Bidirectional histone monoaminylation dynamics regulate neural rhythmicity.

Histone H3 monoaminylations at Gln5 represent an important family of epigenetic marks in brain that have critical roles in permissive gene expression. We previously demonstrated that serotonylation and dopaminylation of Gln5 of histone H3 (H3Q5ser and H3Q5dop, respectively) are catalysed by transglutaminase 2 (TG2), and alter both local and global chromatin states. Here we found that TG2 additionally functions as an eraser and exchanger of H3 monoaminylations, including H3Q5 histaminylation (H3Q5his), which displays diurnally rhythmic expression in brain and contributes to circadian gene expression and behaviour.

Exploring the equity of distribution of general medical services funding allocations in Wales: a time-series analysis.

Background: Good access to quality primary care in high-income countries can improve population health. Access to primary care is however often not equal among socioeconomic groups; our analysis sought to explore whether funding, a determinant of service supply, is equitably distributed among GP practices in Wales.

Aim: We sought to explore the relationship between funding and deprivation among GP practices in Wales, to understand the equity of current funding policies.

Pathologic Features of Primary Pancreatic Malignancies.

This chapter explores the pathologic features of benign and malignant lesions of the pancreas. As pathologic classifications evolve particularly for cystic lesions and neuroendocrine tumors, it is important for physicians who treat patients with gastrointestinal malignance to fully evaluate these pathologic classifications.

Serotonin transporter-dependent histone serotonylation in placenta contributes to the neurodevelopmental transcriptome.

Brain development requires appropriate regulation of serotonin (5-HT) signaling from distinct tissue sources across embryogenesis. At the maternal-fetal interface, the placenta is thought to be an important contributor of offspring brain 5-HT and is critical to overall fetal health. Yet, how placental 5-HT is acquired, and the mechanisms through which 5-HT influences placental functions, are not well understood.

Adhesive Wearable Sensors for Electroencephalography from Hairy Scalp.

Electroencephalography has garnered interest for applications in mobile healthcare, human-machine interfaces, and Internet of Things. Conventional electroencephalography relies on wet and dry electrodes. Despite favorable interface impedance of wet electrodes and skin, the application of a large amount of gel at their interface with skin limits the electroencephalography spatial resolution, increases the risk of shorting between electrodes, and makes them unsuited for long-term mobile recording.

Patent ductus arteriosus (PDA) and response to late surfactant treatment in premature infants.

Objective: To determine the clinical/echocardiography (ECHO) phenotype of patients with hypoxic respiratory failure (HRF) and response to late surfactant, according to patent ductus arteriosus (PDA) status.

Study Design: This retrospective study included infants ≤26 weeks gestation who received ≥1 surfactant dose after 6 postnatal days and where PDA status was available by ECHO. Response to surfactant was appraised based on change in respiratory severity score over 48 h.

Pediatric Myeloid Sarcoma, More than Just a Chloroma: A Review of Clinical Presentations, Significance, and Biology.

Myeloid sarcomas (MS), commonly referred to as chloromas, are extramedullary tumors of acute myeloid leukemia (AML) with varying incidence and influence on outcomes. Pediatric MS has both a higher incidence and unique clinical presentation, cytogenetic profile, and set of risk factors compared to adult patients. Optimal treatment remains undefined, yet allogeneic hematopoietic stem cell transplantation (allo-HSCT) and epigenetic reprogramming in children are potential therapies.

Convergent abnormalities in striatal gene networks in human cocaine use disorder and mouse cocaine administration models.

Cocaine use disorder (CUD) is an intractable syndrome, and rising overdose death rates represent a substantial public health crisis that exacts tremendous personal and financial costs on patients and society. Sharp increases in cocaine use drive the urgent need for better mechanistic insight into this chronic relapsing brain disorder that currently lacks effective treatment options. To investigate the transcriptomic changes involved, we conducted RNA sequencing on two striatal brain regions that are heavily implicated in CUD, the nucleus accumbens and caudate nucleus, from men suffering from CUD and matched controls.

Transcriptional signatures of heroin intake and seeking throughout the brain reward circuit.

Opioid use disorder (OUD) looms as one of the most severe medical crises currently facing society. More effective therapeutics for OUD requires in-depth understanding of molecular changes supporting drug-taking and relapse. Recent efforts have helped advance these aims, but studies have been limited in number and scope.

A Population-Based Analysis of the Risk of Glomerular Disease Relapse after COVID-19 Vaccination.

Background: Although case reports have described relapses of glomerular disease after COVID-19 vaccination, evidence of a true association is lacking. In this population-level analysis, we sought to determine relative and absolute risks of glomerular disease relapse after COVID-19 vaccination.

Methods: In this retrospective population-level cohort study, we used a centralized clinical and pathology registry (2000-2020) to identify 1105 adult patients in British Columbia, Canada, with biopsy-proven glomerular disease that was stable on December 14, 2020 (when COVID-19 vaccines first became available).

Use of Iatrogenic Lipid Emulsion and Subsequent Plasmapheresis for the Treatment of Amitriptyline Overdose.

Plasmapheresis for the treatment of hypertriglyceridemia is relatively uncommon and mostly reported either in patients experiencing hypertriglyceridemia-induced acute pancreatitis or patients with therapy-resistant familial hypercholesterolemia. Standard therapies for hypertriglyceridemia include dietary modification and lipid-lowering medication. For severe hypertriglyceridemia, the risk of pancreatitis increases significantly as triglyceride levels increase above 1000 mg/dL, and current therapies are unable to reduce triglyceride levels rapidly enough.

Crystallin Mu in Medial Amygdala Mediates the Effect of Social Experience on Cocaine Seeking in Males but Not in Females.

Background: Social experiences influence susceptibility to substance use disorder. The adolescent period is associated with the development of social reward and is exceptionally sensitive to disruptions to reward-associated behaviors by social experiences. Social isolation (SI) during adolescence alters anxiety- and reward-related behaviors in adult males, but little is known about females.

Unexplained Hematocrit Increase after Therapeutic Phlebotomy in a Patient with Marked Erythrocytosis.

We report a patient with hereditary erythrocytosis who underwent a therapeutic phlebotomy and had a post-phlebotomy hematocrit that was higher than the pre-phlebotomy hematocrit. We could not discern a reason for this hematocrit increase after phlebotomy. Instead of performing another phlebotomy, we performed an automated red cell depletion via an apheresis instrument.

Gene-Targeted, CREB-Mediated Induction of ΔFosB Controls Distinct Downstream Transcriptional Patterns Within D1 and D2 Medium Spiny Neurons.

Background: The onset and persistence of addiction phenotypes are, in part, mediated by transcriptional mechanisms in the brain that affect gene expression and, subsequently, neural circuitry. ΔFosB is a transcription factor that accumulates in the nucleus accumbens (NAc)-a brain region responsible for coordinating reward and motivation-after exposure to virtually every known rewarding substance, including cocaine and opioids. ΔFosB has also been shown to directly control gene transcription and behavior downstream of both cocaine and opioid exposure, but with potentially different roles in D1 and D2 medium spiny neurons (MSNs) in NAc.

Sperm Transcriptional State Associated with Paternal Transmission of Stress Phenotypes.

Paternal stress can induce long-lasting changes in germ cells potentially propagating heritable changes across generations. To date, no studies have investigated differences in transmission patterns between stress-resilient and stress-susceptible mice. We tested the hypothesis that transcriptional alterations in sperm during chronic social defeat stress (CSDS) transmit increased susceptibility to stress phenotypes to the next generation.

Sex-Specific Transcriptional Changes in Response to Adolescent Social Stress in the Brain's Reward Circuitry.

Background: Sex differences in addiction have been described in humans and animal models. A key factor that influences addiction in both males and females is adolescent experience. Adolescence is associated with higher vulnerability to substance use disorders, and male rodents subjected to adolescent social isolation (SI) stress form stronger preferences for drugs of abuse in adulthood.

Long read, isoform aware sequencing of mouse nucleus accumbens after chronic cocaine treatment.

To better understand the full-length transcriptome of the nucleus accumbens (NAc)-a key brain reward region-in chronic cocaine treatment, we perform the first single molecule, long-read sequencing analysis using the Iso-seq method to detect 42,114 unique transcripts from mouse NAc polyadenylated RNA. Using GENCODE annotation as a reference, we find that over half of the Iso-seq derived transcripts are annotated, while 46% of them harbor novel splicing events in known genes; around 1% of them correspond to other types of novel transcripts, such as fusion, antisense and intergenic. Approximately 34% of the novel transcripts are matched with a compiled transcriptome assembled from published short-read data from various tissues, with the remaining 69% being unique to NAc.

Understanding and responding to COVID-19 in Wales: protocol for a privacy-protecting data platform for enhanced epidemiology and evaluation of interventions.

Introduction: The emergence of the novel respiratory SARS-CoV-2 and subsequent COVID-19 pandemic have required rapid assimilation of population-level data to understand and control the spread of infection in the general and vulnerable populations. Rapid analyses are needed to inform policy development and target interventions to at-risk groups to prevent serious health outcomes. We aim to provide an accessible research platform to determine demographic, socioeconomic and clinical risk factors for infection, morbidity and mortality of COVID-19, to measure the impact of COVID-19 on healthcare utilisation and long-term health, and to enable the evaluation of natural experiments of policy interventions.