Relationship between abuse and neglect in childhood and diabetes in adulthood: Differential effects by sex, national longitudinal study of adolescent health

INTRODUCTION: Few studies have investigated links between child abuse and neglect and diabetes mellitus in nationally representative samples, and none have explored the role of obesity in the relationship. We sought to determine whether child abuse and neglect were associated with diabetes and if so, whether obesity mediated this relationship in a population-representative sample of young adults. METHODS: We used data from 14,493 participants aged 24 to 34 years from Wave IV of the National Longitudinal Study of Adolescent Health to study associations between self-reported child abuse (sexual, physical, or emotional abuse) and neglect as children and diabetes or prediabetes in young adulthood. We conducted sex-stratified logistic regression analyses to evaluate associations in models before and after the addition of body mass index (BMI) as a covariate. RESULTS: Although the prevalence of diabetes was similar for men and women (7.0% vs 6.7%), men were more likely than women to have prediabetes (36.3% vs 24.6%; omnibus P < .001). Among men, recurrent sexual abuse (≥3 lifetime incidents) was significantly associated with diabetes (OR, 3.66; 95% CI, 1.31–10.24), but not with prediabetes. There was no evidence of mediation by BMI. No forms of child abuse or neglect were associated with diabetes or prediabetes among women. CONCLUSIONS: Recurrent sexual abuse is robustly associated with diabetes in young adult men, independently of other forms of child abuse or neglect and BMI. Future research should explore other potential mechanisms for this association to identify avenues for prevention of diabetes among men who have experienced sexual abuse

Structure and Dynamics of AMPA Receptor GluA2 in Resting, Pre-Open, and Desensitized States

SummaryIonotropic glutamate receptors (iGluRs) mediate the majority of fast excitatory signaling in the nervous system. Despite the profound importance of iGluRs to neurotransmission, little is known about the structures and dynamics of intact receptors in distinct functional states. Here, we elucidate the structures of the intact GluA2 AMPA receptor in an apo resting/closed state, in an activated/pre-open state bound with partial agonists and a positive allosteric modulator, and in a desensitized/closed state in complex with fluorowilliardiine. To probe the conformational properties of these states, we carried out double electron-electron resonance experiments on cysteine mutants and cryoelectron microscopy studies. We show how agonist binding modulates the conformation of the ligand-binding domain “layer” of the intact receptors and how, upon desensitization, the receptor undergoes large conformational rearrangements of the amino-terminal and ligand-binding domains. We define mechanistic principles by which to understand antagonism, activation, and desensitization in AMPA iGluRs

A new, long-term daily satellite-based rainfall dataset for operational monitoring in Africa

Rainfall information is essential for many applications in developing countries, and yet, continually updated information at fine temporal and spatial scales is lacking. In Africa, rainfall monitoring is particularly important given the close relationship between climate and livelihoods. To address this information gap, this paper describes two versions (v2.0 and v3.0) of the TAMSAT daily rainfall dataset based on high-resolution thermal-infrared observations, available from 1983 to the present. The datasets are based on the disaggregation of 10-day (v2.0) and 5-day (v3.0) total TAMSAT rainfall estimates to a daily time-step using daily cold cloud duration. This approach provides temporally consistent historic and near-real time daily rainfall information for all of Africa. The estimates have been evaluated using ground-based observations from five countries with contrasting rainfall climates (Mozambique, Niger, Nigeria, Uganda, and Zambia) and compared to other satellite-based rainfall estimates. The results indicate that both versions of the TAMSAT daily estimates reliably detects rainy days, but have less skill in capturing rainfall amount—results that are comparable to the other datasets

Local and Global Well-Posedness for Aggregation Equations and Patlak-Keller-Segel Models with Degenerate Diffusion

Recently, there has been a wide interest in the study of aggregation equations and Patlak-Keller-Segel (PKS) models for chemotaxis with degenerate diffusion. The focus of this paper is the unification and generalization of the well-posedness theory of these models. We prove local well-posedness on bounded domains for dimensions $d\geq 2$ and in all of space for $d\geq 3$, the uniqueness being a result previously not known for PKS with degenerate diffusion. We generalize the notion of criticality for PKS and show that subcritical problems are globally well-posed. For a fairly general class of problems, we prove the existence of a critical mass which sharply divides the possibility of finite time blow up and global existence. Moreover, we compute the critical mass for fully general problems and show that solutions with smaller mass exists globally. For a class of supercritical problems we prove finite time blow up is possible for initial data of arbitrary mass.Comment: 31 page

Effects of diet versus gastric bypass on metabolic function in diabetes

BackgroundSome studies have suggested that in people with type 2 diabetes, Roux-en-Y gastric bypass has therapeutic effects on metabolic function that are independent of weight loss.MethodsWe evaluated metabolic regulators of glucose homeostasis before and after matched (approximately 18%) weight loss induced by gastric bypass (surgery group) or diet alone (diet group) in 22 patients with obesity and diabetes. The primary outcome was the change in hepatic insulin sensitivity, assessed by infusion of insulin at low rates (stages 1 and 2 of a 3-stage hyperinsulinemic euglycemic pancreatic clamp). Secondary outcomes were changes in muscle insulin sensitivity, beta-cell function, and 24-hour plasma glucose and insulin profiles.ResultsWeight loss was associated with increases in mean suppression of glucose production from baseline, by 7.04 μmol per kilogram of fat-free mass per minute (95% confidence interval [CI], 4.74 to 9.33) in the diet group and by 7.02 μmol per kilogram of fat-free mass per minute (95% CI, 3.21 to 10.84) in the surgery group during clamp stage 1, and by 5.39 (95% CI, 2.44 to 8.34) and 5.37 (95% CI, 2.41 to 8.33) μmol per kilogram of fat-free mass per minute in the two groups, respectively, during clamp stage 2; there were no significant differences between the groups. Weight loss was associated with increased insulin-stimulated glucose disposal, from 30.5±15.9 to 61.6±13.0 μmol per kilogram of fat-free mass per minute in the diet group and from 29.4±12.6 to 54.5±10.4 μmol per kilogram of fat-free mass per minute in the surgery group; there was no significant difference between the groups. Weight loss increased beta-cell function (insulin secretion relative to insulin sensitivity) by 1.83 units (95% CI, 1.22 to 2.44) in the diet group and by 1.11 units (95% CI, 0.08 to 2.15) in the surgery group, with no significant difference between the groups, and it decreased the areas under the curve for 24-hour plasma glucose and insulin levels in both groups, with no significant difference between the groups. No major complications occurred in either group.ConclusionsIn this study involving patients with obesity and type 2 diabetes, the metabolic benefits of gastric bypass surgery and diet were similar and were apparently related to weight loss itself, with no evident clinically important effects independent of weight loss. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT02207777.)

Clinical and genetic determinants of warfarin pharmacokinetics and pharmacodynamics during treatment initiation

Variable warfarin response during treatment initiation poses a significant challenge to providing optimal anticoagulation therapy. We investigated the determinants of initial warfarin response in a cohort of 167 patients. During the first nine days of treatment with pharmacogenetics-guided dosing, S-warfarin plasma levels and international normalized ratio were obtained to serve as inputs to a pharmacokinetic-pharmacodynamic (PK-PD) model. Individual PK (S-warfarin clearance) and PD (I max) parameter values were estimated. Regression analysis demonstrated that CYP2C9 genotype, kidney function, and gender were independent determinants of S-warfarin clearance. The values for I max were dependent on VKORC1 and CYP4F2 genotypes, vitamin K status (as measured by plasma concentrations of proteins induced by vitamin K absence, PIVKA-II) and weight. Importantly, indication for warfarin was a major independent determinant of I max during initiation, where PD sensitivity was greater in atrial fibrillation than venous thromboembolism. To demonstrate the utility of the global PK-PD model, we compared the predicted initial anticoagulation responses with previously established warfarin dosing algorithms. These insights and modeling approaches have application to personalized warfarin therapy. © 2011 Gong et al

DSM-5: a collection of psychiatrist views on the changes, controversies, and future directions

The recent release of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) by the American Psychiatric Association has led to much debate. For this forum article, we asked BMC Medicine Editorial Board members who are experts in the field of psychiatry to discuss their personal views on how the changes in DSM-5 might affect clinical practice in their specific areas of psychiatric medicine. This article discusses the influence the DSM-5 may have on the diagnosis and treatment of autism, trauma-related and stressor-related disorders, obsessive-compulsive and related disorders, mood disorders (including major depression and bipolar disorders), and schizophrenia spectrum disorders