Amnion responses to intrauterine inflammation and effects of inhibition of TNF signaling in preterm Rhesus macaque.

Intrauterine infection/inflammation (IUI) is a frequent complication of pregnancy leading to preterm labor and fetal inflammation. How inflammation is modulated at the maternal-fetal interface is unresolved. We compared transcriptomics of amnion (a fetal tissue in contact with amniotic fluid) in a preterm Rhesus macaque model of IUI induced by lipopolysaccharide with human cohorts of chorioamnionitis. Bulk RNA sequencing (RNA-seq) amnion transcriptomic profiles were remarkably similar in both Rhesus and human subjects and revealed that induction of key labor-mediating genes such as IL1 and IL6 was dependent on nuclear factor κB (NF-κB) signaling and reversed by the anti-tumor necrosis factor (TNF) antibody Adalimumab. Inhibition of collagen biosynthesis by IUI was partially restored by Adalimumab. Interestingly, single-cell transcriptomics, flow cytometry, and immunohistology demonstrated that a subset of amnion mesenchymal cells (AMCs) increase CD14 and other myeloid cell markers during IUI both in the human and Rhesus macaque. Our data suggest that CD14+ AMCs represent activated AMCs at the maternal-fetal interface.

A Pilot Single-Site Randomized Control Trial: Investigating the Use of Donor Milk in Late Preterm and Term Infants in the Neonatal Intensive Care Unit.

OBJECTIVE: We aimed to study donor milk (DM) supplementation when mother's own milk (MOM) was unavailable in term and late preterm infants (LPIs) admitted to the neonatal intensive care unit (NICU). We hypothesized that this study would be feasible, defined by the rate of consent, diet adherence, and study completion. We further hypothesized that compared with formula supplementation, DM supplementation, for no longer than 7 days from birth, would be associated with an increase in breastfeeding attempts and the percentage of MOM (MOM%) without adversely affecting growth. Breastfeeding attempts and MOM% were assessed over 48 hours at the end of the intervention, which was defined as NICU discharge or at the end of supplementation, whichever came sooner. STUDY DESIGN: This was a pilot study (n = 32). Infants with a gestational age > 34 weeks admitted to the NICU were included. Infants were randomized to one of two groups: human milk (MOM + DM) or formula (MOM + F). RESULTS: The consent rate was 52%. Adherence to the study diet was 97%, and completion was 100%. When the MOM + DM group was compared with the MOM + F group, there was no difference in breastfeeding attempts (median [interquartile range]: 3.5 [1.5-6] vs. 1.5 [0.5-4] times, p = 0.1) or MOM% (60 vs. 59%, p = 0.9). Weight and length at multiple time points were similar when the groups were compared. CONCLUSION: A study randomizing term and LPIs in the NICU to DM or formula when MOM was unavailable is feasible. It remains unclear if DM improves breastfeeding success in this population. KEY POINTS: · A study that randomizes term and late preterm infants in the NICU to DM or formula supplementation when mother's own milk is not available is feasible.. · It remains unclear if DM compared to formula supplementation improves direct breastfeeding.. · In general, growth was similar in infants who received DM or formula as a supplement..

A Pilot Single-Site Randomized Control Trial: Investigating the Use of Donor Milk in the Late Preterm and Term Infant in the Neonatal Intensive Care Unit.

Objective : We aimed to study the use of donor milk (DM) in term and late preterm infants (LPIs) when mother’s own milk (MOM) was unavailable. We hypothesized this study would be feasible and breastfeeding attempts and the percentage of MOM (MOM%) would increase with DM without adversely affecting growth. Study Design : This was a pilot study (n=32). Infants with gestational age >34 weeks admitted to the neonatal intensive care unit were included. Infants were randomized to: the human milk (MOM+DM) or formula (MOM+F) groups. Result : Consent rate was 52%. Breastfeeding attempts increased significantly over time in the MOM+DM group compared to the MOM+F group (group p=0.41, time p =0.02, group*time p=0.01) . Growth at multiple time points was similar when the two groups were compared. Conclusion : A study randomizing term infants and LPIs to DM or formula when MOM is unavailable is feasible. DM may increase breastfeeding attempts without compromising growth.

Video simulation to learn pediatric resuscitation skills tailored to a low resource setting: A pilot program in Iquitos, Peru.

INTRODUCTION: The Hospital Regional de Loreto in Peru partners with the University of California Los Angeles Global Health Program to enhance educational experiences for US and Peruvian trainees. University of California Los Angeles Pediatric faculty led intermittent in-person code simulation sessions for Peruvian residents, and there is a need for regular education on this topic. METHODS: University of California Los Angeles residents created a video simulation of a patient in respiratory distress. The video was presented to Hospital Regional de Loreto trainees in pediatrics. Stakeholder interviews and reuse of the video after initial presentation assessed acceptability of this mode of education by the site. Pre- and post-surveys using numerical rating scales evaluated the educational utility of this specific simulation video. Paired t-tests compared the pre- and post-surveys in the effectiveness of increasing the trainees' comfort of specific resuscitation skills. RESULTS: Stakeholder interviews revealed the video simulation was integrated into formal intern orientation trainings as well as used for resident and physician trainings multiple times in the year after the introduction. Twenty trainees completed the pre-intervention survey and 19 completed the post-intervention survey. Trainee comfort with code team leadership (2.6 ± 0.9, 3.5 ± 0.09, p = 0.03) and arrhythmia recognition/automated external defibrillator (AED) management (2.4 ± 0.9, 3.1 ± 0.9, p = 0.03) increased significantly with the video intervention. There was no significant difference in comfort with other skills. Overall, trainees rated the helpfulness of the video as an average of 4.2 (±1.1) out of 5. The most common positive feedback included the utility of reviewing medication dosing and the skill of performing chest compressions. The most common suggestions for improvement were to review more pathophysiology and simulate available resources at Hospital Regional de Loreto more realistically. CONCLUSION: E-learning is an acceptable mode of education in a resource-limited setting when tailored to the local context. This pilot project demonstrated short-term improvement in reported confidence and skills with some aspects of pediatric resuscitation.

Race and Ethnicity and Exclusive Breastfeeding Success.

Introduction: Breast milk is the ideal food for infants. However, at 6 months of age, <25% of infants in the United States are exclusively breastfed. While racial disparities in breastfeeding have been documented, questions remain about the contributions of paternal race and ethnicity to breastfeeding. Materials and Methods: This single-site, prospective study investigated the association of parental characteristics and exclusive breastfeeding (EBF). EBF and non-EBF (N-EBF) infants who were >35 weeks gestational age were compared at nursery discharge and ∼30 days of age. Results: At nursery discharge (n = 499), mean birth weight (±standard deviation [SD]) was greater in the EBF versus N-EBF cohort (3.4 ± 0.4 versus 3.3 ± 0.5 kg, p = 0.01). When compared to the N-EBF cohort, infants in the EBF cohort were significantly more likely to have the following characteristics: (1) vaginal birth; (2) non-Hispanic parents; (3) parents with higher socioeconomic status, and (4) parents who are English-speaking (p < 0.01 for all). Similar findings persisted at 30 days. Non-Hispanic parents were 2 (95% confidence interval [CI]: 1.4-3.3) and 3.5 (95% CI: 1.5-7.9) times more likely to exclusively breastfeed than Hispanic parents at nursery discharge and 30 days, respectively. At nursery discharge, families with a Hispanic mother and non-Hispanic father were more likely to EBF than families with a Hispanic mother and father (odds ratio 2.9, 95% CI: 1.1-7.6). In multivariate model, parental ethnicity was associated with EBF at discharge (p = 0.03) and 30 days (p = 0.02). Conclusion: Paternal ethnicity may influence EBF. Addressing disparities in EBF may warrant investigations into culturally inclusive and family-centered interventions.

Lack of utility of tracheal aspirates in the management of suspected pneumonia in intubated neonates.

OBJECTIVES: To evaluate the utility of tracheal aspirates in suspected pneumonia in intubated neonates and to measure the burden of antibiotic use associated with a positive tracheal aspirate culture. DESIGN: Retrospective cohort study between January 2016 and December 2017. SETTING: A level IV neonatal intensive care unit (NICU). PATIENTS: Intubated patients with a tracheal aspirate culture. METHODS: Data on temporally associated clinical measures of illness, laboratory and radiographic testing, and clinical demographic information were analyzed. RESULTS: Positive tracheal aspirate cultures were associated with lower birth weight and a normal immature to total neutrophil ratio (I/T ratio). Positive tracheal aspirates were not significantly associated with clinical, laboratory, or radiographic markers used in clinical practice to screen for infection. Despite the lack of positive clinical associations, a positive tracheal aspirate culture was associated with increased risk of prolonged antibiotic exposure. CONCLUSION: These findings suggest that positive tracheal aspirates do not always represent clinical infection and may result in unnecessary antibiotic exposure.

Synthesis and evaluation of (S)-[(18)F]fesetron in the rat brain as a potential PET imaging agent for serotonin 5-HT3 receptors.

Serotonin 5-HT3 receptors are involved in various brain functions including as an emesis target during cancer chemotherapy. We report here the development of (S)-2,3-dimethoxy-5-(3'-[(18)F]fluoropropyl)-N-(1-azabicyclo[2.2.2]oct-3-yl)benzamide ([(18)F]fesetron) as a potential PET imaging agent for serotonin 5-HT3 receptors. By radiolabeling((S)-2,3-dimethoxy-5-(3'-tosyloxypropyl)-N-(1-azabicyclo[2.2.2]oct-3-yl)benzamide) with fluorine-18, (S)-[(18)F]fesetron was obtained in 5 to 10% decay-corrected yields and with specific activities >74GBq/µmol at the end of radiosynthesis. PET imaging in rats showed low uptake of [(18)F]fesetron in the brain with retention of binding in the striatal and cerebellar regions. Using colliculi as a reference region, ratios were 3.4 for striata and 2.5 for cerebellum. Ex vivo brain PET analysis displayed binding of [(18)F]fesetron in the hippocampus, striatum and cerebellar regions. Cerebellar regions corresponded to area postrema and nucleus tract solitaris known to contain 5-HT3 receptors. Dorsal hippocampus showed the highest uptake with ratio of >17 with respect to colliculi, while area postrema and striata had ratios of >10. Thus, [(18)F]fesetron exhibited a unique binding profile to rat brain regions known to contain significant amounts of serotonin 5-HT3 receptors. However, the very low brain uptake limits its usefulness as a PET radiotracer in this animal model.

Synthesis and biological evaluation of 18F-Norfallypride in the rodent brain using PET imaging.

Norfallypride (N-[(2-pyrolidinyl)methyl]-2,3-dimethoxy-5-(3'-fluoropropyl)benzamide), an analog of fallypride, has been synthesized and evaluated as a potential PET imaging agent for dopamine receptors with increased subtype selectivity. In order to synthesize (18)F-Norfallypride, the substituted benzamide tosylate (S)-N-[(1-BOC-2-pyrolidinyl)methyl]-2,3-dimethoxy-5-(3'-tosyloxypropyl)-benzamide) was radiolabeled with (18)F using Kryptofix and K2CO3 in acetonitrile and deprotected with trifluoroacetic acid to yield (S)-(18)F-Norfallypride in approx. 10% radiochemical yields. Norfallypride exhibited an IC50 of 0.63µM for displacing (18)F-fallypride in rat brain slices. In vitro rat brain autoradiographic studies revealed weak binding of (18)F-norfallypride to striatal regions. PET imaging in rats showed low brain uptake of (18)F-norfallypride in the rat brain. Ex vivo brain PET analysis displayed binding of (18)F-norfallypride in several brain regions. With respect to the cerebellum, ex vivo PET ratios were: striatum>3; hypothalamus>2; hippocampus~2; cerebellar nuclei >2 while autoradiographic ratios were 14, 9, 4 and 6 respectively. (18)F-Norfallypride exhibited a unique binding profile to rat brain regions known to contain significant amounts of dopamine D3 and serotonin 5HT3 receptors. Efforts are currently under way to increase brain permeability and fully characterize the binding of (18)F-norfallypride in vivo.