Necrotizing Enterocolitis and Neurodevelopmental Impairments: Microbiome, Gut, and Brain Entanglements.

There is significant communication and interdependence among the gut, the microbiome, and the brain during development. Diseases, such as necrotizing enterocolitis (NEC), highlight how injury to the immature gastrointestinal tract leads to long-term neurological consequences, due to vulnerabilities of the brain in the early stages of life. A better understanding of the developing gut-microbiota-brain axis is needed to both prevent and treat the devastating consequences of these disease processes.

Disparities in child protective services involvement in pediatric traumatic brain injury.

Purpose: Traumatic brain injury (TBI) is a leading cause of pediatric death and disability. Abusive head trauma confers greater morbidity and mortality compared with accidental TBI. National trends reveal disproportionate involvement of minority children in the child welfare system.

Closing the Trauma Performance Improvement Loop With In-situ Simulation.

Introduction: Continuous performance improvement (PI) programs are essential for excellent trauma care. We incorporated PI identified from trauma cases into an in-situ simulation-based medical education curriculum. This is a proof-of-concept study exploring the efficacy of high-fidelity pediatric trauma simulations in improving self-reported provider comfort and knowledge for identified trauma PI issues.

Determining Outcomes in Nonpenetrating Trauma With qSOFA.

Introduction: The quick Sequential Organ Failure Assessment (qSOFA) score identifies patients with suspected infection at high risk for adverse outcomes. The qSOFA score is the sum of three variables (respiratory rate, systolic blood pressure, and Glasgow Coma Score) with binary thresholds. The role of qSOFA in predicting hospitalization outcomes in nonpenetrating trauma patients was determined at a level 1 and a level 2 trauma center.

A graded neonatal mouse model of necrotizing enterocolitis demonstrates that mild enterocolitis is sufficient to activate microglia and increase cerebral cytokine expression.

Background: Necrotizing enterocolitis (NEC) is an inflammatory gastrointestinal process that afflicts approximately 10% of preterm infants born in the United States each year, with a mortality rate of 30%. NEC severity is graded using Bell's classification system, from stage I mild NEC to stage III severe NEC. Over half of NEC survivors present with neurodevelopmental impairment during adolescence, a long-term complication that is poorly understood but can occur even after mild NEC.

Pediatric Traumatic Brain Injury Outcomes and Disparities During the COVID-19 Pandemic.

Background: To study the impact of the COVID-19 pandemic on traumatic brain injury (TBI) patient demographic, clinical and trauma related characteristics, and outcomes.

Methods: Retrospective chart review was conducted on pediatric TBI patients admitted to a Level I Pediatric Trauma Center between January 2015 and June 2022. The pre-COVID era was defined as January 1, 2015, through March 12, 2020.

Differential regulation of tetramerization of the AMPA receptor glutamate-gated ion channel by auxiliary subunits.

α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) auxiliary subunits are specialized, nontransient binding partners of AMPARs that modulate AMPAR channel gating properties and pharmacology, as well as their biogenesis and trafficking. The most well-characterized families of auxiliary subunits are transmembrane AMPAR regulatory proteins (TARPs), cornichon homologs (CNIHs), and the more recently discovered GSG1-L. These auxiliary subunits can promote or reduce surface expression of AMPARs (composed of GluA1-4 subunits) in neurons, thereby impacting their functional role in membrane signaling.

Differential regulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) receptor tetramerization by auxiliary subunits.

AMPA receptor (AMPAR) auxiliary subunits are specialized, non-transient binding partners of AMPARs that modulate their ion channel gating properties and pharmacology, as well as their biogenesis and trafficking. The most well characterized families of auxiliary subunits are transmembrane AMPAR regulatory proteins (TARPs) and cornichon homologs (CNIHs) and the more recently discovered GSG1-L. These auxiliary subunits can promote or reduce surface expression of AMPARs in neurons, thereby impacting their functional role in membrane signaling.

Juvenile Granulosa Cell Tumor Mimicking HAIR-AN in a 4-year-old: A Case Report.

Predominantly androgen secreting juvenile granulosa cell tumors (JGCT) are uncommon and few reports have been published. We present a case of a JGCT that presented with signs of prepubertal hyperandrogenism and insulin resistance to highlight the possible interaction between hyperandrogenemia and hyperinsulinism. A 4-year-old girl presented with acanthosis nigricans and hyperinsulinism, mimicking the hyperandrogenism, insulin resistance and acanthosis nigricans syndrome at an age much younger than is typical for this diagnosis.

A Young Child With Recurrent Pneumonia and Hemoptysis During the COVID-19 Pandemic.

In July 2020, a previously healthy 6-year-old boy was evaluated in a pulmonary clinic in New York after two episodes of pneumonia in the previous 3 months. For each episode, the patient presented with cough, fever, and hemoptysis, all of which resolved with antibiotic therapy and supportive care. The patient never experienced dyspnea during these episodes of pneumonia.

Automated liquid handling robot for rapid lateral flow assay development.

The lateral flow assay (LFA) is one of the most popular technologies on the point-of-care diagnostics market due to its low cost and ease of use, with applications ranging from pregnancy to environmental toxins to infectious disease. While the use of these tests is relatively straightforward, significant development time and effort are required to create tests that are both sensitive and specific. Workflows to guide the LFA development process exist but moving from target selection to an LFA that is ready for field testing can be labor intensive, resource heavy, and time consuming.

A Novel Malaria Lateral Flow Assay for Detecting Plasmodium falciparum Lactate Dehydrogenase in Busia, Uganda.

Rapid diagnostic tests (RDTs) for Plasmodium falciparum commonly detect histidine-rich protein 2 (HRP-2), but HRP-2 deletions are increasingly recognized. We evaluated a prototype test detecting parasite lactate dehydrogenase (pLDH) and compared it to commercially available RDTs at a health facility in Uganda, using quantitative polymerase chain reaction as a gold standard. The prototype pLDH test had a high sensitivity for infections with at least 100 parasites/µL (98%), comparable to HRP-2, and greater than an existing pLDH RDT (89%).

Antibody Screening Results for Anti-Nucleocapsid Antibodies Toward the Development of a Lateral Flow Assay to Detect SARS-CoV-2 Nucleocapsid Protein.

The global COVID-19 pandemic has created an urgent demand for large numbers of inexpensive, accurate, rapid, point-of-care diagnostic tests. Analyte-based assays are suitably rapid and inexpensive and can be rapidly mass-produced, but for sufficiently accurate performance, they require highly optimized antibodies and assay conditions. We used an automated liquid handling system, customized to handle arrays of lateral flow (immuno)assays (LFAs) in a high-throughput screen, to identify anti-nucleocapsid antibodies that will perform optimally in an LFA.

Field evaluation of a prototype tuberculosis lipoarabinomannan lateral flow assay on HIV-positive and HIV-negative patients.

Detection of tuberculosis at the point-of-care (POC) is limited by the low sensitivity of current commercially available tests. We describe a diagnostic accuracy field evaluation of a prototype urine Tuberculosis Lipoarabinomannan Lateral Flow Assay (TB-LAM LFA) in both HIV-positive and HIV-negative patients using fresh samples with sensitivity and specificity as the measures of accuracy. This prototype combines a proprietary concentration system with a sensitive LFA.

Voltage dependent allosteric modulation of IPSCs by benzodiazepines.

GABA receptors (GABAR) are inhibitory ion channels ubiquitously expressed in the central nervous system and play critical roles in brain development and function. Benzodiazepines are positive allosteric modulators of GABAR, enhancing channel opening frequency when GABA is bound to the receptor. Midazolam is a commonly used benzodiazepine.

Sensitivity enhancement in lateral flow assays: a systems perspective.

Lateral flow assays (LFAs) are rapid, inexpensive, easy-to-manufacture and -use tests widely employed in medical and environmental applications, particularly in low resource settings. Historically, LFAs have been stigmatized as having limited sensitivity. However, as their global usage expands, extensive research has demonstrated that it is possible to substantially improve LFA sensitivity without sacrificing their advantages.

Input-specific maturation of NMDAR-mediated transmission onto parvalbumin-expressing interneurons in layers 2/3 of the visual cortex.

Parvalbumin-expressing (PV) GABAergic interneurons regulate local circuit dynamics. In terms of the excitation driving PV interneuron activity, the N-methyl-d-aspartate receptor (NMDAR)-mediated component onto PV interneurons tends to be smaller than that onto pyramidal neurons but makes a significant contribution to their physiology and development. In the visual cortex, PV interneurons mature during the critical period.

Improving Lateral Flow Assay Performance Using Computational Modeling.

The performance, field utility, and low cost of lateral flow assays (LFAs) have driven a tremendous shift in global health care practices by enabling diagnostic testing in previously unserved settings. This success has motivated the continued improvement of LFAs through increasingly sophisticated materials and reagents. However, our mechanistic understanding of the underlying processes that drive the informed design of these systems has not received commensurate attention.

Analytical Tools to Improve Optimization Procedures for Lateral Flow Assays.

Immunochromatographic or lateral flow assays (LFAs) are inexpensive, easy to use, point-of-care medical diagnostic tests that are found in arenas ranging from a doctor's office in Manhattan to a rural medical clinic in low resource settings. The simplicity in the LFA itself belies the complex task of optimization required to make the test sensitive, rapid and easy to use. Currently, the manufacturers develop LFAs by empirical optimization of material components (e.

Intestinal Metaplasia of the Esophagus in Children With Esophageal Atresia.

Objectives: Patients with esophageal atresia/tracheoesophageal fistula (EA-TEF) can develop Barrett esophagus as a long-term consequence of their condition. Intestinal metaplasia (IM), a risk factor for developing adenocarcinoma of the esophagus, has not been well characterized in the pediatric population.

Methods: Retrospective review of patients with EA-TEF followed at 3 academic pediatric centers between the years 1997 and 2014.

Comparative outcome analysis of the management of pediatric intussusception with or without surgical admission.

Background: Controversy persists about the need to admit patients after successful reduction of intussusception. Our hypothesis is that pediatric intussusception can be managed with discharge from the emergency department (ED) after reduction without increasing morbidity, yielding significant cost savings.

Methods: A chart review over 10 years was performed at two Canadian institutions.

Formal research training during surgical residency: scaffolding for academic success.

Background: The purpose of this study was to determine the impact of a formal surgical research program (leading to a postgraduate degree) during residency, on future research productivity.

Methods: We surveyed all North American graduates of the McGill University general surgery residency program between 1987 and 2005. The survey included questions on research involvement before, during, and after general surgery residency.

Fluorescence resonance energy transfer glucose sensor from site-specific dual labeling of glucose/galactose binding protein using ligand protection.

Background: Site-selective modification of proteins at two separate locations using two different reagents is highly desirable for biosensor applications employing fluorescence resonance energy transfer (FRET), but few strategies are available for such modification. To address this challenge, sequential selective modification of two cysteines in glucose/galactose binding protein (GGBP) was demonstrated using a technique we call "ligand protection."

Method: In this technique, two cysteines were introduced in GGBP and one cysteine is rendered inaccessible by the presence of glucose, thus allowing sequential attachment of two different thiol-reactive reagents.

Antibiotics administration before enema reduction of intussusception: is it necessary?

Background: Some centers advocate using antibiotics before enema reduction to prevent septic complications. Our objective was to determine whether using antibiotics before reduction provided any improvement in outcomes.

Methods: With institutional review board approval, patients from 2 centers were compared: 1 where antibiotics were administered, and one where they were not.

AMPAR removal underlies Abeta-induced synaptic depression and dendritic spine loss.

Beta amyloid (Abeta), a peptide generated from the amyloid precursor protein (APP) by neurons, is widely believed to underlie the pathophysiology of Alzheimer's disease. Recent studies indicate that this peptide can drive loss of surface AMPA and NMDA type glutamate receptors. We now show that Abeta employs signaling pathways of long-term depression (LTD) to drive endocytosis of synaptic AMPA receptors.