Endothelial IGFBP6 suppresses vascular inflammation and atherosclerosis.

Beyond dyslipidemia, inflammation contributes to the development of atherosclerosis. However, intrinsic factors that counteract vascular inflammation and atherosclerosis remain scarce. Here we identify insulin-like growth factor binding protein 6 (IGFBP6) as a homeostasis-associated molecule that restrains endothelial inflammation and atherosclerosis.

High-risk percutaneous coronary intervention in patients with reduced left ventricular ejection fraction deemed not suitable for surgical revascularisation. A clinical consensus statement from the European Association of Percutaneous Cardiovascular Interventions (EAPCI) in collaboration with the ESC Working Group on Cardiovascular Surgery.

This clinical consensus statement of the European Association of Percutaneous Cardiovascular Interventions was developed in association with the European Society of Cardiology Working Group on Cardiovascular Surgery. It aims to define procedural and contemporary technical requirements that may improve the efficacy and safety of percutaneous coronary intervention (PCI), both in the acute phase and at long-term follow-up, in a high-risk cohort of patients on optimal medical therapy when clinical and anatomical high-risk criteria are present that entail unacceptable surgical risks, precluding the feasibility of coronary artery bypass grafting (CABG). This document pertains to patients with surgical contraindication according to the Heart Team, in whom medical therapy has failed (e.

Altered Cellular Metabolism Is a Consequence of Loss of the Ataxia-Linked Protein Sacsin.

Mitochondrial dysfunction is implicated in the pathogenesis of the neurological condition autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), yet precisely how the mitochondrial metabolism is affected is unknown. Thus, to better understand changes in the mitochondrial metabolism caused by loss of the sacsin protein (encoded by the SACS gene, which is mutated in ARSACS), we performed mass spectrometry-based tracer analysis, with both glucose- and glutamine-traced carbon. Comparing the metabolite profiles between wild-type and sacsin-knockout cell lines revealed increased reliance on aerobic glycolysis in sacsin-deficient cells, as evidenced by the increase in lactate and reduction of glucose.

Zonulopathies as Genetic Disorders of the Extracellular Matrix.

The zonular fibres are formed primarily of fibrillin-1, a large extracellular matrix (ECM) glycoprotein, and also contain other constituents such as LTBP-2, ADAMTSL6, MFAP-2 and EMILIN-1, amongst others. They are critical for sight, holding the crystalline lens in place and being necessary for accommodation. Zonulopathies refer to conditions in which there is a lack or disruption of zonular support to the lens and may clinically be manifested as ectopia lens (EL)-defined as subluxation of the lens outside of the pupillary plane or frank displacement (dislocation) into the vitreous or anterior segment.

Imagine, Discover, Inspire: Proceedings of the 4th International Conference of the Trisomy 21 Research Society.

Down syndrome (DS) or trisomy 21 (T21) is present in a significant number of children and adults around the world and is associated with cognitive and medical challenges. Through research, the T21 Research Society (T21RS), established in 2014, unites a worldwide community dedicated to understanding the impact of T21 on biological systems and improving the quality of life of people with DS across the lifespan. T21RS hosts an international conference every two years to support collaboration, dissemination, and information sharing for this goal.

Hypertrophic cardiomyopathy management: a systematic review of the clinical practice guidelines and recommendations.

Aims: In light of recent advances in imaging techniques, molecular understanding and therapeutic options in hypertrophic cardiomyopathy (HCM), we performed a systematic review of current guidelines for the diagnosis and management of HCM in order to identify consensus and discrepant areas in the clinical practice guidelines.

Methods And Results: We systematically reviewed the English language guidelines and recommendations for the management of HCM in adults. MEDLINE and EMBASE databases were searched for guidelines published in the last 10 years.

The association between adverse childhood experiences and adult cardiac function in the UK Biobank.

Aims: The importance of early life factors in determining health in later adulthood is increasingly recognized. This study evaluated the association of adverse childhood experiences (ACEs) with cardiovascular magnetic resonance (CMR) phenotypes.

Methods And Results: UK Biobank participants who had completed CMR and the self-reported questionnaire on traumatic childhood experiences were included.

Aneurysm Is Restricted by CD34 Cell-Formed Fibrous Collars Through the PDGFRb-PI3K Axis.

Aortic aneurysm is a life-threatening disease caused by progressive dilation of the aorta and weakened aortic walls. Its pathogenesis involves an imbalance between connective tissue repair and degradation. CD34 cells comprise a heterogeneous population that exhibits stem cell and progenitor cell properties.

Cardiovascular magnetic resonance in patients with mitral valve prolapse.

With a prevalence of 2-3% in the general population, mitral valve prolapse (MVP) is the most common valvular heart disease. The clinical course is benign in the majority of patients, although severe mitral regurgitation, heart failure, and sudden cardiac death affect a non-negligible subset of patients. Imaging of MVP was confined to echocardiography until a few years ago when it became apparent that cardiovascular magnetic resonance (CMR) could offer comparative advantages for detecting and quantifying mitral valve abnormalities alongside tissue myocardial characterization.

Histopathological domain adaptation with generative adversarial networks: Bridging the domain gap between thyroid cancer histopathology datasets.

Deep learning techniques are increasingly being used to classify medical imaging data with high accuracy. Despite this, due to often limited training data, these models can lack sufficient generalizability to predict unseen test data, produced in different domains, with comparable performance. This study focuses on thyroid histopathology image classification and investigates whether a Generative Adversarial Network [GAN], trained with just 156 patient samples, can produce high quality synthetic images to sufficiently augment training data and improve overall model generalizability.

A flavoromics approach to investigate the effect of Saskatoon berry powder on the sensory attributes, acceptability, volatile components, and electronic nose responses of a low-fat frozen yogurt.

Introduction: Saskatoon berries are grown in Canada and some northwestern states in the United States, and are notable for containing abundant antioxidant polyphenols, vitamins, metal elements, and fiber. To increase consumer interest in and accessibility to Saskatoon berries, some producers have begun to develop processes for refining Saskatoon berries into a powder with an extended shelf life that can be incorporated into a variety of value-added food products. To assess the desirability of this approach, this study sought to determine how the sensory attributes, consumer acceptability, and volatile and non-volatile composition of a plain, Greek-style frozen yogurt (PY) changed when fortified with 16% Saskatoon berry powder (SBP).

Preoperative activation of the renin-angiotensin system and myocardial injury in noncardiac surgery: exploratory mechanistic analysis of the SPACE randomised controlled trial.

Background: Hypertension therapy in older adults is often suboptimal, in part because of inadequate suppression of the renin-angiotensin-aldosterone system (RAAS). We hypothesised that distinct endotypes of RAAS activation before noncardiac surgery are associated with increased risk of myocardial injury.

Methods: This was a prespecified exploratory analysis of a multicentre randomised controlled trial (ISRCTN17251494) which randomised patients ≥60 yr old undergoing elective noncardiac surgery to either continue or stop RAAS inhibitors (determined by pharmacokinetic profiles).

A Systematic Review of Multimodal Analgesic Effectiveness on Acute Postoperative Pain After Adult Cardiac Surgery.

Aim: To synthesise the best available empirical evidence about the effectiveness of multimodal analgesics on pain after adult cardiac surgery.

Design: A systematic review with meta-analysis.

Methods: Indexed full-text papers or abstracts, in any language, of randomised controlled trials of adult patients undergoing cardiac surgery investigating multimodal postoperative analgesic regimen effect on mean level of patient-reported pain intensity at rest.

Pushing the boundaries of radiotherapy-immunotherapy combinations: highlights from the 7 immunorad conference.

Over the last decade, the annual Immunorad Conference, held under the joint auspicies of Gustave Roussy (Villejuif, France) and the Weill Cornell Medical College (New-York, USA) has aimed at exploring the latest advancements in the fields of tumor immunology and radiotherapy-immunotherapy combinations for the treatment of cancer. Gathering medical oncologists, radiation oncologists, physicians and researchers with esteemed expertise in these fields, the Immunorad Conference bridges the gap between preclinical outcomes and clinical opportunities. Thus, it paves a promising way toward optimizing radiotherapy-immunotherapy combinations and, from a broader perspective, improving therapeutic strategies for patients with cancer.

Efficient reinterpretation of rare disease cases using Exomiser.

Whole genome sequencing has transformed rare disease research; however, 50-80% of rare disease patients remain undiagnosed after such testing. Regular reanalysis can identify new diagnoses, especially in newly discovered disease-gene associations, but efficient tools are required to support clinical interpretation. Exomiser, a phenotype-driven variant prioritisation tool, fulfils this role; within the 100,000 Genomes Project (100kGP), diagnoses were identified after reanalysis in 463 (2%) of 24,015 unsolved patients after previous analysis for variants in known disease genes.

Clinical approach to palpitations in pregnancy.

Palpitations are common in pregnancy and warrant investigation. Palpitations may be caused by non-cardiac and cardiac causes. Patients with structural or functional abnormalities or inherited cardiovascular disease are more likely to develop arrhythmia, especially during pregnancy when the mother's body undergoes extensive physiological adaptations, which further contribute to an increased arrhythmia risk.

Leucocyte telomere length and conduction system ageing.

Background: Deterioration of the cardiac conduction system is an important manifestation of cardiac ageing. Cellular ageing is accompanied by telomere shortening and telomere length (TL) is often regarded as a marker of biological ageing, potentially adding information regarding conduction disease over and above chronological age. We therefore sought to evaluate the association between leucocyte telomere length (LTL) on two related, but distinct aspects of the cardiac conduction system: ECG measures of conduction (PR interval and QRS duration) and incident pacemaker implantation in a large population-based cohort.

Prediction of atrial and ventricular arrhythmias using multiple cardiovascular risk-factor polygenic risk scores.

Background: Atrial fibrillation (AF) prediction improves by combining clinical scores with a polygenic risk score (PRS) for AF (AF-PRS), but there are limited studies of PRS for ventricular arrhythmia (VA) prediction.

Objective: We assessed the value of including multiple PRS for cardiovascular risk factors (CV-PRS) for incident AF and VA prediction.

Methods: We used 158,733 individuals of European ancestry from UK Biobank to build 3 models for AF: CHARGE-AF (AF1), AF1 + AF-PRS (AF2), AF2 + CV-PRS (AF3).

Peripheral Neuropathy in Mitochondrial Trifunctional Protein Deficiency due to a Variant in Gene.

We report a 4.5-year-old girl with recurrent episodes of bilateral lower limb weakness following periods of upper respiratory tract infection since the age of 1.5 years.

Roles of the lamin A-specific tail region in the localization to sites of nuclear envelope rupture.

The nuclear lamina (NL) lines the nuclear envelope (NE) to maintain nuclear structure in metazoan cells. The major NL components, the nuclear lamins contribute to the protection against NE rupture induced by mechanical stress. Lamin A (LA) and a short form of the splicing variant lamin C (LC) are diffused from the nucleoplasm to sites of NE rupture in immortalized mouse embryonic fibroblasts (MEFs).

Diagnosis and management of dilated cardiomyopathy: a systematic review of clinical practice guidelines and recommendations.

Dilated cardiomyopathy (DCM) is extensively discussed in numerous expert consensus documents and international guidelines, with differing recommendations. To support clinicians in daily practice and decision-making, we conducted a systematic review of key guidelines and recommendations concerning the diagnosis and clinical management of DCM. Our research encompassed MEDLINE and EMBASE databases for relevant articles published, as well as the websites of relevant scientific societies.

Procedural factors influencing successful coronary sinus reducer implantation for refractory angina: A single-centre experience.

Background: Coronary sinus reducer (CSR) implantation is emerging as a novel effective percutaneous therapy for patients with refractory angina. Limited data exists examining the factors influencing successful CSR implantation. As CSR implantation becomes more widely adopted, a greater understanding of the procedural challenges which operators encounter is required.

Pathogenesis of Sjögren's disease: one year in review 2024.

The pathogenesis of Sjögren's disease (SjD) is still elusive; however, the disease is widely recognised as a multistep disorder triggered by the interplay of environmental, hormonal and genetic factors. Innate immune system plays a crucial role in the initiation of the inflammatory process, but the amplification and the perpetuation of the autoimmune process require a continual interaction between the innate and adaptive immune systems. Several important contributions elucidating SjD pathogenesis have been recently published due to emerging technologies.