Automated Comprehensive CT Assessment of the Risk of Diabetes and Associated Cardiometabolic Conditions.

Background CT performed for various clinical indications has the potential to predict cardiometabolic diseases. However, the predictive ability of individual CT parameters remains underexplored. Purpose To evaluate the ability of automated CT-derived markers to predict diabetes and associated cardiometabolic comorbidities. Materials and Methods This retrospective study included Korean adults (age ≥ 25 years) who underwent health screening with fluorine 18 fluorodeoxyglucose PET/CT between January 2012 and December 2015. Fully automated CT markers included visceral and subcutaneous fat, muscle, bone density, liver fat, all normalized to height (in meters squared), and aortic calcification. Predictive performance was assessed with area under the receiver operating characteristic curve (AUC) and Harrell C-index in the cross-sectional and survival analyses, respectively. Results The cross-sectional and cohort analyses included 32166 (mean age, 45 years ± 6 [SD], 28833 men) and 27 298 adults (mean age, 44 years ± 5 [SD], 24 820 men), respectively. Diabetes prevalence and incidence was 6% at baseline and 9% during the 7.3-year median follow-up, respectively. Visceral fat index showed the highest predictive performance for prevalent and incident diabetes, yielding AUC of 0.70 (95% CI: 0.68, 0.71) for men and 0.82 (95% CI: 0.78, 0.85) for women and C-index of 0.68 (95% CI: 0.67, 0.69) for men and 0.82 (95% CI: 0.77, 0.86) for women, respectively. Combining visceral fat, muscle area, liver fat fraction, and aortic calcification improved predictive performance, yielding C-indexes of 0.69 (95% CI: 0.68, 0.71) for men and 0.83 (95% CI: 0.78, 0.87) for women. The AUC for visceral fat index in identifying metabolic syndrome was 0.81 (95% CI: 0.80, 0.81) for men and 0.90 (95% CI: 0.88, 0.91) for women. CT-derived markers also identified US-diagnosed fatty liver, coronary artery calcium scores greater than 100, sarcopenia, and osteoporosis, with AUCs ranging from 0.80 to 0.95. Conclusion Automated multiorgan CT analysis identified individuals at high risk of diabetes and other cardiometabolic comorbidities. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Pickhardt in this issue.

Metabolic-associated fatty liver disease is associated with colorectal adenomas in young and older Korean adults.

BACKGROUND AND AIMS: Given that the majority of colorectal cancers (CRCs) develop from high-risk adenomas, identifying risk factors for high-risk adenomas is important. The relationship between metabolic dysfunction-associated fatty liver disease (MAFLD) and the risk of colorectal adenoma in young adults remains unclear. We aimed to evaluate this relationship in adults <50 (younger) and ≥50 (older) years of age. METHODS: This cross-sectional study included 184 792 Korean adults (80% <50 years of age) who all underwent liver ultrasound and colonoscopy. Participants were grouped into those with and without MAFLD and classified by adenoma presence into no adenoma, low-risk adenoma, or high-risk adenoma (defined as ≥3 adenomas, any ≥10 mm, or adenoma with high-grade dysplasia/villous features). RESULTS: The prevalence of low- and high-risk adenomas among young and older adults was 9.6% and 0.8% and 22.3% and 4.8%, respectively. MAFLD was associated with an increased prevalence of low- and high-risk adenomas in young and older adults. Young adults with MAFLD had a 1.30 (95% CIs 1.26-1.35) and 1.40 (1.23-1.59) times higher prevalence of low- and high-risk adenomas, respectively, compared to those without MAFLD. These associations were consistent even in lean adults (BMI < 23 kg/m2 ) and those without a family history of CRC. CONCLUSIONS: MAFLD is associated with an increased prevalence of low- and high-risk adenomas in Korean adults, regardless of age or obesity status. Whether reducing metabolic risk factors, such as MAFLD, reduces the risk of precancerous lesions and ultimately reduces the risk of early-onset CRC requires further investigation.

Development and Evaluation of Self-Microemulsifying Drug Delivery System for Improving Oral Absorption of Poorly Water-Soluble Olaparib.

The purpose of this study is to develop and evaluate a self-microemulsifying drug delivery system (SMEDDS) to improve the oral absorption of poorly water-soluble olaparib. Through the solubility test of olaparib in various oils, surfactants and co-surfactants, pharmaceutical excipients were selected. Self-emulsifying regions were identified by mixing the selected materials at various ratios, and a pseudoternary phase diagram was constructed by synthesizing these results. The various physicochemical properties of microemulsion incorporating olaparib were confirmed by investigating the morphology, particle size, zeta potential, drug content and stability. In addition, the improved dissolution and absorption of olaparib were also confirmed through a dissolution test and a pharmacokinetic study. An optimal microemulsion was generated in the formulation of Capmul® MCM 10%, Labrasol® 80% and PEG 400 10%. The fabricated microemulsions were well-dispersed in aqueous solutions, and it was also confirmed that they were maintained well without any problems of physical or chemical stability. The dissolution profiles of olaparib were significantly improved compared to the value of powder. Associated with the high dissolutions of olaparib, the pharmacokinetic parameters were also greatly improved. Taken together with the results mentioned above, the microemulsion could be an effective tool as a formulation for olaparib and other similar drugs.

Association of changes in sleep duration and quality with incidence of depression: A cohort study.

BACKGROUND: The longitudinal relationship between sleep duration, sleep quality, and their changes with the risk of depressive symptoms is unclear. We examined the association between sleep duration, sleep quality, and their changes with incident depressive symptoms. METHODS: A total of 225,915 Korean adults without depression at baseline with a mean age of 38.5 years were followed for an average of 4.0 years. Sleep duration and quality were assessed using the Pittsburgh Sleep Quality Index. The presence of depressive symptoms was assessed using the Center for Epidemiologic Studies Depression scale. Flexible parametric proportional hazard models were used to determine hazard ratios (HRs) and 95 % confidence intervals (CIs). RESULTS: In total, 30,104 participants with incident depressive symptoms were identified. Multivariable-adjusted HRs (95 % CIs) for incident depression comparing sleep durations of ≤5, 6, 8, and ≥9 h with 7 h were 1.15 (1.11-1.20), 1.06 (1.03-1.09), 0.99 (0.95-1.03), and 1.06 (0.98-1.14), respectively. A similar trend was observed in patients with poor sleep quality. Compared with participants with persistently good sleep quality, participants with persistently poor sleep quality or who developed poor sleep quality were associated with the risk of incident depressive symptoms [HRs (95 % CIs) of 2.13 (2.01-2.25) and 1.67 (1.58-1.77), respectively]. LIMITATIONS: Sleep duration was assessed using self-reported questionnaire and the study population may not reflect general population. CONCLUSIONS: Sleep duration, sleep quality and their changes were independently associated with incident depressive symptoms in young adults, suggesting that inadequate sleep quantity and quality play a role in depression risk.

Persistence or regression of prediabetes and coronary artery calcification among adults without diabetes.

OBJECTIVE: The effect of changes in glycemic status on subclinical atherosclerosis is uncertain. We assessed the association of persistence, regression, or progression of prediabetes with coronary artery calcium score (CACS) as a measure of subclinical atherosclerosis. DESIGN: A cross-sectional study, comprising 126 765 adults, and longitudinal sub-study, comprising 40 622 adults (with baseline and at least 1 follow-up computed tomography scan to assess changes in CACS), were undertaken. METHODS: Changes in glycemic status over 1.5 years (interquartile range, 1.0-2.0) before the first CACS assessment were categorized according to 6 groups: persistent normoglycemia (reference), normoglycemia to prediabetes, normoglycemia to diabetes, prediabetes to normoglycemia, persistent prediabetes, and prediabetes to diabetes. Logistic regression was used to calculate the odds ratios (ORs) and 95% CIs for prevalent coronary artery calcification (CAC). Mixed models with random intercepts and random slopes were used to estimate 5-year CAC progression rates. RESULTS: Mean (SD) age was 41.3 (7.0) years (74.7% male) (n = 126 765). Multivariable-adjusted OR for prevalent CAC was 1.13 (95% CI, 1.08-1.18) for persistent prediabetes, 1.05 (0.98-1.12) for regression to normoglycemia, and 1.46 (95% CI, 1.27-1.67) for progression from prediabetes to diabetes, compared with persistent normoglycemia. Coronary artery calcification progression increased significantly in all prediabetes groups. Multivariable-adjusted ratio of 5-year CAC progression rates was 1.19 (95% CI, 1.16-1.22) (persistent prediabetes), 1.11 (1.07-1.14) (regression to normoglycemia), and 1.63 (95% CI, 1.26-2.10) (progression from prediabetes to diabetes). CONCLUSIONS: Unfavorable changes in glycemic status, including persistence of prediabetes or progression to diabetes from prediabetes, were associated with increased risk of CAC.

Risk of CKD Following Detection of Microscopic Hematuria: A Retrospective Cohort Study.

RATIONALE & OBJECTIVE: Microscopic hematuria is an uncertain risk factor for chronic kidney disease (CKD). We investigated the association between persistent or single episodes of microscopic hematuria and the development of incident CKD, overall and separately among men and women. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: A total of 232,220 Korean adults without CKD at baseline who underwent repeated regular health examinations at Kangbuk Samsung Health Study formed the study cohort. EXPOSURE: Microscopic hematuria was defined by≥5 red blood cells per high-power field. Participants were categorized into 1 of 4 groups according to the presence of hematuria at 2 consecutive examinations: (1) no hematuria at both examinations (reference group); (2) hematuria followed by no hematuria (regressed hematuria group); (3) no hematuria followed by hematuria (developed hematuria group); and (4) hematuria at both examinations (persistent hematuria group). OUTCOME: CKD was defined as an estimated glomerular filtration rate<60mL/min/1.73m2 or proteinuria (1+or more on dipstick examination). ANALYTICAL APPROACH: Semiparametric proportional hazards models were used to estimate hazard ratios. RESULTS: During a 4.8-year median follow-up period, 2,392 participants developed CKD. Multivariable-adjusted hazard ratios for incident CKD, comparing the regressed, developed, and persistent hematuria groups to the no-hematuria group were 1.85 (95% CI, 1.35-2.53), 3.18 (95% CI, 2.54-3.98), and 5.23 (95% CI, 4.15-6.59), respectively. The association between persistent hematuria and incident CKD was stronger in men than women (P for interaction<0.001), although a statistically significant association was observed in both sexes. LIMITATIONS: Lack of albuminuria and inability to consider specific glomerular diseases. CONCLUSIONS: Men and women with microscopic hematuria, especially persistent hematuria, may be at increased risk of CKD.

Age-stratified effects of coronary artery calcification on cardiovascular and non-cardiovascular mortality in Korean adults.

AIMS: The role of coronary artery calcium score (CACS) in predicting cardiovascular disease (CVD) and non-CVD mortality in young adults is unclear. We investigated the association of CACS with CVD and non-CVD mortality in young and older individuals. METHODS AND RESULTS: CVD-free Koreans (n = 160 821; mean age, 41.4 years; 73.2% young individuals aged <45 years) who underwent cardiac tomography estimation of CACS (69.7% one-time measurement), were followed-up for a median of 5.6 years. The vital status and cause of death were ascertained from the national death records. Sub-distribution hazard ratios (SHR) and 95% confidence intervals (CIs) for cause-specific mortality were estimated using the Fine and Gray proportional hazards models. Overall, a higher CACS was strongly associated with an increased risk of CVD mortality. Among young individuals, multivariable-adjusted SHR (95% CIs) for CVD mortality comparing a CACS of 1-100, 101-300, and >300 to 0 CACS were 5.67 (2.33-13.78), 22.34 (5.72-87.19), and 74.1 (18.98-239.3), respectively, and among older individuals, corresponding SHR were 1.51 (0.60-3.84), 8.57 (3.05-24.06), and 6.41 (1.98-20.74). The addition of CACS to Framingham risk score significantly but modestly improved risk prediction for CVD mortality in young individuals. Conversely, CACS was significantly associated with non-CVD mortality only in older individuals. CONCLUSIONS: Strong associations of CACS with CVD mortality, but not non-CVD mortality, were observed in young individuals, beginning in the low CACS category. Our findings reaffirm the need for early intervention for young adults even with low CACS to reduce CVD mortality.

Prediabetes diagnosis is associated with the progression of coronary artery calcification: The Kangbuk Samsung Health Study.

AIM: To investigate the associations between prediabetes defined by different diagnostic criteria and coronary artery calcification (CAC) and its progression over time. MATERIALS AND METHODS: This cross-sectional study included 146 436 Korean adults without diabetes who underwent CAC estimation computed tomography (CT) during health examinations from 2011 to 2019. We used multinomial logistic regression models. The longitudinal study comprised 41 100 participants with at least one follow-up cardiac CT and annual CAC progression rates and ratios were estimated. Prediabetes was categorized into three groups: isolated glucose prediabetes (fasting blood glucose [FBG] 100-125 mg/dl, HbA1c < 5.7%), isolated HbA1c prediabetes (FBG < 100 mg/dl, HbA1c 5.7%-6.4%) and prediabetes meeting both FBG and HbA1c criteria (FBG 100-125 mg/dl, HbA1c 5.7%-6.4%). RESULTS: After adjusting for covariates, the prevalence ratios (95% CI) for CAC scores of more than 100 comparing isolated glucose prediabetes, isolated HbA1c prediabetes and prediabetes fulfilling both criteria with those of normoglycaemia were 1.12 (0.99-1.26), 1.24 (1.11-1.39) and 1.31 (1.18-1.45), respectively. The multivariable-adjusted ratio (CIs) of annual CAC progression rates comparing the corresponding groups with the normoglycaemia group were 1.031 (1.023-1.039), 1.025 (1.019-1.032) and 1.054 (1.047-1.062), respectively. CONCLUSIONS: CAC risk and CAC progression were consistently highest in individuals meeting both glucose and HbA1c criteria, while all three prediabetes types showed a significantly increased risk of CAC progression. Atherosclerosis risk reduction management is necessary for prediabetes, especially in patients meeting both criteria.

Skeletal muscle mass to visceral fat area ratio as a predictor of NAFLD in lean and overweight men and women with effect modification by sex.

The effect of sarcopenic visceral obesity on the risk of nonalcoholic fatty liver disease (NAFLD) is uncertain. We investigated (a) whether the skeletal muscle mass to visceral fat area ratio (SV ratio), as a measure of sarcopenic visceral obesity, is a risk factor for NAFLD; and (b) whether the SV ratio adds to conventional adiposity measures to improve prediction of incident NAFLD. Adults without NAFLD (n = 151,017) were followed up for a median of 3.7 years. Hepatic steatosis was measured using ultrasonography, and liver fibrosis scores were estimated using the Fibrosis-4 index (FIB-4) and the NAFLD Fibrosis Score (NFS). Cox proportional hazards models were used to determine sex-specific adjusted hazard ratios (aHRs) (95% confidence intervals [CIs]). The incremental predictive performance was assessed using the area under the receiver operating characteristic curve, net reclassification improvement, and integrated discrimination improvement. Multivariable aHRs (95% CIs) for incident NAFLD comparing the lowest versus the highest quintile of SV ratio were 3.77 (3.56-3.99) for men and 11.69 (10.46-13.06) for women (p-interaction by sex < 0.001). For incident NAFLD with intermediate/high FIB-4, aHRs were 2.83 (2.19-3.64) for men and 7.96 (3.85-16.44) for women (similar results were obtained for NFS). Associations remained significant even after adjustment for body mass index, waist circumference, and time-varying covariates. These associations were also more pronounced in nonobese than obese participants (p-interaction < 0.001). The addition of SV ratio to conventional adiposity measures modestly improved risk prediction for incident NAFLD. SV ratio was inversely associated with risk of developing NAFLD, with effect modification by sex and obesity. Conclusion: Low SV ratio is a complementary index to conventional adiposity measures in the evaluation of NAFLD risk.

The fasciola cinereum subregion of the hippocampus is important for the acquisition of visual contextual memory.

The fasciola cinereum (FC) is a subregion of the hippocampus that has received relatively little attention compared with other hippocampal subregions with respect to anatomical characteristics and functional significance. Here, we show that the FC exhibits clear anatomical borders with the distalmost region of the CA1. Principal neurons in the FC resemble the granule cells in the dentate gyrus (DG). However, adult neurogenesis was not found unlike in the DG. The FC receives inputs mostly from the lateral entorhinal cortex and perirhinal cortex while projecting exclusively to the crest of the DG within the hippocampus. Neurotoxic lesions in the FC using colchicine impaired the acquisition, but not retrieval, of visual contextual memory in rats. FC lesions also impaired place recognition and object-in-place memory. As the rat performed the contextual memory task on the T-maze, place cells in the FC exhibited robust place fields and were indiscriminable from those in CA1 with respect to the basic firing properties. However, place cells in the FC fired only transiently in their place fields on the maze compared with those in CA1. Our findings suggest that the episodic firing patterns of the place cells in the FC may play critical roles in learning a novel contextual environment by facilitating temoporally structured contextual pattern separation in the DG of the hippocampus.

Decrease in Sleep Duration and Poor Sleep Quality over Time Is Associated with an Increased Risk of Incident Non-Alcoholic Fatty Liver Disease.

The impact of changes in sleep duration and sleep quality over time on the risk of non-alcoholic fatty liver disease (NAFLD) is not known. We investigated whether changes in sleep duration and in sleep quality between baseline and follow-up are associated with the risk of developing incident NAFLD. The cohort study included 86,530 Korean adults without NAFLD and with a low fibrosis score at baseline. The median follow-up was 3.6 years. Sleep duration and quality were assessed using the Pittsburgh Sleep Quality Index. Hepatic steatosis (HS) and liver fibrosis were assessed using ultrasonography and the fibrosis-4 index (FIB-4). Cox proportional hazard models were used to determine hazard ratios (HRs) and 95% confidence intervals (Cis). A total of 12,127 subjects with incident HS and 559 with incident HS plus intermediate/high FIB-4 was identified. Comparing the decrease in sleep duration of >1 h, with stable sleep duration, the multivariate-adjusted HR (95% CIs) for incident HS was 1.24 (1.15-1.35). The corresponding HRs for incident HS plus intermediate/high FIB-4 was 1.58 (1.10-2.29). Comparing persistently poor sleep quality with persistently good sleep quality, the multivariate-adjusted HR for incident HS was 1.13 (95% CI, 1.05-1.20). A decrease in sleep duration or poor sleep quality over time was associated with an increased risk of incident NAFLD, underscoring an important potential role for good sleep in preventing NAFLD risk.

Low heart rate variability from 10-s electrocardiograms is associated with development of non-alcoholic fatty liver disease.

Reduced heart rate variability (HRV) is reflective of autonomic imbalance. However, its impact on non-alcoholic fatty liver disease (NAFLD) is unknown. We investigated the association between 10-s HRV and incident NAFLD. A cohort of 154,286 Korean adults with no NAFLD at baseline were followed up. 10-s electrocardiograms were used to estimate two time-domain HRV, the standard deviation of normal-to-normal intervals (SDNN) and the root mean square of successive differences in RR intervals (RMSSD). Hepatic steatosis (HS) and liver fibrosis were assessed using ultrasonography and the fibrosis-4 index (FIB-4). A total of 27,279 incident HS (median follow up of 4.2 years) and 1250 incident HS plus high FIB-4 (median follow up of 4.2 years) cases were identified at follow-up. The multivariable adjusted hazard ratios (aHRs) (95% confidence intervals [CIs]) in a model with time-dependent variables for incident HS, comparing the lowest quintile to the highest and reference quintile of the RMSSD, was 1.43 (1.37-1.49), and the corresponding HR for incident HS plus intermediate/high FIB-4 was 1.70 (1.35-2.15). Similarly, SDNN was inversely associated with incident HS and HS plus intermediate/high FIB-4. The results were similar using the NAFLD fibrosis score. Autonomic imbalance assessed by HRV may help to identify individuals at a high risk of HS and its progression and warrant further studies.

Sleep Duration, Sleep Quality, and the Development of Nonalcoholic Fatty Liver Disease: A Cohort Study.

INTRODUCTION: The longitudinal relationship between sleep duration, sleep quality, and the risk of nonalcoholic fatty liver disease (NAFLD) is unknown. We aimed to examine the association between sleep duration, sleep quality, and NAFLD development. METHODS: Using the Pittsburgh Sleep Quality Index, sleep duration and quality were evaluated for 143,306 NAFLD-free Korean adults with a mean age of 36.6 years, who were followed for an average of 4.0 years. Hepatic steatosis (HS) was assessed using ultrasonography and liver fibrosis by the fibrosis-4 index (FIB-4) or the NAFLD fibrosis score. Flexible parametric proportional hazard models were used to determine the hazard ratios (HRs) and 95% confidence intervals. RESULTS: There were 27,817 subjects with incident HS, of whom 1,471 had incident HS plus intermediate/high FIB-4. Multivariable-adjusted HRs (95% confidence intervals) for incident HS comparing sleep durations of ≤5, 6, 8, and ≥ 9 hours with 7 hours were 1.19 (1.14-1.23), 1.07 (1.04-1.10), 0.98 (0.94-1.02), and 0.95 (0.87-1.03), respectively. The corresponding HRs for incident HS plus intermediate/high FIB-4 were 1.30 (1.11-1.54), 1.14 (1.01-1.29), 1.11 (0.93-1.33), and 1.08 (0.71-1.63). The association between sleep duration and HS plus intermediate/high FIB-4 was inverse in individuals with good sleep quality but tended to be U-shaped in those with poor sleep quality. The results were similar if FIB-4 was replaced by the NAFLD fibrosis score. DISCUSSION: In young adults, short sleep duration was independently associated with an increased risk of incident NAFLD with or without intermediate/high fibrosis score, suggesting a role for inadequate sleep quantity in NAFLD risk and severity.

Intermediate Phase-Free Process for Methylammonium Lead Iodide Thin Film for High-Efficiency Perovskite Solar Cells.

Solvent engineering by Lewis-base solvent and anti-solvent is well known for forming uniform and stable perovskite thin films. The perovskite phase crystallizes from an intermediate Lewis-adduct upon annealing-induced crystallization. Herein, it is explored the effects of trimethyl phosphate (TMP), as a novel aprotic Lewis-base solvent with a low donor number for the perovskite film formation and photovoltaic characteristics of perovskite solar cells (PSCs). As compared to dimethylsulfoxide (DMSO) or dimethylformamide (DMF), the usage of TMP directly crystallizes the perovskite phase, i.e., reduces the intermediate phase to a negligible degree, right after the spin-coating, owing to the high miscibility of TMP with the anti-solvent and weak bonding in the Lewis adduct. Interestingly, the PSCs based on methylammonium lead iodide (MAPbI3 ) derived from TMP/DMF-mixed solvent exhibit a higher average power conversion efficiency of 19.68% (the best: 20.02%) with a smaller hysteresis in the current-voltage curve, compared to the PSCs that are fabricated using DMSO/DMF-mixed (19.14%) or DMF-only (18.55%) solvents. The superior photovoltaic properties are attributed to the lower defect density of the TMP/DMF-derived perovskite film. The results indicate that a high-performance PSC can be achieved by combining a weak Lewis base with a well-established solvent engineering process.

Fatty liver disease and changes in dense breasts in pre- and postmenopausal women: the Kangbuk Samsung Health Study.

PURPOSE: While increased breast density is a risk factor for breast cancer, the effect of fatty liver disease on breast density is unknown. We investigated whether fatty liver is a risk factor for changes in breast density over ~ 4 years of follow-up in pre- and postmenopausal women. METHODS: This study included 74,781 middle-aged Korean women with mammographically determined dense breasts at baseline. Changes in dense breasts were identified by more screening mammograms during follow-up. Hepatic steatosis (HS) was measured using ultrasonography. Flexible parametric proportional hazards models were used to determine the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs), and a Weibull accelerated failure time model (AFT) was used to determine the time ratios (TRs) and 95% CIs. RESULTS: During a median follow-up of 4.1 years, 4022 women experienced resolution of the dense breasts. The association between HS and dense breast resolution differed by the menopause status (P for interaction < 0.001). After adjusting for body mass index and other covariates, the aHRs (95% CI) for dense breast resolution comparing HS to non-HS were 0.81 (0.70-0.93) in postmenopausal women, while the association was converse in premenopausal women with the corresponding HRs of 1.30 (1.18-1.43). As an alternative approach, the multivariable-adjusted TR (95% CI) for dense breast survival comparing HS to non-HS were 0.81 (0.75-0.87) and 1.19 (1.06-1.33) in premenopausal and postmenopausal women, respectively. CONCLUSION: The association between HS and changes in dense breasts differed with the menopause status. HS increased persistent dense breast survival in postmenopausal women but decreased it in premenopausal women.

Regulatory Effect of Cannabidiol (CBD) on Decreased ß-Catenin Expression in Alopecia Models by Testosterone and PMA Treatment in Dermal Papilla Cells.

OBJECTIVES: The hair follicle is composed of more than 20 kinds of cells, and mesoderm derived dermal papilla cells and keratinocytes cooperatively contribute hair growth via Wnt/ß-catenin signaling pathway. We are to investigate ß-catenin expression and regulatory mechanism by CBD in alopecia hair tissues and dermal papilla cells. METHODS: We performed structural and anatomical analyses on alopecia patients derived hair tissues using microscopes. Pharmacological effect of CBD was evaluated by ß-catenin expression using RT-PCR and immunostaining experiment. RESULTS: Morphological deformation and loss of cell numbers in hair shaft were observed in alopecia hair tissues. IHC experiment showed that loss of ß-catenin expression was shown in inner shaft of the alopecia hair tissues, indicating that ß-catenin expression is a key regulatory function during alopecia progression. Consistently, ß-catenin expression was decreased in testosterone or PMA treated dermal papilla cells, suggesting that those treatments are referred as a model on molecular mechanism of alopecia using dermal papilla cells. RT-PCR and immunostaining experiments showed that ß-catenin expression was decreased in RNA level, as well as decreased ß-catenin protein might be resulted from ubiquitination. However, CBD treatment has no changes in gene expression including ß-catenin, but the decreased ß-catenin expression by testosterone or PMA was restored by CBD pretreatment, suggesting that potential regulatory effect on alopecia induction of testosterone and PMA. CONCLUSION: CBD might have a modulating function on alopecia caused by hormonal or excess of signaling pathway, and be a promising application for on alopecia treatment.

Glycemic Status, Insulin Resistance, and the Risk of Nephrolithiasis: A Cohort Study.

RATIONALE & OBJECTIVE: The effect of glycemic status on nephrolithiasis risk remains controversial. This study sought to examine the association of glycemic status and insulin resistance with incident nephrolithiasis. STUDY DESIGN: A retrospective cohort study. SETTING & PARTICIPANTS: 278,628 Korean adults without nephrolithiasis who underwent a comprehensive health examination between 2011 and 2017. EXPOSURES: Glucose level, glycated hemoglobin level, and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). OUTCOME: Nephrolithiasis ascertained using abdominal ultrasound. ANALYTICAL APPROACH: A parametric proportional hazard model was used to estimate adjusted HRs and 95% CIs. We explored prespecified potential sex differences in the association of glycemic status and incident nephrolithiasis. RESULTS: During a median follow-up of 4.2 years, 6,904 participants developed nephrolithiasis. Associations between levels of glycemic status and incident nephrolithiasis were examined separately in men and women (P for interaction = 0.003). Among men, multivariable-adjusted HRs for incident nephrolithiasis comparing glucose levels of 90-99, 100-125, and ≥ 126 mg/dL were 1.10 (95% CI, 1.01-1.19), 1.11 (95% CI, 1.02-1.21), and 1.27 (95% CI, 1.10-1.46), respectively, while HRs for incident nephrolithiasis comparing glycated hemoglobin levels of 5.7%-5.9%, 6.0%-6.4%, and 6.5%-<5.7% were 1.03 (95% CI, 0.96-1.10), 1.18 (95% CI, 1.07-1.31), and 1.20 (95% CI, 1.06-1.37), respectively. The HR for incident nephrolithiasis comparing the highest HOMA-IR quintile to the lowest quintile was 1.18 (95% CI, 1.06-1.31). Among women, no apparent association was found between glycemic status and nephrolithiasis risk. LIMITATIONS: Glucose tolerance testing and computed tomography assessment for nephrolithiasis were not available. CONCLUSIONS: Higher glycemic values, even within the normoglycemic range, and HOMA-IR were positively associated with increased risk for nephrolithiasis, associations that were only observed among men. Insulin resistance and hyperglycemia may contribute to the development of nephrolithiasis, particularly among men.

Low Levels of Alcohol Consumption, Obesity, and Development of Fatty Liver With and Without Evidence of Advanced Fibrosis.

BACKGROUND AND AIMS: The effects of low-level alcohol consumption on fatty liver disease and the potential for effect modification by obesity is uncertain. We investigated associations among low-level alcohol consumption, obesity status, and the development of incident hepatic steatosis (HS), either with or without an increase in noninvasive liver fibrosis score category (from low to intermediate or high category). APPROACH AND RESULTS: A total of 190,048 adults without HS and a low probability of fibrosis with alcohol consumption less than 30 g/day (men) and less than 20 g/day (women) were followed for up to 15.7 years. Alcohol categories of no, light, and moderate consumption were defined as 0, 1-9.9, and 10-29.9 g/day (10-19.9 g/day for women), respectively. HS was diagnosed by ultrasonography, and the probability of fibrosis was estimated using the fibrosis-4 index (FIB-4). Parametric proportional hazards models were used to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 43,466 participants developed HS, 2,983 of whom developed HS with an increase in FIB-4 index (to intermediate or high scores). Comparing light drinkers and moderate drinkers with nondrinkers, multivariable-adjusted HRs (95% CI) for incident HS were 0.93 (0.90-0.95) and 0.90 (0.87-0.92), respectively. In contrast, comparing light drinkers and moderate drinkers with nondrinkers, multivariable-adjusted HRs (95% CI) for developing HS plus intermediate/high FIB-4 were 1.15 (1.04-1.27) and 1.49 (1.33-1.66), respectively. The association between alcohol consumption categories and incident HS plus intermediate/high FIB-4 was observed in both nonobese and obese individuals, although the association was stronger in nonobese individuals (P for interaction by obesity = 0.017). CONCLUSIONS: Light/moderate alcohol consumption has differential effects on the development of different stages of fatty liver disease, which is modified by the presence of obesity.

Attitudes of Korean smokers towards smoke-free public places: findings from the longitudinal ITC Korea Survey, 2005-2010.

OBJECTIVE: Prior to December 2012, restaurants in South Korea were required to implement only partial smoking bans. This study documents the changes in Korean smokers' attitudes towards smoking bans between 2005 and 2010 and explores the effects of anti-smoking advertising as a correlate of support for total smoking bans in public places. DESIGN: Longitudinal cohort study of Korean adult smokers. SETTING: The data were derived from three waves (2005, 2008 and 2010) of the International Tobacco Control (ITC) Korea Survey. PARTICIPANTS: The ITC Korea Survey respondents were a probability-based, nationally representative sample of Korean smokers aged 19 and older. The current analysis includes 995 smokers who participated in Wave 1 (2005), 1737 smokers who participated in Wave 2 (2008) and 1560 smokers who participated in Wave 3 (2010). PRIMARY AND SECONDARY OUTCOME MEASURES: Changes in respondents' awareness of secondhand smoke (SHS) harm, attitudes towards smoking bans and personal rules for smoking in private homes and/or vehicles were analysed. Correlates of support for smoking bans in public places were examined using generalised estimating equation regression models. RESULTS: More than 80% of Korean smokers are aware of the harms of SHS. The proportion of smokers who support smoke-free restaurants or smoke-free bars increased twofold between 2005 and 2010. Smokers who were aware of the dangers of SHS were more likely to support a total smoking ban in workplaces. Noticing anti-smoking advertising or information was not significantly associated with support for a total smoking ban in public places. CONCLUSIONS: Korean smokers became more supportive of smoking bans in public places between 2005 and 2008. These results show that smokers' attitudes towards smoking bans can change with the implementation of smoke-free policies, even in a country that has a high prevalence of smokers.