Role of arterial stiffness and endothelial dysfunction on lower limb performance in older adults with type 2 diabetes: A cross-sectional study

AimTo verify whether arterial stiffness and endothelial dysfunction influence lower limb muscle strength and gait speed in older adults with type 2 diabetes mellitus (T2DM).MethodsCross-sectional study including seventy-eight older adults with T2DM (aged 67 ± 6 years and 42 % male). Arterial stiffness was assessed using pulse wave velocity (PWV), while endothelial function was measured by flow-mediated dilation (FMD). Lower limb muscle strength and gait speed were assessed using the 30-second chair stand test (30s-CST) and 10-Meter Walk Test, respectively.ResultsBoth PWV (m/s) and FMD (%) were univariately associated with number of repetitions in 30s-CST and gait speed (P < 0.05). After control for age, sex and body mass index, PWV remained associated with repetitions in 30s-CST (95 % CI: ?0.494 to ?0.054; P = 0.015) and gait speed (95 % CI: ?0.039 to ?0.002; P = 0.031). After adjustments for control variables, T2DM duration and glycemic control, FMD was associated with repetitions in 30s-CST (95 % CI: 0.008 to 0.324; P = 0.039) and gait speed (95 % CI: 0.011 to 0.038; P = 0.001).ConclusionIn older adults with T2DM, both arterial stiffness and endothelial dysfunction are associated with decreased leg muscle strength and slower gait speed.     

Establishing the doctor of nursing practice project ethical review process to improve standardization,efficiency, and timeliness

BackgroundDNP Scholarly projects require review for scientific merit and human subject protection. Rapid growth of DNP programs and projects has increased Institutional Review Board (IRB) burden and increased the length of project approval time when most DNP scholarly projects are quality improvement (QI) projects and not deemed Human Subjects Research (HSR).PurposeDevelop a process and describe the rationale for creating and implementing a Project Ethical Review Committee (PERC) in the School of Nursing and to evaluate the experience of the first cohort of submissions.ProcessCommittee was formed using expert consensus approach, in collaboration with IRB. Standards of Procedures and training materials created.Outcome measure100 projects submitted to committee; 95 deemed QI (95%) and 5 projects considered HSR (5%). First 94 projects were reviewed, and approval letters sent within 8 weeks.DiscussionThis paper discusses how PERC ensures rigorous and ethical review process for standardization, timeliness, and efficiency.     

An Artificial Gut/Absorption Simulator: Simultaneous Evaluation of Desupersaturation and Absorption from Ketoconazole Supersaturated Solutions

For supersaturating formulations of BCS-II compounds, which by definition have high intestinal permeability, a closed USP apparatus does not provide the necessary absorptive conditions during dissolution. To address this, an artificial gut simulator (AGS) has been constructed consisting of a 2.5 mL donor compartment in which a hollow fiber-based absorption module is suspended. Drug from donor diffuses across the hollow fiber membrane to be absorbed by the continuously flowing intraluminal receiver fluid. The membrane surface area and intraluminal fluid flow rate are tuned to obtain the physiologically observed absorption rate constant for a weakly basic, poorly water-soluble model compound, ketoconazole (KTZ). Supersaturated solutions of KTZ were generated in the donor in pH 6.5 phosphate buffer by the pH-shift method in the absence (closed system, control) and presence (open system, biorelevant) of an optimally or suboptimally tuned absorption module. Drug concentrations in the donor and intraluminal fluids were determined by in-line UV spectroscopy. The presence of an absorptive sink reduced the supersaturated solution's crystallization propensity, more so in the case of the optimally tuned AGS. This study demonstrates the significance of simulating absorption of drug at a physiological rate during dissolution studies, especially to predict the performance of formulations of BCS-II drugs.     

Drug-induced acne with elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis

Elexacaftor/tezacaftor/ivacaftor (ELX-TEZ-IVA) is a Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulator shown to improve lung function and reduce sweat chloride in people with Cystic Fibrosis (CF). The only commonly reported dermatologic adverse effect with CFTR modulators including ELX-TEZ-IVA is rash. In this case series, we describe 19 patients who reported new onset or worsening of acne after initiation of this drug to their CF pharmacist or another member of their CF care team. The mechanism and frequency of this adverse effect is unknown.     

Mitochondrial dysfunction from malathion and chlorpyrifos exposure is associated with degeneration of GABAergic neurons in Caenorhabditis elegans

Toxicity resulting from off-target effects, beyond acetylcholine esterase inhibition, for the commonly used organophosphate (OP) insecticides chlorpyrifos (CPS) and malathion (MA) was investigated using Saccharomyces cerevisiae and Caenorhabditis elegans model systems. Mitochondrial damage and dysfunction were observed in yeast following exposure to CPS and MA, suggesting this organelle is a major target. In the C. elegans model, the mitochondrial unfolded protein response pathway showed the most robust induction from CPS and MA treatment among stress responses examined. GABAergic neurodegeneration was observed with CPS and MA exposure. Impaired movement observed in C. elegans exposed to CPS and MA may be the result of motor neuron damage. Our analysis suggests that stress from CPS and MA results in mitochondrial dysfunction, with GABAergic neurons sensitized to these effects. These findings may aid in the understanding of toxicity from CPS and MA from high concentration exposure leading to insecticide poisoning.     

Inequalities in the Distribution of Childhood Adversity From Birth to 11 Years

ObjectiveExposure to early adversity carries long term harmful consequences for children's health and development. This study aims to 1) estimate the prevalence of childhood adversity for Australian children from infancy to 10–11 years, and 2) document inequalities in the distribution of adversity according to socioeconomic position (SEP), Indigenous status, and ethnicity.MethodsAdversity was assessed every 2 years from 0–1 to 10–11 years in the nationally representative birth cohort of the Longitudinal Study of Australian Children (N = 5107). Adversity included legal problems; family violence; household mental illness; household substance abuse; harsh parenting; parental separation/divorce; unsafe neighborhood; family member death; and bullying (from 4 to 5 years). Adversities were examined individually and summed for a measure of multiple adversity (2+ adverse experiences).ResultsBy 10–11 years, 52.8% (95% confidence interval [CI] 51.0–54.7) of children had been exposed to 2 or more adversities. When combined with low SEP, children from ethnic minority and from Indigenous backgrounds had 4 to 8 times the odds of exposure to 2 or more adversities than children from higher SEP Anglo-Euro backgrounds, respectively (odds ratio [OR] 4.3, 95% CI 2.8–6.6 and OR 8.1, 95% CI 4.4–14.8). Ethnic minority and Indigenous children from higher SEP backgrounds had increased odds of exposure to multiple adversity than similarly advantaged Anglo-Euro children (OR 1.8, 95% CI 1.4–2.3 and OR 2.3, 95% CI 1.3–4.3, respectively).ConclusionsAddressing early adversity is a significant opportunity to promote health over the life course, and reduce health inequalities experienced by marginalized groups of children.