Alcohol (Hanover, York County, Pa.)最新文献

Background: Alcohol use and hepatitis C virus (HCV) often coexist and are associated with cardiovascular disease. One of the underlying drivers is dyslipidemia. We assessed lipid and lipoprotein levels and the relationship between alcohol use and atherogenic lipid profiles, specifically small dense low-density lipoprotein cholesterol (sdLDL-C), in Latinos with and without HCV.

Methods: From June 1, 2002, to January 1, 2016, 150 Latino adults underwent demographic, clinical, metabolic, lipid/lipoprotein, and genetic evaluations. Linear regression (adjusted for age, sex, and recent alcohol use) assessed factors associated with sdLDL-C.

Results: Participant characteristics were as follows: median age 44 years, 64% male, 39% HCV+, and alcohol use in the last 12 months was 19% heavy and 47% moderate. Ancestries were as follows: 52% European, 40% Native American (NA), and 4.3% African. 29% had non-CC PNPLA3, 89% non-CC TM6SF2, and 73% non-CC IL-28b genotypes. High-density lipoprotein (HDL) cholesterol, HDL-3, apolipoprotein A-1, and lipoprotein-associated phospholipase A2 levels differed by alcohol use groups (p < 0.05). On multivariable analysis, female sex (est. -6.08, p < 0.001), HCV+ status (est. -8.49, p < 0.001), and heavy alcohol use (vs. none) (est. -4.32, p = 0.03) were associated with lower, while NA ancestry (est. 0.92; p = 0.01) and adipose tissue insulin resistance (est. 3.30, p < 0.001) were associated with higher sdLDL-C levels. The positive association between NA ancestry and sdLDL-C was dampened by the presence of a non-CC IL28b genotype (interaction est. -1.95, p = 0.01).

Conclusions: In this Latino cohort, ancestry and metabolic dysfunction, independent of alcohol use and HCV, were associated with atherogenic risk. In addition to HCV treatment in this population, cardiometabolic health should be optimized.

Background: Chronic alcohol drinking causes hepatic vitamin A (retinoids and derivatives) decreases, which correlate with the progression and severity of alcohol-associated liver disease (ALD). However, the effects of short-term ethanol (EtOH) intake on liver retinoids and ALD are still undefined.

Methods: Using high-performance liquid chromatography and high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC, HPLC-MS/MS), and molecular biology techniques in mice and cultured human hepatocytes, we investigated the temporal EtOH effects on retinoids and ALD.

Results: In female and male mice, acute EtOH intake caused hepatic retinol (ROL) and retinyl palmitate (RP) decreases within hours, whereas it did not significantly change the retinoic acid (RA) levels, and those of the RA catabolism metabolite, 4-oxo-RA. After EtOH withdrawal, the liver recovered the ROL and RP levels within 48 h, whereas RA and 4-oxo-RA levels remained almost undetectable by this time point. Compared with control diet-fed mice, hepatic ROL and RP levels remained decreased in the 10-day and 3-week-long EtOH treatments, while retinyl oleate and linoleate increased. Interestingly, some of the RA signaling receptors, Rarβ, along with Cyp26a1, revealed dramatic transcript increases during the 10-day-long experiments that attenuated over time (up to 8 weeks), reflecting impaired RA signaling. Our work also showed that primary human hepatocytes serve as a model to better define the role of EtOH in retinoid biology.

Conclusions: This work reveals that acute and short-term exposures to EtOH disrupt retinoid homeostasis, identifying key events in the early pathogenesis of ALD.

Background: Substance use disorder (SUD) is a prodigious public health issue characterized by a substantial treatment gap. Despite challenges, millions have resolved a prior significant alcohol or drug problem, increasingly using online supports as a part of their recovery efforts (e.g., virtual mutual-help group meetings, traditional social networking sites [SNS]). However, the content surrounding SUD recovery-related discussion on SNS such as Twitter remains largely unexamined. To fill this gap, we explored public tweets using SUD recovery-related hashtags.

Methods: From January 1, 2022, to December 31, 2022, 455,968 public tweets were collected using SUD recovery-related hashtags. Natural language processing was used to identify and remove irrelevant groupings of tweets from the dataset, resulting in a final corpus of 186,460 tweets. A random subsample of 1800 tweets was extracted for content analysis, involving codebook development, manual annotation by trained coders, and inter-rater reliability assessment (average Cohen's κ = 0.77).

Results: Nearly half (41.7%) of SUD recovery-related posts were from individuals in or seeking recovery, while 21.3% originated from addiction treatment industry accounts. Common themes included addiction treatment marketing (27.4%; some of which promoted scientifically unsupported products or services), emotional support (15.6%), celebrating a recovery milestone (15.4%), alcohol/drug-related sociopolitical commentary (14.7%), expressions of gratitude (11.5%), and mutual-help group participation (8.7%).

Conclusions: SUD recovery-related content on Twitter reflected individuals seeking social support during efforts to initiate or maintain recovery. However, these accounts may be met with marketing material from entities that misrepresent their services or promote products based on unsubstantiated claims. Stricter (or enforcement of existing) regulations may be warranted to protect vulnerable SNS platform users from entities seeking to exploit them for financial gain.

Background: This study sought to identify effective health warnings about alcohol consumption and breast cancer risk among young adult female participants.

Methods: We tested a pool of health warnings in a national pilot study. We used the most effective designs from the pilot in the main experiment where young (ages 21-29) U.S. adult female participants (N = 1038) reporting past 30-day alcohol consumption were randomly assigned into 1 of 4 conditions where they viewed a health warning about (1) mortality, (2) mastectomy, (3) hair loss, or (4) control (non-health warning message). Participants were then randomly assigned to view 1 of 2 message types within each condition: text-only or pictorial. Warnings were shown apart from products. Outcomes were message reactions (attention to and cognitive elaboration of warnings, fear, hope, and perceived message effectiveness), attitudes and beliefs (perceived severity and susceptibility to alcohol harms, and perceived response and self-efficacy to prevent alcohol harms), and behavioral intentions to stop or to reduce alcohol consumption in the next month.

Results: Multivariate analysis of covariance (MANCOVA) models testing between warning conditions showed estimated marginal means (EMM) for every health warning condition were significantly higher than the control for attention (control = 5.80 vs. mortality = 6.63, mastectomy = 6.81, hair loss = 6.83, all ps < 0.05), fear (control = 2.45 vs. mortality = 4.11, mastectomy = 4.16, hair loss = 4.02, ps < 0.05), perceived message effectiveness (control = 3.44 vs. mortality = 5.75, mastectomy = 5.82, hair loss = 6.09, ps < 0.05), and perceived severity of alcohol harms (control = 5.51 vs. mortality = 6.25, mastectomy = 6.09, hair loss = 6.35, ps < 0.05). There were no significant differences between the health warnings about cancer effects for perceived message effectiveness. EMMs for intentions to reduce alcohol consumption in the next month were significantly higher in the mortality (6.44) and hair loss (6.35) conditions versus control (5.61, ps < 0.05).

Conclusion: Exposure to health warnings about alcohol consumption and breast cancer risk (vs. control) resulted in greater attention, fear, perceived message effectiveness, perceived severity of alcohol harms, and intentions to reduce alcohol consumption.

Background: Alcohol Use Disorder (AUD) and childhood trauma both have detrimental effects on immune regulation. Immunoglobulins, key biomarkers of the adaptive immune system, may be selectively targeted by heavy alcohol consumption as well as childhood trauma. In this study, we investigated the relationship between alcohol drinking behavior, history of childhood trauma, and circulating levels of immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin M (IgM) in individuals with AUD.

Methods: Using linear regression, multiple variables, drinks per drinking day and childhood trauma questionnaire (CTQ) score, were evaluated in relation to immunoglobulin levels. All participants (N = 445) were treatment-seeking and admitted to the National Institutes of Health Clinical Center, where they underwent a battery of laboratory and psychological assessments.

Results: Analyses showed a significant positive association between alcohol consumption and IgA. Furthermore, there was a significant negative association between childhood trauma and IgG. Other significant results include a negative association between substance use disorder diagnosis (other than alcohol) and IgA, while anxiety disorder diagnosis was associated with lower IgG.

Conclusion: Heavy alcohol drinking is associated with elevated IgA levels, which may be a potential risk factor for alcohol-associated liver disease. On the other hand, childhood trauma's association with decreased IgG levels may be indicative of broader immune dysfunction. Taken together, changes in immunoglobulins may be valuable markers linking alcohol consumption and childhood trauma to immune health and disease progression.

Background: Hazardous use of alcohol is associated with cognitive-behavioral impairments and accelerated aging. To date, however, accelerated brain aging has not been tested as a mediating factor between alcohol use and associated task-based behavioral deficits, such as behavioral inflexibility. Here, we evaluated hazardous alcohol use as a predictor of machine learning-derived brain aging and tested if this measure accounted for the relationship between hazardous alcohol use and a task-based measure of behavioral flexibility.

Methods: In this secondary analysis, we applied brainageR, a machine learning algorithm, to anatomical T1-weighted magnetic resonance imaging (MRI) images to estimate brain age for a sample of healthy adults (ages 22-40) who self-reported alcohol use with the alcohol use disorder identification test (AUDIT) and performed the hidden association between images task (HABIT), a behavioral flexibility task. Behavioral inflexibility was quantified as the proportion of perseverative errors performed on the HABIT as a measure of habitual action selection. We then analyzed AUDIT score as a predictor of brain aging, and brain aging as a predictor of behavioral inflexibility. Lastly, we conducted a mediation analysis to evaluate brain aging as a mediator between alcohol use and behavioral inflexibility.

Results: Controlling for chronological age and sex, a higher AUDIT score predicted significantly more accelerated brain aging, which was further associated with more perseverative errors on the HABIT. Moreover, brain aging significantly mediated the association between AUDIT scores and behavioral inflexibility.

Conclusions: Our findings demonstrate that alcohol use is a significant predictor of accelerated brain aging, even in young adulthood. In addition, our findings suggest that such brain changes may mechanistically link more hazardous alcohol use to impaired behavioral flexibility. Future studies should also explore factors, such as other lifestyle behaviors, that may mitigate alcohol- and age-related processes.

Background: Increased survival, prolonged antiretroviral treatment (ART), and lifestyle choices, including alcohol misuse, increase the risk for comorbid conditions, including cardiometabolic comorbidities among people with HIV (PWH). Published studies indicate that dysregulated adipose tissue phenotype, particularly of the visceral adipose depot, contributes to metabolic dysregulation. Using a nonhuman primate model of simian immunodeficiency virus (SIV) infection, we previously demonstrated that chronic binge alcohol (CBA) administration to ART-treated rhesus macaques decreases whole-body glucose-insulin dynamics, increases omental adipose tissue (OmAT) collagen content, decreases OmAT adipocyte size, and alters pancreatic endocrine function. The objective of this study was to delineate the depot-specific effects of CBA on visceral (VAT) and subcutaneous adipose tissue (SAT) extracellular matrix (ECM) phenotype, the potential mechanisms involved in AT ECM remodeling, and the implications of increased tissue stiffness on AT metabolic alterations in female SIV-infected macaques.

Methods: Omental and subcutaneous adipose samples were obtained from female SIV-infected, ART-treated macaques that received intragastric administration of CBA (12-15 g/kg/week, CBA/SIV) or water (VEH/SIV) for 14.5 months.

Results: CBA preferentially altered the ECM phenotype in OmAT, a VAT depot. The CBA-associated changes included increased ECM accumulation, increased collagen I-III ratio, a profibrotic milieu, and decreased matrix metalloproteinase 13 activity. These changes were associated with smaller adipocyte size, decreased triglyceride content, decreased gene expression of perilipins, and a potential dysregulation of peroxisome proliferator-activated receptor gamma signaling.

Conclusions: Collectively, these findings suggest that CBA-mediated ECM remodeling "traps" adipocytes within a stiff environment that we propose disrupts adipocyte metabolic programming and may increase the risk for metabolic comorbidities.

Background: Alcohol use disorder remains a global issue. Thus, understanding the factors that contribute to alcohol abuse, including how food availability can influence drinking behavior, is critical.

Methods: Female and male C57Bl/6 and Swiss mice underwent a two-bottle choice Intermittent Overnight Drinking (IOD) protocol consisting of 12 sessions on alternate nights, three times per week, using lickometer devices. Mice had access to two bottles, containing either water or 10% ethanol, for 16 hours, starting 2 hours before the dark cycle. Animals were initially assigned to two groups: one with access to water, ethanol, and standard rodent chow (FOOD group), and another with access only to water and ethanol (NFOOD group). After six sessions, half of the mice in the second group were reassigned to a new group with delayed access to chow (NFOOD-FOOD group).

Results: Food availability led to increased drinking, but the modulation was liquid dependent for each strain. The presence of food primarily increased ethanol intake in C57Bl/6 mice, while it enhanced water intake in Swiss mice. Microstructure analysis revealed that food heightened ethanol licks in C57Bl/6 mice, whereas it elevated water licks in Swiss mice, without altering numbers of bouts. Additionally, overnight analysis showed that C57Bl/6 mice with access to food had a peak in ethanol licks between 20:00 and 22:00, while Swiss mice exhibited an increase in water licks starting at 20:00 to 2:00, highlighting a strain-specific response to the dark cycle.

Conclusions: This study provides normative data on the temporal patterns of water and ethanol consumption in C57Bl/6 and Swiss female and male mice, contributing valuable insights to the field of voluntary drinking behaviors in murine models.