Co-Designing a Consumer-Focused Digital Reporting Health Platform to Improve Adverse Medicine Event Reporting: Protocol for a Multimethod Research Project (the ReMedi Project).

Background: Adverse medicine events (AMEs) are unintended effects that occur following administration of medicines. Up to 70% of AMEs are not reported to, and hence remain undetected by, health care professionals and only 6% of AMEs are reported to regulators. Increased reporting by consumers, health care professionals, and pharmaceutical companies to medicine regulatory authorities is needed to increase the safety of medicines.

Intraoperative Facet Joint Block Reduces Pain After Oblique Lumbar Interbody Fusion: A Double-Blinded, Randomized, Placebo-Controlled Clinical Trial.

Background: Oblique lumbar interbody fusion (OLIF) results in less tissue damage than in other surgeries, but immediate postoperative pain occurs. Notably, facet joint widening occurs in the vertebral body after OLIF. We hypothesized that the application of a facet joint block to the area of widening would relieve facet joint pain.

Targeting TRPC channels for control of arthritis-induced bone erosion.

Arthritis leads to bone erosion due to an imbalance between osteoclast and osteoblast function. Our prior investigations revealed that the Ca-selective ion channel, Orai1, is critical for osteoclast maturation. Here, we show that the small-molecule ELP-004 preferentially inhibits transient receptor potential canonical (TRPC) channels.

The role of psychosocial factors in mediating the treatment response of epidural steroid injections for low back pain with or without lumbosacral radiculopathy: A scoping review.

Epidural steroid injections (ESIs) are often used to treat low back pain (LBP) due to lumbosacral radiculopathy as well as LBP without a clear component of radiculopathy, in some cases. While it is increasingly recognized that psychosocial factors are associated with pain outcomes, few studies have assessed the contribution of these factors to common pain interventions like ESIs. This study aimed to summarize the scope and nature of how psychosocial factors are accounted for in research on ESIs for the treatment of LBP with or without lumbosacral radiculopathy and to identify gaps and recommendations for future research.

CFTR dictates monocyte adhesion by facilitating integrin clustering but not activation.

Monocytes are critical in controlling tissue infections and inflammation. Monocyte dysfunction contributes to the inflammatory pathogenesis of cystic fibrosis (CF) caused by CF transmembrane conductance regulator (CFTR) mutations, making CF a clinically relevant disease model for studying the contribution of monocytes to inflammation. Although CF monocytes exhibited adhesion defects, the precise mechanism is unclear.

Approach to the Patient with Achondroplasia - New Considerations for Diagnosis, Management and Treatment.

Achondroplasia is the most common disproportionate short-stature skeletal dysplasia. Features associated with achondroplasia are rhizomelia, macrocephaly, midface hypoplasia, and typical cognition. Potential medical complications include foramen magnum stenosis, hydrocephalus, middle ear dysfunction, obstructive and central sleep apnea, spinal stenosis and genu varum.

Palliative Care Initiated in the Emergency Department: A Cluster Randomized Clinical Trial.

Importance: The emergency department (ED) offers an opportunity to initiate palliative care for older adults with serious, life-limiting illness.

Objective: To assess the effect of a multicomponent intervention to initiate palliative care in the ED on hospital admission, subsequent health care use, and survival in older adults with serious, life-limiting illness.

Design, Setting, And Participants: Cluster randomized, stepped-wedge, clinical trial including patients aged 66 years or older who visited 1 of 29 EDs across the US between May 1, 2018, and December 31, 2022, had 12 months of prior Medicare enrollment, and a Gagne comorbidity score greater than 6, representing a risk of short-term mortality greater than 30%.

Exploring the Complex Relationship Between Psychosocial Stress and the Gut Microbiome: Implications for Inflammation and Immune Modulation.

There is growing interest in understanding the complex relationship between psychosocial stress and the human gastrointestinal microbiome (GIM). This review explores the potential physiological pathways connecting these two and how they contribute to a pro-inflammatory environment that can lead to the development and progression of the disease. Exposure to psychosocial stress triggers the activation of the sympathetic nervous system (SNS) and hypothalamic-pituitary axis (HPA), leading to various physiological responses essential for survival and coping with the stressor.

Primary Graft Dysfunction after Heart Transplantation: Current Evidence and Implications for Clinical Practice.

Purpose Of Review: This review summarizes the current literature on primary graft dysfunction highlighting the current definition, reviewing epidemiology, and describing donor, recipient, and perioperative risk factors in the contemporary era.

Recent Findings: PGD, in its most severe form, complicates 8% of heart transplants and portends a 1-year mortality of close to 40%. PGD is multifactorial and heterogeneous with contributions from donor and recipient risk as well as organ recovery and preservation modalities.

Hypomorphic RAG2 Deficiency Promotes Selection of Self-Reactive B Cells.

Reduced function or hypomorphic variants in recombination-activating genes (RAG) 1 or 2 result in a broad clinical phenotype including common variable immunodeficiency (CVID) and even adult-onset disease. Milder RAG variants are less characterized. Here we describe the longitudinal course of a milder combined RAG deficiency in 3 of 7 siblings sharing the same RAG2 mutations over a 50-year study.

Longitudinal qualitative assessment of meaningful symptoms and relevance of WATCH-PD digital measures for people with early Parkinson's.

Background: Longitudinal qualitative data on what matters to people with Parkinson's disease are lacking and needed to guide patient-centered clinical care and development of outcome measures.

Objective: To evaluate change over time in symptoms, impacts, and relevance of digital measures to monitor disease progression in early Parkinson's.

Methods: In-depth, online symptom mapping interviews were conducted with 33 people with early Parkinson's at baseline and 1 year later to evaluate (A) symptoms, (B) impacts, and (C) relevance of digital measures to monitor personally relevant symptoms.

Ocrelizumab dose selection for treatment of pediatric relapsing-remitting multiple sclerosis: results of the OPERETTA I study.

Background: The presented study identified the appropriate ocrelizumab dosing regimen for patients with pediatric-onset multiple sclerosis (POMS).

Methods: Patients with POMS aged 10-17 years were enrolled into cohort 1 (body weight [BW] < 40 kg, ocrelizumab 300 mg) and cohort 2 (BW ≥ 40 kg, ocrelizumab 600 mg) during a 24-week dose-exploration period (DEP), followed by an optional ocrelizumab (given every 24 weeks) extension period.

Primary Endpoints: pharmacokinetics, pharmacodynamics (CD19 B-cell count); secondary endpoint: safety; exploratory endpoints: MRI activity, protocol-defined relapses, Expanded Disability Status Scale (EDSS) score change.

Reduced antioxidant high-density lipoprotein function in heart failure with preserved ejection fraction.

Background: Heart failure (HF) is a heterogeneous clinical syndrome affecting a growing global population. Due to the high incidence of cardiovascular risk factors, a large proportion of the Western population is at risk for heart failure. Oxidative stress and inflammation play a crucial role in the pathophysiology of heart failure with preserved ejection fraction (HFpEF).

Technical considerations of cardiac computed tomography in children.

Cardiac computed tomography angiography (CTA) is a valuable tool in the assessment of congenital and acquired cardiac disease in children. The goal of cardiac CTA is to produce images that are free of motion and provide sufficient characterization of the anatomy in question. Given the complexity of pediatric patient characteristics, including patient size, heart rate, breath-holding capability, and variant anatomy, cardiac CTA technique must be individualized to the patient as well as the indication to answer the clinical question while also minimizing radiation exposure.

Hemodynamic response of the aortic valve during dobutamine onset then progressive aortic banding.

An increasing number of procedures over the past two decades for aortic stenosis (AS) reflects the combination of an aging population and less invasive transcatheter options. As a result, the hemodynamics of the aortic valve (AV) have gained renewed interest to understand its behavior and to optimize patient selection. We studied the hemodynamic relationship between pressure loss (ΔP) and transvalvular flow (Q) of the normal AV as well as the impact of a variable supravalvular stenosis.

Pan-cancer secreted proteome and skeletal muscle regulation: insight from a proteogenomic data-driven knowledge base.

Large-scale, pan-cancer analysis is enabled by data driven knowledge bases that link tumor molecular profiles with phenotypes. A debilitating cancer-related phenotype is skeletal muscle loss, or cachexia, which occurs partly from tumor products secreted into circulation. Using the LinkedOmicsKB knowledge base assembled from the Clinical Proteomics Tumor Analysis Consortium proteogenomic analysis, along with catalogs of human secretome proteins, ligand-receptor pairs and molecular signatures, we sought to identify candidate pan-cancer proteins secreted to blood that could regulate skeletal muscle phenotypes in multiple solid cancers.

Differential diagnosis in immune checkpoint inhibitors neurotoxicity.

Background: Neurologic symptoms seen in patients receiving immune checkpoint inhibitors (ICI) may not be entirely caused by immunotoxicity. We aim to highlight these confounding conditions through clinical cases to encourage early recognition and management.

Methods: We describe a series of seven cases from our institution that were treated with ICI and presented with Neurologic symptoms and were diagnosed with superimposed conditions beyond immunotoxicity.

Investigation of the Gas-Phase N + CHCN Reaction at Low Temperatures.

Rate coefficients for ion-polar-molecule reactions between acetonitrile molecules (CHCN) and nitrogen molecular ions (N), which are of importance to the upper atmospheric chemistry of Saturn's moon Titan, were measured for the first time at low translational temperatures. In the experiments, the reaction between sympathetically cooled N ions embedded in laser-cooled Ca Coulomb crystals and velocity-selected acetonitrile molecules generated using a wavy Stark velocity filter was studied to determine the reaction rate coefficients. Capture rate coefficients calculated by the Su-Chesnavich approach and by the perturbed rotational state theory considering the rotational state distribution of CHCN were compared to the experimental rate coefficients.

Professional improbity: How Hermann J. Muller's ethics affected his science.

The present paper provides an assessment of how the scientific and national policy achievements/goals of Hermann J. Muller were impacted by his ethics and provides several documented episodes in which Muller acted unethically to promote his personal gain-at the expense of others-within the scientific community. Muller manipulated the scientific community in self-serving ways to suppress perspectives that challenged his own views on radiation-induced gene mutation, and hereditary and cancer risk assessment in ways that influenced his significant awards (e.

Circulating Endocannabinoids and Cognitive Function in Older Adults.

The role of endogenous cannabinoids (endocannabinoids; eCBs) in cognitive-related processes has been demonstrated in preclinical studies. However, observational studies are lacking. We examined the associations of multiple circulating eCBs and eCB-like molecules with cognitive function in a sample of dementia-free older adults.

TBC1D15 Inhibits Autophagy of Microglia through Maintaining the Damaged Swelling Lysosome in Alzheimer's Disease.

Autophagy in microglia is essential for the clearance of amyloid-beta (Aβ) and amyloid plaques in Alzheimer's disease. However, reports regarding the levels of autophagy in microglia have been inconsistent; some studies indicate an early enhancement followed by a subsequent reduction, while others describe a persistently weakened state. Notably, there is a lack of systematic studies documenting the temporal changes in microglial autophagy.