Stressful Life Events in Young Adults With Type 1 Diabetes in the U.S. T1D Exchange Clinic Registry

PurposeThe purpose was to test associations among stressful life events, frequency of missed insulin doses, and glycemic control in young adults with type 1 diabetes (T1D).DesignThe study was a cross‐sectional descriptive secondary analysis.MethodsData from 2,921 participants (ages 18–26 years) in the U.S. T1D Exchange Clinic Registry were analyzed. Report of a stressful life event was defined as one or more positive responses on a 17‐item stressful life events index and defined as a dichotomous variable (yes or no). Frequency of missed insulin doses was measured using a single self‐report item and collapsed into two levels (fewer than three times a week, three or more times a week). The glycosylated hemoglobin (A1c) level recorded at the time of enrollment was used to assess glycemic control.FindingsNearly half (48.6%) of the participants reported having a stressful life event during the previous year. The most frequently reported stressful life events were problems at work or school (16.1%), serious arguments with family members or a close friend (15.2%), and financial problems in the family (13.8%). Compared to the participants not reporting stressful life events, those who reported stressful life events were more likely to be older, female, with a higher educational attainment level, and not working or unemployed. Those who reported a stressful life event were more likely than those who did not to say they typically missed insulin doses at least three times a week and less likely to say they typically missed insulin doses fewer than three times a week (p < .001 adjusted for age, sex, race or ethnicity, educational attainment level, duration of T1D diagnosis, and insulin delivery method). Mean A1c level was higher for the group who reported having a stressful life event in the past 12 months compared to the group who did not (8.7 ± 1.8% vs. 8.2 ± 1.6%; adjusted p < .001). The results of a mediation analysis suggest that the measure of frequency of missed insulin doses may be a mediator of the relationship between recent stressful life events and glycemic control (Sobel test: ab = .841, 95% confidence interval = 0.064–1.618).ConclusionsThese findings suggest that, for young adults with T1D, the experience of stressful life events may increase their risk for poorer glycemic control, possibly by disrupting adherence with insulin doses.Clinical RelevanceFurther exploration of these relationships may allow for the potential for identifying those at risk and assisting them with more positive approaches to managing stressful events.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146646/1/jnu12428.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146646/2/jnu12428_am.pd

Cohesion in aphasic language

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Chapter 3: General Interviewing Techniques: Developing Evidence-Based Practices for Standardized Interviewing Appendix 3

Table A3A.1 Summary of Basic Techniques of Standardized Interviewing (adapted from Fowler and Mangione 1990, pp. 35-53) Table A3A.2 Basic Question Forms (Response Formats

The Evolution of Initial Global Aphasia: Implications for Prognosis

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Response Variability in Naming: A Computational Study

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Variant of TYR and Autoimmunity Susceptibility Loci in Generalized Vitiligo.

BACKGROUND Generalized vitiligo is an autoimmune disease characterized by melanocyte loss, which results in patchy depigmentation of skin and hair, and is associated with an elevated risk of other autoimmune diseases. METHODS To identify generalized vitiligo susceptibility loci, we conducted a genomewide association study. We genotyped 579,146 single-nucleotide polymorphisms (SNPs) in 1514 patients with generalized vitiligo who were of European-derived white (CEU) ancestry and compared the genotypes with publicly available control genotypes from 2813 CEU persons. We then tested 50 SNPs in two replication sets, one comprising 677 independent CEU patients and 1106 CEU controls and the other comprising 183 CEU simplex trios with generalized vitiligo and 332 CEU multiplex families. RESULTS We detected significant associations between generalized vitiligo and SNPs at several loci previously associated with other autoimmune diseases. These included genes encoding major-histocompatibility-complex class I molecules (P=9.05×10−23) and class II molecules (P=4.50×10−34), PTPN22 (P=1.31×10−7), LPP (P=1.01×10−11), IL2RA (P=2.78×10−9), UBASH3A (P=1.26×10−9), and C1QTNF6 (P=2.21×10−16). We also detected associations between generalized vitiligo and SNPs in two additional immune-related loci, RERE (P=7.07×10−15) and GZMB (P=3.44×10−8), and in a locus containing TYR (P=1.60×10−18), encoding tyrosinase. CONCLUSIONS We observed associations between generalized vitiligo and markers implicating multiple genes, some associated with other autoimmune diseases and one (TYR) that may mediate target-cell specificity and indicate a mutually exclusive relationship between susceptibility to vitiligo and susceptibility to melanoma

Common variants in FOXP1 are associated with generalized vitiligo

In a recent genome-wide association study of generalized vitiligo, we identified ten confirmed susceptibility loci. By testing additional loci that showed suggestive association in the genome-wide study, using two replication cohorts of European descent, we observed replicated association of generalized vitiligo with variants at 3p13 encompassing FOXP1 (rs17008723, combined P = 1.04 × 10−8) and with variants at 6q27 encompassing CCR6 (rs6902119, combined P = 3.94 × 10−7)

Provider Attitudes toward the Voluntary Medical Male Circumcision Scale-Up in Kenya, South Africa, Tanzania and Zimbabwe.

Countries participating in voluntary medical male circumcision (VMMC) scale-up have adopted most of six elements of surgical efficiency, depending on national policy. However, effective implementation of these elements largely depends on providers' attitudes and subsequent compliance. We explored the concordance between recommended practices and providers' perceptions toward the VMMC efficiency elements, in part to inform review of national policies. As part of Systematic Monitoring of the VMMC Scale-up (SYMMACS), we conducted a survey of VMMC providers in Kenya, South Africa, Tanzania, and Zimbabwe. SYMMACS assessed providers' attitudes and perceptions toward these elements in 2011 and 2012. A restricted analysis using 2012 data to calculate unadjusted odds ratios and 95% confidence intervals for the country effect on each attitudinal outcome was done using logistic regression. As only two countries allow more than one cadre to perform the surgical procedure, odds ratios looking at country effect were adjusted for cadre effect for these two countries. Qualitative data from open-ended responses were used to triangulate with quantitative analyses. This analysis showed concordance between each country's policies and provider attitudes toward the efficiency elements. One exception was task-shifting, which is not authorized in South Africa or Zimbabwe; providers across all countries approved this practice. The decision to adopt efficiency elements is often based on national policies. The concordance between the policies of each country and provider attitudes bodes well for compliance and effective implementation. However, study findings suggest that there may be need to consult providers when developing national policies.\u

phot1 inhibition of ABCB19 primes lateral auxin fluxes in the shoot apex required for phototropism

It is well accepted that lateral redistribution of the phytohormone auxin underlies the bending of plant organs towards light. In monocots, photoreception occurs at the shoot tip above the region of differential growth. Despite more than a century of research, it is still unresolved how light regulates auxin distribution and where this occurs in dicots. Here, we establish a system in Arabidopsis thaliana to study hypocotyl phototropism in the absence of developmental events associated with seedling photomorphogenesis. We show that auxin redistribution to the epidermal sites of action occurs at and above the hypocotyl apex, not at the elongation zone. Within this region, we identify the auxin efflux transporter ATP-BINDING CASSETTE B19 (ABCB19) as a substrate target for the photoreceptor kinase PHOTOTROPIN 1 (phot1). Heterologous expression and physiological analyses indicate that phosphorylation of ABCB19 by phot1 inhibits its efflux activity, thereby increasing auxin levels in and above the hypocotyl apex to halt vertical growth and prime lateral fluxes that are subsequently channeled to the elongation zone by PIN-FORMED 3 (PIN3). Together, these results provide new insights into the roles of ABCB19 and PIN3 in establishing phototropic curvatures and demonstrate that the proximity of light perception and differential phototropic growth is conserved in angiosperm

Interleukin-22 Protects Intestinal Stem Cells from Immune-Mediated Tissue Damage and Regulates Sensitivity to Graft versus Host Disease

SummaryLittle is known about the maintenance of intestinal stem cells (ISCs) and progenitors during immune-mediated tissue damage or about the susceptibility of transplant recipients to tissue damage mediated by the donor immune system during graft versus host disease (GVHD). We demonstrate here that deficiency of recipient-derived IL-22 increased acute GVHD tissue damage and mortality, that ISCs were eliminated during GVHD, and that ISCs as well as their downstream progenitors expressed the IL-22 receptor. Intestinal IL-22 was produced after bone marrow transplant by IL-23-responsive innate lymphoid cells (ILCs) from the transplant recipients, and intestinal IL-22 increased in response to pretransplant conditioning. However, ILC frequency and IL-22 amounts were decreased by GVHD. Recipient IL-22 deficiency led to increased crypt apoptosis, depletion of ISCs, and loss of epithelial integrity. Our findings reveal IL-22 as a critical regulator of tissue sensitivity to GVHD and a protective factor for ISCs during inflammatory intestinal damage