Discovery of Antinociceptive α9α10 Nicotinic Acetylcholine Receptor Antagonists by Stable Receptor Expression.

Chronic neuropathic pain is an increasingly prevalent societal issue that responds poorly to existing therapeutic strategies. The α9α10 nicotinic acetylcholine receptor (nAChR) has emerged as a potential target to treat neuropathic pain. However, challenges in expressing functional α9α10 nAChRs in mammalian cell lines have slowed the discovery of α9α10 ligands and studies into the relationship between α9α10 nAChRs and neuropathic pain.

Nurses' Descriptions of Interdisciplinary Interactions in Stroke and Geriatric Rehabilitation Units: A Case Example of the Registered Practical Nurse.

Aim: To analyse how nurses describe their interactions with other interdisciplinary team members within stroke and geriatric rehabilitation.

Design: A secondary analysis of cross-sectional ethnographic interview data was conducted using Elo and Kyngäs' (2008) deductive content analysis.

Methods: Between April 12 and July 25, 2022, semi-structured interviews were conducted with 31 registered practical nurses recruited through convenience sampling from three tertiary hospital sites in Southwestern Ontario.

Posterior Sacroiliac Fusion Surgery: A Retrospective Single Center Study.

Background: Chronic sacroiliitis has variable etiologies with numerous treatments of varying efficacy. In recent years, a novel posterior approach utilizing bone matrix has been developed although to date, there is limited data in the literature regarding efficacy and safety through this approach. Benefits described include reduced adverse outcomes and quicker recovery when compared to the lateral approach.

Type I interferons induce an epigenetically distinct memory B cell subset in chronic viral infection.

Memory B cells (MBCs) are key providers of long-lived immunity against infectious disease, yet in chronic viral infection, they do not produce effective protection. How chronic viral infection disrupts MBC development and whether such changes are reversible remain unknown. Through single-cell (sc)ATAC-seq and scRNA-seq during acute versus chronic lymphocytic choriomeningitis viral infection, we identified a memory subset enriched for interferon (IFN)-stimulated genes (ISGs) during chronic infection that was distinct from the T-bet subset normally associated with chronic infection.

Assessing Risk Factors and Comorbidities in the Treatment of Chronic Pain: A Narrative Review.

Purpose Of Review: Chronic pain affects a significant portion of the population globally, making it a leading cause of disability. Understanding the multifaceted nature of chronic pain, its various types, and the intricate relationship it shares with risk factors, comorbidities, and mental health issues like depression and anxiety is critical for comprehensive patient care. Factors such as socioeconomic status (SES), age, gender, and obesity collectively add layers of complexity to chronic pain experiences and pose management challenges.

Biofilm exopolysaccharides alter sensory-neuron-mediated sickness during lung infection.

Infections of the lung cause observable sickness thought to be secondary to inflammation. Signs of sickness are crucial to alert others via behavioral-immune responses to limit contact with contagious individuals. Gram-negative bacteria produce exopolysaccharide (EPS) that provides microbial protection; however, the impact of EPS on sickness remains uncertain.

Social media for learning: A qualitative exploration of the factors that impact clinical learners' attitudes and intentions.

Background: Social media has created a revolution in learning and teaching. This study set out to provide a theory-informed exploration of the factors influencing medical students' perspectives of learning with social media using the theory of planned behaviour (TPB) as a framework.

Methods: The study collected data using semi-structured interviews from seven third year medical students at an undergraduate Australian medical school, who were in their first clinical year.

Epilepsy surgery perceptions among general neurologists and epilepsy specialists: A survey.

Objective: Surgical intervention for drug-resistant epilepsy (DRE) is a safe and efficacious evidence-based treatment. Yet, neurologists have historically revealed hesitance in referring patients for surgical evaluations. The present study surveyed general neurologists and epilepsy specialists to assess their views and process in referring patients for specialized epilepsy care and epilepsy surgery.

Bromocriptine and Colesevelam Hydrochloride: Novel Therapies for Type II Diabetes Mellitus.

The increasing prevalence of type II diabetes mellitus (T2DM) is a worldwide healthcare concern. Over the years, our understanding of T2DM has grown considerably in uncovering the pathophysiology of the disease and, in turn, understanding how improved treatment methods can be used to slow disease progression. Some long-term complications that are responsible for most T2DM mortalities include cardiovascular disease, neurological decline, and renal failure.

Heritable changes in chromatin contacts linked to transgenerational obesity.

Burgeoning evidence demonstrates that effects of environmental exposures can be transmitted to subsequent generations through the germline without DNA mutations. This phenomenon remains controversial because underlying mechanisms have not been identified. Therefore, understanding how effects of environmental exposures are transmitted to unexposed generations without DNA mutations is a fundamental unanswered question in biology.

Veno-venous Extracorporeal Membrane Oxygenation: Anesthetic Considerations in Clinical Practice.

Context: After the COVID-19 pandemic, multiple reviews have documented the success of veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Patients who experience hypoxemia but have normal contractility may be switched to veno-venous-ECMO (VV-ECMO).

Purpose: In this review, we present three protocols for anesthesiologists.

Neuromodulators for Skin.

Neurotoxins are the most popular nonsurgical aesthetic procedure for men and women of all ages. Five botulinum toxin A (BoNTA) products represent the current palette of available BoNTA for cosmetic use. Off-label uses of BoNTA continue to expand and are now used for skin rejuvenation, to treat various skin disorders, and in facial nerve paralysis.

An Open-label Pilot Study of NicoBloc as a Novel Smoking Cessation Intervention.

Introduction: NicoBloc is a viscous fluid applied to the cigarette filter designed to block tar and nicotine. This novel and understudied smoking cessation device presents a nonpharmacological means for smokers to gradually reduce nicotine and tar content while continuing to smoke their preferred brand of cigarette. This pilot study aimed to assess the feasibility, acceptability, and initial efficacy of NicoBloc as compared with nicotine replacement therapy (nicotine lozenge).

The role of nurses in inpatient geriatric rehabilitation units: A scoping review.

Aims: (1) To review and synthesize research on the contributions of nurses to rehabilitation in inpatient geriatric rehabilitation units (GRUs), and (2) to compare these reported contributions to the domains of international rehabilitation nursing competency models. The roles and contributions of nurses (e.g.

Case report: Immune profiling links neutrophil and plasmablast dysregulation to microvascular damage in post-COVID-19 Multisystem Inflammatory Syndrome in Adults (MIS-A).

Despite surviving a SARS-CoV-2 infection, some individuals experience an intense post-infectious Multisystem Inflammatory Syndrome (MIS) of uncertain etiology. Children with this syndrome (MIS-C) can experience a Kawasaki-like disease, but mechanisms in adults (MIS-A) are not clearly defined. Here we utilize a deep phenotyping approach to examine immunologic responses in an individual with MIS-A.

Parkin coregulates glutathione metabolism in adult mammalian brain.

We recently discovered that the expression of PRKN, a young-onset Parkinson disease-linked gene, confers redox homeostasis. To further examine the protective effects of parkin in an oxidative stress model, we first combined the loss of prkn with Sod2 haploinsufficiency in mice. Although adult prkn//Sod2 animals did not develop dopamine cell loss in the S.

Neonatal imprinting of alveolar macrophages via neutrophil-derived 12-HETE.

Resident-tissue macrophages (RTMs) arise from embryonic precursors, yet the developmental signals that shape their longevity remain largely unknown. Here we demonstrate in mice genetically deficient in 12-lipoxygenase and 15-lipoxygenase (Alox15 mice) that neonatal neutrophil-derived 12-HETE is required for self-renewal and maintenance of alveolar macrophages (AMs) during lung development. Although the seeding and differentiation of AM progenitors remained intact, the absence of 12-HETE led to a significant reduction in AMs in adult lungs and enhanced senescence owing to increased prostaglandin E production.

Helminth Infection-Induced Increase in Virtual Memory CD8 T Cells Is Transient, Driven by IL-15, and Absent in Aged Mice.

CD8 virtual memory T (TVM) cells are Ag-naive CD8 T cells that have undergone partial differentiation in response to common γ-chain cytokines, particularly IL-15 and IL-4. TVM cells from young individuals are highly proliferative in response to TCR and cytokine stimulation but, with age, they lose TCR-mediated proliferative capacity and exhibit hallmarks of senescence. Helminth infection can drive an increase in TVM cells, which is associated with improved pathogen clearance during subsequent infectious challenge in young mice.

A B1a-natural IgG-neutrophil axis is impaired in viral- and steroid-associated aspergillosis.

The lung naturally resists () in healthy individuals, but multiple conditions can disrupt this resistance, leading to lethal invasive infections. Core processes of natural resistance and its breakdown are undefined. We investigated three distinct conditions predisposing to lethal aspergillosis-severe SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection, influenza A viral pneumonia, and systemic corticosteroid use-in human patients and murine models.

Routine screening of emergency admissions at risk of chronic hepatitis (SEARCH) identifies and links hepatitis B cases to care.

Background And Aims: Significant barriers exist with hepatitis B (HBV) case detection and effective linkage to care (LTC). The emergency department (ED) is a unique healthcare interaction where hepatitis screening and LTC could be achieved. We examined the efficacy and utility of automated ED HBV screening for Overseas Born (OB) patients.

HolistIC: leveraging Hi-C and whole genome shotgun sequencing for double minute chromosome discovery.

Motivation: Double minute (DM) chromosomes are acentric extrachromosomal DNA artifacts that are frequently observed in the cells of numerous cancers. They are highly amplified and contain oncogenes and drug-resistance genes, making their presence a challenge for effective cancer treatment. Algorithmic discovery of DM can potentially improve bench-derived therapies for cancer treatment.

Dexamethasone modulates immature neutrophils and interferon programming in severe COVID-19.

Although critical for host defense, innate immune cells are also pathologic drivers of acute respiratory distress syndrome (ARDS). Innate immune dynamics during Coronavirus Disease 2019 (COVID-19) ARDS, compared to ARDS from other respiratory pathogens, is unclear. Moreover, mechanisms underlying the beneficial effects of dexamethasone during severe COVID-19 remain elusive.

Ribosylation of the CD8αβ heterodimer permits binding of the nonclassical major histocompatibility molecule, H2-Q10.

The CD8αβ heterodimer plays a crucial role in the stabilization between major histocompatibility complex class I molecules (MHC-I) and the T cell receptor (TCR). The interaction between CD8 and MHC-I can be regulated by posttranslational modifications, which are proposed to play an important role in the development of CD8 T cells. One modification that has been proposed to control CD8 coreceptor function is ribosylation.

Amniotic fluid embolism: lessons for rapid recognition and intervention.

Amniotic fluid embolism is a rare, often fatal complication of labor and delivery. The classic presentation is the sudden onset of a triad of clinical manifestations: hypoxia, hypotension and coagulopathy. Understanding of the syndrome as an immunologically mediated, complicated and often catastrophic maternal response to fetal or placental antigens is coming into focus.