Background: Risk factors for anterior cruciate ligament reconstruction (ACLR) construct failure have been studied extensively. However, while some studies account for variables such as activity level, construct types, preoperative physical therapy, or patient demographics individually, comprehensive studies that control for all these factors simultaneously are scarce.
Hypothesis: By utilizing a robust multivariable analysis, the factors associated with an increased risk of ACLR construct failure can be determined.
Hematopoietic progenitor kinase 1 (HPK1/MAP4K1) represents a high interest target for the treatment of cancer through an immune-mediated mechanism. Herein we present highlights of the drug discovery campaign within the lactam/azalactam series of inhibitors that yielded a small molecule (, PF-07265028), which was advanced to a phase 1 clinical trial (NCT05233436). Key components of the discovery effort included optimization of potency through mitigation of ligand strain as guided by the use of cocrystal structures, mitigation of ADME liabilities (plasma instability and fraction metabolism by CYP2D6), and optimization of kinase selectivity, particularly over immune-modulating kinases with high homology to HPK1.
View Article and Find Full Text PDFCannabis is the most used federally illicit drug in the United States (U.S). Understanding how accurate adolescents and emerging adults are at estimating their cannabis use quantity is important, as this lays the groundwork for understanding and studying the outcomes associated with cannabis use.
View Article and Find Full Text PDFArthrosc Sports Med Rehabil
October 2024
Purpose: To assess the biomechanical performance of 2 simplified loop-and-tack biceps tenodesis techniques, all-suture anchor and all-suture anchor with a button, compared with the interference screw technique in an ovine model.
Methods: Twenty-one biceps tenodesis procedures were executed on the humeri and flexor digitorum profundus tendons of skeletally mature, female sheep. Limbs were evenly randomized into 2 experimental groups (all-suture anchor with or without button) and 1 control group (interference screw).
Introduction: COPD is a progressive lung disease with marked airflow limitation. It has a large global prevalence and is managed with antibiotics, bronchodilators, and corticosteroids. Despite the prevalence, corticosteroid prescribing regimens differ widely amongst providers.
View Article and Find Full Text PDFIntroduction: Emergency department (ED)-based peer recovery coach (PRC) programs can improve access to substance use disorder treatment (SUD) for ED patients. As literature on early stages of PRC implementation is limited, we conducted a qualitative assessment of ED PRC program implementation from several US-based PRC programs focusing on barriers and facilitators for implementation and providing recommendations based on the findings.
Methods: We collected qualitative data from 39 key informants (peer recovery coaches, PRC program managers, ED physicians and staff, representatives of community-based organizations) via 6 focus groups and 21 interviews in February-December 2023.
Poor posture can lead to excessive strain of the neck and upper back musculature, leading to irritation of the dorsal scapular nerve (DSN) and spinal accessory nerve (SAN). A 5-in-1 trigger point technique has been described that specifically target trapezius, rhomboids, levator scapulae, SAN and DSN in a single percutaneous injection. We modified the technique to include hydrodissecting the DSN and SAN to provide further pain relief from possible nerve entrapments.
View Article and Find Full Text PDFDespite the record-breaking discovery, development and approval of vaccines and antiviral therapeutics such as Paxlovid, coronavirus disease 2019 (COVID-19) remained the fourth leading cause of death in the world and third highest in the United States in 2022. Here, we report the discovery and characterization of PF-07817883, a second-generation, orally bioavailable, SARS-CoV-2 main protease inhibitor with improved metabolic stability versus nirmatrelvir, the antiviral component of the ritonavir-boosted therapy Paxlovid. We demonstrate the pan-human coronavirus antiviral activity and off-target selectivity profile of PF-07817883.
View Article and Find Full Text PDFBackground: Shoulder arthroscopy is commonly performed at ambulatory surgical centers (ASCs) with use of an interscalene block and inhaled general anesthesia (IGA). However, an alternative option known as total intravenous anesthesia with propofol (TIVA-P) has shown promising results in reducing recovery time for other surgeries. The objective of this study was to assess whether there is a clinically meaningful difference in post-anesthesia care unit phase-I (PACU-I) time following shoulder arthroscopy between patients receiving an interscalene block with IGA and those receiving an interscalene block with TIVA-P.
View Article and Find Full Text PDFJ Dent Anesth Pain Med
October 2023
Background: Dentists bend needles prior to certain injections; however, there are concerns regarding needle fracture, lumen occlusion, and sharps handling. A previous study found that a 30-gauge needle fractures after four to nine 90° bends. This fatigue life study evaluated how many 90° bends a 30-gauge dental needle will sustain before fracture when bent using a needle guide.
View Article and Find Full Text PDFBackground: Since 2005, highly pathogenic avian influenza A H5N1 viruses have spread from Asia worldwide, infecting poultry, humans and wild birds. Subsequently, global interest in avian influenza (AI) surveillance increased.
Objectives: Mongolia presents an opportunity to study viruses in wild birds because the country has very low densities of domestic poultry and supports large concentrations of migratory water birds.
GPR61 is an orphan GPCR related to biogenic amine receptors. Its association with phenotypes relating to appetite makes it of interest as a druggable target to treat disorders of metabolism and body weight, such as obesity and cachexia. To date, the lack of structural information or a known biological ligand or tool compound has hindered comprehensive efforts to study GPR61 structure and function.
View Article and Find Full Text PDFTwo prevalent bacterial diseases in catfish aquaculture are enteric septicemia of catfish and columnaris disease caused by and , respectively. Chronic and recurring outbreaks of these bacterial pathogens result in significant economic losses for producers annually. Determining if these pathogens can persist within sediments of commercial ponds is paramount.
View Article and Find Full Text PDFImportance Chat Generative Pre-Trained Transformer (ChatGPT) has shown promising performance in various fields, including medicine, business, and law, but its accuracy in specialty-specific medical questions, particularly in ophthalmology, is still uncertain. Purpose This study evaluates the performance of two ChatGPT models (GPT-3.5 and GPT-4) and human professionals in answering ophthalmology questions from the StatPearls question bank, assessing their outcomes, and providing insights into the integration of artificial intelligence (AI) technology in ophthalmology.
View Article and Find Full Text PDFBackground: Many factors contribute to the risk of surgical-site infection (SSI) following total shoulder arthroplasty (TSA). Operative time is a modifiable factor that may contribute to SSI occurrence after TSA. This study aimed to determine the correlation between operative time and SSI following TSA.
View Article and Find Full Text PDFBackground: Peresolimab is a humanized IgG1 monoclonal antibody designed to stimulate the endogenous programmed cell death protein 1 (PD-1) inhibitory pathway. Stimulation of this pathway would be a novel approach to the treatment of patients with autoimmune or autoinflammatory diseases.
Methods: In this phase 2a, double-blind, randomized, placebo-controlled trial, we assigned, in a 2:1:1 ratio, adult patients with moderate-to-severe rheumatoid arthritis who had had an inadequate response to, a loss of response to, or unacceptable side effects with conventional synthetic disease-modifying antirheumatic drugs (DMARDs) or to biologic or targeted synthetic DMARDs to receive 700 mg of peresolimab, 300 mg of peresolimab, or placebo intravenously once every 4 weeks.