Better Together: Long-term Behaviors and Perspectives after a Practitioner-Family Writing Intervention in Clinical Practice.

BACKGROUND: An expressive writing intervention, the Three-minute Mental Makeover (3MMM), was previously associated with reduced stress for practitioners, patients, and families. The goal of this follow-up study was to evaluate long-term use of writing and perspectives after participation in the 3MMM. METHODS: The original study involved patients and families in the neonatal and pediatric Intensive Care Units, inpatient units, and outpatient clinics of a children's hospital. Health-care practitioners led the intervention, writing concurrently with patients and families using the 3MMM intervention. Follow-up contact by phone was attempted for all original patient/family participants 12 to 18 months after completing the exercise. Practitioners were contacted via email 24 months after the original study. Participants were surveyed about the 3MMM and continued use of writing to cope with stressful situations. Original and follow-up survey responses were compared using the Mann-Whitney test. RESULTS: Of the 96 original patient/family members, 61 individuals were reached, remembered the 3MMM, and agreed to participate in the follow-up study. Among the 61 participants, 52 (85%) agreed that the 3MMM had been helpful. Thirty-six (59%) reported using writing to help cope with stress at follow-up, compared to only 23 (38%) at baseline (P = 0.005). The majority of clinicians (87%) also continued to use the 3MMM in clinical practice following the original 3MMM study period and ranked it as both feasible (75%) and worth the time investment (75%). CONCLUSION: The 3MMM demonstrated long-term perceived benefits and behavior changes. Findings provide preliminary support for using the 3MMM in routine clinical practice.

Migration of cyclohexanone and 3,3,5-trimethylcyclohexanone from a neonatal enteral feeding system into human milk.

OBJECTIVE: Estimate the migration of volatile organic compounds (VOCs) which have been identified by the EPA as a public health concern, from the enteral feeding system into human milk. STUDY DESIGN: Unfortified human milk samples were infused through an enteral feeding system with varying duration of infusion, incubator temperature, and pre-infusion tube priming. Purge & Trap analysis and GC/MS were used to identify the VOC profile of milk pre- and post-infusion. RESULT: Cyclohexanone and 3,3,5-trimethylcyclohexanone (3,3,5-TMC) accumulated significantly in milk samples post-infusion. Duration of infusion had a significant effect on VOC accumulation (p = 0.001). Accumulation patterns of cyclohexanone and 3,3,5-TMC differed significantly based on milk type (donor vs. mother's own milk). CONCLUSIONS: VOCs, migrate from plastic-based feeding equipment into human milk. Based on these findings, limiting the duration of feeding infusion would reduce VOC exposure derived from enteral feeding in the neonatal intensive care unit.

Exposure to Morphine and Caffeine Induces Apoptosis and Mitochondrial Dysfunction in a Neonatal Rat Brain.

Background: Preterm infants experience rapid brain growth during early post-natal life making them vulnerable to drugs acting on central nervous system. Morphine is administered to premature neonates for pain control and caffeine for apnea of prematurity. Simultaneous use of morphine and caffeine is common in the neonatal intensive care unit. Prior studies have shown acute neurotoxicity with this combination, however, little information is available on the mechanisms mediating the neurotoxic effects. The objective of this study was to determine the effects of morphine and caffeine, independently and in combination on mitochondrial dysfunction (Drp1 and Mfn2), neural apoptosis (Bcl-2, Bax, and cell damage) and endothelin (ET) receptors (ETA and ETB) in neonatal rat brain. Methods: Male and female rat pups were grouped separately and were divided into four different subgroups on the basis of treatments-saline (Control), morphine (MOR), caffeine (CAFF), and morphine + caffeine (M+C) treatment. Pups in MOR group were injected with 2 mg/kg morphine, CAFF group received 100 mg/kg caffeine, and M+C group received both morphine (2 mg/kg) and caffeine (100 mg/kg), subcutaneously on postnatal days (PND) 3-6. Pups were euthanized at PND 7, 14, or 28. Brains were isolated and analyzed for mitochondrial dysfunction, apoptosis markers, cell damage, and ET receptor expression via immunofluorescence and western blot analyses. Results: M+C showed a significantly higher expression of Bax compared to CAFF or MOR alone at PND 7, 14, 28 in female pups (p < 0.05) and at PND 7, 14 in male pups (p < 0.05). Significantly (p < 0.05) increased expression of Drp1, Bax, and suppressed expression of Mfn2, Bcl-2 at PND 7, 14, 28 in all the treatment groups compared to the control was observed in both genders. No significant difference in the expression of ETA and ETB receptors in male or female pups was seen at PND 7, 14, and 28. Conclusion: Concurrent use of morphine and caffeine during the first week of life increases apoptosis and cell damage in the developing brain compared to individual use of caffeine and morphine.

Anti-apoptotic and Immunomodulatory Effect of CB2 Agonist, JWH133, in a Neonatal Rat Model of Hypoxic-Ischemic Encephalopathy.

Introduction: Neonatal HIE is associated with high morbidity and mortality. Current research, is focused on developing alternative treatments to therapeutic hypothermia for treatment of HIE. The endocannabinoid system is known to be influential in neuronal protection. Activation of brain CB2 receptors, has been shown to reduce inflammatory markers and decrease infarct volume in adult cerebral ischemic models. Methods: Rat pups were divided into six groups: 1-Placebo; 2-JWH133; 3-HIE + Placebo; 4-HIE + JWH133; 5-HIE + Hypothermia + Placebo; and 6-HIE + Hypothermia + JWH133. HIE was induced in in groups 3-6 by right carotid ligation on postnatal day 7 followed by placement in a hypoxic chamber. Pups in groups 5 and 6 were treated with hypothermia. Western blot analysis was used to analyze brain tissue for acute inflammatory markers (IL-6, TNFα, MIP1α, and RANTES), immunoregulatory cytokines (TGFß and IL-10), and CB2 receptor expression. DNA fragmentation in the brains of pups was determined via TUNEL staining post HIE. Results: The combination of JWH133 and hypothermia significantly reduced tumor necrosis factor α (TNFα) (-57.7%, P = 0.0072) and macrophage inflammatory protein 1α (MIP1α) (-50.0%, P = 0.0211) as compared to placebo. DNA fragmentation was also significantly reduced, with 6.9 ± 1.4% TUNEL+ cells in HIE+JWH133 and 12.9 ± 2.2% in HIE+Hypothermia + JWH133 vs. 16.6 ± 1.9% in HIE alone. No significant difference was noted between groups for the expression of interleukins 6 and 10, RANTES, or TGFß. After 8 h, CB2 receptor expression increased nearly 2-fold in the HIE and HIE + JWH133 groups (+214%, P = 0.0102 and +198%, P = 0.0209, respectively) over placebo with no significant change in the hypothermia groups. By 24 h post HIE, CB2 receptor expression was elevated over five times that of placebo in the HIE (P < 0.0001) and HIE + JWH133 (P = 0.0002) groups, whereas hypothermia treatment maintained expression similar to that of placebo animals. Conclusion: These results indicate that the combination of CB2 agonist and hypothermia may be neuroprotective in treating HIE, opening the door for further studies to examine alternative or adjuvant therapies to hypothermia.

Health Care Practitioners and Families Writing Together: The Three-Minute Mental Makeover.

INTRODUCTION: Expressive writing, the process of self-expression through writing, appears to have beneficial effects. Our hospital's narrative medicine group developed an expressive writing tool, the Three-Minute Mental Makeover (3MMM). OBJECTIVE: To evaluate the effectiveness of the 3MMM to reduce stress and optimize communication between health care practitioners and their patients/families. METHODS: Patients and families were recruited from a Chicago-area children's hospital from December 2016 through July 2017, from the neonatal intensive care unit, pediatric intensive care unit, inpatient pediatric unit, and outpatient pediatric clinics. Health care practitioners included a pediatric cardiologist, pediatric residents, child development specialists, and pediatric nurses. Practitioner and patient family participants completed prestudy and poststudy surveys to assess perceived stress and communication levels. Using a standardized script, practitioners led the 3MMM activity, writing concurrently with patients/families. Participants then shared their responses. Presurvey and postsurvey data were compared using nonparametric tests. RESULTS: Eight practitioners led 96 patient/family members in 3MMM activities and study surveys. At baseline, all patients, family members, and practitioners reported experiencing 1 or more symptoms of stress. After participating in the 3MMM, patients/family members and practitioners reported reduced stress compared with baseline (p < 0.001). A significant improvement in communication was reported by practitioners (p < 0.001). Eighty-eight percent of patients/families reported that the 3MMM activity was helpful, even though only 35% had used writing or journaling in the past. CONCLUSION: The 3MMM is a short writing exercise that reduces stress for practitioners, patients, and families. Future studies may help determine long-term effects of the 3MMM.

Neuroprotective Effect of IRL-1620, an Endothelin B Receptor Agonist, on a Pediatric Rat Model of Middle Cerebral Artery Occlusion.

Objective: The purpose of this study was to determine the potential neuroprotective effect of endothelin B (ETB) receptor agonist IRL-1620 treatment in a pediatric model of ischemic stroke. Design: A prospective, animal model study. Setting: An experimental laboratory. Subjects: Three-month-old male Wistar Han rats. Interventions: The rats underwent permanent middle cerebral artery occlusion (MCAO). At 2, 4, and 6 h post MCAO, they were treated with saline, IRL-1620 (5 µg/kg, IV), and/or ETB antagonist BQ788 (1 mg/kg, IV). Measurements and Main Results: The rats were evaluated over the course of 7 days for neurological and motor deficit, cerebral blood flow (CBF), and infarct volume. Young rats treated with IRL-1620 following MCAO improved significantly in neurological and motor assessments as compared to the vehicle-treated group, as measured by neurological score (P = 0.00188), grip test (P < 0.0001), and foot-fault error (P = 0.0075). CBF in the infarcted hemisphere decreased by 45-50% in all groups immediately following MCAO. After 7 days, CBF in the infarcted hemisphere of the IRL-1620 group increased significantly (P = 0.0007) when compared to the vehicle-treated group (+2.3 ± 23.3 vs. -45.4 ± 10.2%). Additionally, infarct volume was significantly reduced in IRL-1620-treated rats as compared to vehicle-treated rats (P = 0.0035, 41.4 ± 35.4 vs. 115.4 ± 40.9 mm3). Treatment with BQ788 blocked the effects of IRL-1620. Conclusions: IRL-1620 significantly reduced neurological and motor deficit as well as infarct volume while increasing CBF in a pediatric rat model of cerebral ischemia. These results indicate that selective ETB receptor stimulation may provide a novel therapeutic strategy in the treatment of pediatric ischemic stroke as has been demonstrated in adult ischemic stroke.

Maternal Cannabinoid Use Alters Cannabinoid (CB1) and Endothelin (ETB) Receptor Expression in the Brains of Dams but Not Their Offspring.

According to the 2015 National Survey on Drug Use and Health, cannabis (marijuana) is the most commonly used recreational drug in the US. Among pregnant women aged 14-55 years, 3.4% were cannabis users. Presently, little is known about the neurodevelopmental effect of cannabis use during pregnancy and/or nursing on neonates. Endothelin (ET) is essential for normal development of the central nervous system (CNS). Decreases in ETB receptor expression correlate with a decline in nerve growth factor (NGF) and an increase in vascular endothelial growth factor (VEGF) in postnatal brain. Activation of ETB and cannabinoid 1 (CB1) receptors each promote neurogenesis and enhance angiogenesis, indicating that both ET and CB systems play a critical role during early CNS development. Hence the purpose of this study was to determine whether maternal CB abuse during pregnancy and lactation alters the expression of ETB receptors, CB1 receptors, VEGF, and NGF in the postnatal rat brain. Sixteen pregnant Sprague-Dawley rats were administered either saline or anandamide (AEA) at a dose of 3 mg/kg/day i.p. from gestational day 7 and continued through weaning on postnatal day (PND) 21. Rat pups were subdivided into 4 subgroups and sacrificed on PND 2, 7, 14, and 28. Brain tissue of the pups and dams (sacrificed on PND 21) was analyzed via Western blot for the expression of ETB receptors, CB1 receptors, VEGF, and NGF. AEA-exposed dams had significantly fewer live births (p = 0.027), and their pups presented with significantly lower body weights on PND 7 (p = 0.013) and PND 28 (p = 0.018). There was no significant difference noted in ETB receptor, CB1 receptor, NGF, or VEGF expression in the pup brains. In all pups, brain ETB receptor expression decreased and CB1 receptor expression increased with age. In the AEA-exposed dam brain, however, there was a decrease in ETB receptor (p = 0.043) and an increase in CB1 receptor expression (p = 0.033). AEA exposure during pregnancy appears to affect fetal viability and postnatal weight gain in offspring while not altering the expression patterns of ETB receptors, CB1 receptors, NGF, or VEGF in the pup brain. The observed trend to an increase in CB1 receptor expression concurrent with a decrease in ETB receptor expression in both dams and pups may point to a homeostatic regulation between these 2 systems in CNS development and neuroprotection.

Ghrelin levels in cord blood from concordant and discordant twin pairs: association with birth weight and postnatal catch-up growth.

OBJECTIVE: To determine whether cord blood ghrelin levels in discordant and concordant twins predict postnatal catch-up growth. METHODS: After obtaining parental consent, cord blood samples were collected at delivery for total ghrelin analysis. Infant weight, length and head circumference were obtained at birth, 2, 4, and 6 months of age. Data points post-discharge were obtained from the pediatrician's office or via parent contact. Pearson correlation evaluated the relationship between cord blood ghrelin levels and postnatal catch-up growth. RESULTS: There was a statistically significant correlation between cord blood ghrelin levels and birth weight among concordant twins, but not among the discordant twins. Cord blood ghrelin levels did not predict postnatal growth at 6 months of age overall, but did so in the subset of monochorionic, discordant pairs. CONCLUSION: Cord blood ghrelin levels did not correlate overall with birth size or postnatal catch-up growth in concordant and discordant twin pairs, but did so in selected subsets. Further studies are needed.

Outcomes of early nutrition support in extremely low-birth-weight infants.

BACKGROUND: Early nutrition intervention, both parenteral and enteral, is becoming a standard of care for the extremely low-birth-weight infant (ELBW; <1,000 g) in many neonatal intensive care units (NICU) across the United States. However, there are no published or widely accepted guidelines regarding nutrition support strategies for this population. Most NICU clinicians have developed their own guidelines, so nutrition practices vary widely. In an effort to standardize our practice, we implemented nutrition support guidelines for ELBW infants, initiating both parenteral nutrition (PN) and minimal enteral feedings (MEFs) within the first 24 hours of life, whenever possible. The purpose of this study was 2-fold: (1) to evaluate the adherence to the nutrition guidelines and (2) to compare pre- and postguideline outcomes such as time to regain birth weight, time to reach full enteral feedings, and average daily weight gains. METHODS: The study was conducted at a level III NICU from January 2002 until February 2003. Charts of 70 infants with a birth weight