Sulfonium Moieties as Ammonium Bioisosteres: Novel Ligands for the Alpha7 Nicotinic Acetylcholine Receptor.

In the pressing quest of novel treatments for chronic pain, α7 nAChR silent agonists show efficacy as anti-inflammatory modulators and represent a promising strategy. Recent findings reveal that a sulfonium ion can replace the quaternary ammonium nitrogen as an alternative pharmacophore for nAChR silent activation. This study reports the design, synthesis, and electrophysiological evaluation of a new series of sulfonium-based derivatives inspired by the archetypal silent agonist NS6740.

New onset refractory status epilepticus: Long-term outcomes beyond seizures.

We propose and prioritize important outcome domains that should be considered for future research investigating long-term outcomes (LTO) after new onset refractory status epilepticus (NORSE). The study was led by the international NORSE Institute LTO Working Group. First, literature describing the LTO of NORSE survivors was identified using a PubMed search and summarized to identify knowledge gaps.

Drivers of Palliative Care and Hospice Use Among Patients With Advanced Lung Cancer.

Purpose: Despite rigorous evidence of improved quality of life and longer survival, disparities in the utilization of palliative and hospice care persist for racial and ethnic minority patients with cancer. This study evaluated the impact of psychosocial factors on utilization of these services.

Methods: Patients with advanced lung cancer were recruited at a large academic urban hospital.

Surgical Management of Fibrosing Mediastinitis Presenting as Superior Vena Cava Syndrome.

Fibrosing mediastinitis is a rare chronic inflammatory condition characterized by excessive fibrotic process in the mediastinum. Although various infectious processes are more common causes, it can also be related to several malignancies. We report a case of a 28-year-old woman with fibrosing mediastinitis related to an aggressive primary gray-zone lymphoma causing complete occlusion of the superior vena cava (SVC) and the innominate veins.

Plasma galectin-9 levels correlate with blood monocyte turnover and predict simian/human immunodeficiency virus disease progression.

Background: Late-stage human immunodeficiency virus (HIV) infection is typically characterized by low CD4 + T-cell count. We previously showed that profound changes in the monocyte turnover (MTO) rate in rhesus macaques infected by the simian immunodeficiency virus (SIV) outperforms declining CD4 + T-cell counts in predicting rapid health decline associated with progression to terminal disease. High MTO is associated with increased tissue macrophage death.

Factors Associated with Nonspecialist Quality of Delivery within a Family Strengthening Intervention in Rwanda: a Parallel Latent Growth Model.

In task-shared, mental health, and psychosocial support interventions, monitoring the quality of delivery (fidelity and competence) of nonspecialist providers is critical. Quality of delivery is frequently reported in brief, summary statistics, and while both fidelity and competence scores tend to be high, rarely have factors associated with quality of delivery in low-resource, mental health, and psychosocial support interventions been examined using inferential statistics. Understanding both modifiable and non-modifiable predictors of quality of delivery is important for adapting training and supervision approaches throughout intervention delivery.

Nurse workforce change and metropolitan medically underserved areas in the United States.

Background: The continued healthcare crisis in the United States (US) is worrisome, especially as workforce shortages, particularly for nurses, are highlighted, often in some of the highest need areas. As the need for healthcare services grows, especially for services that nurses can deliver, the inability to meet those needs exacerbates existing disparities in access to care and can jeopardize the quality and timeliness of healthcare delivery in underserved communities. Prior investigations have used varying definitions to describe underserved, under-resourced, rural, or health professional shortage areas to examine the relationship between these areas and workforce shortages.

Horse antithymocyte globulin test doses and infusion reactions in adults with aplastic anemia: A multicenter retrospective experience.

Introduction: Horse antithymocyte globulin carries a black box warning for life-threatening anaphylactic reactions, and prescribing information recommends test doses to identify patients at highest risk of this adverse effect. The predictive value of such test doses is not well validated, and practicality of use is unclear.

Methods: This was a planned secondary analysis of a multicenter, retrospective cohort study in adults with severe aplastic anemia being managed with horse antithymocyte globulin as part of their treatment regimen.

Feasibility and preliminary efficacy of a physical activity intervention in adults with lymphoma undergoing treatment.

Background: To determine the feasibility, acceptability, and preliminary efficacy of a 6-month tailored non-linear progressive physical activity intervention (PAI) for lymphoma patients undergoing chemotherapy.

Methods: Patients newly diagnosed with lymphoma (non-Hodgkin (NHL) or Hodgkin (HL)) were randomized into the PAI or healthy living intervention (HLI) control (2:1). Feasibility was assessed by examining accrual, adherence, and retention rates.

Specialty palliative care use among cancer patients: A population-based study.

Background: Rigorous population-based assessments of the use of specialty palliative care (SPC) in the US are rare.

Settings/subjects: This study examined SPC use among cancer patients in a mid-sized metropolitan area in Southeast US.

Measurements: In this cancer decedent cohort study, data were acquired and linked from the state-wide cancer registry; state-wide hospital discharge dataset; and local SPC providers.

Economic Impact of the Apoyo con Cariño Intervention: Improving Palliative Care for Hispanics with Serious Illness.

Specialty palliative care has been associated with cost savings at the end of life, while patient navigators have been independently associated with cost savings due to screening and treatment early in the course of disease. Evidence is limited regarding patient navigators and cost savings at the end of life. To determine the cost-effectiveness of a lay patient navigator intervention in improving palliative care outcomes for Hispanic persons with serious noncancer illness.

Bilingual Perspectives of Functional Dyspepsia Management in People from Underserved Areas.

Introduction: Disorders of gut-brain interaction (DGBIs), like functional dyspepsia (FD), are prevalent and challenging conditions. In other gastrointestinal (GI) disorders, individuals from underserved areas (UAs) have difficulty accessing care. Little is known about UA FD patient perspectives of their care, especially in those with limited English proficiency (LEP).

Dietary Interventions in Heart Failure With Preserved Ejection Fraction: A Scoping Review.

Patients with heart failure with preserved ejection fraction (HFpEF) are burdened by multiple diet-sensitive comorbidities, including obesity and malnutrition. Despite this, a low percentage of patients with HFpEF have been enrolled in dietary intervention trials in heart failure and few dietary interventions have been conducted in HFpEF exclusively. This scoping review will examine available evidence regarding dietary interventions in patients with HFpEF, highlight existing gaps in knowledge, and discuss emerging dietary therapies in this population.

Predicting Mortality in Patients Hospitalized With Acute Myocardial Infarction: From the National Cardiovascular Data Registry.

Background: In-hospital mortality risk prediction is an important tool for benchmarking quality and patient prognostication. Given changes in patient characteristics and treatments over time, a contemporary risk model for patients with acute myocardial infarction (MI) is needed.

Methods: Data from 313 825 acute MI hospitalizations between January 2019 and December 2020 for adults aged ≥18 years at 784 sites in the National Cardiovascular Data Registry Chest Pain-MI Registry were used to develop a risk-standardized model to predict in-hospital mortality.

Mitochondrial uncouplers inhibit oncogenic E2F1 activity and prostate cancer growth.

Mitochondrial uncouplers dissipate proton gradients and deplete ATP production from oxidative phosphorylation (OXPHOS). While the growth of prostate cancer depends on OXPHOS-generated ATP, the oncogenic pathway mediated by the transcription factor E2F1 is crucial for the progression of this deadly disease. Here, we report that mitochondrial uncouplers, including tizoxanide (TIZ), the active metabolite of the Food and Drug Administration (FDA)-approved anthelmintic nitazoxanide (NTZ), inhibit E2F1-mediated expression of genes involved in cell cycle progression, DNA synthesis, and lipid synthesis.

Multiomics dissection of human RAG deficiency reveals distinctive patterns of immune dysregulation but a common inflammatory signature.

Human recombination-activating gene (RAG) deficiency can manifest with distinct clinical and immunological phenotypes. By applying a multiomics approach to a large group of -mutated patients, we aimed at characterizing the immunopathology associated with each phenotype. Although defective T and B cell development is common to all phenotypes, patients with hypomorphic variants can generate T and B cells with signatures of immune dysregulation and produce autoantibodies to a broad range of self-antigens, including type I interferons.

A Pilot Randomized Controlled Trial to Examine the Impact of a Therapy Dog Intervention on Loneliness in Hospitalized Older Adults.

Background And Objectives: Loneliness is linked to significant health threats and is potentially more dangerous than obesity; it affects as many as 29% of noninstitutionalized older adults. Loneliness is exacerbated for those who require inpatient rehabilitation, are displaced from their social networks, spend little time receiving therapy, and are physically inactive and socially isolated. Emerging evidence suggests that companion animals provide a number of health and well-being benefits and that interacting with a trained therapy dog may reduce loneliness.

Reporting quality of animal research in journals that published the ARRIVE 1.0 or ARRIVE 2.0 guidelines: a cross-sectional analysis of 943 studies.

Background: The adherence to the Animals in Research: Reporting In Vivo Experiments (ARRIVE) guidelines across the journals that initially published the guidelines and if adherence has improved since the guidelines update, remains unknown. We aimed to quantify the level of adherence and analyze factors that might influence reporting quality among these journals.

Methods: This cross-sectional study retrospectively analyzed interventional animal experiments published in journals that released ARRIVE 1.

Global Epidemiology of Alcohol-Related Liver Disease, Liver Cancer, and Alcohol Use Disorder, 2000-2021.

Background/aims: Alcohol represents a leading burden of disease worldwide, including alcohol use disorder (AUD) and alcohol-related liver disease (ALD). We aim to assess the global burden of AUD, ALD, and alcohol-attributable primary liver cancer between 2000-2021.

Methods: We registered the global and regional trends of AUD, ALD, and alcohol-related liver cancer using data from the Global Burden of Disease 2021 Study, the largest and most up-to-date global epidemiology database.

Unidirectional and bidirectional causation between smoking and blood DNA methylation: evidence from twin-based Mendelian randomisation.

Cigarette smoking is associated with numerous differentially-methylated genomic loci in multiple human tissues. These associations are often assumed to reflect the causal effects of smoking on DNA methylation (DNAm), which may underpin some of the adverse health sequelae of smoking. However, prior causal analyses with Mendelian Randomisation (MR) have found limited support for such effects.

Recommended Elements of a Musculoskeletal Course for Fourth-Year Medical Students: A Modified Delphi Consensus.

Background And Objectives: A recognized gap exists between primary care physicians' training in musculoskeletal (MSK) medicine and the burden of MSK complaints in primary care. Family medicine interns often lack adequate baseline MSK physical exam skills, which prompted a proposal to introduce a fourth-year preceptorship to reinforce MSK education. The aim of this study was to prioritize the most important elements to include in this new clinical rotation.

Oxygen transport across the lifespan of male Sprague Dawley rats.

Human populations are experiencing unprecedented growth and longevity with lingering knowledge gaps of the characteristics, mechanisms, and pathologies of senescence. Invasive measurements and long-term control conditions for longitudinal studies are infeasible, necessitating the need for surrogate animal models. Rats have short lifespans (2-3 years) with translatable cardiovascular systems, and Sprague Dawley microcirculatory preparations are key to studying the oxygen transport mechanisms critical to the loss of skeletal muscle function in aging.

Sphingosine kinase 2 (SphK2) depletion alters redox metabolism and enhances inflammation in a diet-induced MASH mouse model.

Background: Sphingosine-1 phosphate (S1P) is a bioactive lipid molecule that modulates inflammation and hepatic lipid metabolism in MASLD, which affects 1 in 3 people and increases the risk of liver fibrosis and hepatic cancer. S1P can be generated by 2 isoforms of sphingosine kinase (SphK). SphK1 is well-studied in metabolic diseases.

Direct oral anticoagulants or warfarin in patients with left ventricular thrombus after ST-elevation myocardial infarction: a pilot trial and a prespecified meta-analysis of randomised trials.

Background: The role of direct oral anticoagulants (DOACs) in the treatment of left ventricular thrombus (LVT) after ST-elevation myocardial infarction (STEMI) remains uncertain.

Aims: We aimed to compare the effect of rivaroxaban versus warfarin in patients with STEMI complicated by LVT.

Methods: Adult patients with STEMI and two-dimensional transthoracic echocardiography showing LVT were assigned to rivaroxaban (15 mg once daily) or warfarin (international normalised ratio goal of 2.