Healthcare Resource Utilization in the Two Years Prior to Total Shoulder Arthroplasty.

Background: Reverse (RTSA) and anatomic total shoulder arthroplasty (ATSA) are the gold standard surgical treatments for symptomatic glenohumeral osteoarthritis (OA). Typically, these procedures are pursued after exhausting medical management and non-arthroplasty procedures. There is little reliable evidence focused on non-arthroplasty treatments for glenohumeral OA, although their use is widespread.

Antimicrobial resistance profiles and molecular epidemiology of isolates from Scottish bovine mastitis cases.

are opportunistic pathogens which can cause mastitis in dairy cattle. mastitis often has a poor cure rate and can lead to the development of chronic infection, which has an impact on both health and production. However, there are few studies which aim to fully characterize by whole-genome sequencing from bovine mastitis cases.

Quantification of heavy metal exposure in a British population cohort links total mercury levels in plasma with skin tissue-specific changes in mitochondrial-related gene expression.

Heavy metals in our direct environment have profound effects on human health and while some are essential for life, others can be toxic. In vivo studies often focus on clinical features caused by overexposure to, or by deprivation of a heavy metal. However, to understand the cellular impact of heavy metals on health, studies in healthy volunteers before symptom onset are needed.

Risk of Home Falls Among Older Adults After Acute Care Hospitalization: A Cohort Study.

Background: Acute care hospitalization has been associated with older adult home falls after discharge, but less is known about the effects of hospital- and patient-related factors on home fall risk.

Objectives: This study compares the effects of hospital length of stay, medical condition, history of falls, and home health care on period rates of home falls after discharge from acute care hospitalization.

Methods: This was a retrospective cohort study comparing period rates of home injury falls among older adults (age ≥ 65) occurring after discharge from an acute care hospitalization.

Advance care planning readiness, barriers, and facilitators among seriously ill Black older adults and their surrogates: A mixed methods study.

Objectives: Advance care planning (ACP) supports communication and medical decision-making and is best conceptualized as part of the care planning continuum. Black older adults have lower ACP engagement and poorer quality of care in serious illness. Surrogates are essential to effective ACP but are rarely integrated in care planning.

The carbon cost of impaired welfare on sheep farms.

In the face of global climate threats, farm and land-management decisions must balance climate concerns with profitability, animal welfare, and ecosystem health. However, few comprehensive studies have quantified the relationship between animal welfare and greenhouse gas (GHG) emissions, and no study focuses specifically on sheep farms. The present study aims to quantify the effects of impaired welfare on GHG emissions for common welfare challenges faced in UK lowland (L) and hill (H) sheep farming systems.

Enhancing oncolytic virotherapy by extracellular vesicle mediated microRNA reprograming of the tumour microenvironment.

Background: There has been limited success of cancer immunotherapies in the treatment of ovarian cancer (OvCa) to date, largely due to the immunosuppressive tumour microenvironment (TME). Tumour-associated macrophages (TAMs) are a major component of both the primary tumour and malignant ascites, promoting tumour growth, angiogenesis, metastasis, chemotherapy resistance and immunosuppression. Differential microRNA (miRNA) profiles have been implicated in the plasticity of TAMs.

Investigating the associations between a dual diagnosis of malnutrition and obesity and length of stay, readmissions, and 12-month mortality in patients aged >65 yrs admitted to hospital - A retrospective observational single-centre study.

Objective: Despite the protective effect of obesity on mortality in older patients, the dual diagnosis of obesity and malnutrition may worsen outcomes. This study aimed to investigate whether obese patients aged 65 years and over with a diagnosis of malnutrition have different outcomes to obese, non-malnourished peers.

Methods: This retrospective study of inpatients included 9 years of data from annual Malnutrition Audits (2011-2019).

Huddles in Hospital Maternity Settings: A Scoping Review.

Background: The Agency for Healthcare Research and Quality recommends the use of safety huddles, in which clinicians are briefly gathered to review a patient's condition, including new or developing changes in acuity or stability. The Joint Commission describes huddles as a "hallmark" of high-reliability organizations. Previous reviews have confirmed the general utility of huddles, including positive regard by clinicians, but there has not been work specifically looking at huddle use in hospital maternity care settings.

Advancing peer support workforce research: Insights and recommendations through the lens of professionalization.

Over the past two decades, peer support providers have increasingly formalized their roles in the addiction treatment workforce through credentialing and professionalization efforts. Despite these advancements, misconceptions regarding their professional identity persist and contribute to challenges such as burnout and high turnover. This commentary underscores the importance of viewing the peer workforce as an emerging profession using a lens that has previously been applied to other healthcare service roles.

Bovine milk consumption affects the transcriptome of porcine adipose stem cells: Do exosomes play any role?

The potential association of milk with childhood obesity has been widely debated and researched. Milk is known to contain many bioactive compounds as well as bovine exosomes rich in micro-RNA (miR) that can have effects on various cells, including stem cells. Among them, adipose stem cells (ASC) are particularly interesting due to their role in adipose tissue growth and, thus, obesity.

Defining benefit: Clinically and biologically meaningful outcomes in the next-generation Alzheimer's disease clinical care pathway.

To understand the potential benefits of emerging Alzheimer's disease (AD) therapies within and beyond clinical trial settings, there is a need to advance current outcome measurements into meaningful information relevant to all stakeholders. The relationship between the impact on disease biology and clinically measurable outcomes in cognition, function, and behavior must be considered when defining the meaningful benefit of early AD therapies. In this review, we discuss: (1) the lack of consideration for biomarkers in the current concept of meaningfulness in AD; (2) the lack of gold standards for determining minimal biologically and clinically important differences (MBCIDs) in AD trials; (3) how the treatment benefits of disease-modifying treatments are cumulative and increase over time; and (4) the different concepts of meaningfulness among key stakeholders.

The Implementation Outcomes and Population Impact of a Statewide IT Deployment for Family Caregivers: Mixed Methods Study.

Background: In 2022, the US Department of Health and Human Services released the first National Strategy to Support Family Caregivers, identifying actions for both government and the private sector. One of the major goals is to expand data, research, and evidence-based practices to support family caregivers. While IT tools are widely deployed in health care settings, they are rarely available at scale in community agencies.

Enabled Discovery of KAI-11101, a Preclinical DLK Inhibitor for the Treatment of Neurodegenerative Disease and Neuronal Injury.

Dual leucine zipper kinase (DLK), expressed primarily in neuronal cells, is a regulator of neuronal degeneration in response to cellular stress from chronic disease or neuronal injury. This makes it an attractive target for the treatment of neurodegenerative diseases such as Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis, and neuronal injury, such as chemotherapy-induced peripheral neuropathy. Here, we describe the discovery of a potent, selective, brain-penetrant DLK inhibitor, KAI-11101 ().

It takes a village to raise a child- A multidisciplinary approach to promoting paediatric health literacy in cystic fibrosis.

Background: In Northern Ireland, approximately 550 people with cystic fibrosis (PwCF) attend the regional paediatric and adult centres within the Belfast Health and Social Care Trust. This autosomal recessive chronic condition necessitates regular clinical monitoring and a high treatment burden, as well as time implications for the maintenance of respiratory devices. Development of health literacy skills at an early age and promoting children with CF (CwCF) to take an active role in their healthcare has many advantages relating to their long-term self-care in preparation for transition from paediatric to adult care, decision-making and partnership engagement with the CF-multidisciplinary team (CF-MDT).

Discovery of a Novel Mutant-Selective Epidermal Growth Factor Receptor Inhibitor Using an Enabled Drug Discovery Platform.

Despite the success of first, second, and third generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for non-small cell lung cancer with classical EGFR mutations (L858R or Exon 19 deletions), disease progression occurs due to the acquisition of T790M and C797S resistance. Herein, we report a physics-based computationally driven lead identification approach that identified structurally unique imidazo[3.2-]pyrazoles as reversible and wild-type-sparing EGFR TKIs of classical mutations bearing both T790M and C797S.

RESTORE ME: a RCT of oxaloacetate for improving fatigue in patients with myalgic encephalomyelitis/chronic fatigue syndrome.

Background: The energy metabolite oxaloacetate is significantly lower in the blood plasma of ME/CFS subjects. A previous open-label trial with oxaloacetate supplementation demonstrated a significant reduction in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)-related fatigue.

Methods: In this follow-up trial, 82 ME/CFS subjects were enrolled in a 3-month randomized, double-blinded, controlled study, receiving either 2,000 mg of oxaloacetate or control per day.

Mechanical loading reveals an intrinsic cardiomyocyte stiffness contribution to diastolic dysfunction in murine cardiometabolic disease.

Cardiometabolic syndromes including diabetes and obesity are associated with occurrence of heart failure with diastolic dysfunction. There are no specific treatments for diastolic dysfunction, and therapies to manage symptoms have limited efficacy. Understanding of the cardiomyocyte origins of diastolic dysfunction is an important priority to identify new therapeutics.

Just a SNP away: The future of massively parallel reporter assay.

The human genome is largely noncoding, yet the field is still grasping to understand how noncoding variants impact transcription and contribute to disease etiology. The massively parallel reporter assay (MPRA) has been employed to characterize the function of noncoding variants at unprecedented scales, but its application has been largely limited by the context. The field will benefit from establishing a systemic platform to study noncoding variant function across multiple tissue types under physiologically relevant conditions.