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BACKGROUND: Polysubstance use is associated with adverse health outcomes, yet little research has measured changes in polysubstance use. We aimed to 1) estimate trends in marijuana and heavy alcohol use by cigarette smoking and demographic subgroups, and 2) examine patient factors associated with concurrent use among adults who were smoking. METHODS: We conducted a repeated cross-sectional analysis of 687,225 non-institutionalized US adults ≥18 years from the 2002-2019 National Survey on Drug Use and Health. Participants were stratified into current, former, and never smoking groups. Main outcomes were prevalence of heavy alcohol use, marijuana use, and concurrent use of both substances. RESULTS: From 2002-2019, heavy alcohol use declined from 7.8 % to 6.4 %, marijuana use rose from 6.0 % to 11.8 %, and concurrent use of alcohol and marijuana remained stable. Among adults who were smoking from 2005 to 2019, higher education was associated with higher odds of heavy alcohol use, while older ages, female gender, non-White race/ethnicity, and government-provided health insurance were associated with lower odds. The odds of marijuana use decreased in females, older ages, and higher incomes while increasing in people with poorer health status, higher education, government-provided or no health insurance, and serious mental illness. Compared to White adults who were smoking, Black counterparts had higher odds of marijuana use (OR=1.23; 95 %CI: 1.15-1.29), while Hispanic (OR=0.68; 95 %CI: 0.63-0.72) and other racial/ethnic identities (OR=0.83; 95 %CI: 0.77-0.90) had lower odds. CONCLUSIONS: Our study suggests marijuana use might not be sensitive to changes in the use of tobacco and alcohol.

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Large library docking can reveal unexpected chemotypes that complement the structures of biological targets. Seeking new agonists for the cannabinoid-1 receptor (CB1R), we docked 74 million tangible molecules, prioritizing 46 high ranking ones for de novo synthesis and testing. Nine were active by radioligand competition, a 20% hit-rate. Structure-based optimization of one of the most potent of these (Ki = 0.7 uM) led to '4042, a 1.9 nM ligand and a full CB1R agonist. A cryo-EM structure of the purified enantiomer of '4042 ('1350) in complex with CB1R-Gi1 confirmed its docked pose. The new agonist was strongly analgesic, with generally a 5-10-fold therapeutic window over sedation and catalepsy and no observable conditioned place preference. These findings suggest that new cannabinoid chemotypes may disentangle characteristic cannabinoid side-effects from their analgesia, supporting the further development of cannabinoids as pain therapeutics.

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The synthetic forms of delta-9-tetrahydrocannabinol (Δ9-THC), dronabinol or nabilone, have been approved to treat several indications. However, due to safety concerns their clinical utility remains limited. Consequently, there is a need for developing cannabinoid (CB) ligands that display better behavioral pharmacological profiles than Δ9-THC. Here, we utilized drug discrimination methods to compare the interoceptive effects of CB ligands that vary in potency, efficacy, and selectivity at the CB receptors, including two ligands, AM411 and AM4089, that show CB1 partial agonist-like actions in vitro. Male rats were trained to discriminate 0.1 mg/kg AM2201 from saline under a fixed-ratio (FR) 10 response schedule of food reinforcement. After establishing AM2201's discriminative-stimulus effects, pretreatment tests with the CB1 antagonist/inverse agonist rimonabant blocked AM2201's effects, whereas the peripherally-restricted antagonist AM6545 had no effect. Next, the generalization profiles of AM411 and AM4089 with CB1 full agonists (JWH-018, CP-55,940, AM8936), partial agonist (Δ9-THC), and non-cannabinoids (fentanyl, atropine) were compared. The CBs either fully (AM2201, CP-55,940, JWH-018, AM8936, Δ9-THC) or partially (AM411, AM4089) substituted for AM2201, whereas fentanyl and atropine did not produce AM2201-like effects. All CB drugs were more potent than Δ9-THC and correlation analysis confirmed that the relative behavioral potencies of CBs corresponded strongly with their relative affinities at the CB1 but not CB2 receptors. Together, our results further demonstrate that AM411 and AM4089 exhibit better pharmacological profiles compared to Δ9-THC, in that they are more potent and display in vivo partial agonist-like actions that are centrally mediated via CB1 receptors.

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OBJECTIVES: To characterize the clinical features, treatment, and outcome of children diagnosed with retinoblastoma (RB) at Vietnam National Cancer Hospital. METHODS: The study enrolled all RB patients newly diagnosed at Vietnam National Cancer Hospital from January 2018 to December 2022. The primary endpoint was overall survival (OS) and the eye salvage rate. RESULTS: In total, 139 patients were enrolled, 51.8% patients were male. Median age was 18.9 months. Most patients presented with leukocoria (63.3%), followed by strabismus (14.4%), and 43.9% had bilateral disease. Of 200 eyes, 129 (64.5%) were classified as group E. Extraocular extension was noted in 10 of 139 patients (7.2%). About one-third of the patients lived more than 300 kilometers (km) away from these hospitals, and 17.3% of the patients belonged to minority groups, both of which were dominated by group E and extraocular or high-risk eyes at the time of consultation. Primary enucleation was done for 57 eyes (28.5%), and 51 of 61 patients (83.6%) received eye salvage therapy in bilateral RB group. At study closure, 127 children were alive at the last follow-up, 12 cases were confirmed dead. The 5-year OS and progression-free survival (PFS) rates were 90.3% and 85.9%, respectively. In particular, ethnic minority, distance to hospital more than 150 km, and extraocular disease were significantly associated with higher mortality among children with RB treated in Vietnam National Cancer Hospital. CONCLUSIONS: There is a need to support for screening RB with early symptoms in grassroots medical facilities and raise awareness among patients' families through health education programs. Besides, caring and supporting treatment for patients from the ethnic minority and who live far from hospitals are also extremely necessary.

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Diabetes mellitus is a chronic metabolic disease relating to steady hyperglycemia resulting from the impairment of the endocrine and non-endocrine systems. Many new drugs having varied targets were discovered to treat this disease, especially type 2 diabetes. Among those, α-glucosidase inhibitors showed their effects by preventing the digestion of carbohydrates through their inhibition against α-amylase and α-glucosidase. Recently, chalcones have attracted considerable attention as they have a simple structure, are easily synthesized as well as have a variety of derivatives. Some reports suggested that chalcone and its derivates could inhibit α-amylase and α-glucosidase. This narrative review provides a comprehensive evaluation of the inhibition of chalcone and its derivatives against α-amylase and α-glucosidase that were reviewed and reported in published scientific articles. Twenty-eight articles were reviewed after screening 207 articles found in four databases, including PubMed, Google Scholar, VHL (Virtual Health Library), and GHL (Global Health Library). This review presented the inhibitory effects of varied chalcones, including chalcones with a basic structural framework, azachalcones, bis-chalcones, chalcone oximes, coumarin-chalcones, cyclohexane chalcones, dihydrochalcones, and flavanone-coupled chalcones. Many of these chalcones had significant inhibition against α-amylase as well as α-glucosidase that were comparable to or even stronger than standard inhibitors. This suggested that such compounds could be potential candidates for the discovery of new anti-diabetic remedies in the years to come.

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The purpose of this review is to summarize the feasibility, acceptability, and efficacy of interventions that utilize mobile health (mHealth) technology to promote health behavior changes or improve healthcare services among the Vietnamese population. Ovid MEDLINE, CINAHL, EMBASE, Scopus, and Web of Science were used to identify studies published from 2011-2022. Studies utilizing mHealth to promote behavior change and/or improve healthcare services among Vietnamese were included. Studies that included Vietnamese people among other Asians but did not analyze the Vietnamese group separately were excluded. Three independent researchers extracted data using Covidence following PRISMA guidelines. Measures of feasibility, acceptability, and efficacy were synthesized. The ROBINS-I and RoB2 tools were used to evaluate methodological quality. Fourteen articles met inclusion criteria and included 5660 participants. Participants rated high satisfaction, usefulness, and efficacy of mHealth interventions. Short message service was most frequently used to provide health education, support smoking cessation, monitor chronic diseases, provide follow-up, and manage vaccination. Measures of feasibility, acceptability, and efficacy varied across studies; overall findings indicated that mHealth is promising for promoting lifestyle behavior change and improving healthcare services. Cost effectiveness and long-term outcomes of mHealth interventions among the Vietnamese population are unknown and merit further research. Recommendations to integrate mHealth interventions are provided to promote the health of Vietnamese people.

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BACKGROUND: Some antihyperglycemic drugs can reduce cardiovascular events, slow the progression of kidney disease, and prevent death, but they are more expensive than older drugs. OBJECTIVES: (1) To estimate trends in use of antihyperglycemic drugs by cost; (2) to examine use of high-cost drugs by race/ethnicity, income, and insurance status DESIGN: Cross-sectional analysis of the 2003-2018 National Health and Nutrition Examination Survey PARTICIPANTS: US adults ≥18 years with type 2 diabetes EXPOSURES: Race/ethnicity, income, and insurance status MAIN MEASURES: Low-cost noninsulin medications included any drugs that had at least one generic version approved by the Food and Drug Administration. Human regular, NPH, and premixed NPH/regular 70/30 insulins were classified as low-cost. All other noninsulin medications and insulins were considered high-cost KEY RESULTS: The sample included 7,394 patients. Prevalence of use of low-cost noninsulin drugs increased from 37% in 2003-2004 to 52% in 2017-2018. Use of high-cost noninsulin drugs decreased from 2003-2004 to 2013-2014 and then slowly increased. Use of low-cost insulin decreased from 7 to 2% while high-cost insulin rose from 4 to 16%. In multivariable analysis, non-White patients had 25-35% lower odds of receiving high-cost drugs than non-Hispanic Whites. Health insurance was associated with more than twice the odds of having high-cost drugs compared to no insurance. Patients with higher HbA1c or moderate obesity were also more likely to use high-cost drugs. Sex, income, and insurance type were not associated with receipt of high-cost drugs. CONCLUSIONS: There was a shift in utilization from high- to low-cost noninsulin drugs, but since 2013-2014 the trend has slowly reversed with increased use of newer, more expensive drug classes. High-cost insulin analogs have almost completely replaced lower cost human insulins. Disparities in receipt of diabetes drugs by race/ethnicity and insurance must be addressed to ensure that cost is not a barrier for disadvantaged populations.

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We report a 51-year-old woman with thyroid eye disease and biopsy-proven pretibial myxedema that was subsequently treated with teprotumumab with improvement.

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Evidence suggests the existence of a functional interaction between endogenous cannabinoid (CB) and opioid systems. Thus, targeting CB1 receptors might be a viable approach to develop new medications for opioid use disorders (OUD). The present studies were undertaken to evaluate the effects of the neutral CB1 antagonist AM4113 and the CB1 antagonist/inverse agonist rimonabant in male rats trained to discriminate 0.032 mg/kg fentanyl from saline under a 10-response fixed-ratio (FR-10) schedule of food reinforcement. Results show that the µ-opioid agonists (fentanyl, oxycodone, and morphine) substituted fully and dose-dependently for fentanyl, whereas pretreatment with the µ-opioid antagonist naltrexone antagonized fentanyl's discriminative-stimulus effects. In interaction studies, AM4113 (0.32 or 1.0 mg/kg) was more effective in blocking fentanyl discrimination at 10-fold lower doses that did not modify rates of food-maintained responding, whereas rimonabant (1.0-10 mg/kg) produced some attenuation of fentanyl's discriminative-stimulus effects at the highest dose tested which also significantly decreased response rates. These results extend our recent work showing that AM4113 can effectively block the behavioral effects of heroin without producing rimonabant-like adverse effects. Taken together, these data suggests that CB1 neutral antagonists effectively block the behavioral effects of structurally distinct morphinan (heroin) and phenylpiperidine-based (fentanyl) opioids and may provide a novel therapeutic option for the treatment of OUD.

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There exists a vast expanse of data in the literature which can be harnessed for accelerated design and discovery of advanced materials for various applications of importance ─ for example, desalination of seawater. Here, we develop a machine learning (ML) model, training it with ∼260 molecular dynamics (MD) computation results, to predict the desalination performance of 2D membranes that exist in the literature. The desalination performance variables of water flux and salt rejection rates are correlated to 49 material features related to the chemistry of the pores and the membranes along with applied pressure, salt concentration, partial charges on the atoms, geometry of the pore, the mechanical properties of the membranes, and the properties of water for the water model used. We used the ML model to screen 3814 structurally optimized 2D materials for maximum water flux and salt rejection rates from the literature. We found some candidates that perform ∼4 times better than the more popularly known 2D materials such as graphene and MoS2. This result is verified using data obtained from MD simulations performed on several representative 2D membranes for different classes. Such validated statistical frameworks using literature data can be very useful in guiding experiments in the field of functional materials for varied applications.

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Oxidative stress, neurodegeneration, neuroinflammation, and vascular leakage are believed to play a key role in the early stage of diabetic retinopathy (ESDR). The aim of this study was to investigate the blockade of cannabinoid receptor 1 (CB1R) and activation of cannabinoid receptor 2 (CB2R) as putative therapeutics for the treatment of the early toxic events in DR. Diabetic rats [streptozotocin (STZ)-induced] were treated topically (20 µL, 10 mg/mL), once daily for fourteen days (early stage DR model), with SR141716 (CB1R antagonist), AM1710 (CB2R agonist), and the dual treatment SR141716/AM1710. Immunohistochemical-histological, ELISA, and Evans-Blue analyses were performed to assess the neuroprotective and vasculoprotective properties of the pharmacological treatments on diabetes-induced retinal toxicity. Activation of CB2R or blockade of CB1R, as well as the dual treatment, attenuated the nitrative stress induced by diabetes. Both single treatments protected neural elements (e.g., RGC axons) and reduced vascular leakage. AM1710 alone reversed all toxic insults. These findings provide new knowledge regarding the differential efficacies of the cannabinoids, when administered topically, in the treatment of ESDR. Cannabinoid neuroprotection of the diabetic retina in ESDR may prove therapeutic in delaying the development of the advanced stage of the disease.

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BACKGROUND: Smoking prevalence rates among people with HIV are nearly 3 times higher than those in the general population. Nevertheless, few smoking cessation trials targeting smokers with HIV have been reported in the literature. Efforts to develop and evaluate sustainable, low-cost, and evidence-based cessation interventions for people with HIV are needed. Given the widespread proliferation of mobile phones, the potential of using mobile health apps to improve the reach and efficacy of cessation interventions is promising, but evidence of efficacy is lacking, particularly among people with HIV. OBJECTIVE: This study will consist of a 2-group randomized controlled trial to evaluate a fully automated smartphone intervention for people with HIV seeking cessation treatment. METHODS: Participants (N=500) will be randomized to receive either standard treatment (ST; 250/500, 50%) or automated treatment (AT; 250/500, 50%). ST participants will be connected to the Florida Quitline and will receive nicotine replacement therapy in the form of transdermal patches and lozenges. This approach, referred to as Ask Advise Connect, was developed by our team and has been implemented in numerous health systems. ST will be compared with AT, a fully automated behavioral treatment approach. AT participants will receive nicotine replacement therapy and an interactive smartphone-based intervention that comprises individually tailored audiovisual and text content. The major goal is to determine whether AT performs better in terms of facilitating long-term smoking abstinence than the more resource-intensive ST approach. Our primary aim is to evaluate the efficacy of AT in facilitating smoking cessation among people with HIV. As a secondary aim, we will explore potential mediators and moderators and conduct economic evaluations to assess the cost and cost-effectiveness of AT compared with ST. RESULTS: The intervention content has been developed and finalized. Recruitment and enrollment will begin in the fall of 2021. CONCLUSIONS: There is a critical need for efficacious, cost-effective, and sustainable cessation treatments for people with HIV who smoke. The AT intervention was designed to help fill this need. If efficacy is established, the AT approach will be readily adoptable by HIV clinics and community-based organizations, and it will offer an efficient way to allocate limited public health resources to tobacco control interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT05014282; https://clinicaltrials.gov/ct2/show/NCT05014282. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/33183.

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INTRODUCTION: Several studies have reported women's worry that sexual intercourse may harm the course of pregnancy. This worry might lead to avoidance of sexual intercourse during pregnancy. AIM: To assess if fears about harming the pregnancy are associated with avoidance of sexual intercourse during pregnancy. METHODS: A cross-sectional study was conducted on 250 Vietnamese pregnant women in the first or second trimester who visited our hospital for antenatal care. We explored 5 types of fears including miscarriage/preterm labor, premature rupture of membranes, bleeding, infection, and injury to the fetus. Fears were measured by modified questions from the Reasons For Not Engaging in Sexual Activity During Pregnancy questionnaire. Using the total fear score, pregnant women were categorized into having low, moderate, and high fear. MAIN OUTCOME MEASURE: Not having sexual intercourse during the past 4 weeks. RESULTS: 72 (28.8%) pregnant women had no sexual intercourse for the past 4 weeks. All types of fear were considered important among pregnant women; the more important fears were infection and injury to the fetus. In multivariable regression analysis, the prevalence of not having sexual intercourse was higher in both women who had moderate (adjusted prevalence ratio = 2.84, 95% CI 1.42-5.67) and high fear (adjusted prevalence ratio = 4.39, 95% CI 2.28-8.44). CONCLUSION: Avoidance of sexual intercourse was common among Vietnamese pregnant women and was associated with the fears about harming the pregnancy. This can be a target in the health education programs for pregnancy couples. Thanh C. Phan, Long B. Hoang, Thanh K. Tran, et al. Fear-Related Reasons for Avoiding Sexual Intercourse in Early Pregnancy: A Cross-Sectional Study. Sex Med 2021;9:100430.

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We developed a method for single-cell resolution longitudinal bioluminescence imaging of PERIOD (PER) protein and TIMELESS (TIM) oscillations in cultured male adult Drosophila brains that captures circadian circuit-wide cycling under simulated day/night cycles. Light input analysis confirms that CRYPTOCHROME (CRY) is the primary circadian photoreceptor and mediates clock disruption by constant light (LL), and that eye light input is redundant to CRY; 3-h light phase delays (Friday) followed by 3-h light phase advances (Monday morning) simulate the common practice of staying up later at night on weekends, sleeping in later on weekend days then returning to standard schedule Monday morning [weekend light shift (WLS)]. PER and TIM oscillations are highly synchronous across all major circadian neuronal subgroups in unshifted light schedules for 11 d. In contrast, WLS significantly dampens PER oscillator synchrony and rhythmicity in most circadian neurons during and after exposure. Lateral ventral neuron (LNv) oscillations are the first to desynchronize in WLS and the last to resynchronize in WLS. Surprisingly, the dorsal neuron group-3 (DN3s) increase their within-group synchrony in response to WLS. In vivo, WLS induces transient defects in sleep stability, learning, and memory that temporally coincide with circuit desynchrony. Our findings suggest that WLS schedules disrupt circuit-wide circadian neuronal oscillator synchrony for much of the week, thus leading to observed behavioral defects in sleep, learning, and memory.

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As a continuation of earlier work on classical cannabinoids bearing bulky side chains we report here the design, synthesis, and biological evaluation of 3'-functionalized oxa-adamantyl cannabinoids as a novel class of cannabinergic ligands. Key synthetic steps involve nucleophilic addition/transannular cyclization of aryllithium to epoxyketone in the presence of cerium chloride and stereoselective construction of the tricyclic cannabinoid nucleus. The synthesis of the oxa-adamantyl cannabinoids is convenient, and amenable to scale up allowing the preparation of these analogs in sufficient quantities for detailed in vitro evaluation. The novel oxa-adamantyl cannabinoids reported here were found to be high affinity ligands for the CB1 and CB2 cannabinoid receptors. In the cyclase assay these compounds were found to behave as potent and efficacious CB1 receptor agonists. Isothiocyanate analog AM10504 is capable of irreversibly labeling both the CB1 and CB2 receptors.

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AIMS: To assess a cost-effective in-house selective plate formula for actively screening carbapenem-resistant Enterobacteriaceae (CRE). METHODOLOGY AND RESULTS: The in-house formula included CHROMagarTM Orientation, meropenem, and ingredients present in the Mac-Conkey formula, such as bile salts and crystal violet (pH 6.9-7.2). American Type Culture Collection strains and 200 clinical strains were used to validate the plate formula. The CRE plates had a sensitivity of 97.4% and a specificity of 98.8% with ATCC andor clinical strains used in the quality control procedure. A point prevalence survey among the 18 inpatients at Viet-Tiep hospital ICU using fecal swabs plated at the in-house agar plate showed a CRE prevalence of 44.4%. CONCLUSION: The in-house plate had high sensitivity and specificity, particularly for Escherichia coli and the KESC group (Klebsiella spp., Enterobacter spp., Serratia marscescens, and Citrobacter spp.), and it may be widely applied as an alternative to other ready-to-use commercial plates. SIGNIFICANCE AND IMPACT OF THE STUDY: The formula developed in the present study may facilitate the early detection and isolation of CRE and decrease transmission, particularly in low- and middle-income countries with a high rate of CRE colonization and limited access to ready-to-use commercial plates.

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A new approach to synthesize cannabilactones using Suzuki cross-coupling reaction followed by one-step demethylation-cyclization is presented. The two key cannabilactone prototypes AM1710 and AM1714 were obtained selectively in high overall yields and in a lesser number of synthetic steps when compared to our earlier synthesis. The new approach expedited the synthesis of cannabilactone analogs with structural modifications at the four potential pharmacophoric regions.

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INTRODUCTION AND AIMS: People who use drugs (PWUD) face several mental health problems. This report aims to examine the prevalence of and factors associated with psychological distress among Cambodian PWUD. DESIGN AND METHODS: Data used in our analysis were from the national survey of 1626 PWUD recruited through respondent-driven sampling method in Cambodia in 2012 to 2013. Distress was measured through self-report by using the 10-item Kessler Psychological Distress Scale (K10). All analyses were weighted. RESULTS: Approximately half of PWUD had mild to severe psychological distress in the past four weeks (K10 ≥ 20). In the adjusted analysis, being female (odds ratio 1.60; 95% confidence interval 1.22, 2.12) and having experienced living in rehabilitation centres (odds ratio 2.46; 95% confidence interval 1.56, 3.87) were associated with a higher risk of having moderate or severe psychological distress (K10 ≥ 25). DISCUSSION AND CONCLUSIONS: Psychological distress was prevalent among Cambodian PWUD. PWUD who were female or experienced living in rehabilitation centres were more likely to report distress. Policy makers should consider shifting further from compulsory institutionalised treatment model to community-based treatment program. Mental health assessment and mental health care services should be included in drug treatment programs and should be gender-sensitive. Further research investigating other mental disorders among PWUD are also needed.

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