Apoptosis-mediated ADAM10 activation removes a mucin barrier promoting T cell efferocytosis.

Efferocytic clearance of apoptotic cells in general, and T cells in particular, is required for tissue and immune homeostasis. Transmembrane mucins are extended glycoproteins highly expressed in the cell glycocalyx that function as a barrier to phagocytosis. Whether and how mucins may be regulated during cell death to facilitate efferocytic corpse clearance is not well understood.

Profound structural conservation of chemically cross-linked HIV-1 envelope glycoprotein experimental vaccine antigens.

Chemical cross-linking is used to stabilize protein structures with additional benefits of pathogen and toxin inactivation for vaccine use, but its use has been restricted by the potential for local or global structural distortion. This is of particular importance when the protein in question requires a high degree of structural conservation for inducing a biological outcome such as the elicitation of antibodies to conformationally sensitive epitopes. The HIV-1 envelope glycoprotein (Env) trimer is metastable and shifts between different conformational states, complicating its use as a vaccine antigen.

Modular capsid decoration boosts adenovirus vaccine-induced humoral immunity against SARS-CoV-2.

Adenovirus vector vaccines have been widely and successfully deployed in response to coronavirus disease 2019 (COVID-19). However, despite inducing potent T cell immunity, improvement of vaccine-specific antibody responses upon homologous boosting is modest compared with other technologies. Here, we describe a system enabling modular decoration of adenovirus capsid surfaces with antigens and demonstrate potent induction of humoral immunity against these displayed antigens.

An immunodominant NP-B*07:02 cytotoxic T cell response controls viral replication and is associated with less severe COVID-19 disease.

NP-B*07:02-specific CD8 T cell responses are considered among the most dominant in SARS-CoV-2-infected individuals. We found strong association of this response with mild disease. Analysis of NP-B*07:02-specific T cell clones and single-cell sequencing were performed concurrently, with functional avidity and antiviral efficacy assessed using an in vitro SARS-CoV-2 infection system, and were correlated with T cell receptor usage, transcriptome signature and disease severity (acute n = 77, convalescent n = 52).

Immunological and pathological outcomes of SARS-CoV-2 challenge following formalin-inactivated vaccine in ferrets and rhesus macaques.

There is an urgent requirement for safe and effective vaccines to prevent COVID-19. A concern for the development of new viral vaccines is the potential to induce vaccine-enhanced disease (VED). This was reported in several preclinical studies with both SARS-CoV-1 and MERS vaccines but has not been reported with SARS-CoV-2 vaccines.

The RNA sensor MDA5 detects SARS-CoV-2 infection.

Human cells respond to infection by SARS-CoV-2, the virus that causes COVID-19, by producing cytokines including type I and III interferons (IFNs) and proinflammatory factors such as IL6 and TNF. IFNs can limit SARS-CoV-2 replication but cytokine imbalance contributes to severe COVID-19. We studied how cells detect SARS-CoV-2 infection.

Inclusion of cGAMP within virus-like particle vaccines enhances their immunogenicity.

Cyclic GMP-AMP (cGAMP) is an immunostimulatory molecule produced by cGAS that activates STING. cGAMP is an adjuvant when administered alongside antigens. cGAMP is also incorporated into enveloped virus particles during budding.

SARS-CoV-2 RNA detected in blood products from patients with COVID-19 is not associated with infectious virus.

Laboratory diagnosis of SARS-CoV-2 infection (the cause of COVID-19) uses PCR to detect viral RNA (vRNA) in respiratory samples. SARS-CoV-2 RNA has also been detected in other sample types, but there is limited understanding of the clinical or laboratory significance of its detection in blood. We undertook a systematic literature review to assimilate the evidence for the frequency of vRNA in blood, and to identify associated clinical characteristics.

Structural and immunologic correlates of chemically stabilized HIV-1 envelope glycoproteins.

Inducing broad spectrum neutralizing antibodies against challenging pathogens such as HIV-1 is a major vaccine design goal, but may be hindered by conformational instability within viral envelope glycoproteins (Env). Chemical cross-linking is widely used for vaccine antigen stabilization, but how this process affects structure, antigenicity and immunogenicity is poorly understood and its use remains entirely empirical. We have solved the first cryo-EM structure of a cross-linked vaccine antigen.

In the setting of paediatric osteomyelitis do not be afraid to CAST an eye.

The case commences with an innocuous right ankle injury (lateral malleolus), for which the patient, a 9-year-old boy, was placed in a temporary cast at his local hospital. Three days following this incident, the patient was diagnosed with new-onset type 1 diabetes mellitus. He was admitted to his local hospital with severe diabetic ketoacidosis appropriately treated and subsequently discharged c.

Performance of Pediatric Risk of Mortality Score Among Critically Ill Children With Heart Disease.

Objective: To evaluate the performance of the Pediatric Risk of Mortality 3 (PRISM-3) score in critically ill children with heart disease.

Methods: Patients <18 years of age admitted with cardiac diagnoses (cardiac medical and cardiac surgical) to one of the participating pediatric intensive care units in the Virtual Pediatric Systems, LLC, database were included. Performance of PRISM-3 was evaluated with discrimination and calibration measures among both cardiac surgical and cardiac medical patients.

Astrocytes Resist HIV-1 Fusion but Engulf Infected Macrophage Material.

HIV-1 disseminates to diverse tissues and establishes long-lived viral reservoirs. These reservoirs include the CNS, in which macrophage-lineage cells, and as suggested by many studies, astrocytes, may be infected. Here, we have investigated astrocyte infection by HIV-1.

Impact of Computerized Order Entry to Pharmacy Interface on Order-Infusion Pump Discrepancies.

Background. The ability of safety technologies to decrease errors, harm, and risk to patients has yet to be demonstrated consistently. Objective.

Chemical Cross-Linking Stabilizes Native-Like HIV-1 Envelope Glycoprotein Trimer Antigens.

Unlabelled: Major neutralizing antibody immune evasion strategies of the HIV-1 envelope glycoprotein (Env) trimer include conformational and structural instability. Stabilized soluble trimers such as BG505 SOSIP.664 mimic the structure of virion-associated Env but nevertheless sample different conformational states.

The Carbomer-Lecithin Adjuvant Adjuplex Has Potent Immunoactivating Properties and Elicits Protective Adaptive Immunity against Influenza Virus Challenge in Mice.

The continued discovery and development of adjuvants for vaccine formulation are important to safely increase potency and/or reduce the antigen doses of existing vaccines and tailor the adaptive immune response to newly developed vaccines. Adjuplex is a novel adjuvant platform based on a purified lecithin and carbomer homopolymer. Here, we analyzed the adjuvant activity of Adjuplex in mice for the soluble hemagglutinin (HA) glycoprotein of influenza A virus.

Macrophage infection via selective capture of HIV-1-infected CD4+ T cells.

Macrophages contribute to HIV-1 pathogenesis by forming a viral reservoir and mediating neurological disorders. Cell-free HIV-1 infection of macrophages is inefficient, in part due to low plasma membrane expression of viral entry receptors. We find that macrophages selectively capture and engulf HIV-1-infected CD4+ T cells leading to efficient macrophage infection.

Relationship between risk-adjustment tools and the pediatric logistic organ dysfunction score.

Background: The Risk-Adjusted Classification for Congenital Heart Surgery (RACHS-1) method and Aristotle Basic Complexity (ABC) scores correlate with mortality. However, low mortality rates in congenital heart disease (CHD) make use of mortality as the primary outcome measure insufficient. Demonstrating correlation between risk-adjustment tools and the Pediatric Logistic Organ Dysfunction (PELOD) score might allow for risk-adjusted comparison of an outcome measure other than mortality.

High-multiplicity HIV-1 infection and neutralizing antibody evasion mediated by the macrophage-T cell virological synapse.

Macrophage infection is considered to play an important role in HIV-1 pathogenesis and persistence. Using a primary cell-based coculture model, we show that monocyte-derived macrophages (MDM) efficiently transmit a high-multiplicity HIV-1 infection to autologous CD4(+) T cells through a viral envelope glycoprotein (Env) receptor- and actin-dependent virological synapse (VS), facilitated by interactions between ICAM-1 and LFA-1. Virological synapse (VS)-mediated transmission by MDM results in high levels of T cell HIV-1 integration and is 1 to 2 orders of magnitude more efficient than cell-free infection.

High multiplicity HIV-1 cell-to-cell transmission from macrophages to CD4+ T cells limits antiretroviral efficacy.

Objective: Few studies have examined the efficacy of antiretroviral therapy (ART) in the context of cell-to-cell transmission. We aimed to determine whether the activity of ART is limited by the mode of HIV-1 spread between cells and the type of immune cell implicated in transmission, or is independent of these variables.

Design: ART activity was evaluated in primary cells using in-vitro cell-free and cell to-cell HIV-1 infection systems.

Bilateral pulmonary artery banding as rescue intervention in high-risk neonates.

Background: Presentation in shock and preoperative infection remain risk factors for neonatal cardiac surgery. This report describes bilateral pulmonary artery banding (bPAB) in ductal-dependent lesions with systemic outflow obstruction as rescue intervention before surgery with cardiopulmonary bypass in these high-risk neonates.

Methods: A retrospective chart review was conducted for 10 patients who underwent bPAB before conventional surgery with cardiopulmonary bypass.

Multiple proviral integration events after virological synapse-mediated HIV-1 spread.

HIV-1 can move directly between T cells via virological synapses (VS). Although aspects of the molecular and cellular mechanisms underlying this mode of spread have been elucidated, the outcomes for infection of the target cell remain incompletely understood. We set out to determine whether HIV-1 transfer via VS results in productive, high-multiplicity HIV-1 infection.

Implementing a regional anesthesia block nurse team in the perianesthesia care unit increases patient safety and perioperative efficiency.

A lack of standardized nursing procedures regarding the management of patients receiving preoperative regional anesthesia in the perianesthesia setting raises a number of issues for perianesthesia nurses. In January 2010, Duke University Hospital's perianesthesia care unit implemented a regional anesthesia "block nurse" team in the preoperative holding area as a patient safety initiative. In January 2011, a retrospective data review was conducted.

Discrepancies between medication orders and infusion pump programming in a paediatric intensive care unit.

Background: Errors and the incorrect use of medications are significant sources of risk and harm to children in US hospitals. The risk associated with medication infusions has led to recommendations for the adoption of technologies including computer order physician entry (CPOE) and 'smart' infusion pumps despite a paucity of evidence demonstrating the ability of these technologies to reduce harm to paediatric inpatients.

Objective: To measure discrepancies between medication orders for infusions entered into a CPOE system and the medication being infused as measured by the programmed settings of the smart infusion pump within a paediatric intensive care unit.