Excessive Alcohol Drinkers Research Articles

Association between serum per- and polyfluoroalkyl substances levels and metabolic dysfunction-associated steatotic liver disease

Experimental evidences have suggested that Per- and polyfluoroalkyl substances (PFASs) were hepatotoxicity, but epidemiologic inconsistencies. There were 1751 participants included in this study after excluding chronic hepatitis, cirrhosis, excessive alcohol drinkers, and those with missing key variables. Totally 30 PFASs were quantified using ultrahigh-pressure liquid chromatography tandem mass spectrometer (UPLC-MS). Metabolic dysfunction-associated steatotic liver disease (MASLD) defined as the presence of hepatic steatosis diagnosed on abdominal B-ultrasound in conjunction with at least one cardiometabolic risk factors (CMRF) and without other discernible cause. After multivariate adjustment, perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluoroalkyl carboxylates (ΣPFCAs), and perfluoroheptanoic acid (PFHpA) were positively associated with the risk of MASLD. Specifically, for each natural log-transformed unit increase in PFOA, PFNA, and ΣPFCAs, the risk of MASLD increased by 27% (95% confidence interval (CI): 1.09–1.48), 10% (95% CI: 0.99–1.23), and 29% (95% CI: 1.09–1.53), respectively. Compared with those in Tertile 1 of PFOA, PFNA, and ΣPFCAs, the risk of MASLD was increased by 35% (95% CI: 1.06–1.71, Ptrend = 0.019), 46% (95% CI: 1.15–1.85, Ptrend = 0.0018), and 43% (95% CI: 1.13–1.82, Ptrend = 0.0032) in Tertile 3, respectively. For PFHpA (detection rate: 14.79%), individuals with PFHpA levels above the detection limit had increased risk of MASLD by 54% (95% CI: 1.17–2.01) compared with those with PFHpA levels below the detection limit. While 8:2 chlorinated polyfluoroethersulfonic acid (8:2 Cl-PFESA) was inversely associated with steatotic liver disease (SLD) combined with 4 or 5 CMRFs (odds ratio per ln-unit = 0.87, 95% CI: 0.77–0.99). Mixed exposure analysis showed PFNA manifested a significant positive effect, while PFUdA had a significant negative effect. No association was found between other PFASs and MASLD prevalence. More prospective studies are needed to validate our conclusions.

The Impact of Physical Activity Intensity on the Dynamic Progression of Cardiometabolic Multimorbidity: Prospective Cohort Study Using UK Biobank Data.

Although many studies have reported on the associations between the amount of physical activity (PA) and the transitions of cardiometabolic multimorbidity (CMM), the evidence for PA intensity has not been fully evaluated. This study aimed to explore the impact of PA intensity on the dynamic progression of CMM. The prospective cohort of this study using data from the UK Biobank included 359,773 participants aged 37-73 years who were recruited from 22 centers between 2006 and 2010. The diagnoses of CMM, which included the copresence of type 2 diabetes (T2D), ischemic heart disease, and stroke, were obtained from first occurrence fields provided by the UK Biobank, which included data from primary care, hospital inpatient record, self-reported medical condition, and death registers. The PA intensity was assessed by the proportion of vigorous PA (VPA) to moderate to vigorous PA (MVPA). Multistate models were used to evaluate the effect of PA intensity on the dynamic progression of CMM. The first model (model A) included 5 transitions, namely free of cardiometabolic disease (CMD) to first occurrence of CMD (FCMD), free of CMD to death, FCMD to CMM, FCMD to mortality, and CMM to mortality. The other model (model B) used specific CMD, namely T2D, ischemic heart disease, and stroke, instead of FCMD and included 11 transitions in this study. The mean age of the included participants (N=359,773) was 55.82 (SD 8.12) years at baseline, and 54.55% (196,271/359,773) of the participants were female. Compared with the participants with no VPA, participants with intensity levels of >0.75 to <1 for VPA to MVPA had a 13% and 27% lower risk of transition from free of CMD to FCMD (hazard ratio [HR] 0.87, 95% CI 0.83-0.91) and mortality (HR 0.73, 95% CI 0.66-0.79) in model A, respectively. The HR for the participants with no moderate PA was 0.82 (95% CI 0.73-0.92) compared with no VPA. There was a substantially protective effect of higher PA intensity on the transitions from free of CMD to T2D and from T2D to mortality, which reveals the importance of PA intensity for the transitions of T2D. More PA and greater intensity had a synergistic effect on decreasing the risk of the transitions from free of CMD to FCMD and mortality. Male participants, younger adults, adults with a higher BMI, current or previous smokers, and excessive alcohol drinkers could obtain more benefits from higher PA intensity for the lower risk of at least 1 transition from free of CMD, then to CMM, and finally to mortality. This study suggests that higher PA intensity is an effective measure for preventing CMM and mortality in the early period of CMM development. Relevant interventions related to higher PA intensity should be conducted.

Predominantly Pro-Inflammatory Phenotype with Mixed M1/M2 Polarization of Peripheral Blood Classical Monocytes and Monocyte-Derived Macrophages among Patients with Excessive Ethanol Intake.

Excessive alcohol consumption impairs the immune system, induces oxidative stress, and triggers the activation of peripheral blood (PB) monocytes, thereby contributing to alcoholic liver disease (ALD). We analyzed the M1/M2 phenotypes of circulating classical monocytes and macrophage-derived monocytes (MDMs) in excessive alcohol drinkers (EADs). PB samples from 20 EADs and 22 healthy controls were collected for isolation of CD14+ monocytes and short-term culture with LPS/IFNγ, IL4/IL13, or without stimulation. These conditions were also used to polarize MDMs into M1, M2, or M0 phenotypes. Cytokine production was assessed in the blood and culture supernatants. M1/M2-related markers were analyzed using mRNA expression and surface marker detection. Additionally, the miRNA profile of CD14+ monocytes was analyzed. PB samples from EADs exhibited increased levels of pro-inflammatory cytokines. Following short-term culture, unstimulated blood samples from EADs showed higher levels of soluble TNF-α and IL-8, whereas monocytes expressed increased levels of surface TNF-α and elevated mRNA expression of pro-inflammatory cytokines and inducible nitric oxide synthase. MDMs from EADs showed higher levels of TNF-α and CD206 surface markers and increased IL-10 production. LPS/IFNγ induced higher mRNA expression of Nrf2 only in the controls. miRNA analysis revealed a distinctive miRNA profile that is potentially associated with liver carcinogenesis and ALD through inflammation and oxidative stress. This study confirms the predominantly pro-inflammatory profile of PB monocytes among EADs and suggests immune exhaustion features in MDMs.

No difference in COVID-19 treatment outcomes among current methamphetamine, cannabis and alcohol users

BackgroundPoor outcomes of COVID-19 have been reported in older males with medical comorbidities including substance use disorder. However, it is unknown whether there is a difference in COVID-19 treatment outcomes between patients who are current cannabis users, excessive alcohol drinkers and those who use a known hazardous stimulant such as methamphetamine (METH).MethodsElectronic medical records (EMR) of COVID-19 patients with current METH (n = 32), cannabis (n = 46), and heavy alcohol use (n = 44) were reviewed. COVID-19 infection was confirmed by positive SARS-CoV-2 PCR test, current drug use was confirmed by positive urine drug testing, and alcohol use was identified by a blood alcohol concentration greater than 11 mg/dl.Multivariate linear regression models as well as the firth logistic regression models were used to examine the effect of substance use group (METH, cannabis, or alcohol) on treatment outcome measures.ResultsA total of 122 patients were included in this analysis. There were no significant differences found between drug groups in regards to key SARS-CoV-2 outcomes of interest including ICU admission, length of stay, interval between SARS-CoV-2 positive test and hospital discharge, delirium, intubation and mortality after adjusting for covariates. About one-fifth (21.9% in METH users, 15.2% in cannabis users, and 20.5% in alcohol users) of all patients required ICU admission. As many as 37.5% of METH users, 23.9% of cannabis users, and 29.5% of alcohol users developed delirium (P = 0.4). There were no significant differences between drug groups in COVID-19 specific medication requirements. Eight patients in total died within 10 months of positive SARS-CoV-2 PCR test. Two patients from the METH group (6.3%), two patients from the cannabis group (4.3%), and four patients from the alcohol group (9.1%) died.DiscussionThe study outcomes may have been affected by several limitations. These included the methodology of its retrospective design, relatively small sample size, and the absence of a COVID-19 negative control group. In addition, there was no quantification of substance use and many covariates relied on clinical documentation or patient self-report. Finally, it was difficult to control for all potential confounders particularly given the small sample size.ConclusionDespite these limitations, our results show that current METH, cannabis, and heavy alcohol users in this study have similar treatment outcomes and suffer from high morbidity including in-hospital delirium and high mortality rates within the first-year post COVID-19. The extent to which co-morbid tobacco smoking contributed to the negative outcomes in METH, cannabis, and alcohol users remains to be investigated.

Outcomes of excessive alcohol drinkers without baseline evidence of chronic liver disease after 15 years follow-up: Heavy burden of cancer and liver disease mortality.

Most long-term heavy drinkers do not have clinically evident chronic liver disease (CLD). However, at any time-point, their risk of developing CLD remains unknown. We aimed to evaluate the long-term outcomes of a group of heavy drinkers, without evidence of CLD at baseline. A cohort of 123 long-term heavy drinkers without CLD were prospectively recruited in 2002 and retrospectively followed until 2018. At baseline (2002), median alcohol consumption was 271±203g/day during 21.5±20 years, 65% being abstinent during the previous 1.75±5 months. Patients were followed for 14±3 years. During follow-up, 53% reported any alcohol intake. Alcohol consumption during follow-up associated weakly with either 1- or 6-months previous abstinence at baseline. Until 2018, progression to CLD occurred in 6%, associating with years of alcohol intake during follow-up (OR 1.15 [1.01-1.31]) and baseline alkaline-phosphatase (OR 1.05 [1.01-1.10]). During follow-up, being abstinent for at least 1 year positively associated with CLD-free survival. 27% died (55% of cancer-mostly oropharyngeal cancer, 27% of cardiovascular disease, and 9% of liver disease), with a mean age of 71 years [69-74] (10 years less than the expected in the Portuguese population). Achieving abstinence for at least 1 year positively associated with overall survival, while smoking, and hepatic steatosis at baseline associated negatively. Long-term heavy drinkers seemed to have a decreased life expectancy compared with the overall Portuguese population. Cancer was the main cause of death. Our results suggest that progression to CLD depends mostly on continued alcohol intake. Alcohol abstinence, even if temporary, seems to decrease the risks of CLD and mortality.

Heightened Exploratory Behavior Following Chronic Excessive Ethanol Drinking: Mediation by Neurotensin Receptor Type 2 in the Anterior Paraventricular Thalamus.

Chronic, excessive alcohol drinkers, even without dependence, can exhibit changes in behavior and neurochemical systems. Identifying these changes and their relationship with one another could provide novel avenues for the prevention and treatment of alcohol use disorder. We recently demonstrated, in rats, that neurotensin (NTS) in the paraventricular thalamus (PVT) regulates excessive ethanol (EtOH) drinking. Here, we investigate the effects of chronic EtOH drinking on the PVT-NTS system and its contribution to EtOH-induced behavioral changes. We gave adult male Long-Evans rats 20% EtOH under the intermittent access 2-bottle-choice paradigm or maintained them on chow and water for up to 11weeks. Prior to EtOH exposure and following several weeks of access, during acute abstinence, we tested these groups for multiple behaviors. In the 12th week, during acute abstinence, we examined gene expression and peptide levels of NTS and its receptors in the anterior and posterior subregions of the PVT. Finally, in chronic EtOH drinkers, during acute abstinence, we microinjected the NTS receptor type 2 (NTS2R) agonist, JMV-431, in the anterior PVT (aPVT) and examined subsequent EtOH intake and behavior. Following chronic intermittent EtOH access, rats were classified by cluster analysis as high or low EtOH drinkers. High EtOH drinkers spent more time in the light chamber of a light-dark box and open arms of an elevated plus maze and entered fewer familiar holes in a hole-board apparatus. These differences were absent prior to EtOH exposure but were detectable as early as 4weeks into drinking. Time in the light chamber following chronic drinking also predicted level of subsequent drinking. High EtOH drinkers also showed elevated protein levels of NTS2R in the aPVT, and pharmacological stimulation of aPVT NTS2R in low drinkers mimicked the increased time spent in the light chamber that was observed in high drinkers. Our findings suggest that chronic, excessive, but not lower level, EtOH drinking induces heightened or flexible exploratory behavior, which predicts future EtOH drinking and is partly mediated by elevated NTS2R signaling in the aPVT. These EtOH-induced alterations represent adaptations that could perpetuate excessive drinking and lead to the development of EtOH dependence.

Alcohol intake patterns for cancer and non-cancer individuals: a population study.

BackgroundAlcohol intake is a leading modifiable cause related to cancer-specific deaths. Various alcohol intake patterns have shown to impact cancer progression differently, however, many studies only evaluated simplified patterns (such as heavy vs. non-heavy drinking) of alcohol intake for cancer survivors. The objective of this study is to provide population-based prevalence of the complex alcohol drinking patterns for cancer survivors, and compare it with that of non-cancer individuals. Additionally, we evaluated the impact of cancer related factors (binary, alcohol-related cancer type, and length of cancer history) to the alcohol intake patterns adjusted for the selected factors.MethodsA total of 193,197 individuals, including 16,504 cancer survivors, with age ≥18 years old in the 2012–2017 National Health Interview Survey (NHIS) were included in this study. The population-based prevalence of alcohol patterns was estimated. To evaluate cancer related factors associated with the alcohol intake patterns, we applied multinomial logistic models with the appropriate sampling weights and adjusted the selected demographic factors and smoking status.ResultsThere were 62.1% of cancer survivors and 66.0% of non-cancer individuals who were current alcohol drinkers in the past year. The prevalence of heavy drinking was identical for 5.2% of cancer and non-cancer individuals. For frequent binge drinking, cancer survivors tended to have less frequent binge than non-cancer individuals (2.8% vs. 4.9%). After adjusting for the selected demographic factors and smoking status, the cancer survivors were less likely to have the intermediate level of alcohol intake (light/moderate or occasional binge drinking) compared with non-cancer individuals, but no difference for the excessive alcohol intake (heavy or frequent binge drinking) was observed for those with and without cancer. As for cancer type, those with non-alcohol related cancer tended to be a current drinker compared with those with alcohol-related cancer. Compared with cancer survivors with a short cancer history (2–4 years), survivors with a cancer history of 5–9 years were more likely to be current drinkers after adjusting for the selected factors. Cancer status, alcohol-related cancer type and length of cancer history had no impact on excessive alcohol intake.ConclusionsIn summary, cancer survivors have similar excessive alcohol drinking patterns but were less likely to have the intermediate level of alcohol intake compared to non-cancer individuals. Alcohol intake may enhance cancer progression, interfere with cancer treatments and increase cancer-related mortality. To improve cancer survivors’ health, custom alcohol interventions and cessation programs should be conducted to minimize alcohol intake for cancer survivors, especially for excessive alcohol drinkers.

Fruit and vegetable intakes, associated characteristics and perceptions of current and future availability in Dutch university students.

To investigate fruit and vegetable (F&amp;V) intakes of university students and associated demographic and lifestyle characteristics, and students' perceptions of F&amp;V availability and F&amp;V intervention strategies in the university environment. Cross-sectional questionnaire data were collected; F&amp;V intakes were measured using a food frequency tool. Multivariable linear regression analyses were used to analyse the associations between demographic and lifestyle characteristics and F&amp;V intakes. Universities in the Netherlands. University students (n 717). The majority of students did not adhere to Dutch F&amp;V guidelines (71 % and 93 %, respectively). Fruit intake was lower among students who were male, living independently, enrolled in a technical study, not adhering to physical activity guidelines, and heavy to excessive alcohol drinkers. Vegetable intake was lower among students who were non-Dutch, living with their parents, not adhering to physical activity guidelines, and moderate and heavy to excessive alcohol drinkers. Most students perceived that their university environment offers sufficient healthy foods (60 %) and F&amp;V (65 %), but also indicated that their F&amp;V intakes would increase with interventions concerning affordable F&amp;V in the university canteen (64 %) or university supermarket (60 %). Students were less disposed to indicate that weekly local farmers' markets, vegetable parcels or a vegetable garden would increase their F&amp;V intakes. Dutch university students do not consume enough F&amp;V. Future efforts that aim to promote students' F&amp;V intakes should consider the differences between subgroups based on demographic and lifestyle characteristics and that affordable F&amp;V in the university environment might be an effective strategy.

Risk factors and survival analysis for synchronous esophageal carcinoma in patients with hypopharyngeal carcinoma

Objective: To investigate the risk factors and survival status of hypopharyngeal carcinoma with synchronous second primary carcinoma of the esophagus. Methods: One hundred and sixty patients with newly diagnosed hypopharyngeal carcinoma from January 2009 to December 2012 were retrospectively reviewed. The clinical data, tumor-related information and follow-up results were collected and analyzed. Results: Forty-three synchronous esophageal carcinomas (27%) were detected in 160 patients with hypopharyngeal carcinoma, and most patients (72%) were at an early stage. On univariate analysis, the median age of less than 55 years old (χ(2)=4.525, P=0.033), excessive alcohol consumption (χ(2)=6.942, P=0.008) and invasion site more than 3 anatomical regions (χ(2)=21.503, P=0.000) had a significant correlation with the occurrence of synchronous esophageal carcinomas. Multivariate analysis showed that excessive alcohol consumption (OR=4.787, P=0.029) and invasion site more than 3 anatomical regions (OR=14.391, P=0.000) were independent risk factors. The median survival time was 26 months in 43 patients with synchronous esophageal carcinomas, which was significantly lower than that (58 months) in patients without secondary primary esophageal carcinomas (χ(2)=11.981, P=0.001). Conclusions: There is a high incidence of synchronous esophageal carcinoma in hypopharyngeal carcinoma patients, affecting the prognosis of hypopharyngeal carcinoma. Surveillance for esophageal carcinomas in patients with hypopharyngeal carcinoma, especially in excessive alcohol drinkers, is warranted.

Should GPs prescribe vitamin B compound strong tablets to alcoholics?

Many medicine management committees are advising their GPs not to prescribe vitamin B compound strong tablets to alcoholics as they believe it is not recommended by the National Institute for Health and Care Excellence (NICE). The NICE guidelines for the management of alcohol problems that they quote do not discuss the use of vitamin B supplements other than thiamine (vitamin B1).1,2 This is not surprising because the clinical guideline is advising about the prevention and treatment of Wernicke–Korsakoff syndrome (WKS) in which just thiamine and not other B vitamin deficiency is implicated. There are many other diseases that can be caused by other B vitamin deficiency. B vitamins are a group of chemically different water-soluble co-factors, co-enzymes, and precursors that are important for many metabolic processes. A range of B vitamin deficiencies have been reported in chronic excessive and regular alcohol drinkers, and …

Ethyl glucuronide in hair of non-excessive alcohol consumers: correlations and gender influence

Hair ethyl glucuronide (hEtG) is a marker used for previous alcohol consumption. Correlations have been reported between the amount of alcohol consumed and hEtG concentration, but little has been published regarding relatively low levels of alcohol consumption and associated hEtG concentrations close to the limit of quantification (LOQ). Here, we investigate hEtG concentrations in non-excessive (<60 g/day) alcohol consumers and address the role of gender differences in hEtG concentration within this population. Daily alcohol consumption over a period of 3 months prior to hair collection was assessed using the Timeline Followback interview in 130 non-excessive (<60 g/day) alcohol consumers. Participants showed large variation in consumption, ranging from 10 g (~1 unit) to 3300 g (~330 units), during the prior 3 months. Eight individuals abstained from alcohol and served as a control group. HEtG was measured using gas chromatography–mass spectrometry in hair segments 0–3 cm in length, and varied from <LOQ to 29.8 pg/mg, showing a linear correlation with the amount of alcohol consumed (r = 0.81; p < 0.001). Gender had no influence on this correlation (gender effect: p < 0.001) or on the detection of nominal hEtG concentrations (p < 0.001). In conclusion, our results showed a correlation between hEtG and the amount of alcohol consumed, with no difference shown based on gender, for non-excessive alcohol consumption, confirming earlier results for excessive alcohol drinkers. We thus propose lowering the current hEtG cut-off value for abstinence assessment to <5 pg/mg.

Alcohol Use and Zinc Status in HIV+ Adults in Miami, Florida

Objective:Zinc (Zn) deficiency is the most common nutrient deficiency in HIV, and is not reversed with ART. Zn deficiency affects the immune system and may be aggravated by excessive alcohol use. We examined the effect of alcohol consumption on plasma and dietary Zn, and its association with disease progression in HIV+ adults.Methods:After consenting, the Alcohol Use Disorders Identification Test (AUDIT) score 蠅8 was used to identify excessive alcohol intake among 274 HIV+ adults. Nutrient intake was estimated with two 24‐hour dietary recalls; blood was drawn for plasma Zn levels, and parameters of HIV disease progression were obtained from medical charts.Results:Mean age was 45.9±7.8, 64% were male, 69% were Black, 43% had excessive alcohol drinking, 65% were Zn deficient, 40% used multivitamins with 15 mg Zn/day. CD4 cell count was lower in excessive alcohol drinkers compared to non‐drinkers or moderate drinkers (374.8±54.1 vs. 459.2±62.6 cells/mm3, P=0.029). CD4 cell count and viral load were better in non‐drinkers and moderate drinkers (β=0.2, SE=1.7, P=0.03 and β=‐0.18, SE=0.22, P=0.049, respectively) than in excessive drinkers. There was no relationship between excessive drinking and Zn deficiency. Excessive drinking was correlated with tobacco (r=0.24, P&lt;0.001) and illicit drug use (r=0.25, P&lt;0.001). Zn intake was correlated with energy (r=0.491, P&lt;0.001) and protein (r=0.718, P&lt;0.001) intake, but not with plasma levels of Zn.ConclusionModerate or no alcohol consumption is associated with better measures of HIV disease progression than excessive drinking, but is not associated with Zn deficiency.Funded by NIDA &amp; NIAAA

Prevalence and risk factors of sleep disturbances in a large HIV-infected adult population.

Introduction Sleep disturbances are frequently reported in HIV-infected patients but there is a lack of large studies on prevalence and risk factors, particularly in the context of current improved immuno-clinical status and use of the newest antiretrovirals (ARV).Method Cross-sectional study to evaluate the prevalence and factors associated with sleep disturbance in adult HIV-infected patients in six French centres of the region “Pays de la Loire”. Patients filled a self-administered questionnaire on their health behaviour, sleep attitudes (Pittsburgh Sleep Quality Index PSQI), quality of life (WHO QOL HIV BREF questionnaire) and depression (Beck depression Inventory (BDI)-II questionnaire). Socio-demographic and immunovirologic data, medical history, ARVs were collected.Results From November 2012 to May 2013, 1354 consecutive non-selected patients were enrolled. Patients’ characteristics were: 73.5% male, median age 47 years, active employment 56.7%, France-native 83% and Africa-native 14.7%, CDC stage C 21%, hepatitis co-infection 13%, lipodystrophy 11.8%, dyslipidemia 20%, high BP 15.1%, diabetes 3%, tobacco smokers 39%, marijuana and cocaine users, 11.7% and 1.7% respectively, and excessive alcohol drinkers 9%. Median (med) duration of HIV infection was 12.4 years, med CD4 count was 604/mm3; 94% of Patients were on ARVs, 87% had undetectable viral load. Median sleeping time was 7 hours. Sleep disturbances (defined as PSQI score >5) were observed in 47% of the patients, more frequently in female (56.4%) than in male (43.9%) (p<0.05) and moderate to serious depressive symptoms (BDI score>19) in 19.7% of the patients. In multivariate analysis, factors associated with sleep disturbances (p<0.05) were depression (odds ratio [OR] 4.6; 95% confidence interval [CI] 3.2–6.8), male gender (OR 0.7; CI 0.5–0.9), active employment (OR 0.7; CI 0.5–0.9), living single (OR 1.5; CI 1.2–2.0), tobacco-smoking (OR 1.3; CI 1.0–1.8), duration of HIV infection (>10 vs. <10 y.) (OR 1.5; CI 1.1–2.0), ARV regimen containing nevirapine (OR 0.7; CI 0.5–0.9) or efavirenz (OR 0.5; CI 0.3–0.7).Conclusions Prevalence of sleep disturbances is high in this HIV population and roughly similar to the French population. Associated factors are rather related to social and psychological status than HIV infection. Depression is frequent and should be taken in care to improve sleep quality.

Increasing serum pre-adipocyte factor-1 (Pref-1) correlates with decreased body fat, increased free fatty acids, and level of recent alcohol consumption in excessive alcohol drinkers

Patients with alcoholic liver disease have been reported to have a significantly lower percentage of body fat (%BF) than controls. The mechanism for the reduction in %BF in heavy alcohol users has not been elucidated. In adipose tissue, Pref-1 is specifically expressed in pre-adipocytes but not in adipocytes. Pref-1 inhibits adipogenesis and elevated levels are associated with reduced adipose tissue mass. We investigated the association between serum Pref-1 and %BF, alcohol consumption, and serum free fatty acids (FFA) in a well-characterized cohort of heavy alcohol users compared to controls. One hundred forty-eight subjects were prospectively recruited. The Time Line Follow-Back (TLFB) questionnaire was used to quantify the amount of alcohol consumed over the 30-day period before their enrollment. Anthropometric measurements were performed to calculate %BF. Serum Pref-1 and FFA were measured. Fifty-one subjects (mean age 32 ± 9 years, 88% men) were non-excessive drinkers whereas 97 were excessive drinkers (mean age 41 ± 18 years, 69% men). Compared to non-excessive drinkers, individuals with excessive drinking had significantly higher levels of Pref-1 (p<0.01), FFA (p < 0.001), and lower %BF (p = 0.03). Serum levels of Pref-1 were associated with the amount of alcohol consumed during the previous 30 days. Serum Pref-1 was negatively correlated with %BF, but positively associated with serum FFA. Our data suggest that elevated Pref-1 levels in excessive drinkers might inhibit the expansion of adipose tissue, decreasing %BF in alcoholics. Further work is needed to validate these findings and to better understand the role of Pref-1 and its clinical significance in subjects with heavy alcohol use.

Tu1823 Early Activation of Peripheral Monocytes With Hallmarks of M1 and M2 Monocytic Cells in Excessive Alcohol Drinkers

Tu1823 Early Activation of Peripheral Monocytes With Hallmarks of M1 and M2 Monocytic Cells in Excessive Alcohol Drinkers

Chronic alcohol exposure, infection, extended circulating white blood cells differentiated by flow cytometry and neutrophil CD64 expression: a prospective, descriptive study of critically ill medical patients

BackgroundA history of prolonged and excessive consumption of alcohol increases the risk for infections. The goal of this study was to investigate circulating white blood cells (WBC) differentiated by flow cytometry and neutrophil CD64 expression in excessive alcohol drinkers versus abstinent or moderate drinkers, and in those with or without infection, in medical patients admitted to the intensive care unit (ICU).MethodsAll patients admitted between September 2009 and March 2010 with an ICU-stay of 3 days or more were eligible for inclusion. Upon admission, hematological exams were conducted by flow cytometry.ResultsOverall, 281 adult were included, with 37% identified as at-risk drinkers. The only significant difference found in circulating WBC between at-risk and not-at-risk drinkers was a lower number of B lymphocytes in at-risk drinkers (P = 0.002). Four groups of patients were defined: not-at-risk drinkers with no infection (n = 66); not-at-risk drinkers with infection (n = 112); at-risk drinkers with no infection (n = 53); and at-risk drinkers with infection (n = 50). Whilst the presence of infection significantly reduced levels of noncytotoxic and cytotoxic T lymphocytes and significantly increased levels of CD16– monocytes in not-at-risk drinkers, with variation related to infection severity, infection had no effect on any of the variables assessed in at-risk drinkers. Post-hoc comparisons showed that B-lymphocyte, noncytotoxic, and cytotoxic T lymphocyte and CD16– counts in at-risk drinkers were similar to those in not-at-risk drinkers with infection and significantly lower than those in not-at-risk drinkers without infection. Neutrophil CD64 index varied significantly between groups, with variations related to infection, not previous alcohol consumption.ConclusionsThese results show that chronic alcohol exposure has an impact on the immune response to infection in critically ill medical patients. The absence of significant variations in circulating WBC seen in at-risk drinkers according to the severity of infection is suggestive of altered immune response.

TP53 codon 72 polymorphism is associated with pancreatic cancer risk in males, smokers and drinkers

Tumor protein p53 (TP53) is the best-known tumor suppressor gene and plays a crucial role in carcinogenesis. The TP53 Arg 72 Pro polymorphism has been reported to be a risk factor for several types of cancer, but its association with pancreatic cancer has not been fully evaluated. Therefore, we investigated the effects of this polymorphism on pancreatic cancer in relation to smoking and drinking habits by examining the distribution of the SNP genotypes in 226 pancreatic cancer patients and 448 healthy controls. The frequencies of Arg/Arg, Arg/Pro and Pro/Pro were found to be 37, 49 and 15% in the pancreatic cancer cases and 44, 46 and 10% in the controls, respectively. Compared to the controls with the Arg/Arg genotype, cases with Pro/Pro homozygosity exhibited a significantly increased risk [adjusted odds ratio (OR)=1.70; 95% confidence interval (CI) 1.01-2.88]. In stratified studies, the association was particularly strong in males (OR=2.62; 95% CI 1.32-5.23), particularly in those smoking in excess of 20 pack-years and drinking in excess of 23 g ethanol/day (OR=5.02; 95% CI 1.12-22.51). We found that the TP53 Pro/Pro genotype compared to the Arg/Arg genotype had a profound effect on pancreatic cancer risk among males, particularly among heavy smokers and excessive alcohol drinkers.

Exploring the role of cognitive and structural forms of social capital in HIV/AIDS trends in the Kagera region of Tanzania – a grounded theory study

The article presents a synthesis of data from three village case studies focusing on how structural and cognitive social capital may have influenced the progression of the HIV epidemic in the Kagera region of Tanzania. Grounded theory was used to develop a theoretical model describing the possible links between structural and cognitive social capital and the impact on sexual health behaviours. Focus group discussions and key informant interviews were carried out to represent the range of experiences of existing social capital. Both structural and cognitive social capital were active avenues for community members to come together, empower each other, and develop norms, values, trust and reciprocal relations. This empowerment created an enabling environment in which members could adopt protective behaviours against HIV infection. On the one hand, we observed that involvement in formal and informal organisations resulted in a reduction of numbers of sexual partners, led people to demand abstinence from sexual relations until marriage, caused fewer opportunities for casual sex, and gave individuals the agency to demand the use of condoms. On the other hand, strict membership rules and regulations excluded some members, particularly excessive alcohol drinkers and debtors, from becoming members of the social groups, which increased their vulnerability in terms of exposure to HIV. Social gatherings (especially those organised during the night) were also found to increase youths’ risk of HIV infection through instances of unsafe sex. We conclude that even though social capital may at times have negative effects on individuals’ HIV-prevention efforts, this study provides initial evidence that social capital is largely protective through empowering vulnerable groups such as women and the poor to protect against HIV infection and by promoting protective sexual behaviours.

Alcohol consumption among patients with hepatitis B infection in northern Portugal considering gender and hepatitis B virus genotype differences

Alcohol abuse is an important public health problem. In Portugal with a population of 10 millions of inhabitants, there are around 10% of alcoholics or excessive alcohol drinkers and 1% of chronically infected patients with hepatitis B virus (HBV). To examine the characteristics of patients with higher levels of alcohol consumption and to investigate the association between alcohol consumption and liver damage a total of 298 chronically infected individuals, with HBV genotyped and submitted to liver biopsy, were classified with Child's grading and separated by habits of alcohol intake, less and greater than 20 g/day. No significant differences were observed about genotype but genotypes A and D were predominant in both of them. A higher percentage of males ( P < .001) were observed in the group with alcohol intake above 20 g/day, as well a lower proportion of patients with HBeAg negativity ( P ≤ .035). In this group, biochemistry parameters, such as alanine aminotransferase ( P = .006), aspartate aminotransferase ( P = .001), gamma-glutamyl transferase ( P < .001) were elevated in a significantly higher proportion than in the other group. The analysis of hematological parameters showed significantly lower values of platelets ( P = .042) and mean corpuscular volume ( P < .001) and significantly higher values of prothrombin time ( P < .001) in the group with higher levels of alcohol consumption. The characteristics of biopsy ( P < .001) and Child–Phug's classification ( P = .002) revealed more severe results in this group. Logistic regression showed a positive association between liver damage and alcohol intake, increasing with age. In female patients, a strong positive association between alcohol intake and liver damage was also found (odds ratio: 9.379; 95% confidence interval: 0.859–468.422; P = .037); however, the most severe cases were only observed in women older than 45 years. In patients with HBV infection, alcohol is associated with a more severe liver disease. No evidence was found concerning association with HBV genotype.

Diagnostic Values of Surface‐Enhanced Laser Desorption/Ionization Technology for Screening of Habitual Drinkers

The currently available biological markers are limited in sensitivity and specificity for screening of excessive alcohol drinkers. We recently purified and identified 3 potential markers for alcoholism (5.9 and 7.8 kDa peptides and 28 kDa protein) by using surface-enhanced laser desorption/ionization (SELDI-TOF MS) technology. In the present study, we determined the diagnostic values of these novel markers in screening habitual drinkers with moderate alcohol consumption (hereafter habitual drinkers) in the general population as compared with 2 conventional markers: gamma-glutamyltransferase (GGT) and carbohydrate-deficient transferrin (CDT). Serum samples obtained from a total of 128 Japanese who sought regular medical checkup were analyzed by SELDI-TOF MS. The relative intensities of the 5.9 and the 28 kDa peak of habitual drinkers were significantly different from those in nondrinkers even in GGT nonresponders. The sensitivity and specificity were the highest in 5.9 kDa. When 5.9, 28 kDa, and GGT were combined, 96.8% of the habitual drinkers were successfully screened with a specificity of 60.9%. The results of this study clearly indicate that the 5.9 kDa peak is a promising novel biological marker for moderate alcohol consumption.