Ketogenic Diet-Associated Worsening of Osteoarthritis Histologic Secerity, Increased Pain Sensitivity and Gut Microbiome Dysbiosis in Mice.

Objectives: Dietary interventions are a potentially powerful treatment option for knee osteoarthritis (OA). The objective of this study was to evaluate a well-formulated ketogenic diet (KD) in the context of knee OA histology and pain using the destabilization of the medial meniscus (DMM) mouse model and correlate with gut microbiome and systemic cytokine levels.

Methods: Adult male mice underwent unilateral DMM or sham surgery and were then fed eight weeks of KD or chow.

Sexually dimorphic metabolic effects of a high fat diet on knee osteoarthritis in mice.

Background: Women have a higher risk of developing osteoarthritis (OA) than men, including with obesity. To better understand this disparity, we investigated sex differences in metabolic and inflammatory factors associated with OA using a diet-induced mouse model of obesity. We hypothesized that 20 weeks of high-fat diet (HFD) would induce sexually dimorphic changes in both systemic and local risk factors of knee OA.

Climate Futures for Lizards and Snakes in Western North America May Result in New Species Management Issues.

We assessed changes in fundamental climate-niche space for lizard and snake species in western North America under modeled climate scenarios to inform natural resource managers of possible shifts in species distributions. We generated eight distribution models for each of 130 snake and lizard species in western North America under six time-by-climate scenarios. We combined the highest-performing models per species into a single ensemble model for each scenario.

Qualitative Insights Into Patients' and Family Members' Experiences of In-Hospital Medication Management After a Critical Care Episode.

Background: Patient recovery after a critical illness can be protracted, requiring a care continuum that extends along a patient pathway from the critical care unit, hospital ward, and into the community care setting. High-quality care on patient transfer from critical care, including medication safety, is facilitated by education for patients and families, family engagement, support systems, and health care professional (HCP)-patient communication. Currently, uncertainty exists regarding how HCPs can and should engage with critical care patients and family members about their medication.

Understanding temporal variability across trophic levels and spatial scales in freshwater ecosystems.

A tenet of ecology is that temporal variability in ecological structure and processes tends to decrease with increasing spatial scales (from locales to regions) and levels of biological organization (from populations to communities). However, patterns in temporal variability across trophic levels and the mechanisms that produce them remain poorly understood. Here we analyzed the abundance time series of spatially structured communities (i.

OA susceptibility in mice is partially mediated by the gut microbiome, is transferrable via microbiome transplantation and is associated with immunophenotype changes.

Objectives: The Murphy Roths Large (MRL)/MpJ 'superhealer' mouse strain is protected from post-traumatic osteoarthritis (OA), although no studies have evaluated the microbiome in the context of this protection. This study characterised microbiome differences between MRL and wild-type mice, evaluated microbiome transplantation and OA and investigated microbiome-associated immunophenotypes.

Methods: Cecal material from mixed sex C57BL6/J (B6) or female MRL/MpJ (MRL) was transplanted into B6 and MRL mice, then OA was induced by disruption of the medial meniscus surgery (DMM).

Murine cartilage microbial DNA deposition occurs rapidly following the introduction of a gut microbiome and changes with obesity, aging, and knee osteoarthritis.

Cartilage microbial DNA patterns have been recently characterized in osteoarthritis (OA). The objectives of this study were to evaluate the gut origins of cartilage microbial DNA, to characterize cartilage microbial changes with age, obesity, and OA in mice, and correlate these to gut microbiome changes. We used 16S rRNA sequencing performed longitudinally on articular knee cartilage from germ-free (GF) mice following oral microbiome inoculation and cartilage and cecal samples from young and old wild-type mice with/without high-fat diet-induced obesity (HFD) and with/without OA induced by destabilization of the medial meniscus (DMM) to evaluate gut and cartilage microbiota.

A Multi-method Exploratory Evaluation of a Service Designed to Improve Medication Safety for Patients with Monitored Dosage Systems Following Hospital Discharge.

Background And Objective: Medication safety problems are common post-hospital discharge, and an important global healthcare improvement target. The Transfers of Care Around Medicines (TCAM) service was launched by a National Health Service Trust in the North-West of England, initially focusing on patients with new or existing Monitored Dosage Systems (MDS). The TCAM service is designed to enable the prompt transfer of medication information, with referrals made by hospitals at discharge to a named community pharmacy.

Sex-Linked Discrepancies in C57BL6/J Mouse Osteoarthritis are Associated With the Gut Microbiome and are Transferrable by Microbiome Transplantation.

Objective: Females have reduced osteoarthritis (OA) in surgical models. The objective of the current study was to evaluate a sex-linked gut microbiome in the pathogenesis of OA.

Methods: We induced OA via destabilization of the medial meniscus surgery in adult male and female C57BL6/J mice with and without opposite-sex microbiome transplantation.

Understanding medication safety involving patient transfer from intensive care to hospital ward: a qualitative sociotechnical factor study.

Objective: To understand the sociotechnical factors affecting medication safety when intensive care patients are transferred to a hospital ward. Consideration of these medication safety factors would provide a theoretical basis, on which future interventions can be developed and evaluated to improve patient care.

Design: Qualitative study using semistructured interviews of intensive care and hospital ward-based healthcare professionals.

Using sociotechnical theory to understand medication safety work in primary care and prescribers' use of clinical decision support: a qualitative study.

Objectives: The concept of safety work draws attention to the intentional work of ensuring safety within care systems. Clinical decision support (CDS) has been designed to enhance medication safety in primary care by providing decision-making support to prescribers. Sociotechnical theory understands that healthcare settings are complex and dynamically connected systems of fluid networks, human agents, changing relationships and social processes.

Peripheral Blood DNA Methylation-Based Machine Learning Models for Prediction of Knee Osteoarthritis Progression: Biologic Specimens and Data From the Osteoarthritis Initiative and Johnston County Osteoarthritis Project.

Objective: The lack of accurate biomarkers to predict knee osteoarthritis (OA) progression is a key unmet need in OA clinical research. The objective of this study was to develop baseline peripheral blood epigenetic biomarker models to predict knee OA progression.

Methods: Genome-wide buffy coat DNA methylation patterns from 554 individuals from the Osteoarthritis Biomarkers Consortium (OABC) were determined using Illumina Infinium MethylationEPIC 850K arrays.

A Pilot Analysis of Genome-Wide DNA Methylation Patterns in Mouse Cartilage Reveals Overlapping Epigenetic Signatures of Aging and Osteoarthritis.

Objective: Cartilage epigenetic changes are strongly associated with human osteoarthritis (OA). However, the influence of individual environmental OA risk factors on these epigenetic patterns has not been determined; herein we characterize cartilage DNA methylation patterns associated with aging and OA in a mouse model.

Methods: Murine knee cartilage DNA was extracted from healthy young (16-week, n = 6), old (82-week, n = 6), and young 4-week post-destabilization of the medial meniscus (DMM) OA (n = 6) C57BL6/J mice.

Understanding factors that could influence patient acceptability of the use of the PINCER intervention in primary care: A qualitative exploration using the Theoretical Framework of Acceptability.

Introduction: Medication errors are an important cause of morbidity and mortality. The pharmacist-led IT-based intervention to reduce clinically important medication errors (PINCER) intervention was shown to reduce medication errors when tested in a cluster randomised controlled trial and when implemented across one region of England. Now that it has been rolled out nationally, and to enhance findings from evaluations with staff and stakeholders, this paper is the first to report patients' perceived acceptability on the use of PINCER in primary care and proposes suggestions on how delivery of PINCER related care could be delivered in a way that is acceptable and not unnecessarily burdensome.

Understanding factors influencing uptake and sustainable use of the PINCER intervention at scale: A qualitative evaluation using Normalisation Process Theory.

Introduction: Medication errors are an important cause of morbidity and mortality. The pharmacist-led IT-based intervention to reduce clinically important medication errors (PINCER) has demonstrated improvements in primary care medication safety, and whilst now the subject of national roll-out its optimal and sustainable use across health contexts has not been fully explored. As part of a qualitative evaluation we aimed to identify factors influencing successful adoption, embedding and sustainable use of PINCER across primary care settings in England, UK.

Persistent Severe Acute Respiratory Syndrome Coronavirus 2 Infection With accumulation of mutations in a patient with poorly controlled Human Immunodeficiency Virus infection.

A 22-year-old woman with uncontrolled advanced human immunodeficiency virus (HIV) infection was persistently infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) beta variant for 9 months, the virus accumulating >20 additional mutations. Antiretroviral therapy suppressed HIV and cleared SARS-CoV-2 within 6 to 9 weeks. Increased vigilance is warranted to benefit affected individuals and prevent the emergence of novel SARS-CoV-2 variants.

The Microbiome in Osteoarthritis: a Narrative Review of Recent Human and Animal Model Literature.

Purpose Of The Review: The microbiome has recently emerged as a powerful contributor to health and illness in chronic, systemic disorders. Furthermore, new microbiome niches beyond traditional gut locations are frequently being described. Over the past 5 years, numerous pivotal studies have demonstrated associations between changes in various microbiome niches and the development of osteoarthritis (OA).

DNA methylation and noncoding RNA in OA: Recent findings and methodological advances.

Introduction: Osteoarthritis (OA) is a chronic musculoskeletal disease characterized by progressive loss of joint function. Historically, it has been characterized as a disease caused by mechanical trauma, so-called 'wear and tear'. Over the past two decades, it has come to be understood as a complex systemic disorder involving gene-environmental interactions.

The mechanistic target of rapamycin as a regulator of metabolic function in oligodendroglia during remyelination.

Despite evidence for prominent metabolic dysfunction within multiple sclerosis (MS) lesions, the mechanisms controlling metabolic shifts in oligodendroglia are poorly understood. The cuprizone model of demyelination and remyelination is a valuable tool for assessing metabolic insult during oligodendrocyte death and myelin degradation, closely resembling the distal oligodendrogliopathy seen in Pattern III MS lesions. In this review we discuss how metabolic processes in oligodendrocytes are disrupted in both MS and the cuprizone model, as well as the evidence for mechanistic target of rapamycin (mTOR) signaling as a key regulator of oligodendroglial metabolic function and efficient remyelination.

Cholesterol biosynthesis defines oligodendrocyte precursor heterogeneity between brain and spinal cord.

Brain and spinal cord oligodendroglia have distinct functional characteristics, and cell-autonomous loss of individual genes can result in different regional phenotypes. However, a molecular basis for these distinctions is unknown. Using single-cell analysis of oligodendroglia during developmental myelination, we demonstrate that brain and spinal cord precursors are transcriptionally distinct, defined predominantly by cholesterol biosynthesis.

Understanding the implementation, impact and sustainable use of an electronic pharmacy referral service at hospital discharge: A qualitative evaluation from a sociotechnical perspective.

Introduction: The transition of patients across care settings is associated with a high risk of errors and preventable medication-related harm. Ensuring effective communication of information between health professionals is considered important for improving patient safety. A National Health Service(NHS) organisation in the North West of England introduced an electronic transfer of care around medicines (TCAM) system which enabled hospital pharmacists to send information about patient's medications to their nominated community pharmacy.