Phenotype-Led Identification of IL-10 Upregulators in Human CD4 T-cells and Elucidation of Their Pharmacology as Highly Selective CDK8/CDK19 Inhibitors.

Therapeutics promoting the endogenous production of IL-10 have the potential to restore homeostasis in inflammatory disorders such as inflammatory bowel disease (IBD). Here we describe the identification of a series of IL-10 upregulators based on a pyrimidyl-piperidine scaffold through a high throughput phenotypic CD4 T-cell multiplex assay. optimization of the initial hit yielded a lead with good potency and an clearance profile, compound 3-7, which additionally demonstrated efficacy in a murine endotoxin challenge PK-PD mechanistic model.

Can I Phone a Friend? Exploring the Use of Digital Devices in Clinical Exams.

Background: Objective structured clinical examinations (OSCEs) are used globally to assess health professional learners' clinical skills and applied knowledge. Despite innovations with simulated participants, manikin technology and real patient involvement, there remains a gap between 'real-life' practice and 'OSCE experience'. For example, although mobile phone use is increasingly common in clinical practice; however, it would represent a significant disruption to established assessment practices in OSCEs.

Case report: Localized coloproctitis caused by novel in a dog.

A 6-year-old male neutered boxer mix canine was presented for a one-month history of dyschezia, hematochezia, and constipation. Colonoscopy and endoscopic biopsies revealed non-specific lymphoplasmacytic, eosinophilic colitis. Despite pursuing various therapies over a 3.

[Disappearing bone disease of the shoulder (Gorham-Stout Syndrom)].

The spontaneous disappearance of a segment of bone in a short period without the existence of a tumoral disease that justifies it is an exceptional event. We report the case of an older adult in whom the upper epiphysis of the right humerus and part of the acromion disappeared in a period of 3 weeks in the absence of a malignant tumor. Bone biopsy revealed osteoclasts, lymphatic vessels, and blood vessels.

How did the COVID-19 pandemic change patient experience during radiation therapy for head and neck cancer: A single centre survey.

Introduction/background: Patients receiving treatment for head and neck cancer (HNC) with curative intent, will potentially undergo primary or adjuvant radiation therapy (RT). These patients require supportive management from an extended multi-disciplinary team, to manage the severe toxicities and distress that a course of treatment can bring. A survey was designed to determine if there were changes in the experience of HNC patients attending for radical RT, from the beginning to the end of their treatment course.

Power failure; an uncomfortable teaching initiative?

Background: Introducing medical students to the concept of Cultural Humility, we devised a teaching initiative for students to consider how power manifests through the use of language in clinical communication, with a focus on General Practice. Cultural Humility is a pedagogical framework, introduced by Tervalon and Murray-Garcia, to address what they consider as the limitations of the Cultural Competence model.

Approach: Our teaching initiative specifically focused on power in clinical communication, both oral consultations and written notes.

A structural basis of T cell cross-reactivity to native and spliced self-antigens presented by HLA-DQ8.

Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease that has a strong HLA association, where a number of self-epitopes have been implicated in disease pathogenesis. Human pancreatic islet-infiltrating CD4 T cell clones not only respond to proinsulin C-peptide (PI GQVELGGGPGAGSLQ) but also cross-react with a hybrid insulin peptide (HIP; PI-IAPP GQVELGGG-NAVEVLK) presented by HLA-DQ8. How T cell receptors recognize self-peptide and cross-react to HIPs is unclear.

The molecular basis underlying T cell specificity towards citrullinated epitopes presented by HLA-DR4.

CD4 T cells recognising citrullinated self-epitopes presented by HLA-DRB1 bearing the shared susceptibility epitope (SE) are implicated in rheumatoid arthritis (RA). However, the underlying T cell receptor (TCR) determinants of epitope specificity towards distinct citrullinated peptide antigens, including vimentin-64cit and α-enolase-15cit remain unclear. Using HLA-DR4-tetramers, we examine the T cell repertoire in HLA-DR4 transgenic mice and observe biased TRAV6 TCR gene usage across these two citrullinated epitopes which matches with TCR bias previously observed towards the fibrinogen β-74cit epitope.

Understanding the treatment experiences of adults diagnosed with early-onset colorectal cancer: A qualitative study.

Objective: Early-onset colorectal cancer (CRC) incidence in adults aged under 50 is increasing. There is a critical lack of knowledge regarding the challenges faced by early-onset CRC patients and their experiences of treatment. The aim of this study was to explore the lived experiences of individuals receiving treatment for early-onset CRC, and the resulting impact on their lives.

[n]Cycloparaphenylenes as Compatible Fluorophores for Melt Electrowriting.

Fluorescent probes are an indispensable tool in the realm of bioimaging technologies, providing valuable insights into the assessment of biomaterial integrity and structural properties. However, incorporating fluorophores into scaffolds made from melt electrowriting (MEW) poses a challenge due to the sustained, elevated temperatures that this processing technique requires. In this context, [n]cycloparaphenylenes ([n]CPPs) serve as excellent fluorophores for MEW processing with the additional benefit of customizable emissions profiles with the same excitation wavelength.

Validation of a new acoustic telemetry transmitter for the study of predation events in small fishes.

Acoustic telemetry has emerged as an important tool for studying the movement and behavior of aquatic animals. Predation-sensing acoustic transmitters combine the functions of typical acoustic transmitters with the added ability to identify the predation of tagged animals. The objective of this paper was to assess the performance of a newly miniaturized acid-based predation-sensing acoustic transmitter (Innovasea V3D; 0.

Measles Outbreak Associated with a Migrant Shelter - Chicago, Illinois, February-May 2024.

Measles, a highly contagious respiratory virus with the potential to cause severe complications, hospitalization, and death, was declared eliminated from the United States in 2000; however, with ongoing global transmission, infections in the United States still occur. On March 7, 2024, the Chicago Department of Public Health (CDPH) confirmed a case of measles in a male aged 1 year residing in a temporary shelter for migrants in Chicago. Given the congregate nature of the setting, high transmissibility of measles, and low measles vaccination coverage among shelter residents, measles virus had the potential to spread rapidly among approximately 2,100 presumed exposed shelter residents.

Time-dependent antidepressant-like effects of reelin and ketamine in the repeated-corticosterone model of chronic stress.

There is an urgent need for novel antidepressants, given that approximately 30% of those diagnosed with depression do not respond adequately to first-line treatment. Additionally, monoaminergic-based antidepressants have a substantial therapeutic time-lag, often taking months to reach full therapeutic effect. Ketamine, an N-methyl-d-aspartate receptor (NMDAR) antagonist is the only current effective rapid-acting antidepressant, demonstrating efficacy within hours and lasting up to two weeks with an acute dose.

Implications of Measles Inclusion by Commercial Syndromic Polymerase Chain Reaction Panels - United States, May 2022-April 2023.

Syndromic polymerase chain reaction (PCR) panels are used to test for pathogens that can cause rash illnesses, including measles. Rash illnesses have infectious and noninfectious causes, and approximately 5% of persons experience a rash 7-10 days after receipt of a measles, mumps, and rubella (MMR) vaccine. MMR vaccine includes live attenuated measles virus, which is detectable by PCR tests.

Conveying the pathogenesis of type 1 diabetes to the blind, low-vision and diverse needs communities through sensory stimulation.

To educate members of the blind, low-vision and diverse needs communities on the pathogenesis of the chronic autoimmune disease, type 1 diabetes, members of our team with research expertise in immune-mediated diseases, participated in the 2023 Monash Sensory Science (MSS) Exhibition. Using QR code linked audio commentary, participants were guided through tactile displays demonstrating normal insulin action in the regulation of blood glucose levels and its vital role in providing energy to tissues, followed by displays describing the various stages of the immune system's aberrant attack and the eventual complete destruction of the insulin producing beta-cells of the pancreatic islets in type 1 diabetes. These models conveyed to the participants the huge effect that this autoimmune-mediated disease has on the quality of life of affected individuals including the subsequent lifelong reliance on insulin injections to maintain glucose homeostasis.

Best practice recommendations for the integration of trauma-informed approaches in maternal mental health care within the context of perinatal trauma and loss: A systematic review of current guidance.

Purpose: The National Health Service (NHS) in England plans to increase accessibility to evidence-based, trauma-informed psychological care for women in the perinatal period. Therefore, this systematic review aimed to 1) synthesise current guidance from clinical guidelines, policy documents, and care standards on trauma-informed approaches to care in maternal mental health settings within the context of pregnancy-related trauma and 2) to offer recommendations informing the implementation and evaluation of this type of care.

Methods: Nine electronic databases were searched and screened.

Role of endometrial sampling to differentiate between advanced endometrial versus ovarian malignancy: retrospective cohort study.

Objective: Distinguishing between advanced stage endometrial and ovarian cancer at diagnosis can be challenging, especially when patients do not present with abnormal uterine bleeding. Given emerging systemic therapies specific for ovarian versus endometrial cancers, it has become increasingly critical to establish the correct diagnosis at presentation to ensure appropriate treatment. This study evaluates the frequency with which advanced endometrial cancer is mistakenly presumed to be ovarian cancer.

Occupational therapy's oversight: How science veiled our humanity.

Background: Occupational therapy's connection to positivist science predates the profession's formal beginning, with important contributing knowledge sources coming from mathematics, physics, psychology, and systems theory. While these sources of objective knowledge provide a rational, defendable position for practice, they can only explain a portion of what it means to exist as an occupational being.

Aims/objectives: This article aims to reveal some of the history of science within occupational therapy and reveal the subjective, ontological nature of doing everyday activities that the profession's preoccupation with positivist science has obscured.

Brain changes: aerobic exercise for traumatic brain injury rehabilitation.

Introduction: Traumatic Brain Injury (TBI) accounts for millions of hospitalizations and deaths worldwide. Aerobic exercise is an easily implementable, non-pharmacological intervention to treat TBI, however, there are no clear guidelines for how to best implement aerobic exercise treatment for TBI survivors across age and injury severity.

Methods: We conducted a PRISMA-ScR to examine research on exercise interventions following TBI in children, youth and adults, spanning mild to severe TBI.

Evaluation of , a novel thromboxane receptor antagonist, in a first-in-human phase I clinical trial.

The thromboxane receptor (TP) antagonist is in clinical development for treatment of cardiopulmonary diseases, such as pulmonary arterial hypertension. In this randomized, placebo-controlled Phase I clinical trial, , administered as the oral formulation , was evaluated for safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) in healthy males. The first-in-human trial had three Parts: A, single ascending dose (SAD) study with seven groups given 0.