Experience-dependent Tip60 nucleocytoplasmic transport is regulated by its NLS/NES sequences for neuroplasticity gene control.

Nucleocytoplasmic transport (NCT) in neurons is critical for enabling proteins to enter the nucleus and regulate plasticity genes in response to environmental cues. Such experience-dependent (ED) neural plasticity is central for establishing memory formation and cognitive function and can influence the severity of neurodegenerative disorders like Alzheimer's disease (AD). ED neural plasticity is driven by histone acetylation (HA) mediated epigenetic mechanisms that regulate dynamic activity-dependent gene transcription profiles in response to neuronal stimulation.

Tip60's Novel RNA-Binding Function Modulates Alternative Splicing of Pre-mRNA Targets Implicated in Alzheimer's Disease.

The severity of Alzheimer's disease (AD) progression involves a complex interplay of genetics, age, and environmental factors orchestrated by histone acetyltransferase (HAT)-mediated neuroepigenetic mechanisms. While disruption of Tip60 HAT action in neural gene control is implicated in AD, alternative mechanisms underlying Tip60 function remain unexplored. Here, we report a novel RNA binding function for Tip60 in addition to its HAT function.

Epilepsy with anterior temporal encephaloceles: Baseline characteristics, post-surgical outcomes, and comparison to mesial temporal sclerosis.

Objective: To review clinical and neuropsychological characteristics and natural history of a series of patients with temporal lobe epilepsy (TLE) and anterior temporal encephaloceles (ATE) and compare them to a similar series of TLE patients with mesial temporal sclerosis (MTS) to identify characteristics suggestive of ATE-related epilepsy.

Methods: Patients with epilepsy and ATE were identified via clinic encounters and consensus epilepsy surgery conference at a Level 4 epilepsy center. The drug-resistant subset of these patients who underwent epilepsy surgery (twenty-two of thirty-five) were compared to age- and laterality-matched patients with MTS.

Geographic disparities in peripartum cardiomyopathy outcomes.

Background: Cardiomyopathy causes more than a third of late postpartum pregnancy-related deaths in the United States, and racial disparities in outcomes among pregnant individuals with cardiomyopathy exist. Underlying community factors may contribute to disparities in peripartum cardiomyopathy outcomes.

Objective: This study aimed to identify the geographic distribution of and disparities in peripartum cardiomyopathy outcomes, hypothesizing that patients living in communities with higher social vulnerability may have worse outcomes.

Epilepsy with myoclonic absences: a case series highlighting clinical heterogeneity and surgical management.

Objective: Epilepsy with myoclonic absences is a rare epilepsy syndrome with distinct features and high rates of drug resistance. Identifying this syndrome may help guide treatment decisions. We highlight clinical heterogeneity in this case series and two cases in which corpus callosotomy was performed.

Electroencephalogram background and head ultrasound together stratify seizure risk in neonates undergoing hypothermia.

The benefits of continuous electroencephalography (cEEG) monitoring in the intensive care unit (ICU) are increasingly appreciated, though expanding indications for cEEG may strain resources. The current standard of care in babies with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH) includes cEEG monitoring throughout the entire TH and rewarming process (at least 72 h). Recent cEEG data demonstrate that most seizures occur within the first 24 h of monitoring.

Underrepresented Populations in Pediatric Epilepsy Surgery.

As awareness of pediatric epilepsy increases, accompanied by advancements in technology and research, it is important to identify certain types of patients that are overlooked for surgical management of epilepsy. Identifying these populations will allow us to study and elucidate the factors contributing to the underutilization and/or delayed application of surgical interventions. Demographically, African-American and Hispanic patients, as well as patients of certain Asian ethnicities, have relatively lower rates of undergoing epilepsy surgery than non-Hispanic and white patients.

Nutritional Formulation for Patients with Angelman Syndrome: A Randomized, Double-Blind, Placebo-Controlled Study of Exogenous Ketones.

Background: Angelman syndrome (AS) patients often respond to low glycemic index therapy to manage refractory seizures. These diets significantly affect quality of life and are challenging to implement. These formulations may have benefits in AS even in the absence of biomarkers suggesting ketosis.

Chromatin and transcriptomic profiling uncover dysregulation of the Tip60 HAT/HDAC2 epigenomic landscape in the neurodegenerative brain.

Disruption of histone acetylation-mediated gene control is a critical step in Alzheimer's Disease (AD), yet chromatin analysis of antagonistic histone acetyltransferases (HATs) and histone deacetylases (HDACs) causing these alterations remains uncharacterized. We report the first Tip60 HAT versus HDAC2 chromatin (ChIP-seq) and transcriptional (RNA-seq) profiling study in brains that model early human AD. We find Tip60 and HDAC2 predominantly recruited to identical neuronal genes.

Amyloid-β Peptide Impact on Synaptic Function and Neuroepigenetic Gene Control Reveal New Therapeutic Strategies for Alzheimer's Disease.

Amyloid-β (Aβ) peptides can form protease-resistant aggregates within and outside of neurons. Accumulation of these aggregates is a hallmark of Alzheimer's disease (AD) neuropathology and contributes to devastating cognitive deficits associated with this disorder. The primary etiological factor for Aβ aggregation is either an increase in Aβ production or a decrease in its clearance.

Tip60 protects against amyloid-β-induced transcriptomic alterations via different modes of action in early versus late stages of neurodegeneration.

Alzheimer's disease (AD) is an age-related neurodegenerative disorder hallmarked by amyloid-β (Aβ) plaque accumulation, neuronal cell death, and cognitive deficits that worsen during disease progression. Histone acetylation dysregulation, caused by an imbalance between reduced histone acetyltransferases (HAT) Tip60 and increased histone deacetylase 2 (HDAC2) levels, can directly contribute to AD pathology. However, whether such AD-associated neuroepigenetic alterations occur in response to Aβ peptide production and can be protected against by increasing Tip60 levels over the course of neurodegenerative progression remains unknown.

Racial disparities in peripartum cardiomyopathy: eighteen years of observations.

Background: Black women have greater than a three-fold risk of pregnancy-associated death compared to White women; cardiomyopathy is a leading cause of maternal mortality.

Objectives: This study examined racial disparities in health outcomes among women with peripartum cardiomyopathy.

Study Design: Retrospective cohort of women with peripartum cardiomyopathy per the National Heart, Lung, and Blood Institute definition from January 2000 to November 2017 from a single referral center.

Low-dose immune challenges result in detectable levels of oxidative damage.

Infection can result in substantial costs to animals, so they frequently respond by removing infectious agents with an immune response. However, immune responses entail their own costs, including upregulation of processes that destroy pathogens (e.g.

Effects of stress-induced increases of corticosterone on circulating triglyceride levels, biliverdin concentration, and heme oxygenase expression.

When exposed to stressors, animals physiologically respond by secreting glucocorticoid hormones. Most birds, reptiles, and amphibians secrete corticosterone (CORT), which allows them to maximize short-term survival, including by modulating lipid metabolism. However, the factors regulating lipid metabolism, particularly during acute (i.

Interventional Radiation Oncology (IRO): Transition of a magnetic resonance simulator to a brachytherapy suite.

Purpose: As a core component of a new gynecologic cancer radiation program, we envisioned, structured, and implemented a novel Interventional Radiation Oncology (IRO) unit and magnetic resonance (MR)-brachytherapy environment in an existing MR simulator.

Methods And Materials: We describe the external and internal processes required over a 6-8 month time frame to develop a clinical and research program for gynecologic brachytherapy and to successfully convert an MR simulator into an IRO unit.

Results: Support of the institution and department resulted in conversion of an MR simulator to a procedural suite.

Heterozygous loss of TSC2 alters p53 signaling and human stem cell reprogramming.

Tuberous sclerosis complex (TSC) is a pediatric disorder of dysregulated growth and differentiation caused by loss of function mutations in either the TSC1 or TSC2 genes, which regulate mTOR kinase activity. To study aberrations of early development in TSC, we generated induced pluripotent stem cells using dermal fibroblasts obtained from patients with TSC. During validation, we found that stem cells generated from TSC patients had a very high rate of integration of the reprogramming plasmid containing a shRNA against TP53.

Postoperative complications following intraoperative radiotherapy in abdominopelvic malignancy: A single institution analysis of 113 consecutive patients.

Background: Intraoperative radiotherapy (IORT) has advantages over external beam radiation therapy (EBRT). Few studies have described side effects associated with its addition. We evaluated our institution's experience with abdominopelvic IORT to assess safety by postoperative complication rates.

Alignment of multiradiation isocenters for megavoltage photon beam.

The accurate measurement of the linear accelerator (linac) radiation isocenter is critical, especially for stereotactic treatment. Traditional quality assurance (QA) procedure focuses on the measurement of single radiation isocenter, usually of 6 megavoltage (MV) photon beams. Single radiation isocenter is also commonly assumed in treatment planning systems (TPS).

Effects of X-ray radiation on complex visual discrimination learning and social recognition memory in rats.

The present report describes an animal model for examining the effects of radiation on a range of neurocognitive functions in rodents that are similar to a number of basic human cognitive functions. Fourteen male Long-Evans rats were trained to perform an automated intra-dimensional set shifting task that consisted of their learning a basic discrimination between two stimulus shapes followed by more complex discrimination stages (e.g.

High-dose-rate intraoperative radiation therapy: the nuts and bolts of starting a program.

High-dose-rate intraoperative radiation therapy (HDR-IORT) has historically provided effective local control (LC) for patients with unresectable and recurrent tumors. However, IORT is limited to only a few specialized institutions and it can be difficult to initiate an HDR-IORT program. Herein, we provide a brief overview on how to initiate and implement an HDR-IORT program for a selected group of patients with gastrointestinal and pelvic solid tumors using a multidisciplinary approach.