Objectives: One of the most widely used pesticides today is chlorpyrifos (CPF). Cytochrome P450 (CYP)2B6, the most prominent catalyst in CPF bioactivation, is highly polymorphic. The objective of our study was to evaluate the role of CYP2B6*6, which contains both 516G>T and 785A>G polymorphisms, in CPF toxicity, as represented by the concentration of 3,5,6-trichloro-2-pyridinol (TCPy), among vegetable farmers in Central Java, Indonesia, where CPF has been commonly used. Methods: A cross-sectional study was conducted among 132 vegetable farmers. Individual socio-demographic and occupational characteristics, as determinants of TCPy levels, were obtained using a structured interviewer-administered questionnaire and subsequently used to estimate the cumulative exposure level (CEL). TCPy levels were detected with liquid chromatography-mass spectrometry. CYP2B6*6 gene polymorphisms were analyzed using a TaqMan® SNP Genotyping Assay and Sanger sequencing. Linear regression analysis was performed to analyze the association between TCPy, as a biomarker of CPF exposure, and its determinants. Results: The prevalence of CYP2B6*6 polymorphisms was 31% for *1/*1, 51% for *1/*6, and 18% for *6/*6. TCPy concentrations were higher among participants with CYP2B6*1/*1 than among those with *1/*6 or *6/*6 genotypes. CYP2B6*6 gene polymorphisms, smoking, CEL, body mass index, and spraying time were retained in the final linear regression model as determinants of TCPy. Conclusions The results suggest that CYP2B6*6 gene polymorphisms may play an important role in influencing susceptibility to CPF exposure. CYP2B6*6 gene polymorphisms together with CEL, smoking habits, body mass index, and spraying time were the determinants of urinary TCPy concentrations, as a biomarker of CPF toxicity.

Objective: This study aims to identify predictors of 72-hour mortality in patients with diabetic ketoacidosis (DKA). Methodology: In this retrospective cohort study, data were obtained from medical records of adult patients with DKA in Cipto Mangunkusumo General Hospital from January 2011 to June 2017. Associations of predictors (age, type of diabetes, history of DKA, comorbidities, level of consciousness, renal function, bicarbonate, potassium, lactate, betahydroxybutyrate levels, and anion gap status) and 72-hour mortality were analyzed. The mortality prediction model was formulated by dividing the coefficient B by the standard error for all variables with p<0.05 in the multivariate analysis. Results: Eighty-six of 301 patients did not survive 72 hours after hospital admission. Comorbidities (HR 2.407; 95% CI 1.181–4.907), level of consciousness (HR 10.345; 95% CI 4.860–22.019), history of DKA (HR 2.126; 95% CI 1.308–3.457), and lactate level (HR 5.585; 95% CI 2.966–10.519) were significant predictors from multivariate analysis and were submitted to the prediction model. The prediction model had good performance. Patients with total score less than 3 points were at 15.41 % risk of mortality, 3 – 4 points were 78.01% and 5 – 6 points were 98.22% risk of mortality. Conclusion The 72-hour mortality rate in Cipto Mangunkusumo General Hospital was 28.57%. The mortality prediction model had a good performance and consisted of comorbidities, history of DKA, level of consciousness and lactate level.
Mortality ; Diabetic Ketoacidosis

Untreated thyroid dysfunction during pregnancy increases morbidity in the mother and fetus. Anti-thyroid medication is the first-line therapy for hyperthyroidism during pregnancy. The diagnosis of thyroid dysfunction in pregnancy is complicated because of seemingly insignificant and non-specific symptoms which overlap with normal changes during pregnancy. Early detection and management should be done to prevent maternal and fetal complications.
Thyroid Gland ; Pregnancy ; Practice Guideline ; Indonesia

Objective: The objective of our study was to determine the genotype frequencies of CYP2C19*2 and *3 gene polymorphisms among Javanese farmers exposed to chlorpyrifos (CPF) in Central Java, Indonesia. Methods: This cross-sectional study was conducted from July to October 2020 in Central Java, Indonesia, involving 151 vegetable farmers aged 18-65 years who used CPF for at least one year. CYP2C19*2 and *3 gene polymorphisms were analyzed using PCR-RFLP. Direct calculations were applied to calculate allele and genotype frequencies. The difference in genotype frequencies among the sex and cumulative exposure level (CEL) group was performed using the Chi-square test. In contrast, the proportion difference of allele frequencies was analyzed using Z-test. Results: The frequency of CYP2C19 genotypes *1/*1, *1/*3, *1/*2, and *2/*2 were 64 %, 7 %, 23 % and 6 %. We observed no significant difference in the genotype distribution according to sex group and CEL group. Conclusion In summary, the prevalence of toxicologically relevant CYP2C19 polymorphisms was determined in the Javanese agricultural population. The CYP2C19 genotype may be helpful as an essential biomarker of genetic susceptibility towards CPF exposure. Nevertheless, further studies to confirm the role of CYP2C19 in this context are still needed.
Cytochrome P-450 CYP2C19 ; Pesticides