Enhancing Drug Development for Paediatric Pulmonary Hypertension-An Integrative Perspective.

As with adult pulmonary hypertension (PH), high morbidity and mortality persist with diverse types of paediatric PH. Despite major advances in pharmacologic therapies based on extensive studies in adult PH, few drugs have been comprehensively studied in neonates, infants, and children, leaving current paediatric PH care largely dependent on small observational studies and extrapolation of evidence from adult clinical trials. Challenges in developing successful clinical trials in children include the need to define distinct disease phenotypes with well-characterised natural history and outcomes, the lack of established age- and disease-specific study endpoints, small and heterogeneous paediatric populations, and the common off-label use of PH-targeted drug therapies without regulatory approval.

How strong is the rhythm of perception? A registered replication of Hickok . (2015).

Our ability to predict upcoming events is a fundamental component of human cognition. One way in which we do so is by exploiting temporal regularities in sensory signals: the ticking of a clock, falling of footsteps and the motion of waves each provide a structure that may facilitate anticipation. But how strong is the effect of rhythmic anticipation on perception? And to what degree do people vary in their ability to capitalize on these regularities? In 2015, Hickok .

Cardiac Structure, Function and Mechanics in Hypertensive Disorders of Pregnancy: A Systematic Review and Meta-Analysis.

Background: Hypertensive disorders of pregnancy (HDP) are among the most common pregnancy complications and leading causes of maternal morbidity and mortality worldwide. This study aimed to perform the largest meta-analysis to date comparing conventional and advanced echocardiographic features in HDP against healthy pregnancy.

Methods: PubMed (MEDLINE) and EMBASE were systematically searched for research articles published up to March 2024.

Cellular Communication Network Protein 2 in the Right Ventricle of Pulmonary Arterial Hypertension.

Cellular communication network 2 (CCN2) is a secreted matricellular protein associated with pulmonary arterial hypertension (PAH) but has not been studied relative to PAH severity, outcomes, or right ventricle (RV) structure and function in a large human cohort and preclinical animal model. This study assessed the associations between CCN2 and PAH severity, survival, hemodynamic measurements, and cardiovascular dysfunction. Serum CCN2 levels were compared in 2548 adults with PAH and 216 controls.

Complications of Pulmonary Embolism in a Pediatric Patient.

A 16-year-old boy presents with a massive acute pulmonary embolism requiring emergent surgical embolectomy and extracorporeal membrane oxygenation for right ventricular failure. Subsequently he was diagnosed with catastrophic antiphospholipid syndrome requiring immunosuppression, and then pneumatoceles causing tension pneumothoraxes. The rarity of presentation in a child required collaboration across pediatric and adult disciplines.

Dynamics of influenza transmission in vampire bats revealed by longitudinal monitoring and a large-scale anthropogenic perturbation.

Interrupting pathogen transmission between species is a priority strategy to mitigate zoonotic threats. However, avoiding counterproductive interventions requires knowing animal reservoirs of infection and the dynamics of transmission within them, neither of which are easily ascertained from the cross-sectional surveys that now dominate investigations into newly discovered viruses. We used biobanked sera and metagenomic data to reconstruct the transmission of recently discovered bat-associated influenza virus (BIV; H18N11) over 12 years in three zones of Peru.

The Role of Imaging in Pulmonary Vascular Disease: The Clinician's Perspective.

Pulmonary vascular diseases, particularly when accompanied by pulmonary hypertension, are complex disorders often requiring multimodal imaging for diagnosis and monitoring. Echocardiography is the primary screening tool for pulmonary hypertension, while cardiac MR imaging (CMR) is used for more detailed characterization and risk stratification in right ventricular failure. Chest computed tomography (CT) is used to detect vascular anomalies and parenchymal lung diseases.

Equivalency of Multiple Biomarkers to Clinical Pulmonary Arterial Hypertension Survival Risk Models.

Background: Risk assessment in pulmonary arterial hypertension (PAH) is fundamental to guiding treatment and improved outcomes. Clinical models are excellent at identifying high-risk patients, but leave uncertainty amongst moderate-risk patients.

Research Question: Can a multiple blood biomarker model of PAH, using previously described biomarkers, improve risk discrimination over current models?

Study Design And Methods: Using a multiplex enzyme-linked immunosorbent assay, we measured N-terminal pro-B-type natriuretic peptide (NT-proBNP), soluble suppressor of tumorigenicity, IL-6, endostatin, galectin 3, hepatoma derived growth factor, and insulin-like growth factor binding proteins (IGFBP1-7) in training (n = 1,623), test (n = 696), and validation (n = 237) cohorts.

Resistin predicts disease severity and survival in patients with pulmonary arterial hypertension.

Background: Abnormal remodeling of distal pulmonary arteries in patients with pulmonary arterial hypertension (PAH) leads to progressively increased pulmonary vascular resistance, followed by right ventricular hypertrophy and failure. Despite considerable advancements in PAH treatment prognosis remains poor. We aim to evaluate the potential for using the cytokine resistin as a genetic and biological marker for disease severity and survival in a large cohort of patients with PAH.

Developing transmissible vaccines for animal infections.

Intrinsically safe designs and a staged transparent development process will be essential.

Advances in understanding bat infection dynamics across biological scales.

Over the past two decades, research on bat-associated microbes such as viruses, bacteria and fungi has dramatically increased. Here, we synthesize themes from a conference symposium focused on advances in the research of bats and their microbes, including physiological, immunological, ecological and epidemiological research that has improved our understanding of bat infection dynamics at multiple biological scales. We first present metrics for measuring individual bat responses to infection and challenges associated with using these metrics.

Management of paediatric sleep-disordered breathing.

Paediatric sleep-disordered breathing is a common condition which varies in severity from snoring to obstructive sleep apnoea. Paediatric sleep-disordered breathing is usually diagnosed clinically, with investigations such as polysomnography reserved for more complex cases. Management can involve watching and waiting, medical or adjunct treatments and adenotonsillectomy.

Recombinant transmissible vaccines will be intrinsically contained despite the ability to superinfect.

Introduction: Transmissible vaccines offer a novel approach to suppressing viruses in wildlife populations, with possible applications against viruses that infect humans as zoonoses - Lassa, Ebola, rabies. To ensure safety, current designs propose a recombinant vector platform in which the vector is isolated from the target wildlife population. Because using an endemic vector creates the potential for preexisting immunity to block vaccine transmission, these designs focus on vector viruses capable of superinfection, spreading throughout the host population following vaccination of few individuals.

Kynurenine pathway metabolism evolves with development of preclinical and scleroderma-associated pulmonary arterial hypertension.

Understanding metabolic evolution underlying pulmonary arterial hypertension (PAH) development may clarify pathobiology and reveal disease-specific biomarkers. Patients with systemic sclerosis (SSc) are regularly surveilled for PAH, presenting an opportunity to examine metabolic change as disease develops in an at-risk cohort. We performed mass spectrometry-based metabolomics on longitudinal serum samples collected before and near SSc-PAH diagnosis, compared with time-matched SSc subjects without PAH, in a SSc surveillance cohort.

Exercise training and resting blood pressure: a large-scale pairwise and network meta-analysis of randomised controlled trials.

Objective: To perform a large-scale pairwise and network meta-analysis on the effects of all relevant exercise training modes on resting blood pressure to establish optimal antihypertensive exercise prescription practices.

Design: Systematic review and network meta-analysis.

Data Sources: PubMed (Medline), the Cochrane library and Web of Science were systematically searched.

Intravenous prostacyclins for right ventricular failure following left ventricular assist device in paediatric heart failure.

Right ventricular failure after placement of left ventricular assist device in paediatric heart failure is associated with increased mortality. We report successful use of intravenous prostacyclin for right ventricular support and pulmonary hypertension after initiation of left ventricular assist device support. This suggests that intravenous prostacyclins may be an important therapy in right ventricular failure following ventricular assist device implantation.

Metabolomic Differences in Connective Tissue Disease-Associated Versus Idiopathic Pulmonary Arterial Hypertension in the PVDOMICS Cohort.

Objective: Patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) experience worse survival and derive less benefit from pulmonary vasodilator therapies than patients with idiopathic PAH (IPAH). We sought to identify differential metabolism in patients with CTD-PAH versus patients with IPAH that might underlie these observed clinical differences.

Methods: Adult participants with CTD-PAH (n = 141) and IPAH (n = 165) from the Pulmonary Vascular Disease Phenomics (PVDOMICS) study were included.

High-Intensity Interval Training and Cardiometabolic Health in the General Population: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

Background: High-intensity interval training (HIIT) remains a promising exercise mode in managing cardiometabolic health. Large-scale analyses are necessary to understand its magnitude of effect on important cardiometabolic risk factors and inform guideline recommendations.

Objective: We aimed to perform a novel large-scale meta-analysis on the effects of HIIT on cardiometabolic health in the general population.

Improved closed test setup for biodegradation testing of slightly volatile substances in water-sediment systems (OECD 308).

Standardized biodegradation testing methods, like the OECD 308 Aerobic and Anaerobic Transformation in Aquatic Sediment Systems, generate data on biodegradation required during environmental risk and hazard assessment of chemicals under different European and international regulations. However, difficulties arise when applying the OECD 308 guideline for testing hydrophobic volatile chemicals. Especially the use of a co-solvent (like acetone) as a measure to facilitate the application of the test chemical in combination with a closed setup to reduce losses due to volatilization tend to deplete/restrict the amount of oxygen in the test system.

Inferring the disruption of rabies circulation in vampire bat populations using a betaherpesvirus-vectored transmissible vaccine.

Transmissible vaccines are an emerging biotechnology that hold prospects to eliminate pathogens from wildlife populations. Such vaccines would genetically modify naturally occurring, nonpathogenic viruses ("viral vectors") to express pathogen antigens while retaining their capacity to transmit. The epidemiology of candidate viral vectors within the target wildlife population has been notoriously challenging to resolve but underpins the selection of effective vectors prior to major investments in vaccine development.

Critical care nursing workforce in crisis: A discussion paper examining contributing factors, the impact of the COVID-19 pandemic and potential solutions.

Aims And Objectives: The critical care nursing workforce is in crisis, with one-third of critical care nurses worldwide intending to leave their roles. This paper aimed to examine the problem from a wellbeing perspective, offering implications for research, and potential solutions for organisations.

Design: Discursive/Position paper.