Phosphorylation of cytochrome c at tyrosine 48 finely regulates its binding to the histone chaperone SET/TAF-Iβ in the nucleus.

Post-translational modifications (PTMs) of proteins are ubiquitous processes present in all life kingdoms, involved in the regulation of protein stability, subcellular location and activity. In this context, cytochrome c (Cc) is an excellent case study to analyze the structural and functional changes induced by PTMS as Cc is a small, moonlighting protein playing different roles in different cell compartments at different cell-cycle stages. Cc is actually a key component of the mitochondrial electron transport chain (ETC) under homeostatic conditions but is translocated to the cytoplasm and even the nucleus under apoptotic conditions and/or DNA damage.

Uplift of genetic diagnosis of rare respiratory disease using airway epithelium transcriptome analysis.

Rare genetic respiratory disease has an incidence rate of more than 1:2500 live births in Northern Europe and carries significant disease burden. Early diagnosis improves outcomes, but many individuals remain without a confident genetic diagnosis. Improved and expanded molecular testing methods are required to improve genetic diagnosis rates and thereby improve clinical outcomes.

An and efficacy evaluation of gene therapy candidate SBT101 in mouse models of adrenomyeloneuropathy and in NHPs.

Adrenomyeloneuropathy is a progressive neurodegenerative disease caused by pathogenic variants in the gene, resulting in very-long-chain fatty acid (VLCFA) accumulation that leads to dying-back axonopathy. Our candidate gene therapy, SBT101 (AAV9-human [h]), aims to ameliorate pathology by delivering functional copies of h to the spinal cord. Transduced cells produce functional ABCD1 protein, thereby repairing the underlying biochemical defect.

Status of the implementation of pharmacogenetics in clinical practice in Spain: from regional to national initiatives.

Introduction: Pharmacogenetics (PGx) has the potential to improve patient care, allowing to transform medical interventions by providing personalized therapeutic strategies. Scientific evidence supports the use of PGx in clinical practice and international organizations are developing clinical guidelines to facilitate the utilization of PGx testing. However, clinical implementation of PGx is limited and unequal worldwide.

Mediterranean Diet Pattern: Potential Impact on the Different Altered Pathways Related to Cardiovascular Risk in Advanced Chronic Kidney Disease.

Background: Cardiovascular disease (CVD) remains the most common cause of mortality in chronic kidney disease (CKD) patients. Several studies suggest that the Mediterranean diet reduces the risk of CVD due to its influence on endothelial function, inflammation, lipid profile, and blood pressure. Integrating metabolomic and proteomic analyses of CKD could provide insights into the pathways involved in uremia-induced CVD and those pathways modifiable by the Mediterranean diet.

Hemodynamic effects of carvedilol plus simvastatin in cirrhosis with severe portal hypertension and suboptimal response to β-blockers: A double-blind, placebo-controlled, randomized-trial.

Background Aims: Carvedilol is a non-selective β-blocker (NSBBs) with anti-α1-adrenergic activity, more effective than traditional NSBBs in reducing portal-pressure (HVPG). However, 35%-45% of patients still have insufficient HVPG-decrease. Statins ameliorate endothelial dysfunction, reduce hepatic vascular resistance, and have pleiotropic effects.

Prevention of cardiometabolic diseases through dietary modifications.

Purpose Of Review: Cardiometabolic diseases (CMDs) increasingly contribute to the cumulative burden of morbidity and mortality worldwide. Here, we reviewed intervention studies using a randomized controlled trial (RCT) design as well as meta-analyses of RCTs aimed at testing the effectiveness of different dietary approaches for CMD prevention.

Recent Findings: Recent studies testing dietary approaches for CMD prevention were summarized narratively, with a focus on interventions based on caloric restriction and fasting, healthy dietary patterns and food-based dietary modifications.

Pressure support, patient effort and tidal volume: a conceptual model for a non linear interaction.

Pressure support ventilation (PSV) is a form of assisted ventilation which has become frequently used, with the aim of partially unloading the patient's inspiratory muscles. Both under- and over-assistance should be avoided to target a lung- and diaphragm- protective ventilation. Herein, we propose a conceptual model, supported by actual data, to describe how patient and ventilator share the generation of tidal volume (Vt) in PSV and how respiratory system compliance (Crs) affects this interaction.

TNF-alpha gene promoter's hypomethylation mediates a pro-inflammatory phenotype in peripheral blood monocytes from apical periodontitis individuals.

Aim: Epigenetic regulation of the key inflammatory genes plays a crucial role in controlling monocyte/macrophage-mediated local and systemic responses to bacterial challenges. However, it has not been addressed in apical periodontitis (AP). We aimed to explore the methylation pattern of the TNF-α gene promoter and its association with the inflammatory phenotype of peripheral blood monocytes from individuals with AP and controls.

Validation of a sensor system for the measurement of breath ammonia using selected-ion flow-tube mass spectrometry.

The measurement of trace breath gases is of growing interest for its potential to provide non-invasive physiological information in health and disease. While instrumental techniques such as selected-ion flow-tube mass spectrometry (SIFT-MS) can achieve this, these are less suitable for clinical application. Sensitive sensor-based systems for breath ammonia could be more widely deployed, but have proven challenging to develop.

Mapping the diagnostic odyssey of congenital disorders of glycosylation (CDG): insights from the community.

Background: Congenital disorders of glycosylation (CDG) are a group of rare metabolic diseases with heterogeneous presentations, leading to substantial diagnostic challenges, which are poorly understood. Therefore, this study aims to elucidate this diagnostic journey by examining families' and professionals' experiences.

Results And Discussion: A questionnaire was designed for CDG families and professionals, garnering 160 and 35 responses, respectively.

ALCOHOL-ASSOCIATED LIVER DISEASE: NATURAL HISTORY, MANAGEMENT AND NOVEL TARGETED THERAPIES.

Alcohol consumption is a leading cause of preventable morbidity and mortality worldwide and the primary cause of advanced liver disease. Alcohol use disorder (AUD) is a chronic, frequently relapsing condition characterized by persistent alcohol consumption despite its negative consequences. Alcohol-associated liver disease (ALD) encompasses a series of stages, from fatty liver (steatosis) to inflammation (steatohepatitis), fibrosis, and, ultimately, liver cirrhosis and its complications.

AI-enabled workflow for automated classification and analysis of feto-placental Doppler images.

Introduction: Extraction of Doppler-based measurements from feto-placental Doppler images is crucial in identifying vulnerable new-borns prenatally. However, this process is time-consuming, operator dependent, and prone to errors.

Methods: To address this, our study introduces an artificial intelligence (AI) enabled workflow for automating feto-placental Doppler measurements from four sites (i.

Exploring mitochondrial blood-based and genetic markers in older adults with mild cognitive impairment and remitted major depressive disorder.

Mild cognitive impairment (MCI) is a prodromal stage in aging to possible progression to Alzheimer's disease and related dementia (ADRD), where co-occurrence of major depressive disorder (MDD) accelerates the progression. Metabolic and mitochondrial abnormalities in ADRD and other neurodegenerative disorders have been widely suggested, while possible mitochondrial dysfunction has been associated with etiopathology of both MCI and MDD. Hence, investigation of mitochondrial markers in MCI, MDD, and presence of both conditions is warranted.

Tobacco use disorder in patients with other mental disorders: a dual disorder perspective from clinical neuroscience.

Tobacco smoking is the leading cause of disability and preventable deaths worldwide, but it should be differentiated from tobacco use disorder, which is, according to the Diagnostic and Statistical Manual of Mental Disorders, a mental disorder. The rapid delivery of nicotine to the brain activates acetylcholine receptors and stimulates the release of dopamine, both systems implicated in other mental disorders. Rates of tobacco use disorder are much higher among people suffering from other mental disorders and these patients find it more difficult to quit.

Personalised Health Behaviour Support Programme in Adults With Post-COVID Syndrome: A Randomised, Controlled Pilot Feasibility Trial.

Background: We investigated whether a novel 8-week personalised health behaviour support programme, focusing on the stability of symptoms and strategies to improve activities of daily living, was feasible and acceptable in adults with post-COVID syndrome.

Methods: In this randomised, controlled, pilot feasibility trial, 32 adults with post-COVID syndrome (continued symptoms for ≥ 12 weeks) were randomised 1:1 to receive personalised health behaviour support (self-reported physical activity and symptom diaries, plus seven one-to-one remotely delivered personalised self-management support sessions), once weekly for 8-weeks, or usual care (referral to online 'your COVID-19 recovery' programme). The primary outcome was the feasibility of recruiting and randomising adults with post-COVID syndrome.

An integrative network-based approach to identify driving gene communities in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is an etiologically complex disease characterized by acute exacerbations and stable phases. We aimed to identify biological functions modulated in specific COPD conditions, using whole blood samples collected in the AERIS clinical study (NCT01360398). Considered conditions were exacerbation onset, severity of airway obstruction, and presence of respiratory pathogens in sputum samples.

Development of Halloysite Nanohybrids-Based Films: Enhancing Mechanical and Hydrophilic Properties for Wound Healing.

Most of the therapeutic systems developed for managing chronic skin wounds lack adequate mechanical and hydration properties, primarily because they rely on a single component. This study addresses this issue by combining organic and inorganic materials to obtain hybrid films with enhanced mechanical behavior, adhesion, and fluid absorption properties. To that aim, chitosan/hydrolyzed collagen blends were mixed with halloysite/antimicrobial nanohybrids at 10% and 20% (/) using glycerin or glycerin/polyethylene glycol-1500 as plasticizers.

Pulsed Field Ablation of Atrial Fibrillation: A Novel Technology for Safer and Faster Ablation.

Atrial fibrillation (AF), the most common arrhythmia, is associated with increased morbidity, mortality, and healthcare costs. Evidence indicates that rhythm control offers superior cardiovascular outcomes compared to rate control, especially when initiated early after the diagnosis of AF. Catheter ablation remains the single best therapy for AF; however, it is not free from severe complications and only a small percentage of AF patients in the Western world ultimately receive ablation.