The University of Connecticut School of Medicine is a medical school located in Farmington, Connecticut. It was founded in 1961, enrolled students in 1968, and graduated its first class in 1972.The school is part of UConn Health, along with the University of Connecticut School of Dental Medicine, Graduate School of Biomedical Sciences, and John Dempsey Hospital. UConn Health is also a renowned biomedical research center, specializing in genetics, aging, orthopaedics and neurology/neurosurgery. In 2012, Dr. Cato Laurencin’s research on ACL tissue regeneration was named one of National Geographic’s 100 Scientific Discoveries That Changed the World.
Prospective, multi-institutional surgical data collection in pediatric neuro-oncology remains limited despite substantial variation in operative and perioperative management across institutions. To address this, we are developing the NeuroPoint Alliance (NPA) Quality Outcomes Database (QOD) Pediatric Tumor Surgery Registry. Here, we used a modified Delphi process to define a core outcome set for the registry. A modified Delphi study was conducted among pediatric neurosurgeons serving as site principal investigators for the proposed registry. Candidate data elements were rated on a 9-point Likert scale. Consensus for inclusion was predefined as ≥70
Ischemic injury triggers extracellular ATP release, activating P2X4 receptors (P2 × 4R) on immune and cardiac cells, which exacerbates inflammation and tissue damage. We evaluated MRS4719, a selective P2 × 4R antagonist, in aged mice subjected to transient middle cerebral artery occlusion (tMCAo) and cardiac ischemia/reperfusion (CI/R) injury. MRS4719 exhibited a nonlinear dose response, with an intermediate dose (2.25 mg/kg/day) and short-term treatment (2 days) optimally improving sensorimotor and cognitive recovery while reducing brain tissue atrophy. Treatment initiated up to 12 h post-stroke significantly decreased infarct volume. Additionally, MRS4719 preserved cardiac contractile function following ischemia/reperfusion injury. These findings suggest that targeted P2X4R inhibition mitigates inflammatory injury across multiple organs and supports functional recovery, highlighting MRS4719’s therapeutic potential for cerebral and cardiac ischemic disorders.
Copper (Cu) is an essential micronutrient that serves as a cofactor for redox enzymes but becomes toxic when unregulated. In bacteria, while Cu efflux systems are well characterized, mechanisms of Cu import remain poorly understood. Here, we characterize the major facilitator superfamily transporter CuiT (STM1486) as a key Cu importer in Salmonella enterica. Comparative genomics revealed that cuiT is evolutionarily conserved across Enterobacteriaceae, and structural modeling predicts a 12-transmembrane-helix architecture with conserved His, Met, and Cys residues suitable for Cu+ coordination. Functional analyses demonstrated that deletion of cuiT reduces intracellular Cu accumulation, slows Cu uptake kinetics, and diminishes expression of Cu-responsive genes, including copA, cueP, cueO, and golB. Conversely, overexpression of CuiT increases intracellular Cu but sensitizes cells to Cu stress, highlighting the need for tight regulation. Kinetic modeling indicates that CuiT mediates rapid Cu import, supporting larger intracellular Cu pools compared to Pseudomonas influx transporters. These findings position CuiT as a central component of the Salmonella Cu homeostasis network, linking Cu import to transcriptional regulation, redox balance, and stress adaptation. Our work provides mechanistic insights into bacterial Cu acquisition and suggests CuiT and associated pathways as potential targets for antimicrobial strategies.
Diffusion models excel at generation, but their latent spaces are high dimensional and not explicitly organized for interpretation or control. We introduce ConDA (Contrastive Diffusion Alignment), a plug-and-play geometry layer that applies contrastive learning to pretrained diffusion latents using auxiliary variables (e.g., time, stimulation parameters, facial action units). ConDA learns a low-dimensional embedding whose directions align with underlying dynamical factors, consistent with recent contrastive learning results on structured and disentangled representations. In this embedding, simple nonlinear trajectories support smooth interpolation, extrapolation, and counterfactual editing while rendering remains in the original diffusion space. ConDA separates editing and rendering by lifting embedding trajectories back to diffusion latents with a neighborhood-preserving kNN decoder and is robust across inversion solvers. Across fluid dynamics, neural calcium imaging, therapeutic neurostimulation, facial expression dynamics, and monkey motor cortex activity, ConDA yields more interpretable and controllable latent structure than linear traversals and conditioning-based baselines, indicating that diffusion latents encode dynamics-relevant structure that can be exploited by an explicit contrastive geometry layer.
OBJECTIVE:To assess the proportion of Level IV NICUs with post-hemorrhagic ventricular dilatation (PHVD) management pathways and compare the pathways. STUDY DESIGN:A survey was distributed to 49 Children's Hospitals Neonatal Consortium (CHNC) Level IV NICUs. A summarized pathway was developed from written pathways. RESULT:Survey response rate was 82%. Twelve (30%) NICUs have written pathways, 11 (28%) report informal consensus, and 17 (43%) lack consensus. Among the 12 written pathways, all serially monitor ventricular dilatation on cranial ultrasound (CUS) using ventricular index (58%) or frontal-occipital-horn-ratio (33%). Threshold for surgery varies: 33% of sites rely on CUS alone, while 67% incorporate clinical symptoms. Half of sites use lumbar puncture to decrease PHVD before surgery. Criteria for converting temporizing to permanent shunt is present in 67% of pathways. CONCLUSION:Amongst centers with written PHVD pathways, variable monitoring and intervention criteria exist. Most NICUs lack formal pathways, demonstrating opportunities to standardize care.
