Perinatal Azithromycin Provides Limited Neuroprotection in an Ovine Model of Neonatal Hypoxic-Ischemic Encephalopathy.

BACKGROUND: Hypoxic-ischemic brain injury/encephalopathy affects about 1.15 million neonates per year, 96% of whom are born in low- and middle-income countries. Therapeutic hypothermia is not effective in this setting, possibly because injury occurs significantly before birth. Here, we studied the pharmacokinetics, safety, and efficacy of perinatal azithromycin administration in near-term lambs following global ischemic injury to support earlier treatment approaches. METHODS: Ewes and their lambs of both sexes (n=34, 141-143 days) were randomly assigned to receive azithromycin or placebo before delivery as well as postnatally. Lambs were subjected to severe global hypoxia-ischemia utilizing an acute umbilical cord occlusion model. Outcomes were assessed over a 6-day period. RESULTS: While maternal azithromycin exhibited relatively low placental transfer, azithromycin-treated lambs recovered spontaneous circulation faster following the initiation of cardiopulmonary resuscitation and were extubated sooner. Additionally, peri- and postnatal azithromycin administration was well tolerated, demonstrating a 77-hour plasma elimination half-life, as well as significant accumulation in the brain and other tissues. Azithromycin administration resulted in a systemic immunomodulatory effect, demonstrated by reductions in proinflammatory IL-6 (interleukin-6) levels. Treated lambs exhibited a trend toward improved neurodevelopmental outcomes while histological analysis revealed that azithromycin supported white matter preservation and attenuated inflammation in the cingulate and parasagittal cortex. CONCLUSIONS: Perinatal azithromycin administration enhances neonatal resuscitation, attenuates neuroinflammation, and supports limited improvement of select histological outcomes in an ovine model of hypoxic-ischemic brain injury/encephalopathy.

Defining Longer-Term Outcomes in an Ovine Model of Moderate Perinatal Hypoxia-Ischemia.

Hypoxic-ischemic encephalopathy (HIE) is the leading cause of neonatal morbidity and mortality worldwide. Approximately 1 million infants born with HIE each year survive with cerebral palsy and/or serious cognitive disabilities. While infants born with mild and severe HIE frequently result in predictable outcomes, infants born with moderate HIE exhibit variable outcomes that are highly unpredictable. Here, we describe an umbilical cord occlusion (UCO) model of moderate HIE with a 6-day follow-up. Near-term lambs (n = 27) were resuscitated after the induction of 5 min of asystole. Following recovery, lambs were assessed to define neurodevelopmental outcomes. At the end of this period, lambs were euthanized, and brains were harvested for histological analysis. Compared with prior models that typically follow lambs for 3 days, the observation of neurobehavioral outcomes for 6 days enabled identification of animals that recover significant neurological function. Approximately 35% of lambs exhibited severe motor deficits throughout the entirety of the 6-day course and, in the most severely affected lambs, developed spastic diparesis similar to that observed in infants who survive severe neonatal HIE (severe, UCOs). Importantly, and similar to outcomes in human neonates, while initially developing significant acidosis and encephalopathy, the remainder of the lambs in this model recovered normal motor activity and exhibited normal neurodevelopmental outcomes by 6 days of life (improved, UCOi). The UCOs group exhibited gliosis and inflammation in both white and gray matters, oligodendrocyte loss, neuronal loss, and cellular death in the hippocampus and cingulate cortex. While the UCOi group exhibited more cellular death and gliosis in the parasagittal cortex, they demonstrated more preserved white matter markers, along with reduced markers of inflammation and lower cellular death and neuronal loss in Ca3 of the hippocampus compared with UCOs lambs. Our large animal model of moderate HIE with prolonged follow-up will help further define pathophysiologic drivers of brain injury while enabling identification of predictive biomarkers that correlate with disease outcomes and ultimately help support development of therapeutic approaches to this challenging clinical scenario.

Adding a Parent to the Brain Tumor Team: Evaluating a Peer Support Intervention for Parents of Children With Brain Tumors.

Childhood brain tumors often present profound challenges to patients and families. To address these challenges, the California Chapter of the Pediatric Brain Tumor Foundation provides hospital-based support services to parents of children with brain tumors from a Veteran Parent (VP). This mixed-methods, cross-sectional study was designed to evaluate the effectiveness of the intervention using validated tools to compare parental resilience and impact of illness on the family between parents who met with the VP and those who did not. Two-tailed t tests assessed significant differences in scores on the PedsQL Family Impact module and Connor-Davidson Resilience Scale (CD-RISC-25). Additional qualitative data gleaned from focus groups with stakeholders (health care providers and parents) were analyzed using key constructs of social support theory with Atlas.ti. Although there were no significant differences in overall scores on the PedsQL Family Impact module or CD-RISC-25 between groups, parents in the intervention group scored better on items related to handling difficult decisions and painful feelings. Overarching themes emerged from focus groups around participants' experiences with the program and included informational and emotional support, peer parent relatedness, changed outlook, and empowerment. Results reveal the impact of peer parent support and need for emotional and instrumental support.

Cognitive Functioning, Health Screening Behaviors and Desire to Improve One's Health in Diabetic versus Healthy Older Women.

AIMS: To attempt to fill a gap in the literature on diabetic versus healthy older women on desire to improve one's health, health screening behaviors, and cognitive health. STUDY DESIGN: Between-subjects design. PLACE AND DURATION OF STUDY: Department of Psychology, California State University Northridge, between July 2013 and June 2015. METHODOLOGY: In this preliminary study, we compared 30 diabetic older women to 42 healthy older women (i.e., respondents who reported having no physical illnesses and not taking any medications) on: desire to improve their health (hypothesized as being higher in the diabetes group), receiving mammograms and regular health screenings (analyzed without any hypotheses, due to the lack of evidence on this topic), as well as cognitive functioning (hypothesized as lower in the diabetes group, based on prior research findings). Participants (N=72, mean age=69.29, SD=6.579, age range=50-90) were multiethnic, non-institutionalized women over the age of 50 residing in Los Angeles County who completed our research packet. The latter contained the first author's demographics list and her original structured interview protocol on older women's health, as well as the well-known Mini-Cog. RESULTS: The results of an Analysis of Variance (ANOVA) showed that, as hypothesized, diabetic women desired to improve their health more than the women in the control group [F (1,70)=11.87, p<.05, η2 =.15]. Additionally, upon implementing Chi-square analyses, we discovered that diabetic respondents were significantly more likely to receive mammograms [X2 (1)=5.87, p<.05] and general health screenings [X2 (1)=4.51, p<.05] than healthy women. Moreover, in contrast with prior literature's findings, cognitive health in the diabetic group obtained marginal significance in an ANOVA as being better than the cognitive health of the control group [F(1,68)=3.30, p=.06, η2 =.05]. CONCLUSION: We have established a significant relationship between diabetes and a) desire to improve one's health and b) health screening behaviors, as well as c) cognitive impairment (at a marginally significant level) among diabetic versus healthy women. This has important clinical and public health implications. Although the findings of prior research suggest that diabetic older women often experience impaired cognitive performance compared to healthy older women, our marginally significant results showed that the opposite is true, at least in our ethnically diverse sample of modest size. Moreover, we found that diabetic older women desired to improve their health significantly more than healthy women and pursued cancer screenings and general health screenings more than their healthy counterpart. The limited size of our sample does not allow for generalizations of our findings. Additional research with larger samples is definitely needed to investigate these topics further.