Mechanism-based myofilament manipulation to treat diastolic dysfunction in HFpEF.

Heart failure with preserved ejection fraction (HFpEF) is a major public health challenge, affecting millions worldwide and placing a significant burden on healthcare systems due to high hospitalization rates and limited treatment options. HFpEF is characterized by impaired cardiac relaxation, or diastolic dysfunction. However, there are no therapies that directly treat the primary feature of the disease.

Differential effects of myosin activators on myocardial contractile function in nonfailing and failing human hearts.

The second-generation myosin activator danicamtiv (DN) has shown improved function compared with the first-generation myosin activator omecamtiv mecarbil (OM) in nonfailing myocardium by enhancing cardiac force generation but attenuating slowed relaxation. However, whether the functional improvement with DN compared with OM persists in remodeled failing myocardium remains unknown. Therefore, this study aimed to investigate the differential contractile responses to myosin activators in nonfailing and failing myocardium.

Severe Carpal Tunnel Syndrome in a Pediatric Patient With a History of Congenital Adrenal Hyperplasia.

The patient is a 17-year-old right-hand-dominant girl with a history of virilizing congenital adrenal hyperplasia (CAH) secondary to 21-hydroxylase enzyme deficiency. Her CAH had been managed with supplemental exogenous steroids, but unfortunately, she had been noncompliant for many years. She subsequently presented with severe progressive numbness and tingling in the bilateral upper extremities that were refractory to conservative management.

Nanosecond anomaly detection with decision trees and real-time application to exotic Higgs decays.

We present an interpretable implementation of the autoencoding algorithm, used as an anomaly detector, built with a forest of deep decision trees on FPGA, field programmable gate arrays. Scenarios at the Large Hadron Collider at CERN are considered, for which the autoencoder is trained using known physical processes of the Standard Model. The design is then deployed in real-time trigger systems for anomaly detection of unknown physical processes, such as the detection of rare exotic decays of the Higgs boson.

Bringing into focus the central domains C3-C6 of myosin binding protein C.

Myosin binding protein C (MyBPC) is a multi-domain protein with each region having a distinct functional role in muscle contraction. The central domains of MyBPC have often been overlooked due to their unclear roles. However, recent research shows promise in understanding their potential structural and regulatory functions.

Hypertrophic cardiomyopathy in carriers in aging.

Hypertrophic cardiomyopathy (HCM) is characterized by abnormal thickening of the myocardium, leading to arrhythmias, heart failure, and elevated risk of sudden cardiac death, particularly among the young. This inherited disease is predominantly caused by mutations in sarcomeric genes, among which those in the cardiac myosin binding protein-C3 () gene are major contributors. HCM associated with mutations usually presents in the elderly and ranges from asymptomatic to symptomatic forms, affecting numerous cardiac functions and presenting significant health risks with a spectrum of clinical manifestations.

Screening for Femoral Head Osteonecrosis Following COVID-19: Is It Worth It?

Objectives: Based on WHO data, as of June 2022, there were 532.2 million confirmed COVID-19 cases globally. In the initial phase of the COVID -19 pandemic, patients experiencing critical illness marked by severe respiratory distress were commonly subjected to corticosteroid treatment.

Effect of the Novel Myotrope Danicamtiv on Cross-Bridge Behavior in Human Myocardium.

Background Omecamtiv mecarbil (OM) and danicamtiv both increase myocardial force output by selectively activating myosin within the cardiac sarcomere. Enhanced force generation is presumably due to an increase in the total number of myosin heads bound to the actin filament; however, detailed comparisons of the molecular mechanisms of OM and danicamtiv are lacking. Methods and Results The effect of OM and danicamtiv on Ca sensitivity of force generation was analyzed by exposing chemically skinned myocardial samples to a series of increasing Ca solutions.

Basic science methods for the characterization of variants of uncertain significance in hypertrophic cardiomyopathy.

With the advent of next-generation whole genome sequencing, many variants of uncertain significance (VUS) have been identified in individuals suffering from inheritable hypertrophic cardiomyopathy (HCM). Unfortunately, this classification of a genetic variant results in ambiguity in interpretation, risk stratification, and clinical practice. Here, we aim to review some basic science methods to gain a more accurate characterization of VUS in HCM.

Risk Factors for Revision Surgery Following Revision Total Knee Arthroplasty Using a Hinged Knee Prosthesis for Septic and Aseptic Indications.

Introduction: The use of hinged knee replacements (HKRs) for limb salvage is a popular option for revision total knee arthroplasty (RTKA). Although recent literature focuses on the outcomes of HKR for septic and aseptic RTKAs, little is reported on the risk factors of returning to the operating room. The purpose of this study was to evaluate risk factors of revision surgery and revision after receiving HKR for septic versus aseptic etiology.

The contribution of N-terminal truncated cMyBPC to in vivo cardiac function.

Cardiac myosin binding protein C (cMyBPC) is an 11-domain sarcomeric protein (C0-C10) integral to cardiac muscle regulation. In vitro studies have demonstrated potential functional roles for regions beyond the N-terminus. However, the in vivo contributions of these domains are mostly unknown.

Transient Exertional Compressive Radial Neuropathy in a Collegiate Baseball Pitcher: A Case Report.

Case: A 21-year-old collegiate baseball pitcher presented with transient lateral arm pain and wrist extension weakness after pitching more than 1 inning. Physical examination was unremarkable at rest. Ultrasound-guided injection of the radial nerve at the level of the lateral intramuscular septum improved his symptoms.

The Role of the Innate Immune System in Wear Debris-Induced Inflammatory Peri-Implant Osteolysis in Total Joint Arthroplasty.

Periprosthetic osteolysis remains a leading complication of total hip and knee arthroplasty, often resulting in aseptic loosening of the implant and necessitating revision surgery. Wear-induced particulate debris is the main cause initiating this destructive process. The purpose of this article is to review recent advances in understanding of how wear debris causes osteolysis, and emergent strategies for the avoidance and treatment of this disease.

Surgical Treatment of Pediatric Scoliosis: Historical Origins and Review of Current Techniques.

The treatment of scoliosis has been explored and debated in medicine since the first recorded texts. Scoliosis treatment has shifted over time from external modalities, such as traction and bracing, to internal stabilization techniques that leverage surgical advances. Surgical fixation constructs can generally be separated into two different modalities: dynamic vs.

A Scalable, Cell-based Method for the Functional Assessment of Ube3a Variants.

The increased use of sequencing in medicine has identified millions of coding variants in the human genome. Many of these variants occur in genes associated with neurodevelopmental disorders, but the functional significance of the vast majority of variants remains unknown. The present protocol describes the study of variants for Ube3a, a gene that encodes an E3 ubiquitin ligase linked to both autism and Angelman syndrome.

Prevalence of bacterial burden on macroscopic contaminants of orthopaedic surgical instruments following sterilization.

Background: Macroscopic contamination of orthopaedic instruments with particulates, including cortical bone and polymethyl methacrylate (PMMA) bone cement, that have previously undergone pre-operative sterilization is frequently encountered peri- or intraoperatively, calling into question the sterility of such instruments.

Aim: To determine if macroscopic contaminants of orthopaedic surgical instrumentation maintain a bacterial burden following sterile processing, and to determine the most commonly contaminated instruments and the most common contaminants.

Methods: Macroscopic contaminants in orthopaedic instrument trays were collected prospectively at a single tertiary referral centre over a 6-month period from August 2021 to May 2022.

Identification of Phosphorylation and Other Post-Translational Modifications in the Central C4C5 Domains of Murine Cardiac Myosin Binding Protein C.

Cardiac myosin binding protein C (cMyBPC) is a critical multidomain protein that modulates myosin cross bridge behavior and cardiac contractility. cMyBPC is principally regulated by phosphorylation of the residues within the M-domain of its N-terminus. However, not much is known about the phosphorylation or other post-translational modification (PTM) landscape of the central C4C5 domains.

Molecular characterization of linker and loop-mediated structural modulation and hinge motion in the C4-C5 domains of cMyBPC.

Introduction: The central C4 and C5 domains (C4C5) of cardiac myosin binding protein C (cMyBPC) contain a flexible interdomain linker and a cardiac-isoform specific loop. However, their importance in the functional regulation of cMyBPC has not been extensively studied.

Methods And Results: We expressed recombinant C4C5 proteins with deleted linker and loop regions and performed biophysical experiments to determine each of their structural and dynamic roles.

Phytoplankton responses to repeated pulse perturbations imposed on a trend of increasing eutrophication.

While eutrophication remains one of the main pressures acting on freshwater ecosystems, the prevalence of anthropogenic and nature-induced stochastic pulse perturbations is predicted to increase due to climate change. Despite all our knowledge on the effects of eutrophication and stochastic events operating in isolation, we know little about how eutrophication may affect the response and recovery of aquatic ecosystems to pulse perturbations. There are multiple ways in which eutrophication and pulse perturbations may interact to induce potentially synergic changes in the system, for instance, by increasing the amount of nutrients released after a pulse perturbation.

Readability assessment of patient educational materials for shoulder arthroplasty from top academic orthopedic institutions.

Background: Previous studies have demonstrated that online patient educational materials are written at reading levels too advanced for the average patient. The average American reads at the eighth-grade reading level. To date, the readability of online educational material of academic centers for shoulder arthroplasty has not been analyzed.

Delayed Postoperative Spinal Cord Injury with Complete Paralysis After Adolescent Idiopathic Surgery: A Case Report.

Case: We report a 14-year-old girl with adolescent idiopathic scoliosis who experienced bilateral lower extremity paralysis related to postoperative hypotension 10 hours after posterior spinal fusion. She returned to the operating room for spinal cord decompression and hardware removal. Six weeks later, reinstrumentation was performed, and complete neurologic recovery was achieved.