Improvements of facial profile and smile aesthetic using temporary anchorage devices and botulinum toxin: a case report.

The severe gummy smile and a skeletal class II profile pose challenges in treatment. This case report outlines an effective alternative for addressing these problems in a patient with skeletal class II division 2, class II molar relationship, retroclination of upper incisors, and lip protrusion. Treatment objectives included normalizing the overjet and overbite, improving the gummy smile, and establishing a satisfactory occlusion. A three-dimensional simulation was performed to consult with the patient, assess possible results, and predict treatment biomechanics. The treatment involved the use of two zygomatic and one inter-radicular temporary anchorage devices, along with botulinum toxin. After the 2-year follow-up, a satisfactory dental occlusion, aesthetic improvement, and adequate function were achieved. This approach offers a viable alternative to orthognathic surgery for adults with skeletal class II malocclusion and a severe gummy smile due to hypermobile lip.

Single-step hydrothermal synthesis of zinc oxide nanorods for potential use as nano-antibiotics without seeding or bases.

The alarming global rise in antibiotic resistance, driven by the widespread overuse of traditional antibiotics, has created an urgent demand for new antimicrobial solutions. This study presents zinc oxide (ZnO) nanorods as a potential nano-antibiotic agent. ZnO nanorods, with a 2:3 aspect ratio, were synthesized using an efficient one-step hydrothermal method at a low temperature of 100°C, reducing the synthesis time to just 5 hours. The synthesized ZnO nanorods' morphology, structure, and composition were characterized using scanning electron microscopy, x-ray diffraction, and energy dispersive x-ray spectroscopy. The potent antimicrobial activity of these nanorods against common bacterial strains such as Escherichia coli, Bacillus subtilis, and Vibrio parahaemolyticus was examined through optical density at 600 nm (OD600) measurements and inhibition zone analysis, demonstrating substantial inhibition of bacterial growth. In particular, at a concentration of 5 mg/mL, ZnO nanorods achieved a 96% reduction of B. subtilis bacteria in OD600 and an impressive 99.87% reduction in culturing assays within one day, showcasing bactericidal efficiency on par with tetracycline at 0.003 mg/mL. Furthermore, a predictive model of bacterial growth was developed and validated, providing insights into the time-dependent bactericidal efficiency of the synthesized nanorods. These results highlight the potential of ZnO-based composites as a promising solution to combat antibiotic resistance, paving the way for next-generation antimicrobial materials.

Non-Pharmacological Management of Gestational Diabetes Mellitus with a High Fasting Glycemic Parameter: A Hospital-Based Study in Vietnam.

Background/Objectives: The prevalence of gestational diabetes mellitus (GDM) is increasing at an alarming rate worldwide. Delayed management can lead to adverse composite outcomes for both mother and her offspring. To our knowledge, the clinical association between glycemic parameters and the results of the non-pharmacological GDM approach remains limited; thus, this study aimed to address this important clinical issue in the literature. Methods: This was a retrospective cross-sectional study of 174 Vietnamese pregnant women with the positive oral glucose tolerance test (OGTT) for a high fasting glycemic parameter at Hung Vuong Hospital from 04/2022 to 07/2022. This study aimed to evaluate the success rate of GDM with an elevated index of fasting glycemic concentration which was managed after 2 weeks of a dietary regimen combined with adequate physical activities and to reveal its related factors. Results: Out of 174 singleton pregnancies that met the inclusion criteria, 103 GDM pregnant women were successfully managed after 2 weeks of monitoring (59.2%; 95% confidence intervals (CI): 51.9-66.5). The study revealed a fair correlation between the corresponding test of blood glucose at OGTT and after 2 weeks of GDM management (r = 0.270-0.290, p < 0.0001). The GDM pregnant women with an elevated fasting glycemic parameter and with any of elevated 1 h or 2 h blood glucose levels and in cases of three elevated glycemic parameters (fasting, 1 h, and 2 h blood glucose at the initial results of OGTT) reduced the success rate of glycemic control to 56.5%, 49.2%, respectively, compared to the group with solely a high fasting index of blood glucose (69.6%). The pregnant women who participated in high-intensity sports activities related to a two-fold increase in success rate compared with the group engaging in light and moderate-intensity physical activity. Conclusions: The success rate of glycemic control in GDM women was highest in the group with solitary fasting hyperglycemia and lower in the contributory groups with two and three high parameters. The application of diet therapy plus physical activities among GDM pregnant women is potentially necessary to improve the effectiveness of treatment, minimize adverse pregnancy outcomes, and reduce substantially the hospitalization rate.

Diet rich in soluble dietary fibres increases excretion of perfluorooctane sulfonic acid (PFOS) in male Sprague-Dawley rats.

Perfluorooctane sulfonic acid (PFOS) belongs to a large group of anthropogenic compounds with high persistency named per- and polyfluorinated substances (PFAS). Widespread use from industry to household appliances and food-contact materials contributes to PFAS exposure with food as the primary source. Association studies suggest that vegetables and fibre rich diet may reduce PFOS levels in humans, but experimental data remain limited. Here, we investigated PFOS uptake and wash-out after seven days of PFOS (3 mg/kg/day) in two groups of rats (N = 12 per group) fed diets either high (HF) or low (LF) in soluble dietary fibres. Two control groups (N = 12/group) were fed the same diets without PFOS. Changes in pH and transit time were monitored alongside intestinal and faecal microbiota composition. We quantified systemic and excreted, linear and branched PFOS. Results revealed significantly lower pH and faster intestinal transit in the HF groups. Importantly, HF rats had lower serum PFOS concentrations and higher PFOS concentrations in caecal content and faeces, indicating a more efficient excretion on the fibre rich diet. In both dietary groups, PFOS affected the gut microbiota composition. Our results suggest that a diet rich in soluble dietary fibres accelerates excretion of PFOS and lowers PFOS concentration in serum.

Mineralized Biopolymers-Based Scaffold Encapsulating with Dual Drugs for Alveolar Ridge Preservation.

Mineralization of scaffolds is essential for alveolar ridge preservation and bone tissue engineering, enhancing the mechanical strength and bioactivity of scaffolds, and promoting better integration with natural bone tissue. While the in situ mineralization method using concentrated SBF solutions is promising, there is limited comprehensive research on its effects. In this study, it is demonstrate that soaking gelatin/alginate scaffolds (GAS) in fivefold concentrated SBF significantly reduces the mineralization time to 3-7 days but also leads to considerable degradation and loss of the scaffold's original microstructure. The ratio of gelatin to alginate is optimized to improve the properties of GAS. The optimized GAS sample, when soaked in concentrated SBF to form GAS/HAp, exhibited hydroxyapatite (HAp) crystal formation starting from day 3, with mature hexagonal crystals forming by day 7. However, this process also caused significant decomposition and deformation of the scaffold's pore structure. Additionally, the biocompatibility of GAS and GAS/HAp is evaluated through in vitro, in ovo, haemolysis, and anti-ROS assays. The findings highlight the impact of SBF5× on the mineralization of GAS, laying the groundwork for further research in alveolar ridge preservation and bone tissue engineering.

Clustering for mitigating subject variability in driving fatigue classification using electroencephalography source-space functional connectivity features.

Objective.While Electroencephalography (EEG)-based driver fatigue state classification models have demonstrated effectiveness, their real-world application remains uncertain. The substantial variability in EEG signals among individuals poses a challenge in developing a universal model, often necessitating retraining with the introduction of new subjects. However, obtaining sufficient data for retraining, especially fatigue data for new subjects, is impractical in real-world settings.Approach.In response to these challenges, this paper introduces a hybrid solution for fatigue detection that combines clustering with classification. Unsupervised clustering groups subjects based on their EEG functional connectivity (FC) in an alert state, and classification models are subsequently applied to each cluster for predicting alert and fatigue states.Main results. Results indicate that classification on clusters achieves higher accuracy than scenarios without clustering, suggesting successful grouping of subjects with similar FC characteristics through clustering, thereby enhancing the classification process.Significance.Furthermore, the proposed hybrid method ensures a practical and realistic retraining process, improving the adaptability and effectiveness of the fatigue detection system in real-world applications.

A decrease in serum dihydrotestosterone levels in 9-year-old Vietnamese children from a dioxin exposure area.

BACKGROUND: Dioxin is an environmental pollutant as well as an endocrine disruptor in humans. Our longitudinal study wants to clarify the relationship between dioxin exposure and endocrine disorders in children living in the Vietnamese dioxin hotspot. METHOD: Seventeen congeners of polychlorinated dibenzo-p-dioxins/polychlorinated dibenzo-furans (PCDDs/PCDFs) in maternal breast milk and seven serum steroid hormones in children of 43 and 46 mothers and their 9-year-old children from the non-exposure and the hotspot areas were measured, respectively. The steroid metabolic enzyme ratios were calculated based on the hormone level ratio. RESULTS: Most dioxin/furan congeners and toxic equivalents (TEQs) levels were significantly higher in the hotspot than in the non-exposure area, except for 2,4,7,8-TeCDF. The height and weight of girls from the hotspot area were substantially lower and inversely correlated with dioxin congener levels/total TEQs level dioxin. The dihydrotestosterone (DHT) levels in the hotspot were markedly lower than those in non-exposed in both genders. The cortisol concentrations were significantly higher in the hotspot than those from the non-exposure area only in the girls. The DHT/testosterone ratios that exhibited the 5α- or 5ß-reductase activity declined by 50% in the hotspot area for both genders. The DHT levels showed strong inverse correlations with almost the PCDDs/PCDFs congeners and total TEQs dioxin in breast milk. CONCLUSIONS: This finding suggests that dioxin exposure in maternal breast milk might impact children's endocrine system until 9 years old, especially on the DHT biosynthesis.

Translation and validation of the CLEO tool in Vietnamese to assess the significance of pharmacist interventions.

BACKGROUND: There is currently no validated tool available for assessing the potential significance of pharmacist interventions in Vietnam. AIM: This study aimed to translate the CLEO tool from French into Vietnamese, validate the Vietnamese version, and demonstrate its feasibility in daily practice. METHOD: The CLEO tool was translated into Vietnamese (CLEOVN) using a 5-step process by bilingual experts. A total of 100 scenarios were compiled from clinical cases from nine hospitals evaluated by seven clinical pharmacists to determine inter-rater reliability and 30 out of 100 scenarios were re-evaluated one month later to determine test-retest reliability. Reliability was quantified using the intra-class correlation coefficient (ICC). A 20-item questionnaire on a 7-point Likert scale assessed the tool's appropriateness, acceptability, precision, and feasibility. RESULTS: Inter-rater reliability was good for clinical dimension (ICCA,1 = 0.71), excellent for economic dimension (ICCA,1 = 0.86), and fair for organizational/operational dimension (ICCA,1 = 0.56). Test-retest reliability scores were excellent for clinical (I̅C̅C̅A,1 = 0.79), excellent for economic (I̅C̅C̅A,1 = 0.84), and fair for organizational/operational (I̅C̅C̅A,1 = 0.56). The tool was rated as appropriate (mean = 5.86; SD = 1.03), acceptable (mean = 5.19; SD = 1.12), precise (mean = 5.71; SD = 1.17), and feasible (mean = 5.05; SD = 1.24). The maximum time required to evaluate an intervention was three minutes. CONCLUSION: The CLEOVN tool was successfully translated and validated for reliability, appropriateness, acceptability, precision, and feasibility. It will be suitable to evaluate the value of clinical pharmacy interventions.

Sol-moiety: Discovery of a water-soluble prodrug technology for enhanced oral bioavailability of insoluble therapeutics.

Though conceptually attractive, the use of water-soluble prodrug technology to enhance oral bioavailability of highly insoluble small molecule therapeutics has not been widely adopted. In large part, this is due to the rapid enzymatic or chemical hydrolysis of prodrugs within the gastrointestinal tract, resulting in drug precipitation and no overall improvement in oral bioavailability relative to standard formulation strategies. We reasoned that an optimal water-soluble prodrug could be attained if the rate of prodrug hydrolysis were reduced to favor drug absorption rather than drug precipitation. In doing so, the rate of hydrolysis provides a pharmacokinetic control point for drug delivery. Herein, we report the discovery of a water-soluble promoiety (Sol-moiety) technology to optimize the oral bioavailability of highly insoluble small molecule therapeutics, possessing various functional groups, without the need for sophisticated, often toxic, lipid or organic solvent-based formulations. The power of the technology is demonstrated with marked pharmacokinetic improvement of the commercial drugs enzalutamide, vemurafenib, and paclitaxel. This led to a successful efficacy study of a water-soluble orally administered prodrug of paclitaxel in a mouse pancreatic tumor model.

Handoffs and Equity: Impact of a Patient Distribution Model on Handoffs for Black Patients.

BACKGROUND: Hospital medicine patient distribution models (PDM) assign patients to inpatient services on hospital admission. Models balance tradeoffs including patient handoffs, physician wellness, subspecialty care, and other factors to ensure optimal outcomes; however, equity is rarely considered. Handoffs during inpatient care can result in medical error and worse patient outcomes. This study evaluates the impact of a PDM that prioritizes use of specialty care services and an overflow service (OS) during high census on racial inequities in handoff frequency. METHODS: A single-center retrospective cohort study of inpatient encounters on hospital medicine services from July 2017 to December 2019 was conducted. The primary exposures included being discharged by a general medicine service (GMS) or cared for by an OS. The primary outcome was handoffs per day of stay, analyzed by multivariable regression adjusted for age, gender, race, ethnicity, insurance, discharge from GMS, and care from OS. RESULTS: A total of 4165 inpatient hospitalizations with the majority of their stay on a hospital medicine service were reviewed. Patients discharged by GMS (78.2% vs. 58.1%, p < .001) and cared for by OS (78.7% vs. 67.0%, p < .001) were more likely to identify as Black. Multivariable analysis showed a handoff risk ratio of 1.53 (p < .001) for OS patients and 1.06 (p = .01) if discharged from GMS, but race alone did not significantly affect risk of handoffs. CONCLUSION: The PDM prioritization drove increased handoffs disproportionately for Black patients. Multivariable analysis showed that race alone did not contribute to increased handoffs suggesting the creation of a systemic bias in patient care.

Neuropeptides regulate embryonic salivary gland branching through the FGF/FGFR pathway in aging klotho-deficient mice.

Salivary gland branching morphogenesis is regulated by the functional integration of neuronal signaling, but the underlying mechanisms are not fully understood in aging accelerated klotho-deficient (Kl-/-) mice. Here, we investigated whether the neuropeptides substance P (SP) and neuropeptide Y (NPY) affect the branching morphogenesis of embryonic salivary glands in aging Kl-/- mice. In the salivary glands of embryonic Kl-/- mice, morphological analysis and immunostaining revealed that epithelial bud formation, neuronal cell proliferation/differentiation, and the expression of the salivary gland functional marker ZO-1 were decreased in embryonic ductal cells. Incubation with SP/NPY at E12-E13d promoted branching morphogenesis, parasympathetic innervation, and epithelial proliferation in salivary glands of embryonic Kl-/- mice. The ERK inhibitor U0126 specifically inhibited neuronal substance-induced epithelial bud formation in the embryonic salivary gland. RNA-seq profiling analysis revealed that the expression of fibroblast growth factors/fibroblast growth factors (FGFs/FGFRs) and their receptors was significantly regulated by SP/NPY treatment in the embryonic salivary gland (E15). The FGFR inhibitor BGJ389 inhibited new branching formation induced by SP and NPY treatment and ERK1/2 expression. These results showed that aging may affect virtually the development of salivary gland by neuronal dysfunction. The neuropeptides SP/NPY induced embryonic salivary gland development through FGF/FGFR/ERK1/2-mediated signaling.

Predictability of Neutrophile to Lymphocyte Ratio and Platelet to Lymphocyte Ratio on the Effectiveness of Immune Checkpoint Inhibitors in Non-small Cell Lung Cancer patients: A Meta-Analysis.

OBJECTIVES: The associations between the neutrophil-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) with the responses of non-small cell lung cancer (NSCLC) patients receiving immune checkpoint inhibitors (ICI) and the NLR/PLR predictive potential were evaluated via meta-analysis. METHODS: A systematic review was conducted using the PubMed, Embase, and The Cochrane Library databases until October 2021. The relationship between NLR/PLR and overall survival (OS) and progression-free survival (PFS) was evaluated using pooled hazard ratios (HR). The relationship between NLR/PLR and overall response rate (ORR) and disease control rate (DCR) was assessed via pooled odds ratios (OR). Heterogeneity between studies, publication bias, subgroup and sensitivity analyses, trim and fill meta-analysis, and the contour-enhanced funnel plot were performed using the R software. RESULTS: A total of 44 (out of 875) studies met the eligibility criteria, providing a sample size of 4597 patients. Patients with a high NLR were statistically significantly associated with worse outcomes, including OS (pooled HR = 2.44; P < 0.001), PFS (pooled HR = 2.06; P < 0.001), DCR (pooled OR = 0.71; P < 0.001), and ORR (pooled OR = 0.33; P < 0.001). Similarly, a high PLR was associated with poorer outcomes in response to ICI drugs, including OS (pooled HR = 2.13; P < 0.001) and PFS (pooled HR = 1.61; P < 0.001). CONCLUSION: High NLR and PLR were associated with a statistically significant reduction in the efficacy of ICI drugs in NSCLC patients. Thereby, it is possible to use NLR and PLR as potential and available biomarkers in the clinical practice to predict the outcome of ICI treatment in NSCLC patients.

Distinct transcriptional profiles in rat thyroid glands after developmental exposure to three in vitro thyroperoxidase inhibiting chemicals.

Thyroperoxidase (TPO) is central in thyroid hormone (TH) synthesis and inhibition can lead to TH deficiency. Many chemicals can inhibit TPO activity in vitro, but how this may manifest in the developing thyroid gland at the molecular level is unclear. Here, we characterized the thyroid gland transcriptome of male rats developmentally exposed to the in vitro TPO-inhibitors amitrole, 2-mercaptobenzimidazole (MBI), or cyanamide by use of Bulk-RNA-Barcoding (BRB) and sequencing. Amitrole exposure caused TH deficiency and 149 differentially expressed genes in the thyroid gland. The effects indicated an activated and growing thyroid gland. MBI caused intermittent changes to serum TH concentrations in a previous study and this was accompanied by 60 differentially expressed genes in the present study. More than half of these were also affected by amitrole, indicating that they could be early effect biomarkers of developmental TH system disruption due to TPO inhibition. Further work to validate the signature is needed, including assessment of substance independency and applicability domain.

Development of oral pH-sensitive redox nanotherapeutics for gastric ulcer therapy.

Gastric ulcer is a common gastrointestinal disorder worldwide. Although its pathogenesis is unclear, the overproduction of reactive oxygen species (ROS), which results in an oxidative imbalance, has been reported as a central driving mechanism. Within the scope of this investigation, we developed two different self-assembling redox nanoparticles (RNPs) with ROS-scavenging features for the oral treatment of gastric ulcers. One of them, referred to as RNPN, disintegrates in response to acidic pH, whereas the other, denoted as RNPO, remains intact regardless of pH variations. Both types of RNPs showed different free radical scavenging activities in vitro. Protonation of the amino linkages in the side chains of RNPN caused the micelle structure to collapse and the nitroxide radicals encapsulated in the core were exposed to the outside, resulting in a significant increase in antioxidant capacity as the pH decreases. In contrast, RNPO maintained its spherical structure and consistent antioxidant reactivity irrespective of pH changes. The in vivo gastric retention of orally administered RNPN was significantly improved compared to that of RNPO which might be explained by the increased exposure of cationic protonating segments in RNPN on the negatively charged gastric mucosal surface. Owing to its improved gastric retention and enhanced ROS scavenging capacity under acidic pH conditions, RNPN exhibited superior protective effects against oxidative stress induced by aspirin in a gastric ulcer mouse model compared to RNPO. In addition, neither RNPN nor RNPO resulted in severe lethal effects or significant changes in the morphology of zebrafish embryos, indicating their biosafety. Our results suggest that the oral administration of RNPs has a high therapeutic potential for gastric ulcer treatment.

Left ventricular thrombus in patient with nonischemic cardiomyopathy: A case report.

Left ventricular thrombus (LVT) is a severe consequence that typically follows acute myocardial infarction (MI) and can occur in nonischemic cardiomyopathies. In patients who have experienced an ST-segment elevation acute myocardial infarction (STEMI), LVT is seen up to 15% of the time; for patients without an ischemic cardiomyopathy, it is only 2% to 36% of the time. According to Virchow's triad, the cornerstone of LVT formation includes endothelial injury, blood stasis, and hypercoagulability. However, LVT increases morbidity and mortality in patients with both ischemic and nonischemic cardiomyopathies by increasing the risk of stroke or systemic embolism. Studies on nonischemic etiology are limited, and the majority of LVT case series concentrate on ischemic cardiomyopathies. We present this case with the nonischemic cardiomyopathies caused by LVT. Specifically, the patient underwent coronary artery assessment using photon-counting computed tomography, which is among the most advanced systems worldwide.

Chemical Compositions, Molecular Docking, Anti-Inflammatory, and Anti-Cancer Effects of the Leaf Essential Oils Isolated from Three Species of the Rutaceae Family in Vietnam.

Three species of the Rutaceae family, including Acronychia pedunculata, Euodia lepta, and Severinia monophylla have been used in traditional medicine. However, the comparison of the chemical composition, anti-cancer, and anti-inflammatory effects of the leaf essential oils of these species have not been investigated yet. A total of 38 compounds were identified via gas chromatography-mass spectrometry, comprising 96.5-99.8 % of the total composition. Both A. pedunculata and E. lepta essential oils exhibited strong inhibitory effects against cancer cells (IC50: 59.04-97.52 µg/mL) while that of S. monophylla showed a lower anti-cancer effect (IC50>100 µg/mL). Among three essential oils, only the E. lepta leaf oil demonstrated a high anti-inflammatory effect on LPS-stimulated macrophages (IC50=6.47±0.65 µg/mL), while the others showed a moderate anti-inflammatory effect (IC50>50 µg/mL). Molecular docking studies also suggested the binding potential of the key compounds from three essential oils against inducible nitric oxide synthase and cyclooxygenase-2, two proteins associated with inflammatory response, with the negative energies ranging from -41.0 to -71.9 kcal/mol. The present findings suggest the leaf essential oils from these species as potential medicines for treatment of cancer or inflammation associated diseases, especially the ones from A. pedunculata and E. lepta oils.

Heterozygosity for neurodevelopmental disorder-associated TRIO variants yields distinct deficits in behavior, neuronal development, and synaptic transmission in mice.

Genetic variants in TRIO are associated with neurodevelopmental disorders (NDDs) including schizophrenia (SCZ), autism spectrum disorder (ASD) and intellectual disability. TRIO uses its two guanine nucleotide exchange factor (GEF) domains to activate GTPases (GEF1: Rac1 and RhoG; GEF2: RhoA) that control neuronal development and connectivity. It remains unclear how discrete TRIO variants differentially impact these neurodevelopmental events. Here, we investigate how heterozygosity for NDD-associated Trio variants - +/K1431M (ASD), +/K1918X (SCZ), and +/M2145T (bipolar disorder, BPD) - impact mouse behavior, brain development, and synapse structure and function. Heterozygosity for different Trio variants impacts motor, social, and cognitive behaviors in distinct ways that align with clinical phenotypes in humans. Trio variants differentially impact head and brain size with corresponding changes in dendritic arbors of motor cortex layer 5 pyramidal neurons (M1 L5 PNs). Although neuronal structure was only modestly altered in the Trio variant heterozygotes, we observe significant changes in synaptic function and plasticity. We also identified distinct changes in glutamate synaptic release in +/K1431M and +/M2145T cortico-cortical synapses. The TRIO K1431M GEF1 domain has impaired ability to promote GTP exchange on Rac1, but +/K1431M mice exhibit increased Rac1 activity, associated with increased levels of the Rac1 GEF Tiam1. Acute Rac1 inhibition with NSC23766 rescued glutamate release deficits in +/K1431M variant cortex. Our work reveals that discrete NDD-associated Trio variants yield overlapping but distinct phenotypes in mice, demonstrates an essential role for Trio in presynaptic glutamate release, and underscores the importance of studying the impact of variant heterozygosity in vivo.

A Brief Alcohol Intervention (BAI) to reduce alcohol use and improve PrEP outcomes among men who have sex with men in Vietnam: study protocol for a randomized controlled trial.

BACKGROUND: In Vietnam and other global settings, men who have sex with men (MSM) have become the population at greatest risk of HIV infection. Although HIV pre-exposure prophylaxis (PrEP) has been implemented as a prevention strategy, PrEP outcomes may be affected by low persistence and adherence among MSM with unhealthy alcohol use. MSM have a high prevalence of unhealthy alcohol use in Vietnam, which may affect PrEP outcomes. METHODS: Design: We will conduct a two-arm hybrid type 1 effectiveness-implementation randomized controlled trial of a brief alcohol intervention (BAI) compared to the standard of care (SOC) at the Sexual Health Promotion (SHP) clinic Hanoi, Vietnam. PARTICIPANTS: Sexually active MSM (n=564) who are newly initiating PrEP or re-initiating PrEP and have unhealthy alcohol use will be recruited and randomized 1:1 to the SOC or BAI arm. A subgroup of participants (n=20) in each arm will be selected for longitudinal qualitative interviews; an additional subset (n=48) in the BAI arm will complete brief quantitative and qualitative interviews after completion of the BAI to assess the acceptability of the intervention. Additional implementation outcomes will be assessed through interviews with clinic staff and stakeholders (n=35). INTERVENTION: Study participants in both arms will receive standard care for PrEP clients. In the BAI arm, each participant will receive two face-to-face intervention sessions and two brief booster phone sessions, based on cognitive behavioral therapy and delivered in motivational interviewing informed style, to address their unhealthy alcohol use. OUTCOMES: Effectiveness (PrEP and alcohol use) and cost-effectiveness outcomes will be compared between the two arms. Intervention implementation outcomes (acceptability, feasibility, adoption) will be assessed among MSM participants, clinic staff, and stakeholders. DISCUSSION: This proposed trial will assess an alcohol intervention for MSM with unhealthy alcohol use who initiate or re-initiate PrEP, while simultaneously preparing for subsequent implementation. The study will measure the effectiveness of the BAI for increasing PrEP persistence through reducing unhealthy alcohol use in a setting where excessive alcohol consumption is a normative behavior. If effective, implementation-focused results will inform future scale-up of the BAI in similar settings. TRIAL REGISTRATION: NCT06094634 on clinicaltrials.gov. Registered 16 October 2023.