Alcohol Treatment Research Articles

Anticancer Effects of New Disulfiram Analogs.

Disulfiram (DSF), an irreversible aldehyde dehydrogenase 2 (ALDH2) inhibitor, is an U.S. Food and Drug Administration (FDA)-approved drug for the treatment of chronic alcoholism. Recent studies have reported an interesting antitumor activity of DSF against a wide range of human malignancies, while a growing number of ongoing and completed clinical trials have provided evidence supporting the repurposing of DSF as an anticancer treatment. Nevertheless, despite its current clinical indications and potential future therapeutic applications for treating various diseases, DSF is associated with serious side effects attributed to the inhibition of ALDH2. We have recently synthesized DSF analogs (2a-v) with limited inhibition of ALDH2. Here, we report the anticancer activity of these molecules by highlighting their effects on cell signaling in Jurkat cells. DSF and two DSF analogs, 2g and 2r, all stimulated apoptotic signaling pathways, although the 2g analog activated more apoptosis-related genes and induced higher levels of apoptosis in vitro. Differential gene expression data suggested that compounds 2g and 2r specifically reprogram target cells to downregulate pathways related to cell growth and division, while upregulating pathways related to apoptosis or differentiation. Interestingly, both compounds 2g and 2r had more differentially expressed genes related to DNA damage pathways (including those related to apoptosis) when compared to DSF, which may offer insights into their mechanisms of action.

Long-term effectiveness of SBIRT by outreach visits on subsequent alcohol treatment utilization among inpatients from general hospital: a 36-months follow-up

Aim To investigate the long-term effect of Screening, Brief Intervention, and Referral to Treatment (SBIRT) on alcohol treatment utilization among general hospital inpatients. Methods This 36-month follow-up of a randomized controlled trial included general hospital inpatients who were screened using the Alcohol Use Disorder Identification Test (AUDIT). Patients with an AUDIT score of 8+ were included. Patients were randomized to either SBIRT (Relay) or treatment as-usual (TAU). Outcome was attendance at a specialized outpatient treatment institution or prescription of pharmacological alcohol treatment in general practice. Using the Danish Civil Registration System, patients were followed in the Danish National Patient Registry, Danish National Alcohol Treatment Register, and the Danish National Prescription Registry. Data was collected up to 36 months after discharge. Results The study population consisted of 258 patients in the Relay group and 303 patients in the TAU group. In the Relay group, 36 (14.0%) patients received treatment versus 23 (7.6%) in the TAU group. Patients in the Relay group had higher odds for receiving treatment compared to the TAU group (OR: 1.97, 95% CI: 1.1–3.4, p = 0.01). Significantly more patients in the Relay group scored 16+ on the AUDIT and had already tried to change their alcohol consumption (both p < 0.01). Adjusted for potential confounders, the effect of the Relay intervention was reduced (OR: 1.37, 95%CI: 0.7–2.5, p = 0.31). Conclusions This study did not find evidence that SBIRT is better than TAU at sustaining significant long-term alcohol treatment utilization after discharge among inpatients from general hospital.

Daily cigarette smoking among inpatients for substance use disorders in France, 2010-2020: Commonalities and specificities across substances.

This study aims to estimate the prevalence and factors associated with cigarette smoking among patients in treatment for substance use disorders (SUD) in France. We analyze a nation-wide dataset retrieving information on patients entering treatment for alcohol, opioid and stimulant use disorders between 2010 and 2020. We conduct multilevel Poisson regressions to determine the main factors associated with daily cigarette smoking among all patients who entered treatment for alcohol (n=607122), opioid (n=283381) or stimulant (n=57189) use disorders, and zero-truncated negative-binomial regressions to predict the average number of cigarettes per day. Daily cigarette smoking remains a widespread behavior among patients with SUD (overall prevalence: 72.2%, 95% CI: 72.1-72.3), with lower prevalence of daily cigarette smoking among patients treated for alcohol use disorders (69.9%, 95% CI: 69.8-70.0), and higher for patients treated for opioid (78.8%, 95% CI: 78.6-79.0) or stimulant use disorders (75.8%, 95% CI: 75.4-76.2). There was an overall increase in daily cigarette smoking over time (69.9%, 95% CI: 69.8-70.0 in 2010 vs 76.8%, 95% CI: 76.5-76.9 in 2020); however, the average number of cigarettes per day decreased (17.8 per day, 95% CI: 17.7-17.9 in 2010 vs 16.3 per day, 95% CI: 16.2-16.4 in 2020). The higher the education level, the fewer number of cigarettes per day; conversely, the higher the occupational status, the higher the number of cigarettes. The high prevalence of smoking among patients treated for SUD in France departs from the decreasing trend observed in the general population and remains a source of concern. It is necessary to implement tailored prevention strategies that target specific patient subgroups and increase staff awareness.

미술치료 전공 학부생의 임상실습, 수퍼비전, 학부과정 경험에 대한 질적 연구

Objectives The purpose of this study is to explore through qualitative research the experiences of undergraduate students majoring in art therapy in clinical practice, supervision, and undergraduate courses, and to analyze the intrinsic meaning of these experiences. Methods Data were collected through two in-depth interviews with six undergraduate students majoring in alco-hol treatment. The interviews used a semi-structured questionnaire to encourage undergraduate students to talk freely about their experiences in clinical practice, supervision, and undergraduate courses. The collected data were analyzed using open coding according to qualitative research methodology, and themes were derived inductively. Through this, the main themes and subcategories experienced by the participants were identified and the research results were derived. Results As a result of the analysis, 6 main areas, 14 categories, and 37 subcategories were derived. In clinical practice, external factors such as conditions of the practice institution, workload, communication between thera-pists, and changes in clients, and internal factors such as self-criticism, tension while performing roles, and sense of accomplishment after practice were identified. The supervision experience consisted of process aspects such as close supervision and shared experiences with colleagues, as well as academic and emotional support from the supervisor. During the bachelor's course, self-exploration, anxiety and burden about art work, and interaction with classmates served as factors that promoted improved future vision and psychological growth. Conclusions These findings provide significant implications for establishing criteria for selecting clinical practice institutions, improving supervision education, and enhancing the role of school education in undergraduate pro-grams aimed at training art therapists.

Interest in the Use of Herbal Supplements to Close the Treatment Gap for Hazardous Alcohol Use Among Men Who Have Sex With Men: Secondary Analysis of a Cross-Sectional Study.

Hazardous alcohol consumption is highly prevalent for men who have sex with men (MSM). The 4 treatments currently approved by the Food and Drug Administration for alcohol use are reaching an alarmingly low percentage of people who would benefit from a reduction in their alcohol use. There is increasing interest in alternative methods of treatment, such as herbal supplements, to address hazardous drinking. However, research on the acceptability of alternative pharmacotherapies among MSM remains limited. We examined the prevalence and correlates of expressing interest in using herbal supplements for alcohol treatment among MSM with hazardous alcohol consumption. We conducted a secondary data analysis from a cross-sectional study of MSM who use alcohol, conducted from March 2015 to July 2017 in San Francisco, California, to assess the overall prevalence of interest in using herbal supplements to help reduce alcohol consumption. Associations between expressing interest in herbal supplements and demographic, social, and clinical characteristics were examined using bivariate and multivariable logistic regression models. One-third (66/200, 33%) of the participants expressed interest in an herbal supplement for reducing alcohol consumption. In the multivariable analyses, weekly binge drinking (adjusted odds ratio [aOR] 2.85, 95% CI 1.17-6.93), interest in abstaining from alcohol use (aOR 5.04, 95% CI 1.46-17.40), higher severity of alcohol dependence score (aOR 1.22, 95% CI 1.04-1.41), and interest in naltrexone (aOR 3.22, 95% CI 2.12-4.91) were independently associated with higher odds of being interested in using an herbal supplement to reduce alcohol consumption, adjusting for age, race or ethnicity, and education. We found that MSM who have hazardous drinking habits, more severe alcohol dependence, and interest in pharmacotherapy were more likely to express interest in using an herbal supplement for reducing alcohol consumption. To our knowledge, this is the first study that has evaluated correlates of interest in herbal supplements for alcohol use among MSM. As researchers implement novel alcohol treatment studies, they should focus on recruitment efforts among MSM with a motivation to reduce their alcohol use patterns.

Psychometric Properties of the Credibility/Expectancy Questionnaire in Individuals with Opioid Use Disorder

ABSTRACT Credibility and expectancy are important aspects of therapy/treatment processes. We aimed to perform cross-cultural validation and examine the psychometric properties of the Credibility/Expectancy Questionnaire (CEQ). Ninety-one patients with opioid use disorder from Tobacco, Alcohol, and Drug Addiction Treatment Program were included in the study. Sociodemographic data form, CEQ, Beck Depression Inventory (BDI), State and Trait Anxiety Inventory (STAI), and Attitudes Toward Seeking Psychological Professional Help Scale-Short Form (ATSPPHS-SF) were filled out by participants. Confirmatory factor analyses showed that CEQ has two factors in our sample, similar to the original version. Reliability analyses showed that CEQ has a high internal consistency and test-retest reliability. Regarding convergent validity results, CEQ was correlated with ATSPPHS-SF. No significant correlation was found between CEQ and BDI and STAI regarding discriminant validity results. In conclusion, the Turkish version of CEQ is a valid, reliable scale and could be used in patients with opioid use disorder. In patients with opioid use disorder, we contributed to the addiction literature by adapting a short and effective survey that measures trust and expectation.

Altered Expression of Neuroplasticity-Related Genes in Alcohol Addiction and Treatment

Alcohol use disorder’s complexity arises from genetic and environmental factors, with alcohol metabolism genes and neurotransmitter pathways being critical. This study aims to analyze synaptic plasticity gene expression changes in individuals with AUD in order to study their contribution to AUD development and to identify potential biomarkers of treatment response. RNA was extracted from whole peripheral blood (20 patients, 10 healthy controls), before and after treatment (Qiagen AllPrep RNA/DNA Mini Kit), and the gene expression of 84 genes related to neuroplasticity was studied using the RT2 Profiler for Human Synaptic Plasticity RT-PCR Array (PAHS-126ZA, Qiagen), comparing AUD patients to control and responders to non-responders. The potential prognostic/predictive biomarkers were searched using machine learning models. A total of 35 dysregulated genes were found in AUD patients. EPHB2, EGR, and AKT1 were increased, while TIMP1, NCAM1, and GRM2 were decreased. Responders showed distinct gene expression profiles at baseline. After treatment, the expression of 57 genes was normalized, while NCAM1, GRM2, and BDNF showed the most significant recovery. EGR4, INHBA, and NCAM1 emerged as potential biomarkers to predict treatment success. These results indicate that gene profiles in peripheral blood can serve as prognostic markers for the prognosis and treatment of AUD, although further validation is required.

Effect of Benzyl Alcohol on Main Defense System Components of Galleria mellonella (Lepidoptera).

Benzyl alcohol (E1519) is an aromatic alcohol used in the pharmaceutical and food industry. It is used to protect food products against microorganisms during storage, as a flavoring in the production of chocolate and confectionery products, as an important ingredient in fragrance, and as a preservative in medical products. However, little is known of its effect on insects. The main aim of this study was to determine the influence of benzyl alcohol on the defense systems of the wax moth Galleria mellonella, i.e., its cuticular lipid composition and critical elements of its immune system. A gas chromatography/mass spectrometry (GC/MS) analysis found benzyl alcohol treatment to elicit significant quantitative and qualitative differences in cuticular free fatty acid (FFA) profiles. Our findings indicate that benzyl alcohol treatment increased the levels of HSP70 and HSP90 and decreased those of HSF1, histamine, and cysteinyl leukotriene. Benzyl alcohol application also increased dismutase level in the hemolymph and lowered those of catalase and 8-OHdG. The treatment also had negative effects on G. mellonella hemocytes and a Sf9 cell line in vitro: 48-h treatment resulted in morphological changes, with the remaining cells being clearly spindle-shaped with numerous granules. The high insecticidal activity of compound and its lack of toxicity towards vertebrates suggest it could be an effective insecticide.

How to motivate adolescents who are afraid of treatment?

Motivation has long been considered key to sending substance use disorder (SUD) patients in the direction of recovery. But how do you motivate an adolescent, to whom motivational approaches may feel like a call to battle — or even worse, an excuse for running away? Lauren Sbarbaro, Ph.D., a psychologist licensed in alcohol and drug treatment who trained at Hazelden, shared some insights with attendees at the Cape Cod Symposium on Addictive Disorders (CCSAD) in Hyannis, Massachusetts last week.

Routine outcome monitoring and feedback in alcohol and other drug treatment: A qualitative study of client perspectives on implementation.

Routine outcome monitoring (ROM) and feedback is an evidence-supported strategy for evaluating alcohol and other drug (AOD) treatment outcomes. However, the implementation of ROM and feedback into AOD services remains a significant challenge. Research aimed at understanding client perspectives on ROM and feedback is needed to facilitate successful implementation. This study examined experiences with and perceptions of ROM and feedback in a sample of clients receiving AOD treatment. Interviews and online surveys were conducted with N = 26 people (13 male; Mage = 36.12 years, SD = 10.29) enrolled in an AOD treatment program in Australia. Data analysis of the transcripts was guided by thematic analysis, while descriptive statistics were used to analyse quantitative survey data. Four major themes were identified in the qualitative data: (i) ROM and feedback is valuable to AOD treatment; (ii) clear and concise outcome measures with an integrated feedback loop are vital to reliable ROM; (iii) desire for visual and verbal feedback that highlights progress; and (iv) ROM and feedback can be emotionally challenging. Participants valued ROM when it was clearly integrated within AOD treatment and they received feedback on their responses. Potential facilitators to implementing and improving the provision of ROM and feedback in AOD treatment include: (i) a clear, treatment-based rationale to foster client buy-in for ROM and maximise AOD treatment benefit; (ii) brief outcome measure surveys; and (iii) graphical visualisations of ROM feedback.

Development of an accelerometer-based wearable sensor approach for alcohol consumption detection.

Alcohol is a commonly used substance associated with significant public health consequences. Treatment is often stigmatized and limited with regard to both access and affordability, demonstrating the need for innovations in alcohol treatment. Accelerometer sensors can detect drinking without user input and are widely incorporated into wearable devices, increasing accessibility and affordability. We compared a distributional and random forest classification approach to detect and evaluate sensor-based drinking data. Data were collected at a local state fair (n = 194), where participants drank water at specified intervals interspersed with confounding behaviors (e.g., touching nose, rubbing forehead, or yawning) while wearing an Android-based smartwatch for 10 min. Participants were randomized to receive one of three drinking container shapes: pint, martini, or wine. The random forest model achieved an overall testing accuracy of 93% (sensitivity = 0.32; specificity = 0.99; positive predictive value = 0.74). The distributional algorithm achieved an overall accuracy of 95% (sensitivity = 0.76; specificity = 0.97; positive predictive value = 0.72). The distributional algorithm had a significantly greater accuracy (t(193) = 7.73, p < 0.001, d = 0.56) and sensitivity (t(193) = 24.5, p < 0.001, d = 1.76). Equivalency testing demonstrated significant equivalency to the ground truth for sip duration (tlower(193) = 16.92, p < 0.001; tupper(193) = -9.85, p < 0.001) and between-sip interval (tlower(193) = 1.72, p = 0.044; thigher(193) = -3.96, p < 0.001). However, the random forest did not have significant equivalency to the ground truth for between-sip interval (tlower(193) = 1.98, p = 0.025; thigher(193) = 0.160, p = 0.564). Overall, the results indicated that consumer-grade smartwatches can be utilized to detect and measure alcohol use behavior using machine learning and distributional algorithms. This work provides the methodological foundation for future research to analyze the behavioral pharmacology of alcohol use and develop accessible just-in-time clinical interventions.

Protective mechanisms of Hovenia dulcis Thunb extracts on acute alcoholism and liver injury

As a traditional Chinese medicine for anti-alcoholism, Hovenia dulcis Thunb (HDT) is widely used in the treatment of alcoholism and alcohol-related liver diseases. However, the scientific evidence of its mechanism has not been clearly established. In this study, a mouse model of acute alcoholism was established to explore the protective mechanisms of three kinds of HDT extracts on acute alcoholism and liver injury from the perspectives of behavioral indicators, serum and liver biochemical indicators, alcohol metabolic enzyme activity, intestinal flora, and liver metabolomics. The results showed that the extracts of HDT shortened the time of sobering up, significantly increased the activity of alcohol metabolic enzymes and antioxidant capacity, promoted ethanol metabolism, and had a certain preventive effect on alcoholic liver injury while preventing adverse reactions caused by alcohol. Notably, HDT water extract (HDTs) demonstrated superior anti-alcohol and liver protective properties compared to polysaccharide and polyphenol extracts of HDTs. It may be through the regulation of intestinal flora imbalance, specifically Muribaculaceae and Dubosiella to modulate biosynthetic pathways of phenylalanine, tyrosine, and tryptophan, ultimately mitigating oxidative stress caused by ethanol consumption. This suggests that HDTs may have potential in preventing acute alcoholism and liver injury.

British South Asian and Muslim Community's Perceptions and Experiences of Addiction and Traditional Drug and Alcohol Treatment Services.

Within traditional drug and alcohol (D&A) treatment services, the majority of those accessing support are of white ethnicity, with only a small percentage of people from the British South Asian (BSA) and Muslim community engaging in treatment services. This paper aims to explore perceived barriers to accessing traditional D&A services within the British South Asian and Muslim communities, based on qualitative data from interviews with family members and a practitioner. Qualitative data were obtained via 11 semi-structured interviews involving a practitioner (n = 1), and family and friends (n = 10) of those with historic and current D&A use in the community. Reflexive thematic analysis revealed four themes: (1) awareness of drug and alcohol use in the community, (2) drug and alcohol use as a taboo topic and the impact of admitting use, (3) knowledge of services for treatment, (4) how to increase awareness and accessibility of treatment. There was an increasing awareness of D&A use in the BSA and Muslim community. Despite this, limited conversations and misconceptions around D&A use and recovery led to those using D&A and their family members feeling stigmatised within their community and unable to seek support. This paper concludes by recommending increased communication between the BSA and Muslim communities and D&A treatment services to ensure accessibility of treatment by improving cultural competency.

How to motivate adolescents: Treatment can be scary

Motivation has long been considered key to sending adolescents with mental or substance use disorders in the direction of recovery. But how do you motivate an adolescent, to whom motivational approaches may feel like a call to battle — or even worse, an excuse for running away? Lauren Sbarbaro, Ph.D., a psychologist licensed in alcohol and drug treatment who trained at Hazelden, shared some insights with attendees at the Cape Cod Symposium on Addictive Disorders (CCSAD) in Hyannis, Massachusetts in September.

Effectiveness and experience of implementing digital interventions to promote smoking cessation among adults with severe mental illness: A systematic review and meta-analysis.

Digital technology is increasingly used to support interventions targeting smoking cessation in people with severe mental illness (SMI). However, little is known about their implementation and effectiveness in this population. We aimed to determine their effectiveness, stakeholder experiences, factors influencing implementation, and quality of reporting of digital interventions for smoking cessation in adults living with SMI. Five online bibliographic databases were searched for articles published between 31 December 2000 and 31 January 2023. Studies involving adults accessing treatment for alcohol and substance use disorders, neurocognitive disorders and terminal illnesses were excluded. Risk of bias was assessed using the Mixed Methods Appraisal Tool (MMAT). A Mantel-Haenszel random-effects meta-analysis of randomized controlled trials (RCTs) was conducted. Participant experience and intervention implementation were explored using a narrative synthesis. Quality of reporting of interventions was assessed using the Template for Intervention Description and Replication (TIDieR) checklist. Thirty-one studies enrolling 3,794 participants were included. Meta-analysis of biochemically verified abstinence at longest follow-up (month-1 to month-6) did not find an overall effect in favour of intervention [risk ratio (RR) = 0.66, 95% confidence interval (CI) = -0.005 - 1.37]. Interventions tailored to people with SMI were perceived as acceptable. Implementation strategies concentrated on overcoming practical challenges at the participant/user level. No evidence of the effectiveness of digital interventions to support smoking cessation in people with SMI was found. The importance of tailoring interventions to the needs of people with SMI is highlighted. Robust reporting of implementation is required to enhance future efforts to support smoking cessation in adults with SMI. The findings of this review add to the emerging evidence on digital interventions to support smoking cessation among people with SMI. We highlight the importance of tailoring interventions to the population, particularly considering the role of mental illness and the side effects of psychotropic medication in the accessibility and usability of digital interventions.

Integration of a facilitated access pathway for contraception into alcohol and other drug treatment services: A cohort study comparing metropolitan and regional settings.

Women who attend alcohol and other drug (AOD) services experience higher rates of unintended pregnancy, and access less contraception, than the general population. This study aims to observe contraceptive initiation and use after contraception services were offered at metropolitan and regional AOD services. Clinical staff were provided contraception education. One hundred women aged 16-49 were recruited from two services between 2017 and 2021. Women completed a questionnaire on their obstetrics and gynaecological history, pregnancy plans and contraception use. Women were provided education on contraception options and offered referral to a contraception pathway. The primary outcome was initiation of highly reliable contraception; secondary outcomes were the types of contraception initiated, and contraception use and pregnancy at 12 months. We compared the initiation of contraception across the two study sites. At baseline, 91% of women were not planning a pregnancy within 12 months, with 21% of these using highly reliable contraception. Of all women not planning a pregnancy, 28% initiated highly reliable contraception via the pathway (2% metropolitan, 51% regional, p < 0.001), with intrauterine devices being the most frequent method initiated (15%). At 12 months, 44% were using highly reliable contraception and 15% had recorded pregnancies. Contraception pathways for women in AOD treatment can improve initiation of highly reliable methods of contraception, although pregnancy rates were still high and there were large differences between the study sites. Care navigation and clinical champions are some potential facilitators to contraception access, and understanding additional barriers to access may be useful.

Reasons for not seeking alcohol treatment among a sample of Florida adults with HIV who perceived the need for treatment

BackgroundA minority of people who need alcohol treatment receive it. Unhealthy alcohol use is common among people with HIV (PWH) and can lead to negative health outcomes. The aims of this multi-methods study are to (1) quantitatively describe the prevalence, psychosocial characteristics, and demographic traits of a sample of PWH currently receiving HIV care in Florida who had a self-reported need for alcohol treatment but did not seek care and (2) qualitatively explore reasons why PWH did not seek treatment.MethodsPWH enrolled in the Florida Cohort Study between October 2020 and February 2023 who had drinking history (N = 487) completed a cross-sectional survey that asked if there was a time when they recognized they needed help for their drinking but did not seek it. If yes, they were asked an open-ended follow-up question about reasons why they did not seek care. Demographic and behavioral differences between those who did and did not endorse a time when they needed alcohol treatment were determined using multivariable logistic regression, while qualitative data were analyzed with thematic analysis based in the Social-Ecological Model to assess reasons for not seeking care at the individual, social, and systems levels.ResultsA quarter of PWH (n = 129) with lifetime drinking indicated a time they needed care but did not seek it. Patients who endorsed a time where they perceived the need for treatment but did not seek it were more likely to endorse current at-risk drinking and a history of ever trying to reduce their drinking or formally seek professional alcohol treatment. The most common reasons participants did not seek care were individual level factors and included shame, denial, fear, wanting to do it on their own, not feeling ready, and not wanting to seek care.ConclusionsPWH experienced barriers largely at the individual level that prevented them from seeking alcohol treatment despite a recognized need, though many eventually sought care. Providers and public health professionals should consider helping to address various barriers, particularly internal barriers, when designing interventions to help PWH seek care.

Efcab7 deletion sensitizes mice to the teratogenic effects of gastrulation-stage alcohol exposure

Alcohol exposure during the gastrulation stage of development can disrupt Sonic hedgehog (Shh) signaling and cause eye, craniofacial, and brain defects. One of the genes that regulates Shh signaling is Efcab7, which encodes a protein that facilitates the actions of Smoothened (Smo), a critical component of the Shh pathway. Previous work from our lab has demonstrated that Efcab7 is differentially expressed between two sub-strains of C57BL/6 mice that differ in their sensitivity to gastrulation-stage alcohol exposure. The more alcohol-sensitive C57BL/6 J mice express lower levels of Efcab7 during gastrulation than do the less alcohol-sensitive C57BL/6NHsd mice. The current study examined whether partial or full Efcab7 deletions render mice more sensitive to gastrulation-stage alcohol exposure and affect the sensitivity to other modulators of Shh signaling that cause craniofacial malformations. Efcab7+/- dams were mated with Efcab7+/- sires to produce Efcab7+/+, Efcab7+/-, and Efcab7-/- fetuses. On gestational day 7 (GD 7), they received either alcohol (two doses of 2.9 g/kg, i.p., given 4 hours apart), the Smo antagonist vismodegib (40 mg/kg, or vehicle, p.o.), the Smo agonist SAG (20 mg/kg) or the appropriate vehicles. GD 17 fetuses were collected and examined for ocular and craniofacial dysmorphology. As compared to Efcab7+/+ fetuses, Efcab7-/- fetuses exposed to alcohol or vismodegib treatment had more severe ocular and craniofacial malformations. In contrast, Efcab7-/- fetuses had less severe malformations induced by SAG. These results confirm that Efcab7 can modify responses to Shh agonists and antagonists and further identify Efcab7 as a gene important for the sensitivity to gastrulation-stage alcohol exposure.

Alkoxy Exchange Strategy for the Synthesis of N,N'-Dimethylated (Alkoxy)triazinediones as Solid Reagents for Acid-Catalyzed O-Alkylation.

N,N'-Dimethylated (alkoxy)triazinediones (DMATs-R) with eight different O-alkyl groups (R), such as benzyl, allyl, and tert-butyl groups, were synthesized in 61-94% yield through the alkoxy exchange reaction of DMAT-Me with the corresponding alcohol. Molecular sieves were added to the reaction mixture to shift the alkoxy exchange equilibrium toward the product via the absorptive removal of the methanol formed in situ. All the DMATs-R were obtained as stable solids, in contrast to previously reported N,N'-diallyl analogs that included oil compounds. The treatment of alcohols with DMATs-R in the presence of an acid catalyst afforded the corresponding alkyl ethers in up to 92% yield. A base-labile bromoalkyl group is compatible with these reactions. The O-tert-butylation of a sterically hindered tert-alcohol with DMAT-tBu yielded the di-tert-butyl ether product. The DMATs-R are suitable reagents for the O-alkylative protection of alcohols under nonbasic conditions.

Alcohol use disorders among healthcare professionals: a call for action.

Alcohol consumption and harmful and hazardous drinking are significant contributors to the global burden of disease, accounting for about 3 million deaths each year globally. Owing to their stressful work environment, healthcare professionals are at a high risk of experiencing physical and mental health problems, particularly alcohol use disorders. Alcohol use disorder among healthcare professionals is of concern as it is associated with decreased work productivity and performance and associated ill health and cognitive impairment. This review, therefore, aimed to gather evidence on the prevalence and associated factors for alcohol use disorders among healthcare professionals. The findings revealed a high prevalence of alcohol use disorders among healthcare professionals, which were worsened during the COVID-19 pandemic. Additionally, there was a glaring dearth of studies conducted in low- and middle-income countries. Urgent interventions and support systems are therefore needed to address these issues. A comprehensive approach, considering individual and organizational factors, alongside evidence-based interventions, training and support programs, can promote workforce well-being and improve the quality of patient care. It is imperative to integrate alcohol use screening, preventive and treatment interventions with primary healthcare and psychiatry services.This will help ensureearly diagnosis and timelyinitiation of preventive and therapeutic measures, reducing the risk of missed opportunities. Furthermore, offering effective human resource management support services to healthcare professionals would significantly enhance their well-being and help prevent alcohol use disorders.