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Samuel GrossmanDepartment of Veterans Affairs, New York Harbor Healthcare System, New York, NY, USA; Diabetes Care On-The-Go Inc, Brooklyn, NY, USA; Hunter-Bellevue School of Nursing, Hunter College, City University of New York, New York, NY, USA; Arnold and Marie Schwartz College of Pharmacy of Long Island University, Brooklyn, NY, USA; Garden State Association of Diabetes Educators, Edison, NJ, USAAbstract: Intensive glycemic control using insulin therapy may be appropriate for many healthy older adults to reduce premature mortality and morbidity, improve quality of life, and reduce health care costs. However, frail elderly people are more prone to develop complications from hypoglycemia, such as confusion and dementia. Overall, older persons with type 2 diabetes mellitus are at greater risk of death from cardiovascular disease (CVD) than from intermittent hyperglycemia; therefore, diabetes management should always include CVD prevention and treatment in this patient population. Pharmacists can provide a comprehensive medication review with subsequent recommendations to individualize therapy based on medical and cognitive status. As part of the patient’s health care team, pharmacists can provide continuity of care and communication with other members of the patient’s health care team. In addition, pharmacists can act as educators and patient advocates and establish patient-specific goals to increase medication effectiveness, adherence to a medication regimen, and minimize the likelihood of adverse events.Keywords: glycemic control, hyperglycemia, continuity of care, hypertension and cardiovascular disease, elderly, type 2 diabetes, pharmacist

Iterative P450 enzymes are powerful biocatalysts for selective late-stage C-H oxidation of complex natural product scaffolds. These enzymes represent useful tools for selectivity and cascade reactions, facilitating direct access to core structure diversification. Recently, we reported the structure of the multifunctional bacterial P450 TamI and elucidated the molecular basis of its substrate binding and strict reaction sequence at distinct carbon atoms of the substrate. Here, we report the design and characterization of a toolbox of TamI biocatalysts, generated by mutations at Leu101, Leu244, and/or Leu295, that alter the native selectivity, step sequence, and number of reactions catalyzed, including the engineering of a variant capable of catalyzing a four-step oxidative cascade without the assistance of the flavoprotein and oxidative partner TamL. The tuned enzymes override inherent substrate reactivity, enabling catalyst-controlled C-H functionalization and alkene epoxidation of the tetramic acid-containing natural product tirandamycin. Five bioactive tirandamycin derivatives (6-10) were generated through TamI-mediated enzymatic synthesis. Quantum mechanics calculations and MD simulations provide important insights into the basis of altered selectivity and underlying biocatalytic mechanisms for enhanced continuous oxidation of the iterative P450 TamI.

Background The ventroanterior insula is implicated in the experience, expression, and recognition of disgust; however, whether this brain region is required for recognizing disgust or regulating disgusting behaviors remains unknown. Methods We examined the brain correlates of the presence of disgusting behavior and impaired recognition of disgust using voxel-based morphometry in a sample of 305 patients with heterogeneous patterns of neurodegeneration. Permutation-based analyses were used to determine regions of decreased gray matter volume at a significance level p