INTRODUCTIONNecrotizing enterocolitis (NEC) is an inflammatory bowel disease of neonates and remains one of the most common gastrointestinal emergencies in newborn infants [1] . Onset of NEC is often within the first three months of life and neonates who are of extremely low birth weight (< 1000 g) and under 28 wk gestation are the most susceptible [2] . Full term neonates account for 10% of all NEC cases while premature infants account for 90% [3] . With an incidence rate of 1%-5% for all newborns admitted to the NICU [1] , a prevalence of 7%-14% of very low birth weight infants (VLBW, 500-1500 g) [4] and a mortality rate approaching 20%-50% [5] , NEC continues to represent a significant clinical problem. In Canada, the incidence rate is 1.8 per 100 live births with a prevalence of 7% of VLBW infants [1] . Advances in obstetric and neonatal care have improved survival rates for smaller, more immature infants, and as more VLBW preterm infants survive the neonatal period, the population at risk for NEC increases [1] .No consistent association between sex, race, and rates of NEC has been identified. However, male VLBW infants and black infants are at greater risk of death [6] . Due to inadequate treatments and no effective preventative strategy, an estimated 20%-40% of babies with NEC require surgery [1] and 10%-30% experience significant morbidity including neurodevelopmental impairment, vision and hearing impairment, failure to thrive, feeding abnormalities, diarrhea, bowel obstruction, and short bowel syndrome [1,2,7] . The case fatality rate with surgical intervention is as high as 50% [1] . NEC is also a financial burden to the health care system with yearly hospital charges reported to be as high as $6.5 million in the US [8] . Thus, NEC continues to be an important health issue for preterm neonates. DIAGNOSIS Clinical signs and symptomsThe onset of NEC can occur suddenly within a few AbstractNecrotizing enterocolitis is an inflammatory bowel disease of neonates with significant morbidity and mortality in preterm infants. Due to the multifactorial nature of the disease and limitations in disease models, early diagnosis remains challenging and the pathogenesis elusive. Although preterm birth, hypoxic-ischemic events, formula feeding, and abnormal bacteria colonization are established risk factors, the role of genetics and vasoactive/inflammatory mediators is unclear. Consequently, treatments do not target the specific underlying disease processes and are symptomatic and surgically invasive. Breast-feeding is the most effective preventative measure. Recent advances in the prevention of necrotizing enterocolitis have focused on bioactive nutrients and trophic factors in human milk. Development of new disease models including the aspect of prematurity that consistently predisposes neonates to the disease with multiple risk factors will improve our understanding of the pathogenesis and lead to discovery of innovative therapeutics.

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Background: COVID serological tests are essential to determine the overall seroprevalence of a population, and to facilitate exposure estimates within that population. Methods: We performed a head-to-head assessment of enzyme immunoassays (EIA) and point of care lateral flow assays (POCT) to detect SARS-CoV-2 antibodies. Demographics, symptoms, co-morbidities, treatment, and mortality of patients whose sera was used were also reviewed. Results: Six EIAs (Abbott, Affinity, BioRad, DiaSorin, Euroimmun, and Roche), and six POCTs (BTNX, Biolidics, Deep Blue, Genrui, Getein BioTech, and Innovita) were evaluated for the detection of SARS-CoV-2 antibodies in known COVID-19 infected individuals. Sensitivity of EIAs ranged from 50-100%, with only four assays having overall sensitivities >95% after 21 days post symptom onset. Notably, cross-reactivity with other respiratory viruses (PIV-4 (n=5), hMPV (n=3), rhinovirus/enterovirus (n=1), CoV-229E (n=2), CoV-NL63 (n=2), and CoV-OC43 (n=2) was observed; however, overall specificity for EIAs was good (92-100%; where all but one assay had specificity above 95%). POCTs were 0-100% sensitive >21 days post onset, with specificity ranging from 96-100%. However, many POCTs had faint banding and were often difficult to interpret. Conclusions: Serology assays can detect SARS-CoV-2 antibodies as early as 10 days post onset. Serology assays vary in their sensitivity based on the marker (IgA/M vs. IgG vs. total) and by manufacturer; however, overall only 4 EIA and 4 POCT assays had sensitivities >95% >21 days post symptom onset. Cross-reactivity with other seasonal coronaviruses is of concern. The use of serology assays should not be used for the diagnosis of acute infection, but rather for use in carefully designed serosurveys to facilitate understanding of seroprevalence in a population and to identify previous exposure to SARS-CoV-2.

The clinically approved antioxidant cardioprotective agent dexrazoxane (ICRF-187) was examined for its ability to protect neonatal rat cardiac myocytes from doxorubicin-induced damage. Doxorubicin is thought to induce oxidative stress on the heart muscle, both through reductive activation to its semiquinone form, and by the production of hydroxyl radicals mediated by its complex with iron. Hydrolyzed dexrazoxane metabolites prevent site-specific iron-based oxygen radical damage by displacing iron from doxorubicin and chelating free and loosely bound iron. The mitochondrial stain MitoTracker Green FM and doxorubicin were shown by epifluorescence microscopy to accumulate in the myocyte mitochondria. An epifluorescence microscopic image analysis method to measure mitochondrial damage was developed using the mitochondrial membrane potential sensing ratiometric dye JC-1. This method was used to show that dexrazoxane protected against doxorubicin-induced depolarization of the myocyte mitochondrial membrane. Dexrazoxane also attenuated doxorubicin-induced oxidation of intracellular dichlorofluorescin. Annexin V-FITC/propidium iodide staining of myocytes was used to demonstrate that, depending on the concentration, doxorubicin caused both apoptotic and necrotic damage. These results suggest that doxorubicin may be cardiotoxic by damaging the mitochondria and dexrazoxane may be protective by preventing iron-based oxidative damage.

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Gangliosides are integral to the structure and function of cell membranes. Ganglioside composition of the intestinal brush border and apical surface of the colon influences numerous cell processes including microbial attachment, cell division, differentiation, and signaling. Accelerated catabolism of ganglioside in intestinal disease results in increased proinflammatory signaling. Restoring proper structure and function to the diseased intestine can resolve inflammation, increase resistance to infection, and improve gut integrity to induce remission of conditions like necrotizing enterocolitis (NEC) and Crohn's disease (CD). Maintaining inactive state of disease may be achieved by reducing the rate that gangliosides are degraded or by increasing intake of dietary ganglioside. Collectively, the studies outlined in this paper indicate that the amount of gangliosides GM3 and GD3 in intestinal mucosa is decreased with inflammation, low level of GM3 is associated with higher production of proinflammatory signals, and ganglioside content of intestinal mucosa can be increased by dietary ganglioside.

A bowel protective effect of gangliosides is indicated by modulation of vasoactive mediators and proinflammatory signal suppression.

Impaired intestinal integrity characteristic of IBD results in increased permeability to bacterial antigens and decreased nutrient absorption. Intestinal integrity may be improved by dietary treatment with specific species of ganglioside. Ganglioside is a safe, bioavailable dietary compound that can be consumed to potentially improve quality of life in patients with IBD and treat other disorders involving altered ganglioside metabolism. This study was registered at clinicaltrials.gov as NCT02139709.