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People with type 1 diabetes are at risk for early- and late-onset hypoglycemia following exercise. Reducing this risk may be possible with strategic modifications in carbohydrate intake and insulin use. We examined the exercise preparations and management techniques used by individuals with type 1 diabetes before and after physical activity and sought to determine whether use of differing diabetes technologies affects these health-related behaviours.We studied 502 adults from the Type 1 Diabetes Exchange's online patient community, Glu, who had completed an online survey focused on diabetes self-management and exercise.Many respondents reported increasing carbohydrate intake before (79%) and after (66%) exercise as well as decreasing their meal boluses before (53%) and after (46%) exercise. Most reported adhering to a target glucose level before starting exercise (77%). Despite these accommodations, the majority reported low blood glucose (BG) levels after exercise (70%). The majority of users of both insulin pump therapy (CSII) and continuous glucose monitoring (CGM) (Combined) reported reducing basal insulin around exercise (55%), with fewer participants adjusting basal insulin when using other devices (SMBG only = 20%; CGM = 34%; CSII = 42%; p0.001). However, CSII and Combined users reported that exercise makes their BG levels harder to control (p0.05) and makes them feel less able to predict their BG levels while exercising (p0.001); they show agreement that fear of low BG levels keeps them from exercising (p0.01).These findings highlight the need for exercise-management strategies tailored to individuals' overall diabetes management, for despite making exercise-specific adjustments for care, many people with type 1 diabetes still report significant difficulties with BG control when it comes to exercise.

Adult stem cells possess the ability to differentiate and mature into defined cell types; however, tissue-specificity and donor and culture inconsistencies have presented a challenge in identifying these cells. Adult adherent dermal cell-products have been efficiently utilized for isogenic cosmetic therapies. The purpose of this study is to identify, isolate, and characterize progenitor subsets from adult adherent dermal cells capable of ex vivo differentiation. LAVIV® adult dermal cells were independently immunoselected for CD146, CD271, and CD73/CD90/CD105 to investigate the mesenchymal differentiation capacity and possible enrichment in the purified fractions. After differentiation, the osteogenic, chondrogenic, and adipogenic potential and cell-specific gene expression were evaluated and compared for each phenotype. Adult dermal cells possess the ability to differentiate into the three cell lineages, osteocyte, chondrocyte, and adipocyte that co-express the adult stem cell immunophenotypic markers CD146 and CD271 with independent enrichment of the multipotent capacity for both fractions. We conclude that subpopulations in human dermal primary cultures possess the potential to differentiate into other cell types providing a novel source of multipotent cells for regenerative medicine.

Urea cycle disorders are incurable enzymopathies that affect nitrogen metabolism and typically lead to hyperammonemia. Arginase deficiency results from a mutation in Arg1, the enzyme regulating the final step of ureagenesis and typically results in developmental disabilities, seizures, spastic diplegia, and sometimes death. Current medical treatments for urea cycle disorders are only marginally effective, and for proximal disorders, liver transplantation is effective but limited by graft availability. Advances in human induced pluripotent stem cell research has allowed for the genetic modification of stem cells for potential cellular replacement therapies. In this study, we demonstrate a universally-applicable CRISPR/Cas9-based strategy utilizing exon 1 of the hypoxanthine-guanine phosphoribosyltransferase locus to genetically modify and restore arginase activity, and thus ureagenesis, in genetically distinct patient-specific human induced pluripotent stem cells and hepatocyte-like derivatives. Successful strategies restoring gene function in patient-specific human induced pluripotent stem cells may advance applications of genetically modified cell therapy to treat urea cycle and other inborn errors of metabolism.

Pluripotent stem cells offer great therapeutic promise for personalized treatment platforms for numerous injuries, disorders, and diseases. Octamer-binding transcription factor 4 (OCT4) is a key regulatory gene maintaining pluripotency and self-renewal of mammalian cells. With site-specific integration for gene correction in cellular therapeutics, use of the OCT4 promoter may have advantages when expressing a suicide gene if pluripotency remains. However, the human OCT4 promoter region is 4 kb in size, limiting the capacity of therapeutic genes and other regulatory components for viral vectors, and decreasing the efficiency of homologous recombination. The purpose of this investigation was to characterize the functionality of a novel 967bp OCT4-short response element during pluripotency and to examine the OCT4 titer-dependent response during differentiation to human derivatives not expressing OCT4. Our findings demonstrate that the OCT4-short response element is active in pluripotency and this activity is in high correlation with transgene expression in vitro, and the OCT4-short response element is inactivated when pluripotent cells differentiate. These studies demonstrate that this shortened OCT4 regulatory element is functional and may be useful as part of an optimized safety component in a site-specific gene transferring system that could be used as an efficient and clinically applicable safety platform for gene transfer in cellular therapeutics.