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Phthalate exposure in Thai children and adolescents

Abstract

Background

Phthalates are found in products made of plastic. Because of concerns regarding the hazards of phthalate exposure, including endocrine disruption, many countries have regulations to restrict their use in products used by children. However, in Thailand, no such restrictions exist, and data relating to phthalate exposure are scarce.

Objectives

To determine the level of exposure of Thai children and adolescents to phthalates, and study its associations with sociodemographic data and the exposure to potential sources of phthalates.

Methods

Healthy children aged 2–18 y were enrolled into the present cross-sectional study between January 2016 and December 2016 inclusive. Their anthropometric indices and Tanner staging were determined. Urinary concentrations of the phthalate metabolites, monomethyl phthalate (MMP) and mono-n-butyl phthalate (MBP), were determined in spot samples by high-performance liquid chromatography to estimate the level of phthalate exposure. Associations between sociodemographic data, exposure to potential sources of phthalates, and phthalate metabolite concentrations were analyzed.

Results

We included 103 boys and 118 girls with a mean age of 9.4 ± 3.64 (range 2.8–17.1) y and detected MMP in 28.5% and MBP in 88.6%. The geometric means (interquartile range) of urinary MMP and MBP were 3400 (2489, 4642) and 214.4 (164, 279) μg/g creatinine (Cr), respectively. Significant associations were found between exposure to floor cleaning products and Cr-adjusted urinary MMP level (P < 0.05), and paint and Cr-adjusted urinary MMP and MBP levels (P < 0.05). Prepuberty was significantly associated with urinary Cr-adjusted MMP level.

Conclusion

Urinary phthalate metabolite levels were high in a proportion of Thai children and adolescents. Exposure to floor cleaning products and paint is associated with phthalate exposure, and advanced Tanner stage is negatively associated with urinary Cr-adjusted MBP.

Open access
Potassium channel inhibitors induce oxidative stress in breast cancer cells

Abstract

Background

Antioxidant levels increase to protect cell homeostasis when oxidant generation is increased by drug or inhibitor treatment. If the oxidant–antioxidant equilibrium is disrupted, oxidative stress will occur.

Objectives

To determine the effects of various potassium channel inhibitors in the disruption of oxidant–antioxidant equilibrium in breast cancer cell lines with various phenotypes.

Methods

MCF-7 or MDA-MB-231 breast cancer cells were treated with tetraethylammonium chloride (5 mM; TEA), 4-aminopyridine (5 mM; 4-AP), margatoxin (25 nM; MgTX), or astemizole (200 nM; AST). After treatment, total antioxidant, oxidant, and oxidative stress levels were determined.

Results

Incubation with TEA, 4-AP, MgTX, and AST increased oxidative stress in both MCF-7 and MDA-MB-231 cells (P < 0.001). Specific inhibitors of calcium-activated potassium channels and ether á go-go 1-related potassium channels produce greater oxidative stress than other inhibitors in MCF-7 breast cancer cells, whereas in MDA-MB-231 cells, the nonselective channel inhibitor 4-AP produces the greatest oxidative stress.

Conclusions

Potassium channel inhibitors used in our study disrupted the antioxidant–oxidant equilibrium and increased oxidative stress in the cancer cell lines. Although all of the channel inhibitors increased oxidative stress in cells, TEA and AST were the most effective inhibitors in MCF-7 cells. 4-AP was the most effective inhibitor in MDA-MB-231 cells. Voltage-gated potassium channels are attractive targets for anticancer therapy, and their inhibitors may enhance the effects of anticancer drugs.

Open access
Reactogenicity and safety of AS03B-adjuvanted H5N1 influenza vaccine in children: an open-label, one-way, crossover trial

Abstract

Background

Human cases of highly pathogenic avian-origin influenza A/H5N1 infection continue to be reported to the World Health Organization, and recent outbreaks of human cases of other zoonotic influenza strains highlight the continued need for strategies to mitigate influenza pandemic potential.

Methods

A Phase II–III randomized, placebo-controlled, observer-blind trial was conducted to assess the immunogenicity, reactogenicity, and safety of two 1.9 μg hemagglutinin doses of AS03B-adjuvanted H5N1 (AS03B-H5N1; A/Indonesia) vaccine in children (6 months to <18 years old) of Thailand, the United States, and Canada (Year 1, published elsewhere). After database lock in Year 1, the trial was unblinded, and children who had been randomized to receive placebo and continued to fulfill the eligibility criteria were invited to participate in an open-label, one-way, crossover safety extension phase, in which they received AS03B-H5N1 vaccine. Here we report the safety analysis in Year 2.

Results

A total of 155 children were vaccinated in Year 2. The most frequent solicited adverse event (AE) during 7 days post vaccination was injection site pain. Irritability or fussiness was reported in about one-third of younger children (aged <6 years) during 7 days post vaccination and was the most common solicited general AE in this age group. Postvaccination temperature (≥38°C) was reported in 4 (5.1%) children. The most common solicited general AEs in older children (aged ≥6 years) were muscle aches, headache, and fatigue. The AS03B-H5N1 vaccine had a clinically acceptable safety profile up to 385 days post vaccination.

Conclusions

Safety in the crossover phase was acceptable and consistent with that observed in vaccine recipients in the randomized, blinded phase of the study.

Clinical trial registration

ClinicalTrials.gov: NCT01310413.

Open access
Screening antibiotics using an Hoechst 33342 dye-accumulation assay to detect efflux activity in Acinetobacter baumannii clinical isolates

Abstract

Background

Understanding the contribution of efflux pumps to the resistance of antibiotics is useful when considering strategies for antimicrobial therapy.

Objectives

To assess the role of efflux activity on the resistance of antibiotics commonly used in hospitals.

Methods

We analyzed the efflux activity of 120 clinical isolates of Acinetobacter baumannii using an Hoechst 33342 (H33342) dye-accumulation assay. We compared the indicators for efflux activity of susceptible and non-susceptible groups of each of 16 tested antibiotics. To determine the role of efflux activity on resistance to an antibiotic, we used 3 criteria based on the results of the H33342-accumulation assay.

Results

The evaluation suggests that efflux activity contributed to resistance to the following 11 antibiotics: cefepime, cefotaxime, ceftazidime, ciprofloxacin, gentamicin, imipenem, meropenem, piperacillin, piperacillin/tazobactam, ticarcillin/ clavulanic acid, and tigecycline. However, ampicillin/sulbactam, minocycline, and trimethoprim/sulfamethoxazole did not meet the criteria, suggesting resistance may not be mediated by efflux activity. A significant difference in efflux activity was observed between bacteria belonging to the multidrug-resistant Acinetobacter baumannii (MDRAB) group and those belonging to the non-MDRAB group.

Conclusions

Efflux activity may contribute to multidrug resistance and particularly resistance to numerous antibiotics used in hospitals. These antibiotics would be good candidates for combination therapeutic regimens consisting of an antibiotic and an efflux pump inhibitor as an adjuvant to combat drug efflux.

Open access
Two decades’ contribution of occupational medicine training in Thailand: experience from the foundation with a view toward the future

Abstract

For 2 decades, the Department of Preventive and Social Medicine, Faculty of Medicine, Chulalongkorn University, has served the Occupational Medicine Residency training program in Thailand. Graduates of this program undertake to work in occupational medicine to promote health and prevent morbidity and mortality in the workplace and provide occupational medical services for the working population in Thailand. Qualifying for a Postgraduate Diploma in Occupational Medicine in Thailand can be achieved in 2 ways: through a 3-year residency training or 5 years of working experience in the field of occupational medicine combined with an elective 2-month short course. There are currently 159 Thai board-certified occupational medicine physicians. Occupational medicine physicians in Thailand work in both public and private healthcare facilities. A number of certified occupational physicians occupy leading national health positions in various government and academic organizations. Knowledge of occupational medicine is currently essential for undergraduate medical students as specified in the medical competency assessment criteria of the Thai Medical Council. Updating content and incorporating needs of employers are keys to success for Thailand, as a country with an occupational medicine training program in its initial stages. In Thailand, the supply of occupational medicine physicians is still less than the increasing demand. Advancement of health research schemes would contribute to the curriculum. Occupational medicine development in Thailand needs to address challenges in local issues including work in the informal sector, particularly in agriculture, and incorporate standardization and international consistency into the training curriculum and qualifying management.

Open access
The use of Monte Carlo simulation to predict vancomycin dosage for methicillin-resistant Staphylococcus aureus in Thai patients of various ages and with varying degrees of renal function

Abstract

Background

To our knowledge, no study reported so far has investigated appropriate vancomycin dosing, which is important for treatment of methicillin-resistant Staphylococcus aureus (MRSA) infection in Thai patients of various ages and with varying degrees of renal function.

Objectives

To predict vancomycin dosing for MRSA in Thai patients of various ages and with varying degrees of renal functions.

Methods

Monte Carlo simulation and minimal inhibitory concentration (MIC) distribution of MRSA from a hospital in Thailand were used to predict the area under the curve in 24 h/MIC >400 and trough concentration (C trough) <20 mg/L of 9 vancomycin dosage regimens for Thai patients stratified by age and renal function.

Results

Vancomycin dosing at least 2.5 g per day can attain cumulative fraction of response (CFR) of ≥90% in every age group. Vancomycin dosage achieving CFR of ≥90% for simulated patients with creatinine clearance (CLcr) was calculated using the Cockcroft–Gault equation. Appropriate vancomycin doses for Thai patients infected with MRSA with CLcr of <40, 40–60, >60–80, and >80 mL/min were 1.5 g every 24 h, 1.25 g every 12 h, 1 g every 8 h, and 1.75 g every 12 h, respectively. However, more than a half of patients simulated using these regimens have a vancomycin C trough of >20 mg/L.

Conclusions

Although vancomycin doses attaining a CFR of ≥90% can treat MRSA infection effectively, the regimens may cause kidney injury. The regimens have a probability of target attainment of 100%, and most patients can attain C trough of <20 mg/L.

Open access
Validity, reliability, and sensitivity to change of the Thai version of the Migraine-Specific Quality of Life Questionnaire version 2.1

Abstract

Background

The Migraine-Specific Quality of Life Questionnaire version 2.1 (MSQv2.1) is used to evaluate the impact of symptoms on the quality of life (QoL) of migraineurs.

Objective

To evaluate primarily the concurrent validity, test–retest reliability, and internal consistency, and secondarily the sensitivity to change of a Thai version of the MSQv2.1.

Methods

The original English version of the MSQv2.1 was translated into a Thai version. The Thai version of the MSQv2.1 was assessed for content and language equivalence. Validity of the Thai version of the MSQv2.1 was assessed using migraine characteristics in a prospective study conducted at the Chulalongkorn Comprehensive Headache Centre of King Chulalongkorn Memorial Hospital. Test–retest reliability and internal consistency were tested in migraineurs. Sensitivity to change was evaluated in another group of migraineurs using an 8-week follow-up.

Results

We recruited 30 migraineurs to test the validity, test–retest reliability, and internal consistency of the Thai version of the MSQv2.1 and 11 migraineurs to test its sensitivity to change. The Thai version of the MSQv2.1 scores were significantly correlated with migraine symptoms (inverse coefficient range from –0.62 to –0.39) except for associated symptoms, which had no correlation with any of the dimensions or overall QoL score. Spearman’s correlation coefficient for test–retest reliability was 0.56–0.83, and Cronbach’s α for internal consistency was 0.91–0.96. Headache, including average pain duration per attack, pain severity score (numeric rating scale), associated symptoms and dimensions, and overall QoL score of the Thai version of MSQv2.1 improved over time (P < 0.05). Moreover, improvement in headache correlated (coefficient range 0.67–0.77) with improvement in overall QoL score and some dimensions of the Thai version of the MSQv2.1 (coefficient range 0.66–0.77).

Conclusion

The Thai version of the MSQv2.1 had validity, acceptable internal consistency, moderate-to-strong test–retest reliability, and strong correlation between improvement in headache severity and overall QoL score. A future study with a larger sample size and longer follow-up is required for better estimates of internal consistency and sensitivity to change.

Open access
Determinants of consanguinity and inbreeding coefficient in the multiethnic population of Mardan, Khyber Pakhtunkhwa, Pakistan

Abstract

Background

Despite the high sociocultural preferences in contracting marriages among close relatives in Pakistan, marked regional differences exist in the prevalence of consanguinity. There is great interest to elucidate the sociodemographic variables underlying the heterogeneity in consanguinity prevalence in the various populations. The present study was conducted in the Mardan district of Pakistan, the second largest multiethnic Pashtun metropolis.

Objective

To find determinants of consanguineous unions.

Methods

In a cross-sectional study design, a convenience sample of 1,202 ever-married men from 3 tehsils of Mardan district was recruited in an unselected manner and data regarding their marital union types and sociodemographic variables were obtained by a structured interview. Descriptive statistics and multivariable logistic regression analyses were used.

Results

Consanguineous unions accounted for 44% of all marriages, and the inbreeding coefficient was calculated as 0.0258. Regression analyses revealed that 6 variables were significant predictors of consanguinity, namely, tehsil, age, year of marriage, caste (zaat/biradari) system, area of house, and marriage arrangement of the respondent, while 6 other variables, namely, rural/urban origin, literacy, occupation, monthly income, household type, and number of family members, were not found to be significant. Regression analyses showed that there were different combinations of variables predictive of consanguinity among the various tehsils.

Conclusions

The prevalence of consanguinity in the Mardan district was found to be lower than that in many other districts of Pakistan. National regional differences exist in consanguinity, and the combination of predictive factors varies greatly.

Open access
Epidemiological, clinical, and genotype characterization of spinocerebellar ataxia type in families in Buriram province, northeast Thailand

Abstract

Background

In Thais, the most prevalent type of spinocerebellar ataxia (SCA) is type 3, most commonly known as Machado–Joseph disease (MJD), followed by SCA type 1 (SCA1), SCA2, and SCA6.

Objectives

To describe the epidemiological, clinical, and genotypic features of SCA in northeastern Thailand and to study 2 associations: between syndromic features and the genotype of SCA, and between health determinants and scores on the scale for the assessment and rating of ataxia (SARA).

Methods

We conducted a cross-sectional study of 24 patients with autosomal dominant SCA from 13 families recruited from Buriram province in northeast Thailand between December 2009 and January 2014. Patients provided a clinical history and were examined by a neurologist. DNA was extracted from the peripheral blood of each patient. We analyzed associations between the type of SCA and sex, age, family history, clinical features, any underlying disease, age at onset, body weight, smoking status, family history, alcohol consumption, head injury history, and SARA.

Results

Seven of the families were positive for SCA1 and 6 for MJD. There were 24 index patients from these autosomal dominant SCA families, including 13 with SCA1 and 11 with MJD. Their average age was 43.7 years (range 20–72 years), whereas their average age at disease onset was 36.9 years (range 18–59 years). Pyramidal signs between MJD and SCA1 were not significantly different. Extrapyramidal features appeared uncommon. Horizontal nystagmus and upward gaze paresis were significantly associated with MJD. There were no significant differences in demographic data between the groups with SARA scores ≥15 or <15.

Conclusions

MJD and SCA1 were the 2 adult-onset cerebellar degenerative diseases found in Buriram province. Clinical clues for differentiating between them were upward gaze paresis and horizontal nystagmus, which were significantly more common in MJD.

Open access
Factors associated with glycemic control in children and adolescents with type 1 diabetes mellitus at a tertiary-care center in Thailand: a retrospective observational study

Abstract

Background

Children and adolescents with type 1 diabetes mellitus (T1D), even those with intensive insulin treatment regimens, often have higher glycated hemoglobin (HbA1c) levels than adults.

Objective

To delineate the medical and psychosocial factors associated with glycemic control in an unselected pediatric population with T1D.

Methods

We included a cross-section of 58 adolescents (28 boys and 30 girls) aged 13.6 ± 4.0 years with T1D ≥1 year attending a well-established pediatric diabetes clinic in Thailand. Median diabetes duration was 4.1 years (range 1–18 years). Participants were divided into 2 subgroups according to their average HbA1c level over the past year. Those with good control (HbA1c <8%) (n = 13) were compared with those with poor control (HbA1c ≥8%) (n = 45). Data collected from self-report standardized questionnaires and medical records were used to compare variables between groups.

Results

Adolescents with good control used significantly less daily insulin and had higher family income, higher scores for family support, and quality of life (QoL) than those in the group with poor control (P < 0.05). Age, sex, puberty, duration of diabetes, insulin regimen, frequency of blood glucose monitoring, and self-report adherence did not differ between groups. By univariate logistic regression, the only factor associated significantly with poor glycemic control was a QoL score <25.

Conclusion

Adolescents with T1D may be at a higher risk of poor glycemic control if they have poor QoL, impaired family functioning, poor coping skills, and lower socioeconomic status, suggesting that psychosocial interventions could potentially improve glycemic control in this population.

Open access