Clinical neurocardiology: defining the value of neuroscience-based cardiovascular therapeutics - 2024 update.

The intricate role of the autonomic nervous system (ANS) in regulating cardiac physiology has long been recognized. Aberrant function of the ANS is central to the pathophysiology of cardiovascular diseases. It stands to reason, therefore, that neuroscience-based cardiovascular therapeutics hold great promise in the treatment of cardiovascular diseases in humans.

Phase 1 trial of selinexor in pediatric recurrent/refractory solid and CNS tumors (ADVL1414): A Children's Oncology Group Phase 1 Consortium Trial.

Background: Selinexor is a first-in-class, central nervous system (CNS)-penetrant, oral inhibitor of exportin 1 (XPO1), the main nuclear exporter of many key tumor suppressors. We report a phase 1 trial of selinexor in children and adolescents with recurrent CNS and solid tumors (NCT02323880).

Methods: A rolling-six design was used to evaluate the maximum tolerated dose (MTD) and first dose pharmacokinetics (PK) of selinexor administered once (QW, 35-45 mg/m2) or twice (BIW, 20-35 mg/m2) weekly during a 28-day cycle (Part A).

Thalamic deep brain stimulation for central poststroke pain syndrome: an international multicenter study.

Objective: The effectiveness and optimal stimulation site of deep brain stimulation (DBS) for central poststroke pain (CPSP) remain elusive. The objective of this retrospective international multicenter study was to assess clinical as well as neuroimaging-based predictors of long-term outcomes after DBS for CPSP.

Methods: The authors analyzed patient-based clinical and neuroimaging data of previously published and unpublished cohorts from 6 international DBS centers.

COVID-Related Discrimination and Health Care Access among a Nationally Representative, Diverse Sample of US Adults.

Background: In the United States, COVID-related discrimination towards racial and ethnic minority populations is well documented; however, its impact on healthcare access during the pandemic has not been assessed.

Methods: We used data from our nationally representative, online survey of 5,500 American Indian/Alaska Native (AIAN), Asian, Black, Native Hawaiian/Pacific Islander, Latino, White, and multiracial adults conducted between 12/2020-2/2021 (baseline) and 8/2021-9/2021 (6-month follow-up; 35.1% response rate).

Longevity, enhanced memory, and altered density of dendritic spines in hippocampal CA3 and dentate gyrus after hemizygous deletion of Pde2a in mice.

Studies using acute or subchronic pharmacological inhibition of phosphodiesterase 2 A (PDE2A) have led to its proposal as a target for treatment of cognitive deficits associated with neuropsychiatric and neurodegenerative disease. However, the impact of continuous inhibition of PDE2A on memory is unknown. Moreover, the neuroanatomical regions mediating memory enhancement have not been categorically identified.

Cortico-thalamic tremor circuits and their associations with deep brain stimulation effects in essential tremor.

Essential tremor (ET) is one of the most common movement disorders in adults. Deep brain stimulation (DBS) of the ventralis intermediate nucleus (VIM) of the thalamus and/or the posterior subthalamic area (PSA) has been shown to provide significant tremor suppression in patients with ET, but with significant inter-patient variability and habituation to the stimulation. Several non-invasive neuromodulation techniques targeting other parts of the central nervous system, including cerebellar, motor cortex, or peripheral nerves, have also been developed for treating ET, but the clinical outcomes remain inconsistent.

Muscarinic receptors mediate motivation via preparatory neural activity in humans.

Motivation depends on dopamine, but might be modulated by acetylcholine which influences dopamine release in the striatum, and amplifies motivation in animal studies. A corresponding effect in humans would be important clinically, since anticholinergic drugs are frequently used in Parkinson's disease, a condition that can also disrupt motivation. Reward and dopamine make us more ready to respond, as indexed by reaction times (RT), and move faster, sometimes termed vigour.

Effect of Microbubble Size, Composition, and Multiple Sonication Points on Sterile Inflammatory Response in Focused Ultrasound-Mediated Blood-Brain Barrier Opening.

Blood-brain barrier opening (BBBO) using focused ultrasound (FUS) and microbubbles (MBs) has emerged as a promising technique for delivering therapeutics to the brain. However, the influence of various FUS and MB parameters on BBBO and subsequent sterile inflammatory response (SIR) remains unclear. In this study, we investigated the effects of MB size and composition, as well as the number of FUS sonication points, on BBBO and SIR in an immunocompetent mouse model.

PRMT5 Maintains Tumor Stem Cells to Promote Pediatric High-Grade Glioma Tumorigenesis.

Pediatric high-grade gliomas (PHGG) are aggressive, undifferentiated central nervous system tumors with poor outcomes, for which no standard-of-care drug therapy currently exists. Through a knockdown (KD) screen for epigenetic regulators, we identified PRMT5 as essential for PHGG cell growth. We hypothesized that, similar to its effect in normal cells, PRMT5 promotes self-renewal of stem-like PHGG tumor-initiating cells essential for tumor growth.

Protection efforts have resulted in ~10% of existing fish biomass on coral reefs.

The amount of ocean protected from fishing and other human impacts has often been used as a metric of conservation progress. However, protection efforts have highly variable outcomes that depend on local conditions, which makes it difficult to quantify what coral reef protection efforts to date have actually achieved at a global scale. Here, we develop a predictive model of how local conditions influence conservation outcomes on ~2,600 coral reef sites across 44 ecoregions, which we used to quantify how much more fish biomass there is on coral reefs compared to a modeled scenario with no protection.

The Y498T499-SARS-CoV-2 spike (S) protein interacts poorly with rat ACE2 and does not affect the rat lung.

The rat is a useful laboratory model for respiratory diseases. SARS-CoV-2 proteins, such as the spike (S) protein, can induce inflammation. This study has investigated the ability of the Q498Y, P499T (QP-YT) amino acid change, described in the S-protein of the mouse-adapted laboratory SARS-CoV-2 MA strain, to interact with rat angiotensin converting enzyme-2 (ACE2) and stimulate responses in rat lungs.

Application of diceCT to Study the Development of the Zika Virus-Infected Mouse Brain.

Zika virus (ZIKV) impacts the developing brain. Here, a technique was applied to define, in 3D, developmental changes in the brains of ZIKV-infected mice. Postnatal day 1 mice were uninfected or ZIKV-infected, then analysed by iodine staining and micro-CT scanning (diffusible iodine contrast-enhanced micro-CT; diceCT) at 3-, 6-, and 10-days post-infection (dpi).

Treatment patterns of patients with migraine eligible for anti-CGRP pathway monoclonal antibodies.

Introduction: Migraine is a debilitating neurological disorder, with a wide range of symptoms and disease burden, underscoring the heterogeneity of patients' disease characteristics and treatment needs. To characterize the profile of migraine patients in the US who may be eligible for preventive treatment with an anti-CGRP pathway mAb and to better understand treatment patterns and real-world use of acute and preventive medications for migraine, we conducted a retrospective cohort study of adult patients.

Methods: These patients were identified as having migraine using diagnosis codes or migraine-specific medication use (first = index) in the IQVIA PharMetrics® Plus database.

Deep Brain Stimulation for Consciousness Disorders; Technical and Ethical Considerations.

Disorders of Consciousness (DoC) result in profound functional impairment, adversely affecting the lives of a predominantly younger patient population. Currently, effective treatment options for those who have reached chronicity (prolonged symptom duration over 4 weeks) are extremely limited, with the majority of such cases facing life-long dependence on carers and a poor quality of life. Here we briefly review the current evidence on caseload, diagnostic and management options in the United Kingdom (UK), United States of America (USA) and the European Union (EU).

Sociodemographic and Socioeconomic Factors Correlate with Late-Stage Pediatric Hodgkin Lymphoma and Rhabdomyosarcoma: A Report from the Children's Oncology Group Registries.

Background: We examined the association between late-stage diagnosis and individual- and community-level sociodemographic and socioeconomic characteristics among patients with pediatric Hodgkin lymphoma and rhabdomyosarcoma (RMS).

Methods: We obtained Children's Oncology Group data from 1999 to 2021 including summary stage [local (L), regional (R), and distant (D)], tumor subtype, demographics, and ZIP Code at diagnosis. We linked ZIP Codes to county-level redlining scores (C, D = greatest redlining), the Child Opportunity Index, and measures of segregation (racial dissimilarity indices).

Comprehensive assessment of blood-brain barrier opening and sterile inflammatory response: unraveling the therapeutic window.

Microbubbles (MBs) combined with focused ultrasound (FUS) has emerged as a promising noninvasive technique to permeabilize the blood-brain barrier (BBB) for drug delivery into the brain. However, the safety and biological consequences of BBB opening (BBBO) remain incompletely understood. This study aims to investigate the effects of two parameters mediating BBBO: microbubble volume dose (MVD) and mechanical index (MI).

Effect of Microbubble Size, Composition and Multiple Sonication Points on Sterile Inflammatory Response in Focused Ultrasound-Mediated Blood-Brain Barrier Opening.

Blood-brain barrier opening (BBBO) using focused ultrasound (FUS) and microbubbles (MBs) has emerged as a promising technique for delivering therapeutics to the brain. However, the influence of various FUS and MB parameters on BBBO and subsequent sterile inflammatory response (SIR) remains unclear. In this study, we investigated the effects of MB size and composition, as well as the number of FUS sonication points, on BBBO and SIR in an immunocompetent mouse model.

Auditory cues modulate the short timescale dynamics of STN activity during stepping in Parkinson's disease.

Background: Gait impairment has a major impact on quality of life in patients with Parkinson's disease (PD). It is believed that basal ganglia oscillatory activity at β frequencies (15-30 Hz) may contribute to gait impairment, but the precise dynamics of this oscillatory activity during gait remain unclear. Additionally, auditory cues are known to lead to improvements in gait kinematics in PD.