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MCA yielded a high control coefficient for GCK in all three groups. We confirmed these findings in studies of hepatic GCK knockdown using an antisense oligonucleotide. Reduced liver glycogen synthesis in lipid-induced hepatic insulin resistance and increased glycogen synthesis during portal glucose infusion were explained by concordant changes in translocation of GCK. Taken together, these data indicate that the rate of insulin-stimulated hepatic glycogen synthesis is controlled chiefly through GCK translocation. MEK inhibitor side effects Copyright © 2020 the Author(s). Published by PNAS.Dispersal is one of the fundamental life-history strategies of organisms, so understanding the selective forces shaping the dispersal traits is important. In the Wright's island model, dispersal evolves due to kin competition even when dispersal is costly, and it has traditionally been assumed that the living conditions are the same everywhere. To study the effect of spatial heterogeneity, we extend the model so that patches may receive different amounts of immigrants, foster different numbers of individuals, and give different reproduction efficiency to individuals therein. We obtain an analytical expression for the fitness gradient, which shows that directional selection consists of three components As in the homogeneous case, the direct cost of dispersal selects against dispersal and kin competition promotes dispersal. The additional component, spatial heterogeneity, more precisely the variance of so-called relative reproductive potential, tends to select against dispersal. We also obtain an expression for the second derivative of fitness, which can be used to determine whether there is disruptive selection Unlike the homogeneous case, we found that divergence of traits through evolutionary branching is possible in the heterogeneous case. Our numerical explorations suggest that evolutionary branching is promoted more by differences in patch size than by reproduction efficiency. Our results show the importance of the existing spatial heterogeneity in the real world as a key determinant in dispersal evolution. Copyright © 2020 the Author(s). Published by PNAS.OBJECTIVE With rising health care costs and finite health care resources, understanding the population needs of different type 2 diabetes mellitus (T2DM) patient subgroups is important. Sparse data exist for the application of population segmentation on health care needs among Asian T2DM patients. We aimed to segment T2DM patients into distinct classes and evaluate their differential health care use, diabetes-related complications, and mortality patterns. RESEARCH DESIGN AND METHODS Latent class analysis was conducted on a retrospective cohort of 71,125 T2DM patients. Latent class indicators included patient's age, ethnicity, comorbidities, and duration of T2DM. Outcomes evaluated included health care use, diabetes-related complications, and 4-year all-cause mortality. The relationship between class membership and outcomes was evaluated with the appropriate regression models. RESULTS Five classes of T2DM patients were identified. The prevalence of depression was high among patients in class 3 (younger females with short-to-moderate T2DM duration and high psychiatric and neurological disease burden) and class 5 (older patients with moderate-to-long T2DM duration and high disease burden with end-organ complications). They were the highest tertiary health care users. Class 5 patients had the highest risk of myocardial infarction (hazard ratio [HR] 12.05, 95% CI 10.82-13.42]), end-stage renal disease requiring dialysis initiation (HR 25.81, 95% CI 21.75-30.63), stroke (HR 19.37, 95% CI 16.92-22.17), lower-extremity amputation (HR 12.94, 95% CI 10.90-15.36), and mortality (HR 3.47, 95% CI 3.17-3.80). CONCLUSIONS T2DM patients can be segmented into classes with differential health care use and outcomes. Depression screening should be considered for the two identified classes of patients. © 2020 by the American Diabetes Association.OBJECTIVE There is a controversy over the association between obesity and end-stage renal disease (ESRD) in people with or without type 2 diabetes; therefore, we examined the effect of BMI on the risk of ESRD according to glycemic status in the Korean population. RESEARCH DESIGN AND METHODS The study monitored 9,969,848 participants who underwent a National Health Insurance Service health checkup in 2009 from baseline to the date of diagnosis of ESRD during a follow-up period of ∼8.2 years. Obesity was categorized by World Health Organization recommendations for Asian populations, and glycemic status was categorized into the following five groups normal, impaired fasting glucose (IFG), newly diagnosed diabetes, diabetes less then 5 years, and diabetes ≥5 years. RESULTS Underweight was associated with a higher risk of ESRD in all participants after adjusting for all covariates. In the groups with IFG, newly diagnosed type 2 diabetes, diabetes duration less then 5 years, and diabetes ≥5 years, the hazard ratio (HR) of the underweight group increased with worsening glycemic status (HR 1.431 for IFG; 2.114 for newly diagnosed diabetes; 4.351 for diabetes less then 5 years; and 6.397 for diabetes ≥5 years), using normal weight with normal fasting glucose as a reference. The adjusted HRs for ESRD were also the highest in the sustained underweight group regardless of the presence of type 2 diabetes (HR 1.606 for nondiabetes, and 2.14 for diabetes). CONCLUSIONS Underweight showed more increased HR of ESRD according to glycemic status and diabetes duration in the Korean population. These associations also persisted in the group with sustained BMI during the study period. © 2020 by the American Diabetes Association.To estimate the prevalence and factors associated with HIV and five other STIs among outdoor female sex workers (OSFW) and indoor FSW (IFSW). METHODS Cross-sectional survey using respondent-driven sampling methodology. Participants answered a bio-behavioural questionnaire and were tested for Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT), Trichomonas vaginalis (TV), syphilis (lifetime contact) and Mycoplasma genitalium (MG). Weighted HIV and other STIs prevalence and 95% CIs were calculated. Weighted multivariate logistic regression was performed to identify factors associated with having at least one STI (including HIV). RESULTS Between October 2017 and July 2018, 385 FSW participants were recruited, among whom 206 (53.5%) were IFSW and 179 (46.5%) were OFSW. The mean age was 31.4 years. Weighted HIV prevalence was 3.1% (95% CI 1.5 to 7.0). Weighted prevalence of other STIs was 4.1% (95% CI 2.2 to 8.0) for NG, 8.8% (95% CI 5.9 to 13.0) for CT, 12.7% (95% CI 8.6 to 18.0) for TV, 13.9% (95% CI 9.9 to 19.

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