Total versus partial knee replacement in patients with medial compartment knee osteoarthritis: the TOPKAT RCT.

Background: Late-stage medial compartment knee osteoarthritis can be treated using total knee replacement or partial (unicompartmental) knee replacement. There is high variation in treatment choice and insufficient evidence to guide selection.

Objective: To assess the clinical effectiveness and cost-effectiveness of partial knee replacement compared with total knee replacement in patients with medial compartment knee osteoarthritis.

A compounding compliance team at an academic medical center.

Purpose: Highly publicized safety issues arising from poor sterile compounding practices in facilities around the United States have garnered substantial attention in recent years. This attention has led to increased scrutiny of health systems by regulatory bodies, new regulatory requirements, and changes to existing regulations or their interpretation. Health systems are often resource constrained, and the added work resulting from this scrutiny challenges pharmacy departments in meeting regulatory requirements and United States Pharmacopeia chapter 797 standards for sterile compounding.

Delayed stabilisation of dynamically unstable syndesmotic injuries results in worse functional outcomes.

Purpose: Patients with primarily ligamentous injuries of the distal tibiofibular joint comprise up to 12% of all ankle sprains. Patients frequently present late after a syndesmosis injury and delayed treatment potentially leads to pain, prolonged disability and arthritis in the long term. This study aimed to assess clinical outcomes in patients who required syndesmosis fixation in the presence of arthroscopically proven instability, the hypothesis being that a delay to treatment would be associated with worse function.

Detection of Cross-Correlation between Gravitational Lensing and γ Rays.

In recent years, many γ-ray sources have been identified, yet the unresolved component hosts valuable information on the faintest emission. In order to extract it, a cross-correlation with gravitational tracers of matter in the Universe has been shown to be a promising tool. We report here the first identification of a cross-correlation signal between γ rays and the distribution of mass in the Universe probed by weak gravitational lensing.

Systematic review of thromboprophylaxis in patients having orthognathic surgery.

Orthognathic surgery is an elective procedure that is done in healthy individuals so complications such as thromboembolic events are rare. Pharmacological thromboprophylaxis, which reduces the risk of these events, may also increase blood loss and potentially the risk of life-threatening haemorrhage, so a state of clinical equipoise exists about whether it should be given routinely. We systematically reviewed published papers to identify the incidence of venous thromboembolism and haemorrhage in patients treated by orthognathic surgery who were, and were not, given pharmacological thromboprophylaxis.

Meibomian gland dropout is associated with immunodeficiency at HIV diagnosis: Implications for dry eye disease.

Aim: To characterize anterior eye health and tear film characteristics in individuals with human immunodeficiency virus (HIV) undergoing anti-retroviral therapy.

Methods: This cross-sectional study involved 35 adults, categorized as healthy controls (n = 18) or as HIV-positive patients (n = 17), with no history of opportunistic infection or current ocular fundus abnormalities. Participants underwent a comprehensive anterior eye assessment.

Gastropharyngeal Anastomotic Leak in Medullary Thyroid Carcinoma Following Initiation of a Tyrosine Kinase Inhibitor: A Case Report of an Unusual Side Effect of Cabozantinib.

Background: Medullary thyroid carcinoma (MTC) accounts for 1% to 2% of thyroid cancers in the United States. When identified early, total thyroidectomy is most often curative. However, in advanced disease, more aggressive treatment such as laryngectomy and esophagectomy may be indicated.

Fc functional antibody responses to adjuvanted versus unadjuvanted seasonal influenza vaccination in community-dwelling older adults.

Background: Seasonal influenza vaccination with a standard trivalent influenza vaccine (TIV) induces a modest, and cross-reactive, Fc functional antibody response in older adults. Recent improvements to influenza vaccines include a quadrivalent influenza vaccine (QIV) and a TIV adjuvanted with the squalene-based oil-in-water emulsion MF59.

Methods: Pre- and post-vaccination serum samples from older adults vaccinated with QIV (n = 27) and adjuvanted TIV (n = 44) were studied using hemagglutination inhibition (HAI) assays and dimeric Fc-gamma receptor IIIa binding ELISAs, as a surrogate of antibody-dependent cellular cytotoxicity (ADCC).

Low-Fouling Fluoropolymers for Bioconjugation and In Vivo Tracking.

The conjugation of hydrophilic low-fouling polymers to therapeutic molecules and particles is an effective approach to improving their aqueous stability, solubility, and pharmacokinetics. Recent concerns over the immunogenicity of poly(ethylene glycol) has highlighted the importance of identifying alternative low fouling polymers. Now, a new class of synthetic water-soluble homo-fluoropolymers are reported with a sulfoxide side-chain structure.

An Inflammatory Story: Antibodies in Tuberculosis Comorbidities.

() resides in a quarter of the world's population and is the causative agent for tuberculosis (TB), the most common infectious reason of death in humans today. Although cellular immunity has been firmly established in the control of , there is growing evidence that antibodies may also modulate the infection. More specifically, certain antibody features are associated with inflammation and are divergent in different states of human infection and disease.

Butyrophilin 2A1 is essential for phosphoantigen reactivity by γδ T cells.

Gamma delta (γδ) T cells are essential to protective immunity. In humans, most γδ T cells express Vγ9Vδ2 T cell receptors (TCRs) that respond to phosphoantigens (pAgs) produced by cellular pathogens and overexpressed by cancers. However, the molecular targets recognized by these γδTCRs are unknown.

The protective potential of Fc-mediated antibody functions against influenza virus and other viral pathogens.

In recent years, there has been a renewed interest in utilizing antibody fragment crystallizable (Fc) functions to prevent and control viral infections. The protective and therapeutic potential of Fc-mediated antibody functions have been assessed for some clinically important human viruses, including HIV, hemorrhagic fever viruses and influenza virus. There is mounting evidence that influenza-specific antibodies with Fc-mediated functions, such as antibody-dependent cellular cytotoxicity and antibody-dependent phagocytosis, can aid in the clearance of influenza virus infection.

Serum IgA Fc effector functions in infectious disease and cancer.

Immunoglobulin (Ig) A is the most abundant antibody isotype present at mucosal surfaces and the second most abundant in human serum. In addition to preventing pathogen entry at mucosal surfaces, IgA can control and eradicate bacterial and viral infections through a variety of antibody-mediated innate effector cell mechanisms. The role of mucosal IgA in infection (e.

Low pH Exposure During Immunoglobulin G Purification Methods Results in Aggregates That Avidly Bind Fcγ Receptors: Implications for Measuring Fc Dependent Antibody Functions.

Evaluating the biophysical and functional nature of IgG is key to defining correlates of protection in infectious disease, and autoimmunity research cohorts, as well as vaccine efficacy trials. These studies often require small quantities of IgG to be purified from plasma for downstream analysis with high throughput immunoaffinity formats which elute IgG at low-pH, such as Protein G and Protein A. Herein we sought to compare Protein G purification of IgG with an immunoaffinity method which elutes at physiological pH (Melon Gel).

Immunoreactive trypsinogen levels in newborn screened infants with an inconclusive diagnosis of cystic fibrosis.

Background: Newborn screening (NBS) for cystic fibrosis (CF) not only identifies infants with a diagnosis of CF, but also those with an uncertain diagnosis of cystic fibrosis (CF), i.e. CF transmembrane conductance regulator (CFTR)-related metabolic syndrome (CRMS) or CF screen positive inconclusive diagnosis (CFSPID).

Impact of HIV-1 viremia or sexually transmitted infection on semen-derived anti-HIV-1 antibodies and the immunosuppressive capacity of seminal plasma.

Semen from HIV-1-infected men contains anti-HIV-1 antibodies and immunosuppressive factor(s). We assessed if suppression of viremia with antiretroviral therapy impacted seminal plasma immunosuppressive capacity or the Fc-dependent functions of seminal anti-HIV-1 antibodies. We also tested if active bacterial sexually transmitted infections altered the immunosuppressive capacity of seminal plasma.

Differential Roles of Plasma Protein Corona on Immune Cell Association and Cytokine Secretion of Oligomeric and Fibrillar Beta-Amyloid.

Alzheimer's disease (AD) is a primary neurological disease with no effective cure. A hallmark of AD is the presence of intracellular tangles and extracellular plaques derived from the aberrant aggregation of tau- and beta-amyloid (Aβ). Aβ presents in the brain as well as in cerebrospinal fluid and the circulation, and Aβ toxicity has been attributed to amyloidosis and inflammation, among other causes.

Improving immunological insights into the ferret model of human viral infectious disease.

Ferrets are a well-established model for studying both the pathogenesis and transmission of human respiratory viruses and evaluation of antiviral vaccines. Advanced immunological studies would add substantial value to the ferret models of disease but are hindered by the low number of ferret-reactive reagents available for flow cytometry and immunohistochemistry. Nevertheless, progress has been made to understand immune responses in the ferret model with a limited set of ferret-specific reagents and assays.

Trait mindfulness and the Effort-Reward Imbalance workplace stress model: Higher trait mindfulness is associated with increased salivary immunoglobulin A.

Individuals who are high in trait mindfulness are less stressed at work, better adjusted, and healthier than individuals who are low in this trait (Allen et al., 2015; Irving et al., 2009; Lomas et al.

Characterization of Key Bio-Nano Interactions between Organosilica Nanoparticles and .

Nanoparticle-cell interactions between silica nanomaterials and mammalian cells have been investigated extensively in the context of drug delivery, diagnostics, and imaging. While there are also opportunities for applications in infectious disease, the interactions of silica nanoparticles with pathogenic microbes are relatively underexplored. To bridge this knowledge gap, here, we investigate the effects of organosilica nanoparticles of different sizes, concentrations, and surface coatings on surface association and viability of the major human fungal pathogen .

The Challenge of Transparency and Validation in Health Economic Decision Modelling: A View from Mount Hood.

Transparency in health economic decision modelling is important for engendering confidence in the models and in the reliability of model-based cost-effectiveness analyses. The Mount Hood Diabetes Challenge Network has taken a lead in promoting transparency through validation with biennial conferences in which diabetes modelling groups meet to compare simulated outcomes of pre-specified scenarios often based on the results of pivotal clinical trials. Model registration is a potential method for promoting transparency, while also reducing the duplication of effort.

Public Understanding and Opinions regarding Genetic Research on Alzheimer's Disease.

Background: Participants willing to provide genetic samples are needed to propel research on Alzheimer's disease (AD) treatment and prevention forward. A limited public understanding of what AD genetic research entails and concerns about participation may constitute recruitment challenges.

Objectives: This study seeks to understand how well older adults understand AD genetic research and whether their understanding is related to concerns about participation or willingness to engage.

The clinical and cost-effectiveness of total versus partial knee replacement in patients with medial compartment osteoarthritis (TOPKAT): 5-year outcomes of a randomised controlled trial.

Background: Late-stage isolated medial knee osteoarthritis can be treated with total knee replacement (TKR) or partial knee replacement (PKR). There is high variation in treatment choice and little robust evidence to guide selection. The Total or Partial Knee Arthroplasty Trial (TOPKAT) therefore aims to assess the clinical effectiveness and cost-effectiveness of TKR versus PKR in patients with medial compartment osteoarthritis of the knee, and this represents an analysis of the main endpoints at 5 years.

Boosting of Markers of Fcγ Receptor Function in Anti-HIV Antibodies During Structured Treatment Interruption.

Anti-HIV envelope (Env) antibodies elicit important Fc receptor functions, including FcγRIIIa-mediated natural killer cell killing of opsonized infected targets. How these antibodies evolve during HIV infection and treatment remains poorly understood. We describe changes in anti-HIV Env IgG using longitudinal samples from seroconverter subjects treated soon after infection and later during periods of structured treatment interruption (STI).

Knowns and Unknowns of Assaying Antibody-Dependent Cell-Mediated Cytotoxicity Against HIV-1.

It is now well-accepted that Fc-mediated effector functions, including antibody-dependent cellular cytotoxicity (ADCC), can contribute to vaccine-elicited protection as well as post-infection control of HIV viremia. This picture was derived using a wide array of ADCC assays, no two of which are strictly comparable, and none of which is qualified at the clinical laboratory level. An earlier comparative study of assay protocols showed that while data from different ADCC assay formats were often correlated, they remained distinct in terms of target cells and the epitopes and antigen(s) available for recognition by antibodies, the effector cells, and the readout of cytotoxicity.