In utero delivery of targeted ionizable lipid nanoparticles facilitates in vivo gene editing of hematopoietic stem cells.

Monogenic blood diseases are among the most common genetic disorders worldwide. These diseases result in significant pediatric and adult morbidity, and some can result in death prior to birth. Novel ex vivo hematopoietic stem cell (HSC) gene editing therapies hold tremendous promise to alter the therapeutic landscape but are not without potential limitations.

Optimized microfluidic formulation and organic excipients for improved lipid nanoparticle mediated genome editing.

mRNA-based gene editing platforms have tremendous promise in the treatment of genetic diseases. However, for this potential to be realized , these nucleic acid cargos must be delivered safely and effectively to cells of interest. Ionizable lipid nanoparticles (LNPs), the most clinically advanced non-viral RNA delivery system, have been well-studied for the delivery of mRNA but have not been systematically optimized for the delivery of mRNA-based CRISPR-Cas9 platforms.

Adult Inception of Ketogenic Diet Therapy Increases Sleep during the Dark Cycle in C57BL/6J Wild Type and Fragile X Mice.

Sleep problems are a significant phenotype in children with fragile X syndrome. Our prior work assessed sleep-wake cycles in male mice and wild type (WT) littermate controls in response to ketogenic diet therapy where mice were treated from weaning (postnatal day 18) through study completion (5-6 months of age). A potentially confounding issue with commencing treatment during an active period of growth is the significant reduction in weight gain in response to the ketogenic diet.

A Retrospective Study to Evaluate Discrepancies in Urban Versus Rural Mortality Due to Brain Cancer in the United States.

Introduction: The study aims to examine the disparities in mortality rates attributed to brain cancer between urban and rural areas over a 22-year period, totaling 315,538 deaths. This investigation serves as a crucial step in identifying areas within healthcare that require improvement. By pinpointing the variations in mortality rates between urban and rural settings, healthcare authorities can strategically implement necessary interventions.

Seizure Assessment and Forecasting With Efficient Rapid-EEG: A Retrospective Multicenter Comparative Effectiveness Study.

Background And Objectives: Approximately 30% of critically ill patients have seizures, and more than half of these seizures do not have an overt clinical correlate. EEG is needed to avoid missing seizures and prevent overtreatment with antiseizure medications. Conventional-EEG (cEEG) resources are logistically constrained and unable to meet their growing demand for seizure detection even in highly developed centers.

Three-Year Analysis of the Rectal Cancer Care Trajectory after the COVID-19 Pandemic.

The global pandemic period from 2020 to 2022 caused important alterations in oncology care. This study aimed to describe the trends and variations in patient characteristics, comorbidities, and treatment approaches during this time in Romania. We conducted a retrospective database search to identify patients with rectal cancer who underwent surgical intervention between 2020 and 2022 and the year 2019, which served as a pre-pandemic period control.

Ketogenic Diet Affects Sleep Architecture in C57BL/6J Wild Type and Fragile X Mice.

Nearly half of children with fragile X syndrome experience sleep problems including trouble falling asleep and frequent nighttime awakenings. The goals here were to assess sleep-wake cycles in mice in response to genotype and a dietary intervention that reduces hyperactivity. Electroencephalography (EEG) results were compared with published rest-activity patterns to determine if actigraphy is a viable surrogate for sleep EEG.

Shorter Is Better: The α-(l)-Threofuranosyl Nucleic Acid Modification Improves Stability, Potency, Safety, and Ago2 Binding and Mitigates Off-Target Effects of Small Interfering RNAs.

Chemical modifications are necessary to ensure the metabolic stability and efficacy of oligonucleotide-based therapeutics. Here, we describe analyses of the α-(l)-threofuranosyl nucleic acid (TNA) modification, which has a shorter 3'-2' internucleotide linkage than the natural DNA and RNA, in the context of small interfering RNAs (siRNAs). The TNA modification enhanced nuclease resistance more than 2'--methyl or 2'-fluoro ribose modifications.

Longitudinal Analysis of Pulmonary Function Impairment One Year Post-COVID-19: A Single-Center Study.

Persistent pulmonary impairment post-COVID-19 has been reported, albeit variably. This single-center observational study aims to longitudinally evaluate pulmonary function in 140 COVID-19 survivors one year after recovery, assessing associations with disease severity and pre-existing lung conditions. Participants aged 18 and older, with confirmed SARS-CoV-2 infection, were evaluated using spirometry and Diffusion Capacity of Lungs for Carbon Monoxide (DLCO) tests.

The Effects of Vitamin D Supplementation before 20 Weeks of Gestation on Preeclampsia: A Systematic Review.

Preeclampsia is a leading cause of maternal and fetal morbidity and mortality worldwide. The role of vitamin D supplementation during early pregnancy in the prevention of preeclampsia remains unclear. Our objective was to synthesize and critically appraise the available evidence from observational and interventional studies to determine the effects of early pregnancy vitamin D supplementation on the risk of preeclampsia.

Multi-shell connectome DWI-based graph theory measures for the prediction of temporal lobe epilepsy and cognition.

Temporal lobe epilepsy (TLE) is the most common epilepsy syndrome that empirically represents a network disorder, which makes graph theory (GT) a practical approach to understand it. Multi-shell diffusion-weighted imaging (DWI) was obtained from 89 TLE and 50 controls. GT measures extracted from harmonized DWI matrices were used as factors in a support vector machine (SVM) analysis to discriminate between groups, and in a k-means algorithm to find intrinsic structural phenotypes within TLE.

Late dominance of the right hemisphere during narrative comprehension.

PET and fMRI studies suggest that auditory narrative comprehension is supported by a bilateral multilobar cortical network. The superior temporal resolution of magnetoencephalography (MEG) makes it an attractive tool to investigate the dynamics of how different neuroanatomic substrates engage during narrative comprehension. Using beta-band power changes as a marker of cortical engagement, we studied MEG responses during an auditory story comprehension task in 31 healthy adults.

Dual orexin antagonist normalized sleep homeostatic drive, enhanced GABAergic inhibition, and suppressed seizures after traumatic brain injury.

Study Objectives: Traumatic brain injury (TBI) can result in posttraumatic epilepsy (PTE) and sleep disturbances. We hypothesized that treatment with sleep aids after TBI can ameliorate PTE.

Methods: CD-1 mice underwent controlled cortical impact (CCI), sham injury, or no craniotomy.

Cognitive status in a 62-year-old male with lifelong temporal lobe epilepsy and multiple comorbidities.

This is a case report of a 62-year-old male with lifelong temporal lobe epilepsy presented with an interesting matrix of clinical, cognitive, psychiatric, neuroinaging and psychosocial features. This was one of the cases presented for review and discussion at the ILAE Neuropsychology Training Course as part of a case series discussion and is highlighted to illustrate the potential for neuropsychological resilience in a patient with epilepsy.

Deficits in Behavioral and Neuronal Pattern Separation in Temporal Lobe Epilepsy.

In temporal lobe epilepsy, the ability of the dentate gyrus to limit excitatory cortical input to the hippocampus breaks down, leading to seizures. The dentate gyrus is also thought to help discriminate between similar memories by performing pattern separation, but whether epilepsy leads to a breakdown in this neural computation, and thus to mnemonic discrimination impairments, remains unknown. Here we show that temporal lobe epilepsy is characterized by behavioral deficits in mnemonic discrimination tasks, in both humans (females and males) and mice (C57Bl6 males, systemic low-dose kainate model).

Sleep Deprivation Exacerbates Seizures and Diminishes GABAergic Tonic Inhibition.

Patients with epilepsy report that sleep deprivation is a common trigger for breakthrough seizures. The basic mechanism of this phenomenon is unknown. In the Kv1.

Network topology of the cognitive phenotypes of temporal lobe epilepsy.

Purpose: The neuropsychological complications of temporal lobe epilepsy are characterized by a spectrum of reproducible cognitive phenotypes that vary in the presence, type and degree of impairment. The nature of the disruptions to the neuropsychological networks that underlie these phenotypes remain to be characterized and represent the subject of this investigation.

Methods: Participants included 30 healthy controls and 104 patients with temporal lobe epilepsy who fell into three cognitive phenotypes (intact, focal impairment, generalized impairment).

Proceedings of the Sleep and Epilepsy Workshop: Section 1 Decreasing Seizures-Improving Sleep and Seizures, Themes for Future Research.

Epileptic seizures, sleep, and circadian timing share bilateral interactions, but concerted work to characterize these interactions and to leverage them to the advantage of patients with epilepsy remains in beginning stages. To further the field, a multidisciplinary group of sleep physicians, epileptologists, circadian timing experts, and others met to outline the state of the art, gaps of knowledge, and suggest ways forward in clinical, translational, and basic research. A multidisciplinary panel of experts discussed these interactions, centered on whether improvements in sleep or circadian rhythms improve decrease seizure frequency.

Proceedings of the Sleep and Epilepsy Workshop: Section 3 Mortality: Sleep, Night, and SUDEP.

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in patients with refractory epilepsy. Likely pathophysiological mechanisms include seizure-induced cardiac and respiratory dysregulation. A frequently identified feature in SUDEP cases is that they occur at night.

Sleep-wake characteristics in a mouse model of severe traumatic brain injury: Relation to posttraumatic epilepsy.

Study Objectives: Traumatic brain injury (TBI) results in sequelae that include posttraumatic epilepsy (PTE) and sleep-wake disturbances. Here, we sought to determine whether sleep characteristics could predict development of PTE in a model of severe TBI.

Methods: Following controlled cortical impact (CCI) or sham injury (craniotomy only), CD-1 mice were implanted with epidural electroencephalography (EEG) and nuchal electromyography (EMG) electrodes.

Untangling a Web: Basic Mechanisms of the Complex Interactions Between Sleep, Circadian Rhythms, and Epilepsy.

Seizures have sleep-wake and circadian patterns in various epilepsies and, in turn, disrupt sleep and circadian rhythms. The resultant sleep deprivation (SD) is an exacerbating factor for seizures that sets up a vicious cycle that can potentially lead to disease progression and even to epilepsy-related mortality. A variety of cellular or network electrophysiological changes and changes in expression of clock-controlled genes or other transcription factors underlie sleep-wake and circadian distribution of seizures, as well as the disruptions seen in both.