A novel indole derivative, 2-{3-[1-(benzylsulfonyl)piperidin-4-yl]-2-methyl-1H-indol-1-yl}-1-(pyrrolidin-1-yl)ethenone, suppresses hedgehog signaling and drug-resistant tumor growth.

The Hedgehog (Hh) signaling pathway plays important roles in various physiological functions. Several malignancies, such as basal cell carcinoma (BCC) and medulloblastoma (MB), have been linked to the aberrant activation of Hh signaling. Although therapeutic drugs have been developed to inhibit Hh pathway-dependent cancer growth, drug resistance remains a major obstacle in cancer treatment. Here, we show that the newly identified, 2-{3-[1-(benzylsulfonyl)-1,2,3,6-tetrahydropyridin-4-yl]-2-methyl-1H-indol-1-yl}-1-(pyrrolidin-1-yl)ethenone analog (LKD1214) exhibits comparable potency to vismodegib in suppressing the Hh pathway activation. LKD1214 represses Smoothened (SMO) activity by blocking its ciliary translocation. Interestingly, we also identified that it has a distinctive binding interface with SMO compared with other SMO-regulating chemicals. Notably, it maintains an inhibitory activity against the SmoD477H mutant, as observed in a patient with vismodegib-resistant BCC. Furthermore, LKD1214 inhibits tumor growth in the mouse model of MB. Collectively, these findings suggest that LKD1214 has the therapeutic potential to overcome drug-resistance in Hh-dependent cancers.

BMI trajectory and inflammatory effects on metabolic syndrome in adolescents.

BACKGROUND: Various life course factors can affect susceptibility to diseases during adolescence and adulthood, and those relationships are complex. However, few studies have assessed the potential mediating factors. Therefore, we assessed the mediating effects of factors related to growth and inflammation between perinatal factors and metabolic syndrome risk during adolescence. METHODS: The study was conducted on adolescents who participated in the follow-up in the Ewha Birth and Growth Cohort. We considered the ponderal index (PI) as a perinatal factor and the continuous metabolic syndrome score (cMetS) as the outcome and confirmed the mediating effects of body mass index (BMI) trajectory pattern in childhood and inflammation levels by using the PROCESS macro for SAS. RESULTS: Although the direct effect of BMI trajectory on the relationship between PI and cMetS was not significant (0.545), the indirect effect was significant (1.044). In addition, the indirect effect was statistically significant in the pathways mediating the BMI trajectory pattern and inflammation (ß = 1.456). CONCLUSIONS: The direct and indirect effects on the relationship between PI and cMetS suggest that childhood factors related to growth may be involved in disease susceptibility. Therefore, appropriate interventions for the management of obesity during the growth phase are necessary. IMPACT: Unlike other existing studies, this study assessed multiple mediating effects by considering the BMI trajectory pattern and inflammatory indexes as mediating factors between the ponderal index and the continuous metabolic syndrome score during adolescence. We found significant indirect effects of the BMI trajectory between PI and cMetS, and also significant indirect effects in the pathways mediating the BMI trajectory and hs-CRP. The significant indirect mediating effects support that childhood factors related to growth may be involved in disease susceptibility.

Impact of community health interventions on maternal and child health indicators in the upper east region of Ghana.

BACKGROUND: This paper reports on results of a health system strengthening implementation research initiative conducted the Upper East Region of northern Ghana. Transformative interventions to accelerate and strengthen the health delivery were implemented that included empowering community leaders and members to actively participate in health delivery, strengthening the referral systems through the provision of community transport systems, providing basic medical equipment to community clinics, and improving the skills of critical health staff through training. METHODS: A mixed method design was used to evaluate the impact of the interventions. A quantitative evaluation employed a flexible research design to test the effects of various component activities of the project. To assess impact, a pre-versus-post randomized cluster survey design was used. Qualitative research was conducted with focus group data and individual in depth interviews to gauge the views of various stakeholders associated with the implementation process. RESULTS: After intervention, significant improvements in key maternal and child health indicators such as antenatal and postnatal care coverage were observed and increases in the proportion of deliveries occurring in health facilities and assisted by skilled health personnel relative to pre-intervention conditions. There was also increased uptake of oral rehydration salts (ORS) for treatment of childhood diarrhoea, as well as marked reductions in the incidence of upper respiratory infections (URI). CONCLUSIONS: A pre-and post-evaluation of impact suggests that the programme had a strong positive impact on the functioning of primary health care. Findings are consistent with the proposition that the coverage and content of the Ghana Community-based Health Planning and Services programme was improved by program interventions and induced discernable changes in key indicators of health system performance.

Factors predicting different times for brushing teeth during the day: multilevel analyses.

BACKGROUND: The most effective and simple intervention for preventing oral disease is toothbrushing. However, there is substantial variation in the timing of brushing teeth during the day. We aimed to identify a comprehensive set of predictors of toothbrushing after lunch and after dinner and estimated contextual (i.e., geographic) variation in brushing behavior at different times of the day. METHODS: We constructed a conceptual framework for toothbrushing by reviewing health behavior models. The main data source was the 2017 Community Health Survey. We performed a four-level random intercept logistic regression to predict toothbrushing behavior. (individual, household, Gi/Gun/Gu, and Si/Do). RESULTS: Individuals under 30 years of age had higher likelihood of brushing after lunch, while brushing after dinner was higher among those aged 40-79 years. People engaged in service/sales, agriculture/fishing/labor/mechanics, as well as student/housewife/unemployed were 0.60, 0.41, and 0.49 times less likely to brush their teeth after lunch, respectively, compared to those working in the office, but the gap narrowed to 0.97, 0.96, 0.94 for brushing after dinner. We also found significant area-level variations in the timing of brushing. CONCLUSIONS: Different patterns in association with various factors at individual-, household- and Si/Gun/Gu-levels with toothbrushing after lunch versus toothbrushing after dinner suggests a need for tailored interventions to improve toothbrushing behavior depending on the time of day.

Geographic variation in caesarean delivery in India.

BACKGROUND: The rate of caesarean delivery has increased markedly both globally and within India. However, there is considerable variation within countries. No previous studies have examined the relative importance of multiple geographic levels in shaping the distribution of caesarean delivery and to what extent they can be explained by individual-level risk factors. OBJECTIVES: To describe geographic variation in caesarean delivery and quantify the contribution of individual-level risk factors to the variation in India. METHODS: We conducted four-level logistic regression analysis to partition total variation in caesarean delivery to three geographic levels (states, districts and communities) and quantify the extent to which variance at each level was explained by a set of 20 sociodemographic, medical and institutional risk factors. Stratified analyses were conducted by the type of delivery facility (public/private). RESULTS: Overall prevalence of caesarean delivery was 19.3% in India in 2016. Most geographic variation was attributable to states (44%), followed by communities (32%), and lastly districts (24%). Adjustment for all risk factors explained 44%, 52% and 46% of variance for states, districts and communities, respectively. The proportion explained by individual risk factors was larger in public facilities than in private facilities at all three levels. A substantial proportion of between-population variation still existed even after clustering of individual risk factors was comprehensively adjusted for. CONCLUSIONS: Diverse contextual factors driving high or low rate of caesarean delivery at each geographic level should be explored in future studies so that tailored intervention can be implemented to reduce the overall variation in caesarean delivery.

Machine Learning Based Prediction Model for Closed-Loop Small Bowel Obstruction Using Computed Tomography and Clinical Findings.

PURPOSE: The aim of the study was to develop a prediction model for closed-loop small bowel obstruction integrating computed tomography (CT) and clinical findings. METHODS: The radiology database and surgical reports from 2 suburban teaching hospitals were retrospectively reviewed for patients undergoing surgery for suspected closed-loop small bowel obstruction (CLSBO). Two observers independently reviewed the CT scans for the presence of imaging features of CLSBO, blinded to the surgically confirmed diagnosis and clinical parameters. Random forest analysis was used to train and validate a prediction model for CLSBO, by combining CT and clinical findings, after randomly splitting the sample into 80% training and 20% test subsets. RESULTS: Surgery confirmed CLSBO in 185 of 223 patients with clinically suspected CLSBO. Age greater than 52 years showed 2.82 (95% confidence interval = 1.13-4.77) times higher risk for CLSBO (P = 0.021). Sensitivity/specificity of CT findings included proximal dilatation (97/5%), distal collapse (96/2%), mesenteric edema (94/5%), pneumatosis (1/100%), free air (1/98%), and portal venous gas (0/100%). The random forest model combining imaging/clinical findings yielded an area under receiver operating curve of 0.73 (95% confidence interval = 0.58-0.94), sensitivity of 0.72 (0.55-0.85), specificity of 0.8 (0.28-0.99), and accuracy of 0.73 (0.57-0.85). Prior surgery, age, lactate, whirl sign, U/C-shaped bowel configuration, and fecalization were the most important variables in predicting CLSBO. CONCLUSIONS: A random forest model found clinical factors including prior surgery, age, lactate, and imaging factors including whirl sign, fecalization, and U/C-shaped bowel configuration are helpful in improving the prediction of CLSBO. Individual CT findings in CLSBO had either high sensitivity or specificity, suggesting that accurate diagnosis requires systematic assessment of all CT signs.

Mutually constructive roles of Ail and LPS in Yersinia pestis serum survival.

The outer membrane is a key virulence determinant of gram-negative bacteria. In Yersinia pestis, the deadly agent that causes plague, the protein Ail and lipopolysaccharide (LPS)6 enhance lethality by promoting resistance to human innate immunity and antibiotics, enabling bacteria to proliferate in the human host. Their functions are highly coordinated. Here we describe how they cooperate to promote pathogenesis. Using a multidisciplinary approach, we identify mutually constructive interactions between Ail and LPS that produce an extended conformation of Ail at the membrane surface, cause thickening and rigidification of the LPS membrane, and collectively promote Y. pestis survival in human serum, antibiotic resistance, and cell envelope integrity. The results highlight the importance of the Ail-LPS assembly as an organized whole, rather than its individual components, and provide a handle for targeting Y. pestis pathogenesis.

CHARMM-GUI Supports Hydrogen Mass Repartitioning and Different Protonation States of Phosphates in Lipopolysaccharides.

Hydrogen mass repartitioning (HMR) that permits time steps of all-atom molecular dynamics simulation up to 4 fs by increasing the mass of hydrogen atoms has been used in protein and phospholipid bilayers simulations to improve conformational sampling. Molecular simulation input generation via CHARMM-GUI now supports HMR for diverse simulation programs. In addition, considering ambiguous pH at the bacterial outer membrane surface, different protonation states, either -2e or -1e, of phosphate groups in lipopolysaccharides (LPS) are also supported in CHARMM-GUI LPS Modeler. To examine the robustness of HMR and the influence of protonation states of phosphate groups on LPS bilayer properties, eight different LPS-type all-atom systems with two phosphate protonation states are modeled and simulated utilizing both OpenMM 2-fs (standard) and 4-fs (HMR) schemes. Consistency in the conformational space sampled by standard and HMR simulations shows the reliability of HMR even in LPS, one of the most complex biomolecules. For systems with different protonation states, similar conformations are sampled with a PO41- or PO42- group, but different phosphate protonation states make slight impacts on lipid packing and conformational properties of LPS acyl chains. Systems with PO41- have a slightly smaller area per lipid and thus slightly more ordered lipid A acyl chains compared to those with PO42-, due to more electrostatic repulsion between PO42- even with neutralizing Ca2+ ions. HMR and different protonation states of phosphates of LPS available in CHARMM-GUI are expected to be useful for further investigations of biological systems of diverse origin.

Thromboembolic complications of COVID-19.

The symptomology of patients afflicted with novel 2019 coronavirus disease (SARS-CoV-2 or COVID-19) has varied greatly, ranging from the asymptomatic state to debilitating hypoxemic respiratory failure caused by severe atypical viral pneumonia. Patients may also develop a hyper-inflammatory state that can lead to multi-organ failure. It has become increasingly apparent that, as part of the hyper-inflammatory state, COVID-19 infection increases susceptibility to systemic thromboembolic complications that can contribute to rapid clinical deterioration or demise. This article aims to review imaging features of various systemic thrombotic complications in six patients with moderate to severe disease. This case series includes examples of pulmonary embolism, stroke, right ventricular thrombosis, renal vein thrombosis, and aortic thrombosis with leg ischemia.

Role of Dendritic Cell in Diabetic Nephropathy.

Diabetic nephropathy (DN) is one of the most significant microvascular complications in diabetic patients. DN is the leading cause of end-stage renal disease, accounting for approximately 50% of incident cases. The current treatment options, such as optimal control of hyperglycemia and elevated blood pressure, are insufficient to prevent its progression. DN has been considered as a nonimmune, metabolic, or hemodynamic glomerular disease initiated by hyperglycemia. However, recent studies suggest that DN is an inflammatory disease, and immune cells related with innate and adaptive immunity, such as macrophage and T cells, might be involved in its development and progression. Although it has been revealed that kidney dendritic cells (DCs) accumulation in the renal tissue of human and animal models of DN require activated T cells in the kidney disease, little is known about the function of DCs in DN. In this review, we describe kidney DCs and their subsets, and the role in the pathogenesis of DN. We also suggest how to improve the kidney outcomes by modulating kidney DCs optimally in the patients with DN.

Changes in socio-economic patterns of energy consumption and insufficient energy intake across India from 1993-94 to 2011-12.

OBJECTIVE: To assess whether disparities in energy consumption and insufficient energy intake in India have changed over time across socio-economic status (SES). DESIGN: This cross-sectional, population-based survey study examines the relationship between several SES indicators (i.e. wealth, education, caste, occupation) and energy consumption in India at two time points almost 20 years apart. Household food intake in the last 30 d was assessed in 1993-94 and in 2011-12. Average dietary energy intake per person in the household (e.g. kilocalories) and whether the household consumed less than 80 % of the recommended energy intake (i.e. insufficient energy intake) were calculated. Linear and relative risk regression models were used to estimate the relationship between SES and average energy consumed per day per person and the relative risk of consuming an insufficient amount of energy. SETTING: Rural and urban areas across India. PARTICIPANTS: A nationally representative sample of households. RESULTS: Among rural households, there was a positive association between SES and energy intake across all four SES indicators during both survey years. Similar results were seen for energy insufficiency vis-à-vis recommended energy intake levels. Among urban households, wealth was associated with energy intake and insufficiency at both time points, but there was no educational patterning of energy insufficiency in 2011-12. CONCLUSIONS: Results suggest little overall change in the SES patterning of energy consumption and percentage of households with insufficient energy intake from 1993-94 to 2011-12 in India. Policies in India need to improve energy intake among low-SES households, particularly in rural areas.

Association of community level social trust and reciprocity with mortality: a retrospective cohort study.

BACKGROUND: Whether community level social capital is associated with mortality within an Asian population is yet unclear. METHODS: The study population was derived from the Korean National Health Insurance Service-National Sample Cohort. A total of 636,055 participants were followed-up during 2012-2013 for deaths from all causes, cardiovascular disease (CVD), cancer, and other causes. Community level social trust and reciprocity at the administrative district level were derived from the Korean Community Health Survey. Cox proportional hazards regression was used to determine the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for mortality according to levels of community level social trust and reciprocity. RESULTS: Compared to participants who reside in areas within the lower half of community level social trust, those who reside in areas within the upper half had lower risk of death from all causes (aHR 0.84, 95% CI 0.78-0.89), CVD (aHR 0.82, 95% CI 0.67-0.99), and cancer (aHR 0.85, 95% CI 0.73-0.98). Similarly, residing in areas in the upper half of community level social reciprocity was associated with reduced risk for all-cause mortality (aHR 0.80, 95% CI 0.75-0.86). The protective association of high community level social trust and reciprocity on mortality remained after additional adjustments for smoking, alcohol intake, and physical activity. CONCLUSIONS: Residing in areas with high community level social trust and reciprocity may be associated with better population health status.

Maternal, neonatal, and child health systems under rapid urbanization: a qualitative study in a suburban district in Vietnam.

BACKGROUND: Vietnam has been successful in increasing access to maternal, neonatal, and child health (MNCH) services during last decades; however, little is known about whether the primary MNCH service utilization has been properly utilized under the recent rapid urbanization. We aimed to examine current MNCH service utilization patterns at a district level. METHODS: The study was conducted qualitatively in a rural district named Quoc Oai. Women who gave a birth within a year and medical staff at various levels participated through 43 individual in-depth interviews and 3 focus group interviews. RESULTS: Primary MNCH services were underutilized due to a failure to meet increased quality needs. Most of the mothers preferred private clinics for antenatal care and the district hospital for delivery due to the better service quality of these facilities compared to that of the commune health stations (CHSs). Mothers had few sociocultural barriers to acquiring service information or utilizing services based on their improved standard of living. A financial burden for some services, including caesarian section, still existed for uninsured mothers, while their insured counterparts had relatively few difficulties. CONCLUSIONS: For the improved macro-efficiency of MNCH systems, the government needs to rearrange human resources and/or merge some CHSs to achieve economies of scale and align with service volume distribution across the different levels.

Is there a female disadvantage in child undernutrition in South India?: Exploring gender differences in height in infancy, childhood, and adolescence in Andhra Pradesh and Telangana.

OBJECTIVE: The aim of this study was to investigate whether gender-based disparities in health and well-being extend to a female disadvantage in height in infancy, childhood, and adolescence in Andhra Pradesh and Telangana. METHODS: Using longitudinal data from the Young Lives study in Andhra Pradesh and Telangana, India, linear mixed effects and linear regression models examined associations between gender and height and the modifying influences of birth order and older siblings' gender composition. RESULTS: In the younger cohort, at 6-18 months, girls were 0.17-SDs of height for age z-scores (HAZ) taller than boys (P = .01). In the same cohort, the girls' advantage in HAZ was attenuated to 0.02 (P = .58) by 11-12 years. In the older cohort, the difference in HAZ between girls and boys was 0.04 (P = .61) at the beginning of the study when they were 7-8 years old; by 18-19 years of age, the difference had switched, with boys being 0.22-SD (P = .05) taller. There was no difference by birth order except in the younger cohort in which children with 2 or more siblings experienced height deficits compared with only children at 7-8 and 11-12 years. There was no differential effect of gender by birth order nor by the gender composition of siblings. CONCLUSION: A female disadvantage in undernutrition, as manifest in differences between girls and boys in HAZ, did not appear until later ages. Identifying how and why gendered disparities in standardized height emerge in late adolescence will help target more resources to improve conditions for girls and women in south India.

Use of high-level health facilities and catastrophic expenditure in Vietnam: can health insurance moderate this relationship?

BACKGROUND: Overcrowding of high-level health facilities is a major concern in a Vietnamese health system. This may increase an economic burden to the households since health insurance is still insufficient in providing financial risk protection. This paper sought to examine the association between the use of high-level health facilities and household-level expenditure status such as out-of-pocket (OOP), and catastrophic expenditure on health, as well as a moderating effect of health insurances in rural and urban districts of Vietnam. METHODS: Data utilized a health system community survey collected between 2015 and 2017 in two districts of Vietnam (one from rural area in northern part, and the other one from urban area in sourthern part). The world Health Organization's definition of catastrophic expenditure was used. Multivariate tobit and logistic regression were employed for catastrophic expenditure and OOP respectively. Interaction term between health insurance status and visit frequency in high-level facilities was included to investigate the moderating effect of health insurance. RESULTS: Health insurance status was associated with neither OOP health expenditure nor catastrophic expenditure occurrence, whereas visit frequency of high-level health facilities was strongly associated with both outcomes in both districts(e.g., for catastrophic expenditure, ORs are 1.77 and 1.30 in northern and southern district respecitvely. P values are < 0.001). Significant interaction between health insurance status and use of high-level facilities on catastrophic expenditure occurrence was found in Quoc Oai district (OR = 0.68, p < 0.05). CONCLUSIONS: The present study demonstrated negative financial impact of utilizing high-level facility on household financial status and weak role of health insurance in decreasing this impact. Multi-faceted approach is called for to mitigate the patient's financial burden.

Study Design for the 2016 Baseline Survey of a Health System Strengthening Project in Quoc Oai District, Hanoi, Vietnam.

BACKGROUND: In order to provide essential scientific evidence on the population's health status and social health determinants as well as the current capacity of the health care system in Vietnam to health policy makers and managers, Vietnam Ministry of Health, Hanoi University of Public Health, Hanoi Medical University, and Ho Chi Minh University of Medicine and Pharmacy collaborated with Seoul National University (Korea) and conducted a health system survey in the Quoc Oai district (of Hanoi capital) that represented northern rural Vietnam. METHODS: The study design was a cross-sectional study. The survey covered different topics (more than 200 questions) and was administered in three separate questionnaires: 1) Basic information of all household members; 2) Household characteristics; and 3) Individual characteristics. Socio-demographic characteristics among the households and individuals were collected from 2,400 households sampled by multi-stage cluster sampling method: more than 200 questions. RESULTS: The household size of Quoc Oai was larger than the national average and there was no significant difference in gender composition. In addition, the proportions of pre-elderly, age 55-64, and elderly group (65 years old and over) were higher than the national population statistics. In this context, demographic transition has begun in Quoc Oai. CONCLUSION: This study design description provides the basic information about a baseline survey of a future prospective cohort (as a part of a collaborative project on strengthening the health system in Vietnam) to the prospective data user of this survey.

Influence of clozapine on neurodevelopmental protein expression and behavioral patterns in animal model of psychiatric disorder induced by low-level of lead.

Exposure to lead during pregnancy is a risk factor for the development of psychiatric disorders in the offspring. In this study, we investigated whether exposure to low levels of lead acetate (0.2%) in drinking water during pregnancy and lactation causes behavioral impairment and affects the expression of proteins associated with neurodevelopment. Lead exposure altered several parameters in rat offspring compared with those unexposed in open-field, social interaction, and pre-pulse inhibition tests. These parameters were restored to normal levels after clozapine treatment. Western blot and immunohistochemical analyses of the hippocampus revealed that several neurodevelopmental proteins were downregulated in lead-exposed rats. The expression was normalized after clozapine treatment (5 mg/kg/day, postnatal day 35-56). These findings demonstrate that downregulation of several proteins in lead-exposed rats affected subsequent behavioral changes. Our results suggest that lead exposure in early life may induce psychiatric disorders and treatment with antipsychotics such as clozapine may reduce their incidence.

Ixeris dentata Extract Increases Salivary Secretion through the Regulation of Endoplasmic Reticulum Stress in a Diabetes-Induced Xerostomia Rat Model.

This study aimed to investigate the molecular mechanism of diabetes mellitus (DM)-induced dry mouth and an application of natural products from Ixeris dentata (IXD), a recently suggested regulator of amylase secretion in salivary cells. Vehicle-treated or diabetic rats were orally treated with either water or an IXD extract for 10 days to observe the effect on salivary flow. We found that the IXD extract increased aquaporin 5 (AQP5) and alpha-amylase protein expression in the submandibular gland along with salivary flow rate. Similarly, the IXD extract and its purified compound increased amylase secretion in high glucose-exposed human salivary gland cells. Furthermore, increased endoplasmic reticulum stress response in the submandibular gland of diabetic rats was inhibited by treatment with the IXD extract, suggesting that IXD extract treatment improves the ER environment by increasing the protein folding capacity. Thus, pharmacological treatment with the IXD extract is suggested to relieve DM-induced dry mouth symptoms.

Bringing Cancer Prevention Research Competencies to the Classroom.

The field of cancer prevention incorporates research all along the spectrum from basic science studies at the laboratory bench to epidemiology, behavioral sciences, and clinical studies, with the convergence of evidence from these different approaches aimed at implementing public health interventions that reduce the burden of this disease. Due to the necessity of multiple disciplines interacting in order to achieve a public health outcome, traditional discipline-specific training may not be adequately preparing the cancer prevention research workforce. We propose that cancer prevention researchers establish defined professional competencies which will allow them to shape the future directions of the field as well as to collaborate effectively in multidisciplinary teams, disseminate new findings beyond their own scientific circles, and advocate for their implementation for the public good. We previously proposed that these core competencies focus on knowledge of issues in other research fields, interdisciplinary communication, and leadership/teamwork. Here, we describe the reorganization of an existing course to incorporate activities deliberately designed to foster these competencies. We provide details about the course structure, student feedback, and ideas for future versions of this course. We hope this framework will be useful to others who are engaged in the collective effort to develop leaders in the field of cancer prevention research.

Effects of Adrenal Androgen Levels on Bone Age Advancement in Prepubertal Children: Using the Ewha Birth and Growth Cohort Study.

Bone age (BA) advancement in prepubertal children may be associated with earlier onset of puberty and obesity. This study aimed to define the effects of adrenal androgen levels on the advancement of BA in prepubertal children, independent of obesity. During July and August 2011, we examined BA in 200 prepubertal children aged 7-9 years who were part of the Ewha Birth & Growth Cohort Study. BA was assessed by the Greulich-Pyle method. An index of BA advancement was calculated as the ratio of BA to chronological age (CA) (BA/CA), and this ratio was classified into 3 tertiles. We analyzed the relationship between BA advancement and anthropometric characteristics and adrenal hormone levels. The number of overweight children increased from the first group to the third group (P(Trend) = 0.03). The levels of adrenal androgens showed a significant positive correlation with the tertile groups after adjusting for age and sex (testosterone: r = 0.26, P < 0.001; dehydroepiandrosterone: r = 0.21, P < 0.001; androstenedione: r = 0.20, P < 0.001). Further, after controlling for body mass index (BMI), sex, and age, the BA/CA was found to be positively correlated with androstenedione (ß = 0.04, R² = 3.7%) and testosterone levels (ß = 0.05, R² = 4.7%). Based on our results, it is suggested that adrenal androgen levels are associated with BA advancement independent of BMI.