Utility of genetic risk scores in type 1 diabetes.

Iterative advances in understanding of the genetics of type 1 diabetes have identified >70 genetic regions associated with risk of the disease, including strong associations across the HLA class II region that account for >50% of heritability. The increased availability of genetic data combined with the decreased costs of generating these data, have facilitated the development of polygenic scores that aggregate risk variants from associated loci into a single number: either a genetic risk score (GRS) or a polygenic risk score (PRS). PRSs incorporate the risk of many possibly correlated variants from across the genome, even if they do not reach genome-wide significance, whereas GRSs estimate the cumulative contribution of a smaller subset of genetic variants that reach genome-wide significance.

A scoping review of legibility of hand-written prescriptions and drug-orders: the writing on the wall.

Introduction: Prescription and drug order writing are key components of patient care allowing physicians communicate their therapeutic plans. Although electronic prescriptions are becoming more common, handwritten prescriptions are still quite prevalent and a persistent issue with handwritten prescriptions is the illegibility of physician handwritings. Prescriptions have to be legible to avoid delays in healthcare provision and consequences as serious as patient death.

Pregnancy and superior moral status: a proposal for two thresholds of personhood.

In this paper, I suggest that, if we are committed to accepting a threshold approach to personhood, according to which all beings above the threshold are persons with equal moral status, there are strong reasons to also recognise a second threshold that would be reached through human pregnancy, and that would confer on pregnant women a temporary superior moral status. This proposal is not based on the moral status of the fetus, but on the moral status of the pregnant woman. It is not only the fetus which is an organism sui generis: the pregnant woman, also, is a unique being.

Type 2 Diabetes risk alleles in Peptidyl-glycine Alpha-amidating Monooxygenase influence GLP-1 levels and response to GLP-1 Receptor Agonists.

Patients with type 2 diabetes vary in their response to currently available therapeutic agents (including GLP-1 receptor agonists) leading to suboptimal glycemic control and increased risk of complications. We show that human carriers of hypomorphic T2D-risk alleles in the gene encoding peptidyl-glycine alpha-amidating monooxygenase as well as -knockout mice, display increased resistance to GLP-1 . inactivation in mice leads to reduced gastric GLP-1R expression and faster gastric emptying: this persists during GLP-1R agonist treatment and is rescued when GLP-1R activity is antagonized, indicating resistance to GLP-1's gastric slowing properties.

Improving social justice in observational studies: protocol for the development of a global and Indigenous STROBE-equity reporting guideline.

Background: Addressing persistent and pervasive health inequities is a global moral imperative, which has been highlighted and magnified by the societal and health impacts of the COVID-19 pandemic. Observational studies can aid our understanding of the impact of health and structural oppression based on the intersection of gender, race, ethnicity, age and other factors, as they frequently collect this data. However, the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline, does not provide guidance related to reporting of health equity.

Comparison of different methods for isolating CD8 T lymphocyte-derived extracellular vesicles and supramolecular attack particles.

CD8 T lymphocytes play vital roles in killing infected or deranged host cells, recruiting innate immune cells, and regulating other aspects of immune responses. Like any other cell, CD8 T cells also produce extracellular particles. These include extracellular vesicles (EVs) and non-vesicular extracellular particles (NVEPs).

Safety of drugs used for the treatment of migraine during pregnancy: a narrative review.

Introduction: Migraine is common in females of childbearing age and negatively impacts quality of life. The majority of those with migraine who become pregnant see an improvement in their condition but not all do. Providing evidence-based recommendations for the pharmacological management of migraine in pregnancy is challenging.

Age of Diagnosis Does Not Alter the Presentation or Progression of Robustly Defined Adult-Onset Type 1 Diabetes.

Objective: To determine whether presentation, progression, and genetic susceptibility of robustly defined adult-onset type 1 diabetes (T1D) are altered by diagnosis age.

Research Design And Methods: We compared the relationship between diagnosis age and presentation, C-peptide loss (annual change in urine C-peptide-creatinine ratio [UCPCR]), and genetic susceptibility (T1D genetic risk score [GRS]) in adults with confirmed T1D in the prospective StartRight study, 1,798 adults with new-onset diabetes. T1D was defined in two ways: two or more positive islet autoantibodies (of GAD antibody, IA-2 antigen, and ZnT8 autoantibody) irrespective of clinical diagnosis (n = 385) or one positive islet autoantibody and a clinical diagnosis of T1D (n = 180).

Risk management of medication errors: a novel conceptual framework.

Background: Medication error is a common cause of patient harm. The study aims to propose a way to manage the risk of medication errors in a novel way, by identifying practice areas where mitigating patient harm should be prioritized using a risk management approach.

Methods: Suspected Adverse Drug Reactions (sADRs) in Eudravigilance database over three years were reviewed to identify preventable medication errors.

Pre-natal testing, excessive parenting and care ethics.

This article explores the current parenting culture, particularly the promotion of competitive and excessive parenting, as an important background issue against which the debates around pre-natal testing take place. It offers an alternative vision of parenting, relying on care ethics, which sees parenting as a relationship, rather than a job. A relationship that should change a parent's understanding of what is valuable in life.

Mapping Principal Navigations in the Levant.

Richard Hakluyt's is a seminal work in the historical narrative of English exploration and colonisation, but not an unbiased one. By comparing social network maps of the contemporary Anglo-Levant community with textual analysis of , this article will demonstrate the ways in which editorial practices reinforced Hakluyt's personal biases in the text's portrayal of the Levant and eastern Mediterranean, how this bias has resonated in the following centuries to colour conceptions of the late sixteenth century English-Levant relationship, and suggest avenues for the study of unexplored perspectives on this history.

Prenatal testing, disability equality, and the limits of the law.

This article will review reasons why it is argued that the law on abortion on the grounds of disability is discriminatory, as well as recent unsuccessful attempts to address this discrimination in the law. These attempts include ones which would have moderately restricted access to abortion in certain limited cases, and another that might have opened to door to a number of different possibilities, including both to options that could have restricted access to abortion, and to other options that might have increased access. Finally, this article will also examine reasons why some of the most important challenges surrounding disability equality cannot be sufficiently addressed through legal change alone.

Early clinical exposure in undergraduate medical education: A questionnaire survey of 30 European countries.

Purpose: Fifteen years ago, a European survey demonstrated widespread adoption of early clinical exposure (ECE) programmes but little emphasis in the curricula of medical schools. We now repeat the survey in light of the ample emerging data suggesting multiple positive outcomes of ECE.

Methods: Online cross-sectional survey in European medical schools conducted by the EURACT Basic Medical Education Committee in 2021.

Cost-effectiveness models for Alzheimer's disease and related dementias: IPECAD modeling workshop cross-comparison challenge.

Introduction: The credibility of model-based economic evaluations of Alzheimer's disease (AD) interventions is central to appropriate decision-making in a policy context. We report on the International PharmacoEconomic Collaboration on Alzheimer's Disease (IPECAD) Modeling Workshop Challenge.

Methods: Two common benchmark scenarios, for the hypothetical treatment of AD mild cognitive impairment (MCI) and mild dementia, were developed jointly by 29 participants.

Milder loss of insulin-containing islets in individuals with type 1 diabetes and type 2 diabetes-associated TCF7L2 genetic variants.

Aims/hypothesis: TCF7L2 variants are the strongest genetic risk factor for type 2 diabetes. In individuals with type 1 diabetes, these variants are associated with a higher C-peptide AUC, a lower glucose AUC during an OGTT, single autoantibody positivity near diagnosis, particularly in individuals older than 12 years of age, and a lower frequency of type 1 diabetes-associated HLA genotypes. Based on initial observations from clinical cohorts, we tested the hypothesis that type 2 diabetes-predisposing TCF7L2 genetic variants are associated with a higher percentage of residual insulin-containing cells (ICI%) in pancreases of donors with type 1 diabetes, by examining genomic data and pancreatic tissue samples from the Network for Pancreatic Organ donors with Diabetes (nPOD) programme.

Routine Islet Autoantibody Testing in Clinically Diagnosed Adult-Onset Type 1 Diabetes Can Help Identify Misclassification and the Possibility of Successful Insulin Cessation.

Objective: Recent joint American Diabetes Association and European Association for the Study of Diabetes guidelines recommend routine islet autoantibody testing in all adults newly diagnosed with type 1 diabetes. We aimed to assess the impact of routine islet autoantibody testing in this population.

Research Design And Methods: We prospectively assessed the relationship between islet autoantibody status (GADA, IA-2A, and ZNT8A), clinical and genetic characteristics, and progression (annual change in urine C-peptide-to-creatinine ratio [UCPCR]) in 722 adults (≥18 years old at diagnosis) with clinically diagnosed type 1 diabetes and diabetes duration <12 months.

Drug repurposing and sequence analysis in S-glycoprotein variants reveals critical signature patterns and destabilization of receptor-binding domain in omicron variant.

The evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus since its emergence in 2019 has yielded several new viral variants with varied infectivity, disease severity, and antigenicity. Although most mutations are expected to be relatively neutral, mutations at the Spike region of the genome have shown to have a major impact on the viral transmission and infection in humans. Therefore, it is crucial to survey the structures of spike protein across the global virus population to contextualize the rate of therapeutic success against these variants.

Live enteroviruses, but not other viruses, detected in human pancreas at the onset of type 1 diabetes in the DiViD study.

Aims/hypothesis: Enterovirus (EV) infection of pancreatic islet cells is one possible factor contributing to type 1 diabetes development. We have reported the presence of EV genome by PCR and of EV proteins by immunohistochemistry in pancreatic sections. Here we explore multiple human virus species in the Diabetes Virus Detection (DiViD) study cases using innovative methods, including virus passage in cell cultures.

Beta cell and immune cell interactions in autoimmune type 1 diabetes: How they meet and talk to each other.

Background: The highly complex pathogenesis of Type 1 Diabetes is driven by several immune cell types with both effector and regulatory characteristics, which ultimately ends in the destruction of the insulin-producing beta cells. There are multiple layers of interaction between these immune cell populations and the pancreatic islets.

Scope Of Review: In this review article, we aim to discuss important recent insights into the multiple layers of interaction between immune cell populations and the pancreatic islets.