Design and rationale of a pragmatic randomized clinical trial of early dronedarone versus usual care to change and improve outcomes in persons with first-detected atrial fibrillation - the CHANGE AFIB study.

Background: While there are several completed clinical trials that address treatment strategies in patients with symptomatic and recurrent atrial fibrillation (AF), there are no randomized clinical trials that address first-line rhythm control of new-onset AF. Recent data suggest that early initiation of rhythm control within 1 year can improve outcomes.

Methods: In this open-label pragmatic clinical trial nested within the Get with The Guidelines Atrial Fibrillation registry, approximately 3,000 patients with first-detected AF will be enrolled at approximately 200 sites.

Laryngeal Myasthenia Gravis in Voice Patients: Clinical, Serologic, and Neuromuscular Characterization of Seronegative Patients for Antibodies Against the Acetylcholine Receptor and Muscle-Specific Kinase.

Objective: Laryngeal myasthenia gravis (MG) is a focal manifestation of MG, and most patients are seronegative for antibodies against the acetylcholine receptor (AChR) and muscle-specific kinase (MuSK). The purpose of this study was to determine the incidence of anti-AChR and anti-Musk antibodies in voice patients and to characterize the clinical and neuromuscular profiles of these patients in order to guide the diagnosis of laryngeal MG.

Study Design: This was a retrospective case-control study that included patients over the age of 18 who underwent laryngeal electromyography (LEMG) as part of their evaluation for neuromuscular junction dysfunction.

Analysis of Neoadjuvant Chemotherapy Utilization, Pathologic Response, and Overall Survival in Upper Tract Urothelial Carcinoma.

Introduction: Upper tract urothelial carcinoma (UTUC) is a rare malignancy with poor prognosis. Radical nephroureterectomy (RNU) remains the standard treatment for high-risk UTUC. Considering the decline in renal function with RNU and results from prospective trials, NAC has emerged as a favored perioperative treatment for chemo-eligible patients with UTUC.

"Pseudosubstrate Envelope"/Free Energy Perturbation-Guided Design and Mechanistic Investigations of Benzothiazole HIV Capsid Modulators with High Ligand Efficiency.

Based on our proposed "pseudosubstrate envelope" concept, 25 benzothiazole-bearing HIV capsid protein (CA) modulators were designed and synthesized under the guidance of free energy perturbation technology. The most potent compound, , exhibited an EC of 2.69 nM against HIV-1, being 393 times more potent than the positive control PF74.

A Case of Pneumomediastinum and Pneumorrhachis in a Patient With Multiple Risk Factors.

Pneumomediastinum is the presence of gas (usually air) in the mediastinum, which is rare and typically benign. Pneumomediastinum is classified into primary and secondary based on etiology. Its pathophysiology is due to high intra-alveolar pressures causing alveolar rupture, which releases air that travels along bronchoalveolar sheaths into the mediastinum.

Biased Signaling Agonists Promote Distinct Phosphorylation and Conformational States of the Dopamine D3 Receptor.

Biased agonists of G-protein-coupled receptors (GPCRs) have emerged as promising selective modulators of signaling pathways by offering therapeutic advantages over unbiased agonists to minimize side effects. The dopamine D3 receptor (D3R), a pivotal GPCR in the central nervous system, has gained significant attention as a therapeutic target for neurological diseases, including Parkinson's disease (PD), addiction, psychosis, depression, and anxiety. We have recently designed and tested SK609, a G-protein biased D3R selective agonist, and demonstrated its efficacy in reducing motor impairment and improving cognitive effects in a rodent model of PD.

Developing methods to identify resilience and improve communication about diagnosis in pediatric primary care.

Communication underlies every stage of the diagnostic process. The Dialog Study aims to characterize the pediatric diagnostic journey, focusing on communication as a source of resilience, in order to ultimately develop and test the efficacy of a structured patient-centered communication intervention in improving outpatient diagnostic safety. In this manuscript, we will describe protocols, data collection instruments, methods, analytic approaches, and theoretical frameworks to be used in to characterize the patient journey in the Dialog Study.

Immunotherapy Induced Adrenal Insufficiency: An Underdiagnosed Cause of Persistent Hypotension in Cancer.

Endocrinopathies following immunotherapy have infrequently been documented in the literature. Adrenal insufficiency is a rare consequence of pembrolizumab immunotherapy, with incidence reported to be between 0.98 and 1.

How Biologics Have Changed the Drug Discovery Landscape.

Advances in molecular biology and molecular genetics as well as major scientific breakthroughs in immunology and oncology have led to the rapid growth of biologic therapeutics. Their success has resulted in significant changes to virtually every step in the drug discovery and development process. Biologics are produced by living organisms, and screening libraries are generated by immunization or phage display.

A Stochastic Dynamic Operator Framework That Improves the Precision of Analysis and Prediction Relative to the Classical Spike-Triggered Average Method, Extending the Toolkit.

Here we test the stochastic dynamic operator (SDO) as a new framework for describing physiological signal dynamics relative to spiking or stimulus events. The SDO is a natural extension of existing spike-triggered average (STA) or stimulus-triggered average techniques currently used in neural analysis. It extends the classic STA to cover state-dependent and probabilistic responses where STA may fail.

Exploring the 6-year Trend in Dedicated Research Years among Integrated Plastic and Reconstructive Surgery Residents.

Background: The plastic and reconstructive surgery (PRS) match has become more competitive with an emphasis on research productivity. With the transition of the US Medical Licensing Examination step 1 examination to pass-fail grading, alternative evaluation metrics for residency applications are needed. Our study provides a landscape of the incidence of research years amongst integrated PRS residents and the potential impacts of gender and race.

Pharmacokinetic Research in Pediatric Extracorporeal Therapies: Current State and Future Directions.

Extracorporeal life support (ECLS), including extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT), are life-saving therapies for critically ill children. Despite this, these modalities carry frustratingly high mortality rates. One driver of mortality may be altered drug disposition due to a combination of underlying illness, patient-circuit interactions, and drug-circuit interactions.