Impacts of climate change on food security and resulting perinatal health impacts.

Climate change's impact on global food security is a pressing concern with profound consequences. Climate change disrupts the global food system through a number of mechanisms including extreme weather events, rising food prices, and compromised food quality. In this article, we explore the effect of climate change on food security and the resulting health impacts of poor nutrition on pregnant women and infants in the perinatal period.

Pan American climate resilient health systems: a training course for health professionals.

Objectives: To describe the development, implementation, and results of a training course designed to equip health professionals from the Pan American Health Organization region with the knowledge and tools needed to adapt health systems to current climate realities.

Methods: The course was a 9-week live-virtual course in March-April 2023, which was delivered through Zoom and offered in English, Spanish, and French. All lectures were delivered by local and regional climate and health experts.

Characterization of therapeutic antibody efficacy against multiple SARS-CoV-2 variants in the hamster model.

The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and onset of the coronavirus disease-19 (COVID-19) pandemic led to an immediate need for therapeutic treatment options. Therapeutic antibodies were developed to fill a gap when traditional antivirals were not available. In late 2020, the United States Government undertook an effort to compare candidate therapeutic antibodies in virus neutralization assays and in the hamster model of SARS-CoV-2 infection.

Connecting single-cell transcriptomes to projectomes in mouse visual cortex.

The mammalian brain is composed of diverse neuron types that play different functional roles. Recent single-cell RNA sequencing approaches have led to a whole brain taxonomy of transcriptomically-defined cell types, yet cell type definitions that include multiple cellular properties can offer additional insights into a neuron's role in brain circuits. While the Patch-seq method can investigate how transcriptomic properties relate to the local morphological and electrophysiological properties of cell types, linking transcriptomic identities to long-range projections is a major unresolved challenge.

Morphoelectric and transcriptomic divergence of the layer 1 interneuron repertoire in human versus mouse neocortex.

Neocortical layer 1 (L1) is a site of convergence between pyramidal-neuron dendrites and feedback axons where local inhibitory signaling can profoundly shape cortical processing. Evolutionary expansion of human neocortex is marked by distinctive pyramidal neurons with extensive L1 branching, but whether L1 interneurons are similarly diverse is underexplored. Using Patch-seq recordings from human neurosurgical tissue, we identified four transcriptomic subclasses with mouse L1 homologs, along with distinct subtypes and types unmatched in mouse L1.

Clinical and Immunologic Correlates of Vasodilatory Shock Among Ebola Virus-Infected Nonhuman Primates in a Critical Care Model.

Background: Existing models of Ebola virus infection have not fully characterized the pathophysiology of shock in connection with daily virologic, clinical, and immunologic parameters. We implemented a nonhuman primate critical care model to investigate these associations.

Methods: Two rhesus macaques received a target dose of 1000 plaque-forming units of Ebola virus intramuscularly with supportive care initiated on day 3.

Early predictors of prolonged intensive care utilization following liver transplantation.

Introduction: Creatinine, bilirubin, and fibrinolysis resistance are associated with multi-organ dysfunction and likely risk factors for prolonged intensive care unit (pICU) stay following liver transplantation (LT). We hypothesize postoperative day-1 (POD-1) labs will predict pICU.

Methods: LT recipients had clinical laboratories and viscoelastic testing with tissue plasminogen activator thrombelastography (tPA TEG) to quantify fibrinolysis resistance (LY30) on POD-1.

Ebola Virus Disease Features Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome in the Rhesus Macaque Model.

Background: Ebola virus (EBOV) disease (EVD) is one of the most severe and fatal viral hemorrhagic fevers and appears to mimic many clinical and laboratory manifestations of hemophagocytic lymphohistiocytosis syndrome (HLS), also known as macrophage activation syndrome. However, a clear association is yet to be firmly established for effective host-targeted, immunomodulatory therapeutic approaches to improve outcomes in patients with severe EVD.

Methods: Twenty-four rhesus monkeys were exposed intramuscularly to the EBOV Kikwit isolate and euthanized at prescheduled time points or when they reached the end-stage disease criteria.

Towards an affinity-free, centrifugal microfluidic system for rapid, automated forensic differential extraction.

Biological evidence originating from victims of sexual assault is often comprised of unbalanced cellular mixtures with significantly higher contributions from the victim's genetic material. Enrichment of the forensically-critical sperm fraction (SF) with single-source male DNA relies on differential extraction (DE), a manually-intensive process that is prone to contamination. Due to DNA losses from sequential washing steps, some existing DE methods often fail to generate sufficient sperm cell DNA recovery for perpetrator(s) identification.

Mechanisms underlying food insecurity in the aftermath of climate-related shocks: a systematic review.

Food insecurity is prevalent, affecting 1·2 billion people globally in 2021. However, the effects of food insecurity are unequally distributed across populations and climate-related shocks threaten to exacerbate food insecurity and associated health consequences. The mechanisms underlying this exacerbation at the household level are largely unknown.

Antiviral innate immunity is diminished in the upper respiratory tract of severe COVID-19 patients.

Understanding early innate immune responses to coronavirus disease 2019 (COVID-19) is crucial to developing targeted therapies to mitigate disease severity. Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection elicits interferon expression leading to transcription of IFN-stimulated genes (ISGs) to control viral replication and spread. SARS-CoV-2 infection also elicits NF-κB signaling which regulates inflammatory cytokine expression contributing to viral control and likely disease severity.

Fallacy of Median Door-to-ECG Time: Hidden Opportunities for STEMI Screening Improvement.

Background ST-segment elevation myocardial infarction (STEMI) guidelines recommend screening arriving emergency department (ED) patients for an early ECG in those with symptoms concerning for myocardial ischemia. Process measures target median door-to-ECG (D2E) time of 10 minutes. Methods and Results This 3-year descriptive retrospective cohort study, including 676 ED-diagnosed patients with STEMI from 10 geographically diverse facilities across the United States, examines an alternative approach to quantifying performance: proportion of patients meeting the goal of D2E≤10 minutes.

Prospective multicentre head-to-head validation of host blood transcriptomic biomarkers for pulmonary tuberculosis by real-time PCR.

Background: Sensitive point-of-care screening tests are urgently needed to identify individuals at highest risk of tuberculosis. We prospectively tested performance of host-blood transcriptomic tuberculosis signatures.

Methods: Adults without suspicion of tuberculosis were recruited from five endemic South African communities.

Characterization of a Centrifugal Microfluidic Orthogonal Flow Platform.

To bring to bear the power of centrifugal microfluidics on vertical flow immunoassays, control of flow orthogonally through nanoporous membranes is essential. The on-disc approach described here leverages the rapid print-cut-laminate (PCL) disc fabrication and prototyping method to create a permanent seal between disc materials and embedded nanoporous membranes. Rotational forces drive fluid flow, replacing capillary action, and complex pneumatic pumping systems.

Effects of BCG vaccination on donor unrestricted T cells in two prospective cohort studies.

Background: Non-protein antigen classes can be presented to T cells by near-monomorphic antigen-presenting molecules such as CD1, MR1, and butyrophilin 3A1. Such T cells, referred to as donor unrestricted T (DURT) cells, typically express stereotypic T cell receptors. The near-unrestricted nature of DURT cell antigen recognition is of particular interest for vaccine development, and we sought to define the roles of DURT cells, including MR1-restricted MAIT cells, CD1b-restricted glucose monomycolate (GMM)-specific T cells, CD1d-restricted NKT cells, and γδ T cells, in vaccination against Mycobacterium tuberculosis.

Allelic variation in class I HLA determines CD8 T cell repertoire shape and cross-reactive memory responses to SARS-CoV-2.

Effective presentation of antigens by human leukocyte antigen (HLA) class I molecules to CD8 T cells is required for viral elimination and generation of long-term immunological memory. In this study, we applied a single-cell, multiomic technology to generate a unified ex vivo characterization of the CD8 T cell response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) across four major HLA class I alleles. We found that HLA genotype conditions key features of epitope specificity, TCRα/β sequence diversity, and the utilization of pre-existing SARS-CoV-2-reactive memory T cell pools.

Delayed-Onset Neuropathological Complications From a Foramen Magnum and Occipital Crest Focused TBI of the Vietnam War and Other Conflicts: Part III, Critique of Existing TBI Criteria and Their Operational Controversies.

Introduction: In this report, we discuss the controversy of the diverse traumatic brain injury (TBI) categorization and taxonomy and the need to develop a new multidimensional and multidisciplinary categorization system that can be an aid in improved diagnostic and prognostic outcomes. Of interest, the heterogeneity of TBI marks the major obstacle to develop effective therapeutic interventions. Currently, the Glasgow Coma Scale has been utilized to guide in the prognosis and clinical management of TBI; it does not encompass the pathophysiological mechanisms leading to neurological deficits that can impede therapeutic interventions and consequently the failure of clinical trials.

Delayed-Onset Neuropathological Complications From a Foramen Magnum and Occipital Crest Focused Traumatic Brain Injury of the Vietnam War and Other Conflicts: Part I, Case Report.

Introduction: The diagnosis of traumatic brain injuries is typically based on hemispheric blasts resulting in degrees of unconsciousness and associated cerebral injuries. This case report describes a Vietnam War era setting in which a traumatic blast wave struck the posterior cranium in the region of the foramen magnum, occipital crest, and other skull openings (orbit, oronasal, and ear) and the unique secondary clinical signs and symptoms experienced over time.

Materials And Methods: This case report describes secondary delayed-onset clinical signs and symptoms consistent with progressive decades-long physical and functional complications.

Delayed-Onset Neuropathological Complications From a Foramen Magnum and Occipital Crest-Focused Traumatic Brain Injury of the Vietnam War and Other Conflicts: Part II, Research Analysis.

Introduction: Much of the research impacting diagnosis, outcome, and treatment of traumatic brain injuries (TBIs) has favored time of consciousness criteria indicative of hemispheric blast focus alone. However, recent animal-based research has widely expanded the diagnostic knowledge base and potential treatment options.

Methods: Recent animal-based research findings of foramen magnum and occipital crest-focused blast injuries in laboratory rats were reviewed and compared to the Part I human case report.

Human neocortical expansion involves glutamatergic neuron diversification.

The neocortex is disproportionately expanded in human compared with mouse, both in its total volume relative to subcortical structures and in the proportion occupied by supragranular layers composed of neurons that selectively make connections within the neocortex and with other telencephalic structures. Single-cell transcriptomic analyses of human and mouse neocortex show an increased diversity of glutamatergic neuron types in supragranular layers in human neocortex and pronounced gradients as a function of cortical depth. Here, to probe the functional and anatomical correlates of this transcriptomic diversity, we developed a robust platform combining patch clamp recording, biocytin staining and single-cell RNA-sequencing (Patch-seq) to examine neurosurgically resected human tissues.

Longitudinal Dynamics of a Blood Transcriptomic Signature of Tuberculosis.

Performance of blood transcriptomic tuberculosis (TB) signatures in longitudinal studies and effects of TB-preventive therapy and coinfection with HIV or respiratory organisms on transcriptomic signatures has not been systematically studied. We evaluated longitudinal kinetics of an 11-gene blood transcriptomic TB signature, RISK11, and effects of TB-preventive therapy (TPT) and respiratory organisms on RISK11 signature score, in HIV-uninfected and HIV-infected individuals. RISK11 was measured in a longitudinal study of RISK11-guided TPT in HIV-uninfected adults, a cross-sectional respiratory organisms cohort, or a longitudinal study in people living with HIV (PLHIV).

Scaled, high fidelity electrophysiological, morphological, and transcriptomic cell characterization.

The Patch-seq approach is a powerful variation of the patch-clamp technique that allows for the combined electrophysiological, morphological, and transcriptomic characterization of individual neurons. To generate Patch-seq datasets at scale, we identified and refined key factors that contribute to the efficient collection of high-quality data. We developed patch-clamp electrophysiology software with analysis functions specifically designed to automate acquisition with online quality control.