Implementation of a Macroporous Polyhydroxyethylmethacrylate Cryogel-Based Mini-Bioreactor System to Improve Monoclonal Antibody Production.

Background: Monoclonal antibodies (mAbs) are pioneers in the diagnosis and treatment of many diseases, such as cancer, asthma, poisoning, viral infections, etc. As the market value of mAbs increases in the biopharma industry, the demand for high quantities is met by upscaled production using bioreactor systems. Thus, disposable, porous matrices called cryogels have gained the primary focus for adherent support in the proliferation of hybridoma cells.

State of the art of sepsis care for the emergency medicine clinician.

Sepsis impacts 1.7 million Americans annually. It is a life-threatening disruption of organ function because of the body's host response to infection.

Towards enhanced functionality of vagus neuroprostheses through in silico optimized stimulation.

Bioelectronic therapies modulating the vagus nerve are promising for cardiovascular, inflammatory, and mental disorders. Clinical applications are however limited by side-effects such as breathing obstruction and headache caused by non-specific stimulation. To design selective and functional stimulation, we engineered VaStim, a realistic and efficient in-silico model.

Ultrasound Neuromodulation of an Anti-Inflammatory Pathway at the Spleen Improves Experimental Pulmonary Hypertension.

Background: Inflammation is pathogenically implicated in pulmonary arterial hypertension; however, it has not been adequately targeted therapeutically. We investigated whether neuromodulation of an anti-inflammatory neuroimmune pathway involving the splenic nerve using noninvasive, focused ultrasound stimulation of the spleen (sFUS) can improve experimental pulmonary hypertension.

Methods: Pulmonary hypertension was induced in rats either by Sugen 5416 (20 mg/kg SQ) injection, followed by 21 (or 35) days of hypoxia (sugen/hypoxia model), or by monocrotaline (60 mg/kg IP) injection (monocrotaline model).

Consensus-Driven Recommendations to Support Physician Pregnancy, Adoption, Surrogacy, Parental Leave, and Lactation in Emergency Medicine.

The emergency department clinical environment is unique, and guidelines for promoting supportive and equitable workplace cultures ensure success and longevity for pregnant persons and parents in emergency medicine. There is paucity, variability, and dissatisfaction with current parental (historically referred to as maternity and paternity) leave policies. This paper describes the development of consensus-derived recommendations to serve as a framework for emergency departments across the country for incorporating family-friendly policies.

A comprehensive review of recent developments in the gram-negative bacterial UDP-2,3-diacylglucosamine hydrolase (LpxH) enzyme.

The emergence of multidrug resistance has provided a great challenge to treat nosocomial infections, which have become a major health threat around the globe. Lipid A (an active endotoxin component), the final product of the Raetz lipid A metabolism pathway, is a membrane anchor of lipopolysaccharide (LPS) of the gram-negative bacterial outer membrane. It shields bacterial cells and serves as a protective barrier from antibiotics, thereby eliciting host response and making it difficult to destroy.

Corticosteroids in Sepsis and Septic Shock: A Systematic Review, Pairwise, and Dose-Response Meta-Analysis.

Objectives: To perform a systematic review and meta-analysis to assess the efficacy and safety of corticosteroids in patients with sepsis.

Data Sources: We searched PubMed, Embase, and the Cochrane Library, up to January 10, 2023.

Study Selection: We included randomized controlled trials (RCTs) comparing corticosteroids with placebo or standard care with sepsis.

Voltammetry in the spleen assesses real-time immunomodulatory norepinephrine release elicited by autonomic neurostimulation.

Background: The noradrenergic innervation of the spleen is implicated in the autonomic control of inflammation and has been the target of neurostimulation therapies for inflammatory diseases. However, there is no real-time marker of its successful activation, which hinders the development of anti-inflammatory neurostimulation therapies and mechanistic studies in anti-inflammatory neural circuits.

Methods: In mice, we performed fast-scan cyclic voltammetry (FSCV) in the spleen during intravenous injections of norepinephrine (NE), and during stimulation of the vagus, splanchnic, or splenic nerves.

Transspinal Focused Ultrasound Suppresses Spinal Reflexes in Healthy Rats.

Objectives: Low-intensity, focused ultrasound (FUS) is an emerging noninvasive neuromodulation approach, with improved spatial and temporal resolution and penetration depth compared to other noninvasive electrical stimulation strategies. FUS has been used to modulate circuits in the brain and the peripheral nervous system, however, its potential to modulate spinal circuits is unclear. In this study, we assessed the effect of trans-spinal FUS (tsFUS) on spinal reflexes in healthy rats.

Atomic visualization of flipped-back conformations of high mannose glycans interacting with cargo lectins: An MD simulation perspective.

Protein-carbohydrate interactions play a crucial role in mediating several biomolecular recognition events. We attempt to unravel its intricacies by understanding how carbohydrate-binding proteins interpret the glycan code. We aim to decipher lectin-mediated recognition in the endoplasmic reticulum (ER), which plays a crucial role in ER-mediated quality control (ER-QC).

Organ- and function-specific anatomical organization of vagal fibers supports fascicular vagus nerve stimulation.

Vagal fibers travel inside fascicles and form branches to innervate organs and regulate organ functions. Existing vagus nerve stimulation (VNS) therapies activate vagal fibers non-selectively, often resulting in reduced efficacy and side effects from non-targeted organs. The transverse and longitudinal arrangement of fibers inside the vagal trunk with respect to the functions they mediate and organs they innervate is unknown, however it is crucial for selective VNS.

A roadmap for developing an emergency department based critical care consultation service: Building the early intervention team (EIT).

Emergency Department (ED) crowding and boarding impact safe and effective health care delivery. ED clinicians must balance caring for new arrivals who require stabilization and resuscitation as well as those who need longitudinal care and re-evaluation. These challenges are magnified in the setting of critically ill patients boarding for the intensive care unit.

Neurological monitoring in ECMO patients: current state of practice, challenges and lessons.

Background: Extracorporeal membrane oxygenation (ECMO) in critically ill patients serves as a management option for end-stage cardiorespiratory failure in medical and surgical conditions. Patients on ECMO are at a high risk of neurologic adverse events including intracranial hemorrhage (ICH), acute ischemic stroke (AIS), seizures, diffuse cerebral edema, and hypoxic brain injury. Standard approaches to neurological monitoring for patients receiving ECMO support can be challenging for multiple reasons, including the severity of critical illness, deep sedation, and/or paralysis.

kHz-frequency electrical stimulation selectively activates small, unmyelinated vagus afferents.

Background: Vagal reflexes regulate homeostasis in visceral organs and systems through afferent and efferent neurons and nerve fibers. Small, unmyelinated, C-type afferents comprise over 80% of fibers in the vagus and form the sensory arc of autonomic reflexes of the gut, lungs, heart and vessels and the immune system. Selective bioelectronic activation of C-afferents could be used to mechanistically study and treat diseases of peripheral organs in which vagal reflexes are involved, but it has not been achieved.

Patient perspectives of the climate of diversity, equity, and inclusion in the emergency department.

Objective: Assessing the diversity, equity, and inclusion (DEI) climate of emergency departments (EDs) can inform organizational change to provide equitable, inclusive, and high-quality care to their diverse patient populations. The purpose of this project was to investigate patient perspectives on the climate of DEI in an urban ED.

Methods: This was a cross-sectional survey study conducted in a large-volume, urban ED in Detroit, MI, from November 2018 to January 2019.

Ultrasound Neuromodulation of the Spleen Has Time-Dependent Anti-Inflammatory Effect in a Pneumonia Model.

Interfaces between the nervous and immune systems have been shown essential for the coordination and regulation of immune responses. Non-invasive ultrasound stimulation targeted to the spleen has recently been shown capable of activating one such interface, the splenic cholinergic anti-inflammatory pathway (CAP). Over the past decade, CAP and other neuroimmune pathways have been activated using implanted nerve stimulators and tested to prevent cytokine release and inflammation.

Nervous necrosis virus titration and antigen quantitation by indirect sandwich enzyme linked immunosorbent assay.

Viral nervous necrosis (VNN) is a serious disease of marine and brackishwater fishes caused by nervous necrosis virus (NNV) resulting in up to 100% mortality in early larval and juvenile stages. Adult fish when infected are asymptomatic and spread the virus vertically to the offspring through milt and eggs. Prevention of vertical transmission of the disease is by using disease free broodstock and vaccinating the brooders.

Prospective Validation of a Rapid Host Gene Expression Test to Discriminate Bacterial From Viral Respiratory Infection.

Importance: Bacterial and viral causes of acute respiratory illness (ARI) are difficult to clinically distinguish, resulting in the inappropriate use of antibacterial therapy. The use of a host gene expression-based test that is able to discriminate bacterial from viral infection in less than 1 hour may improve care and antimicrobial stewardship.

Objective: To validate the host response bacterial/viral (HR-B/V) test and assess its ability to accurately differentiate bacterial from viral infection among patients with ARI.

Accelerated Critical Therapy Now in the Emergency Department Using an Early Intervention Team: The Impact of Early Critical Care Consultation for ICU Boarders.

Unlabelled: Evaluate the impact of an emergency department (ED)-based critical care consultation service, hypothesizing early consultation results in shorter hospital length of stay (LOS).

Design: Retrospective observational study from February 2018 to 2020.

Setting: An urban academic quaternary referral center.

Structure and Carbohydrate Recognition by the Nonmitogenic Lectin Horcolin.

Lectins are sugar-binding proteins that have shown considerable promise as antiviral agents because of their ability to interact with envelope glycoproteins present on the surface of viruses such as HIV-1. However, their therapeutic potential has been compromised by their mitogenicity that stimulates uncontrolled division of T-lymphocytes. Horcolin, a member of the jacalin family of lectins, tightly binds the HIV-1 envelope glycoprotein gp120 and neutralizes HIV-1 particles but is nonmitogenic.

A fully implantable wireless bidirectional neuromodulation system for mice.

Novel research in the field of bioelectronic medicine requires neuromodulation systems that pair high-performance neurostimulation and bio-signal acquisition hardware with advanced signal processing and control algorithms. Although mice are the most commonly used animal in medical research, the size, weight, and power requirements of such bioelectronic systems either preclude use in mice or impose significant constraints on experimental design. Here, a fully-implantable recording and stimulation neuromodulation system suitable for use in mice is presented, measuring 2.

Spike Protein and the Various Cell-Surface Carbohydrates: An Interaction Study.

The SARS-CoV-2 virus has been known to gain entry into the host cell through the spike protein that binds to the host ACE2 cell surface protein. However, the role of the putative sugar-binding sites in the spike protein has remained unclear. We provide a comprehensive outlook into the infection initiation wherein the virus first recognizes the sialosides on the cell via its S1A domain of the spike protein as it surfs over the cell surface.