Background: Poor adherence to oral bisphosphonates is a challenge to treatment and prevention of osteoporosis. The Veterans Health Administration (VA) operates the largest integrated health care system in the United States and offers certain advantages to possibly improve medication adherence. We aimed to determine adherence to weekly alendronate for osteoporosis in Veterans, and investigate predictors and outcomes related to adherence. Methods: A retrospective study cohort was generated from VA databases selecting Veterans who were treated with weekly alendronate. Adherence was measured by medication possession ratio (MPR) and persistence. Two groups were defined as low and high adherence based on MPR <80% or ≥80%, respectively. Regression models were used to investigate predictors of adherence and included clinically relevant covariates. Further regressions were used to investigate the impact of adherence on change in bone mineral density measured by dual energy X-ray absorptiometry and incident fracture. Results: In a cohort of 913 (female/male, 207/706) Veterans, 48% had high adherence in year 1. Distribution for gender, race, and age were similar between the 2 groups, MPR <80% or MPR ≥80%. Baseline fracture [odds ratio OR: 0.64, 95%CI: (0.41, 0.98)], alcohol abuse [0.40 (0.21, 0.74)] and tobacco use [0.44 (0.31, 0.63)] were associated with low adherence in the unadjusted analyses, but only tobacco use [0.45 (0.30, 0.67)] was associated with low adherence after adjustment. Among males, tobacco use was associated with low adherence while prostate cancer predicted high adherence in adjusted models. High adherence was associated with a 30% [hazard ratio HR: 0.70, 95% CI: (0.47, 1.03)] decreased risk of incident fracture in the whole cohort, and a 40% [0.60 (0.38, 0.95)] decrease risk in males. Conclusion: Year one adherence to weekly alendronate was a relevant determinant to long-term clinical outcomes including changes in bone mineral density and incident fracture in Veterans.

FeS-1, VS-1 or CuS-1 precursors are loaded and highly dispersed on the surface of mesoporous materials SBA-15, MCM-41 or SiO2by impregnating method. The samples were characterized by X-ray diffraction, FT-IR spectroscopy, TEM and N2adsorption. Their catalytic performances for styrene epoxidation with anhydrous TBHP as an oxidant agent were studied. The results suggest that zeolite primary and secondary building units are highly dispersed on the samples and the samples have still retained mesoporous structure. All of the catalysts exhibit good catalytic activities, producing styrene oxide and benzaldehyde as the main products. Cu/SBA-15 shows high activity and selectivity, which are comparable with that of other samples. We find that, under the conditions of preferable precursors,n(TBHP)/n(styrene) =1.5, reaction temperature 80°C, and reaction time 2.0h, the conversion and yield of styrene epoxide reached 65.9% and 42.2%, respectively.

Case 1 was a 33-year-old male with type 1 diabetes since age 6 years and hypothyroidism due to Hashimoto’s thyroiditis; the patient missed annual labs for 2 years. He used continuous subcutaneous insulin infusion (CSII) and had achieved an HbA1c level of <7% for several years. Case 2 was a 38-year-old male with type 1 diabetes, hypertension, hyperlipidemia, and selective IgM deficiency who had significant albuminuria on routine screening. Type 1 diabetes was diagnosed at age 12 years and was well controlled with HbA1c levels ranging from 6–7.5%.

Introduction: Poor glycemic control is considered an important contributor to cardiovascular disease in patients with diabetes. Episodic hyperglycemia as a surrogate for glycemic variability promotes monocyte adhesion and increases the prevalence of proinflammatory monocytes within atherosclerotic plaques of patients with diabetes. We previously found that acute hyperglycemia-induced a pro-inflammatory phenotype and promoted the development of foamy monocytes by increasing total cholesterol deposition, cholesterol ester, and free cholesterol content by enhancing oxidized LDL uptake. However, the mechanism by which acute hyperglycemia induces monocyte cholesterol deposition and inflammation remains unknown. Methods: Monocytes isolated from healthy individuals (age range 20–40; n=5) were cultured in low (5mM) or high (16.7mM) glucose conditions with or without a glycolysis inhibitor (2-deoxyglucose, 2DG, 5 mM) or an endoplasmic reticulum stress inhibitor (4-phenylbutyric acid, PBA; 20mM) for 6 hrs. After treatment, cytokine release, oxidized LDL uptake, and metabolic assays using Seahorse Technology were performed. Results: Healthy human monocytes exposed under high glucose conditions showed a pro-atherosclerotic phenotype with higher levels of the pro-inflammatory cytokines, TNFα(median of differences 6.34 pg/ml, p=0.002) and IL1β(12.04 pg/ml, p=0.003), and increased oxidized LDL uptake (5062ug Dil-Ox LDL/mg, p=0.001). Furthermore, hyperglycemia resulted in higher levels of glycolysis (basal glycolysis 12.94 pmol/min, p=0.01; basal proton efflux rate 15.5 pmol/min, p=0.03) and mitochondrial respiration (percentage of respiratory capacity 16pmol/min p=0.04), suggesting a significant alteration in the metabolic programming of these monocytes. Treatment with 2-DG or PBA attenuated the pro-atherosclerotic phenotype induced by hyperglycemia, promoting a reduction of cytokine release, a reduction of oxidized LDL uptake, and near normalization of the glycolic rate and mitochondrial respiration, stabilizing cellular bioenergetics. Conclusions: Altogether, our results suggest that monocyte ER stress in response to acute hyperglycemia promotes a hypermetabolic state characterized by a proinflammatory and proatherogenic monocyte phenotype. Therefore, acute hyperglycemia is a potential mechanism promoting atherosclerosis in patients with type 2 diabetes.