Prevalence and Correlates of Active Amphetamine-Type Stimulant Use Among Female Sex Workers in Malaysia.

The use of amphetamine-type stimulants (ATS) has been associated with increased sexual risk behaviors and HIV transmission, among other adverse health outcomes. However, ATS use among female sex workers (FSWs) in Malaysia has not yet been characterized. We examined the prevalence and correlates associated with ATS use among Malaysian FSW. Between February and December 2016, 492 FSWs, including cisgender (n = 299) and transgender (n = 193) women, were recruited using respondent-driven sampling in Greater Kuala Lumpur, Malaysia. A structured questionnaire was used to collect demographic characteristics, sexual behaviors, ATS and other substance use, behavioral health issues, involvement in criminal justice, and experience of physical and sexual trauma. Logistic regression analyses were conducted to determine factors associated with active ATS use, defined as ATS use in the last 30 days. Nearly one-third (32.3%) of participants reported active ATS use. In the multivariable model, ATS use was associated with drug use during sex work (aOR = 17.10; 8.32-35.15), having moderate to severe level of substance use disorder (aOR = 3.38; 1.48-7.70), and engaging in sex work with multiple clients per day (two clients: aOR = 3.39; 1.36-8.46; three clients: aOR = 5.06; 1.81-14.10). A high prevalence of ATS use was documented in our sample. The presence of moderate to severe substance use disorder, the use of drugs during sex work activity, and having multiple sex work clients per day were significantly associated with active ATS use. Given these findings, prevention and harm reduction strategies need to be tailored to address the increasing ATS use and the associated adverse health consequences among FSWs in Malaysia.

Prevalence and psychosocial impact of atopic dermatitis in Bangladeshi children and families.

BACKGROUND: Skin conditions are the fourth leading cause of nonfatal disease globally, with atopic dermatitis (AD) a major and rising contributor. Though atopic dermatitis (AD) is rising in prevalence, little is known about its psychosocial effects on children and families in low- and middle-income countries (LMICs). METHODS: We conducted a community-based, cross-sectional survey of 2242 under-5 children in rural Bangladesh using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire to measure AD prevalence and severity, the Patient-Oriented Eczema Measure (POEM) to measure severity, and the Infants' Dermatitis Quality of Life index (IDQoL) and Dermatitis Family Index (DFI) to measure quality of life. FINDINGS: Overall AD prevalence in under-five children was 11.9% [95% confidence interval (CI) 10.6-13.3%]. Prevalence was highest in children age 30-35 months [16.2% (95% CI 11.4-21.0)]. IDQoL was significantly higher in males (2.67) vs. females (1.95, p = 0.015), the lowest (3.06) vs. highest (1.63) wealth quintile (p<0.001), and among mothers with < primary (2.41) vs. > secondary (1.43) education (p = 0.039). POEM severity was correlated with IDQoL (r = 0.77, p<0.001) and DFI (r = 0.56, p<0.001). Severe disease as rated by caretakers was correlated with POEM (r = 0.73, p<0.001), IDQoL (r = 0.82, p<0.001) and DFI (r = 0.57, p<0.001). CONCLUSIONS: Severe AD significantly affects quality of life for children and families in Bangladesh. As access to healthcare expands in LMICs, identification and treatment of both the medical and psychosocial morbidities associated with the disease are needed.

Prevalence of atopic dermatitis, asthma and rhinitis from infancy through adulthood in rural Bangladesh: a population-based, cross-sectional survey.

OBJECTIVE: Describe the pattern of atopic disease prevalence from infancy to adulthood. DESIGN: Cross-sectional household survey. SETTING: Community-based demographic surveillance site, Mirzapur, Bangladesh. PARTICIPANTS: 7275 individuals in randomly selected clusters within 156 villages. PRIMARY AND SECONDARY OUTCOME MEASURES: The 12-month prevalence of atopic dermatitis (by UK Working Party Criteria (UK criteria) and International Study of Asthma and Allergies in Childhood (ISAAC)), asthma and rhinitis (by ISAAC); disease severity (by ISAAC); history of ever receiving a medical diagnosis. RESULTS: Children aged 2 years had the highest prevalence of atopic dermatitis-18.8% (95% CI 15.2% to 22.4%) by UK criteria and 14.9% (95% CI 11.6% to 18.1%) by ISAAC- and asthma (20.1%, 95% CI 16.4% to 23.8%). Prevalence of rhinitis was highest among 25-29 year olds (6.0%, (95% CI% 4.5 to 7.4%). History of a medical diagnosis was lowest for atopic dermatitis (4.0%) and highest for rhinitis (27.3%) and was significantly associated with severe disease compared with those without severe disease for all three conditions (atopic dermatitis: 30.0% vs 11.7%, p=0.015; asthma; 85.0% vs 60.4%, p<0.001; rhinitis: 34.2% vs 7.3%, p<0.001) and having a higher asset-based wealth score for asthma (29.7% (highest quintile) vs 7.5% (lowest quintile), p<0.001) and rhinitis (39.8% vs 12.5%, p=0.003). Prevalence of having >1 condition was highest (36.2%) at 2 years and decreased with age. Having atopic dermatitis (ISAAC) was associated with significantly increased odds ratios (OR) for comorbid asthma (OR 5.56 (95% CI 4.26 to 7.26)] and rhinitis (3.68 (95% CI 2.73 to 4.96)). Asthma and rhinitis were also strongly associated with each other (OR 8.39 (95% CI 6.48 to 10.86)). CONCLUSIONS: Atopic disease burden was high in this rural Bangladeshi population. Having one atopic condition was significantly associated with the presence of another. Low incidence of ever obtaining a medical diagnosis highlights an important opportunity to increase availability of affordable diagnosis and treatment options for all age groups.

Factors Associated With Influenza in an Emergency Department Setting.

BACKGROUND: Emergency departments (EDs) become more overcrowded during peak respiratory virus season. Distinguishing influenza from other viruses is crucial to implement social distancing practices, early treatment, and prompt disposition. OBJECTIVES: We sought to determine factors associated with influenza among a prospective cohort of consecutive ED patients with acute respiratory illness (ARI). METHODS: Between December 2016 and March 2017, trained research assistants screened consecutive ED patients with ARI symptoms. ARI criteria included measured fever at home or in the ED >38°C and a cough, sore throat, or rhinorrhea with a duration of symptoms >12 hours and <1 week. After consent, research assistants collected demographics and clinical history using a standardized data form, and patients had a polymerase chain reaction-based assay that is nearly 100% sensitive for influenza. Univariate analysis was conducted on all predictor variables. Significant variables were entered into a multivariate logistic regression model to find factors that were independently associated with influenza. RESULTS: One hundred nineteen patients consented to enrollment and 31% were found to be positive for influenza. Myalgia, the absence of gastrointestinal symptoms (no diarrhea or vomiting), sore throat, chills, headache, and oxygen saturation ≥97% were significant on univariate analysis and were entered into the multivariate model. Myalgia (adjusted odds ratio [AOR] 3.9), the absence of gastrointestinal symptoms (AOR 4.7), and oxygen saturation ≥97% (AOR 2.8) were significant independent factors of influenza. CONCLUSION: The presence of myalgia, the absence of gastrointestinal symptoms, and oxygen saturation ≥97% are factors that can help distinguish influenza from other acute respiratory illnesses in the ambulatory ED population.

Using a novel rapid viral test to improve triage of emergency department patients with acute respiratory illness during flu season.

BACKGROUND: Acute respiratory illnesses (ARI) are mostly viral in etiology and cause significant morbidity and mortality. Point of care PCR (POC-PCR) is a promising new technology for rapid virus identification but utility in the Emergency Department (ED) is not yet defined. OBJECTIVES: Primarily, to investigate the value of POC-PCR in rapidly identifying RSV and influenza in the setting of ED triage. Additionally, to assess whether rapid knowledge of accurate test results would improve patient management by preventing nosocomial transmission and optimizing the prescription of antimicrobials for ARIs. STUDY DESIGN: A prospective cohort study of consecutive ED patients with ARI symptoms during peak flu season was conducted. Patient nasopharyngeal swabs were collected and tested using a POC-PCR device; physicians and patients were blinded to results. Virus positive and negative groups were compared by ED patient room placement and antimicrobial therapy ordered. Specificity and sensitivity were calculated using laboratory-PCR as the gold standard. RESULTS: Of 119 participants, 52.9% were POC-PCR positive - Influenza A (42.9%), RSV (41.3%), influenza B (15.9%). Nearly 70% of virus positive patients were placed rooms shared with non-ARI patients. Antibiotics were prescribed for 27.3% of virus positive patients, and 77.8% of oseltamivir-eligible patients did not receive therapy. POC-PCR was 100% sensitive (95% CI, 80.5-100.0%) and 95.2% specific (95% CI, 76.2-99.9%). CONCLUSIONS: Rapid POC-PCR for influenza and RSV in ED triage has excellent sensitivity and specificity and the potential to improve social distancing practices through better triage and increase appropriate prescription of antimicrobials.

A community-based evaluation of proximity to unconventional oil and gas wells, drinking water contaminants, and health symptoms in Ohio.

Over 4 million Americans live within 1.6 km of an unconventional oil and gas (UO&G) well, potentially placing them in the path of toxic releases. We evaluated relationships between residential proximity to UO&G wells and (1) water contamination and (2) health symptoms in an exploratory study. We analyzed drinking water samples from 66 Ohio households for 13 UO&G-related volatile organic compounds (VOCs) (e.g., benzene, disinfection byproducts [DBPs]), gasoline-range organics (GRO), and diesel-range organics. We interviewed participants about health symptoms and calculated metrics capturing proximity to UO&G wells. Based on multivariable logistic regression, odds of detection of bromoform and dibromochloromethane in surface water decreased significantly as distance to nearest UO&G well increased (odds ratios [OR]: 0.28-0.29 per km). Similarly, distance to nearest well was significantly negatively correlated with concentrations of GRO and toluene in ground water (rSpearman: -0.40 to -0.44) and with concentrations of bromoform and dibromochloromethane in surface water (rSpearman: -0.48 to -0.50). In our study population, those with higher inverse-distance-squared-weighted UO&G well counts within 5 km around the home were more likely to report experiencing general health symptoms (e.g. stress, fatigue) (OR: 1.52, 95%CI: 1.02-2.26). This exploratory study, though limited by small sample size and self-reported health symptoms, suggests that those in closer proximity to multiple UO&G wells may be more likely to experience environmental health impacts. Further, presence of brominated DBPs (linked to UO&G wastewater) raises the question of whether UO&G activities are impacting drinking water sources in the region. The findings from this study support expanded studies to advance knowledge of the potential for water quality and human health impacts; such studies could include a greater number of sampling sites, more detailed chemical analyses to examine source attribution, and objective health assessments.

Prevalence of Human Immunodeficiency Virus and Sexually Transmitted Infections Among Cisgender and Transgender Women Sex Workers in Greater Kuala Lumpur, Malaysia: Results From a Respondent-Driven Sampling Study.

BACKGROUND: Sex workers face a disproportionate burden of human immunodeficiency virus (HIV) and sexually transmitted infections (STI) worldwide. For cisgender women sex workers (CWSW), global HIV prevalence is over 10%, whereas transgender women sex workers (TWSW) face an HIV burden of 19% to 27%. METHODS: We used respondent-driven sampling to recruit 492 sex workers, including CWSW (n = 299) and TWSW (n = 193) in Greater Kuala Lumpur, Malaysia. Participants completed an in-depth survey and were screened for HIV, syphilis, Chlamydia trachomatis, and Neisseria gonorrhoeae. Sample characteristics stratified by gender identity and interview site are presented. Bivariate analyses comparing CWSW and TWSW were conducted using independent samples t tests for continuous variables and χ tests for categorical variables. RESULTS: Pooled HIV prevalence was high (11.7%; 95% confidence interval [CI], 8.8-14.5), and was similar for CWSW (11.1%) and TWSW (12.4%). Rates of syphilis 25.5% (95% CI, 21.6-29.5), C. trachomatis (14.8%; 95% CI, 11.6-18.0) and N. gonorrhoeae (5.8%; 95% CI, 3.7-7.9) were also concerning. Both groups reported lifetime HIV testing (62.4%), but CWSW were less likely to have ever been HIV tested (54.5%) than TWSW (74.6%). Median time since last HIV test was 24 months. Previous screening for STI was low. Inconsistent condom use and drug use during sex work were not uncommon. CONCLUSIONS: High HIV and STI prevalence, coupled with infrequent HIV and STI screening, inconsistent condom use, and occupational drug use, underscore the need for expanded HIV and STI prevention, screening, and treatment efforts among CWSW and TWSW in Malaysia.

Serine 129 phosphorylation reduces the ability of alpha-synuclein to regulate tyrosine hydroxylase and protein phosphatase 2A in vitro and in vivo.

Alpha-synuclein (a-Syn), a protein implicated in Parkinson disease, contributes significantly to dopamine metabolism. a-Syn binding inhibits the activity of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis. Phosphorylation of TH stimulates its activity, an effect that is reversed by protein phosphatase 2A (PP2A). In cells, a-Syn overexpression activates PP2A. Here we demonstrate that a-Syn significantly inhibited TH activity in vitro and in vivo and that phosphorylation of a-Syn serine 129 (Ser-129) modulated this effect. In MN9D cells, a-Syn overexpression reduced TH serine 19 phosphorylation (Ser(P)-19). In dopaminergic tissues from mice overexpressing human a-Syn in catecholamine neurons only, TH-Ser-19 and TH-Ser-40 phosphorylation and activity were also reduced, whereas PP2A was more active. Cerebellum, which lacks excess a-Syn, had PP2A activity identical to controls. Conversely, a-Syn knock-out mice had elevated TH-Ser-19 phosphorylation and activity and less active PP2A in dopaminergic tissues. Using an a-Syn Ser-129 dephosphorylation mimic, with serine mutated to alanine, TH was more inhibited, whereas PP2A was more active in vitro and in vivo. Phosphorylation of a-Syn Ser-129 by Polo-like-kinase 2 in vitro reduced the ability of a-Syn to inhibit TH or activate PP2A, identifying a novel regulatory role for Ser-129 on a-Syn. These findings extend our understanding of normal a-Syn biology and have implications for the dopamine dysfunction of Parkinson disease.

14-3-3zeta contributes to tyrosine hydroxylase activity in MN9D cells: localization of dopamine regulatory proteins to mitochondria.

The 14-3-3 proteins stimulate the activation of tyrosine hydroxylase (TH), the rate-limiting catecholamine biosynthetic enzyme. To explore if particular endogenous 14-3-3 isoforms specifically affected TH activity and dopamine synthesis, we utilized rodent nigrostriatal tissues and midbrain-derived MN9D dopaminergic cells. Extracts from ventral midbrain and MN9D cells contained similar pools of 14-3-3 mRNAs, with 14-3-3zeta being relatively abundant in both. Protein levels of 14-3-3zeta were also abundant. [(32)P]Orthophosphate labeling of MN9D cells, followed by co-immunoprecipitation with pan-TH and pan-14-3-3 antibodies brought down similar amounts of phosphorylated TH in each, confirming that 14-3-3-bound phosphorylated TH in our cells. Co-immunoprecipitation of striatal tissues with a pan-TH antibody precipitated 14-3-3zeta but not another potential TH regulatory isoform, 14-3-3eta. In whole cell extracts from MN9D cells after 14-3-3 small interfering RNA treatments, we found that 14-3-3zeta knockdown significantly reduced TH activity and dopamine synthesis whereas knockdown of 14-3-3eta had no effect. 14-3-3zeta was found co-localized on mitochondria with TH, and its knockdown by small interfering RNA reduced TH phosphorylation and TH activity in the mitochondrial pool. Together the data support a role for 14-3-3zeta as an endogenous activator of TH in midbrain dopaminergic neurons and furthermore, identify mitochondria as a potential novel site for dopamine synthesis, with implications for Parkinson disease.