Drs. Michael Miles, Laura Nagy, Tammy Chung, and Howard Becker with the Board of Field Editors and the Editorial Office of Alcohol: Clinical and Experimental Research would like to express gratitude to the following investigators who have reviewed manuscripts submitted to the Journal for publication from October 1, 2023, through September 30, 2024. It is the rigor of the peer review process that ultimately determines the quality of the Journal. Your continued support of the Journal is greatly appreciated.
We apologize if any reviewer has been inadvertently omitted from the list. Please let us know, as we intend to publish an addendum as necessary.
Background: Chronic alcohol consumption in alcohol use disorder (AUD) is associated with autonomic nervous system dysregulation, increasing cardiovascular risk, and high alcohol cravings. Heart rate variability (HRV), a marker of autonomic nervous system responsiveness to stressors, may mediate alcohol's impact on the cardiovascular system. While pregnenolone (PREG) has been shown to normalize heart rate and blood pressure in individuals with AUD, its effects on sympathetic and parasympathetic components of HRV and related alcohol craving are not known.
Methods: Fifty-five treatment-seeking individuals with AUD were randomized to placebo (n = 21) or daily pregnenolone at 300 mg (n = 18) or 500 mg (n = 16), in a double-blind, 8-week pilot clinical trial. In week 2, participants underwent three randomized, counterbalanced 5-minute personalized guided imagery provocations (stress, alcohol, and neutral/relaxing cues) on separate days. HRV indices were assessed during each session and analyzed using linear mixed-effects models (LMEs), including association between HRV indices and anxiety and alcohol craving.
Results: A medication group × condition interaction was found for parasympathetic, high-frequency (HF) (p = 0.028) and sympathetic/parasympathetic, low-frequency/high-frequency (LF/HF) ratio (p = 0.017) indices of HRV. Placebo had higher HF during alcohol cue (p = 0.011), while 500 mg PREG demonstrated lower HF in response to stress (p = 0.050) and alcohol cues (p = 0.047). Placebo showed lower LF/HF ratio during stress (p = 0.006) and alcohol cue (p = 0.001), while the PREG groups showed no changes. Overall, the LF/HF response to alcohol cue was significantly lower in placebo compared to the 300 mg PREG (p = 0.012) and 500 mg PREG (p = 0.037) groups. Lastly, HF was found to predict alcohol craving regardless of PREG doses.
Conclusions: We found a normalization of autonomic response in PREG groups. These findings suggest that PREG holds therapeutic potential for enhancing autonomic function in AUD.
Alcohol use is measured in diverse ways across settings. Harmonization of measures is necessary to assess effects of alcohol use in multi-cohort collaborations, such as studies of people with HIV (PWH).
Data were combined from 14 HIV cohort studies (nine European, five North American) participating in the Antiretroviral Therapy Cohort Collaboration. We analyzed data on adult PWH with measured alcohol use at any time from 6 months before starting antiretroviral therapy. Five cohorts measured alcohol use with AUDIT-C and others used cohort-specific measures. We harmonized alcohol use as grams/day, calculated using country-level definitions of a standard drink. For Alcohol Use Disorders Identification Test (AUDIT-C), we used Items 1 (frequency) and 2 (number of drinks on a typical day). Where alcohol was measured in categories, we used the mid-point to calculate grams/day. We used multivariable Cox models to estimate associations of alcohol use with mortality.
Alcohol use data were available for 83,424 PWH, 22,447 (27%) had AUDIT-C measures and 60,977 (73%) recorded the number of drinks/units per week/day. Of the sample, 19,150 (23%) were female, 54,006 (65%) had White ethnicity, and median age was 42 years. Median alcohol use was 0.3 g/day (interquartile range [IQR] 0–4.8) and 0 g/day (IQR 0–20) for those with and without AUDIT-C. There was a J-shaped relationship between grams/day and mortality, with higher mortality for PWH reporting no alcohol use (adjusted hazard ratio [aHR] 1.46; 95% CI: 1.23–1.72) and heavier (>61.0 g/day) alcohol use (aHR 1.92; 1.41–2.59) compared with 0.1–5.5 g/day among those with AUDIT-C measures. Associations were similar among those with non-AUDIT-C measures.
Grams/day is a useful metric to harmonize diverse measures of alcohol use. Magnitudes of associations of alcohol use with mortality may differ by setting and measurement method. Higher mortality among those with heavier alcohol use strengthens the case for interventions to reduce drinking.
Therapeutic options for managing intestinal and hepatic inflammation associated with alcohol consumption, a prevalent health problem worldwide, remain unavailable. This study examines the potential efficacy of polyethylene glycol (PEG) in mitigating the intestinal and hepatic damage, employing a mouse model for assessment.
First, the mixture of ethanol (4 g/kg body weight) and PEG (2 g/kg body weight) or an equivalent volume of vehicle was administered orally alcohol consumption.
Acute alcohol consumption was found to damage not only the liver but also the small intestine, as evidenced by histological findings and mRNA expression analysis of inflammatory cytokines. We also identified impaired motor function in the mouse model of binge drinking. Interestingly, PEG significantly mitigated both the impaired motor function and the injury and inflammation of the small intestine following binge drinking in mice. Furthermore, PEG exhibited hepatoprotective effects, as indicated by reduced hepatic enzyme levels in serum, less liver injury observed through H & E staining, and decreased neutrophil infiltration within the liver.
Collectively, these findings suggest that co-administration of PEG with binge ethanol could serve as an effective therapeutic strategy to prevent intestinal and hepatic inflammation.
Background: During the coronavirus disease 2019 (COVID-19) pandemic, there was a marked increase in alcohol consumption. COVID-19 superimposed on underlying liver disease notably worsens the outcome of many forms of liver injury. The goal of a current pilot study was to test the dual exposure of alcohol and COVID-19 infection in an experimental animal model of alcohol-associated liver disease (ALD).
Methods: After 4 weeks of ethanol (EtOH) feeding, C57BL/6 male mice received SARS-CoV-2 (SARS2-N501YMA30) intranasally at 3 × 102, 1 × 103, 3 × 103, and 1 × 104 plaque-forming units (PFU). Mice were then weighed/monitored daily for morbidity/mortality for 10 days while continuing EtOH consumption. Markers of liver inflammation, injury, and intestinal barrier integrity were evaluated.
Results: A similar gradual weight loss was observed in all inoculated mice (slightly less in the 3 × 102 group) up to post-infection day 4. Greater mortality was observed in mice receiving the highest viral dose at days 3 and 4 post-infection. The majority of the surviving mice subjected to EtOH and inoculated with 3 × 103 or 1 × 104 PFU rapidly lost 25% of their body weight and were euthanized on post-infection day 4. Analysis of liver health in animals that survived to the end of the experiment exhibited no significant changes in hepatic steatosis but had a limited increase in plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels at all viral doses versus EtOH alone. However, the 1 × 104 PFU viral dose exacerbated EtOH-induced hepatic inflammation characterized by elevated levels of several pro-inflammatory cytokines, including Il-6 and Tnf-α. There was limited effect of viral infection on the intestine.
Conclusions: SARS-CoV-2 infection caused a dose-dependent negative impact on body weight and survival in mice fed EtOH. This pilot study suggests that early mortality observed after high-dose SARS-CoV-2 challenge could be due, in part, to hepatic dysfunction following chronic EtOH feeding.
Preliminary evaluations of 212 drinking offspring from the San Diego Prospective Study (SDPD) indicated that over 50% developed alcohol use disorder (AUD) by their mid-20s. The present analysis evaluated if those findings remained robust when the group increased to 454 individuals, a sample size that facilitated a search for potential contributors to the high AUD prevalence.
Semistructured interviews were used to evaluate lifetime AUD diagnoses in 224 daughters and 230 sons from the SDPS (N = 454) by mean age 26. Analyses compared participants with and without AUD regarding demography, alcohol use, personality, and psychiatric diagnoses. Characteristics associated with AUD were entered together in a backward elimination regression analysis, and the results were entered in a structural equation model (SEM) to evaluate potential mediation of risks for alcohol problems.
Lifetime AUD was documented for 61% of the sons and 41% of the daughters. Offspring with AUD reported averages of 13 maximum and five usual drinks per occasion and endorsed an average of 4 DSM AUD criteria. Even after considering personality characteristics, family AUD histories, and personal psychiatric histories, significant contributions to the regression analysis were limited to lower levels of response to alcohol, higher positive alcohol expectancies, and drinking to cope. Key elements of the hypothesized SEM were supported, and mediation between the low alcohol response and the number of alcohol problems was documented for expectancies, drinking to cope, and peer heavier drinking.
The results support prior high AUD rates in SDPS offspring and demonstrate that the AUD diagnoses were associated with robust alcohol intake and problems. The data also indicated mediation of the impact of the low alcohol response on the development of AUD through several characteristics proposed by prior work in other populations.
Alcohol misuse is prevalent among firefighters, and associated adverse cardiometabolic health consequences could negatively impact readiness for duty. Mental health conditions may confer additional risk. Therefore, we aimed to determine whether alcohol misuse increases cardiometabolic risk among firefighters and whether mental health conditions modify these relationships.
Deidentified data from firefighters (N = 2405; 95.8% males, 38 ± 9 years, 29.6 ± 4.6 kg/m2) included demographics, Alcohol Use Disorders Identification Test (AUDIT) and AUDIT-C scores, mental health screening scores, anthropometrics, metabolic panel, and cardiorespiratory testing results. Differences in cardiometabolic parameters between firefighters with low AUDIT-C (<3 [females] or <4 [males]; no or low-risk alcohol use) or high AUDIT-C (≥3 [females] or ≥4 [males]; hazardous alcohol use) were determined and odds ratios for clinical risk factors were calculated. Posttraumatic stress disorder (PTSD), insomnia, depression, and anxiety were assessed as moderators.
Firefighters with high AUDIT-C had significantly (p < 0.05) higher total cholesterol (TC), high-density lipoprotein (HDL-C), and systolic blood pressure (SBP) and diastolic blood pressure (DBP) and lower hemoglobin A1C (HbA1c) than those with low AUDIT-C. In unadjusted and/or adjusted analyses, those with high AUDIT-C had increased risk for overweight/obesity, hypercholesterolemia, and prehypertension/hypertension, and decreased risk for low HDL and elevated HbA1c. There were inverse moderation effects by posttraumatic stress disorder (PTSD), depression, and anxiety on relationships between AUDIT-C score and BP. Insomnia (directly) and anxiety (inversely) moderated relationships between AUDIT-C score and circulating lipids.
Firefighters with high AUDIT-C have differential cardiometabolic risk, with specific relationships altered by mental health status. Whether higher HDL and lower HbA1c with high AUDIT-C in firefighters is protective long-term remains to be explored. Overall, these results underscore the need for alcohol screening and intervention to maintain cardiometabolic health and long-term occupational readiness among firefighters.
Background: Pituitary adenylate cyclase-activating polypeptide (PACAP) has been found to be involved in a wide range of motivated and affective behaviors. While the PACAP-38 isoform is more densely expressed than PACAP-27 in most of the brain, PACAP-27 is more highly expressed in the rodent paraventricular nucleus of the thalamus (PVT), where females also have greater expression than males. Notably, the role of PACAP-27 expression in cells of the PVT has not been explored.
Methods: Adult, female Long-Evans rats were injected in the PVT with an adeno-associated virus (AAV) to increase expression of PACAP or a control AAV. They were then investigated for subsequent ethanol drinking and preference; sucrose drinking and preference; or locomotor activity in a novel chamber, behavior in a light-dark box, behavior in a novelty suppression of feeding test, locomotor activity in a familiar activity chamber, and behavior in a forced swim test.
Results: Injection with the PACAP AAV resulted in a specific increase in levels of PACAP-27. Rats injected with the PACAP AAV demonstrated reduced drinking and preference for ethanol under the intermittent-access procedure compared to those injected with the control AAV. In contrast, rats injected with the PACAP AAV showed no significant difference in drinking or preference for sucrose, or in any affective behavior tested, except that they spent less time swimming in the forced swim test.
Conclusions: In light of the low overall level of expression of PACAP-27 in the brain, the ability of PACAP-27 in the PVT to control ethanol drinking, with minimal effects on other motivated or affective behaviors, supports the idea that compounds related to PACAP-27 should be investigated as potential therapeutics for the treatment of alcohol use disorder.
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：