Nitinol Compression Staple Versus Headless Compression Screw Fixation for Scaphoid Waist Fractures.

Background: There are a variety of ways to surgically manage patients with scaphoid waist fractures. The purpose of this study is to compare the rate of union achieved with a nitinol compression staple versus that of a headless compression screw in the treatment of scaphoid waist fractures.

Methods: We performed a retrospective review of patients with middle-third scaphoid fractures treated surgically.

Immunological landscape of human lymphoid explants during measles virus infection.

In humans, lymph nodes are the primary site of measles virus (MeV) replication. To understand the immunological events that occur at this site, we infected human lymphoid tissue explants using a pathogenic strain of MeV that expresses GFP. We found that MeV infected 5%-15% of cells across donors.

Broad-spectrum RNA antiviral inspired by ISG15 deficiency.

Unlabelled: Type I interferons (IFN-I) are cytokines with potent antiviral and inflammatory capacities. IFN-I signaling drives the expression of hundreds of IFN-I stimulated genes (ISGs), whose aggregate function results in the control of viral infection. A few of these ISGs are tasked with negatively regulating the IFN-I response to prevent overt inflammation.

Scaphoid Fractures Requiring Bone Graft: Does Graft Source Matter?

Background: Treatment of scaphoid fractures often requires bone grafting. In such cases, bone graft is traditionally harvested from the iliac crest, but utilizing the distal radius carries less morbidity and is becoming more popular. The purpose of this study is to compare the outcomes of treatment of scaphoid waist fractures with the use of distal radius and iliac crest bone grafts.

SARS-CoV-2 hijacks p38β/MAPK11 to promote virus replication.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the coronavirus disease 2019 (COVID-19) pandemic, drastically modifies infected cells to optimize virus replication. One such modification is the activation of the host p38 mitogen-activated protein kinase (MAPK) pathway, which plays a major role in inflammatory cytokine production, a hallmark of severe COVID-19. We previously demonstrated that inhibition of p38/MAPK activity in SARS-CoV-2-infected cells reduced both cytokine production and viral replication.

Generation of host-directed and virus-specific antivirals using targeted protein degradation promoted by small molecules and viral RNA mimics.

Targeted protein degradation (TPD), as exemplified by proteolysis-targeting chimera (PROTAC), is an emerging drug discovery platform. PROTAC molecules, which typically contain a target protein ligand linked to an E3 ligase ligand, recruit a target protein to the E3 ligase to induce its ubiquitination and degradation. Here, we applied PROTAC approaches to develop broad-spectrum antivirals targeting key host factors for many viruses and virus-specific antivirals targeting unique viral proteins.

A Chemical Proteomics Approach to Discover Regulators of Innate Immune Signaling.

Innate immune pathways are tightly regulated to balance an appropriate response to infectious agents and tolerable levels of inflammation. Dysregulation of innate immune pathways can lead to severe autoinflammatory disorders or susceptibility to infections. Here, we aimed to identify kinases in common cellular pathways that regulate innate immune pathways by combining small-scale kinase inhibitor screening with quantitative proteomics.

Archaeal Kink-Turn Binding Protein Mediates Inhibition of Orthomyxovirus Splicing Biology.

Despite lacking a DNA intermediate, orthomyxoviruses complete their replication cycle in the nucleus and generate multiple transcripts by usurping the host splicing machinery. This biology results in dynamic changes of relative viral transcripts over time and dictates the replicative phase of the infection. Here, we demonstrate that the family of archaeal L7Ae proteins uniquely inhibit the splicing biology of influenza A virus, influenza B virus, and Salmon isavirus, revealing a common strategy utilized by members to achieve this dynamic.

Generation of a high yield vaccine backbone for influenza B virus in embryonated chicken eggs.

Influenza B virus (IBV) strains are one of the components of seasonal influenza vaccines in both trivalent and quadrivalent formulations. The vast majority of these vaccines are produced in embryonated chickens' eggs. While optimized backbones for vaccine production in eggs exist and are in use for influenza A viruses, no such backbones exist for IBVs, resulting in unpredictable production yields.

Immunization of Mice with Virus-Like Vesicles of Kaposi Sarcoma-Associated Herpesvirus Reveals a Role for Antibodies Targeting ORF4 in Activating Complement-Mediated Neutralization.

Infection by Kaposi sarcoma-associated herpesvirus (KSHV) can cause severe consequences, such as cancers and lymphoproliferative diseases. Whole inactivated viruses (WIV) with chemically destroyed genetic materials have been used as antigens in several licensed vaccines. During KSHV productive replication, virus-like vesicles (VLVs) that lack capsids and viral genomes are generated along with virions.

Intramedullary Nailing Versus Plate Fixation for Humeral Shaft Fractures: A Systematic Review and Meta-Analysis.

Background: The two techniques most utilized in the surgical treatment of humeral shaft fractures are open reduction internal fixation (ORIF) and intramedullary nailing (IMN). Although there have been multiple comparative clinical studies comparing outcomes for these two treatments, studies have not suggested one approach to be superior to the other. The purpose of this study is to perform a systematic literature review and meta-analysis of studies that evaluated the treatment of humeral shaft fractures with either ORIF or intramedullary nail.

Connecting animal trainers and behavior analysts through loopy training.

The communities of behavior analysts and animal trainers remain relatively disconnected despite potentially beneficial links between behavioral principles and the practices of animal training. Describing existing links between research by behavior analysts and practices used by animal trainers may foster connections. In this paper, we describe an approach used by many clicker trainers, referred to as loopy training.

Global post-translational modification profiling of HIV-1-infected cells reveals mechanisms of host cellular pathway remodeling.

Viruses must effectively remodel host cellular pathways to replicate and evade immune defenses, and they must do so with limited genomic coding capacity. Targeting post-translational modification (PTM) pathways provides a mechanism by which viruses can broadly and rapidly transform a hostile host environment into a hospitable one. We use mass spectrometry-based proteomics to quantify changes in protein abundance and two PTM types-phosphorylation and ubiquitination-in response to HIV-1 infection with viruses harboring targeted deletions of a subset of HIV-1 genes.

Evolution of Surgical Management of Metastatic Disease of the Pelvis.

The surgical management of acetabular and pelvic lesions due to metastatic bone disease is complex in nature. These patients are typically in a frail state, having severe pain, limited mobility, and impaired wound healing. This causes a potential for complications, a high concern for the surgeon.

Radiographic Scoring of Humeral Shaft Fractures Helps Identify Patients at Risk of Surgery for Delayed Union.

Objectives: Assessing external validity and clinical relevance of modified radiographic union score (mRUS) to predict delayed union in closed humeral shaft fractures initially treated with conservative management.

Design: Retrospective cohort.

Setting: Single urban academic level 1 trauma center.

Distal Radius Salter-Harris III Transitional Fracture in an Adolescent Male.

In contrast to the well-described Tillaux fracture of the distal tibia, transitional fractures of the distal radius are exceedingly rare and have yet to be well described. Thus far, their presence in the literature has been limited to case reports and a singular series. None have involved a Salter-Harris III fracture pattern.

Endosomal cAMP production broadly impacts the cellular phosphoproteome.

Endosomal signaling downstream of G-protein-coupled receptors (GPCRs) has emerged as a novel paradigm with important pharmacological and physiological implications. However, our knowledge of the functional consequences of intracellular signaling is incomplete. To begin to address this gap, we combined an optogenetic approach for site-specific generation of the prototypical second messenger generated by active GPCRs, cyclic AMP (cAMP), with unbiased mass-spectrometry-based analysis of the phosphoproteome.

Intra-Articular Osteotomy for Genu Valgum in the Knee with a Lateral Compartment Deficiency.

Background: A deficiency of the lateral compartment of the knee, often in the setting of skeletal dysplasia, is an intra-articular deformity resulting in genu valgum. Historically, this abnormality has been treated using an extra-articular approach. Lateral hypoplasia of the femoral condyle can be treated with advancement of the lateral femoral condyle without creating a secondary deformity.

Heads and tails: simultaneous exposed and buried interface imaging of monolayers.

We have simultaneously imaged the chemically bound head groups and exposed tail groups in bicomponent alkanethiolate self-assembled monolayers on Au{111} with molecular resolution. This has enabled us to resolve the controversy of scanning tunneling microscopy image interpretation and to measure the molecular polar tilt and azimuthal angles. Our local measurements demonstrate that ordered domains with different superstructures also have varied buried sulfur head group structures.

Self-assembly of carboranethiol isomers on Au111: intermolecular interactions determined by molecular dipole orientations.

Self-assembled monolayer (SAM) structures and properties are dominated by two interactions: those between the substrate and adsorbate and those between the adsorbates themselves. We have fabricated self-assembled monolayers of m-1-carboranethiol (M1) and m-9-carboranethiol (M9) on Au[111]. The two isomers are nearly identical geometrically, but calculated molecular dipole moments show a sizable difference at 1.

In vivo beta-defensin gene expression in rat gingival epithelium in response to Actinobacillus actinomycetemcomitans infection.

Background And Objective: Human beta-defensins have been identified in the oral cavity and are predicted to play a role in the defense against pathogenic bacteria. Homologous rat beta-defensins (RBDs) have been identified, but their expression in the oral cavity has not been examined. Therefore, the aim of this study was to investigate the expression of innate immune mediators in the rat gingival epithelium.

Anion-pi interactions in cyanuric acids: a combined crystallographic and computational study.

Several structures of pi complexes of isocyanuric acid and of several thio derivatives with anions have been computed by using high level ab initio calculations. The nature of the complexes has been studied by means of the method of molecular interaction potential with polarization (MIPp) and Bader's theory of atoms-in-molecules. These molecules form favorable complexes with anions and can be used as binding units for building receptors for the molecular recognition of anions.

Inhibition of activator protein-1 transcription factor activation by omega-3 fatty acid modulation of mitogen-activated protein kinase signaling kinases.

Background: Lipopolysaccharide (LPS)-stimulated macrophages (Mphi) produce excess tumor necrosis factor (TNF), and the direct inhibition of IkappaB phosphorylation and its subsequent separation from the nuclear factor kappaB (NFkappaB)-IkappaB complex has been experimentally supported as a mechanism for omega-3 fatty acid (FA) inhibition of this TNF response. However, TNF production is a "late" event in the LPS-induced Mpsi inflammatory cascade, and in addition to NFkappaB-associated pathways, a separate transcription factor, activator protein-1 (AP-1) is an important pathway for Mpsi proinflammatory cytokine production. The mitogen-activated protein kinase (MAPK) cascade regulates both NFkappaB-IkappaB--and AP-1-associated gene transcription through several cross-amplifying phosphorylation kinases, specifically p44/42 [ie, extracellular signal-regulated kinase (ERK) 1/2], p38, and c//jun N-terminal kinase (JNK)/stress-activated protein kinase (SAPK).

Novel detection and differential utilization of a c-myc transcriptional block in colon cancer chemoprevention.

Mutations in the adenomatous polyposis coli (APC) gene, which initiate almost all human colon cancers, directly target the proto-oncogene, c-myc, by elevating beta-catenin/T-cell factor (TCF) signaling. We have shown that agents ascribed chemopreventive activity for colon cancer in fact also stimulate beta-catenin/TCF activity in vitro. Their effects on c-myc transcription were assayed using a novel variant of fluorescence in situ hybridization that detects c-myc transcription sites in intact nuclei.