Automatic Determination of Endothelial Cell Density From Donor Cornea Endothelial Cell Images.

Purpose: To determine endothelial cell density (ECD) from real-world donor cornea endothelial cell (EC) images using a self-supervised deep learning segmentation model.

Methods: Two eye banks (Eversight, VisionGift) provided 15,138 single, unique EC images from 8169 donors along with their demographics, tissue characteristics, and ECD. This dataset was utilized for self-supervised training and deep learning inference.

Peptide Blockers of PD-1-PD-L1 Interaction Reinvigorate PD-1-Suppressed T Cells and Curb Tumor Growth in Mice.

The programmed cell death protein 1 (PD-1) plays a critical role in cancer immune evasion. Blocking the PD-1-PD-L1 interaction by monoclonal antibodies has shown remarkable clinical efficacy in treating certain types of cancer. However, antibodies are costly to produce, and antibody-based therapies can cause immune-related adverse events.

Discovery of an antivirulence compound that targets the Staphylococcus aureus SaeRS two-component system to inhibit toxic shock syndrome toxin-1 production.

Menstrual toxic shock syndrome (mTSS) is a rare but severe disorder associated with the use of menstrual products such as high-absorbency tampons and is caused by Staphylococcus aureus strains that produce the toxic shock syndrome toxin-1 (TSST-1) superantigen. Herein, we screened a library of 3920 small bioactive molecules for the ability to inhibit transcription of the TSST-1 gene without inhibiting the growth of S. aureus.

Streptolysin S is required for Streptococcus pyogenes nasopharyngeal and skin infection in HLA-transgenic mice.

Streptococcus pyogenes is a human-specific pathogen that commonly colonizes the upper respiratory tract and skin, causing a wide variety of diseases ranging from pharyngitis to necrotizing fasciitis and toxic shock syndrome. S. pyogenes has a repertoire of secreted virulence factors that promote infection and evasion of the host immune system including the cytolysins streptolysin O (SLO) and streptolysin S (SLS).

Vaginal community state types (CSTs) alter environmental cues and production of the toxic shock syndrome toxin-1 (TSST-1).

Menstrual toxic shock syndrome (mTSS) is a rare but life-threatening disease associated with the use of high-absorbency tampons. The production of the toxic shock syndrome toxin-1 (TSST-1) superantigen is involved in nearly all cases of mTSS and is tightly controlled by regulators responding to the environment. In the prototypic mTSS strain MN8, the major repressor of TSST-1 is the carbon catabolite protein A (CcpA), which responds to glucose concentrations in the vaginal tract.

Novel insights into the immune response to bacterial T cell superantigens.

Bacterial T cell superantigens (SAgs) are a family of microbial exotoxins that function to activate large numbers of T cells simultaneously. SAgs activate T cells by direct binding and crosslinking of the lateral regions of MHC class II molecules on antigen-presenting cells with T cell receptors (TCRs) on T cells; these interactions alter the normal TCR-peptide-MHC class II architecture to activate T cells in a manner that is independent of the antigen specificity of the TCR. SAgs have well-recognized, central roles in human diseases such as toxic shock syndrome and scarlet fever through their quantitative effects on the T cell response; in addition, numerous other consequences of SAg-driven T cell activation are now being recognized, including direct roles in the pathogenesis of endocarditis, bloodstream infections, skin disease and pharyngitis.

Interplay between Staphylococcus aureus and the vaginal microbiota.

Staphylococcus aureus is a proficient colonizer and opportunistic pathogen which can lead to vaginal dysbiosis, aerobic vaginitis, or life-threatening menstrual toxic shock syndrome. Here we explore the complex but underappreciated interactions that S. aureus may impose on the vaginal environment leading to additional disease outcomes.

Transposable elements drive the evolution of metazoan zinc finger genes.

Cys2-His2 zinc finger genes (ZNFs) form the largest family of transcription factors in metazoans. ZNF evolution is highly dynamic and characterized by the rapid expansion and contraction of numerous subfamilies across the animal phylogeny. The forces and mechanisms underlying rapid ZNF evolution remain poorly understood, but there is growing evidence that, in tetrapods, the targeting and repression of lineage-specific transposable elements (TEs) plays a critical role in the evolution of the Krüppel-associated box ZNF (KZNF) subfamily.

The fadXDEBA locus of Staphylococcus aureus is required for metabolism of exogenous palmitic acid and in vivo growth.

In Staphylococcus aureus, genes that should confer the capacity to metabolize fatty acids by β-oxidation occur in the fadXDEBA locus, but their function has not been elucidated. Previously, incorporation into phospholipid through the fatty acid kinase FakA pathway was thought to be the only option available for S. aureus to metabolize exogenous saturated fatty acids.

Does surgeon sex and anthropometry matter for tool usability in traditional laparoscopic surgery? A systematic review and meta-analysis.

Introduction: Hand size, strength, and stature all impact a surgeon's ability to perform Traditional Laparoscopic Surgery (TLS) comfortably and effectively. This is due to limitations in instrument and operating room design. This article aims to review performance, pain, and tool usability data based on biological sex and anthropometry.

The Streptococcus pyogenes hyaluronic acid capsule promotes experimental nasal and skin infection by preventing neutrophil-mediated clearance.

Streptococcus pyogenes is a globally prominent human-specific pathogen responsible for an enormous burden of human illnesses, including >600 million pharyngeal and >100 million skin infections each year. Despite intensive efforts that focus on invasive indications, much remains unknown about this bacterium in its natural state during colonization of the nasopharynx and skin. Using acute experimental infection models in HLA-transgenic mice, we evaluated how the hyaluronic acid (HA) capsule contributes to S.

Workload effects of online consultation implementation from a Job-Characteristics Model perspective: a qualitative study.

Background: Online consultation (OC) was previously promoted by the NHS to solve primary care workload challenges. Its implementation was sped up during the COVID-19 pandemic. Workload effects are widely debated.

Glucose Mediates Niche-Specific Repression of Staphylococcus aureus Toxic Shock Syndrome Toxin-1 through the Activity of CcpA in the Vaginal Environment.

Staphylococcus aureus chronically colonizes up to 30% of the human population on the skin or mucous membranes, including the nasal tract or vaginal canal. While colonization is often benign, this bacterium also has the capability to cause serious infections. Menstrual toxic shock syndrome (mTSS) is a serious toxinosis associated with improper use of tampons, which can induce an environment that is favorable to the production of the superantigen known as toxic shock syndrome toxin-1 (TSST-1).

Staphylococcus lugdunensis Uses the Agr Regulatory System to Resist Killing by Host Innate Immune Effectors.

Coagulase-negative staphylococci (CoNS) are frequently commensal bacteria that rarely cause disease in mammals. Staphylococcus lugdunensis is an exceptional CoNS that causes disease in humans similar to virulent Staphylococcus aureus, but the factors that enhance the virulence of this bacterium remain ill defined. Here, we used random transposon insertion mutagenesis to identify the quorum sensing system as a regulator of hemolysins in .

Intravascular lithotripsy-assisted PCI for severely calcified coronary lesions: evaluating the impact on quality of life and outcomes.

Background: Despite the increased uptake of intravascular lithotripsy (IVL) for treating severely calcified coronary lesions, there is limited patient-level data examining the effect of IVL on quality of life, symptomatology, and outcomes beyond 30 days. We sought to assess demographics, procedural characteristics, outcomes, and impact of IVL on patient-reported angina after a minimum of 6 months follow-up.

Methods: A retrospective single-center study was conducted of patients treated with coronary IVL between January and October 2020.

Superantigens promote bloodstream infection by eliciting pathogenic interferon-gamma production.

is a foremost bacterial pathogen responsible for a vast array of human diseases. Staphylococcal superantigens (SAgs) constitute a family of exotoxins from that bind directly to major histocompatibility complex (MHC) class II and T cell receptors to drive extensive T cell activation and cytokine release. Although these toxins have been implicated in serious disease, including toxic shock syndrome, the specific pathological mechanisms remain unclear.

Nitrous oxide-induced myeloneuropathy: an emerging public health issue.

Increasing use of nitrous oxide as a recreational drug has been reported among young adults in western countries over the past decade. We present two cases of young males presenting to the Emergency Department (ED) of a large urban university hospital in Dublin with progressive neurological dysfunction related to nitrous oxide use. We review the pathophysiology, clinical features and treatment of nitrous oxide neurotoxicity.

Streptococcal superantigens and the return of scarlet fever.

Streptococcus pyogenes (group A Streptococcus) is a globally disseminated and human-adapted bacterial pathogen that causes a wide range of infections, including scarlet fever. Scarlet fever is a toxin-mediated disease characterized by the formation of an erythematous, sandpaper-like rash that typically occurs in children aged 5 to 15. This infectious disease is caused by toxins called superantigens, a family of highly potent immunomodulators.

Increasing radiation exposure from computed tomography in liver transplant recipients over time.

Objectives: To evaluate changes in radiation exposure from computed tomography (CT) among patients undergoing liver transplantation in our unit over a 10-year period.

Methods: We evaluated 134 elective patients, without hepatocellular carcinoma or cholangiocarcinoma who underwent transplantation in 2007-2008 and 2017-2018. CT scans performed in our hospital up to 2 years pre transplant and 1 year post transplant were evaluated.

Validation of 3-Space Wireless Inertial Measurement Units Using an Industrial Robot.

Inertial Measurement Units (IMUs) are beneficial for motion tracking as, in contrast to most optical motion capture systems, IMU systems do not require a dedicated lab. However, IMUs are affected by electromagnetic noise and may exhibit drift over time; it is therefore common practice to compare their performance to another system of high accuracy before use. The 3-Space IMUs have only been validated in two previous studies with limited testing protocols.

First recurrence of small cell lung cancer presenting as subacute monoarticular arthritis.

We describe a case of recurrent small cell lung cancer presenting as an acute monoarticular arthritis. This patient had recently undergone comprehensive review and surveillance imaging under a local oncology unit, 18 months after undergoing chemoradiotherapy for limited disease small cell lung cancer. He had presented to the emergency department on multiple occasions and been managed as an outpatient for a provisional diagnosis of spontaneous haemarthrosis in the setting of rivaroxaban therapy.

Reducing Time to Discharge after Chemotherapy by Standardizing Workflow and Providing Outpatient Intravenous Hydration.

Introduction: Patients receiving cyclophosphamide or ifosfamide chemotherapy require intravenous fluid hydration to prevent hemorrhagic cystitis. In selected patients without medical contraindications (ie, excess nausea/vomiting), this hydration may be completed after discharge. We aimed to reduce the time to discharge after completing mesna in patients receiving cyclophosphamide or ifosfamide therapy on an inpatient chemotherapy service.

Anticoagulation in the obese patient with COVID-19-associated venous thromboembolism.

A 61-year-old obese man who had recently tested positive for COVID-19 presented to the emergency department following an unwitnessed collapse, with a brief period of unresponsiveness. CT pulmonary angiography confirmed the presence of extensive bilateral pulmonary embolism despite the patient reporting full compliance with long-term dabigatran. The patient was initially anticoagulated with low-molecular-weight heparin and was treated with non-invasive ventilation and dexamethasone for COVID-19 pneumonia.

HLA class I-associated expansion of TRBV11-2 T cells in multisystem inflammatory syndrome in children.

Multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory syndrome associated with SARS-CoV-2 infection, shares clinical features with toxic shock syndrome, which is triggered by bacterial superantigens. Superantigen specificity for different Vβ chains results in Vβ skewing, whereby T cells with specific Vβ chains and diverse antigen specificity are overrepresented in the T cell receptor (TCR) repertoire. Here, we characterized the TCR repertoire of MIS-C patients and found a profound expansion of TCRβ variable gene 11-2 (TRBV11-2), with up to 24% of clonal T cell space occupied by TRBV11-2 T cells, which correlated with MIS-C severity and serum cytokine levels.