2,895 research outputs found

    Parental mastery of continuous subcutaneous insulin infusion skills and glycemic control in youth with type 1 diabetes

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    OBJECTIVE: The purpose of this study is to determine whether parental knowledge of the continuous subcutaneous insulin infusion (CSII) device affects glycemic control as measured by hemoglobin A1c (A1C) level. SUBJECTS AND METHODS: Parents of children with type 1 diabetes mellitus (T1DM) using CSII completed a 14-item questionnaire. Questions 1-10 were knowledge-based questions that required the parent to extract specific information from their child\u27s CSII device. Questions 11-14 asked parents to provide a self-assessment of their CSII knowledge. RESULTS: Twenty-two parents of youth with T1DM participated in the study. Ten of the youth were in the Low-A1C group (A1C/=8%). Parents of youth in the Low-A1C group scored statistically better on the 10-item performance survey than parents of youth in the High-A1C group. Most of the parents of children in the Low-A1C group responded that they knew their child\u27s insulin pump very well and that their pump knowledge had increased since their child started on the insulin pump. CONCLUSIONS: Our findings reveal that youth with T1DM whose parents are more knowledgeable about pump functions have optimal glycemic control as evidenced by A1C. These findings underscore the importance of ongoing pump training for both pediatric patients and their parents

    Impact of \u3cem\u3eMYH6\u3c/em\u3e Variants in Hypoplastic Left Heart Syndrome

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    Hypoplastic left heart syndrome (HLHS) is a clinically and anatomically severe form of congenital heart disease (CHD). Although prior studies suggest that HLHS has a complex genetic inheritance, its etiology remains largely unknown. The goal of this study was to characterize a risk gene in HLHS and its effect on HLHS etiology and outcome. We performed next-generation sequencing on a multigenerational family with a high prevalence of CHD/HLHS, identifying a rare variant in the α-myosin heavy chain (MYH6) gene. A case-control study of 190 unrelated HLHS subjects was then performed and compared with the 1000 Genomes Project. Damaging MYH6 variants, including novel, missense, in-frame deletion, premature stop, de novo, and compound heterozygous variants, were significantly enriched in HLHS cases (P \u3c 1 × 10−5). Clinical outcomes analysis showed reduced transplant-free survival in HLHS subjects with damaging MYH6 variants (P \u3c 1 × 10−2). Transcriptome and protein expression analyses with cardiac tissue revealed differential expression of cardiac contractility genes, notably upregulation of the β-myosin heavy chain (MYH7) gene in subjects with MYH6 variants (P \u3c 1 × 10−3). We subsequently used patient-specific induced pluripotent stem cells (iPSCs) to model HLHS in vitro. Early stages of in vitro cardiomyogenesis in iPSCs derived from two unrelated HLHS families mimicked the increased expression of MYH7 observed in vivo (P \u3c 1 × 10−2), while revealing defective cardiomyogenic differentiation. Rare, damaging variants in MYH6 are enriched in HLHS, affect molecular expression of contractility genes, and are predictive of poor outcome. These findings indicate that the etiology of MYH6-associated HLHS can be informed using iPSCs and suggest utility in future clinical applications

    Characterizing the gut microbiome in trauma: significant changes in microbial diversity occur early after severe injury.

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    Background:Recent studies have demonstrated the vital influence of commensal microbial communities on human health. The central role of the gut in the response to injury is well described; however, no prior studies have used culture-independent profiling techniques to characterize the gut microbiome after severe trauma. We hypothesized that in critically injured patients, the gut microbiome would undergo significant compositional changes in the first 72 hours after injury. Methods:Trauma stool samples were prospectively collected via digital rectal examination at the time of presentation (0 hour). Patients admitted to the intensive care unit (n=12) had additional stool samples collected at 24 hours and/or 72 hours. Uninjured patients served as controls (n=10). DNA was extracted from stool samples and 16S rRNA-targeted PCR amplification was performed; amplicons were sequenced and binned into operational taxonomic units (OTUs; 97% sequence similarity). Diversity was analyzed using principle coordinates analyses, and negative binomial regression was used to determine significantly enriched OTUs. Results:Critically injured patients had a median Injury Severity Score of 27 and suffered polytrauma. At baseline (0 hour), there were no detectable differences in gut microbial community diversity between injured and uninjured patients. Injured patients developed changes in gut microbiome composition within 72 hours, characterized by significant alterations in phylogenetic composition and taxon relative abundance. Members of the bacterial orders Bacteroidales, Fusobacteriales and Verrucomicrobiales were depleted during 72 hours, whereas Clostridiales and Enterococcus members enriched significantly. Discussion:In this initial study of the gut microbiome after trauma, we demonstrate that significant changes in phylogenetic composition and relative abundance occur in the first 72 hours after injury. This rapid change in intestinal microbiota represents a critical phenomenon that may influence outcomes after severe trauma. A better understanding of the nature of these postinjury changes may lead to the ability to intervene in otherwise pathological clinical trajectories. Level of evidence:III. Study type:Prognostic/epidemiological

    Gender differences in the trajectories of late-life depressive symptomology and probable depression in the years prior to death

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    BACKGROUND: Gender differences in depression are well established. Whether these differences persist into late life and in the years preceding death is less clear. There is a suggestion that there is no increased likelihood of depression in late life, but that there is an increase in depressive symptomology, particularly with proximity to death. We compared trajectories of probable depression and depressive symptomology between men and women over age and distance-to-death metrics to determine whether reports of depressive symptoms are more strongly related to age or mortality. METHODS: Participants (N = 2,852) from the Dynamic Analyses to Optimise Ageing (DYNOPTA) project had a mean age of 75 years (SD = 5.68 years) at baseline and were observed for up to 16 years prior to death. Multi-level regression models estimated change in depressive symptomology and probable depression over two time metrics, increasing age, and distance-to-death. RESULTS: Increases in depressive symptomology were reported over increasing age and in the years approaching death. Only male participants reported increased probable depression in the years preceding death. Models that utilized distance-to-death metrics better represented changes in late-life depression, although any changes in depression appear to be accounted for by co-varying physical health status. CONCLUSIONS: As death approaches, there are increases in the levels of depressive symptomology even after controlling for socio-demographic and health covariates. In line with increases in suicide rates in late life, male participants were at greater risk of reporting increases in depressive symptomology.NHMRC (National Health and Medical Research Council of Australia
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