Echocardiographic Assessment in Patients with Vascular Ehlers-Danlos Syndrome: Insights from an Unexplored Field.

Introduction: Vascular Ehlers-Danlos syndrome (vEDS) is an inherited connective tissue disorder characterized by arterial fragility. Celiprolol is a β1-adrenoceptor antagonist with partial β2 agonist activity that has been shown to reduce rates of vascular events in this setting, though the underlying mechanisms are not yet fully understood. Moreover, very few echocardiographic data are available in patients with vEDS.

Reflection on the landscape of education in the area of exposure modelling.

Exposure models are essential for a range of contexts involving exposure science. The Exposure Models Working Group, established under ISES Europe, identified that to improve model use, suitable training and education is required. However, there is currently no formal educational training programme for exposure modelling in Europe.

Physiologically based pharmacokinetic modeling of metal nanoparticles for risk assessment of inhalation exposures: a state-of-the-science expert panel review.

A critical review of the current state-of-the-science for the physiologically based pharmacokinetic (PBPK) modeling of metal nanoparticles and their application to human health risk assessment for inhalation exposures was conducted. A systematic literature search was used to identify four model groups (defined as a primary publication along with multiple supplementary publications) subject to review. Using a recent guideline document from the Organization for Economic Cooperation and Development (OECD) for PBPK model evaluation, these model groups were critically peer-reviewed by an independent panel of experts to identify those to be considered for modeling and simulation application.

Epistaxis and Clinic Blood Pressure Values: Is There a Relationship?

Introduction: Epistaxis is the most common otorhinolaryngological emergency and historically there have been an important debate whether there is a cause-effect relationship with high blood pressure.

Aim: This retrospective study explored whether hypertension is a significant risk factor for epistaxis in Emergency Department (ED) patients and examined associations between blood pressure levels and epistaxis episodes.

Materials And Methods: Two groups were studied: Group A (patients with epistaxis) and Group B (control).

Advancing PFAS risk assessment: Integrative approaches using agent-based modelling and physiologically-based kinetic for environmental and health safety.

Per- and polyfluoroalkyl substances (PFAS), ubiquitous in a myriad of consumer and industrial products, and depending on the doses of exposure represent a hazard to both environmental and public health, owing to their persistent, mobile, and bio accumulative properties. These substances exhibit long half-lives in humans and can induce potential immunotoxic effects at low exposure levels, sparking growing concerns. While the European Food Safety Authority (EFSA) has assessed the risk to human health related to the presence of PFAS in food, in which a reduced antibody response to vaccination in infants was considered as the most critical human health effect, a comprehensive grasp of the molecular mechanisms spearheading PFAS-induced immunotoxicity is yet to be attained.

Serum Uric Acid, Hypertriglyceridemia, and Carotid Plaques: A Sub-Analysis of the URic Acid Right for Heart Health (URRAH) Study.

High levels of serum uric acid (SUA) and triglycerides (TG) might promote high-cardiovascular-risk phenotypes, including subclinical atherosclerosis. An interaction between plaques xanthine oxidase (XO) expression, SUA, and HDL-C has been recently postulated. Subjects from the URic acid Right for heArt Health (URRAH) study with carotid ultrasound and without previous cardiovascular diseases (CVD) (n = 6209), followed over 20 years, were included in the analysis.

Systematic evaluation of high-throughput PBK modelling strategies for the prediction of intravenous and oral pharmacokinetics in humans.

Physiologically based kinetic (PBK) modelling offers a mechanistic basis for predicting the pharmaco-/toxicokinetics of compounds and thereby provides critical information for integrating toxicity and exposure data to replace animal testing with in vitro or in silico methods. However, traditional PBK modelling depends on animal and human data, which limits its usefulness for non-animal methods. To address this limitation, high-throughput PBK modelling aims to rely exclusively on in vitro and in silico data for model generation.

Report of the First ONTOX Stakeholder Network Meeting: Digging Under the Surface of ONTOX Together With the Stakeholders.

The first Stakeholder Network Meeting of the EU Horizon 2020-funded ONTOX project was held on 13-14 March 2023, in Brussels, Belgium. The discussion centred around identifying specific challenges, barriers and drivers in relation to the implementation of non-animal new approach methodologies (NAMs) and probabilistic risk assessment (PRA), in order to help address the issues and rank them according to their associated level of difficulty. ONTOX aims to advance the assessment of chemical risk to humans, without the use of animal testing, by developing non-animal NAMs and PRA in line with 21st century toxicity testing principles.

Despite celiprolol therapy, patients with vascular Ehlers-Danlos syndrome remain at risk of vascular events: A 12-year experience in an Italian referral center.

Background: Vascular Ehlers-Danlos syndrome (vEDS) is an inherited connective tissue disorder characterized by arterial fragility. Celiprolol has been suggested to significantly reduce rates of vascular events in this setting, though real-world evidence is limited. The aim of this study was to report our experience with celiprolol therapy in vEDS management.

Reproductive toxicity in birds predicted by physiologically-based kinetics and bioenergetics modelling.

Effects on the growth and reproduction of birds are important endpoints in the environmental risk assessment (ERA) of pesticides. Toxicokinetic-toxicodynamic models based on dynamic energy budget theory (DEB) are promising tools to predict these effects mechanistically and make extrapolations relevant to ERA. However, before DEB-TKTD models are accepted as part of ERA for birds, ecotoxicological case studies are required so that stakeholders can assess their capabilities.

Use of non-invasive respiratory supports in high-intensity internal medicine setting during the first two waves of the COVID-19 pandemic emergency in Italy: a multicenter, real-life experience.

During the first two waves of the COVID-19 emergency in Italy, internal medicine high-dependency wards (HDW) have been organized to manage patients with acute respiratory failure (ARF). There is heterogeneous evidence about the feasibility and outcomes of non-invasive respiratory supports (NIRS) in settings outside the intensive care unit (ICU), including in patients deemed not eligible for intubation (i.e.

FAIR environmental and health registry (FAIREHR)- supporting the science to policy interface and life science research, development and innovation.

The environmental impact on health is an inevitable by-product of human activity. Environmental health sciences is a multidisciplinary field addressing complex issues on how people are exposed to hazardous chemicals that can potentially affect adversely the health of present and future generations. Exposure sciences and environmental epidemiology are becoming increasingly data-driven and their efficiency and effectiveness can significantly improve by implementing the FAIR (findable, accessible, interoperable, reusable) principles for scientific data management and stewardship.

Ascending aorta dilatation is associated to hard cardiovascular events, follow-up from multicentric ARGO-Perspective project.

Aortic root dilatation has been proposed as hypertension-mediated organ damage (HMOD). Nevertheless, the role of the aortic root dilatation as a possible additional HMOD is still unclear since studies conducted so far are quite heterogeneous regarding the type of population analyzed, the aortic tract considered, and the type of outcomes accounted for. The aim of the present study is to assess whether the presence of aortic dilatation is associated with strong cardiovascular (CV) events (MACE: heart failure, CV death, stroke, acute coronary syndrome, myocardial revascularization) in a population of patients affected by essential hypertension.

OECD harmonised template 201: Structuring and reporting mechanistic information to foster the integration of new approach methodologies for hazard and risk assessment of chemicals.

In the European Union, the Chemicals Strategy for Sustainability (CSS) highlights the need to enhance the identification and assessment of substances of concern while reducing animal testing, thus fostering the development and use of New Approach Methodologies (NAMs) such as in silico, in vitro and in chemico. In the United States, the Tox21 strategy aims at shifting toxicological assessments away from traditional animal studies towards target-specific, mechanism-based and biological observations mainly obtained by using NAMs. Many other jurisdictions around the world are also increasing the use of NAMs.

Serum uric acid and left ventricular mass index independently predict cardiovascular mortality: The uric acid right for heart health (URRAH) project.

Unlabelled: A relationship between serum uric acid (SUA) and cardiovascular (CV) events has been documented in the Uric Acid Right for Heart Health (URRAH) study.

Aim: of this study was to investigate the association between SUA and left ventricular mass index (LVMI) and whether SUA and LVMI or their combination may predict the incidence of CV death.

Methods: Subjects with echocardiographic measurement of LVMI included in the URRAH study (n=10733) were part of this analysis.

An Overview of Physiologically-Based Pharmacokinetic Models for Forensic Science.

A physiologically-based pharmacokinetic (PBPK) model represents the structural components of the body with physiologically relevant compartments connected via blood flow rates described by mathematical equations to determine drug disposition. PBPK models are used in the pharmaceutical sector for drug development, precision medicine, and the chemical industry to predict safe levels of exposure during the registration of chemical substances. However, one area of application where PBPK models have been scarcely used is forensic science.

Advancing New Approach Methodologies (NAMs) for Tobacco Harm Reduction: Synopsis from the 2021 CORESTA SSPT-NAMs Symposium.

New approach methodologies (NAMs) are emerging chemical safety assessment tools consisting of in vitro and in silico (computational) methodologies intended to reduce, refine, or replace (3R) various in vivo animal testing methods traditionally used for risk assessment. Significant progress has been made toward the adoption of NAMs for human health and environmental toxicity assessment. However, additional efforts are needed to expand their development and their use in regulatory decision making.

Unattended versus Attended Blood Pressure Measurement: Relationship with Retinal Microcirculation.

Though the relationship between both “attended” and “unattended” BP and several forms of target organ damage have been evaluated, data on retinal arteriolar alterations are lacking. The aim of our study was to evaluate the relationship between “attended” or “unattended” BP values and retinal arteriolar changes in consecutive individuals undergoing a clinical evaluation and assessment of retinal fundus at an ESH Excellence Centre. An oscillometric device programmed to perform 3 BP measurements, at 1 min intervals and after 5 min of rest was used on all individuals to measure BP with the patient alone in the room (“unattended”) or in the presence of the physician (“attended”) in the same day in a random order.

Computational modelling and simulation for immunotoxicity prediction induced by skin sensitisers.

In many domains regulating chemicals and chemical products, there is a legal requirement to determine skin sensitivity to allergens. While many in vitro assays to detect contact hypersensitivity have been developed as alternatives to animal testing over the past ten years and significant progress has been made in this area, there is still a need for continued investment in the creation of techniques and strategies that will allow accurate identification of potential contact allergens and their potency in vitro. In silico models are promising tools in this regard.

Subclinical HMOD in Hypertension: Left Ventricular Diastolic Dysfunction.

Arterial hypertension represents an important risk factor for the development of cardiac, vascular and renal events, predisposing to heart failure, acute coronary syndromes, peripheral artery disease, stroke, and chronic renal disease. Arterial hypertension leads to the development of subclinical hypertension mediated organ damage (HMOD) which has prognostic relevance and may influence the choice of treatment options. Alterations of cardiac structure and function represent the more widely assessed form of HMOD.

Proceedings of a workshop to address animal methods bias in scientific publishing.

Animal methods bias in scientific publishing is a newly defined type of publishing bias describing a preference for animal-based methods where they may not be necessary or where nonanimal-based methods may already be suitable, which impacts the likelihood or timeliness of a manuscript being accepted for publication. This article covers the output from a workshop between stakeholders in publishing, academia, industry, government, and non-governmental organizations. The intent of the workshop was to exchange perspectives on the prevalence, causes, and impact of animal methods bias in scientific publishing, as well as to explore mitigation strategies.