ALS Motor Observational Telemedicine Objective Rasch-Built Assessment: A Quantitative Scale for the Era of Teleneurology.

Background And Objectives: Telemedicine has become a mainstay of ALS clinical care, but there is currently no standardized approach for assessing and tracking changes to the neurologic examination in this format. The goal of this study was to create a standardized telemedicine-based motor examination scale to objectively and reliably track ALS progression and use Rasch methodology to validate the scale and improve its psychometric properties.

Methods: A draft telemedicine examination scale with 25 items assessing movement in the bulbar muscles, neck, trunk, and extremities was created by an ALS expert panel, incorporating input from patient advisors.

Phase 1b/2a safety study of lemborexant as an adjunctive treatment for insomnia to buprenorphine-naloxone for opioid use disorder: A randomized controlled trial.

Background: Evidence supports the common incidence of sleep disturbance in opioid use disorder (OUD) as a potential marker of disrupted orexin system functioning. This study evaluated the initial safety and tolerability of a challenge dose of lemborexant, a dual orexin antagonist, as an adjunct to buprenorphine/naloxone.

Methods: Patients (18-65 years old) with OUD receiving sublingual buprenorphine/naloxone, with a Pittsburgh Sleep Quality Index total score of 6 or higher, were recruited from outpatient clinics.

Paracrine role of endothelial IGF-1 receptor in depot-specific adipose tissue adaptation in male mice.

During recent decades, changes in lifestyle have led to widespread nutritional obesity and its related complications. Remodelling adipose tissue as a therapeutic goal for obesity and its complications has attracted much attention and continues to be actively explored. The endothelium lines all blood vessels and is close to all cells, including adipocytes.

Use of Affimer technology for inhibition of α2-antiplasmin and enhancement of fibrinolysis.

Hypofibrinolysis is a documented abnormality in conditions with high risk of vascular occlusion. A key inhibitor of fibrinolysis is α2-antiplasmin (α2AP), and we hypothesize that the Affimer technology, comprising small conformational proteins with 2 9-amino-acid variable regions, can be used to modulate α2AP activity and facilitate fibrinolysis. Using a phage display system, a library of Affimers was screened against α2AP.

Small molecule modulation of insulin receptor-insulin like growth factor-1 receptor heterodimers in human endothelial cells.

Objectives: The insulin receptor (IR) and insulin like growth factor-1 receptor (IGF-1R) are heterodimers consisting of two extracellular α-subunits and two transmembrane β -subunits. Insulin αβ and insulin like growth factor-1 αβ hemi-receptors can heterodimerize to form hybrids composed of one IR αβ and one IGF-1R αβ. The function of hybrids in the endothelium is unclear.

Fundamentals of Descriptive Statistics.

Descriptive statistics (DS) play a crucial role in establishing a solid foundation for study analysis and are important for understanding the results of a study or data set. If the data from DS is used incorrectly, the study may be misinterpreted. Descriptive statistics summarizes and organizes data, making analysis easier and providing an overview of the characteristics of sampled data.

Clinical Features and HLA Genetics Differ in Children at Type 1 Diabetes Onset by Hispanic Ethnicity.

Context: Type 1 diabetes incidence continues to increase in children, especially among Hispanic Whites (HW).

Objective: We investigated the clinical, immunologic, and genetic characteristics of HW and Non-Hispanic White (NHW) children that presented at type 1 diabetes diagnosis.

Methods: In this single-center, observational study, children who were diagnosed with type 1 diabetes (<20 years old) and tested for islet autoantibodies within 1 year of diagnosis were included in the study and divided into two groups by Hispanic ethnicity.

A tale of two societies: implications of conflicting Rh-immunoglobulin guidelines.

National guidance conflicts regarding the use of RhD immune globulin administration <12w. Recent Society for Maternal Fetal Medicine (SMFM) guidelines suggest liberal use of this product while other guidelines, including Society of Family Planning and the World Health Organization, propose a more conservative approach. Medicine is not practiced in a vacuum, and potential harms must include not only individual but communal and public health effects.

Identification of Ribonuclease Inhibitors for the Control of Pathogenic Bacteria.

Bacteria are known to be constantly adapting to become resistant to antibiotics. Currently, efficient antibacterial compounds are still available; however, it is only a matter of time until these compounds also become inefficient. Ribonucleases are the enzymes responsible for the maturation and degradation of RNA molecules, and many of them are essential for microbial survival.

Using site-directed mutagenesis to further the understanding of insulin receptor-insulin like growth factor-1 receptor heterodimer structure.

Type 2 diabetes is characterised by the disruption of insulin and insulin-like growth factor (IGF) signalling. The key hubs of these signalling cascades - the Insulin receptor (IR) and Insulin-like growth factor 1 receptor (IGF1R) - are known to form functional IR-IGF1R hybrid receptors which are insulin resistant. However, the mechanisms underpinning IR-IGF1R hybrid formation are not fully understood, hindering the ability to modulate this for future therapies targeting this receptor.

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.

Early-life infection depletes preleukemic cells in a mouse model of hyperdiploid B-cell acute lymphoblastic leukemia.

Epidemiological studies report opposing influences of infection on childhood B-cell acute lymphoblastic leukemia (B-ALL). Although infections in the first year of life appear to exert the largest impact on leukemia risk, the effect of early pathogen exposure on the fetal preleukemia cells (PLC) that lead to B-ALL has yet to be reported. Using cytomegalovirus (CMV) infection as a model early-life infection, we show that virus exposure within 1 week of birth induces profound depletion of transplanted E2A-PBX1 and hyperdiploid B-ALL cells in wild-type recipients and in situ-generated PLC in Eμ-ret mice.

Pharmacist-Led Deprescribing of Aspirin in Older People in an Outpatient Setting.

In 2019, the American College of Cardiology and American Heart Association updated their joint guidelines stating low-dose aspirin should not be used on a routine basis for primary prevention of atherosclerotic cardiovascular disease (ASCVD) among people older than 70 years of age because of increased bleeding risk. In addition to these updated guidelines, a statement released by the US Preventive Services Task Force in April 2022 recommends against the initiation of low-dose aspirin for primary prevention of cardiovascular disease in people 60 years of age or older.² Despite these updated recommendations, aspirin continues to be a common medication older patients take, providing an opportunity for a clinical pharmacist deprescribing intervention.

The TWK-26 potassium channel governs nutrient absorption in the intestine.

Ion channels are necessary for proper water and nutrient absorption in the intestine, which supports cellular metabolism and organismal growth. While a role for Na co-transporters and pumps in intestinal nutrient absorption is well defined, how individual K uniporters function to maintain ion homeostasis is poorly understood. Using , we show that a gain-of-function mutation in , which encodes a two-pore domain K ion channel orthologous to human KCNK3, facilitates nutrient absorption and suppresses the metabolic and developmental defects displayed by impaired intestinal MAP Kinase (MAPK) signaling.

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.

The β-Secretase BACE1 Drives Fibroblast Activation in Systemic Sclerosis through the APP/β-Catenin/Notch Signaling Axis.

BACE1 is well-known for its role in the development of Alzheimer's disease. Recent publications, including our own, have demonstrated a role for this enzyme in other chronic diseases. The aim of this study was to investigate the role of BACE1 in the autoimmune disease systemic sclerosis (SSc).

Pan-Enterovirus Characterization Reveals Cryptic Circulation of Clinically Relevant Subtypes in Arizona Wastewater.

Background: Most seasonally circulating enteroviruses result in asymptomatic or mildly symptomatic infections. In rare cases, however, infection with some subtypes can result in paralysis or death. Of the 300 subtypes known, only poliovirus is reportable, limiting our understanding of the distribution of other enteroviruses that can cause clinical disease.

A Phenomenological Study of Postgraduate Medical Trainees' Incidental Learning Experiences and Psychological Well-Being During the COVID-19 Pandemic.

Background:  During the COVID-19 pandemic, postgraduate medical trainees contributed significantly to the healthcare workforce, as multiple vulnerabilities in the healthcare system and medical training were expounded. The burden of training, learning, and working at this time introduced unique psychological and emotional stressors within a context of generalized volatility and radically different ways to work and learn. This study explored postgraduate trainees' experiences with coping, managing, and learning during the COVID-19 pandemic.