503 research outputs found

    “I had to adapt to continue being a student to the best of my ability”: Identifying Occupational Therapy Students’ Processes of Adapting to Academic Disruption

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    In the wake of COVID-19, practitioners, educators, and students had to shift to virtual interactions while experiencing significant unknowns and valid fears. This project describes the lived experiences of 37 occupational therapy students who lived through this international pandemic examining their reflections of how occupational therapy theories and models of practice could inform approaches to adapt to the changing context of their lives. Narratives of students collected as part of routine educational assessments in an introduction to occupational therapy theory course were examined using methods of content analysis to understand the perspectives of students’ needs, supports, and mechanisms of adaption as well as how students used personal experiences as part of transformative learning in the process of understanding approaches used clinically in occupational therapy practice. Three thematic categories emerged: ‘the demand to adapt,’ ‘engagement,’ and ‘mastery/agency.’ More students describe connecting to concepts from the model of Occupational Adaption (OA; Schkade & Schultz, 1992) versus other models of practice to achieve satisfactory engagement with occupations. Understanding these mechanisms of adaption may help faculty and university administrators effectively develop intervention strategies to help manage students’ reactions to disruptions in the future

    Understanding Occupational Therapy Admissions Decisions Related to Diversity

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    The vast majority of occupational therapy (OT) practitioners are white, leaving gaps between the representation of our profession and those we serve. Admission practices determine the future of the profession. This cross-sectional study aimed to understand how admission requirements, particularly the Graduate Record Examination (GRE) and interview, influenced OT graduate students\u27 application decisions, specifically those who identified as a first-generation college student (FGCS), underrepresented minority, English as a second language, or receiving public assistance. Methods included an online survey distributed to current OT graduate students. The survey consisted of background information, closed-ended questions on influence of application requirements, open-ended questions on priority factors in application decision-making, and barriers and supports to the application process. Of the 263 participants, 37.4% agreed that the GRE requirement influenced their application, most frequently citing test-taking ability and cost as reasons; 16.2% agreed that an in-person interview requirement influenced their application, most frequently citing cost and interviewing ability as reasons. Participants identifying as FGCS (

    Structure of the lectin mannose 6-phosphate receptor homology (MRH) domain of glucosidase II an enzyme that regulates glycoprotein folding quality control in the endoplasmic reticulum

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    Here we report for the first time the three-dimensional structure of a mannose 6-phosphate receptor homology (MRH) domain present in a protein with enzymatic activity, glucosidase II (GII). GII is involved in glycoprotein folding in the endoplasmic reticulum. GII removes the two innermost glucose residues from the Glc3Man9GlcNAc2 transferred to nascent proteins and the glucose added by UDP-Glc:glycoprotein glucosyltransferase. GII is composed of a catalytic GIIα subunit and a regulatory GIIβ subunit. GIIβ participates in the endoplasmic reticulum localization of GIIα and mediates in vivo enhancement of N-glycan trimming by GII through its C-terminal MRH domain. We determined the structure of a functional GIIβ MRH domain by NMR spectroscopy. It adopts a β-barrel fold similar to that of other MRH domains, but its binding pocket is the most shallow known to date as it accommodates a single mannose residue. In addition, we identified a conserved residue outside the binding pocket (Trp-409) present in GIIβ but not in other MRHs that influences GII glucose trimming activity.Fil: Olson, Linda J.. Medical College Of Wisconsin; Estados UnidosFil: Orsi, Ramiro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Alculumbre, Solana G.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Peterson, Francis C.. Medical College Of Wisconsin; Estados UnidosFil: Stigliano, Ivan Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Parodi, Armando Jose A.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: D'alessio, Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universidad de Buenos Aires; ArgentinaFil: Dahms, Nancy M.. Medical College Of Wisconsin; Estados Unido

    Reproducibility of ambulatory blood pressure changes from the initial values on two different days

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    OBJECTIVE: We tested the reproducibility of changes in the ambulatory blood pressure (BP) from the initial values, an indicator of BP reactivity and cardiovascular health outcomes, in young, healthy adults. METHOD: The subjects wore an ambulatory BP monitor attached by the same investigator at the same time of day until the next morning on two different days (day 1 and day 2) separated by a week. We compared the ambulatory BP change from the initial values at hourly intervals over 24 waking and sleeping hours on days 1 and 2 using linear regression and repeated measures analysis of covariance. RESULTS: The subjects comprised 88 men and 57 women (mean age±SE 22.4±0.3 years) with normal BP (118.3±0.9/69.7±0.6 mmHg). For the total sample, the correlation between the ambulatory BP change on day 1 vs. day 2 over 24, waking, and sleeping hours ranged from 0.37-0.61; among women, the correlation was 0.38-0.71, and among men, it was 0.24-0.52. Among women, the ambulatory systolic/diastolic BP change was greater by 3.1±1.0/2.4±0.8 mmHg over 24 hours and by 3.0±1.1/2.4±0.8 mmHg over waking hours on day 1 than on day 2. The diastolic ambulatory BP change during sleeping hours was greater by 2.2±0.9 mmHg on day 1 than on day 2, but the systolic ambulatory BP change during sleeping hours on days 1 and 2 did not differ. Among men, the ambulatory BP change on days 1 and 2 did not differ. CONCLUSION: Our primary findings were that the ambulatory BP change from the initial values was moderately reproducible; however, it was more reproducible in men than in women. These results suggest that women, but not men, may experience an alerting reaction to initially wearing the ambulatory BP monitor

    Exome-Wide Association Study of Endometrial Cancer in a Multiethnic Population

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    Endometrial cancer (EC) contributes substantially to total burden of cancer morbidity and mortality in the United States. Family history is a known risk factor for EC, thus genetic factors may play a role in EC pathogenesis. Three previous genome- wide association studies (GWAS) have found only one locus associated with EC, suggesting that common variants with large effects may not contribute greatly to EC risk. Alternatively, we hypothesize that rare variants may contribute to EC risk. We conducted an exome-wide association study (EXWAS) of EC using the Infinium HumanExome BeadChip in order to identify rare variants associated with EC risk. We successfully genotyped 177,139 variants in a multiethnic population of 1,055 cases and 1,778 controls from four studies that were part of the Epidemiology of Endometrial Cancer Consortium (E2C2). No variants reached global significance in the study, suggesting that more power is needed to detect modest associations between rare genetic variants and risk of EC

    State of Type 1 Diabetes Management and Outcomes from the T1D Exchange in 2016–2018

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    Objective: To provide a snapshot of the profile of adults and youth with type 1 diabetes (T1D) in the United States and assessment of longitudinal changes in T1D management and clinical outcomes in the T1D Exchange registry. Research Design and Methods: Data on diabetes management and outcomes from 22,697 registry participants (age 1–93 years) were collected between 2016 and 2018 and compared with data collected in 2010–2012 for 25,529 registry participants. Results: Mean HbA1c in 2016–2018 increased from 65 mmol/mol at the age of 5 years to 78 mmol/mol between ages 15 and 18, with a decrease to 64 mmol/mol by age 28 and 58–63 mmol/mol beyond age 30. The American Diabetes Association (ADA) HbA1c goal of 10-fold in children <12 years old. HbA1c levels were lower in CGM users than nonusers. Severe hypoglycemia was most frequent in participants ≥50 years old and diabetic ketoacidosis was most common in adolescents and young adults. Racial differences were evident in use of pumps and CGM and HbA1c levels. Conclusions: Data from the T1D Exchange registry demonstrate that only a minority of adults and youth with T1D in the United States achieve ADA goals for HbA1c

    Huntingtin Interacting Proteins Are Genetic Modifiers of Neurodegeneration

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    Huntington's disease (HD) is a fatal neurodegenerative condition caused by expansion of the polyglutamine tract in the huntingtin (Htt) protein. Neuronal toxicity in HD is thought to be, at least in part, a consequence of protein interactions involving mutant Htt. We therefore hypothesized that genetic modifiers of HD neurodegeneration should be enriched among Htt protein interactors. To test this idea, we identified a comprehensive set of Htt interactors using two complementary approaches: high-throughput yeast two-hybrid screening and affinity pull down followed by mass spectrometry. This effort led to the identification of 234 high-confidence Htt-associated proteins, 104 of which were found with the yeast method and 130 with the pull downs. We then tested an arbitrary set of 60 genes encoding interacting proteins for their ability to behave as genetic modifiers of neurodegeneration in a Drosophila model of HD. This high-content validation assay showed that 27 of 60 orthologs tested were high-confidence genetic modifiers, as modification was observed with more than one allele. The 45% hit rate for genetic modifiers seen among the interactors is an order of magnitude higher than the 1%–4% typically observed in unbiased genetic screens. Genetic modifiers were similarly represented among proteins discovered using yeast two-hybrid and pull-down/mass spectrometry methods, supporting the notion that these complementary technologies are equally useful in identifying biologically relevant proteins. Interacting proteins confirmed as modifiers of the neurodegeneration phenotype represent a diverse array of biological functions, including synaptic transmission, cytoskeletal organization, signal transduction, and transcription. Among the modifiers were 17 loss-of-function suppressors of neurodegeneration, which can be considered potential targets for therapeutic intervention. Finally, we show that seven interacting proteins from among 11 tested were able to co-immunoprecipitate with full-length Htt from mouse brain. These studies demonstrate that high-throughput screening for protein interactions combined with genetic validation in a model organism is a powerful approach for identifying novel candidate modifiers of polyglutamine toxicity
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