Leucine zipper-based SAIM imaging identifies therapeutic agents to disrupt the cancer cell glycocalyx for enhanced immunotherapy.

The abnormally thick glycocalyx of cancer cells can provide a physical barrier to immune cell recognition and effective immunotherapy. Here, we demonstrate an optical method based on Scanning Angle Interference Microscopy (SAIM) for the screening of therapeutic agents that can disrupt the glycocalyx layer as a strategy to improve anti-cancer immune responses. We developed a new membrane labeling strategy utilizing leucine zipper pairs to fluorescently mark the glycocalyx layer boundary for precise and robust measurement of glycocalyx thickness with SAIM.

Bioengineered lubricin alters the lubrication modes of cartilage in a dose-dependent manner.

The low friction nature of articular cartilage has been attributed to the synergistic interaction between lubricin and hyaluronic acid in the synovial fluid (SF). Lubricin is a mucinous glycoprotein that lowers the boundary mode coefficient of friction of articular cartilage in a dose-dependent manner. While there have been multiple attempts to produce recombinant lubricin and lubricin mimetic cartilage lubricants over the last two decades, these materials have not found clinical use due to challenges associated with large scale production, manufacturing, and purification.

Specific Degradation of the Mucin Domain of Lubricin in Synovial Fluid Impairs Cartilage Lubrication.

Progressive cartilage degradation, synovial inflammation, and joint lubrication dysfunction are key markers of osteoarthritis. The composition of synovial fluid (SF) is altered in OA, with changes to both hyaluronic acid and lubricin, the primary lubricating molecules in SF. Lubricin's distinct bottlebrush mucin domain has been speculated to contribute to its lubricating ability, but the relationship between its structure and mechanical function in SF is not well understood.

Mineralization of equine proximal sesamoid bones precedes articular cartilage and fibrocartilaginous enthesis maturation in early postgestational development.

Objective: To describe the development and maturation of equine proximal sesamoid bones (PSBs) in fetuses and young horses using radiography, microcomputed (micro)-CT, and histology.

Methods: A descriptive study. Forelimb PSBs from 12 equids ranging in age from 105 days of gestation to 540 days postgestation were evaluated.

Loss of effective lubricating viscosity is the primary mechanical marker of joint inflammation in equine synovitis.

Inflammation of the synovium, known as synovitis, plays an important role in the pathogenesis of osteoarthritis (OA). Synovitis involves the release of a wide variety of pro-inflammatory mediators in synovial fluid (SF) that damage the articular cartilage extracellular matrix and induce death and apoptosis in chondrocytes. The composition of synovial fluid is dramatically altered by inflammation in OA, with changes to both hyaluronic acid and lubricin, the primary lubricating molecules in SF.

Targeted Analysis of the Size Distribution of Heavy Chain-Modified Hyaluronan with Solid-State Nanopores.

The glycosaminoglycan hyaluronan (HA) plays important roles in diverse physiological functions where the distribution of its molecular weight (MW) can influence its behavior and is known to change in response to disease conditions. During inflammation, HA undergoes a covalent modification in which heavy chain subunits of the inter-alpha-inhibitor family of proteins are transferred to its structure, forming heavy chain-HA (HC•HA) complexes. While limited assessments of HC•HA have been performed previously, determining the size distribution of its HA component remains a challenge.

Equine non-septic tenosynovitis: A systematic literature review of site-specific pathological lesions, outcomes and surgical complications.

Background: Non-septic tenosynovitis is a clinically relevant and often performance limiting musculoskeletal injury in the horse.

Objectives: To review the published literature to determine which tendon sheaths are commonly affected by non-septic tenosynovitis and to describe the most frequently reported pathological lesions, outcomes, and surgical complications in equine non-septic tenosynovitis.

Study Design: Systematic review.

Equine synovial sepsis laboratory submissions yield a low rate of positive bacterial culture and a high prevalence of antimicrobial resistance.

Objective: To investigate (1) variables associated with the likelihood of obtaining a positive culture, (2) commonly isolated microorganisms, and (3) antimicrobial resistance patterns of isolates from horses with presumptive synovial sepsis.

Samples: Synovial fluid, synovium, and bone samples from equine cases with presumptive synovial sepsis submitted to the Cornell University Animal Health Diagnostic Center from 2000 to 2020 for microbial culture and antimicrobial sensitivity testing.

Procedures: Univariable and multivariable analyses were performed to determine the effect of variables on the likelihood of positive culture.

Synovial sepsis diagnostics and antimicrobial resistance: a one-health perspective.

This article, as part of the Currents in One Health series, reviews the current state of diagnostics for synovial sepsis. Synovial sepsis is a condition that affects veterinary and human medicine and requires coordinated efforts from both parties, as well as environmental considerations to accurately diagnose and preserve effective treatments. The article discusses best practices to identify the causative agent in septic synovitis, trends in bacterial identification and antimicrobial resistance patterns across common bacterial species, and a one-health perspective to optimize diagnostics across species.

Metacarpophalangeal Joint Pathology and Bone Mineral Density Increase with Exercise but Not with Incidence of Proximal Sesamoid Bone Fracture in Thoroughbred Racehorses.

Proximal sesamoid bone (PSB) fracture is the leading cause of fatal musculoskeletal injury in Thoroughbred racehorses in Hong Kong and the US. Efforts are underway to investigate diagnostic modalities that could help identify racehorses at increased risk of fracture; however, features associated with PSB fracture risk are still poorly understood. The objectives of this study were to (1) investigate third metacarpal (MC3) and PSB density and mineral content using dual-energy X-ray absorptiometry (DXA), computed tomography (CT), Raman spectroscopy, and ash fraction measurements, and (2) investigate PSB quality and metacarpophalangeal joint (MCPJ) pathology using Raman spectroscopy and CT.

Feasibility of Same-Day Discharge After Laparoscopic Roux-en-Y Gastric Bypass in Patients with Well-Regulated Obstructive Sleep Apnea.

Introduction: Same-day discharge after bariatric surgery is increasingly being performed. In current practice, patients with only minor comorbidities are considered eligible for same-day discharge after laparoscopic Roux-en-Y gastric bypass (RYGB). Obstructive sleep apnea (OSA) is a common comorbidity in patients with morbid obesity, with a prevalence of around 70-80% among patients undergoing bariatric surgery.

High flow nasal cannula for acute respiratory failure due to COVID-19 in patients with a 'do-not-intubate' order: A survival analysis.

Introduction: High flow nasal cannula (HFNC) reduces the need for intubation in patients with hypoxaemic acute respiratory failure (ARF), but its added value in patients with severe coronavirus disease 2019 (COVID-19) and a do-not-intubate (DNI) order is unknown. We aimed to assess (variables associated with) survival in these patients.

Materials And Methods: We described a multicentre retrospective observational cohort study in five hospitals in the Netherlands and assessed the survival in COVID-19 patients with severe acute respiratory failure and a DNI order who were treated with high flow nasal cannula.

Recombinant mucin biotechnology and engineering.

Mucins represent a largely untapped class of polymeric building block for biomaterials, therapeutics, and other biotechnology. Because the mucin polymer backbone is genetically encoded, sequence-specific mucins with defined physical and biochemical properties can be fabricated using recombinant technologies. The pendent O-glycans of mucins are increasingly implicated in immunomodulation, suppression of pathogen virulence, and other biochemical activities.

Radiomics Modeling of Catastrophic Proximal Sesamoid Bone Fractures in Thoroughbred Racehorses Using μCT.

Proximal sesamoid bone (PSB) fractures are the most common musculoskeletal injury in race-horses. X-ray CT imaging can detect expressed radiological features in horses that experienced catastrophic fractures. Our objective was to assess whether expressed radiomic features in the PSBs of 50 horses can be used to develop machine learning models for predicting PSB fractures.

Identification of a Novel HBV Encoded miRNA Using Next Generation Sequencing.

Hepatitis B Virus (HBV) encoded miRNAs were previously described and suggested to play a role in HBV replication and pathogenesis. In this study we aim to identify novel HBV encoded miRNAs in plasma and liver tissue samples from chronic hepatitis B (CHB) patients and determine their role in CHB pathogenesis and HBV replication. RNA next generation sequencing was performed on plasma and liver tissue samples from ten CHB patients and uninfected controls.

Identification of Liver and Plasma microRNAs in Chronic Hepatitis B Virus infection.

Background And Aims: With current standard of care a functional cure for Chronic Hepatitis B (CHB) is only achieved in 1-3% of patients and therefore novel therapies are needed. Disease activity during CHB can be determined by a broad range of virological biomarkers, however these biomarkers are also targets for novel treatment strategies. The aim of this study was to identify novel miRNAs that are differentially expressed in plasma and liver in CHB, and determine whether these miRNAs may serve as biomarkers of disease stage or treatment outcome.

A Prospective Five-Year Follow-up After peg-Interferon Plus Nucleotide Analogue Treatment or no Treatment in HBeAg Negative Chronic Hepatitis B Patients.

Background: Currently available treatment options for chronic hepatitis B (CHB) are not recommended for HBeAg-negative patients with a low viral load. These patients may however benefit from treatment by achieving a functional cure, defined by HBsAg-loss and undetectable HBV DNA. This study evaluated the long-term effect of combination treatment with peg-interferon-alpha-2a (peg-IFN) and adefovir or tenofovir compared to no treatment in these patients.

Proximal sesamoid bone microdamage is localized to articular subchondral regions in Thoroughbred racehorses, with similar fracture toughness between fracture and controls.

Objective: To determine whether proximal sesamoid bone (PSB) microdamage and fracture toughness differ between Thoroughbred racehorses sustaining PSB fracture and controls.

Study Design: Cadaveric case-control.

Animals: Twenty-four Thoroughbred racehorses (n = 12 PSB fracture, n = 12 control).

The history of buffy coat platelet concentrates: The Dutch story.

The buffy coat method as a source for platelet concentrates was developed in the 1970s and is still used in many blood centres around the world. Development of the method sparked various technological advances in blood collection, processing and storage. At the time, the need for platelet concentrates sharply increased because of better treatment regimens for (onco)haematological diseases, which forced blood centres to standardize and automate their production processes as much as the technology would allow.

Quantified integrated hepatitis B virus is related to viral activity in patients with chronic hepatitis B.

Background And Aims: HBV can integrate in the host genome of the hepatocyte and recent findings suggest that integrated HBV contributes to the persistent production of viral proteins. Here, we quantified the levels of integrated HBV in patients with chronic hepatitis B (CHB) and analyzed the relation between HBV integration, virological activity (plasma HBV DNA and HBsAg levels), and clinical outcomes.

Approach And Results: We developed and validated a multistep Arthrobacter luteus (Alu)-PCR that specifically amplifies integrated HBV and RT-Alu-PCR detecting mRNA transcripts derived from integrated HBV.