Alcohol Treatment Research Articles

Advances in the management of alcohol-associated liver disease.

Alcohol-associated liver disease (ALD) is a significant global health challenge, encompassing a spectrum from steatotic liver disease to cirrhosis and alcohol-associated hepatitis, and contributed to 25% of global cirrhosis deaths in 2019. The identification of both modifiable (e.g. heavy drinking, metabolic syndromes) and non-modifiable risk factors (e.g. genetic predispositions) is crucial for effective disease management. Alcohol use assessment and treatment, by using both behavioral therapy and pharmacotherapeutic modalities, nutrition support, and optimization of liver disease modifiers, form the cornerstone of management. Advances in medical therapies, such as fecal microbiota transplantation and novel agents such as IL-22, are being explored for their therapeutic potential. A unifying theme in ALD care is the need for a personalized approach to management, accounting for the spectrum of the disease and individual patient characteristics, to tailor interventions effectively. Finally, it is essential to address the challenges to effective ALD treatment, including socioeconomic, logistical, and stigma-related barriers, to improve patient outcomes. This review discusses the current knowledge on ALD, including epidemiology, pathophysiology, risk factors, and management strategies, highlighting the critical role of integrated care models.

Effectiveness of Different Online Intervention Modalities for Middle-Aged Adults with Overweight and Obesity: A 20-Year Systematic Review and Meta-analysis.

The main objectives of this systematic review and meta-analysis study include evaluating the methodological quality of existing randomized controlled trials (RCTs) for weight loss and features of online intervention [OI]s in each trial, examining the associations between the methodological quality, intervention features and the effectiveness of OIs, and comparing the effectiveness of OIs and other intervention modalities through systematic review and meta-analysis. Systematic searches were conducted using PubMed, Cochrane Library, CINAHL, and PsycINFO in the past two decades (2000 through 2019). Inclusion criteria includes Online intervention (intervention modality), middle-aged adults with overweight or obesity, at least six months or longer study period, an RCT, and 70% plus retention rate. Risk of Bias was assessed using Miller et al. in (Hester, Miller (eds) Handbook of alcoholism treatment approaches: Effective alternatives (3rd ed.). Allyn & Bacon, Boston, 2003)'s Methodological Quality Rating Scale (MQRS) and GRADE. MOOSE guidelines was referred for data synthesis. In total, 29 OIs were evaluated using 10 criteria for methodological quality and eight criteria for intervention features. Results revealed that the mean methodological quality score of the RCTs was 12.1 (out of 16), and the mean intervention features score was 6.6 (out of 8). RCTs with higher scores were more effective in weight loss than those with lower scores. Results of meta-regression showed that methodological quality was more important than intervention features to increase the effectiveness. Results of meta-analysis showed that OIs were significantly more effective than controls. Compared to OIs only, OIs with interactions with others and professionals were more effective. The study limitation includes assessing 'effectiveness' based on weight only due to lack of other indicators to compare between studies; some results are self-reported; and feedback from intervention participants were hard to review. Nevertheless, this study may contribute to improving the effectiveness of existing OIs for weight loss considering methodological quality and better intervention features.

Diet quality, nutritional status and taste recognition are impaired in men with substance use disorder.

This study aimed to (1) evaluate the nutritional status, prevalence of malnutrition and dietary habits in individuals using substances and (2) examine the possible effects of substance use on the perception of five basic tastes. Ninety male individuals with substance use disorder (SUD) (heroin = 78, cocaine = 12) and 32 non-users participated in the study conducted at Manisa Alcohol and Substance Addiction Treatment Center (AMATEM), Turkey. To determine the quality of the diet, the mean nutrient adequacy ratio (MAR) was calculated based on 24-h recall food consumption records of the individuals. Subjective Global Assessment (SGA) was employed to determine nutritional status, and anthropometric measurements were also taken from the individuals. The taste detection and recognition thresholds were determined with solutions with different concentrations for bitter, sour, sweet, umami and salty tastes and scored, with higher scores indicating lower thresholds. Mild-moderate malnutrition was determined in 50% of the individuals with SUD based on SGA. The body mass index (BMI) of individuals with SUD was found to be 21.2 ± 1.88 kg/m2 , and 24.1 ± 1.64 kg/m2 for non-users (p < 0.001). Diet quality, evaluated by MAR, was lower in individuals with SUD (54.7 ± 18.9%) than in non-users (93.5 ± 9.0%) (p < 0.001). The taste detection and taste recognition thresholds of individuals with SUD were impaired, and the threshold scores for sour, salty, sweet and umami taste recognition were significantly lower compared with non-users, with the lowest substance user threshold scores observed for the sweet recognition threshold. Standardised nutritional and behavioural interventions designed by dietitians should be provided for drug users in treatment centres and integrated with medical treatment practices.

Antimicrobial Activity of N,N-Diethyldithiocarbamate against Ureaplasma parvum and Ureaplasma urealyticum.

Ureaplasma species (Ureaplasma spp.) are commonly found as commensals in the human urogenital tracts, although their overgrowth can lead to infection in the urogenital tract and at distal sites. Furthermore, ureaplasmas lack a cell wall and do not synthesize folic acid, which causes all β-lactam and glycopeptide antibiotics, and sulfonamides and diaminopyrimidines, to be of no value. The antibiotics used in therapy belong to the fluoroquinolone, tetracycline, chloramphenicol and macrolide classes. However, the growing incidence of antibiotic-resistant Ureaplasma spp. in the population becomes a problem. Thus, there is a need to search for new drugs effective against these bacteria. Since 1951, the FDA-approved, well-tolerated, inexpensive, orally administered drug disulfiram (DSF) has been used in the treatment of chronic alcoholism, but recently, its antimicrobial effects have been demonstrated. The main biological metabolite of DSF, i.e., N,N-diethyldithiocarbamate (DDC), is generally believed to be responsible for most of the observed pharmacological effects of DSF. In the presented studies, the effect of DDC at concentrations of 2 µg/mL, 20 µg/mL and 200 µg/mL on the growth and survival of Ureaplasma urealyticum and Ureaplasma parvum was tested for the first time. The results indicated that all the used DDC concentrations showed both bacteriostatic and bactericidal activity against both tested strains.

Effects of virtual reality-based cue exposure therapy on craving and physiological responses in alcohol-dependent patients-a randomised controlled trial

BackgroundCue exposure therapy is used to treat alcohol dependence. However, its effectiveness is controversial due to the limitations of the clinical treatment setting. Virtual reality technology may improve the therapeutic effect. The aim of this study is to explore whether virtual reality-based cue exposure therapy can reduce the psychological craving and physiological responses of patients with alcohol dependence.MethodsForty-four male alcohol-dependent patients were recruited and divided into the study group (n = 23) and the control group (n = 21) according to a random number table. The control group received only conventional clinical treatment for alcohol dependence. The study group received conventional clinical treatment with the addition of VR cue exposure (treatment). The primary outcome was to assess psychological craving and physiological responses to cues of patients before and after treatment.ResultsAfter virtual reality-based cue exposure therapy, the changes in VAS and heart rate before and after cue exposure in the study group were significantly lower than those in the control group (P < 0.05), while the changes in skin conductance and respiration between the study group and the control group were not significantly different (P > 0.05). The changes in VAS and heart rate before and after cue exposure in the study group were significantly lower than those before treatment (P < 0.05), while the changes in skin conductance and respiration were not significantly different from those before treatment (P > 0.05). The changes in VAS, heart rate, skin conductance and respiration before and after cue exposure in the control group were not significantly different from those before treatment (P > 0.05).ConclusionVirtual reality-based cue exposure therapy can reduce the psychological craving and part of the physiological responses of alcohol-dependent patients during cue exposure in the short term and may be helpful in the treatment of alcohol dependence.Trial registrationThe study protocol was registered at the China Clinical Trial Registry on 26/02/2021 (www.chictr.org.cn; ChiCTR ID: ChiCTR2100043680).

Subjective stress and any drinking during alcohol treatment: Disentangling within and between person autoregressive effects

Alcohol use has been shown to increase stress, and there is some evidence that stress predicts subsequent alcohol use during treatment for alcohol use disorder (AUD), particularly among females who are more likely to report coping-motivated drinking. Gaining a better understanding of the processes by which stress and alcohol use are linked during treatment could potentially inform AUD treatment planning. The current study aimed to characterize the association between stress and drinking during the course of AUD treatment and whether there were sex differences in these associations. Secondary data analyses of the COMBINE study (N = 1375; 69% male, 76.3% non-Hispanic and white, average age of 44.4 years) were conducted to examine self-reported perceived stress and alcohol consumption across 16 weeks of treatment for AUD using a Bayesian random-intercept cross-lagged panel model. There was stronger evidence for any alcohol use predicting greater than typical stress in subsequent weeks and less strong evidence for stress increasing the subsequent probability of alcohol use, particularly among males. For females, greater stress predicted subsequent drinking earlier in the treatment period, and a lower probability of subsequent drinking in the last week of treatment. Interventions might specifically focus on targeting reductions in stress following drinking occasions.

‘Ageing with an alcohol problem is not what I envision’: reclaiming agency in shaping personal ageing trajectory and recovery from alcohol problems

BackgroundEliciting and understanding older persons’ descriptions of their resources for healthy ageing and the interaction of these resources with alcohol use and alcohol problems can facilitate health promotion. It can also inform clinicians when identifying areas of recovery capital that present risks and strength for older people seeking alcohol treatment. The objective of this study was to illuminate the experiences and perspectives of older persons on ageing, alcohol use, treatment, and recovery from alcohol problems, as well as their understanding of healthy ageing.MethodsEight men and two women, aged 61 to 73 years, with moderate drinking as a treatment goal and treated at an outpatient alcohol clinic in Sweden, participated in semi-structured audio-recorded virtual interviews. A qualitative content analysis examined the transcribed interviews.ResultsThree themes were identified: “Tipping the balance”, “Staying behind a veil” and “Lifting the vail”. First, participants understood healthy ageing as a personal and multidimensional process that involved actively expanding, maintaining or adjusting to the resources needed to lead an active and meaningful life while preserving autonomy, dignity and independence for as long as possible. Second, most participants viewed moderate alcohol use as a contributor to healthy ageing. They sought treatment when their drinking became unsustainable and an immediate threat to their healthy ageing resources. Stigma, ambivalence and a lack of treatment options, however, contributed to delayed treatment. Third, the participants responded to treatment approaches that elicited their concern, incorporated their expertise and treatment and life goals, appreciated their autonomy and agency, and considered them partners in goal setting and decision making. Reduced drinking helped participants regain their agency and improved their healthy ageing capital which in turn catalyzed continuing recovery.ConclusionsOlder persons in non-abstinent recovery perceive healthy ageing and alcohol recovery as personal and interacting multidimensional processes involving their agency to improve biopsychosocial functioning. Treatment approaches that recognize older persons’ desire for healthy ageing, incorporate their treatment goals and respect their autonomy are likely to be acceptable and effective.

Microgel Encapsulated Nanoparticles for Intra-articular Disulfiram Delivery to Treat Osteoarthritis.

Osteoarthritis (OA) affects numerous patients worldwide, and there are no approved disease-modifying drugs. Repurposing FDA-approved small molecular drugs could be a promising alternative strategy to treat OA. Disulfiram (DSF), a clinically approved drug for treatment of alcoholism, inhibits inflammasome activation and exhibits a protective role in interleukin-1β-induced cardiac injury. However, its efficacy in treating OA remains to be explored due to its poor water solubility and stability, which limit its use in OA treatment. Here, the anti-inflammatory effect of DSF is evaluated in vitro, and a double-layer encapsulation approach is developed for intra-articular delivery of DSF for OA treatment in vivo. DSF is loaded into poly(lactic-co-glycolic acid)-based nanoparticles and encapsulated in gelatin methacrylate microgels through a microfluidic device. Results show that DSF effectively inhibits the expression of key inflammatory cytokines in OA chondrocytes, and the double-layer encapsulation approach reduces the burst release of DSF and prolongs its retention time in the in vitro study. Sustained release of DSF from microgels mitigates cartilage inflammation and subchondral bone erosion in a monoiodoacetate-induced rat OA model. This work demonstrates the potential of repurposing FDA-approved drugs for OA treatment and provides a promising platform for intra-articular delivery of small molecules for superior therapeutic effect.

ABHD5 protects cardiac function in alcoholic cardiomyopathy via HDAC4-NT to inhibit CAMKII/MEF2 axis.

Excessive intake of Alcohol is associated with a high incidence of alcoholic cardiomyopathy (ACM), which may impair cardiac function. In our study, we explored the Abhydrolase Domain Containing 5 (ABHD5) mechanism in ACM about histone deacetylase 4 (HDAC4) and CaM-CaMKII/MEF2 signaling pathway. Rat models of ACM were established in Wistar rats, and in vitro cell models were constructed in rat cardiomyocytes H9C2 utilizing 12-h of treatment of Alcohol (200 mM) to study the regulatory role of ABHD5 in ACM with the involvement of HDAC4 and CaM-CaMKII/MEF2 signaling pathway, as evidenced by determination of cardiac function, myocardial fibrosis, apoptosis of cardiomyocytes and oxidative stress condition. We found that both ABHD5 mRNA and protein expression was significantly lower in the ACM rats and rat cardiomyocytes H9C2. ACM rats with oe-ABHD5 injection showed repressed myocardial hypertrophy and myocardial fibrosis. Also, overexpression of ABHD5 reduced apoptosis and oxidative stress in H9C2 cells. Mechanistic studies demonstrated that ABHD5 via HDAC4-NT inhibits CAMKII/MEF2 axis. This study highlighted that ABHD5 decreased cardiac hypertrophy and myocardial fibrosis and limited cardiomyocyte apoptosis and oxidative stress injury in ACM.

Participation in Australian drug treatment programs for individuals engaging in high-risk substance use: Data from a nationally representative sample.

Substance use, including drugs, alcohol and smoking have a significant health, social and economic impact. We aim to assess the rate and factors associated with treatment access among individuals with high-risk substance use. This study is a cross-sectional analysis of the 2019 Australian National Drug Strategy Household Survey (N = 22,015). Participants were persons with high-risk substance use based on the Alcohol, Smoking and Substance Involvement Screening Test-Lite (ASSIST-Lite) and current smokers. We measured self-reports of past 12-month engagement in a tobacco, alcohol or other drugs treatment program. Overall, 0.4% had high-risk drug use (0.3% cannabis, 0.1% meth/amphetamine or 0.1% opioids), 7.4% had high-risk alcohol use, and 14.0% currently smoked. Among high-risk users, past 12-month treatment access rates were 50.6% [22.3-78.9%] for opioids, 27.1% [8.1-46.1%] for meth/amphetamine, 14.5% [4.3-24.7%] for cannabis, 9.6% [8.1-11.0%] for alcohol and 11.7% [10.6-12.9%] for current smoking. The primary source of treatment support was information and education (12.7% drugs, 4.6% alcohol, 4.0% smoking), followed by counselling (6.7% drugs, 4.5% alcohol, 3.0% smoking). Online or internet support was accessed by 5.9% (drug) and 1.6% (alcohol) people with high-risk use. Psychological distress was associated with treatment access (drugs: odds ratio 3.03 [0.77-11.95], p = 0.111; alcohol: odds ratio 3.16 [2.20-4.56], p ≤ 0.001; smoking: odds ratio 1.95 [1.52-2.49], p ≤ 0.001). The proportion of people engaging in risky substance use who had used treatment programs remains low, especially for alcohol. Public health strategies to scale up treatment access are warranted.

Waiting for inpatient detoxification: A qualitative analysis of patient experiences

BackgroundThere is limited provision of inpatient detoxification relative to other treatments for alcohol and other drug (AOD) use. This means people often need to wait prior to detoxifying. However, waiting for healthcare is generally perceived as negative and stressful. This paper aims to understand patients’ experiences of waiting for inpatient AOD detoxification to ascertain whether and how service-level policies and practices might be improved. MethodsSemi-structured telephone interviews were conducted with 32 people (20 males, 12 females; aged 25–67 years) who were waiting for inpatient detoxification. Data collection was part of a wider evaluation of a policy initiative started in 2021 to increase detoxification service capacity in England, UK. Interviews were professionally transcribed and data on waiting experiences were coded using qualitative software. Analyses were informed by new materialist thinking and undertaken via Iterative Categorisation. ResultsWe found that waiting was constituted through five dimensions: i. duration; ii. support; iii. information; iv. preparations; and v. emotions. These five dimensions were multi-faceted and operated in and through wider interacting social, material, and affective forces (e.g., professional judgements, formal and informal relationships, the availability of beds and funding, bureaucratic procedures, the utility and relevance of information, and participants’ diverse feelings, including desperation for treatment). Not all accounts of waiting were negative. The experience was complex, non-uniform and variable over time. Moreover, it affected how people felt and how they behaved. ConclusionsChanges to service-level policies and practices can potentially minimise the stress of waiting for inpatient AOD detoxification. The negative impact of waiting may be reduced if professionals more consistently engage patients in a wider range of constructive pre-treatment activities, offer regular ‘check-ins’ to mitigate any anxiety, explain changes in wait duration to help with planning and demonstrate fairness, and facilitate contact between those waiting to lessen feelings of isolation.

Mediational Analyses of the Effects of Social Behaviour and Network Therapy on Alcohol Use

Introduction: Social behaviour and network therapy involves an active participation of the practitioner in recruiting a supportive network to change the client’s alcohol use. Despite achieving beneficial effects on alcohol consumption, its possible mechanisms of change are a relatively under-studied topic compared to those of other alcohol treatment interventions. This study aimed to explore therapist skills through which social behaviour and network therapy may achieve effects on alcohol consumption in comparison with motivational enhancement therapy. Methods: This study was secondary analysis of data from the UK Alcohol Treatment Trial, a multicentre, pragmatic, randomized controlled trial. The sample comprised 376 participants randomized to motivational enhancement therapy or social behaviour and network therapy. We used the UK Alcohol Treatment Trial Process Rating Scale to assess therapist skills. Outcomes drinks per drinking day and percentage of days abstinent were assessed 12 months after treatment initiation. Analyses were conducted in a simple mediation framework. Results: Therapist skills score (combining frequency and quality) for involving others in behaviour change mediated social behaviour and network therapy effects on percentage of days abstinent (b = 0.06, 95% CI: 0.02; 0.10, p = 0.01). The frequency with which therapists acted as an active agent for change also mediated the effects of social behaviour and network therapy on percentage of days abstinent (b = 0.03, 95% CI: 0.003; 0.05, p = 0.03). The frequency with which the therapist stressed social support as a key factor in achieving change unexpectedly mediated an increase in drinks per drinking day (b = 0.10, 95% CI: 0.01; 0.18, p = 0.02). The two latter mediation effects were not sustained when quality was considered. All other indirect effects tested were non-significant. Discussion/Conclusions: How social behaviour and network therapy exerts effects on alcohol outcomes is not yet well understood and in this study was not attributable to observed ratings of therapist treatment-specific skills. Therapist skill in planning the involvement of others during treatment, however, warrants further study. We suggest that the present findings should be regarded as hypothesis generating as it identifies specific targets for further investigation in alcohol treatment process studies.

Alterations in sperm RNAs persist after alcohol cessation and correlate with epididymal mitochondrial dysfunction.

Chronic preconception paternal alcohol use adversely modifies the sperm epigenome, inducing fetoplacental and craniofacial growth defects in the offspring of exposed males. A crucial outstanding question in the field of paternal epigenetic inheritance concerns the resilience of the male germline and its capacity to recover and correct sperm-inherited epigenetic errors after stressor withdrawal. We set out to determine if measures of the sperm-inherited epigenetic program revert to match the control treatment 1 month after withdrawing the daily alcohol treatments. Using a voluntary access model, we exposed C57BL/6J males to 6% or 10% alcohol for 10 weeks, withdrew the alcohol treatments for 4 weeks, and used RNA sequencing to examine gene expression patterns in the caput section of the epididymis. We then compared the abundance of sperm small RNA species between treatments. In the caput section of the epididymis, chronic alcohol exposure induced changes in the transcriptional control of genetic pathways related to the mitochondrial function, oxidative phosphorylation, and the generalized stress response (EIF2 signaling). Subsequent analysis identified region-specific, alcohol-induced changes in mitochondrial DNA copy number across the epididymis, which correlated with increases in the mitochondrial DNA content of alcohol-exposed sperm. Notably, in the corpus section of the epididymis, increases in mitochondrial DNA copy number persisted 1 month after alcohol cessation. Analysis of sperm noncoding RNAs between control and alcohol-exposed males 1 month after alcohol withdrawal revealed a ∼100-fold increase in mir-196a, a microRNA induced as part of the nuclear factor erythroid 2-related factor 2 (Nrf2)-driven cellular antioxidant response. Our data reveal that alcohol-induced epididymal mitochondrial dysfunction and differences in sperm noncoding RNA content persist after alcohol withdrawal. Further, differences in mir-196a and sperm mitochondrial DNA copy number may serve as viable biomarkers of adverse alterations in the sperm-inherited epigenetic program.

Concurrent opioid and alcohol withdrawal management.

Concurrent alcohol and opioid withdrawal syndrome is a common and challenging clinical scenario with little published evidence or guidance to inform pharmacotherapy strategies. Concurrent use of benzodiazepines and opioid agonists, which are considered first-line agents for management of each withdrawal syndrome independently, is controversial and often avoided in clinical practice. Strategies to provide effective, simultaneous medication treatment of alcohol and opioid withdrawal while optimizing patient safety are demonstrated through 3 patient cases.

NEUROPROTECTIVE EFFECT OF PERILLYL ALCOHOL IN EXPERIMENTAL SPORADIC AD

AbstractBackgroundAlzheimer’s is most common neurodegenerative disorder characterized by memory loss due to accumulation of amyloid‐ β fibrils. There are different pathologies that count for AD like neuro inflammation. This study highlights the role of oxidative stress and inflammation in progression of AD where as Perillyl alcohol (POH) shows antioxidative &amp; anti‐inflammatory properties.MethodSprague Dawley ICV‐STZ (3mg/kg) rats (250‐300g, 7‐8 weeks) were treated with Perillyl alcohol treated with three different doses of (25, 50 and 100mg/kg p.o.) for 13 days from 15th to 27th day. Weight measured on 1st and 28th day. Behavioral analysis done using Open Field Test and Morris Water Maze.ResultPerillyl alcohol treatment significantly attenuates declined body weight in ICV‐STZ induced dementia in rats, showed significant increase in crossing number, and active time. Dementia induced rats were unable to discriminate familiar and novel objects, which is improved by POH. POH attenuates STZ induced acquisition deficits and retention time, increased MDA and nitrite levels. POH attenuated depleted levels of GSH, Catalase, SOD comparable to standard drug donepezil, POH decreased AChE levels in cortex and hippocampus.ConclusionStudy outcomes demonstrate neuroprotective potential of Perillyl alcohol against ICV‐STZ administration of streptozotocin induced behavioural and biochemical abnormalities. Biventricular STZ infusion produced significant impairment in learning, memory, cholinergic hypofunction and elevation in hippocampal oxidative stress in rats. Rats showed poor learning, memory and unable to discriminate between familiar &amp; novel objects in MWM and ORT. POH administration significantly attenuated STZ induced biochemical consequences. Observed beneficial effects of POH include restored cholinergic functions and antioxidant mechanism

Effects of binge alcohol administration on tauopathy and neuroinflammation in PS19 mice

AbstractBackgroundIt is estimated that 50 million people worldwide are suffering from dementia, the most common being Alzheimer’s disease (AD). Even as the population ages and the incidence of AD increases, there are limited disease‐modifying treatments to date. Alcohol use disorders (AUD) have been identified as a modifiable risk factors for developing AD. Heavy alcohol intake in elderly individuals is associated with more rapid progression of AD pathology and an elevated neuroinflammatory state. The objective of this study was to investigate the interaction of high ethanol ‘binge’ treatments in a mouse model of tauopathy.MethodPS19 mice, a widely used tauopathy model, were subjected to a 5‐week binge paradigm of IP ethanol administration, 3.0g/kg, three times per week, beginning at 6 months of age. Prior to initiation of the binge ethanol regimen, mice received subcutaneous biotransponder implantations to record body temperature changes in response to ethanol. Blood ethanol concentrations were determined in a subset of mice at 30 minutes following the last ethanol administration. Frailty measures were completed one week after ethanol administration. NanoString unbiased gene expression, MesoScale Discovery ELISA, Western blotting, and Immunohistochemistry were performed to examine neuroimmune changes and markers of tau pathology.ResultOverall, ethanol treatment resulted in reduced body weight, which was further exacerbated in female PS19 mice.. Measures of frailty (i.e. cerebellar ataxia and grip strength) were impaired in PS19 mice, however, female PS19 mice receiving ethanol treatment had the greatest impairments compared to WT controls. Alterations in inflammatory signaling pathways were observed in the PS19 animals receiving alcohol treatment compared to PS19 or WT mice.ConclusionWe have examined the result of intermittent alcohol exposure on tau pathogenesis. In the present study we found that alcohol can induce biometric and behavioral changes in mice, which are further exacerbated by alcohol. Transcriptomic analysis indicated changes in both innate and inflammatory signaling, suggesting a increased inflammatory response in the ethanol treated animals. Taken together, these results suggest that intermittent environmental influences, such as ethanol, can result in more rapid progression of AD pathogenesis.

Neuroprotective Effect of Perillyl Alcohol in Experimental Sporadic Alzheimer’s Disease

AbstractBackgroundAlzheimer’s is most common neurodegenerative disorder characterized by memory loss due to accumulation of amyloid‐ β fibrils. There are different pathologies that count for AD like neuroinflammation. This study highlights the role of oxidative stress and inflammation in progression of AD whereas Perillyl alcohol (POH) shows antioxidative &amp; antiinflammatory properties.Method‐Sprague Dawley ICV‐STZ (3mg/kg) rats (250‐300g, 7‐8 weeks) were treated with Perillyl alcohol treated with three different doses of (25, 50 and 100mg/kg p.o.) for 13 days from 15th to 27th day.ResultPerillyl alcohol treatment significantly attenuates declined body weight in ICV‐STZ induced dementia in rats, showed significant increase in crossing number, and active time. Dementia induced rats were unable to discriminate familiar and novel objects, which is improved by POH. POH attenuates STZ induced acquisition deficits and retention time, increased MDA and nitrite levels. POH attenuated depleted levels of GSH, Catalase, SOD comparable to standard drug donepezil, POH decreased AChE levels in cortex and hippocampus.ConclusionIn summary, present study has shown that Perillyl Alcohol is effective in amelorating i.c.v. STZ induced behavioral alterations, cholinergic dysfunctions and oxidative‐ nitrative stress.

Spidroins under the Influence of Alcohol: Effect of Ethanol on Secondary Structure and Molecular Level Solvation of Silk-Like Proteins.

Future sustainable materials based on designer biomolecules require control of the solution assembly, but also interfacial interactions. Alcohol treatments of protein materials are an accessible means to this, making understanding of the process at the molecular level of seminal importance. We focus here on the influence of ethanol on spidroins, the main proteins of silk. By large-scale atomistically detailed molecular dynamics (MD) simulations and interconnected experiments, we characterize the protein aggregation, secondary structure changes, molecular level origins of them, and solvation environment changes for the proteins, as induced by ethanol as a solvation additive. The MD and circular dichoroism (CD) findings jointly show that ethanol promotes ordered structure in the protein molecules, leading to an increase of helix content and turns but also increased aggregation, as revealed by dynamic light scattering (DLS) and light microscopy. The structural changes correlate at the molecular level with increased intramolecular hydrogen bonding. The simulations reveal that polar amino acids, such as glutamine and serine, are most influenced by ethanol, whereas glycine residues are most prone to be involved in the ethanol-induced secondary structure changes. Furthermore, ethanol engages in interactions with the hydrophobic alanine-rich regions of the spidroin, significantly decreasing the hydrophobic interactions of the protein with itself and its surroundings. The protein solutes also change the microstructure of water/ethanol mixtures, essentially decreasing the level of larger local clustering. Overall, the work presents a systematic characterization of ethanol effects on a widely used, common protein type, spidroins, and generalizes the findings to other intrinsically disordered proteins by pinpointing the general features of the response. The results can aid in designing effective alcohol treatments for proteins, but also enable design and tuning of protein material properties by a relatively controllable solvation handle, the addition of ethanol.

1835. Factors impact Longevity in Persons Living with HIV

Abstract Background In contrast to high mortality including young patient in 1990’s, persons living with HIV (PLWHIV) can expect a near-normal life expectancy of 77 years. Recent mortality data suggests significant number of HIV positive patients pass before the age of 70 years. There is a current paucity of literature looking at characteristics of the elderly PLWHIV when comparing to patients who died from HIV at a younger age. The goal of this study was to compare factors between the current HIV population living longer than age 70 and the population that did not survive until age 70 at the Positive Health Clinic (PHC). PHC is an urban city Ryan White funded HIV Care Medical Home Clinic, at Pittsburgh, PA, that provides care to ∼920 PLWHIV Methods A retrospective chart review of patient records at PHC; with patients from period between 2015 -2022 was queried for HIV viral load, recent CD4 counts, and social history. Smoking, alcohol, and drug use were used as primary social measures due to their known impact in early development of prevalent chronic comorbidities. A Chi squared test was then employed to analyze for statistical significance of these factors (P &amp;lt; 0.05) between the cohort of patients that are living beyond the age of 70 (longevity) and the cohort of patients who died prior to age of 70 Results A total of 149 records were obtained (122M/ 27F, 95W/54B). The median age of HIV diagnosis and death was 44 and 60, respectively. There was no statistical difference between two groups in gender, race, and initial HIV transmission route, but being diagnosed with HIV after the age of 40 was associated with longevity. Unsurprisingly, patient with last viral load above 500 or CD4 below 200 were less likely to survive past age 70. HIV viral load &amp;lt; 200, persistently, in past 5 years and absence of smoking in last 15 years were the 2 factors most strongly associated longevity. Alcohol abuse and drug use were less likely to survive age 70. Statistical data between the two groups are listed in Table attached. Comparing factors associated with living beyond 70 versus dying before 70 Conclusion Common comorbidities such as diseases of heart, lung, kidney and cancer are impacted by substance misuse, and as a result may serve as a barrier to reaching old age in PLWHIV. Counseling against tobacco use, treatment of alcohol and drug addiction while sustaining viral control with HAART can promote the longevity of PLWHIV. Disclosures Chiu-bin hsiao, MD, Gilead: Grant/Research Support|ViiV: Advisor/Consultant|ViiV: Grant/Research Support|ViiV: Honoraria

GLP-1 receptor agonists are promising but unproven treatments for alcohol and substance use disorders.

GLP-1 receptor agonists are promising but unproven treatments for alcohol and substance use disorders.