The disruption to daily routines altered people’s cues for physical activity and eating; some participants spoke of comfort eating and increased alcohol intake in the early days of lockdown, and how they consciously tried to change these when restrictions lasted longer than first anticipated. Others spoke of adapting to the restrictions using food preparation and meals to provide both routine and social time for families. Disruptions from the closure of workplaces resulted in flexible working times for some, allowing for physical activity to be built into the day. In later stages of restrictions, physical activity became an opportunity for social interaction and several participants reported intending to continue to replace sedentary means of socialising (e.g., meeting in cafes) with more active, outdoor activities (e.g., walking) once restrictions were lifted. Staying active and building activity into the day was seen as important to support physical and mental health during the challenging times of the pandemic.ConclusionsWhilst many participants found the UK lockdown challenging, adaptations to cope with the restrictions presented some positive changes related to physical activity and diet behaviours. Helping people sustain their new healthier activities since restrictions have lifted is a challenge but presents an opportunity for public health promotion.

Sex-related differences in the efficacy of Baclofen enantiomers on self-administered alcohol in a binge drinking pattern and dopamine release in the core of the nucleus accumbens.

Introduction: Clinical studies on the effectiveness of Baclofen in alcohol use disorder (AUD) yielded mixed results possibly because of differential effects of the enantiomers and sex-related differences. Here we examined the effect of the different Baclofen enantiomers on alcohol intake and on evoked dopamine release in the core of the nucleus accumbens (NAcc) in male and female Long Evans rats. Methods: Rats were trained to chronically self-administer 20% alcohol solution in daily binge drinking sessions and were treated with the different forms of Baclofen [RS(±), R(+) and S(-)]. The effects on the evoked dopamine release within the core of the nucleus accumbens were measured in brain slices from the same animals and the alcohol naïve animals using the fast scan cyclic voltammetry technique. Results: RS(±)-Baclofen reduced alcohol intake regardless of sex but more females were non-responders to the treatment. R(+)-Baclofen also reduced alcohol intake regardless of sex but females were less sensitive than males. S(-)-Baclofen did not have any effect on average but in some individuals, especially in the females, it did increase alcohol intake by at least 100%. There were no sex differences in Baclofen pharmacokinetic but a strong negative correlation was found in females with a paradoxical effect of increased alcohol intake with higher blood Baclofen concentration. Chronic alcohol intake reduced the sensitivity to the effect of Baclofen on evoked dopamine release and S(-)-Baclofen increased dopamine release specifically in females. Discussion: Our results demonstrate a sex-dependent effect of the different forms of Baclofen with no or negative effects (meaning an increase in alcohol self-administration) in subgroup of females that could be linked to a differential effect on dopamine release and should warrant future clinical studies on alcohol use disorder pharmacotherapy that will deeply analyze sex difference.

The effects of lipopolysaccharide exposure on social interaction, cytokine expression, and alcohol consumption in male and female mice

Much recent research has demonstrated a role of inflammatory pathways in depressive-like behavior and excess alcohol consumption. Lipopolysaccharide (LPS) is a cell wall component of gram-negative bacteria that can be used to trigger a strong inflammatory response in rodents in a preclinical research setting to study the mechanisms behind this relationship. In our study, we exposed male and female mice to LPS and assessed depressive-like behavior using the social interaction (SI) test, alcohol consumption in the two-bottle choice procedure, and expression of inflammatory mediators using quantitative PCR. We found that LPS administration decreased SI in female mice but had no significant impact on male mice when assessed 24 h after injection. LPS resulted in increased proinflammatory cytokine expression in both male and female mice; however, some aspects of the cytokine upregulation observed was greater in female mice as compared to males. A separate cohort of male and female mice underwent drinking for 12 days before receiving a saline or LPS injection, which we found to increase alcohol intake in both males and females. We have previously observed a role of the neurokinin-1 receptor (NK1R) in escalated alcohol intake, and in the inflammatory and behavioral response to LPS. The NK1R is the endogenous target of the neuropeptide SP, and this system has wide ranging roles in depression, anxiety, drug/alcohol seeking, pain, and inflammation. Thus, we administered a NK1R antagonist prior to alcohol access. This treatment reduced escalated alcohol consumption in female mice treated with LPS but did not affect drinking in males. Taken together, these results indicate that females are more sensitive to some physiological and behavioral effects of LPS administration, but that LPS escalates alcohol consumption in both sexes. Furthermore, NK1R antagonism can reduce alcohol consumption that is escalated by LPS treatment, in line with our previous findings.

Different risk factors distinguish myalgic encephalomyelitis/chronic fatigue syndrome from severe fatigue

Fatigue is a common reason that patients seek medical care. Only a fraction of these patients meet criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). To determine if ME/CFS is just a more extreme form of fatigue, or a qualitatively different condition, we assessed whether risk factors for ME/CFS and for Severe Fatigue were similar. An email questionnaire that inquired about symptoms of Severe Fatigue and ME/CFS was completed by 41,802 US female nurses from whom detailed medical and lifestyle information had been collected since 1989: 102 met criteria for ME/CFS, 522 had Severe Fatigue, and 41,178 individuals were without significant chronic fatigue. We used Cox proportional hazards regression to estimate the Hazard Ratio (HR) of Severe Fatigue and of ME/CFS with each of several potential risk factors, according to the level of exposure to each risk factor. The risk of Severe Fatigue was significantly increased among participants who were older, had a higher BMI in adulthood, used hormone therapy, had increased alcohol intake and decreased caffeine intake. In contrast, these risk factor associations were not seen in people with ME/CFS. A self-reported past history of acute infectious mononucleosis was associated with a non-significantly increased Hazard Ratio of later ME/CFS (HR 1.77, 0.87–3.61) and, to a lesser extent, of Severe Fatigue (HR 1.28, 0.98–1.66). The different contribution of various risk factors to Severe Fatigue and ME/CFS suggests that ME/CFS has a qualitatively different underlying biology from the more common state of Severe Fatigue.

Differential Effects of Nicotine, Alcohol, and Coexposure on Neuroimmune-Related Protein and Gene Expression in Corticolimbic Brain Regions of Rats.

Nicotine and alcohol co-use is extremely common and their use constitutes two of the most common causes of preventable death, yet the underlying biological mechanisms are largely understudied. Activation of neuroimmune toll-like receptors (TLRs) promotes the induction of proinflammatory cascades and increases alcohol intake in rodents, which further promotes TLRs in the brain; nicotine may decrease central proinflammatory signaling. The current studies sought to determine the effects of nicotine ± alcohol (alone or in combination) on circulating blood plasma and TLR protein/gene expression in addiction-associated corticolimbic brain regions, including the prefrontal cortex-prelimbic (mPFC-PL) and nucleus accumbens core (AcbC). Adult rats were treated with alcohol (0 or 2 g/kg, IG) and exposed to nicotine vapor (0 or 30 mg/mL solution) daily for 2, 14, or 28 days. Plasma studies indicated no effects of independent exposure or coexposure in males. Coexposure decreased plasma nicotine levels versus nicotine-only treated females, yet alcohol and cotinine concentrations were unchanged. By 28 days, the anti-inflammatory cytokine IL-13 was decreased in alcohol-only females. Divergent changes in TLR3 (but not TLR4) protein occurred for independent-drug exposed males (but not coexposure), with reductions in the mPFC-PL after 14 days and increases in the AcbC by 28 days. Gene expression following chronic coexposure suggests nicotine may regionally counteract alcohol-induced inflammation, including increased AcbC-TLR3/4/7 and several downstream markers in females and increased mPFC-PL-TLR3 and -STAT3 (but not IRF3) evident in males with exposure to either drug alone. These findings give further insight into the role of sex and the neuroimmune system in independent exposure and coexposure to nicotine ± alcohol.