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1.
J Biomater Sci Polym Ed ; : 1-15, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38949409

ABSTRACT

The interest in wound dressings increased ten years ago. Wound care practitioners can now use interactive/bioactive dressings and tissue-engineered skin substitutes. Several bandages can heal burns, but none can treat all chronic wounds. This study formulates a composite material from 70% polyvinyl alcohol (PVA) and 30% polyethylene glycol (PEG) with 0.2, 0.4, and 0.6 wt% magnesium oxide nanoparticles. This study aims to create a biodegradable wound dressing. A Fourier Transform Infrared (FTIR) study shows that PVA, PEG, and MgO create hydrogen bonding interactions. Hydrophilic characteristics are shown by the polymeric blend's 56.289° contact angle. MgO also lowers the contact angle, making the film more hydrophilic. Hydrophilicity improves film biocompatibility, live cell adhesion, wound healing, and wound dressing degradability. Differential Scanning Calorimeter (DSC) findings suggest the PVA/PEG combination melted at 53.16 °C. However, adding different weight fractions of MgO nanoparticles increased the nanocomposite's melting temperature (Tm). These nanoparticles improve the film's thermal stability, increasing Tm. In addition, MgO nanoparticles in the polymer blend increased tensile strength and elastic modulus. This is due to the blend's strong adherence to the reinforcing phase and MgO nanoparticles' ceramic material which has a great mechanical strength. The combination of 70% PVA + 30% PEG exhibited good antibacterial spatially at 0.2% MgO, according to antibacterial test results.

2.
J Ethn Subst Abuse ; : 1-16, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38949863

ABSTRACT

In Greenland, where addiction-related concerns significantly affect well-being, research has explored alcohol's impact on health and mortality. However, no studies have focused on mortality among those who received addiction treatment. This study investigates whether individuals treated for addiction in Greenland experience elevated mortality rates compared to the general population. The study encompassed individuals receiving addiction treatment through the national system between 2012 and December 31, 2022. Data on treatment were sourced from the National Addiction Database, and Statistics Greenland. Person-years at risk were calculated and used to estimate crude mortality rates (CMRs). Adjusted standardized mortality rates (SMRs), accounting for age, sex, and calendar year, were estimated using an indirect method based on observed and expected deaths. Of the 3286 in treatment, 53.9% were women, with a median age of 37. About a third had undergone multiple treatment episodes, and 60.1% received treatment in 2019 or later. The cohort was followed for a median of 2.89 years, yielding 12,068 person-years. The overall CMR was 7.79 deaths per 1000 person-years, with a SMR of 1.42 (95% confidence interval: 1.15; 1.74). Significantly, SMRs differed by age at treatment entry, with younger groups exhibiting higher SMRs (p value = .021). This study found that individuals seeking treatment for addiction problems in Greenland had a higher mortality rate than the general population. Importantly, these SMRs were substantially lower than those observed in clinical populations in other countries.

3.
Addict Biol ; 29(7): e13419, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38949209

ABSTRACT

Substance use disorders (SUDs) are seen as a continuum ranging from goal-directed and hedonic drug use to loss of control over drug intake with aversive consequences for mental and physical health and social functioning. The main goals of our interdisciplinary German collaborative research centre on Losing and Regaining Control over Drug Intake (ReCoDe) are (i) to study triggers (drug cues, stressors, drug priming) and modifying factors (age, gender, physical activity, cognitive functions, childhood adversity, social factors, such as loneliness and social contact/interaction) that longitudinally modulate the trajectories of losing and regaining control over drug consumption under real-life conditions. (ii) To study underlying behavioural, cognitive and neurobiological mechanisms of disease trajectories and drug-related behaviours and (iii) to provide non-invasive mechanism-based interventions. These goals are achieved by: (A) using innovative mHealth (mobile health) tools to longitudinally monitor the effects of triggers and modifying factors on drug consumption patterns in real life in a cohort of 900 patients with alcohol use disorder. This approach will be complemented by animal models of addiction with 24/7 automated behavioural monitoring across an entire disease trajectory; i.e. from a naïve state to a drug-taking state to an addiction or resilience-like state. (B) The identification and, if applicable, computational modelling of key molecular, neurobiological and psychological mechanisms (e.g., reduced cognitive flexibility) mediating the effects of such triggers and modifying factors on disease trajectories. (C) Developing and testing non-invasive interventions (e.g., Just-In-Time-Adaptive-Interventions (JITAIs), various non-invasive brain stimulations (NIBS), individualized physical activity) that specifically target the underlying mechanisms for regaining control over drug intake. Here, we will report on the most important results of the first funding period and outline our future research strategy.


Subject(s)
Substance-Related Disorders , Humans , Animals , Germany , Behavior, Addictive , Alcoholism
4.
Appl Environ Microbiol ; : e0101424, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38953370

ABSTRACT

Bacterial and fungal copper radical oxidases (CROs) from Auxiliary Activity Family 5 (AA5) are implicated in morphogenesis and pathogenesis. The unique catalytic properties of CROs also make these enzymes attractive biocatalysts for the transformation of small molecules and biopolymers. Despite a recent increase in the number of characterized AA5 members, especially from subfamily 2 (AA5_2), the catalytic diversity of the family as a whole remains underexplored. In the present study, phylogenetic analysis guided the selection of six AA5_2 members from diverse fungi for recombinant expression in Komagataella pfaffii (syn. Pichia pastoris) and biochemical characterization in vitro. Five of the targets displayed predominant galactose 6-oxidase activity (EC 1.1.3.9), and one was a broad-specificity aryl alcohol oxidase (EC 1.1.3.7) with maximum activity on the platform chemical 5-hydroxymethyl furfural (EC 1.1.3.47). Sequence alignment comparing previously characterized AA5_2 members to those from this study indicated various amino acid substitutions at active site positions implicated in the modulation of specificity.IMPORTANCEEnzyme discovery and characterization underpin advances in microbial biology and the application of biocatalysts in industrial processes. On one hand, oxidative processes are central to fungal saprotrophy and pathogenesis. On the other hand, controlled oxidation of small molecules and (bio)polymers valorizes these compounds and introduces versatile functional groups for further modification. The biochemical characterization of six new copper radical oxidases further illuminates the catalytic diversity of these enzymes, which will inform future biological studies and biotechnological applications.

5.
Bull Exp Biol Med ; 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38954302

ABSTRACT

The effectiveness of ethylmethylhydroxypyridine succinate (EMHPS) in acute alcohol intoxication was tested in a study on SPF male outbred ICR mice. Ethanol (concentration 40%) was administered to animals once intraperitoneally at a dose of 4 g/kg. Control animals were injected with saline in an equivalent volume. In 15 min after the administration of alcohol, the animals were injected intravenously or intramuscularly with EMHPS at a dose of 50 or 100 mg/kg or with saline via the same route in an equivalent volume. Animal behavior was tested 3 and 24 h later after administration of the substances. After 3 and 24 h, mice in the pathological control groups developed semiptosis, the gait and the turning over reflex were impaired, the strength of the hind limbs decreased and the distance between the hind limbs increased when landing; in the open-field test, the latency of the first movement increased, and the number of rearing postures decreased. Intravenous and intramuscular administration of EMHPS in doses of 50 and 100 mg/kg had a pronounced antitoxic and neuroprotective effect in acute alcohol intoxication: all studied parameters did not differ significantly from the control.

6.
Biomater Adv ; 163: 213934, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38954877

ABSTRACT

Sample partitioning is a crucial step towards digitization of biological assays on polymer microfluidic platforms. However, effective liquid filling into microwells and long-term hydrophilicity remain a challenge in polymeric microfluidic devices, impeding the applicability in diagnostic and cell culture studies. To overcome this, a method to produce permanent superhydrophilic 3-dimensional microwells using cyclic olefin copolymer (COC) microfluidic chips is presented. The COC substrate is oxidized using UV treatment followed by ultrasonic spray coating of polyvinyl alcohol solution, offering uniform and long-term coating of high-aspect ratio microfeatures. The coated COC surfaces are UV-cured before bonding with a hydrophobic pressure-sensitive adhesive to drive selective filling into the wells. The surface hydrophilicity achieved using this method remains unchanged (water contact angle of 9°) for up to 6 months and the modified surface is characterized for physical (contact angle & surface energy, morphology, integrity of microfeatures and roughness), chemical composition (FTIR, Raman spectroscopy) and coating stability (pH, temperature, time). To establish the feasibility of the modified surface in biological applications, PVA-coated COC microfluidic chips are tested for DNA sensing (digital LAMP detection of CMV), and biocompatibility through protein adsorption and cell culture studies (cell adhesion, viability, and metabolic activity). Kidney and breast cells remained viable for the duration of testing (7 days) on this modified surface, and the coating did not affect the protein content, morphology or quality of the cultured cells. The ultrasonic spray coated system, coating with 0.25 % PVA for 15 cycles with 0.12 A current after UV oxidation, increased the surface energy of the COC (naturally hydrophobic) from 22.04 to 112.89 mJ/m2 and improved the filling efficiency from 40 % (native untreated COC) to 94 % in the microwells without interfering with the biocompatibility of the surface, proving to be an efficient, high-throughput and scalable method of microfluidic surface treatment for diagnostic and cell growth applications.

7.
Article in English | MEDLINE | ID: mdl-38955138

ABSTRACT

This work aims to improve the post stabilty of reusable potassium iodide hydrogel dosimter. A reusable and low-cost radiochromic dosimeter containing a gel matrix of polyvinyl alcohol, potassium iodide dye, froctose as reducing agent and glutaraldehyde as cross-linking agent was developed for dose calibration in radiotherapy. The gel samples were exposed to different absorbed doses using a medical linear acceleration. UV-Vis Spectrophotometry was utilized to investigate the changes in optical-properties of irradiated gels with regard to peak wavelength of 353 nm. The stability of the gel (one of the most limitation of using this dosimeter) was improved significantly by the addition of certain concentrations of dimethyl sulfoxide. The two-dimensional optical imaging system of charge-coupled-device (CCD) camera with a uniform RGB light-emitting-diode (LED) array source was used for diffusion coefficient purpose using two dimensional gel template. The value of diffusion coefficient reported is significant and highly reduced compared with other dosimeters reported in the literatures. Moreover, heating the improved gels to certain temperatures results in resetting their optical properties, which makes it possible to reuse for multiple times.

8.
J Subst Use Addict Treat ; : 209448, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38955251

ABSTRACT

INTRODUCTION: Although Black Americans tend to consume less alcohol than non-Hispanic/Latine White Americans, Black Americans who do drink alcohol appear at especially high risk for negative alcohol-related problems. This alcohol-based health disparity indicates a need to identify psycho-sociocultural factors that may play a role in drinking and related problems to inform prevention and treatment efforts. Minority stress-based models posit that stressors such as racism increase negative emotions, which may be associated with using substances such as alcohol to cope with negative emotions. Yet, little research has directly assessed emotional reactions to racism and whether it plays a role in drinking-related behaviors. METHOD: Participants were 164 Black American undergraduates at a racially/ethnically diverse university who endorsed current alcohol use 18-48 (M = 21.7, SD = 4.3). Participants completed an online survey regarding their experiences with racism and alcohol-related behaviors. RESULTS: Experiencing more frequent racism was related to greater negative emotions experienced in response to racism (i.e., negative emotional reactivity to racism) and alcohol-related problems. More frequent racism was related to more alcohol-related problems via the sequential effects of negative emotional reactivity to racism and coping motivated drinking. CONCLUSIONS: These data indicate that the experience of negative emotions that occur after experiencing racism and attempts to cope with those negative emotions by consuming alcohol play important roles in drinking behaviors among Black Americans.

9.
Pain Manag Nurs ; 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38955553

ABSTRACT

BACKGROUND: Morton's neuroma (MN) is one of the most frequent neurological pathologies in feet, affecting approximately 4% of the general population. The treatment of MN can be surgical, conservative, and infiltrative, with different substances used in the injections for MN, as steroids, sclerosing solutions, and others. This review aims to evaluate the efficacy of current infiltrative therapy for Morton's neuroma and, additionally, to define adverse effects of this therapy. MATERIAL AND METHODS: A literature search was performed in PubMed, Embase, CINHAL, Epistemonikos, Web of Science (WOS), SPORTSDiscus and Cochrane Library. This search involved the application of all types of infiltrative treatment applicable to MN. The search was limited to original data describing clinical outcomes and pain using the Visual Analogue pain Scale (VAS) or the Johnson Satisfaction Scale, between February and June 2023. RESULTS: Twelve manuscripts were selected (six randomized controlled trials and six longitudinal observational studies) involving 1,438 patients. Capsaicin was reported to produce a VAS score reduction of 51.8%. Corticosteroids also reported a high level of efficacy. Alcohol and Hyaluronic Acid injections are well tolerated, but the effects of their application need further research. There were no serious adverse events. CONCLUSIONS: Corticosteroids, sclerosant injections, hyaluronic acid and capsaicin have been shown to be effective in reducing the pain related to MN.

10.
BMC Health Serv Res ; 24(1): 772, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38951799

ABSTRACT

BACKGROUND: Alcohol-related mortality and morbidity increased during the COVID-19 pandemic in England, with people from lower-socioeconomic groups disproportionately affected. The North East and North Cumbria (NENC) region has high levels of deprivation and the highest rates of alcohol-related harm in England. Consequently, there is an urgent need for the implementation of evidence-based preventative approaches such as identifying people at risk of alcohol harm and providing them with appropriate support. Non-alcohol specialist secondary care clinicians could play a key role in delivering these interventions, but current implementation remains limited. In this study we aimed to explore current practices and challenges around identifying, supporting, and signposting patients with Alcohol Use Disorder (AUD) in secondary care hospitals in the NENC through the accounts of staff in the post COVID-19 context. METHODS: Semi-structured qualitative interviews were conducted with 30 non-alcohol specialist staff (10 doctors, 20 nurses) in eight secondary care hospitals across the NENC between June and October 2021. Data were analysed inductively and deductively to identify key codes and themes, with Normalisation Process Theory (NPT) then used to structure the findings. RESULTS: Findings were grouped using the NPT domains 'implementation contexts' and 'implementation mechanisms'. The following implementation contexts were identified as key factors limiting the implementation of alcohol prevention work: poverty which has been exacerbated by COVID-19 and the prioritisation of acute presentations (negotiating capacity); structural stigma (strategic intentions); and relational stigma (reframing organisational logics). Implementation mechanisms identified as barriers were: workforce knowledge and skills (cognitive participation); the perception that other departments and roles were better placed to deliver this preventative work than their own (collective action); and the perceived futility and negative feedback cycle (reflexive monitoring). CONCLUSIONS: COVID-19, has generated additional challenges to identifying, supporting, and signposting patients with AUD in secondary care hospitals in the NENC. Our interpretation suggests that implementation contexts, in particular structural stigma and growing economic disparity, are the greatest barriers to implementation of evidence-based care in this area. Thus, while some implementation mechanisms can be addressed at a local policy and practice level via improved training and support, system-wide action is needed to enable sustained delivery of preventative alcohol work in these settings.


Subject(s)
Alcoholism , COVID-19 , Qualitative Research , Secondary Care , Humans , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19/psychology , England/epidemiology , SARS-CoV-2 , Female , Male , Pandemics/prevention & control , Adult , Interviews as Topic
11.
Alcohol Alcohol ; 59(4)2024 May 14.
Article in English | MEDLINE | ID: mdl-38953742

ABSTRACT

AIMS: Reward processing and regulation of emotions are thought to impact the development of addictive behaviors. In this study, we aimed to determine whether neural responses during reward anticipation, threat appraisal, emotion reactivity, and cognitive reappraisal predicted the transition from low-level to hazardous alcohol use over a 12-month period. METHODS: Seventy-eight individuals aged 18-22 with low-level alcohol use [i.e. Alcohol Use Disorder Identification Test (AUDIT) score <7] at baseline were enrolled. They completed reward-based and emotion regulation tasks during magnetic resonance imaging to examine reward anticipation, emotional reactivity, cognitive reappraisal, and threat anticipation (in the nucleus accumbens, amygdala, superior frontal gyrus, and insula, respectively). Participants completed self-report measures at 3-, 6-, 9-, and 12-month follow-up time points to determine if they transitioned to hazardous use (as defined by AUDIT scores ≥8). RESULTS: Of the 57 participants who completed follow-up, 14 (24.6%) transitioned to hazardous alcohol use. Higher baseline AUDIT scores were associated with greater odds of transitioning to hazardous use (odds ratio = 1.73, 95% confidence interval 1.13-2.66, P = .005). Brain activation to reward, threat, and emotion regulation was not associated with alcohol use. Of the neural variables, the amygdala response to negative imagery was numerically larger in young adults who transitioned to hazardous use (g = 0.31), but this effect was not significant. CONCLUSIONS: Baseline drinking levels were significantly associated with the transition to hazardous alcohol use. Studies with larger samples and longer follow-up should test whether the amygdala response to negative emotional imagery can be used to indicate a future transition to hazardous alcohol use.


Subject(s)
Emotional Regulation , Magnetic Resonance Imaging , Reward , Humans , Male , Female , Young Adult , Emotional Regulation/physiology , Adolescent , Alcoholism/psychology , Alcoholism/physiopathology , Alcoholism/diagnostic imaging , Brain/diagnostic imaging , Alcohol Drinking/psychology , Alcohol Drinking/physiopathology , Amygdala/diagnostic imaging , Amygdala/physiopathology , Emotions/physiology , Adult
12.
Alcohol Alcohol ; 59(4)2024 May 14.
Article in English | MEDLINE | ID: mdl-38953743

ABSTRACT

INTRODUCTION: This study aims to clarify differences in mood, craving, and treatment response between reward and relief/habit individuals in a study of naltrexone, varenicline, and placebo. We hypothesized that relief/habit individuals would have a poorer mood during early abstinence and higher levels of alcohol craving than reward individuals. We hypothesized that reward individuals would demonstrate better drinking outcomes on naltrexone versus placebo. METHODS: Data were culled from a randomized, double-blind, placebo-controlled human trial of 53 individuals (18F/16M) with alcohol use disorder randomized to varenicline (n = 19), naltrexone (n = 15), or matched placebo (n = 19). In this 6-day practice quit trial, participants attempted to abstain from drinking and completed daily diaries. Participants were classified into reward or relief/habit subgroups based on self-reported motivation for drinking. Multilinear models tested differences in mood and alcohol craving between reward and relief/habit individuals. General linear models tested differences between reward and relief/habit individuals' drinking outcomes on each medication versus placebo. RESULTS: Relief/habit individuals showed decreases in positive mood and increases in negative mood over the quit attempt across medications, compared to reward individuals (P's < .05). Reward individuals' tension decreased on naltrexone, while relief/habit individuals' tension remained stable (F = 3.64, P = .03). Reward individuals in the placebo group had higher percent days abstinent than relief individuals in the placebo group (P < .001). DISCUSSION: This study suggests relief/habit individuals' mood worsens during early abstinence. Our finding that reward individuals' tension decreased on naltrexone and increased on placebo may suggest a clinical response to the medication.


Subject(s)
Affect , Alcoholism , Craving , Naltrexone , Reward , Varenicline , Humans , Naltrexone/therapeutic use , Male , Varenicline/therapeutic use , Female , Double-Blind Method , Adult , Alcoholism/drug therapy , Alcoholism/psychology , Craving/drug effects , Middle Aged , Affect/drug effects , Narcotic Antagonists/therapeutic use , Alcohol Drinking/psychology , Alcohol Drinking/drug therapy , Treatment Outcome
13.
Front Neurosci ; 18: 1375440, 2024.
Article in English | MEDLINE | ID: mdl-38957186

ABSTRACT

Introduction: Alcohol use disorder (AUD) is commonly associated with anxiety disorders and enhanced stress-sensitivity; symptoms that can worsen during withdrawal to perpetuate continued alcohol use. Alcohol increases neuroimmune activity in the brain. Our recent evidence indicates that alcohol directly modulates neuroimmune function in the central amygdala (CeA), a key brain region regulating anxiety and alcohol intake, to alter neurotransmitter signaling. We hypothesized that cannabinoids, such as cannabidiol (CBD) and ∆9-tetrahydrocannabinol (THC), which are thought to reduce neuroinflammation and anxiety, may have potential utility to alleviate alcohol withdrawal-induced stress-sensitivity and anxiety-like behaviors via modulation of CeA neuroimmune function. Methods: We tested the effects of CBD and CBD:THC (3:1 ratio) on anxiety-like behaviors and neuroimmune function in the CeA of mice undergoing acute (4-h) and short-term (24-h) withdrawal from chronic intermittent alcohol vapor exposure (CIE). We further examined the impact of CBD and CBD:THC on alcohol withdrawal behaviors in the presence of an additional stressor. Results: We found that CBD and 3:1 CBD:THC increased anxiety-like behaviors at 4-h withdrawal. At 24-h withdrawal, CBD alone reduced anxiety-like behaviors while CBD:THC had mixed effects, showing increased center time indicating reduced anxiety-like behaviors, but increased immobility time that may indicate increased anxiety-like behaviors. These mixed effects may be due to altered metabolism of CBD and THC during alcohol withdrawal. Immunohistochemical analysis showed decreased S100ß and Iba1 cell counts in the CeA at 4-h withdrawal, but not at 24-h withdrawal, with CBD and CBD:THC reversing alcohol withdrawal effects.. Discussion: These results suggest that the use of cannabinoids during alcohol withdrawal may lead to exacerbated anxiety depending on timing of use, which may be related to neuroimmune cell function in the CeA.

14.
Front Nutr ; 11: 1400815, 2024.
Article in English | MEDLINE | ID: mdl-38957869

ABSTRACT

Introduction: The term emotional eating (EE) describes the tendency to eat as an automatic response to negative emotions and has been linked to anxiety and depression, common symptoms among the university population. The EE tendencies have also been associated with excessive internet use and an increase in alcohol intake among young university students. Methods: The aim of this study is to examine the relationship between the tendency towards EE and other health-compromising behaviors, such as excessive internet use or high alcohol intake. Additionally, it aims to investigate the association of these risky behaviors with the participants' performance level in a virtual reality (VR) task that assesses their executive functioning, and to assess impulsivity and levels of anxiety and depression. Results: The results associate EE with excessive internet (r = 0.332; p < 0.01). use but not with alcohol consumption. Alcohol consumption was not associated with anxiety, depression, or impulsivity, but it was related to altered executive functions in the VR task: flexibility and working memory explained 24.5% of the variance. By contrast, EE and internet overuse were not related to executive function but were associated with impulsivity, depression, and anxiety. Impulsivity and depressive symptoms accounted for 45% of the variance in EE. Depression, trait anxiety and impulsivity explained 40.6% of the variance in internet overuse. Discussion: The results reveal distinct patterns of psychological and neuropsychological alterations associated with alcohol consumption compared to emotional eating (EE) and excessive internet use. These findings underscore significant differences in the contributing factors between addictions and other substance-free addictive behaviors. For a deeper understanding of the various contributing factors to EE in college students, further research is recommended.

15.
Food Chem ; 458: 140236, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38959805

ABSTRACT

Coffee, a globally consumed beverage, has raised concerns in Islamic jurisprudence due to the possible presence of alcohol compounds. This research aims to utilise the sensitivity and reliability of 1H NMR spectroscopy in the quantification of alcohol compounds such as ethanol, furfuryl alcohol, and 5-(hydroxymethyl) furfural (HMF) in commercial instant coffee. Analysis of seven products was performed using advanced 1H Nuclear Magnetic Resonance (NMR) spectroscopy together with Statistical Total Correlation Spectroscopy (STOCSY) and Resolution-Enhanced (RED)-STORM. The analysis of the 100 mg sample revealed the absence of ethanol. The amount of furfuryl alcohol and HMF in the selected commercial instant coffee samples was 0.817 µg and 0.0553 µg, respectively. This study demonstrates the utility of 1H NMR spectroscopy in accurate quantification of trace components for various applications.

16.
Cell Host Microbe ; 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38959900

ABSTRACT

The gut microbiota and diet-induced changes in microbiome composition have been linked to various liver diseases, although the specific microbes and mechanisms remain understudied. Alcohol-related liver disease (ALD) is one such disease with limited therapeutic options due to its complex pathogenesis. We demonstrate that a diet rich in soluble dietary fiber increases the abundance of Bacteroides acidifaciens (B. acidifaciens) and alleviates alcohol-induced liver injury in mice. B. acidifaciens treatment alone ameliorates liver injury through a bile salt hydrolase that generates unconjugated bile acids to activate intestinal farnesoid X receptor (FXR) and its downstream target, fibroblast growth factor-15 (FGF15). FGF15 promotes hepatocyte expression of ornithine aminotransferase (OAT), which facilitates the metabolism of accumulated ornithine in the liver into glutamate, thereby providing sufficient glutamate for ammonia detoxification via the glutamine synthesis pathway. Collectively, these findings uncover a potential therapeutic strategy for ALD involving dietary fiber supplementation and B. acidifaciens.

17.
Article in English | MEDLINE | ID: mdl-38960894

ABSTRACT

BACKGROUND: Alcohol craving is related to problematic alcohol use; therefore, pharmacotherapies that modulate alcohol craving are of interest. N-acetylcysteine, an over-the-counter antioxidant, is a candidate pharmacotherapy for adolescent alcohol use with the potential to impact craving. Cue-reactivity paradigms using functional magnetic resonance imaging (fMRI) can identify neural regions implicated in craving and serve as a screening tool for novel pharmacotherapy options. METHODS: This preliminary study examined the effect of N-acetylcysteine on neural reactivity to alcohol cues and subjective craving among 31 non-treatment-seeking adolescents (17.6-19.9 years old, 55% female) who use alcohol heavily. In a randomized cross-over design, participants completed three fMRI sessions: baseline and after a 10-day course of N-acetylcysteine (1200 mg twice daily) and matched placebo. The primary outcome was neural response to alcohol versus non-alcohol beverage cues after N-acetylcysteine versus placebo, with a secondary outcome of self-reported subjective craving. RESULTS: In the full sample (n = 31), there was no effect of N-acetylcysteine versus placebo on neural alcohol reactivity (ps ≥ 0.49; η p 2 $$ {\upeta_{\mathrm{p}}}^2 $$ s = 0.00-0.07) or self-reported acute alcohol craving (p = 0.18, η p 2 $$ {\upeta_{\mathrm{p}}}^2 $$ = 0.06). However, N-acetylcysteine did reduce self-reported generalized alcohol craving (p = 0.03, η p 2 $$ {\upeta_{\mathrm{p}}}^2 $$ = 0.15). In a subsample of youth who met criteria for past-year alcohol use disorder (n = 19), results remained unchanged. CONCLUSIONS: N-acetylcysteine may not alter neural reactivity to alcohol cues or acute craving; however, it may reduce general subjective alcohol craving among adolescents who consume alcohol heavily.

18.
Daru ; 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38963538

ABSTRACT

BACKGROUND: Melanoma poses a significant threat to human health, making the development of a safe and effective treatment a crucial challenge. Disulfiram (DS) is a proven anticancer drug that has shown effectiveness when used in combination with copper (DS-Cu complex). OBJECTIVES: This study focuses on encapsulation of DS-copper complex into nanofiber scaffold from polyvinyl alcohol (PVA) (DS-Cu@PVA). In order to increase bioavailability towards melanoma cell lines and decrease its toxicity. METHODS: The scaffold was fabricated through an electrospinning process using an aqueous solution, and subsequently analyzed using ART-Fourier transform infrared spectroscopy (ART-FTIR), scanning electron microscopy (SEM), and energy dispersive X-ray analysis (EDX). Additionally, cellular cytotoxicity, flow cytometry analysis, and determination of caspase 3 activity were conducted to further characterize the scaffold. RESULTS: The results confirmed that encapsulation of DS-Cu complex into PVA was successful via different characterization. The scanning electron microscopy (SEM) analysis revealed that the diameter of the nanofibers remained consistent despite the addition of DS-Cu. Additionally, ATR-FTIR confirmed that the incorporation of DS-Cu into PVA did not significantly alter the characteristic peaks of PVA. Furthermore, the cytotoxicity assessment of the DS-Cu@PVA nanofibrous scaffold using human normal skin cells (HFB4) demonstrated its superior biocompatibility compared to DS-Cu-free counterparts. Notably, the presence of DS-Cu maintained its effectiveness in promoting apoptosis by increasing cellular reactive oxygen species, proapoptotic gene expression, and caspase 3 activity, while simultaneously reducing glutathione levels and oncogene expression in human and mouse melanoma cell lines (A375 and B16F10, respectively). Overall, these findings suggest that the addition of DS-Cu to PVA nanofibers enhances their biocompatibility and cytotoxic effects on melanoma cells, making them a promising candidate for biomedical applications. CONCLUSION: The findings indicate that the targeted delivery of DS-Cu onto a PVA nanofiber scaffold holds potential approach to enhance the efficacy of DS-Cu in combating melanoma.

19.
J Addict Dis ; : 1-6, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38946394

ABSTRACT

Wernicke's encephalopathy (WE) is a dangerous and potentially fatal neurological condition associated with thiamin deficiency. The standard treatment for WE is intravenous (IV) thiamin, but limited research describes optimal dosing. We present a case of a 40-year-old male with severe alcohol use disorder (AUD) and chronic malnourishment who developed WE. Upon administration of 100 mg IV thiamin, symptoms of WE persisted, but when the dose was increased to 500 mg, altered mental status and ophthalmoplegia resolved rapidly. IV thiamin is a reliable and low-risk treatment for WE, even when administered at high doses. High-dose IV thiamin (i.e., >/100 mg) can treat neurological symptoms and cognitive dysfunction in WE and should be considered for first-line treatment. Further study of WE diagnostic and treatment guidelines is warranted to maximize recovery potential.

20.
Subst Use Misuse ; : 1-12, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38956825

ABSTRACT

Background: Prior studies suggest that lower levels of mindfulness contribute to the motivation of using alcohol to cope with distress. Research examining this possibility is scarce or limited to alcohol, but not marijuana, related outcomes. Objectives: We examined separate models (for alcohol and for marijuana) to determine the associations between trait mindfulness (describing, acting with awareness, non-judging, non-reactivity) and alcohol and marijuana outcomes (use indicators and negative consequences) via emotional psychopathology (i.e., a latent variable assessing symptoms of depression and anxiety) and alcohol/marijuana coping motives. Results: The final analytic sample consisted of 456 participants (Mean age = 22.96 ± 3.12 years; 66.2% women) for the alcohol model; and 232 participants (Mean age = 22.96 ± 3.01 years; 66.2% women) for the marijuana model. Two path models were conducted, such that indirect paths were examined for each trait mindfulness facet on alcohol/marijuana outcomes (e.g., describing → emotional psychopathology → alcohol coping motives → binge drinking frequency). Within the comprehensive alcohol model, describing, acting with awareness, non-judging and non-reactivity were associated with less binge drinking frequency and lower number of alcohol-related negative consequences via lower severity of emotional psychopathology symptoms and lower endorsement of drinking to cope motives. For the marijuana model, describing, acting with awareness, and non-judging of inner experience were associated with less marijuana quantity (grams) consumed and lower number of marijuana-related negative consequences via lower severity of emotional psychopathology symptoms and lower endorsement of marijuana coping motives. Conclusions: Prevention and intervention programs of alcohol and marijuana in Argentina may benefit from improving mindfulness skills and targeting emotional psychopathology and motives to use drugs, to prevent or reduce negative drug-related consequences.

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