Interferon-α promotes HLA-B-restricted presentation of conventional and alternative antigens in human pancreatic β-cells.

Interferon (IFN)-α is the earliest cytokine signature observed in individuals at risk for type 1 diabetes (T1D), but the effect of IFN-α on the antigen repertoire of HLA Class I (HLA-I) in pancreatic β-cells is unknown. Here we characterize the HLA-I antigen presentation in resting and IFN-α-exposed β-cells and find that IFN-α increases HLA-I expression and expands peptide repertoire to those derived from alternative mRNA splicing, protein cis-splicing and post-translational modifications. While the resting β-cell immunopeptidome is dominated by HLA-A-restricted peptides, IFN-α largely favors HLA-B and only marginally upregulates HLA-A, translating into increased HLA-B-restricted peptide presentation and activation of HLA-B-restricted CD8 T cells.

Staff Safety and Experiences with Electronic Safety Devices among a Sample of Veterans Affairs Homeless Service Providers.

The current survey examined Veterans Affairs (VA) homeless service providers' experiences with electronic personal protective safety devices (EPPSDs). The survey was completed by 153 homeless service providers based at VA medical centers in New York, New Jersey, and Florida. The survey asked about feelings of safety while performing work duties, safety incidents, use of EPPSDs, and experiences with EPPSDs.

Managing Health Without Stable Housing: Dimensions of Treatment Burden and Patient Capacity for People With Chronic Health Conditions Experiencing Homelessness.

Although chronic health conditions and homelessness are prevalent problems in the United States and globally, little research has used the lens of burden of treatment theory to examine the experiences of people facing these challenges simultaneously. This study aimed to illuminate dimensions of treatment burden, which refers to the work of being a patient with chronic conditions, and patient capacity to manage this burden in a sample of people experiencing homelessness and chronic health problems in Buffalo, New York, United States. We completed in-depth interviews with men and women recruited from a homelessness services organization ( = 27) and applied core concepts from burden of treatment theory to our analysis to probe how participants navigated tasks related to treatment and self-care.

Subchronic elevation in ambient temperature drives alterations to the sperm epigenome and accelerates early embryonic development in mice.

Forecasted increases in the prevalence and severity of extreme weather events accompanying changes in climatic behavior pose potential risk to the reproductive capacity of humans and animals of ecological and agricultural significance. While several studies have revealed that heat stress induced by challenges such as testicular insulation can elicit a marked negative effect on the male reproductive system, and particularly the production of spermatozoa, less is known about the immediate impact on male reproductive function following subchronic whole-body exposure to elevated ambient temperature. To address this knowledge gap, we exposed unrestrained male mice to heat stress conditions that emulate a heat wave (daily cycle of 8 h at 35 °C followed by 16 h at 25 °C) for a period of 7 d.

Surrogate End Points in Apolipoprotein L1 - Associated Kidney Disease : Evaluation in Three Cohorts.

Key Points: Apolipoprotein L1 (APOL1) high-risk genotype had higher risk of 3-year GFR-related surrogate end points and long-term kidney failure than those with the low-risk genotype. No consistent difference in surrogate–clinical outcome associations by APOL1 genotype, supporting the use of surrogates in APOL1 kidney disease.

Background: Surrogate end points for the clinical outcome of kidney failure have been accepted by the US Food and Drug Administration.

Navigating Ankle Fracture Surgery in the Shadow of COVID-19.

Background: This case control study aimed to evaluate the impact of preoperative COVID-19 diagnosis on postoperative complications in patients undergoing ankle fracture surgery using the National COVID-19 Cohort Collaborative (N3C) database. The investigation focused on the interplay between COVID-19 diagnosis timing, patient characteristics, and clinical outcomes, particularly considering the potential mechanisms by which COVID-19 may contribute to increased complications.

Methods: This case control study included patients who underwent ankle fracture surgery using the N3C database.

Molecular Imaging of p53 in Mouse Models of Cancer Using a Radiolabeled Antibody TAT Conjugate with SPECT.

Mutations of p53 protein occur in over half of all cancers, with profound effects on tumor biology. We present the first-to our knowledge-method for noninvasive visualization of p53 in tumor tissue in vivo, using SPECT, in 3 different models of cancer. Anti-p53 monoclonal antibodies were conjugated to the cell-penetrating transactivator of transcription (TAT) peptide and a metal ion chelator and then radiolabeled with In to allow SPECT imaging.

The efficacy and functional consequences of interactions between human spermatozoa and seminal fluid extracellular vesicles.

Abstract: Seminal fluid extracellular vesicles (SFEVs) have previously been shown to interact with spermatozoa and influence their fertilisation capacity. Here, we sought to extend these studies by exploring the functional consequences of SFEV interactions with human spermatozoa. SFEVs were isolated from the seminal fluid of normozoospermic donors prior to assessing the kinetics of sperm-SFEV binding in vitro, as well as the effects of these interactions on sperm capacitation, acrosomal exocytosis, and motility profile.

Early Dysglycemia Is Detectable Using Continuous Glucose Monitoring in Very Young Children at Risk of Type 1 Diabetes.

Objective: Continuous glucose monitoring (CGM) can detect early dysglycemia in older children and adults with presymptomatic type 1 diabetes (T1D) and predict risk of progression to clinical onset. However, CGM data for very young children at greatest risk of disease progression are lacking. This study aimed to investigate the use of CGM data measured in children being longitudinally observed in the Australian Environmental Determinants of Islet Autoimmunity (ENDIA) study from birth to age 10 years.

Matrix Metalloproteinase-2 and CKD Progression: The Chronic Renal Insufficiency Cohort (CRIC) Study.

Rationale & Objective: Matrix metalloproteinase 2 (MMP-2) plays an important role in the development of fibrosis, the final common pathway of chronic kidney disease (CKD). This study aimed to assess the relationship between repeated measures of MMP-2 and CKD progression in a large, diverse prospective cohort.

Study Design: In a prospective cohort of Chronic Renal Insufficiency Cohort (CRIC) participants (N = 3,827), MMP-2 was measured at baseline.

Clonal hematopoiesis of indeterminate potential is associated with reduced risk of cognitive impairment in patients with chronic kidney disease.

Introduction: Clonal hematopoiesis of indeterminate potential (CHIP) and dementia disproportionately burden patients with chronic kidney disease (CKD). The association between CHIP and cognitive impairment in CKD patients is unknown.

Methods: We conducted time-to-event analyses in up to 1452 older adults with CKD from the Chronic Renal Insufficiency Cohort who underwent CHIP gene sequencing.

Target Trial Emulation: A Call for More Widespread Use.

Causal inference methods intended for use with observational data have been widely available for decades, but barriers exist to their widespread adoption. These likely include lack of familiarity with several methodologic techniques often used in combination in these investigations such as inverse probability of treatment weighting and g-estimation, and the intensity of computational effort to employ these techniques. Even with these methods, critical design flaws undermine the ability to make valid causal inference in some studies.

Environmental Determinants of Islet Autoimmunity (ENDIA) longitudinal prospective pregnancy to childhood cohort study of Australian children at risk of type 1 diabetes: parental demographics and birth information.

Introduction: The Environmental Determinants of Islet Autoimmunity (ENDIA) Study is an ongoing Australian prospective cohort study investigating how modifiable prenatal and early-life exposures drive the development of islet autoimmunity and type 1 diabetes (T1D) in children. In this profile, we describe the cohort's parental demographics, maternal and neonatal outcomes and human leukocyte antigen (HLA) genotypes.

Research Design And Methods: Inclusion criteria were an unborn child, or infant aged less than 6 months, with a first-degree relative (FDR) with T1D.

neomorphic mutation confers sensitivity to vitamin B12 in .

In humans, a neomorphic isocitrate dehydrogenase mutation () causes increased levels of cellular D-2-hydroxyglutarate (D-2HG), a proposed oncometabolite. However, the physiological effects of increased D-2HG and whether additional metabolic changes occur in the presence of an mutation are not well understood. We created a model to study the effects of the mutation in a whole animal.

We Rely on Relationships: Homeless Service Providers' Experiences in Coordinating Care Transitions During COVID-19.

Purpose Of Study: Care coordination occurring across multiple sectors of care, such as when professionals in health or social service organizations collaborate to transition patients from hospitals to community-based settings like homeless shelters, happens regularly in practice. While health services research is full of studies on the experiences of case management and care coordination professionals within health care settings, few studies highlight the perspective of nonclinical homeless service providers (HSPs) in coordinating care transitions.

Primary Practice Setting: This study explores the experience of nonclinical HSPs, employed in a large homeless service agency in New York, United States, responsible for coordinating care transitions of patients presenting to a homeless shelter after hospitalization, with attention to COVID-19 impact.

Five-Year Cumulative Cardiovascular Health and Clinical Events in Patients With Chronic Kidney Disease: The CRIC Study.

Background: Higher cardiovascular health (CVH) score is associated with lower risks of cardiovascular disease (CVD) and mortality in the general population. However, it is unclear whether cumulative CVH is associated with CVD, end-stage kidney disease (ESKD), and death in patients with chronic kidney disease.

Methods And Results: Among individuals from the prospective CRIC (Chronic Renal Insufficiency Cohort) Study, we used the percentage of the maximum possible CVH score attained from baseline to the year 5 visit to calculate cumulative CVH score.

Management of Recurrent Giant Cell Tumor of Distal Tibia With Intramedullary Hindfoot Fusion Nail and Trabecular Metal Implant Construct.

Reconstruction options for giant cell tumors (GCTs) of bone are limited and challenging due to the amount of structural compromise and the high recurrence rates. This is especially true for GCTs of the foot and ankle, as the area is vital for weight bearing and function. The typical treatment for GCTs is currently excision, curettage, and cementation, although that is not always effective.

Association of Integrated Proteomic and Metabolomic Modules with Risk of Kidney Disease Progression.

Key Points: Integrated analysis of proteome and metabolome identifies modules associated with CKD progression and kidney failure. Ephrin transmembrane proteins and podocyte-expressed CRIM1 and NPNT emerged as central components and warrant experimental and clinical investigation.

Background: Proteins and metabolites play crucial roles in various biological functions and are frequently interconnected through enzymatic or transport processes.

Phosphoproteomic analysis of the adaption of epididymal epithelial cells to corticosterone challenge.

Background: The epididymis has long been of interest owing to its role in promoting the functional maturation of the male germline. More recent evidence has also implicated the epididymis as an important sensory tissue responsible for remodeling of the sperm epigenome, both under physiological conditions and in response to diverse forms of environmental stress. Despite this knowledge, the intricacies of the molecular pathways involved in regulating the adaptation of epididymal tissue to paternal stressors remains to be fully resolved.

neomorphic mutation confers sensitivity to vitamin B12 via increased dependency on one-carbon metabolism in .

The isocitrate dehydrogenase neomorphic mutation ( ) generates increased levels of cellular D-2-hydroxyglutarate (D-2HG), a proposed oncometabolite. However, the physiological effects of increased D-2HG and whether additional metabolic changes occur in the presence of an mutation are not well understood. We created a model to study the effects of the mutation in a whole animal.

Depressive Symptoms, Antidepressants, and Clinical Outcomes in Chronic Kidney Disease: Findings from the CRIC Study.

Rationale & Objective: The extent to which depression affects the progression of chronic kidney disease (CKD) and leads to adverse clinical outcomes remains inadequately understood. We examined the association of depressive symptoms (DS) and antidepressant medication use on clinical outcomes in 4,839 adults with nondialysis CKD.

Study Design: Observational cohort study.

Oral interview in place of traditional objective structured clinical examinations for assessing placement readiness in nutrition and dietetics education.

Aim: Objective structured clinical examinations have long been used in dietetics education. This observational study aims to describe the development, deployment, feasibility and validity of assessment using an oral interview in place of traditional objective structured clinical examinations, and to determine the ability of this assessment to identify students who are either not ready for placement or may require early support and/or remediation.

Methods: Student assessment data were collected over a two-and-a-half-year period and used to test the predictive ability of an oral interview to determine dietetic placement outcomes and highlight a need for early remediation.

Assessment of the impact of direct in vitro PFAS treatment on mouse spermatozoa.

Abstract: Poly- and per-fluoroalkyl substances (PFAS) are synthetic environmentally persistent chemicals. Despite the phaseout of specific PFAS, their inherent stability has resulted in ubiquitous and enduring environmental contamination. PFAS bioaccumulation has been reported globally with omnipresence in most populations wherein they have been associated with a range of negative health effects, including strong associations with increased instances of testicular cancer and reductions in overall semen quality.

Metabolites Associated With Uremic Symptoms in Patients With CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.

Rationale & Objective: The toxins that contribute to uremic symptoms in patients with chronic kidney disease (CKD) are unknown. We sought to apply complementary statistical modeling approaches to data from untargeted plasma metabolomic profiling to identify solutes associated with uremic symptoms in patients with CKD.

Study Design: Cross-sectional.