Multilayered hydrogel scaffold construct with native tissue matched elastic modulus: A regenerative microenvironment for urethral scar-free healing.

The unsuitable deformation stimulus, harsh urine environment, and lack of a regenerative microenvironment (RME) prevent scaffold-based urethral repair and ultimately lead to irreversible urethral scarring. The researchers clarify the optimal elastic modulus of the urethral scaffolds for urethral repair and design a multilayered PVA hydrogel scaffold for urethral scar-free healing. The inner layer of the scaffold has self-healing properties, which ensures that the wound effectively resists harsh urine erosion, even when subjected to sutures. In addition, the scaffold's outer layer has an extracellular matrix-like structure that synergizes with adipose-derived stem cells to create a favorable RME. In vivo experiments confirm successful urethral scar-free healing using the PVA multilayered hydrogel scaffold. Further mechanistic study shows that the PVA multilayer hydrogel effectively resists the urine-induced inflammatory response and accelerates the transition of urethral wound healing to the proliferative phase by regulating macrophage polarization, thus providing favorable conditions for urethral scar-free healing. This study provides mechanical criteria for the fabrication of urethral tissue-engineered scaffolds, as well as important insights into their design.

Alcohol use, civilian interference, and other possible risk factors for death during restraint.

Physical restraint is usually used when trying to control and terminate a violent episode. Many causes are possible behind aggressive, agitated, and violent behavior. Some of these are such factors that can either be detected in forensic autopsies or can be evident from the person's medical records. Various causes for deaths during physical restraint have been suggested. In this study, we wanted to review all incidents in which physical restraint was employed, ending in death of the restrained person, whether the restraint was applied by police officers, security guards, police custody personnel, health care personnel or ordinary civilians. The main aim was to see if this new kind of study design would increase our knowledge in circumstances and causes leading to death in restraint situations. Data was collected retrospectively from all forensic autopsies performed in the Southern Finland area during 2010-2015. We went through 21,036 forensic autopsy cases and found 12 cases (0.06 %) in which a physical restraint was employed before death. Police officers were involved in the physical restraint in 7/12 of the cases: in two of these cases, police alone; in three cases, police and guards; and in two cases, police and health care personnel. Civilians carried out the restraint in 5/12 cases. With civilians responsible for the restraint, the cause of death was more likely considered to be a result of the restraint itself than in cases where police and other authorities were responsible for the restraint. This could be because civilians aren't educated about safe restraint methods, and they might themselves be intoxicated. Alcohol was the most common psychoactive substance found in this study and could be a risk factor for not only aggressive behavior but also death, since alcohol use can provoke cardiac arrhythmias and even sudden death. Based on this study, and previously published studies, we see restraint deaths as a varying spectrum of deaths, in which the death is often possibly a result of many factors, including the effects of agitation and restraint, intoxication, and cardiac and other illnesses.

Multi-dimensional predictors of first drinking initiation and regular drinking onset in adolescence: A prospective longitudinal study.

Early adolescent drinking onset is linked to myriad negative consequences. Using the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) baseline to year 8 data, this study (1) leveraged best subsets selection and Cox Proportional Hazards regressions to identify the most robust predictors of adolescent first and regular drinking onset, and (2) examined the clinical utility of drinking onset in forecasting later binge drinking and withdrawal effects. Baseline predictors included youth psychodevelopmental characteristics, cognition, brain structure, family, peer, and neighborhood domains. Participants (N=538) were alcohol-naïve at baseline. The strongest predictors of first and regular drinking onset were positive alcohol expectancies (Hazard Ratios [HRs]=1.67-1.87), easy home alcohol access (HRs=1.62-1.67), more parental solicitation (e.g., inquiring about activities; HRs=1.72-1.76), and less parental control and knowledge (HRs=.72-.73). Robust linear regressions showed earlier first and regular drinking onset predicted earlier transition into binge and regular binge drinking (ßs=0.57-0.95). Zero-inflated Poisson regressions revealed that delayed first and regular drinking increased the likelihood (Incidence Rate Ratios [IRR]=1.62 and IRR=1.29, respectively) of never experiencing withdrawal. Findings identified behavioral and environmental factors predicting temporal paths to youthful drinking, dissociated first from regular drinking initiation, and revealed adverse sequelae of younger drinking initiation, supporting efforts to delay drinking onset.

Biomarkers for prediction of alcohol-related liver cirrhosis- A general population-based Swedish study of 537 250 individuals.

BACKGROUND AND AIMS: To examine which biomarkers have the best predictive capabilities for future Alcohol-related liver cirrhosis (ARLC) in a general population setting. METHOD: This population-based cohort study includes approximately 35% of the inhabitants of Stockholm County who had left a blood sample at an outpatient visit in primary care or occupational health screening from 1985 to 1996. All subjects with a blood sample measurement of ALT and AST were included, exclusions were made for persons with known liver disease. We ascertained incident ARLC by linkage to Swedish national health registers between to the end of 2011. Associations between biomarkers and incident ARLC were analyzed with Cox regression models and discrimination was assessed using C-statistics. RESULTS: In all 537,230 adult subjects were included. Mean age was 45 years and 53% were men. During a mean follow-up of 19.0 years, 2725 (0.51%) subjects developed ARLC. The biomarkers with the highest discrimination (C-index) for incident ARLC at 5 years were: AST (0.89), mean corpuscular volume (0.88), and gamma-glutamyl transferase (0.81). Scoring systems including FIB-4 (0.86) and the AST/ALT ratio (0.81) performed similarly well. The negative predictive value for ARLC was generally high (∼99.6%) across biomarkers, using routine clinical cut-offs to identify pathological values. However, positive predictive values were generally low (0.6-15.9%). CONCLUSION: Biomarkers commonly used in primary care settings are highly associated with incident ARLC in the general population. Elevation of these commonly available biomarkers should prompt consideration of further investigation of a possible high level of alcohol consumption.

Systematic review of patient contribution to the development of alcohol craving measurements.

Craving is considered one of the defining characteristics for alcohol or substance use disorders. There is no consensus on the underlying processes of craving, although multiple models exist. Craving is a very individualistic symptom and has to be self-reported. Several instruments have been developed to measure craving, without a recognized gold standard. The patient's perspective appears critical to determine the relevance of the numerous existing tools. We assessed the contribution of patients to the development of these instruments. We performed a systematic review of instruments measuring alcohol craving published from 2012 to 2023 from three databases (PubMed, PsycInfo, and Embase) in addition to those identified in a previous review by Kavanagh et al. from 1990 to 2012. We included all articles related to the development or validation of instruments for the assessment of alcohol craving. We identified and included in this review the corresponding instruments. Articles translating existing instruments without validation or on single-item instruments were excluded. We analyzed the articles in accordance with COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) recommendations to assess patient involvement in the creation of patient-reported outcome measures (PROM). Two key aspects were investigated: (1) the general design, encompassing the quality of construct description, identification of elements pertinent to a PROM, particularly the inclusion of concepts provided by patients, and (2) the quality of cognitive interviews (when conducted), to evaluate the comprehensiveness and comprehensibility of the PROM. We included 22 articles identifying 16 instruments for measuring alcohol craving. Patients only contributed to item development for one instrument and its short version (QAU and AUQ). None of the instruments met all of the developmental quality criteria, with 14 classed as "inadequate" and two as "doubtful." The current instruments measuring alcohol craving were developed with poor patient contribution, although most articles did not adequately report patient involvement. Patients' perspectives on craving should be explored for future patient-centered approach.

Substance Use Among Illinois Farmers.

BACKGROUND:  People in agriculture face unique stressors and occupational hazards, and relatively little is known about substance use in this population. The purpose of this study was to describe substance use among farmers in Illinois. METHODS:  We conducted a mail survey of Illinois farmers that included the Brief ASSIST to assess substance use for lifetime and past three-month use of ten different substances. The survey also included questions about farming characteristics, mental health, stress, coping, social support, and demographic characteristics. We used chi-square and non-parametric tests to assess group differences. RESULTS:  Alcohol, tobacco, cannabis, and sedatives were most reported as used for a lifetime and in the past three months. About three-quarters of the sample had recently used alcohol. Recent tobacco use was associated with not being married, less education, and less concern about climate-related farm stress. Recent sedative use was associated with greater concern about isolation-related farm stress. People who reported multiple substance use were at a greater risk for suicide and were more likely to meet the criteria for generalized anxiety disorder. None of the participants reported recent use of cocaine, heroin, inhalants, or hallucinogens. CONCLUSION:  Specific social and cultural aspects of farming and farm communities may contribute to substance use among people working in agriculture. Future research can help to better understand this intersection and make recommendations for programs and resources to promote adaptive coping strategies.

Alcohol does not impact chronic hepatitis C treatment outcomes but increases risk for progressive liver disease: Findings from a prospective multicentre Australian study (OPERA-C).

INTRODUCTION: Alcohol use is common in patients with chronic hepatitis C virus (HCV) infection. We examined the impact of alcohol use on direct-acting antiviral (DAA) therapy outcome and the clinical course of liver disease and 2-year survival for patients receiving HCV DAA therapy. METHODS: Adults (n = 2624) recruited from 26 Australian hospital liver clinics during 2016-2021 were followed up for 2 years. Risky alcohol use was defined by a combination of self-report (≥40 g/day of ethanol), physician-reported history of problematic alcohol use, and anti-craving medication prescription via population-based database linkage. We examined factors associated with advanced liver fibrosis and survival using multivariable logistic and Cox regression. RESULTS: Among 1634 patients (62.3%) with risky alcohol use, 24.6% reported consuming ≥40 g/day of alcohol, 98.3% physician-reported problematic alcohol use; only 4.1% were dispensed naltrexone/acamprosate. One hundred and forty-three patients with cirrhosis reported ≥40 g/day of alcohol, 6 (4.3%) were prescribed naltrexone/acamprosate. Risky alcohol use was associated with advanced fibrosis (adjusted-odds ratio 1.69, 95% confidence interval 1.32-2.17) and patients were over-represented for cirrhosis (45.1% vs. 25.6% in no-risky alcohol use [p < 0.001]) and hepatocellular carcinoma (5.7% vs. 2.5% [p < 0.001]). Sustained viral response (p = 0.319) and 2-year survival (adjusted-hazard ratio 1.98, 95% confidence interval 0.84-4.63) after DAA therapy were not associated with risky alcohol use. DISCUSSION AND CONCLUSIONS: Risky alcohol use in HCV patients was prevalent, but did not reduce HCV cure. Treatment for alcohol dependence was low. Risky alcohol use may be under-recognised in liver clinics. Better integration of addiction medicine into liver services and increased resourcing and addiction medicine training opportunities for hepatologists may help address this.

Electrospun PCL/PVA/PHMB nanofibers incorporating Ziziphus jujuba fruit extract as promising wound dressings with potent antibacterial and antidiabetic properties.

This investigation examined the potential antibacterial and antidiabetic effects of wound dressings created using electrospun nanofibers containing Ziziphus jujuba fruit extract (ZJ). These nanofibers were composed of a combination of Polycaprolactone (PCL), Polyvinyl Alcohol (PVA), and Polyhexamethylene Biguanide (PHMB). The process of creating these nanofibers involved electrospinning. The nanofiber products, which included PCL, PCL/PVA, PCL/PVA/ZJ, PCL/PVA/PHMB, and PCL/PVA/PHMB/ZJ, underwent a morphology, physicochemical, and biological assessment. Incorporating PHMB into the nanofibers enhanced the antibacterial properties, effectively preventing bacterial infections in wounds. Furthermore, including ZJ fruit extract in the nanofibers provided antidiabetic properties, making these dressings suitable for diabetic patients. The PCL/PVA/PHMB/ZJ combination exhibited exceptional healing capabilities and superior antibacterial efficiency in MRSA-infected wounds. The histological assay confirmed complete wound healing by day 14, accompanied by reduced inflammation. Based on these findings, using PCL/PVA/PHMB/ZJ as innovative wound dressings is recommended, as they can expedite wound healing while offering significant antidiabetic and antibacterial features. Ultimately, these electrospun nanofibers possess the potential to serve as advanced wound dressings with enhanced antibacterial and anti-diabetes properties.

Antimicrobial effect of two fluoride-releasing adhesive tapes on Streptococcus mutans biofilm.

Fluoride-releasing adhesive tapes have been developed as a new fluoride delivery agent. However, application as caries prevention agents remains underexplored. This study aimed at evaluating the antimicrobial activity of two fluoride-releasing adhesive tapes against S. mutans biofilm. Two polyvinyl alcohol (PVA) tapes were investigated: (i) a fluoride-PVA (F-PVA) tape, (ii) a pullulan incorporated F-PVA (PF-PVA) tape. S. mutan strains were cultured and treated with the tapes. Antimicrobial effects were evaluated using the agar diffusion test, field-emission scanning electron microscopy (FE-SEM), and confocal laser scanning microscopy (CLSM). F-PVA tapes showed higher inhibition-zone diameters than PF-PVA at 48 h and 72 h. However, there were no significant differences (p > 0.05) between the effects of F-PVA and PF-PVA. The bio-volume of S. mutans and extracellular polymeric substances significantly decreased in the F-PVA tapes than in the PF-PVA tapes (p < 0.05). FE-SEM micrographs revealed less S. mutans colonization in F-PVA. F-PVA exhibited better antimicrobial activity against S. mutans than PF-PVA.

GET73 modulates lipopolysaccharide- and ethanol-induced increase in cytokine/chemokine levels in primary cultures of microglia of rat cerebral cortex.

BACKGROUND: - Alcohol-induced pro-inflammatory activation might influence cellular and synaptic pathology, thus contributing to the behavioral phenotypes associated with alcohol use disorders. In the present study, the possible anti-inflammatory properties of N-[(4-trifluoromethyl)-benzyl]4-methoxybutyramide (GET73), a promising therapeutic agent for alcohol use disorder treatment, were evaluated in primary cultures of rat cortical microglia. METHODS: - Primary cultures of cerebral cortex microglial cells were treated with 100 ng/ml lipopolysaccharide (LPS; 8 h, 37 °C) or 75 mM ethanol (EtOH; 4 days, 37 °C) alone or in the presence of GET73 (1-30 µM). At the end of the incubation period, multiparametric quantification of cytokines/chemokines was performed by using the xMAP technology and Luminex platform. Furthermore, cultured microglial cell viability following the treatment with EtOH and GET73, alone or in combination, has been measured by a colorimetric assay (i.e. MTT assay). RESULTS: - GET73 (10 and 30 µM) partially or fully prevented the LPS-induced increase of IL-6, IL-1ß, RANTES/CCL5 protein and MCP-1/CCL2 levels. On the contrary, GET73 failed to attenuate the TNF-α level increase induced by LPS. Furthermore, GET73 treatment (10-30 µM) significantly attenuated or prevented the EtOH-induced increase of TNF-α, IL-6, IL-1ß and MCP-1/CCL2 levels. Finally, at all the concentrations tested (1-30 µM), the GET73 treatment did not alter the EtOH-induced reduction of microglial cell viability. CONCLUSIONS: - The current results provide the first in vitro evidence of GET73 protective properties against EtOH-induced neuroinflammation. These data add more information on the complex and multifactorial profile of action of the compound, further supporting the significance of developing GET73 as a therapeutic tool for the treatment of individuals with alcohol use disorders.

Causal attributions of impulsive and compulsive behaviors.

Introduction: Aggression, and therefore gender-based violence, can be an impulsive or compulsive behavior, depending on the consumption of alcohol and/or drugs. In Europe, the prevalence of gender-based violence is 16 to 23%. This prevalence shows that there is a need to make further progress in the treatment of aggression against women. Qualitative techniques allow us to understand perceptions and attributions holistically by analyzing what people who commit the crime say, why they say it and how they say it. Aim: To explore the experience of physical and verbal aggression by a partner, dependent on the presence or absence of alcohol and drug use, in the prison population. Method: A mixed methodology was used (combining qualitative and quantitative techniques). The sample was made up of 140 men divided into two focus groups [with alcohol and/or drug consumption (SAD) and without alcohol and/or drug consumption (NSAD)] who completed the Demographic, Criminal and Behavioral Interview in Penitentiary Institutions; the Gender Violence Questionnaire (both developed for this study) and the MultiCAGE CAD-4 Questionnaire. Qualitative data were analyzed using thematic analysis and quantitative data were obtained using contingency tables. Results: It was found that the SAD group attributed the crime committed to alcohol and/or drug consumption, while the NSAD group attributed it to jealousy and to their partner. The SAD group revealed that the consequence of the physical aggressions was to get what they were looking for from their partner and the consequences of the verbal aggressions was regret, unlike the NSAD group that did not get anything from the aggressions. The SAD group recognized that to avoid future aggressions they would have to avoid alcohol and/or drug use, while the NSAD group mentioned that they would have to avoid contact with their partner. Discussion: The need to include perceptions and attributions as well as the use of alcohol and/or drugs is emphasized when assessing individuals who commit the crime of gender-based violence.

Epigenetic associations of GPNMB rs199347 variant with alcohol consumption in Parkinson's disease.

Introduction: Alcohol consumption can induce a neuroinflammatory response and contribute to the progression of neurodegeneration. However, its association with Parkinson's disease (PD), the second most common neurodegenerative disorder, remains undetermined. Recent studies suggest that the glycoprotein non-metastatic melanoma protein B (GPNMB) is a potential biomarker for PD. We evaluated the association of rs199347, a variant of the GPNMB gene, with alcohol consumption and methylation upstream of GPNMB. Methods: We retrieved genetic and DNA methylation data obtained from participants enrolled in the Taiwan Biobank (TWB) between 2008 and 2016. After excluding individuals with incomplete or missing information about potential PD risk factors, we included 1,357 participants in our final analyses. We used multiple linear regression to assess the association of GPNMB rs199347 and chronic alcohol consumption (and other potential risk factors) with GPNMB cg17274742 methylation. Results: There was no difference between the distribution of GPNMB rs199347 genotypes between chronic alcohol consumers and the other study participants. A significant interaction was observed between the GPNMB rs199347 variant and alcohol consumption (p = 0.0102) concerning cg17274742 methylation. Compared to non-chronic alcohol consumers with the AA genotype, alcohol drinkers with the rs199347 GG genotype had significantly lower levels (hypomethylation) of cg17274742 (p = 0.0187). Conclusion: Alcohol consumption among individuals with the rs199347 GG genotype was associated with lower levels of cg17274742 methylation, which could increase expression of the GPNMB gene, an important neuroinflammatory-related risk gene for PD.

Cognitive impairment among alcohol treatment service users in South Wales: an exploratory examination of typologies of behaviour, impairment, and service attendance.

Introduction: Alcohol dependence is a global issue with many negative consequences, including alcohol-related brain damage (ARBD). Assessment of the sociodemographic and cognitive characteristics of individuals with confirmed or suspected ARBD presenting to alcohol services warrants further investigation. Methods: This study retrospectively examined rates of cognitive impairment using Montreal Cognitive Assessment (MoCA) data from 300 adults who visited three alcohol support services. We demonstrate that 55.3% of the sample had significant levels of cognitive impairment. Females' cognitive performance was disproportionately negatively affected by historical alcohol use relative to males. Results: The analysis identified four categories of participants, and the majority had a long history (+10 years) of alcohol use and were still actively drinking. Those taking part in active treatment for ARBD or practising abstinence demonstrated lower levels of cognitive impairment. Additionally, prior access to specialised ARBD care was associated with higher MoCA scores. Discussion: This research has identified a range of key service engagement, sociodemographic and cognitive characteristics that could be used to optimise support for those with alcohol dependence, whilst also highlighting some critical questions to be addressed in future research.

An Evaluation of the Changing Trends in Substance Use Behavior Among Patients in the Tertiary Care Setting After the Implementation of Liquor Prohibition in Bihar, India: A Cross-Sectional Study.

Background and objective Substance use disorders pose significant global public health challenges, with India being no exception. Bihar, one of India's most populous states, implemented alcohol prohibition in April 2016 to address the adverse effects of alcohol abuse. However, the impact of this policy on overall substance use behavior among patients in healthcare settings remains to be explored. This cross-sectional study aimed to evaluate the changing trends in substance use behavior among patients in the tertiary care setting following the prohibition of alcohol use in Bihar. Methods A total of 372 patients diagnosed with substance use disorders were recruited from tertiary care facilities in Bihar. Data on demographic characteristics, types of substances used, frequency and quantity of use, reasons for use, and awareness of prohibition laws were collected through structured interviews and reviews of medical records. Descriptive and inferential statistics were used for data analysis. Results The majority of the participants were male (n = 346, 93.01%), with a mean age of 38.5 years. While tobacco use remains stable, there are significant increases in opioid and cannabis consumption post-prohibition, highlighting unintended consequences (p-values - opioids: 0.008, cannabis: 0.021). Additionally, heightened daily and weekly substance use after prohibition is evident (p-values: daily: 0.008, weekly: 0.021), emphasizing the necessity for nuanced policy considerations. Reasons for substance use, including coping with stress and peer pressure, showed significant differences before and after the prohibition (p<0.05). Moreover, awareness of alcohol prohibition laws increased significantly after the implementation of the prohibition (p = 0.003). Conclusions Our findings suggest that while alcohol prohibition in Bihar did not significantly lead to any changes in terms of the types of substances used among patients in tertiary care settings, it did influence the frequency and quantity of tobacco and cannabis consumption. Increased awareness of prohibition laws underscores the importance of policy enforcement and public education initiatives in addressing substance use behavior.

DPPA4 increases aggressiveness of pituitary neuroendocrine tumors by enhancing cell stemness.

BACKGROUND: Pituitary neuroendocrine tumors, PitNETs, are often aggressive and precipitate in distant metastases that are refractory to current therapies. However, the molecular mechanism in PitNETs' aggressiveness is not well understood. Developmental pluripotency-associated 4 (DPPA4) is known as a stem cell regulatory gene and overexpressed in certain cancers, but its function in the context of PitNETs' aggressiveness is not known. METHODS: We employed both rat and human models of PitNETs. In the rat pituitary tumor model (RPT), we used prenatal-alcohol-exposed (PAE) female Fischer rats which developed aggressive PitNETs following estrogen treatment, while in the human pituitary tumor (HPT) model, we used aggressively proliferative cells from pituitary tumors of patients undergone surgery. Various molecular, cellular, and epigenetic techniques were used to determine the role of DPPA4 in PitNETs' aggressiveness. RESULTS: We show that DPPA4 is overexpressed in association with increased cell stemness factors in aggressive PitNETs of PAE rats and of human patients. Gene-editing experiments demonstrate that DPPA4 increases the expression of cell stemness and tumor aggressiveness genes and promotes proliferation, colonization, migration, and tumorigenic potential of PitNET cells. ChIP assays and receptor antagonism studies reveal that DPPA4 binds to canonical WINTs promoters and increases directly or indirectly the Wnt/ß-catenin control of cell stemness, tumor growth, and aggressiveness of PitNETs. Epigenetic studies show involvement of histone methyltransferase in alcohol activation of DPPA4. CONCLUSIONS: These findings support a role of DPPA4 in tumor stemness and aggressiveness and provide a preclinical rationale for modulating this stemness regulator for the treatment of PitNETs.

Neuroimaging of the effects of drug exposure or self-administration in rodents: A systematic review.

A systematic review of functional neuroimaging studies on drug (self-) administration in rodents is lacking. Here, we summarized effects of acute or chronic drug administration of various classes of drugs on brain function and determined consistency with human literature. We performed a systematic literature search and identified 125 studies on in vivo rodent resting-state functional magnetic resonance imaging (n = 84) or positron emission tomography (n = 41) spanning depressants (n = 27), opioids (n = 23), stimulants (n = 72), and cannabis (n = 3). Results primarily showed alterations in the striatum, consistent with the human literature. The anterior cingulate cortex and (nonspecific) prefrontal cortex were also frequently implicated. Upregulation was most often found after shorter administration and downregulation after long chronic administration, particularly in the striatum. Importantly, results were consistent across study design, administration models, imaging method, and animal states. Results provide evidence of altered resting-state brain function in rodents upon drug administration, implicating the brain's reward network analogous to human studies. However, alterations were more dynamic than previously known, with dynamic adaptation depending on the length of drug administration.

Binge drinking and progression of white matter hyperintensities of presumed vascular origin in older men.

BACKGROUND: Information on trajectories of diffuse subcortical brain damage of vascular origin associated with binge drinking in older adults is limited. We sought to evaluate the impact of this drinking pattern on the progression of white matter hyperintensities (WMH) of presumed vascular origin in individuals aged ≥60 years taken from the community. METHODS: Following a longitudinal prospective design, participants of the Atahualpa Project Cohort received interviews to assess patterns of alcohol intake as well as baseline and follow-up brain MRIs. Only men were included because alcohol consumption in women is negligible and tend not to engage in binge drinking in our studied population. Poisson regression models were fitted to assess the incidence rate ratio of WMH progression by patterns of alcohol use (binge drinking or not), after adjusting for demographics, level of education and cardiovascular risk factors. RESULTS: The study included 114 men aged ≥60 years (mean age: 65.1±5.4 years). Thirty-seven participants (32%) reported binge drinking for more than 30 years. Follow-up MRIs revealed WMH progression in 45 participants (39%) after a median of 7.2 years. In unadjusted analysis, the risk of WMH progression among individuals with binge drinking was 2.08 (95% C.I.: 1.16 - 3.73). After adjustment for age, education level and vascular risk factors, participants with this drinking pattern were 2.75 times (95% C.I.: 1.42 - 5.30) more likely to have WMH progression than those who did not. CONCLUSIONS: Study results show an independent association between binge drinking and WMH progression in community-dwelling older men.

Alcohol-exacerbates post-traumatic stress psychiatric behavior and its neuropathological sequalae in experimental mice: preventive effects of morin.

Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) are very prevalent and co-occurring. It is unclear how alcohol exacerbates PTSD predicaments owing to less characterized pathophysiological mechanisms. Also, studies on pharmacological agents that can effectively reverse PTSD-AUD comorbidity have, to date, been scarce. Hence, we designed a methodological approach to investigate the pathophysiological mechanisms and pharmacological outcomes of morin, a neuroprotective flavonoid in mice. After 7 days of PTSD following single-prolonged stress (SPS) induction in mice, the PTSD mice were exposed to intermittent binge ethanol administration using ethanol (2g/kg, oral gavage) every other day, alongside daily morin (50 and 100mg/kg) or fluoxetine (10mg/kg) from days 8-21. The consequences of PTSD-AUD behavior, hypothalamic-pituitary-adrenal-axis (HPA-axis) dysfunction, neurochemistry, oxidative/nitrergic stress, and inflammation were evaluated in the prefrontal-cortex (PFC), striatum, and hippocampus of mice. The exacerbated anxiety-like behavior, and spatial/non-spatial memory deficits, with general depressive phenotypes and social stress susceptibility by SPS-ethanol interaction, were alleviated by morin and fluoxetine, evidenced by reduced corticosterone release and adrenal hypertrophy. SPS-ethanol exacerbates dopamine, serotonin, and glutamic acid decarboxylase alterations, and monoamine oxidase-B and acetylcholinesterase hyperactivities in the striatum, PFC, and hippocampus, respectively, which were prevented by morin. Compared to SPS-ethanol aggravation, morin prevented TNF-α, and IL-6 release, malondialdehyde and nitrite levels, with improved antioxidant (glutathione, superoxide-dismutase, catalase) levels in the hippocampus, PFC, and striatum. Overall, these findings suggest that AUD exacerbated PTSD might be primarily connected, among other mechanisms, with aggravated HPA-axis dysfunction, upregulated neurochemical degradative enzymes, enhancement of oxidative/nitrergic stress and neuroinflammation, stereo-selectively in the mice brains, which morin abated via the preventive mechanisms.

Synthesis and analysis of multifunctional graphene oxide/Ag2O-PVA/chitosan hybrid polymeric composite for wound healing applications.

The requirement for accurate treatments for skin diseases and wounds, generated a rising interest towards multifunctional polymer composites, that are capable of mimicking the natural compositions in human body. Also, electroactive composite films disseminate endogenous electrical stimulations that encourage cell migration and its proliferation at wound site, proposing greater opportunities in upgrading the conventional wound patches. In this work, the composite film made of graphene oxide, Ag2O, PVA and chitosan were developed for wound healing applications, by the solution casting method. The even dispersibility of nanofiller in polymeric matrix was validated from the physicochemical analyses. The increment in roughness of the composite film surface was noted from AFM images. The thermal stability and porous nature of the polymer composite were also verified. A conductivity value of 0.16 × 10-4 Scm-1 was obtained for the film. From MTT assay, it was noted that the films were non-cytotoxic and supported cell adhesion along with cell proliferation of macrophage (RAW 264.7) cells. Moreover, the composite film also demonstrated non-hemolytic activity of <2 %, as well as excellent antibacterial activity towards E. coli and S. aureus. Thus, the obtained results validated that the prepared composite film could be chosen as an innovative candidate for developing state-of-the-art wound dressings.

Mindfulness facets are differentially related with reward processing stages in striatum and alcohol use in adolescence.

Attenuated functional processing of non-drug rewards in striatal regions is an important mechanism in the transition from normal to hazardous alcohol use. Recent interventions seek to enhance nondrug reward processing through mindfulness, a mechanism that targets attention regulation and self-regulatory processes. It is yet unclear which specific aspects of mindfulness and which stages of reward processing are relevant preventive targets, particularly in adolescence, where alcohol use is often initiated and reward relating processing streams undergo continuous maturation. Fifty-four 14- and 16-year-old adolescents (54% female) completed the monetary incentive delay task (MID) during event-related functional magnetic resonance imaging. Alcohol use and dispositional mindfulness facets were measured using self-report instruments. Mindful Attention Regulation was positively associated with anticipatory reward processing in ventral striatum, whereas feedback-related processing in dorsal striatum was associated with the mindfulness facet Body-Listening. Only Attention Regulation was additionally associated with frequency of alcohol consumption and mediated the relationship between functional activation in ventral striatum during reward anticipation and alcohol use. Attention Regulation, beyond other mindfulness facets, might contribute to potentially triggering neural mechanisms of anticipatory, but not feedback-related reward processing and alcohol use, presenting a potential target for preventive efforts in combating transitions to substance-related disorders in adolescents.