PURPOSE: The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 43 million people resulting in over 1 million deaths. Approximately 2% of cases in the United States are children, and in most cases the child is either asymptomatic or has mild symptoms. However, some pediatric cases can present with Multisystem Inflammatory Syndrome (MIS-C). Understanding the epidemiology, clinical presentation, and management of MIS-C related to SARS-CoV-2 will help to streamline early diagnosis and treatment, particularly in pediatric patients with complex medical conditions. METHODS: This scoping review adopted methods from the Joanna Briggs Institute (JBI) manual for evidence synthesis and preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews (PRISMA-ScR) guidelines. Primary studies of patients meeting the Centers for Disease Control and Prevention (CDC) criteria for MIS-C from December 31st, 2019 to Oct 5th, 2020 were identified using PubMed and Scopus. Articles were screened for eligibility, and data collection was conducted on those fulfilling inclusion criteria. RESULTS: Of 417 studies identified, 57 met inclusion criteria, accounting for 875 patients from 15 countries. Globally, 57% of children affected with MIS-C were males. The median age was 9 years old, ranging from 6 months to 21 years. Forty-five percent of the patients had underlying comorbidities including obesity and lung disease. Fever, conjunctivitis and GI symptoms were common. Most MIS-C patients had high biomarkers including troponin I, N-terminal prohormone of B-type natriuretic peptide (NT-proBNP), D-dimer, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), white blood cells (WBCs), interleukin 6 (IL-6), procalcitonin, and ferritin. The treatment for most patients included IVIG and inotropic support. CONCLUSION: MIS-C can be a unique and potentially life-threatening manifestation of SARS-CoV-2 in children and often requires medical intervention.

Rotarod test was performed to assess locomotive coordination of C57/Bl6 WT and βeIF4G1KO mice, over the course of 4 days (n=7, 5) (A). Body weight of 2-months-old male (B) and female (C) Rip-Cre WT, eIF4G1f/+, βeIF4G1HET, eIF4G1f/f and βeIF4G1KO (n=7, 8, 11, 7, 11 males; n=5, 5, 6, 5, 7 females). In vivo glucose tolerance (2 g/kg glucose, i.p.) was performed on 5months-old Male C57/Bl6 WT, eIF4G1f/f and βeIF4G1KO (n=7, 5, 5). Area under curve (AUC) of

During mitosis, tension develops across the centromere as a result of spindle-based forces. Metaphase tension may be critical in preventing mitotic chromosome segregation errors, however, the nature of force transmission at the centromere and the role of centromere mechanics in controlling metaphase tension remains unknown. We combined quantitative, biophysical microscopy with computational analysis to elucidate the mechanics of the centromere in unperturbed, mitotic human cells. We discovered that the mechanical stiffness of the human centromere matures during mitotic progression, which leads to amplified centromere tension specifically at metaphase. Centromere mechanical maturation is disrupted across multiple aneuploid cell lines, leading to a weak metaphase tension signal. Further, increasing deficiencies in centromere mechanical maturation are correlated with rising frequencies of lagging, merotelic chromosomes in anaphase, leading to segregation defects at telophase. Thus, we reveal a centromere maturation process that may be critical to the fidelity of chromosome segregation during mitosis.

Protein translation is essential for cell physiology, and dysregulation of this process has been linked to aging-related diseases such as type 2 diabetes. Reduced protein level of a requisite scaffolding protein of the initiation complex, eIF4G1, downstream of nutrients and insulin signaling is associated with diabetes in humans and mice. In the current study, we tested the hypothesis that eIF4G1 is critical for β-cell function and glucose homeostasis by genetically ablating eIF4G1 specifically in β-cells in vivo (βeIF4G1 knockout [KO]). Adult male and female βeIF4G1KO mice displayed glucose intolerance but normal insulin sensitivity. β-Cell mass was normal under steady state and under metabolic stress by diet-induced obesity, but we observed increases in proliferation and apoptosis in β-cells of βeIF4G1KO. We uncovered deficits in insulin secretion, partly due to reduced mitochondrial oxygen consumption rate, glucose-stimulated Ca2+ flux, and reduced insulin content associated with loss of eIF4E, the mRNA 5′ cap-binding protein of the initiation complex and binding partner of eIF4G1. Genetic reconstitution of eIF4E in single β-cells or intact islets of βeIF4G1KO mice recovers insulin content, implicating an unexplored role for eIF4G1/eIF4E in insulin biosynthesis. Altogether these data demonstrate an essential role for the translational factor eIF4G1 on glucose homeostasis and β-cell function.

Stroke-like migraine attacks after radiation therapy (SMART) syndrome is a rare, delayed complication of radiation therapy to the brain. We present a case of a 49-year-old female with a past medical history of malignant neoplasm of the brain status following resection and radiation. She initially presented with increased work of breathing. Initial labs and a chest X-ray were suggestive of aspiration pneumonia leading to sepsis. Upon hospitalization, seizure-like activity was noted. Electroencephalogram showed electrographic seizures originating from the left occipital and parietal lobe. She received numerous medications to control the seizures with minimal improvement. Magnetic resonance imaging was performed to characterize the origin of seizures, which showed extensive post-radiation changes including a new meningioma. The patient was subsequently managed with magnesium and Solu Medrol. After this regimen, her condition improved and there were no clinical seizures present.

Protein translation is essential for cell physiology, and dysregulation of this process has been linked to aging-related diseases such as type 2 diabetes. Reduced protein level of a requisite scaffolding protein of the initiation complex, eIF4G1, downstream of nutrients and insulin signaling, is associated with diabetes in both humans and mice. In the present study, we tested the hypothesis that eIF4G1 is critical for β-cell function and glucose homeostasis by genetically ablating eIF4G1 specifically in β-cells <i>in vivo</i> (βeIF4G1KO). Adult male and female βeIF4G1KO mice displayed glucose intolerance but normal insulin sensitivity. β-cell mass was normal under steady state and under metabolic stress by diet-induced obesity, but we observed increases in both proliferation and apoptosis in β-cells of βeIF4G1KO. We uncovered deficits in insulin secretion, partly due to reduced mitochondrial oxygen consumption rate, glucose-stimulated Ca²⁺ flux, and reduced insulin content associated with loss of eIF4E, the mRNA 5’-cap binding protein of the initiation complex and binding partner of eIF4G1. Genetic reconstitution of eIF4E in single β-cells or intact islets of βeIF4G1KO mice recovers insulin content, implicating an unexplored role for eIF4G1/eIF4E in insulin biosynthesis. Altogether these data demonstrate an essential role for the translational factor eIF4G1 on glucose homeostasis and β-cell function.

Protein translation is essential for cell physiology, and dysregulation of this process has been linked to aging-related diseases such as type 2 diabetes. Reduced protein level of a requisite scaffolding protein of the initiation complex, eIF4G1, downstream of nutrients and insulin signaling, is associated with diabetes in both humans and mice. In the present study, we tested the hypothesis that eIF4G1 is critical for β-cell function and glucose homeostasis by genetically ablating eIF4G1 specifically in β-cells <i>in vivo</i> (βeIF4G1KO). Adult male and female βeIF4G1KO mice displayed glucose intolerance but normal insulin sensitivity. β-cell mass was normal under steady state and under metabolic stress by diet-induced obesity, but we observed increases in both proliferation and apoptosis in β-cells of βeIF4G1KO. We uncovered deficits in insulin secretion, partly due to reduced mitochondrial oxygen consumption rate, glucose-stimulated Ca²⁺ flux, and reduced insulin content associated with loss of eIF4E, the mRNA 5’-cap binding protein of the initiation complex and binding partner of eIF4G1. Genetic reconstitution of eIF4E in single β-cells or intact islets of βeIF4G1KO mice recovers insulin content, implicating an unexplored role for eIF4G1/eIF4E in insulin biosynthesis. Altogether these data demonstrate an essential role for the translational factor eIF4G1 on glucose homeostasis and β-cell function.