Protection against induced by OMV-based Meningococcal Vaccines are associated with cross-species directed humoral and cellular immune responses.

Limited protective immunologic responses to natural infection and a lack of knowledge about mechanisms of protection have hampered development of an effective vaccine. Recent studies in humans and mice have found meningococcal outer membrane vesicle-containing vaccines (OMV) induce cross species immune responses against gonococci and are associated with protection. The exact mechanisms or how humoral and cellular immunity are related to protection, remain unclear.

Dynamics of cytokine and antibody responses in community versus hospital SARS-CoV-2 infections.

Introduction: Dysregulated host cytokine responses to SARS-CoV-2 infection are a primary cause of progression to severe disease, whereas early neutralizing antibody responses are considered protective. However, there are gaps in understanding the early temporal dynamics of these immune responses, and the profile of productive immune responses generated by non-hospitalized people with mild infections in the community.

Methods: Here we conducted a prospective cohort study of people with suspected infections/exposures in the US state of North Carolina, before vaccine availability.

Investigating the role of allelochemicals in the interaction between Alexandrium monilatum and other phytoplankton species.

Species of the dinoflagellate genus Alexandrium can release bioactive extracellular compounds with allelopathic effects (e.g., immobilization, inhibition of growth, photosynthesis or lysis) towards other phytoplanktonic organisms.

Irradiated whole cell Chlamydia vaccine confers significant protection in a murine genital tract challenge model.

Chlamydia trachomatis infections are the most common bacterial STIs globally and can lead to serious morbidity if untreated. Development of a killed, whole-cell vaccine has been stymied by coincident epitope destruction during inactivation. Here, we present a prototype Chlamydia vaccine composed of elementary bodies (EBs) from the related mouse pathogen, Chlamydia muridarum (Cm).

Chief medical officers in the United Kingdom: maintaining 'independence' inside government.

Background: The Chief Medical Officer (CMO), one of the UK's most senior public health leadership roles, was crucial in supporting policymakers in responding to COVID-19. Yet, there exist only a handful of (largely historical) accounts of the role in England. This article is the first to empirically examine how the scope, focus and boundaries of the CMO role vary over time across the four UK nations, including during public health emergencies.

Cross-linguistic effects of the speech-to-song illusion in speakers of Bangla and English.

The speech-to-song illusion is a phenomenon in which the continuous repetition of a spoken utterance induces the listeners to perceive it as more song-like. Thus far, this perceptual transformation has been observed in mostly European languages, such as English; however, it is unclear whether the illusion is experienced by speakers of Bangla (Bengali), an Indo-Aryan language. The current study, therefore, investigates the illusion in 28 Bangla and 31 English-speaking participants.

Improved influenza vaccine responses after expression of multiple viral glycoproteins from a single mRNA.

Influenza viruses cause substantial morbidity and mortality every year despite seasonal vaccination. mRNA-based vaccines have the potential to elicit more protective immune responses, but for maximal breadth and durability, it is desirable to deliver both the viral hemagglutinin and neuraminidase glycoproteins. Delivering multiple antigens individually, however, complicates manufacturing and increases cost, thus it would be beneficial to express both proteins from a single mRNA.

Neural Decoding of the Speech Envelope: Effects of Intelligibility and Spectral Degradation.

During continuous speech perception, endogenous neural activity becomes time-locked to acoustic stimulus features, such as the speech amplitude envelope. This speech-brain coupling can be decoded using non-invasive brain imaging techniques, including electroencephalography (EEG). Neural decoding may provide clinical use as an objective measure of stimulus encoding by the brain-for example during cochlear implant listening, wherein the speech signal is severely spectrally degraded.

Comprehensive Flow Cytometric, Immunohistologic, and Molecular Assessment of Thymus Function in Rhesus Macaques.

The critical importance of the thymus for generating new naive T cells that protect against novel infections and are tolerant to self-antigens has led to a recent revival of interest in monitoring thymic function in species other than humans and mice. Nonhuman primates such as rhesus macaques (Macaca mulatta) provide particularly useful animal models for translational research in immunology. In this study, we tested the performance of a 15-marker multicolor Ab panel for flow cytometric phenotyping of lymphocyte subsets directly from rhesus whole blood, with validation by thymectomy and T cell depletion.

Sources of variability in Luminex bead-based cytokine assays: Evidence from twelve years of multi-site proficiency testing.

Bead array assays, such as those sold by Luminex, BD Biosciences, Sartorius, Abcam and other companies, are a well-established platform for multiplexed quantification of cytokines and other biomarkers in both clinical and discovery research environments. In 2011, the National Institute of Allergy and Infectious Diseases (NIAID)-funded External Quality Assurance Program Oversight Laboratory (EQAPOL) established a proficiency assessment program to monitor participating laboratories performing multiplex cytokine measurements using Luminex bead array technology. During every assessment cycle, each site was sent an assay kit, a protocol, and blinded samples of human sera spiked with recombinant cytokines.

Vaccination with antigenically complex hemagglutinin mixtures confers broad protection from influenza disease.

Current seasonal influenza virus vaccines induce responses primarily against immunodominant but highly plastic epitopes in the globular head of the hemagglutinin (HA) glycoprotein. Because of viral antigenic drift at these sites, vaccines need to be updated and readministered annually. To increase the breadth of influenza vaccine-mediated protection, we developed an antigenically complex mixture of recombinant HAs designed to redirect immune responses to more conserved domains of the protein.

Characteristics and contributing factors of diagnostic error in surgery: analysis of closed medico-legal cases and complaints in Canada.

Background: Diagnostic errors lead to patient harm; however, most research has been conducted in nonsurgical disciplines. We sought to characterize diagnostic error in the pre-, intra-, and postoperative surgical phases, describe their contributing factors, and quantify their impact related to patient harm.

Methods: We performed a retrospective analysis of closed medico-legal cases and complaints using a database representing more than 95% of all Canadian physicians.

Assessing the effects of population-level political, economic and social exposures, interventions and policies on inclusive economy outcomes for health equity in high-income countries: a systematic review of reviews.

Background: A fairer economy is increasingly recognised as crucial for tackling widening social, economic and health inequalities within society. However, which actions have been evaluated for their impact on inclusive economy outcomes is yet unknown.

Objective: Identify the effects of political, economic and social exposures, interventions and policies on inclusive economy (IE) outcomes in high-income countries, by systematically reviewing the review-level evidence.

A Narrative Review on Spontaneous Clearance of Urogenital Chlamydia trachomatis: Host, Microbiome, and Pathogen-Related Factors.

Chlamydia trachomatis (CT) is the most commonly reported sexually transmitted infection in the United States. Untreated urogenital infection in women can result in adverse sequelae such as pelvic inflammatory disease and infertility. Despite national screening and treatment guidelines, rates continue to rise; because most infections are asymptomatic, the actual prevalence of CT infection is likely significantly higher than reported.

Development of a cross-sectoral antimicrobial resistance capability assessment framework.

Antimicrobial resistance (AMR) is an urgent and growing global health concern, and a clear understanding of existing capacities to address AMR, particularly in low-income and middle-income countries (LMICs), is needed to inform national priorities, investment targets and development activities. Across LMICs, there are limited data regarding existing mechanisms to address AMR, including national AMR policies, current infection prevention and antimicrobial prescribing practices, antimicrobial use in animals, and microbiological testing capacity for AMR. Despite the development of numerous individual tools designed to inform policy formulation and implementation or surveillance interventions to address AMR, there is an unmet need for easy-to-use instruments that together provide a detailed overview of AMR policy, practice and capacity.

The TLR2/TLR6 ligand FSL-1 mitigates radiation-induced hematopoietic injury in mice and nonhuman primates.

Thrombocytopenia, hemorrhage, anemia, and infection are life-threatening issues following accidental or intentional radiation exposure. Since few therapeutics are available, safe and efficacious small molecules to mitigate radiation-induced injury need to be developed. Our previous study showed the synthetic TLR2/TLR6 ligand fibroblast stimulating lipopeptide (FSL-1) prolonged survival and provided MyD88-dependent mitigation of hematopoietic acute radiation syndrome (H-ARS) in mice.

Medico-legal cases associated with older physicians' cognitive ability to practice medicine.

Background: Dementia increases as individuals age. Aging physicians represent a growing population. Studies have demonstrated there are physicians with cognitive impairments practicing medicine.

Synthetic Biology Toolbox for Nitrogen-Fixing Soil Microbes.

The soil environment adjacent to plant roots, termed the rhizosphere, is home to a wide variety of microorganisms that can significantly affect the physiology of nearby plants. Microbes in the rhizosphere can provide nutrients, secrete signaling compounds, and inhibit pathogens. These processes could be manipulated with synthetic biology to enhance the agricultural performance of crops grown for food, energy, or environmental remediation, if methods can be implemented in these nonmodel microbes.

Transient inhibition of lysosomal functions potentiates nucleic acid vaccines.

Nucleic acid vaccines have shown promising results in the clinic against infectious diseases and cancers. To robustly improve the vaccine efficacy and safety, we developed an approach to increase the intracellular stability of nucleic acids by transiently inhibiting lysosomal function in targeted tissues using sucrose. To achieve efficient and localized delivery of sucrose in animals, we designed a biomimetic lipid nanoparticle (LNP) to target the delivery of sucrose into mouse muscle cells.

Medico-Legal Cases in Breast Imaging in Canada: A Trend Analysis.

Breast imaging accounts for a large proportion of medico-legal cases involving radiologists in several countries and may be a disincentive to breast imaging. As this has not been well studied in Canada, we evaluated the key medico-legal issues of breast imaging in Canada and their implications for health care providers and patient safety. In collaboration with Canadian Medical Protective Association (CMPA), we obtained information from the medico-legal repository, including civil-legal, medical regulatory authority (College) and hospital complaints occurring between 2002-2021.

A retrospective observational study of labour ward work Intensity: The challenge of maternity staffing.

Background: The UK and Ireland are facing significant challenges in the recruitment and retention of midwifery staff. Deficiencies in staffing, training and leadership have been cited as contributory factors to substandard care in both regional and global independent maternity safety reports. Locally, workforce planning is critical to maintaining 'one to one' care for all women in labor and to meet the peaks of daily birthing suite activity.

Development and validation of an automated assay for anti-drug-antibodies in rat serum.

The potential immunogenicity of therapeutic human and humanized monoclonal antibodies (mAb) is a significant concern, and so preclinical testing of therapeutic mAbs routinely includes assessment of anti-drug antibody (ADA) induction. Here, we report the development of automated screening and confirmatory bridging ELISAs for the detection of rat antibodies against DH1042, an engineered human mAb for the SARS-CoV-2 receptor-binding domain. The assays were evaluated for specificity, sensitivity, selectivity, absence of a prozone effect, linearity, intra- and inter- assay precision, and robustness, and found to be suitable for purpose.

Neonatal SHIV infection in rhesus macaques elicited heterologous HIV-1-neutralizing antibodies.

Infants and children infected with human immunodeficiency virus (HIV)-1 have been shown to develop neutralizing antibodies (nAbs) against heterologous HIV-1 strains, characteristic of broadly nAbs (bnAbs). Thus, having a neonatal model for the induction of heterologous HIV-1 nAbs may provide insights into the mechanisms of neonatal bnAb development. Here, we describe a neonatal model for heterologous HIV-1 nAb induction in pathogenic simian-HIV (SHIV)-infected rhesus macaques (RMs).

Plant-Pathogenic Phylotypes Evolved Divergent Respiratory Strategies and Behaviors To Thrive in Xylem.

Bacterial pathogens in the Ralstonia solanacearum species complex (RSSC) infect the water-transporting xylem vessels of plants, causing bacterial wilt disease. Strains in RSSC phylotypes I and III can reduce nitrate to dinitrogen via complete denitrification. The four-step denitrification pathway enables bacteria to use inorganic nitrogen species as terminal electron acceptors, supporting their growth in oxygen-limited environments such as biofilms or plant xylem.