Selective autophagy impedes KSHV entry after recruiting the membrane damage sensor galectin-8 to virus-containing endosomes.

Kaposi sarcoma-associated herpesvirus (KSHV) is an oncogenic γ-herpesvirus. Autophagy during KSHV entry has remained unexplored. We show that LC3 lipidation as a hallmark of autophagy is induced shortly after KSHV entry.

ACE2-independent sarbecovirus cell entry can be supported by TMPRSS2-related enzymes and can reduce sensitivity to antibody-mediated neutralization.

The COVID-19 pandemic, caused by SARS-CoV-2, demonstrated that zoonotic transmission of animal sarbecoviruses threatens human health but the determinants of transmission are incompletely understood. Here, we show that most spike (S) proteins of horseshoe bat and Malayan pangolin sarbecoviruses employ ACE2 for entry, with human and raccoon dog ACE2 exhibiting broad receptor activity. The insertion of a multibasic cleavage site into the S proteins increased entry into human lung cells driven by most S proteins tested, suggesting that acquisition of a multibasic cleavage site might increase infectivity of diverse animal sarbecoviruses for the human respiratory tract.

ChatGPT and Google Provide Mostly Excellent or Satisfactory Responses to the Most Frequently Asked Patient Questions Related to Rotator Cuff Repair.

Purpose: To assess the differences in frequently asked questions (FAQs) and responses related to rotator cuff surgery between Google and ChatGPT.

Methods: Both Google and ChatGPT (version 3.5) were queried for the top 10 FAQs using the search term "rotator cuff repair.

Medical Malpractice Litigation Following Hindfoot Arthrodesis.

Given high patient expectations in the setting of complex surgeries, orthopedic surgeons are at risk of being subject to malpractice claims which can impose significant economic and psychological burden. This study investigates malpractice claims against orthopedic surgeons and podiatrists performing hindfoot arthrodesis and determine factors associated with plaintiff verdicts and settlements using the Westlaw legal database. The database was queried for all cases involving hindfoot arthrodesis using the terms "malpractice" and either "ankle fusion," "arthrodesis," "subtalar fusion," "tibiotalar fusion," "tibiotalocalcaneal fusion," "TTC fusion," or "tibiofibular fusion" from 1987 to 2023.

Evaluation of Patient Education Materials From Large-Language Artificial Intelligence Models on Carpal Tunnel Release.

Background: ChatGPT, an artificial intelligence technology, has the potential to be a useful patient aid, though the accuracy and appropriateness of its responses and recommendations on common hand surgical pathologies and procedures must be understood. Comparing the sources referenced and characteristics of responses from ChatGPT and an established search engine (Google) on carpal tunnel surgery will allow for an understanding of the utility of ChatGPT for patient education.

Methods: A Google search of "carpal tunnel release surgery" was performed and "frequently asked questions (FAQs)" were recorded with their answer and source.

Female Authorship Is Driving Studies of Female Athletes: A Systematic Review.

Background: Patient sex is known to affect patient outcomes in sports medicine. Historically, many studies on athletes have focused on male athletes and been generalized to female athletes.

Hypothesis: Studies with female first or senior authors will isolate female athletes as study participants more frequently than studies with male first or senior authors.

Metabolic remodeling in cardiac hypertrophy and heart failure with reduced ejection fraction occurs independent of transcription factor EB in mice.

Background: A metabolic shift from fatty acid (FAO) to glucose oxidation (GO) occurs during cardiac hypertrophy (LVH) and heart failure with reduced ejection fraction (HFrEF), which is mediated by PGC-1α and PPARα. While the transcription factor EB (TFEB) regulates the expression of both /PGC-1α and /PPARα, its contribution to metabolic remodeling is uncertain.

Methods: Luciferase assays were performed to verify that TFEB regulates expression.

Preoperative Factors Associated With Worse PROMIS Pain Interference 2 Years After Hand and Wrist Surgery.

Background: The purpose of this study was to identify preoperative factors associated with worse postoperative Patient-Reported Outcomes Measurement Information System (PROMIS) pain interference (PI) scores 2 years after hand and wrist surgery. We hypothesized that older age, more comorbidities, increased substance use, and lower socioeconomic status would correlate with worse 2-year PROMIS PI scores.

Methods: This study was a retrospective review of prospectively acquired data on 253 patients.

Intraobserver and Interobserver Reliability of the Snyder and Expanded SLAP Classification System: A Video Study.

Background: Superior labral anterior and posterior (SLAP) tears are a common finding in overhead athletes. The original classification system produced by Snyder in 1990 contained 4 types of SLAP tears and was later expanded to 10 types. The classification has been challenging because of inconsistencies between surgeons making diagnoses and treatments based on the diagnosis.

Kaposi's sarcoma-associated herpesvirus glycoprotein K8.1 is critical for infection in a cell-specific manner and functions at the attachment step on keratinocytes.

Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of several B cell malignancies and Kaposi's sarcoma. We analyzed the function of K8.1, the major antigenic component of the KSHV virion in the infection of different cells.

Outcomes and Complications Following Chronic Patellar Tendon Repair: A Systematic Review.

The purpose of this systematic review is to report outcomes and complications following the reconstruction of chronic patellar tendon ruptures. Four databases (Cochrane Database of Systematic Reviews, PubMed, Embase, MEDLINE) were searched from inception to July 2021. Inclusion criteria included articles that (1) analyzed outcomes and complications following chronic patellar tendon reconstruction (>4 weeks from injury to repair), (2) were written in English, (3) greater than five patients, and (4) a minimum 2-year follow-up.

Swan Neck Deformity: An Unusual Complication Following Trigger Finger Release.

Introduction: Swan neck deformity (SND) is a common pathologic finding often observed in patients with severe rheumatoid arthritis. However, it has also been seen in injuries such as mallet finger, flexor digitorum superficialis laceration, and intrinsic contracture. Open surgical release of a trigger finger most commonly involves the release of the A1 pulley to relieve a mechanical impingement.

Prospective registration of randomized clinical trials for total shoulder arthroplasty is low: a systematic review.

Background: Prospective trial registration has become an important means of improving the transparency and reproducibility of randomized controlled trials (RCTs) and is recommended by the Journal of Shoulder and Elbow Surgery (JSES) per the Consolidated Standards of Reporting Trials (CONSORT) guidelines. Herein, we performed a cross-sectional evaluation of RCTs published in JSES from 2010 to present to determine the prevalence of trial registration and consistency of outcome reporting.

Methods: The electronic database PubMed was searched to identify all RCTs on total shoulder arthroplasty (TSA) published in JSES from 2010 to 2022 using the search terms "randomized controlled trial" AND "shoulder" AND "arthroplasty OR replacement.

Biomechanical Comparison of Four- versus Six-Strand Transosseous Suture Repair for Patellar Tendon Rupture.

Background:  Surgical repair is indicated for patellar tendon ruptures that result in loss of knee extensor mechanism function. However, biomechanical studies report conflicting results when comparing transosseous suture versus suture anchor repair techniques. This discrepancy may be due to inconsistencies in experimental design as these studies use various numbers of suture strands.

Comparison of a Genotype 1 and a Genotype 2 Macaque Foamy Virus Gene Indicates Distinct Infectivity and Cell-Cell Fusion but Similar Tropism and Restriction of Cell Entry by Interferon-Induced Transmembrane Proteins.

Foamy viruses (FVs) are naturally found in many different animals and also in primates with the notable exception of humans, but zoonotic infections are common. In several species, two different envelope () gene sequence clades or genotypes exist. We constructed a simian FV (SFV) clone containing a reporter gene cassette.

The Transcription Factor EB (TFEB) Sensitizes the Heart to Chronic Pressure Overload.

The transcription factor EB (TFEB) promotes protein degradation by the autophagy and lysosomal pathway (ALP) and overexpression of TFEB was suggested for the treatment of ALP-related diseases that often affect the heart. However, TFEB-mediated ALP induction may perturb cardiac stress response. We used adeno-associated viral vectors type 9 (AAV9) to overexpress TFEB (AAV9-Tfeb) or Luciferase-control (AAV9-Luc) in cardiomyocytes of 12-week-old male mice.

Antibodies Targeting KSHV gH/gL Reveal Distinct Neutralization Mechanisms.

Kaposi's sarcoma herpesvirus (KSHV) is associated with a significant disease burden, in particular in Sub-Sahara Africa. A KSHV vaccine would be highly desirable, but the mechanisms underlying neutralizing antibody responses against KSHV remain largely unexplored. The complex made of glycoproteins H and L (gH/gL) activates gB for the fusion of viral and cellular membranes in all herpesviruses.

Functional analysis of polymorphisms at the S1/S2 site of SARS-CoV-2 spike protein.

Several SARS-CoV-2 variants emerged that harbor mutations in the surface unit of the viral spike (S) protein that enhance infectivity and transmissibility. Here, we analyzed whether ten naturally-occurring mutations found within the extended loop harboring the S1/S2 cleavage site of the S protein, a determinant of SARS-CoV-2 cell tropism and pathogenicity, impact S protein processing and function. None of the mutations increased but several decreased S protein cleavage at the S1/S2 site, including S686G and P681H, the latter of which is found in variants of concern B.

Interferon-Induced Transmembrane Proteins Inhibit Infection by the Kaposi's Sarcoma-Associated Herpesvirus and the Related Rhesus Monkey Rhadinovirus in a Cell-Specific Manner.

The interferon-induced transmembrane proteins (IFITMs) are broad-spectrum antiviral proteins that inhibit the entry of enveloped viruses. We analyzed the effect of IFITMs on the gamma-2 herpesviruses Kaposi's sarcoma-associated herpesvirus (KSHV) and the closely related rhesus monkey rhadinovirus (RRV). We used CRISPR/Cas9-mediated gene knockout to generate A549 cells, human foreskin fibroblasts (HFF), and human umbilical vein endothelial cells (HUVEC) with combined IFITM1/2/3 knockout and identified IFITMs as cell-dependent inhibitors of KSHV and RRV infection in A549 cells and HFF but not HUVEC.

Sepsis induces interleukin 6, gp130/JAK2/STAT3, and muscle wasting.

Background: Sepsis and inflammation can cause intensive care unit-acquired weakness (ICUAW). Increased interleukin-6 (IL-6) plasma levels are a risk factor for ICUAW. IL-6 signalling involves the glycoprotein 130 (gp130) receptor and the JAK/STAT-pathway, but its role in sepsis-induced muscle wasting is uncertain.

Preoperative characteristics predictive of PROMIS Pain Interference two years after shoulder surgery.

Introduction: The objective of this study was to identify preoperative characteristics associated with worse Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference (PI) two years after shoulder surgery.

Methods: This was a retrospective analysis of prospectively collected data on 293 patients who underwent elective shoulder surgery. Survey questionnaires were collected within one week of surgery and then two years postoperatively.

Inhibition of the NLRP3/IL-1β axis protects against sepsis-induced cardiomyopathy.

Background: Septic cardiomyopathy worsens the prognosis of critically ill patients. Clinical data suggest that interleukin-1β (IL-1β), activated by the NLRP3 inflammasome, compromises cardiac function. Whether or not deleting Nlrp3 would prevent cardiac atrophy and improve diastolic cardiac function in sepsis was unclear.

SARS-CoV-2 variants B.1.351 and P.1 escape from neutralizing antibodies.

The global spread of SARS-CoV-2/COVID-19 is devastating health systems and economies worldwide. Recombinant or vaccine-induced neutralizing antibodies are used to combat the COVID-19 pandemic. However, the recently emerged SARS-CoV-2 variants B.

Plxdc family members are novel receptors for the rhesus monkey rhadinovirus (RRV).

The rhesus monkey rhadinovirus (RRV), a γ2-herpesvirus of rhesus macaques, shares many biological features with the human pathogenic Kaposi's sarcoma-associated herpesvirus (KSHV). Both viruses, as well as the more distantly related Epstein-Barr virus, engage cellular receptors from the Eph family of receptor tyrosine kinases (Ephs). However, the importance of the Eph interaction for RRV entry varies between cell types suggesting the existence of Eph-independent entry pathways.