A Psychosocial Critique of the Consequences of the COVID-19 Pandemic on UK Care Home Staff Attitudes to the Flu Vaccination: A Qualitative Longitudinal Study.

Vaccinating care home staff is essential to protect vulnerable residents by reducing infection risks and creating a safer care environment. However, vaccine hesitancy amongst staff remains a challenge, particularly since the COVID-19 pandemic raised concerns about side effects and vaccination mandates. This study examines how the pandemic influenced flu vaccine hesitancy amongst UK care home staff.

ISPAD Clinical Practice Consensus Guidelines 2024: Screening, Staging, and Strategies to Preserve Beta Cell Function in Children and Adolescents with Type 1 Diabetes.

Introduction This guideline serves as an update to the 2022 International Society for Pediatric and Adolescent Diabetes (ISPAD) consensus guideline on staging for Type 1 Diabetes (T1D). Key additions include an evidence-based summary of recommendations for screening for risk of T1D and monitoring those with early-stage T1D. In addition, a review of clinical trials designed to delay progression to Stage 3 T1D and efforts seeking to preserve beta cell function in those with Stage 3 T1D is included.

Trajectory of beta cell function and insulin clearance in stage 2 type 1 diabetes: natural history and response to teplizumab.

Aims/hypothesis: We aimed to analyse TrialNet Anti-CD3 Prevention (TN10) data using oral minimal model (OMM)-derived indices to characterise the natural history of stage 2 type 1 diabetes in placebo-treated individuals, to describe early metabolic responses to teplizumab and to explore the predictive capacity of OMM measures for disease-free survival rate.

Methods: OMM-estimated insulin secretion, sensitivity and clearance and the disposition index were evaluated at baseline and at 3, 6 and 12 months post randomisation in placebo- and teplizumab-treated groups, and, within each group, in slow- and rapid-progressors (time to stage 3 disease >2 or 2 years). OMM metrics were also compared with the standard AUC C-peptide.

Beta cell extracellular vesicle PD-L1 as a novel regulator of CD8 T cell activity and biomarker during the evolution of type 1 diabetes.

Aims/hypothesis: Surviving beta cells in type 1 diabetes respond to inflammation by upregulating programmed death-ligand 1 (PD-L1) to engage immune cell programmed death protein 1 (PD-1) and limit destruction by self-reactive immune cells. Extracellular vesicles (EVs) and their cargo can serve as biomarkers of beta cell health and contribute to islet intercellular communication. We hypothesised that the inflammatory milieu of type 1 diabetes increases PD-L1 in beta cell EV cargo and that EV PD-L1 may protect beta cells against immune-mediated cell death.

Emerging Concepts and Success Stories in Type 1 Diabetes Research: A Road Map for a Bright Future.

Type 1 diabetes treatment stands at a crucial and exciting crossroad since the 2022 U.S. Food and Drug Administration approval of teplizumab to delay disease development.

Beta cell extracellular vesicle PD-L1 as a novel regulator of CD8+ T cell activity and biomarker during the evolution of Type 1 Diabetes.

Aims/hypothesis: Surviving beta cells in type 1 diabetes respond to inflammation by upregulating programmed death-ligand 1 (PD-L1) to engage immune cell programmed death-1 (PD-1) and limit destruction by self-reactive immune cells. Extracellular vesicles (EVs) and their cargo can serve as biomarkers of beta cell health and contribute to islet intercellular communication. We hypothesized that the inflammatory milieu of type 1 diabetes increases PD-L1 in beta cell EV cargo and that EV PD-L1 may protect beta cells against immune-mediated cell death.

Quality of life, pain and use of analgesic, anxiolytic and antidepressant medication, in people living in care homes.

Background: People living in care homes often have problems with pain, anxiety and depression. Whether being on analgesia, anxiolytics or antidepressants has any bearing on pain severity and quality of life (QoL) in this population, requires further investigation.

Objectives: (i) to examine the relationship between pain, anxiety and depression and medication use in care home residents and (ii) to compare those on medications to treat pain, anxiety and depression, and those who were not, and associations with pain severity and overall QoL.

Development of a National Ménière's Disease Registry: A Feasibility Study.

Ménière's disease is a disabling condition causing vertigo and hearing loss yet remains incompletely understood. Registry studies have the potential to answer important questions about phenotypes and natural history of clinical conditions. The aim of this study was to explore the feasibility of a patient-centered national Ménière's disease registry.

Immune checkpoints and pancreatic beta cell dysfunction in HIV.

We explored the impact of immune dysregulation on pancreatic beta cell injury in HIV patients. Analyzing 105 participant samples, we observed lower IL-21 levels and elevated immune checkpoint levels (e.g.

Exploring the relationship between depression and delinquency: a sibling comparison design using the NLSY.

Relative to the general population, adolescents with psychiatric disorders such as major depression disorder are incarcerated (and reincarcerated) at higher rates. Current research is mixed on whether this association is a cause, consequence, or the product of selection. For example, aggression can lead to more depressive symptoms, yet depression is associated with antisocial behaviors (e.

Consensus Guidance for Monitoring Individuals With Islet Autoantibody-Positive Pre-Stage 3 Type 1 Diabetes.

Given the proven benefits of screening to reduce diabetic ketoacidosis (DKA) likelihood at the time of stage 3 type 1 diabetes diagnosis, and emerging availability of therapy to delay disease progression, type 1 diabetes screening programs are being increasingly emphasized. Once broadly implemented, screening initiatives will identify significant numbers of islet autoantibody-positive (IAb+) children and adults who are at risk for (confirmed single IAb+) or living with (multiple IAb+) early-stage (stage 1 and stage 2) type 1 diabetes. These individuals will need monitoring for disease progression; much of this care will happen in nonspecialized settings.

Consensus guidance for monitoring individuals with islet autoantibody-positive pre-stage 3 type 1 diabetes.

Given the proven benefits of screening to reduce diabetic ketoacidosis (DKA) likelihood at the time of stage 3 type 1 diabetes diagnosis, and emerging availability of therapy to delay disease progression, type 1 diabetes screening programmes are being increasingly emphasised. Once broadly implemented, screening initiatives will identify significant numbers of islet autoantibody-positive (IAb) children and adults who are at risk of (confirmed single IAb) or living with (multiple IAb) early-stage (stage 1 and stage 2) type 1 diabetes. These individuals will need monitoring for disease progression; much of this care will happen in non-specialised settings.

Inhibition of the Eukaryotic Initiation Factor-2-α Kinase PERK Decreases Risk of Autoimmune Diabetes in Mice.

Preventing the onset of autoimmune type 1 diabetes (T1D) is feasible through pharmacological interventions that target molecular stress-responsive mechanisms. Cellular stresses, such as nutrient deficiency, viral infection, or unfolded proteins, trigger the integrated stress response (ISR), which curtails protein synthesis by phosphorylating eIF2α. In T1D, maladaptive unfolded protein response (UPR) in insulin-producing β cells renders these cells susceptible to autoimmunity.

Inhibition of the eukaryotic initiation factor-2α kinase PERK decreases risk of autoimmune diabetes in mice.

Preventing the onset of autoimmune type 1 diabetes (T1D) is feasible through pharmacological interventions that target molecular stress-responsive mechanisms. Cellular stresses, such as nutrient deficiency, viral infection, or unfolded proteins, trigger the integrated stress response (ISR), which curtails protein synthesis by phosphorylating eukaryotic translation initiation factor-2α (eIF2α). In T1D, maladaptive unfolded protein response (UPR) in insulin-producing β cells renders these cells susceptible to autoimmunity.

U.S. Preparedness and Response to Increasing Clade I Mpox Cases in the Democratic Republic of the Congo - United States, 2024.

Clade I monkeypox virus (MPXV), which can cause severe illness in more people than clade II MPXVs, is endemic in the Democratic Republic of the Congo (DRC), but the country has experienced an increase in suspected cases during 2023-2024. In light of the 2022 global outbreak of clade II mpox, the increase in suspected clade I cases in DRC raises concerns that the virus could spread to other countries and underscores the importance of coordinated, urgent global action to support DRC's efforts to contain the virus. To date, no cases of clade I mpox have been detected outside of countries in Central Africa where the virus is endemic.

Pediatric Endocrine Society Statement on Considerations for Use of Teplizumab (Tzield™) in Clinical Practice.

Teplizumab (TzieldTM, Provention Bio), a monoclonal antibody directed at T-cell marker CD3, is the first medication approved by the FDA to delay progression from stage 2 to stage 3 type 1 diabetes. To date, the overwhelming majority of pediatric endocrinologists do not have experience using immunotherapeutics and seek guidance on the use of teplizumab in clinical practice. To address this need, the Pediatric Endocrine Society (PES) Diabetes Special Interest Group (Diabetes SIG) and Drug and Therapeutics Committee assembled a task force to review clinical trial data and solicit expert recommendations on the approach to teplizumab infusions.

Proinflammatory stress activates neutral sphingomyelinase 2 based generation of a ceramide-enriched β cell EV subpopulation.

Unlabelled: β cell extracellular vesicles (EVs) play a role as paracrine effectors in islet health, yet mechanisms connecting β cell stress to changes in EV cargo and potential impacts on diabetes remain poorly defined. We hypothesized that β cell inflammatory stress engages neutral sphingomyelinase 2 (nSMase2)-dependent EV formation pathways, generating ceramide-enriched EVs that could impact surrounding β cells. Consistent with this, proinflammatory cytokine treatment of INS-1 β cells and human islets concurrently increased β cell nSMase2 and ceramide expression, as well as EV ceramide staining.

Early Metabolic Endpoints Identify Persistent Treatment Efficacy in Recent-Onset Type 1 Diabetes Immunotherapy Trials.

Objective: Mixed-meal tolerance test-stimulated area under the curve (AUC) C-peptide at 12-24 months represents the primary end point for nearly all intervention trials seeking to preserve β-cell function in recent-onset type 1 diabetes. We hypothesized that participant benefit might be detected earlier and predict outcomes at 12 months posttherapy. Such findings would support shorter trials to establish initial efficacy.

Comparisons of Metabolic Measures to Predict T1D vs Detect a Preventive Treatment Effect in High-Risk Individuals.

Context: Metabolic measures are frequently used to predict type 1 diabetes (T1D) and to understand effects of disease-modifying therapies.

Objective: Compare metabolic endpoints for their ability to detect preventive treatment effects and predict T1D.

Methods: Six-month changes in metabolic endpoints were assessed for (1) detecting treatment effects by comparing placebo and treatment arms from the randomized controlled teplizumab prevention trial, a multicenter clinical trial investigating 14-day intravenous teplizumab infusion and (2) predicting T1D in the TrialNet Pathway to Prevention natural history study.