Virtual family-centered hospital rounds in the neonatal intensive care unit: protocol for a cluster randomized controlled trial.

BACKGROUND: Family-centered rounds is recognized as a best practice for hospitalized children, but it has only been possible for children whose families can physically be at the bedside during hospital rounds. The use of telehealth to bring a family member virtually to the child's bedside during hospital rounds is a promising solution. We aim to evaluate the impact of virtual family-centered hospital rounds in the neonatal intensive care unit on parental and neonatal outcomes. METHODS: This two-arm cluster randomized controlled trial will randomize families of hospitalized infants to have the option to use telehealth for virtual hospital rounds (intervention) or usual care (control). The intervention-arm families will also have the option to participate in hospital rounds in-person or to not participate in hospital rounds. All eligible infants who are admitted to this single-site neonatal intensive care unit during the study period will be included. Eligibility requires that there be an English-proficient adult parent or guardian. We will measure participant-level outcome data to test the impact on family-centered rounds attendance, parent experience, family-centered care, parent activation, parent health-related quality of life, length of stay, breastmilk feeding, and neonatal growth. Additionally, we will conduct a mixed methods implementation evaluation using the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework. DISCUSSION: The findings from this trial will increase our understanding about virtual family-centered hospital rounds in the neonatal intensive care unit. The mixed methods implementation evaluation will enhance our understanding about the contextual factors that influence the implementation and rigorous evaluation of our intervention. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05762835. Status: Not yet recruiting. First posted: March 10, 2023; last update posted: March 10, 2023.

Virtual Family-Centered Rounds in the Neonatal Intensive Care Unit: Protocol for a Cluster Randomized Controlled Trial.

Background: Family-centered rounds is recognized as a best practice for hospitalized children, but it has only been possible for children whose families can physically be at the bedside during hospital rounds. The use of telehealth to bring a family member virtually to the child’s bedside during rounds is a promising solution. We aim to evaluate the impact of virtual family-centered rounds in the neonatal intensive care unit on parental and neonatal outcomes. Methods: This two-arm cluster randomized controlled trial will randomize families of hospitalized infants to have the option to use telehealth for virtual rounds (intervention) or usual care (control). The intervention-arm families will also have the option to participate in rounds in-person or to not participate in rounds. All eligible infants who are admitted to this single-site neonatal intensive care unit during the study period will be included. Eligibility requires that there be an English-proficient adult parent or guardian. We will measure participant-level outcome data to test the impact on family-centered rounds attendance, parent experience, family-centered care, parent activation, parent health-related quality of life, length of stay, breastmilk feeding, and neonatal growth. Additionally, we will conduct a mixed methods implementation evaluation using the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework. Discussion: The findings from this trial will increase our understanding about virtual family-centered rounds in the neonatal intensive care unit. The mixed methods implementation evaluation will enhance our understanding about the contextual factors that influence the implementation and rigorous evaluation of our intervention. Trial registration: ClinicalTrials.gov Identifier: NCT05762835. Status: Not yet recruiting. First Posted: 3/10/2023; Last Update Posted: 3/10/2023.

MicroRNAs are Necessary for BMP-7-induced Dendritic Growth in Cultured Rat Sympathetic Neurons.

Neuronal connectivity is dependent on size and shape of the dendritic arbor. However, mechanisms controlling dendritic arborization, especially in the peripheral nervous system, are not completely understood. Previous studies have shown that bone morphogenetic proteins (BMPs) are important initiators of dendritic growth in peripheral neurons. In this study, we examined the hypothesis that post-transcriptional regulation mediated by microRNAs (miRNAs) is necessary for BMP-7-induced dendritic growth in these neurons. To examine the role of miRNAs in BMP-7-induced dendritic growth, microarray analyses was used to profile miRNA expression in cultured sympathetic neurons from the superior cervical ganglia of embryonic day 21 rat pups at 6 and 24 h after treatment with BMP-7 (50 ng/mL). Our data showed that BMP-7 significantly regulated the expression of 43 of the 762 miRNAs. Of the 43 miRNAs, 22 showed robust gene expression; 14 were upregulated by BMP-7 and 8 were downregulated by BMP-7. The expression profile for miR-335, miR-664-1*, miR-21, and miR-23b was confirmed using qPCR analyses. Functional studies using morphometric analyses of dendritic growth in cultured sympathetic neurons transfected with miRNA mimics and inhibitors indicated that miR-664-1*, miR-23b, and miR-21 regulated early stages of BMP-7-induced dendritic growth. In summary, our data provide evidence for miRNA-mediated post-transcriptional regulation as important downstream component of BMP-7 signaling during early stages of dendritic growth in sympathetic neurons.

Repurposing the KCa3.1 inhibitor senicapoc for Alzheimer's disease.

OBJECTIVE: Microglia play a pivotal role in the initiation and progression of Alzheimer's disease (AD). We here tested the therapeutic hypothesis that the Ca2+-activated potassium channel KCa3.1 constitutes a potential target for treating AD by reducing neuroinflammation. METHODS: To determine if KCa3.1 is relevant to AD, we tested if treating cultured microglia or hippocampal slices with Aß oligomer (AßO) activated KCa3.1 in microglia, and if microglial KCa3.1 was upregulated in 5xFAD mice and in human AD brains. The expression/activity of KCa3.1 was examined by qPCR, Western blotting, immunohistochemistry, and whole-cell patch-clamp. To investigate the role of KCa3.1 in AD pathology, we resynthesized senicapoc, a clinically tested KCa3.1 blocker, and determined its pharmacokinetic properties and its effect on microglial activation, Aß deposition and hippocampal long-term potentiation (hLTP) in 5xFAD mice. RESULTS: We found markedly enhanced microglial KCa3.1 expression/activity in brains of both 5xFAD mice and AD patients. In hippocampal slices, microglial KCa3.1 expression/activity was increased by AßO treatment, and its inhibition diminished the proinflammatory and hLTP-impairing activities of AßO. Senicapoc exhibited excellent brain penetrance and oral availability, and in 5xFAD mice, reduced neuroinflammation, decreased cerebral amyloid load, and enhanced hippocampal neuronal plasticity. INTERPRETATION: Our results prompt us to propose repurposing senicapoc for AD clinical trials, as senicapoc has excellent pharmacological properties and was safe and well-tolerated in a prior phase-3 clinical trial for sickle cell anemia. Such repurposing has the potential to expedite the urgently needed new drug discovery for AD.