Trimannose-coupled antimiR-21 for macrophage-targeted inhalation treatment of acute inflammatory lung damage.

Recent studies of severe acute inflammatory lung disease including COVID-19 identify macrophages to drive pulmonary hyperinflammation and long-term damage such as fibrosis. Here, we report on the development of a first-in-class, carbohydrate-coupled inhibitor of microRNA-21 (RCS-21), as a therapeutic means against pulmonary hyperinflammation and fibrosis. MicroRNA-21 is among the strongest upregulated microRNAs in human COVID-19 and in mice with acute inflammatory lung damage, and it is the strongest expressed microRNA in pulmonary macrophages.

Second Harmonic Generation Microscopy as a Novel Intraoperative Assessment of Rat Median Nerve Injury.

Purpose: Nerves that are functionally injured but appear macroscopically intact pose the biggest clinical dilemma. Second Harmonic Generation (SHG) Microscopy may provide a real-time assessment of nerve damage, with the ultimate goal of allowing surgeons to accurately quantify the degree of nerve damage present. The aim of this study was to demonstrate the utility of SHG microscopy to detect nerve damage in vivo in an animal model.

Outcomes of Arthroscopic Elbow Contracture Release: Improvement for Severe Prosupination and Flexion Contracture.

Purpose: The purpose of this study was to investigate outcomes following arthroscopic elbow contracture release to describe the use of arthroscopy for improvement in extension/flexion and pronation/supination arcs of motion at a single institution for degenerative and posttraumatic etiologies.

Methods: Consecutive arthroscopic elbow arthrolysis performed between 2003 and 2015 were retrospectively reviewed. Basic patient demographics, indications for surgery, preoperative and postoperative elbow range of motion, postoperative patient outcome score, and all complications were recorded and analyzed.

Cra and cAMP Receptor Protein Have Opposing Roles in the Regulation of in Vibrio cholerae.

The Gram-negative bacterium adapts to changes in the environment by selectively producing the necessary machinery to take up and metabolize available carbohydrates. The import of fructose by the fructose-specific phosphoenolpyruvate (PEP) phosphotransferase system (PTS) is of particular interest because of its putative connection to cholera pathogenesis and persistence. Here, we describe the expression and regulation of , which encodes an EIIA-FPr fusion protein as part of the fructose-specific PTS in Using a series of transcriptional reporter fusions and additional biochemical and genetic assays, we identified Cra (catabolite repressor/activator) and cAMP receptor protein (CRP) as regulators of expression and determined that this regulation is dependent upon the presence or absence of PTS sugars.

MicroRNA-21-Dependent Macrophage-to-Fibroblast Signaling Determines the Cardiac Response to Pressure Overload.

Background: Cardiac macrophages (cMPs) are increasingly recognized as important regulators of myocardial homeostasis and disease, yet the role of noncoding RNA in these cells is largely unknown. Small RNA sequencing of the entire miRNomes of the major cardiac cell fractions revealed microRNA-21 (miR-21) as the single highest expressed microRNA in cMPs, both in health and disease (25% and 43% of all microRNA reads, respectively). MiR-21 has been previously reported as a key microRNA driving tissue fibrosis.

The β-encapsulation cage of rearrangement hotspot (Rhs) effectors is required for type VI secretion.

Bacteria deploy rearrangement hotspot (Rhs) proteins as toxic effectors against both prokaryotic and eukaryotic target cells. Rhs proteins are characterized by YD-peptide repeats, which fold into a large β-cage structure that encapsulates the C-terminal toxin domain. Here, we show that Rhs effectors are essential for type VI secretion system (T6SS) activity in (ECL).

The Early Effects of COVID-19 on Plastic Surgery Residency Training: The University of Washington Experience.

Plastic surgeons have the unique perspective of working with all types of patients and care teams from almost all specialties in surgery and medicine, which creates unique challenges in times of distress. As the initial epicenter of coronavirus disease 2019 cases in the United States, the University of Washington program was required to rapidly develop strategies to deal with the escalating crisis. All aspects of the program were affected, including the need to triage the urgency of plastic surgery care, safe staffing of plastic surgery teams, and the role of plastic surgery in the greater hospital community.

AntimiR-21 Prevents Myocardial Dysfunction in a Pig Model of Ischemia/Reperfusion Injury.

Background: miR-21 is a central regulator of cardiac fibrosis, and its inhibition in small-animal models has been shown to be an effective antifibrotic strategy in various organs, including the heart. Effective delivery of therapeutic antisense micro-ribonucleic acid (antimiR) molecules to the myocardium in larger organisms is challenging, though, and remains to be established for models of chronic heart failure.

Objectives: The aims of this study were to test the applicability and therapeutic efficacy of local, catheter-based delivery of antimiR-21 in a pig model of heart failure and determine its effect on the cardiac transcriptomic signature and cellular composition.

Intramedullary Screw Fixation of Metacarpal Fractures Results in Excellent Functional Outcomes: A Literature Review.

Background: Intramedullary fixation of a comminuted subcapital metacarpal fracture using a headless compression screw was first described in 2010. The purpose of this study was to identify and evaluate all studies reporting clinical outcomes of intramedullary screw fixation of metacarpal fractures.

Methods: A comprehensive search of the literature was performed under Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines to identify all relevant studies.

Comparative strength of elbow splint designs: a new splint design as a stronger alternative to posterior splints.

Background: Musculoskeletal injuries of the upper extremity are frequently treated with temporary external immobilization. Traditionally, long arm posterior splints have been used to limit flexion/extension of the elbow. However, long arm posterior splints have been observed to fail clinically, necessitating a stronger alternative.

Varus posteromedial rotatory instability: a biomechanical analysis of posterior bundle of the medial ulnar collateral ligament reconstruction.

Background: Recently, there has been growing interest in the involvement of the posterior bundle of the medial ulnar collateral ligament (pMUCL) in varus posteromedial rotatory instability (PMRI). Varus PMRI has been observed clinically, but the degree of involvement of the pMUCL remains unclear. This study assessed the degree to which the pMUCL is involved in stabilizing the elbow and the feasibility of a pMUCL reconstruction to restore stability.

The effect of screw trajectory for the reduction and association of the scaphoid and lunate (RASL) procedure: a biomechanical analysis.

The purpose of this study was to determine if screw placement in the reduction and association of the scaphoid and the lunate (RASL) procedure affected the ability of the scapholunate joint to withstand force. After completely disrupting of the scapholunate ligament in 29 fresh-frozen cadaveric wrists, we placed the RASL screw either distal or proximal to the lateral aspect of the dorsal ridge of the scaphoid and into the dorsal or volar aspect of the lunate. Specimens were subjected to repeated cycles of transcarpal axial force, mimicking clenched-fist loading, until failure.

Activation of an anti-bacterial toxin by the biosynthetic enzyme CysK: mechanism of binding, interaction specificity and competition with cysteine synthase.

Contact-dependent growth inhibition (CDI) is a wide-spread mechanism of inter-bacterial competition. CDI bacteria deliver CdiA-CT toxins into neighboring bacteria and produce specific immunity proteins that protect against self-intoxication. The CdiA-CT toxin from uropathogenic Escherichia coli 536 is a latent tRNase that is only active when bound to the cysteine biosynthetic enzyme CysK.

CdiA Effectors Use Modular Receptor-Binding Domains To Recognize Target Bacteria.

Contact-dependent growth inhibition (CDI) systems encode CdiA effectors, which bind to specific receptors on neighboring bacteria and deliver C-terminal toxin domains to suppress target cell growth. Two classes of CdiA effectors that bind distinct cell surface receptors have been identified, but the molecular basis of receptor specificity is not understood. Alignment of BamA-specific CdiA from EC93 and OmpC-specific CdiA from 536 suggests that the receptor-binding domain resides within a central region that varies between the two effectors.

Risk factors for and timing of adverse events after total shoulder arthroplasty.

Background: Total shoulder arthroplasty (TSA) is a likely target for future bundled payment initiatives, necessitating accurate preoperative risk stratification. The purpose of this study was to identify risk factors for unplanned readmission and severe adverse events, to risk stratify TSA patients based on these risk factors, and to assess timing of complications after TSA.

Methods: Data were collected from patients undergoing TSA from 2009 to 2014 in the American College of Surgeons National Surgical Quality Improvement Program.

Day of Surgery and Surgical Start Time Affect Hospital Length of Stay After Total Hip Arthroplasty.

Background: The United States spends $12 billion each year on ∼332,000 total hip arthroplasty (THA) procedures with the postoperative period accounting for ∼40% of costs. The purpose of this study was to evaluate the effect of surgical scheduling (day of week and start time) on clinical outcomes, hospital length of stay (LOS), and rate of nonhome discharge in THA patients.

Methods: Analysis of perioperative variables was performed for patients who underwent THA at an urban tertiary care teaching hospital from 2009 to 2014.

CdiA Effectors from Uropathogenic Escherichia coli Use Heterotrimeric Osmoporins as Receptors to Recognize Target Bacteria.

Many Gram-negative bacterial pathogens express contact-dependent growth inhibition (CDI) systems that promote cell-cell interaction. CDI+ bacteria express surface CdiA effector proteins, which transfer their C-terminal toxin domains into susceptible target cells upon binding to specific receptors. CDI+ cells also produce immunity proteins that neutralize the toxin domains delivered from neighboring siblings.

Unraveling the essential role of CysK in CDI toxin activation.

Contact-dependent growth inhibition (CDI) is a widespread mechanism of bacterial competition. CDI(+) bacteria deliver the toxic C-terminal region of contact-dependent inhibition A proteins (CdiA-CT) into neighboring target bacteria and produce CDI immunity proteins (CdiI) to protect against self-inhibition. The CdiA-CT(EC536) deployed by uropathogenic Escherichia coli 536 (EC536) is a bacterial toxin 28 (Ntox28) domain that only exhibits ribonuclease activity when bound to the cysteine biosynthetic enzyme O-acetylserine sulfhydrylase A (CysK).

Anterior Chamber Air Bubble to Achieve Graft Attachment After DMEK: Is Bigger Always Better?

Purpose: To analyze the influence of the size of the air bubble subsequent to Descemet membrane endothelial keratoplasty (DMEK) surgery on the rate of graft detachment and need for rebubbling, the incidence of pupillary block, and the observed endothelial cell loss.

Methods: This is a single-center, retrospective, consecutive case series of 74 cases undergoing DMEK and fulfilling the inclusion criteria concerning the size of the air bubble at the end of surgery. Based on the medical records, patients were divided into 2 groups (n = 37, respectively).

Moonlighting O-acetylserine sulfhydrylase: New functions for an old protein.

O-acetylserine sulfhydrylase A (CysK) is the pyridoxal 5'-phosphate-dependent enzyme that catalyzes the final reaction of cysteine biosynthesis in bacteria. CysK was initially identified in a complex with serine acetyltransferase (CysE), which catalyzes the penultimate reaction in the synthetic pathway. This "cysteine synthase" complex is stabilized by insertion of the CysE C-terminus into the active-site of CysK.

The proton-motive force is required for translocation of CDI toxins across the inner membrane of target bacteria.

Contact-dependent growth inhibition (CDI) is a mode of bacterial competition orchestrated by the CdiB/CdiA family of two-partner secretion proteins. The CdiA effector extends from the surface of CDI(+) inhibitor cells, binds to receptors on neighbouring bacteria and delivers a toxin domain derived from its C-terminal region (CdiA-CT). Here, we show that CdiA-CT toxin translocation requires the proton-motive force (pmf) within target bacteria.

The F pilus mediates a novel pathway of CDI toxin import.

Contact-dependent growth inhibition (CDI) is a widespread form of inter-bacterial competition that requires direct cell-to-cell contact. CDI(+) inhibitor cells express CdiA effector proteins on their surface. CdiA binds to specific receptors on susceptible target bacteria and delivers a toxin derived from its C-terminal region (CdiA-CT).