Induction of Antigen-Specific Tolerance in a Multiple Sclerosis Model without Broad Immunosuppression.

Multiple sclerosis (MS) is a severe autoimmune disorder that wreaks havoc on the central nervous system, leading to a spectrum of motor and cognitive impairments. There is no cure, and current treatment strategies rely on broad immunosuppression, leaving patients vulnerable to infections. To address this problem, our approach aims to induce antigen-specific tolerance, a much-needed shift in MS therapy.

Evaluating the outcomes of Australia's first all-age public hospital Sport and Exercise Medicine Outpatient Clinic: a retrospective cross-sectional study.

ObjectivesThis study aimed to evaluate the outcomes of Australia's first public hospital all-age Sport and Exercise Medicine Outpatient Clinic (SEMOC).MethodsA retrospective cross-sectional study of patients referred to and reviewed in the SEMOC, during a study period from March to October 2023, was performed. Outcomes were the number of appointments, number of patients reviewed, proportion reviewed within Queensland Health recommended timeframes, patient satisfaction, proportion of Aboriginal and Torres Strait Islander patients, and the rurality of the patients based on the Modified Monash Model of remoteness.

NMR studies of amyloid interactions.

Amyloid fibrils are insoluble, fibrous nanostructures that accumulate extracellularly in biological tissue during the progression of several human disorders, including Alzheimer's disease (AD) and type 2 diabetes. Fibrils are assembled from protein monomers via the transient formation of soluble, cytotoxic oligomers, and have a common molecular architecture consisting of a spinal core of hydrogen-bonded protein β-strands. For the past 25 years, NMR spectroscopy has been at the forefront of research into the structure and assembly mechanisms of amyloid aggregates.

Pertussis vaccination in adults: a behavioral study of physicians from the US, France, and Germany.

Background: Pertussis is a highly contagious respiratory tract infection that affects all ages, though it is most severe in young infants. Adults, especially those with respiratory conditions or other chronic illnesses can also suffer serious consequences of pertussis. Pertussis vaccination is the best method of disease prevention in a lifetime.

Implementing sensor-based digital health technologies in clinical trials: Key considerations from the eCOA Consortium.

The increased use of sensor-based digital health technologies (DHTs) in clinical trials brought to light concerns about implementation practices that might introduce burden on trial participants, resulting in suboptimal compliance and become an additional complicating factor in clinical trial conduct. These concerns may contribute to the lower-than-anticipated uptake of DHT deployment and data use for regulatory decision-making, despite well-articulated benefits. The Electronic Clinical Outcome Assessment (eCOA) Consortium gathered collective experience on deploying sensor-based DHTs and supplemented this with relevant literature focusing on mechanisms that may enhance participant compliance.

Comparison of emulsion and spray methods for fabrication of rapamycin-loaded acetalated dextran microparticles.

Rapamycin (rapa), an immunosuppressive medication, has demonstrated considerable effectiveness in reducing organ transplant rejection and treating select autoimmune diseases. However, the standard oral administration of rapa results in poor bioavailability, broad biodistribution, and harmful off-target effects, necessitating improved drug delivery formulations. Polymeric microparticles (MPs) are one such solution and have demonstrated promise in pre-clinical studies to improve the therapeutic efficacy of rapa.

Limited gut bacterial response of tuatara (Sphenodon punctatus) to dietary manipulation and captivity.

The bacteria of a host's digestive tract play crucial roles in digestion and pathogen resistance. Hosts living in captivity often have more human interaction and antibiotic use, in addition to differences in diet and environment, compared to their wild counterparts. Consequently, wild and captive animals frequently harbour different bacterial communities.

Characterization of Olive Oil Phenolic Extracts and Their Effects on the Aggregation of the Alzheimer's Amyloid-β Peptide and Tau.

The dietary consumption of extra virgin olive oil (EVOO) is believed to slow the progression of Alzheimer's disease (AD) symptoms. Its protective mechanisms are unclear, but specific EVOO phenolic compounds can individually impede the aggregation of amyloid-β (Aβ) peptides and the microtubule-associated protein tau, two important pathological manifestations of AD. It is unknown, however, whether the numerous and variable phenolic compounds that are consumed in dietary EVOO can collectively alter tau and Aβ aggregation as effectively as the individual compounds.

Critical reviews of exposure assessment in carcinogenic hazard identification: the IARC experience.

Objectives: To summarise the rationale, workflow and recommendations for the conduct of exposure assessment critiques in key human studies evaluated for International Agency for Research on Cancer (IARC) on the Identification of Carcinogenic Hazards.

Methods: Approaches to evaluating exposure assessment quality in human cancer and mechanistic studies were reviewed according to the precepts outlined in the IARC Preamble, using two agents as case studies. Exposure assessment 'domains', that is, salient aspects of exposure assessment for the agent under evaluation, were selected for review across the key human studies.

Public health management of pertussis in adults: Practical challenges and future strategies.

A panel of 24 international experts met in July 2022 to discuss challenges associated with pertussis detection, monitoring, and vaccination in adults; conclusions from this meeting are presented. There has been a shift in the epidemiology of pertussis toward older children and adults. This shift has been attributed to the waning of infection- or vaccine-induced immunity, newer detection techniques causing detection bias, and possibly the replacement of whole-cell pertussis with acellular vaccines in high-income countries, which may lead to immunity waning more quickly.

Harmonization of Longitudinal Diffusion Tensor Imaging Data of the Pediatric Cervical and Thoracic Spinal Cord at 3T Using Longitudinal ComBat.

Diffusion tensor imaging (DTI) of the spinal cord has been extensively used to identify biomarkers for spinal cord pathology. Previously, the longitudinal ComBat (longComBat) technique was examined to reduce scanner effects in multi-site, multi-scanner spinal cord DTI data. This study aimed to assess its effectiveness on longitudinal scans using a single-scanner pediatric dataset, including healthy and spinal cord injury (SCI) subjects.

Hot beverage consumption in the African Esophageal Cancer Corridor: A community-based thermal exposure measurement study across the lifespan.

"Very hot beverage" (>65°C) consumption is an IARC probable carcinogen and may contribute to the African esophageal cancer burden. We conducted community cross-sectional exposure studies of hot beverage consumption in Kenya and Malawi during 2018-2019, aiming to: (i) implement a detailed measurement protocol incorporating three measurements of sip temperature and volume so as to predict each sip's intra-esophageal liquid temperature (IELT); (ii) examine variations by seasonality, drinking venue and age, including children. 246 participants were included, of whom 236 had drink measurements (52 children and 183 adults).

Going (Anti)Viral: Improving HIV and HCV Screening and HPV Vaccination in Primary Care.

Background: Human immunodeficiency virus (HIV) and hepatitis C (HCV) screening and human papillomavirus (HPV) vaccine uptake remain suboptimal. To improve HIV and HCV screening and HPV vaccination, the authors implemented a quality improvement project in three southwestern Pennsylvania family medicine residency practices.

Methods: From June 1 to November 30, 2021, participating practices used universal screening and vaccination guidelines and chose from multiple strategies at the office (for example, standing orders), provider (for example, multiple forms of provider reminders), and patient (for example, incentives) levels derived from published literature and tailored to local context.

Building the African American/Black Community's Capacity to Elucidate Factors for High Smoking Rates in Jackson, MS: Results from Implementing a Community-Led Needs Assessment.

Introduction: Although smoking has decreased dramatically over the last 50 years, reductions are uneven by race and income, specifically in the Southern United States. There is a need for intentional collaboration with communities located where large tobacco disparities exist to make lasting change. Using community-based participatory research principles, we provided intensive capacity building to a community advisory group (CAG) of 14 Jackson, MS, residents to conduct a community-led needs assessment.

Variants of NLRP3 Protein in Haemonchus contortus Infected Sheep: Impact on Immune Cell Responsiveness to LPS In Vitro.

Pathogen recognition is an essential component to achieve the desired outcome of host protection. Nod-like receptor pyrin containing domain 3 (NLRP3) is a cytoplasmic pattern recognition receptor (PRR) with a wide array of agonists, such as PAMPs, DAMPs, ATP, bacterial product and viral products. Stimulation of the NLRP3 inflammasome results in proteolytic activation of IL-1β and IL-18, cell pyroptosis and classically, the induction of proinflammatory responses.

Allele Frequency Net Database.

The allele frequency net database (AFND, http://www.allelefrequencies.net ) is an online web-based repository that contains information on the frequencies of immune-related genes and their corresponding alleles in worldwide human populations.

Microparticles incorporating dual apoptotic factors to inhibit inflammatory effects in macrophages.

New approaches to treat autoimmune diseases are needed, and we can be inspired by mechanisms in immune tolerance to guide the design of these approaches. Efferocytosis, the process of phagocyte-mediated apoptotic cell (AC) disposal, represents a potent tolerogenic mechanism that we could draw inspiration from to restore immune tolerance to specific autoantigens. ACs engage multiple avenues of the immune response to redirect aberrant immune responses.

Gut microbiome of the sole surviving member of reptile order Rhynchocephalia reveals biogeographic variation, influence of host body condition and a substantial core microbiota in tuatara across New Zealand.

Tuatara are the sole extant species in the reptile order Rhynchocephalia. They are ecologically and evolutionarily unique, having been isolated geographically for ~84 million years and evolutionarily from their closest living relatives for ~250 million years. Here we report the tuatara gut bacterial community for the first time.

Solid-state NMR chemical shift analysis for determining the conformation of ATP bound to Na,K-ATPase in its native membrane.

Structures of membrane proteins determined by X-ray crystallography and, increasingly, by cryo-electron microscopy often fail to resolve the structural details of unstable or reactive small molecular ligands in their physiological sites. This work demonstrates that C chemical shifts measured by magic-angle spinning (MAS) solid-state NMR (SSNMR) provide unique information on the conformation of a labile ligand in the physiological site of a functional protein in its native membrane, by exploiting freeze-trapping to stabilise the complex. We examine the ribose conformation of ATP in a high affinity complex with Na,K-ATPase (NKA), an enzyme that rapidly hydrolyses ATP to ADP and inorganic phosphate under physiological conditions.

Harmonization of multi-site diffusion tensor imaging data for cervical and thoracic spinal cord at 1.5 T and 3 T using longitudinal ComBat.

MRI scanner hardware, field strengths, and sequence parameters are major variables in diffusion studies of the spinal cord. Reliability between scanners is not well known, particularly for the thoracic cord. DTI data was collected for the entire cervical and thoracic spinal cord in thirty healthy adult subjects with different MR vendors and field strengths.