SUMMARY Monkeypox (MPXV) and cowpox (CPXV) are emerging agents that cause severe human infections on an intermittent basis, and variola virus (VARV) has potential for use as an agent of bioterror. Vaccinia immune globulin (VIG) has been used therapeutically to treat severe poxvirus infections, but is in short supply. We generated a large panel of orthopoxvirus-specific human monoclonal Abs from immune subjects to investigate the molecular basis of broadly neutralizing antibody responses for diverse orthopoxviruses. Detailed analysis revealed the principal neutralizing antibody specificities that are cross-reactive for VACV, CPXV, MPXV and VARV and that are determinants of protection in murine challenge models. Optimal protection following respiratory or systemic infection required a mixture of Abs that targeted several membrane proteins, including proteins on enveloped and mature virion forms of virus. This work reveals orthopoxvirus targets for human Abs that mediate cross-protective immunity and identifies new candidate Ab therapeutic mixtures to replace VIG.

To quantify and contextualize the risk for coronavirus disease 2019 (COVID-19)related hospitalization and illness severity in type 1 diabetes. RESEARCH DESIGN AND METHODS We conducted a prospective cohort study to identify case subjects with COVID-19 across a regional health care network of 137 service locations. Using an electronic health record query, chart review, and patient contact, we identified clinical factors influencing illness severity. RESULTS We identified COVID-19 in 6,138, 40, and 273 patients without diabetes and with type 1 and type 2 diabetes, respectively. Compared with not having diabetes, people with type 1 diabetes had adjusted odds ratios of 3.90 (95% CI 1.75-8.69) for hospitalization and 3.35 (95% CI 1.53-7.33) for greater illness severity, which was similar to risk in type 2 diabetes. Among patients with type 1 diabetes, glycosylated hemoglobin (HbA 1c), hypertension, race, recent diabetic ketoacidosis, health insurance status, and less diabetes technology use were significantly associated with illness severity. CONCLUSIONS Diabetes status, both type 1 and type 2, independently increases the adverse impacts of COVID-19. Potentially modifiable factors (e.g., HbA 1c) had significant but modest impact compared with comparatively static factors (e.g., race and insurance) in type 1 diabetes, indicating an urgent and continued need to mitigate severe acute respiratory syndrome coronavirus 2 infection risk in this community. The medical community currently lacks sufficient data to adequately mitigate the impact of the novel coronavirus disease 2019 (COVID-19) in the type 1 diabetes community. At present, our knowledge is largely extrapolated from recent retrospective analyses of hospitalized patients (1-5), which have strongly suggested "diabetes" increases risk for COVID-19 morbidity and mortality. These studies did not, however, distinguish between type 1 diabetes and type 2 diabetesdtwo pathophysiologically distinct conditions. Although reports of COVID-19 in type 1 diabetes are emerging, the scope of these investigations to date has been limited by including only hospitalized

Background Oral colostrum priming (OCP) after birth in preterm infants is associated with improved weight gain and modification of the oral immuno-microbial environment. We hypothesized OCP would modify salivary immune peptides and the oral microbiota in preterm infants. Methods We conducted a prospective, randomized clinical trial to determine the effects of OCP on salivary immune peptide representation in preterm infants (<32 weeks completed gestation at birth). Saliva samples were collected prior to and after OCP. Salivary immune peptide representation was determined via mass spectroscopy. Oral microbiota representation was determined via sequencing of 16S rRNA gene. Results Neonates that received OCP (n = 48) had a 16-day reduction in the median length of hospitalization as compared to infants that did not receive OCP (n = 51). No differences in salivary immune peptide sequence representation prior to OCP between groups were found. Longitudinal changes in peptides were detected (lysozyme C, immunoglobulin A, lactoferrin) but were limited to a single peptide difference (alpha defensin 1) between primed and unprimed infants after OCP. We found no difference in microbial diversity between treatment groups at any time point, but diversity decreased significantly over time in both groups. OCP treatment marginally modified oral taxa with a decline in abundance of Streptococci in the OCP group at 30 days of life. Conclusions OCP had neither an effect on the salivary peptides we examined nor on overall oral bacterial diversity and composition. Infants that received OCP had a reduced length of hospitalization and warrants further investigation.

Summary Every year 15 million preterm infants are born, and most spend their first weeks in neonatal intensive care units (NICUs)[1]. Although essential for the support and survival of these infants, NICU sensory environments are dramatically different from those in which full-term infants mature, and, thus, likely impact the development of functional brain organization[2]. Yet, the integrity of sensory systems determines effective perception and behaviour[3,4]. In neonates, touch is a cornerstone of interpersonal interactions and sensory-cognitive development[5–7]. NICU treatments used to improve neurodevelopmental outcomes rely heavily on touch[8]. Yet, we understand little of how brain maturation at birth (i.e. prematurity) and quality of early-life experiences (e.g. supportive vs. painful touch) interact to shape the development of the somatosensory system[9]. Here, we identified the spatial, temporal and amplitude characteristics of cortical responses to light touch differentiating them from sham stimuli in full-term infants. We then utilized this data-driven analytical framework to show that the degree of prematurity at birth determines the extent to which brain responses to light touch (but not sham) are attenuated at the time of discharge from the hospital. Building on these results, we showed that when controlling for prematurity and analgesics, supportive experiences (e.g. breastfeeding, skin-to-skin care) are associated with stronger brain responses, whereas painful experiences (e.g. skin punctures, tube insertions) are associated with reduced brain responses to the same touch stimuli. Our results shed crucial insights into the mechanisms through which common early perinatal experiences may shape the somatosensory scaffolding of later perceptual, cognitive and social development.

Background: Diagnostic testing for chronic esophageal disorders rely on histopathology analysis of biopsies or uncomfortable transnasal catheters or wireless pH monitoring, which capture abnormal intraluminal refluxate. We therefore developed a balloon mucosal impedance (MI) catheter system that instantly detects changes in esophageal mucosal integrity during endoscopy over a long segment of the esophagus. We performed a prospective study to evaluate the ability of a balloon-incorporated MI catheter to detect and evaluate esophageal disorders, including gastroesophageal reflux disease (GERD) and eosinophilic esophagitis (EoE). Methods: We performed a prospective study of 69 patients undergoing esophagogastroduodenoscopy with or without wireless pH monitoring. Patients were classified as having GERD (erosive esophagitis or abnormal pH; n = 24), EoE (confirmed with pathology

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BACKGROUND Neonatal abstinence syndrome (NAS) is a postnatal opioid withdrawal syndrome. Factors associated with development of the syndrome are poorly understood; however, infant sex may influence the risk of NAS. Our objective was to determine if infant sex was associated with the development or severity of the syndrome in a large population-based cohort. METHODS This retrospective cohort study used vital statistics and prescription, outpatient, and inpatient administrative data for mothers and infants enrolled in the Tennessee Medicaid program between 2009 and 2011. Multivariable logistic regression models were used to evaluate the association between male sex and diagnosis of NAS, accounting for potential demographic and clinical confounders. NAS severity, as evidenced by hospital length of stay, was modeled by using negative binomial regression. RESULTS Of 102 695 infants, 927 infants were diagnosed with NAS (484 male subjects and 443 female subjects). Adjustments were made for the following: maternal age, race, and education; maternal hepatitis C infection, anxiety, or depression; in utero exposure to selective serotonin reuptake inhibitors and cigarettes; infant birth weight, small for gestational age, and year; and the interaction between opioid type and opioid amount. Male infants were more likely than female infants to be diagnosed with NAS (adjusted odds ratio, 1.18 [95% confidence interval, 1.05–1.33]) and NAS requiring treatment (adjusted odds ratio, 1.24 [95% confidence interval, 1.04–1.47]). However, there was no sex-based difference in severity for those diagnosed with NAS. CONCLUSIONS Treatment of NAS should be tailored to an infant’s individual risk for the syndrome. Clinicians should be mindful that male sex is an important risk factor in the diagnosis of NAS.

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