Perceived Benefits and Barriers to Implementing Occupational Health Recommendations Among Immigrant-Owned Nail Salons in the Greater Philadelphia Region.

Introduction. Immigrant nail salon owners and employees face multiple barriers to accessing occupational health training and services. We formed an academic-community-based organization-business owner partnership-unique in that all partners were culturally congruent-to develop a pilot intervention program for the nail salon community. Methods. Eighteen individuals (nine salon owners and nine employees) from the Greater Philadelphia region received the training in their native language and provided feedback through in-depth qualitative interviews. Interview guide was developed using the Consolidated Framework for Implementation Research (CFIR). Themes of perceived benefits and barriers were identified and aligned with relevant CFIR constructs to gain better understanding of the implementation challenges. Results. Reported benefits of program were improved knowledge of the workplace hazards and safety practices, and the potential to attract more customers and retain employees. Perceived barriers to implementing recommended practices were limited availability of safer products and high cost, challenges communicating with customers, lack of engagement from some owners, organizational management practices affecting employees' motivation, and limited partnership with local government to assist small immigrant-owned businesses. Conclusions. Our study revealed multiple factors that pit long-term health protection of nail salon workers against the economic viability of the businesses that employ them. Our research highlights the need to (1) advocate for federal policies making safer products to be more accessible to the masses, (2) establish local policy and culturally appropriate technical support programs that engage community-based organizations, and (3) develop economic opportunities and mentorship for immigrant entrepreneurs to operate profitable healthy salons.

A participatory approach to designing and implementing an occupational health intervention for the nail salon community in the Greater Philadelphia region.

BACKGROUND: The nail salon industry in the US comprises mostly immigrant-owned, small mom-and-pop salons that employ primarily first-generation immigrant workers from Asia. Because of the cultural and language barriers, both owners and workers may not avail themselves of the occupational safety resources. We formed an academic-community partnership to co-design a feasibility study and multi-level occupational health intervention for Vietnamese-speaking salon owners, workers, and community-based organization. METHODS: The intervention for each salon included (i) 2-h in-person training covering chemical safety, infection control, musculoskeletal prevention, and workers' rights for both the owners and their employees, (ii) a tailored recommendation report for the owner, and (iii) check-ins with the owner during the 3-month follow-up. Community partner was trained to deliver the in-language training with technical assistance from the research team. Baseline and post-intervention individual data about health symptoms and behaviors, as well as personal chemical exposures were collected and analyzed. RESULTS: A total of 44 participants from 12 consented salons enrolled in the study. One salon dropped out at follow-up due to change of ownership. Analysis of the differences between post-and pre-intervention showed a tendency toward reduction in some self-reported symptoms in the respiratory system, skin, and eyes, neurotoxicity score, as well as chemical exposures. We could not rule out seasonality as an explanation for these trends. Increase in self-efficacy in some areas was observed post-intervention. CONCLUSIONS: Our study demonstrated a successful academic-community partnership to engage community members in the intervention study. While the intervention effects from this feasibility study should be interpreted with caution, our preliminary results indicated that our community-based intervention is a promising approach to reduce work-related exposures among Asian American nail salon workers.

Automatic Acne Object Detection and Acne Severity Grading Using Smartphone Images and Artificial Intelligence.

Skin image analysis using artificial intelligence (AI) has recently attracted significant research interest, particularly for analyzing skin images captured by mobile devices. Acne is one of the most common skin conditions with profound effects in severe cases. In this study, we developed an AI system called AcneDet for automatic acne object detection and acne severity grading using facial images captured by smartphones. AcneDet includes two models for two tasks: (1) a Faster R-CNN-based deep learning model for the detection of acne lesion objects of four types, including blackheads/whiteheads, papules/pustules, nodules/cysts, and acne scars; and (2) a LightGBM machine learning model for grading acne severity using the Investigator's Global Assessment (IGA) scale. The output of the Faster R-CNN model, i.e., the counts of each acne type, were used as input for the LightGBM model for acne severity grading. A dataset consisting of 1572 labeled facial images captured by both iOS and Android smartphones was used for training. The results show that the Faster R-CNN model achieves a mAP of 0.54 for acne object detection. The mean accuracy of acne severity grading by the LightGBM model is 0.85. With this study, we hope to contribute to the development of artificial intelligent systems to help acne patients better understand their conditions and support doctors in acne diagnosis.

Severe loss of adipose tissue in a Vietnamese lipodystrophy patient caused by LMNA p.G465D mutation: a first clinical characterization and two-year follow-up.

OBJECTIVES: Familial partial lipodystrophy type 2 is the most well-known subtype of lipodystrophy. We describe for the first time the phenotype of a case with lipodystrophy, who carried heterozygous mutation c.G1394A (p.G465D) in the LMNA gene. CASE PRESENTATION: A 17-year-old girl was diagnosed with FPLD2 due to severe loss of subcutaneous fat in the extremities, buttocks and metabolic complications. However, there was no accumulation of fat over her face and neck, which is remarkably different from the FPLD2 clinical phenotypes. Two years of surveillance showed the challenge due to unable control of insulin resistance, glucose and lipid metabolism. Whole exome sequencing revealed the heterozygous mutation c.1394G>A at exon 11 of LMNA gene (p.G465D). CONCLUSIONS: Our case displayed an atypical phenotype of FPLD2 with metabolic anomalies, not cardiovascular diseases. The difficulties of medical management in this case pointed out the urgent need for more effective treatment for individuals suffering from this rare disease.

Population Structure, Genetic Connectivity, and Signatures of Local Adaptation of the Giant Black Tiger Shrimp (Penaeus monodon) throughout the Indo-Pacific Region.

The giant black tiger shrimp (Penaeus monodon) is native to the Indo-Pacific and is the second most farmed penaeid shrimp species globally. Understanding genetic structure, connectivity, and local adaptation among Indo-Pacific black tiger shrimp populations is important for informing sustainable fisheries management and aquaculture breeding programs. Population genetic and outlier detection analyses were undertaken using 10,593 genome-wide single nucleotide polymorphisms (SNPs) from 16 geographically disparate Indo-Pacific P. monodon populations. Levels of genetic diversity were highest for Southeast Asian populations and were lowest for Western Indian Ocean (WIO) populations. Both neutral (n = 9,930) and outlier (n = 663) loci datasets revealed a pattern of strong genetic structure of P. monodon corresponding with broad geographical regions and clear genetic breaks among samples within regions. Neutral loci revealed seven genetic clusters and the separation of Fiji and WIO clusters from all other clusters, whereas outlier loci revealed six genetic clusters and high genetic differentiation among populations. The neutral loci dataset estimated five migration events that indicated migration to Southeast Asia from the WIO, with partial connectivity to populations in both oceans. We also identified 26 putatively adaptive SNPs that exhibited significant Pearson correlation (P < 0.05) between minor allele frequency and maximum or minimum sea surface temperature. Matched transcriptome contig annotations suggest putatively adaptive SNPs involvement in cellular and metabolic processes, pigmentation, immune response, and currently unknown functions. This study provides novel genome-level insights that have direct implications for P. monodon aquaculture and fishery management practices.

Resistance mechanisms and genetic relatedness among carbapenem-resistant Pseudomonas aeruginosa isolates from three major hospitals in Hanoi, Vietnam (2011-15).

BACKGROUND: MDR bacteria including carbapenem-resistant Pseudomonas aeruginosa are recognized as an important cause of hospital-acquired infections worldwide. This investigation seeks to determine the molecular characterization and antibiotic resistance genes associated with carbapenem-resistant P. aeruginosa. METHODS: We conducted WGS and phylogenetic analysis of 72 carbapenem-resistant P. aeruginosa isolated from hospital-acquired infection patients from August 2011 to March 2015 in three major hospitals in Hanoi, Vietnam. RESULTS: We identified three variants of IMP gene, among which bla IMP-15 was the most frequent (n = 34) in comparison to bla IMP-26 (n = 2) and bla IMP-51 (n = 12). We observed two isolates with imipenem MIC >128 mg/L that co-harboured bla IMP-15 and bla DIM-1 genes and seven isolates (imipenem MIC > 128 mg/L) with a bla KPC-1 gene from the same hospital. MLST data shows that these 72 isolates belong to 18 STs and phylogenetic tree analysis has divided these isolates into nine groups. CONCLUSIONS: Our results provide evidence that not only bla IMP-26 but other IMP variants such as bla IMP-15 and bla IMP-51 genes and several STs (ST235, ST244, ST277, ST310, ST773 and ST3151) have been disseminating in healthcare settings in Vietnam. In addition, we report the emergence of two isolates belonging to ST1240 and ST3340 that harboured two important carbapenemase genes (bla IMP-15 and bla DIM-1) and seven isolates belonging to ST3151 of P. aeruginosa that carried the bla KPC-1 gene in Vietnam, which could potentially cause serious restricted availability of treatment options in healthcare settings.

Understanding Knowledge and Barriers Related to Hepatitis B for Vietnamese Nail Salon Workers in the City of Philadelphia and Some of Its Environs.

In the United States (U.S.), up to 2.2 million individuals have been chronically infected with hepatitis B virus (HBV). Many nail salon workers are at risk for HBV as they are coming from high-risk and traditionally underserved communities. To understand barriers and knowledge associated with HBV in the Vietnamese nail salon community, the Health Belief Model (HBM) was used to qualitatively assess the health needs for the prevention of HBV among Vietnamese nail salon workers in Philadelphia through focus groups and interviews (N = 19). Results revealed several themes that highlight barriers within the Vietnamese nail community. Major themes were the lack of knowledge related to hepatitis B, including significant misconceptions related to symptoms, and how hepatitis B is transmitted and prevented. There were also several barriers to health care access within the Vietnamese nail community including the cost of health care, long work hours, lack of insurance and lack of understanding of current community resources. Additionally, discrimination and stigma related to those infected with hepatitis B emerged as a theme from this data. Those interviewed also noted that the nail training and licensing they received did not highlight hepatitis B and other infectious diseases that can be spread within the nail salon.

Fine-scale population structure and evidence for local adaptation in Australian giant black tiger shrimp (Penaeus monodon) using SNP analysis.

BACKGROUND: Restrictions to gene flow, genetic drift, and divergent selection associated with different environments are significant drivers of genetic differentiation. The black tiger shrimp (Penaeus monodon), is widely distributed throughout the Indian and Pacific Oceans including along the western, northern and eastern coastline of Australia, where it is an important aquaculture and fishery species. Understanding the genetic structure and the influence of environmental factors leading to adaptive differences among populations of this species is important for farm genetic improvement programs and sustainable fisheries management. RESULTS: Based on 278 individuals obtained from seven geographically disparate Australian locations, 10,624 high-quality SNP loci were used to characterize genetic diversity, population structure, genetic connectivity, and adaptive divergence. Significant population structure and differentiation were revealed among wild populations (average FST = 0.001-0.107; p <  0.05). Eighty-nine putatively outlier SNPs were identified to be potentially associated with environmental variables by using both population differentiation (BayeScan and PCAdapt) and environmental association (redundancy analysis and latent factor mixed model) analysis methods. Clear population structure with similar spatial patterns were observed in both neutral and outlier markers with three genetically distinct groups identified (north Queensland, Northern Territory, and Western Australia). Redundancy, partial redundancy, and multiple regression on distance matrices analyses revealed that both geographical distance and environmental factors interact to generate the structure observed across Australian P. monodon populations. CONCLUSION: This study provides new insights on genetic population structure of Australian P. monodon in the face of environmental changes, which can be used to advance sustainable fisheries management and aquaculture breeding programs.

CRISPR/Cas9-mediated mutation of OsSWEET14 in rice cv. Zhonghua11 confers resistance to Xanthomonas oryzae pv. oryzae without yield penalty.

BACKGROUND: Bacterial blight of rice, caused by Xanthomonas oryzae pv. oryzae (Xoo), is a devastating rice disease in Southeast Asia and West Africa. OsSWEET14, encoding a sugar transporter, is known to be a major susceptible gene of bacterial blight targeted by four different transcription activator-like (TAL) effectors from either Asian or African Xoo strains. However, the OsSWEET14 single knockout or promoter mutants in the Kitaake background are moderately resistant or even susceptible to African Xoo strains. Therefore, in this study, we knocked out OsSWEET14 in rice cv. Zhonghua 11 background for disease assessment. RESULTS: In this study, CRISPR/Cas9 was utilized to disrupt the function of OsSWEET14 by modifying its corresponding coding region in the genome of rice cv. Zhonghua 11 (CR-S14). In total, we obtained nine different OsSWEET14-mutant alleles. Besides conferring broad-spectrum resistance to Asian Xoo strains, tested mutant alleles also showed strong resistance to African Xoo strain AXO1947. Moreover, the expression of OsSWEET14 was detected in vascular tissues, including the stem, leaf sheath, leaf blade and root. The disruption of OsSWEET14 led to increased plant height without a reduction in yield. CONCLUSIONS: Disruption of OsSWEET14 in the Zhonghua 11 background is able to confer strong resistance to African Xoo strain AXO1947 and Asian Xoo strain PXO86. CR-S14 has normal reproductive growth and enhanced plant height under normal growth conditions. These results imply that CR-S14 may serve as a better tester line than sweet14 single-knockout mutant in the Kitaake background for the diagnostic kit for rice blight resistance. The genetic background and increased plant height need to be taken into consideration when utilizing OsSWEET14 for resistant rice breeding.

Amphetamine-Type-Stimulants (ATS) Use and Homosexuality-Related Enacted Stigma Are Associated With Depression Among Men Who Have Sex With Men (MSM) in Two Major Cities in Vietnam in 2014.

BACKGROUND: Men who have sex with men (MSM) are disproportionately affected by mental health concerns, including depression. Amphetamine-type-stimulants (ATS) use and homosexuality-related stigma and discrimination have been found associated with depression among MSM. OBJECTIVES: To assess the prevalence of depression and its associations with ATS use and homosexuality-related stigma and discrimination among MSM in Vietnam. METHODS: 622 MSM were conveniently recruited in Hanoi and Ho Chi Minh city, Vietnam, from September to December 2014. We collected information on demographic characteristics, ATS, alcohol and other drug use, sexual behaviors, homosexuality-related and discrimination stigma, and sexual sensation-seeking. Depression and suicidal thoughts were assessed by the Patient Health Questionnaire (PHQ-9). We assessed associations of depression with ATS use and homosexuality-related stigma and discrimination using logistic regression. RESULTS: Of 622 sampled MSM, 11.3% were classified as having major depression, 9.8% reported any suicidal thoughts in the last two weeks, 30.4% ever had used any ATS, 88.8% ever ad drank alcohol and 21.5% had ever used any other drugs. In multivariate analysis, depression was significantly associated with ATS use (Adjusted Odds Ratio [AOR: 2.20; (95% Confidence Interval (CI): 1.32-3.67], younger age of sexual debut with another man (AOR: 0.09; 95% CI: 0.02-0.50), and greater enacted homosexuality-related stigma (AOR: 1.97; 95% CI: 1.19-3.26). CONCLUSIONS: We found a moderate prevalence of depression among sampled MSM, which was associated with ATS use and enacted homosexuality-related stigma. We recommend integrating assessment and interventions regarding depression and methamphetamine use into gay-friendly, culturally adapted holistic HIV prevention for MSM in Vietnam.

The Relationship Between Methamphetamine Use, Sexual Sensation Seeking and Condomless Anal Intercourse Among Men Who Have Sex With Men in Vietnam: Results of a Community-Based, Cross-Sectional Study.

This study assessed the relationship between methamphetamine use and condomless anal intercourse (CAI) among men who have sex with men (MSM) in Hanoi and Ho Chi Minh City, Vietnam. Of 622 MSM participants, 75.7% reported any CAI in the last three months, 23.2% reported engaging in sex work in the last three months, 21.1% reported group sex in the last twelve months (21.1%) and 14.3% had used methamphetamine for sex in the last three months. CAI was associated with living in Ho Chi Minh City vs. Hanoi, being versatile during anal sex, a greater degree of sexual sensation-seeking, and more strongly agreeing that withdrawal before ejaculation is effective in preventing HIV. Effect-modification analysis showed that recent sex-related methamphetamine use was related to a higher probability of CAI for men with low sexual sensationseeking scores. Methamphetamine assessment and/or interventions should be incorporated into HIV prevention and research with Vietnam's MSM population.

Cigarette Smoking among Adolescents aged 13-15 in Viet Nam and Correlates of Current Cigarette Smoking: Results from GYTS 2014 Data.

The aim of this paper is to report the rate of current and ever cigarette smoking and explore correlates of current cigarette smoking among adolescents aged 13-15 in Viet Nam. This analysis was derived from GYTS survey, which comprised of 3,430 adolescents aged 13-15, conducted in 2014 in 13 cities and provinces of Viet Nam. We calculated the weighted rates of current and ever cigarette smoking and reported patterns of smoking behavior. We also performed logistic regression to explore correlates of current cigarette smoking behavior. The weighted rate of ever cigarette smoking was 9.5% (95% confidence interval (CI): 8.5 %-10.5%), in which the weighted rate among males (15.4%; 95% CI: 13.6%-17.0%) was higher than that among females (4.2%; 95% CI: 3.3%-5.1%). The weighted rate of current cigarette smoking was relatively low at 2.5% (95%CI: 2.0%- 3.0%) with higher weighted rate among males (4.9%; 95% CI: 3.8%-5.9%) compared to the corresponding figure among females (0.2%; 95% CI: 0.0 %-0.5%). Current cigarette smoking was significantly higher among males than females, in students aged 15 versus 13 years old, and in students who had several or all close friends smoking and students with daily observation of smoking at school. For greater smoking reduction outcomes, we recommend that tobacco interventions for adolescents should consider targeting more male students at older ages, establish stricter adherence to school-based banning of cigarette smoking, engage both smoking and nonsmoking adolescents and empower adolescents to resist peer smoking influence as well as changing their norms or beliefs towards smoking benefits.

The Prevalence and Correlates of HIV and Undiagnosed Infection among Men Who Have Sex with Men in Hanoi, Vietnam: Findings from a Cross-sectional, Biobehavioral Study.

INTRODUCTION: Men who have sex with men (MSM) are a key population for HIV infection in Vietnam, and the use of amphetamine type substances (ATS) is prevalent and possibly increasing in this population. The reported analysis examines the association between ATS use before or during sex and HIV infection among MSM in Hanoi, Vietnam. METHODS: This cross-sectional study of 210 MSM was conducted in Hanoi, Vietnam, in late 2014. Men tested for HIV and answered questions about demographic characteristics, sexual sensation seeking, depression, belief in HIV prevention strategies, homosexuality-related stigma and discrimination, recent accessing of HIV prevention services, sexual behaviors and ATS, and other drug use behaviors. We performed logistic regression to assess correlates of HIV infection. RESULTS: HIV prevalence was 6.7% (14/210), and 85.7% (12/14) of HIV-positive men were not aware of their HIV status. Of the 210 participants, 10.5, 2.9, and 3.8% of men had used methamphetamine, amphetamine, and ecstasy before or during sex in the last 3 months. In multivariable analysis, HIV infection was associated with recent sex-related methamphetamine use [adjusted odds ratio (AOR): 5.03, 95% confidence interval (CI): 1.35-18.68], engaging in recent sex work (AOR: 3.55, 95% CI: 1.07-11.75), and homosexuality-related perceived stigma (AOR: 2.32, 95% CI: 0.98-5.47). CONCLUSION: Findings underscore the importance of integrating methamphetamine use interventions into HIV prevention services and scaling-up of gay-friendly, non-stigmatizing HIV testing services for MSM in Hanoi. We recommend the routine assessment of ATS use and undiagnosed infection in this population.

Amphetamine-type stimulant use among men who have sex with men (MSM) in Vietnam: Results from a socio-ecological, community-based study.

INTRODUCTION: Amphetamine-type-stimulants (ATS) use is associated with HIV-related sexual risk behaviours and is an emergent problem among men who have sex with men (MSM) in Vietnam. The purpose of this study is to describe ATS use patterns and understand the correlates of recent methamphetamine use from a socio-ecological perspective. METHODS: From September through December, 2014, 622 MSM were recruited in Hanoi and Ho Chi Minh City, Vietnam. We collected information on demographic characteristics, HIV testing behaviours, use of ATS and other recreational drugs (ever and recently), sexual sensation seeking, depressive mood, experienced and internalized stigma related to homosexuality, social involvement with other MSM, and perceptions of ATS use in MSM networks. We performed descriptive statistics to describe ATS use patterns and multivariate logistic regression to establish independent correlates of recent methamphetamine use. RESULTS: Nearly one-third (30.4%) had ever used ATS, including 23.6% who had used methamphetamine, 4.3% who had used amphetamine ('speed') and 20.9% who had used ecstasy. 20.1% and 11.9% had ever used methamphetamine and ecstasy, respectively, during sex. Eighteen percent of methamphetamine users were classified as engaged in high-risk use. Recent methamphetamine use (in the last 3 months) was associated with participants perceiving more methamphetamine use in their MSM network, recent sex work, and higher sexual sensation seeking scores. CONCLUSIONS: ATS use is relatively prevalent among MSM sampled in Vietnam's main cities. Interventions to address methamphetamine are warranted for MSM in Vietnam. Methamphetamine treatments are needed for high-risk users.

Ultra-Performance Liquid Chromatographic Determination of Manufacturing Intermediates and Subsidiary Colors in D&C Red No. 6, D&C Red No. 7, and Their Lakes.

An ultra-performance LC (UPLC) method was developed to determine the manufacturing intermediates and subsidiary colors in the monosulfo monoazo color additives D&C Red No. 6 and D&C Red No. 7 and their lakes. This method is intended for use in batch certification of the color additives by the U. S. Food and Drug Administration to ensure that each lot meets published specifications for coloring drugs and cosmetics. The intermediates are 2-amino-5-methylbenzenesulfonic acid (PTMS) and 3-hydroxy-2-naphthalenecarboxylic acid (3-hydroxy-2-naphthoic acid). The subsidiary colors are 3-hydroxy-4-[(4-methylphenyl)azo]-2-naphthalenecarboxylic acid (unsulfonated subsidiary color) and 1-[(4-methylphenyl) azo]-2-naphthalenol (4-methyl Sudan I). The analytes were identified by comparing their UPLC retention times and UV-Vis absorption spectra with those of standards. Validation studies showed that calibration curves were linear (average R2=0.9994), and recoveries were 96-106%. Average LOD was 0.0014-0.0061% and average LOQ was 0.0047-0.020%. Results for RSD at the specification levels ranged from 0.67 to 5.79%. Survey analyses of 42 samples from 14 domestic and foreign manufacturers yielded results by the new UPLC method and a previously reported HPLC method that were consistent within experimental error. The new UPLC method provided increased sensitivity, faster analysis times, and improved separations compared to the HPLC method.

Cryptic Hepatitis B and E in Patients With Acute Hepatitis of Unknown Etiology.

BACKGROUND: Up to 30% of acute viral hepatitis has no known etiology. To determine the disease etiology in patients with acute hepatitis of unknown etiology (HUE), serum specimens were obtained from 38 patients residing in the United Kingdom and Vietnam and from 26 healthy US blood donors. All specimens tested negative for known viral infections causing hepatitis, using commercially available serological and nucleic acid assays. METHODS: Specimens were processed by sequence-independent complementary DNA amplification and next-generation sequencing (NGS). Sufficient material for individual NGS libraries was obtained from 12 HUE cases and 26 blood donors; the remaining HUE cases were sequenced as a pool. Read mapping was done by targeted and de novo assembly. RESULTS: Sequences from hepatitis B virus (HBV) were detected in 7 individuals with HUE (58.3%) and the pooled library, and hepatitis E virus (HEV) was detected in 2 individuals with HUE (16.7%) and the pooled library. Both HEV-positive cases were coinfected with HBV. HBV sequences belonged to genotypes A, D, or G, and HEV sequences belonged to genotype 3. No known hepatotropic viruses were detected in the tested normal human sera. CONCLUSIONS: NGS-based detection of HBV and HEV infections is more sensitive than using commercially available assays. HBV and HEV may be cryptically associated with HUE.

Amphetamine-type stimulants and HIV infection among men who have sex with men: implications on HIV research and prevention from a systematic review and meta-analysis.

INTRODUCTION: HIV infections and the use of amphetamine-type stimulants (ATS) among men who have sex with men (MSM) have been increasing internationally, but the role of ATS use as a co-factor for HIV infection remains unclear. We aimed to summarize the association between ATS use and HIV infection among MSM. METHODS: We conducted a systematic search of MEDLINE, EMBASE, GLOBAL HEALTH and PsycINFO for relevant English, peer-reviewed articles of quantitative studies published between 1980 and 25 April 2013. Pooled estimates of the association--prevalence rate ratios (PRR, cross-sectional studies), odds ratio (OR, case-control studies) and hazard ratio (HR, longitudinal studies), with 95% Confidence Intervals (CI)--were calculated using random-effects models stratified by study design and ATS group (meth/amphetamines vs. ecstasy). We assessed the existence of publication bias in funnel plots and checked for sources of heterogeneity using meta-regression and subgroup analysis. RESULTS: We identified 6710 article titles, screened 1716 abstracts and reviewed 267 full text articles. A total of 35 publications were eligible for data abstraction and meta-analysis, resulting in 56 records of ATS use. Most studies (31/35) were conducted in high-income countries. Published studies used different research designs, samples and measures of ATS use. The pooled association between meth/amphetamine use and HIV infection was statistically significant in all three designs (PRR = 1.86; 95% CI: 1.57-2.17; OR = 2.73; 95% CI: 2.16-3.46 and HR = 3.43; 95% CI: 2.98-3.95, respectively, for cross-sectional, case-control and longitudinal studies). Ecstasy use was not associated with HIV infection in cross-sectional studies (PRR = 1.15; 95% CI: 0.88-1.49; OR = 3.04; 95% CI: 1.29-7.18 and HR = 2.48; 95% CI: 1.42-4.35, respectively, for cross-sectional, case-control and longitudinal studies). RESULTS in cross-sectional studies were highly heterogeneous due to issues with ATS measurement and different sampling frames. CONCLUSIONS: While meth/amphetamine use was significantly associated with HIV infection among MSM in high-income countries in all study designs, evidence of the role of ecstasy in HIV infection was lacking in cross-sectional studies. Cross-sectional study design, measurement approaches and source populations may also be important modifiers of the strength and the direction of associations. Event-specific measure of individual drug is required to establish temporal relationship between ATS use and HIV infection. HIV prevention programmes targeting MSM should consider including interventions designed to address meth/amphetamine use.

1,2,5-Thiadiazolidin-3-one 1,1-dioxide-based heterocyclic sulfides are potent inhibitors of human tryptase.

We describe herein the design, synthesis, and in vitro biochemical evaluation of a series of potent, time-dependent inhibitors of the mast cell-derived serine protease tryptase. The inhibitors were readily obtained by attaching various heterocyclic thiols, as well as a basic primary specificity residue P(1), to the 1,2,5-thiadiazolidin-3-one 1,1-dioxide scaffold. The inhibitors were found to be devoid of any inhibitory activity toward a neutral (elastase) or cysteine (papain) protease, however they were also fairly efficient inhibitors of bovine trypsin. The differential inhibition observed with trypsin suggests that enzyme selectivity can be optimized by exploiting differences in the S' subsites of the two enzymes. The results described herein demonstrate the versatility of the heterocyclic scaffold in fashioning mechanism-based inhibitors of neutral, basic, and acidic (chymo)trypsin-like serine proteases.

In vitro characterization of ephedrine-related stereoisomers at biogenic amine transporters and the receptorome reveals selective actions as norepinephrine transporter substrates.

Ephedrine is a long-studied stimulant available both as a prescription and over-the-counter medication, as well as an ingredient in widely marketed herbal preparations, and is also used as a precursor for the illicit synthesis of methamphetamine. Ephedrine is related to phenylpropanolamine, a decongestant removed from the market place due to concerns that its use increased the risk of hemorrhagic stroke. Standard pharmacology texts emphasize that ephedrine is both a direct and indirect adrenergic agonist, activating adrenergic receptors both by direct agonist activity as well as by releasing norepinephrine via a carrier-mediated exchange mechanism. Chemically, ephedrine possesses two chiral centers. In the present study, we characterized the stereoisomers of ephedrine and the closely related compounds pseudoephedrine, norephedrine, pseudonorephedrine (cathine), methcathinone, and cathinone at biogenic amine transporters and a large battery of cloned human receptors (e.g., "receptorome"). The most potent actions of ephedrine-type compounds were as substrates of the norepinephrine transporter (EC50 values of about 50 nM) followed by substrate activity at the dopamine transporter. Screening the receptorome demonstrated weak affinity at alpha2-adrenergic and 5-hydroxytryptamine7 receptors (Ki values 1-10 microM) and no significant activity at beta-adrenergic or alpha1-adrenergic receptors. Viewed collectively, these data indicate that the pharmacological effects of ephedrine-like phenylpropanolamines are likely mediated by norepinephrine release, and although sharing mechanistic similarities with, they differ in important respects from those of the phenylpropanonamines methcathinone and cathinone and the phenyisopropylamines methamphetamine and amphetamine.