Characterization of the roles of PPP1R15A (GADD34) and PPP1R15B (CReP) in ER stress-induced apoptosis in vivo

Failure to balance synthesis, folding and degradation of secreted proteins results in the accumulation of unfolded proteins in the endoplasmic reticulum, termed ER stress. Cells respond to ER stress by activating a signaling pathway known as the unfolded protein response (UPR). The UPR induces phosphorylation of eIF2α to attenuate global protein translation, allowing the ER to clear misfolded proteins. Opposing this function, eIF2α phosphatases contain a catalytic subunit, Protein Phosphatase 1, and either of two homologous scaffolding subunits, GADD34 and CReP. Inhibition of eIF2α phosphatases has been shown to prolong UPR signaling and promote survival in many cells types and has reduced the progression of neurodegenerative diseases in several mouse models. Despite the clinical significance of GADD34 and CReP, their precise roles in UPR signaling and ER stress-induced apoptosis are largely unknown. Zebrafish are an ideal model for studying eIF2ɑ phosphatases in the UPR due to the efficiency of reverse genetics and the susceptibility of the caudal fin epidermal cells to ER stress-induced apoptosis. In acute ER stress, these cells undergo apoptosis mediated by p63-puma, but under chronic stress, apoptosis is mediated by CHOP, a downstream UPR target. We sought to determine the role of eIF2α phosphatases in both apoptotic programs by inducing eIF2α phosphatase loss- or gain-of-function and measuring the effect on apoptosis in response to ER stress. Inhibition of both eIF2ɑ phosphatases protected cells against both apoptotic responses, primarily through GADD34 inhibition. We speculate that survival is promoted through enhanced eIF2ɑ phosphorylation, stalling the UPR in an early state and preventing accumulation of the late-stage target, CHOP. GADD34 overexpression protected cells against acute apoptosis, which we hypothesize is through a transient promotion of autophagy. Our results indicate that altering the influence of eIF2α phosphatases in the UPR may be a promising therapeutic for diseases exacerbated by ER stress

Social Belonging Perceptions Across FHSU Students

Social belonging is a critical aspect of student success and well-being in higher education. Research on social belonging has thus far primarily focused on traditional, on campus students in higher education; however, higher education institutions have seen an increased number of online students post pandemic (D’Agostino, 2022). Fort Hays State University (FHSU) has likewise seen a growing number of online students, with 3,807 on campus students compared to 6,604 online students for the 2021-2022 school year. Data from the 2021 NISS Diagnostic Analysis resulted in the following executive summary, “Improve outcomes for online students by better understanding the specific obstacles they are facing and by targeting supports in response”. To address the growing need to understand the unique perspectives of FHSU’s online students and to contribute to the overall FHSU student success the Teaching Innovations and Learning Technologies (TILT) department designed a mixed methods research project with the intention to build a faculty facing workshop that is data driven by FHSU students. A design-based research approach was taken to support the project’s lofty goals. An initial analysis of past data was conducted using 2021 NSSE survey data, 2021 NISS Diagnostic Analysis and Playbook, and the FHSU’s 2021 Post-Pandemic survey data. This data was used to construct the theoretical framework of social belonging for this project, which includes social capital and social presence. Next, a sequential mixed methods approach was deployed using a qualitative survey followed by qualitative, semi-structured interviews. This poster will report on the project’s design, theoretical framework, and preliminary findings

Institution specific risk factors for 30 day readmission at a community hospital: a retrospective observational study

Background: As of October 1, 2012, hospitals in the United States with excess readmissions based on the Centers for Medicare and Medicaid Services (CMS) risk-adjusted ratio began being penalized. Given the impact of high readmission rates to hospitals nationally, it is important for individual hospitals to identify which patients may be at highest risk of readmission. The objective of this study was to assess the association of institution specific factors with 30-day readmission. Methods: The study is a retrospective observational study using administrative data from January 1, 2009 through December 31, 2010 conducted at a 257 bed community hospital in Massachusetts. The patients included inpatient medical discharges from the hospitalist service with the primary diagnoses of congestive heart failure, pneumonia or chronic obstructive pulmonary disease. The outcome was 30-day readmission rates. After adjusting for known factors that impact readmission, provider associated factors (i.e. hours worked and census on the day of discharge) and hospital associated factors (i.e. floor of discharge, season) were compared. Results: Over the study time period, there were 3774 discharges by hospitalists, with 637 30-day readmissions (17% readmission rate). By condition, readmission rates were 19.6% (448/2284) for congestive heart failure, 13.0% (141/1083) for pneumonia, and 14.7% (200/1358) for chronic obstructive lung disease. After adjusting for known risk factors (gender, age, length of stay, Elixhauser sum score, admission in the previous year, insurance, disposition, primary diagnosis), we found that patients discharged in the winter remained significantly more likely to be readmitted compared to the summer (OR 1.54, p = 0.0008). Patients discharged from the cardiac floor had a trend toward decreased readmission compared a medical/oncology floor (OR 0.85, p = 0.08). Hospitalist work flow factors (census and hours on the day of discharge) were not associated with readmission. Conclusions: We found that 30 day hospital readmissions may be associated with institution specific risk factors, even after adjustment for patient factors. These institution specific risk factors may be targets for interventions to prevent readmissions

Experiences with grandparents and attitudes toward custodial grandparenting

The goals of the current study were to examine attitudes about custodial grandparents and to examine whether personal experiences with grandparents influenced those attitudes. Data were provided by 730 younger adults (mean age about 20 years) who completed surveys regarding their experiences with their own grandparents, attitudes toward custodial grandparenting, and openness to becoming a custodial grandparent in the future. Mean differences in attitudes as a function of experience did emerge. In addition, a mixed structural model showed that young adults who felt their grandparents helped to raise them perceived custodial grandparenting as less distressing, and it was these perceptions of distress that related to being more open to accepting the role of custodial grandparent themselves. Results are discussed in terms of changing norms and their relevance to policies affecting families

Affected Family Members\u27 Communicative Management of Opioid Misuse Stigma: Applying and Rethinking the Stigma Management Communication Typology

Opioid misuse is a prevalent health problem in the United States with consequences extending past the person who misuses opioids to affected family members (AFM) through courtesy stigma. The goals of this study were to understand the stigma management communication (SMC) strategies employed by AFMs when they experience courtesy stigma and changes in strategies used over time. The findings from interviews with 34 AFMs suggest the SMC strategies they employ range from those that indicate acceptance of stigma and avoidance of stigma situations to strategies where AFMs actively challenge opioid misuse stigma. However, strategy use depended on the social context and AFMs’ perceptions of opioid misuse stigma at a given moment in time. Further, findings suggest changes in AFMs’ SMC strategies over time are related to changes in their perceptions of opioid misuse stigma. Theoretical and practical implications of how families manage stigma are discussed

Inflammatory Pseudotumors Induced by AdCre in Transgenic Oncopigs After In Situ Induction

https://openworks.mdanderson.org/sumexp23/1106/thumbnail.jp

A Note on False Positives and Power in G × E Modelling of Twin Data

The variance components models for gene–environment interaction proposed by Purcell in 2002 are widely used. In both the bivariate and the univariate parameterization of these models, the variance decomposition of trait T is a function of moderator M. We show that if M and T are correlated, and moderator M is correlated between twins as well, the univariate parameterization produces a considerable increase in false positive moderation effects. A simple extension of this univariate moderation model prevents this elevation of the false positive rate provided the covariance between M and T is itself not also subject to moderation. If the covariance between M and T varies as a function of M, then moderation effects observed in the univariate setting should be interpreted with care as these can have their origin in either moderation of the covariance between M and T or in moderation of the unique paths of T. We conclude that researchers should use the full bivariate moderation model to study the presence of moderation on the covariance between M and T. If such moderation can be ruled out, subsequent use of the extended univariate moderation model, as proposed in this paper, is recommended as this model is more powerful than the full bivariate moderation model

Landsat 9 Thermal Infrared Sensor 2 Architecture and Design

The Thermal Infrared Sensor 2 (TIRS-2) will fly aboard the Landsat 9 spacecraft and leverages the Thermal Infrared Sensor (TIRS) design currently flying on Landsat 8. TIRS-2 will provide similar science data as TIRS, but is not a buildto-print rebuild due to changes in requirements and improvements in absolute accuracy. The heritage TIRS design has been modified to reduce the influence of stray light and to add redundancy for higher reliability over a longer mission life. The TIRS-2 development context differs from the TIRS scenario, adding to the changes. The TIRS-2 team has also learned some lessons along the way

Implementation of a patient-centered remote wound monitoring system for management of diabetic foot ulcers

BackgroundRegular clinical assessment is critical to optimize lower extremity wound healing. However, family and work obligations, socioeconomic, transportation, and time barriers often limit patient follow-up. We assessed the feasibility of a novel, patient-centered, remote wound management system (Healthy.io Minuteful for Wound Digital Management System) for the surveillance of lower extremity wounds.MethodsWe enrolled 25 patients from our outpatient multidisciplinary limb preservation clinic with a diabetic foot ulcer, who had undergone revascularization and podiatric interventions prior to enrollment. Patients and their caregivers were instructed on how to use the digital management system and asked to perform one at-home wound scan per week for a total of 8 weeks using a smartphone application. We collected prospective data on patient engagement, smartphone app useability, and patient satisfaction.ResultsTwenty-five patients (mean age 65.5 ± 13.7 years, 60.0% male, 52.0% Black) were enrolled over 3 months. Mean baseline wound area was 18.0 ± 15.2 cm2, 24.0% of patients were recovering from osteomyelitis, and post-surgical WiFi stage was 1 in 24.0%, 2 in 40.0%, 3 in 28.0%, and 4 in 8.00% of patients. We provided a smartphone to 28.0% of patients who did not have access to one that was compatible with the technology. Wound scans were obtained by patients (40.0%) and caregivers (60.0%). Overall, 179 wound scans were submitted through the app. The mean number of wound scans acquired per patient was 0.72 ± 0.63 per week, for a total mean of 5.80 ± 5.30 scans over the course of 8 weeks. Use of the digital wound management system triggered an early change in wound management for 36.0% of patients. Patient satisfaction was high; 94.0% of patients reported the system was useful.ConclusionThe Healthy.io Minuteful for Wound Digital Management System is a feasible means of remote wound monitoring for use by patients and/or their caregivers