Imaging the large-scale and cellular response to focal traumatic brain injury in mouse neocortex.

Traumatic brain injury (TBI) affects neural function at the local injury site and also at distant, connected brain areas. However, the real-time neural dynamics in response to injury and subsequent effects on sensory processing and behaviour are not fully resolved, especially across a range of spatial scales. We used in vivo calcium imaging in awake, head-restrained male and female mice to measure large-scale and cellular resolution neuronal activation, respectively, in response to a mild/moderate TBI induced by focal controlled cortical impact (CCI) injury of the motor cortex (M1).

Obesity and leptin in breast cancer angiogenesis.

At the time of breast cancer diagnosis, most patients meet the diagnostic criteria to be classified as obese or overweight. This can significantly impact patient outcome: breast cancer patients with obesity (body mass index > 30) have a poorer prognosis compared to patients with a lean BMI. Obesity is associated with hyperleptinemia, and leptin is a well-established driver of metastasis in breast cancer.

A Microphysiological HHT-on-a-Chip Platform Recapitulates Patient Vascular Lesions.

Hereditary Hemorrhagic Telangiectasia (HHT) is a rare congenital disease in which fragile vascular malformations (VM) - including small telangiectasias and large arteriovenous malformations (AVMs) - focally develop in multiple organs. There are few treatment options and no cure for HHT. Most HHT patients are heterozygous for loss-of-function mutations affecting Endoglin (ENG) or Alk1 (ACVRL1); however, why loss of these genes manifests as VMs remains poorly understood.

Ventilatory Assistance Before Umbilical Cord Clamping in Extremely Preterm Infants: A Randomized Clinical Trial.

Importance: Providing assisted ventilation during delayed umbilical cord clamping may improve outcomes for extremely preterm infants.

Objective: To determine whether assisted ventilation in extremely preterm infants (23 0/7 to 28 6/7 weeks' gestational age [GA]) followed by cord clamping reduces intraventricular hemorrhage (IVH) or early death.

Design, Setting, And Participants: This phase 3, 1:1, parallel-stratified randomized clinical trial conducted at 12 perinatal centers across the US and Canada from September 2, 2016, through February 21, 2023, assessed IVH and early death outcomes of extremely preterm infants randomized to receive 120 seconds of assisted ventilation followed by cord clamping vs delayed cord clamping for 30 to 60 seconds with ventilatory assistance afterward.

Imaging the large-scale and cellular response to focal traumatic brain injury in mouse neocortex.

Traumatic brain injury (TBI) affects neural function at the local injury site and also at distant, connected brain areas. However, the real-time neural dynamics in response to injury and subsequent effects on sensory processing and behavior are not fully resolved, especially across a range of spatial scales. We used calcium imaging in awake, head-restrained male and female mice to measure large-scale and cellular resolution neuronal activation, respectively, in response to a mild/moderate TBI induced by focal controlled cortical impact (CCI) injury of the motor cortex (M1).

SARS-CoV-2 infection of endothelial cells, dependent on flow-induced ACE2 expression, drives hypercytokinemia in a vascularized microphysiological system.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for COVID-19, has caused nearly 7 million deaths worldwide. Severe cases are marked by an aggressive inflammatory response known as hypercytokinemia, contributing to endothelial damage. Although vaccination has reduced hospitalizations, hypercytokinemia persists in breakthrough infections, emphasizing the need for disease models mimicking this response.

A Microphysiological HHT-on-a-Chip Platform Recapitulates Patient Vascular Lesions.

Unlabelled: Hereditary Hemorrhagic Telangiectasia (HHT) is a rare congenital disease in which fragile vascular malformations focally develop in multiple organs. These can be small (telangiectasias) or large (arteriovenous malformations, AVMs) and may rupture leading to frequent, uncontrolled bleeding. There are few treatment options and no cure for HHT.

Virtual Obstetric Hospitalist Support for Obstetric Emergencies and Deliveries: The Mayo Clinic Experience.

To implement use of obstetric (OB) hospitalist telemedicine services (TeleOB) to support clinicians facing OB emergencies in low-resource hospital settings. TeleOB was staffed by OB hospitalists working at a tertiary maternity center. The service was available via real-time high-definition audio/video technology for providers at 17 outlying hospitals across a health system spanning two states.

The impact of teleneonatology on the Transport Risk Index of Physiologic Stability score for outborn neonates: A prospective, observational study.

Introduction: Teleneonatology (TN) allows neonatologists to use real-time, audio-video telemedicine to manage critically ill neonates located in community hospitals (CHs). The California Transport Risk Index of Physiologic Stability (Ca-TRIPS) score is a validated metric that predicts the risk of 7-day mortality for neonates undergoing medical transport. We hypothesized that neonates born in CHs who received TN consults would have lower (better) Ca-TRIPS scores upon arrival of the transport team than those who did not.

Telesimulation for neonatal resuscitation training.

Telesimulation uses telecommunication and simulation to educate and assess remote learners, obviating the need for instructors or learners to travel off site. Telesimulation increases access to and convenience of simulation-based education for sites that do not have formal simulation centers, including rural/remote areas. Telesimulation is feasible, improves knowledge and skills, and is favorably received by learners and instructors.

Evaluating the feasibility of a multicenter teleneonatology clinical effectiveness trial.

Background: Our research consortium is preparing for a prospective multicenter trial evaluating the impact of teleneonatology on the health outcomes of at-risk neonates born in community hospitals. We completed a 6-month pilot study to determine the feasibility of the trial protocol.

Methods: Four neonatal intensive care units ("hubs") and four community hospitals ("spokes") participated in the pilot-forming four hub-spoke dyads.

Connexin 37 sequestering of activated-ERK in the cytoplasm promotes p27-mediated endothelial cell cycle arrest.

Connexin37-mediated regulation of cell cycle modulators and, consequently, growth arrest lack mechanistic understanding. We previously showed that arterial shear stress up-regulates Cx37 in endothelial cells and activates a Notch/Cx37/p27 signaling axis to promote G1 cell cycle arrest, and this is required to enable arterial gene expression. However, how induced expression of a gap junction protein, Cx37, up-regulates cyclin-dependent kinase inhibitor p27 to enable endothelial growth suppression and arterial specification is unclear.

A Predictive Model of Adaptive Resistance to BRAF/MEK Inhibitors in Melanoma.

The adaptive acquisition of resistance to BRAF and MEK inhibitor-based therapy is a common feature of melanoma cells and contributes to poor patient treatment outcomes. Leveraging insights from a proteomic study and publicly available transcriptomic data, we evaluated the predictive capacity of a gene panel corresponding to proteins differentially abundant between treatment-sensitive and treatment-resistant cell lines, deciphering predictors of treatment resistance and potential resistance mechanisms to BRAF/MEK inhibitor therapy in patient biopsy samples. From our analysis, a 13-gene signature panel, in both test and validation datasets, could identify treatment-resistant or progressed melanoma cases with an accuracy and sensitivity of over 70%.

Connexin 43-mediated neurovascular interactions regulate neurogenesis in the adult brain subventricular zone.

The subventricular zone (SVZ) is the largest neural stem cell (NSC) niche in the adult brain; herein, the blood-brain barrier is leaky, allowing direct interactions between NSCs and endothelial cells (ECs). Mechanisms by which direct NSC-EC interactions in the adult SVZ control NSC behavior are unclear. We found that Cx43 is highly expressed by SVZ NSCs and ECs, and its deletion in either leads to increased NSC proliferation and neuroblast generation, suggesting that Cx43-mediated NSC-EC interactions maintain NSC quiescence.

Sociodemographic factors and family use of remote infant viewing in neonatal intensive care.

Objective: We aimed to determine whether the use of remote infant viewing (RIV) in a neonatal intensive care unit (NICU) differed based on maternal sociodemographic factors.

Methods: The number of RIV camera views and view duration were obtained for NICU patients between 10/01/2019 and 3/31/2021 and standardized relative to patient days. Maternal sociodemographic and neonatal characteristics were obtained from institutional databases.

Connexin37 Regulates Cell Cycle in the Vasculature.

Control of vascular cell growth responses is critical for development and maintenance of a healthy vasculature. Connexins - the proteins comprising gap junction channels - are key regulators of cell growth in diseases such as cancer, but their involvement in controlling cell growth in the vasculature is less well appreciated. Connexin37 (Cx37) is one of four connexin isotypes expressed in the vessel wall.

Family Use of Remote Infant Viewing in the Neonatal Intensive Care Unit: Impact of the COVID-19 Pandemic and Patient Room Type.

Remote infant viewing (RIV) uses a bedside camera to allow families to view a livestream video of their neonate 24/7 from anywhere with internet access. The aim of this study was to evaluate family use of RIV for infants in the neonatal intensive care unit (NICU) during the COVID-19 pandemic and whether RIV use varied by patient room type. Use of RIV was evaluated for NICU patients between October 1, 2019, and March 31, 2021.

A quality improvement initiative to reduce necrotizing enterocolitis in high-risk neonates.

Objective: Prompted by an acute increase in necrotizing enterocolitis (NEC) rates, we aimed to decrease the rate of stage 2 or greater NEC in infants born at <1500 grams or <30 weeks gestational age from 19.5% to less than 9.7% (a 50% reduction) within 18 months, without adversely affecting central line-associated bloodstream infection (CLABSI) rates.

IL27 Signaling Serves as an Immunologic Checkpoint for Innate Cytotoxic Cells to Promote Hepatocellular Carcinoma.

Unlabelled: Although inflammatory mechanisms driving hepatocellular carcinoma (HCC) have been proposed, the regulators of anticancer immunity in HCC remain poorly understood. We found that IL27 receptor (IL27R) signaling promotes HCC development in vivo. High IL27EBI3 cytokine or IL27RA expression correlated with poor prognosis for patients with HCC.

A mitochondrial contribution to anti-inflammatory shear stress signaling in vascular endothelial cells.

Atherosclerosis, the major cause of myocardial infarction and stroke, results from converging inflammatory, metabolic, and biomechanical factors. Arterial lesions form at sites of low and disturbed blood flow but are suppressed by high laminar shear stress (LSS) mainly via transcriptional induction of the anti-inflammatory transcription factor, Kruppel-like factor 2 (Klf2). We therefore performed a whole genome CRISPR-Cas9 screen to identify genes required for LSS induction of Klf2.