Self-assembly of Microcapsules via Colloidal Bond Hybridization and Anisotropy

Particles with directional interactions are promising building blocks for new functional materials and may serve as models for biological structures. Mutually attractive nanoparticles that are deformable due to flexible surface groups, for example, may spontaneously order themselves into strings, sheets and large vesicles. Furthermore, anisotropic colloids with attractive patches can self-assemble into open lattices and colloidal equivalents of molecules and micelles. However, model systems that combine mutual attraction, anisotropy, and deformability have---to the best of our knowledge---not been realized. Here, we synthesize colloidal particles that combine these three characteristics and obtain self-assembled microcapsules. We propose that mutual attraction and deformability induce directional interactions via colloidal bond hybridization. Our particles contain both mutually attractive and repulsive surface groups that are flexible. Analogous to the simplest chemical bond, where two isotropic orbitals hybridize into the molecular orbital of H2, these flexible groups redistribute upon binding. Via colloidal bond hybridization, isotropic spheres self-assemble into planar monolayers, while anisotropic snowman-like particles self-assemble into hollow monolayer microcapsules. A modest change of the building blocks thus results in a significant leap in the complexity of the self-assembled structures. In other words, these relatively simple building blocks self-assemble into dramatically more complex structures than similar particles that are isotropic or non-deformable

Diabetes-Specific Nutrition Algorithm: A Transcultural Program to Optimize Diabetes and Prediabetes Care

Type 2 diabetes (T2D) and prediabetes have a major global impact through high disease prevalence, significant downstream pathophysiologic effects, and enormous financial liabilities. To mitigate this disease burden, interventions of proven effectiveness must be used. Evidence shows that nutrition therapy improves glycemic control and reduces the risks of diabetes and its complications. Accordingly, diabetes-specific nutrition therapy should be incorporated into comprehensive patient management programs. Evidence-based recommendations for healthy lifestyles that include healthy eating can be found in clinical practice guidelines (CPGs) from professional medical organizations. To enable broad implementation of these guidelines, recommendations must be reconstructed to account for cultural differences in lifestyle, food availability, and genetic factors. To begin, published CPGs and relevant medical literature were reviewed and evidence ratings applied according to established protocols for guidelines. From this information, an algorithm for the nutritional management of people with T2D and prediabetes was created. Subsequently, algorithm nodes were populated with transcultural attributes to guide decisions. The resultant transcultural diabetes-specific nutrition algorithm (tDNA) was simplified and optimized for global implementation and validation according to current standards for CPG development and cultural adaptation. Thus, the tDNA is a tool to facilitate the delivery of nutrition therapy to patients with T2D and prediabetes in a variety of cultures and geographic locations. It is anticipated that this novel approach can reduce the burden of diabetes, improve quality of life, and save lives. The specific Southeast Asian and Asian Indian tDNA versions can be found in companion articles in this issue of Current Diabetes Reports

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes.

Abstract BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown. METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy. RESULTS: In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P<0.001 for noninferiority) but was not superior to placebo with respect to efficacy (P=0.06 for superiority). The rates of death from cardiovascular causes, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, hospitalization for heart failure, and hospitalization for acute coronary syndrome, and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the two groups. CONCLUSIONS: Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo. (Funded by Amylin Pharmaceuticals; EXSCEL ClinicalTrials.gov number, NCT01144338 .)