Mechanical Failure of the Stryker T2 Alpha Retrograde Femoral Nail.

Objective: To evaluate mechanical failure rates of retrograde femoral nails in the treatment of distal femur fractures.

Methods: Design: Retrospective chart review.

Setting: Urban Academic Level 1 Trauma Center.

Conventional Synthetic Disease-modifying Drugs Remain the Mainstay of Therapy for Rheumatoid Arthritis in India.

Background: There are limited data on the real-world utilization of disease-modifying antirheumatic drugs (DMARDs) in Indian patients with rheumatoid arthritis (RA).

Methods: This was a cross-sectional study of a multicentric observational cohort of RA patients across rheumatology clinics at six centers across India. Patients who met the American College of Rheumatology (ACR) 2010 criteria for RA were included.

A Translation-Independent Directed Evolution Strategy to Engineer Aminoacyl-tRNA Synthetases.

Using directed evolution, aminoacyl-tRNA synthetases (aaRSs) have been engineered to incorporate numerous noncanonical amino acids (ncAAs). Until now, the selection of such novel aaRS mutants has relied on the expression of a selectable reporter protein. However, such translation-dependent selections are incompatible with exotic monomers that are suboptimal substrates for the ribosome.

Factors that influence surgical decision-making for geriatric displaced femoral neck fractures: Bullet Health Analysis (BHA) I : Worldwide Orthopaedic Research Collaboration: Leveraging Big Data (WORLD) I.

Purpose: The management of geriatric femoral neck fractures, which includes options like hemiarthroplasty (HA), total hip arthroplasty (THA), and fixation, exhibits regional and healthcare setting variations. However, there is a lack of information on global variations in practice patterns and surgical decision factors for this injury.

Methods: Survey data were collected from April 2020 to June 2023 via Orthobullets Case Studies, a global clinical case collaboration platform hosted on a prominent orthopedic educational website.

Are patients with knee osteoarthritis aware that platelet-rich plasma is a treatment option?

Osteoarthritis (OA) is a prevalent joint disease, particularly affecting the knees. This condition is often managed through various treatments, including intra-articular injections such as corticosteroids (CS), hyaluronic acid (HA), and platelet-rich plasma (PRP). PRP has shown promising outcomes in recent studies although it does lack strong endorsement in some clinical guidelines due to inconsistent results and lack of standardized results.

Molecular basis of anaphylatoxin binding, activation, and signaling bias at complement receptors.

The complement system is a critical part of our innate immune response, and the terminal products of this cascade, anaphylatoxins C3a and C5a, exert their physiological and pathophysiological responses primarily via two GPCRs, C3aR and C5aR1. However, the molecular mechanism of ligand recognition, activation, and signaling bias of these receptors remains mostly elusive. Here, we present nine cryo-EM structures of C3aR and C5aR1 activated by their natural and synthetic agonists, which reveal distinct binding pocket topologies of complement anaphylatoxins and provide key insights into receptor activation and transducer coupling.

Cutting Edge: TLR2 Signaling in B Cells Promotes Autoreactivity to DNA via IL-6 Secretion.

Autoantibodies to chromatin and dsDNA are a hallmark of systemic lupus erythematosus (SLE). In a mouse model of monogenic human SLE caused by DNASE1L3 deficiency, the anti-DNA response is dependent on endosomal nucleic acid-sensing TLRs TLR7 and TLR9. In this study, we report that this response also required TLR2, a surface receptor for microbial products that is primarily expressed on myeloid cells.

Secreted mammalian DNases protect against systemic bacterial infection by digesting biofilms.

Extracellular DNase DNASE1L3 maintains tolerance to self-DNA in humans and mice, whereas the role of its homolog DNASE1 remains controversial, and the overall function of secreted DNases in immunity is unclear. We report that deletion of murine DNASE1 neither caused autoreactivity in isolation nor exacerbated lupus-like disease in DNASE1L3-deficient mice. However, combined deficiency of DNASE1 and DNASE1L3 rendered mice susceptible to bloodstream infection with Staphylococcus aureus.

A Facile Platform to Engineer Tyrosyl-tRNA Synthetase Adds New Chemistries to the Eukaryotic Genetic Code, Including a Phosphotyrosine Mimic.

The tyrosyl-tRNA synthetase (EcTyrRS)/tRNA pair offers an attractive platform for genetically encoding new noncanonical amino acids (ncAA) in eukaryotes. However, challenges associated with a eukaryotic selection system, which is needed to engineer the platform, have impeded its success in the past. Recently, using a facile -based selection system, we showed that EcTyrRS could be engineered in a strain where the endogenous tyrosyl pair was substituted with an archaeal counterpart.

Theory-guided experimental design in battery materials research.

A reliable energy storage ecosystem is imperative for a renewable energy future, and continued research is needed to develop promising rechargeable battery chemistries. To this end, better theoretical and experimental understanding of electrochemical mechanisms and structure-property relationships will allow us to accelerate the development of safer batteries with higher energy densities and longer lifetimes. This Review discusses the interplay between theory and experiment in battery materials research, enabling us to not only uncover hitherto unknown mechanisms but also rationally design more promising electrode and electrolyte materials.

Novel Liposomal Rolipram Formulation for Clinical Application to Reduce Emesis.

Introduction: The phosphodiesterase 4 (PDE4) inhibitor, rolipram, has beneficial effects on tissue inflammation, injury and fibrosis, including in the liver. Since rolipram elicits significant CNS side-effects in humans (ie, nausea and emesis), our group developed a fusogenic lipid vesicle (FLV) drug delivery system that targets the liver to avoid adverse events. We evaluated whether this novel liposomal rolipram formulation reduces emesis.

Corrigendum: The Role of Nucleases and Nucleic Acid Editing Enzymes in the Regulation of Self-Nucleic Acid Sensing.

[This corrects the article DOI: 10.3389/fimmu.2021.

Autoantibody-mediated impairment of DNASE1L3 activity in sporadic systemic lupus erythematosus.

Antibodies to double-stranded DNA (dsDNA) are prevalent in systemic lupus erythematosus (SLE), particularly in patients with lupus nephritis, yet the nature and regulation of antigenic cell-free DNA (cfDNA) are poorly understood. Null mutations in the secreted DNase DNASE1L3 cause human monogenic SLE with anti-dsDNA autoreactivity. We report that >50% of sporadic SLE patients with nephritis manifested reduced DNASE1L3 activity in circulation, which was associated with neutralizing autoantibodies to DNASE1L3.

The Role of Nucleases and Nucleic Acid Editing Enzymes in the Regulation of Self-Nucleic Acid Sensing.

Detection of microbial nucleic acids by the innate immune system is mediated by numerous intracellular nucleic acids sensors. Upon the detection of nucleic acids these sensors induce the production of inflammatory cytokines, and thus play a crucial role in the activation of anti-microbial immunity. In addition to microbial genetic material, nucleic acid sensors can also recognize self-nucleic acids exposed extracellularly during turn-over of cells, inefficient efferocytosis, or intracellularly upon mislocalization.

A comprehensive mobile application tool for disease surveillance, workforce management and supply chain management for Malaria Elimination Demonstration Project.

Background: Health care technologies are now offering accountability, quality, robustness, and accuracy in disease surveillance and health care delivery programmes. With the advent of mobile hand-held devices, these technologies have become more accessible and adaptable for use by field staff working in remote areas. The Malaria Elimination Demonstration Project started collection of data and conduct of routine operations using paper-based reporting systems.

Recent advances in cathode engineering to enable reversible room-temperature aluminium-sulfur batteries.

The rigorous requirements, such as high abundance, cost-effectiveness, and increased storage capacities, pose severe challenges to the existing Li-ion batteries' long-term sustainability. Room-temperature aluminum-sulfur (Al-S) chemistry, in particular, is gaining importance due to its high theoretical energy density (1700 W h kg). Al-S battery technology is one of the emerging metal-sulfur candidates that can surpass current Li-ion chemistries.

TLR7 Negatively Regulates B10 Cells Predominantly in an IFNγ Signaling Dependent Manner.

IL-10 producing B cells (B10 cells) play an important immunoregulatory role in various autoimmune and infection conditions. However, the factors that regulate their development and maintenance are incompletely understood. Recently, we and others have established a requirement for TLR7 in promoting autoimmune antibody forming cell (AFC) and germinal center (GC) responses.

Plasmacytoid Dendritic Cells and Type I Interferon Promote Extrafollicular B Cell Responses to Extracellular Self-DNA.

Class-switched antibodies to double-stranded DNA (dsDNA) are prevalent and pathogenic in systemic lupus erythematosus (SLE), yet mechanisms of their development remain poorly understood. Humans and mice lacking secreted DNase DNASE1L3 develop rapid anti-dsDNA antibody responses and SLE-like disease. We report that anti-DNA responses in Dnase1l3 mice require CD40L-mediated T cell help, but proceed independently of germinal center formation via short-lived antibody-forming cells (AFCs) localized to extrafollicular regions.

Self-DNA at the Epicenter of SLE: Immunogenic Forms, Regulation, and Effects.

Self-reactive B cells generated through V(D)J recombination in the bone marrow or through accrual of random mutations in secondary lymphoid tissues are mostly purged or edited to prevent autoimmunity. Yet, 10-20% of all mature naïve B cells in healthy individuals have self-reactive B cell receptors (BCRs). In patients with serologically active systemic lupus erythematosus (SLE) the percentage increases up to 50%, with significant self-DNA reactivity that correlates with disease severity.

Selenium supplementation suppresses immunological and serological features of lupus in B6.Sle1b mice.

Systemic lupus erythematosus (SLE) is a debilitating multi-factorial immunological disorder characterized by increased inflammation and development of anti-nuclear autoantibodies. Selenium (Se) is an essential trace element with beneficial anti-cancer and anti-inflammatory immunological functions. In our previous proteomics study, analysis of Se-responsive markers in the circulation of Se-supplemented healthy men showed a significant increase in complement proteins.

deletion causes aberrations in length and end-motif frequencies in plasma DNA.

Circulating DNA in plasma consists of short DNA fragments. The biological processes generating such fragments are not well understood. DNASE1L3 is a secreted DNASE1-like nuclease capable of digesting DNA in chromatin, and its absence causes anti-DNA responses and autoimmunity in humans and mice.