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Dilatation of the ascending aorta (AAD) is a prevalent aortopathy that occurs frequently associated with bicuspid aortic valve (BAV), the most common human congenital cardiac malformation. The molecular mechanisms leading to AAD associated with BAV are still poorly understood. The search for differentially expressed genes in diseased tissue by quantitative real-time PCR (qPCR) is an invaluable tool to fill this gap. However, studies dedicated to identify reference genes necessary for normalization of mRNA expression in aortic tissue are scarce. In this report, we evaluate the qPCR expression of six candidate reference genes in tissue from the ascending aorta of 52 patients with a variety of clinical and demographic characteristics, normal and dilated aortas, and different morphologies of the aortic valve (normal aorta and normal valve n = 30; dilated aorta and normal valve n = 10; normal aorta and BAV n = 4; dilated aorta and BAV n = 8). The expression stability of the candidate reference genes was determined with three statistical algorithms, GeNorm, NormFinder and Bestkeeper. The expression analyses showed that the most stable genes for the three algorithms employed were CDKN1β, POLR2A and CASC3, independently of the structure of the aorta and the valve morphology. In conclusion, we propose the use of these three genes as reference genes for mRNA expression analysis in human ascending aorta. However, we suggest searching for specific reference genes when conducting qPCR experiments with new cohort of samples.

Background During the last decade, the use of ministernotomy in cardiac surgery has increased. Quality of life and patient satisfaction after ministernotomy have never been compared to conventional full sternotomy in randomised trials. The aim of the study is to determine if this minimally invasive approach improves quality of life, satisfaction and clinical morbimortality outcomes. Methods/design The QUALITY-AVR trial is a single-blind, single-centre, independent, and pragmatic randomised clinical trial comparing ministernotomy (“J” shaped upper hemisternotomy toward right 4th intercostal space) to full sternotomy in patients with isolated severe aortic stenosis scheduled for elective aortic valve replacement. One hundred patients will be randomised in a 1:1 computational fashion. Sample size was determined for the primary end point with alpha error of 0.05 and with power of 90% in detecting differences between intervention groups of ≥ 0.10 points in change from baseline quality of life Questionnaire EuroQOL-index (EQ-5D-5 L®), measured at 1, 6 or 12 months. Secondary endpoints are: the differences in change from other baseline EQ-5D-5 L® utilities (visual analogue scale, Health Index and Severity Index), cardiac surgery specific satisfaction questionnaire (SATISCORE®), a combined safety endpoint of four major adverse complications at 1 month (all-cause mortality, acute myocardial infarction, neurologic events and acute renal failure), bleeding through drains within the first 24 h, intubation time, postoperative hospital and intensive care unit length of stay, transfusion needs during the first 72 h and 1-year survival rates. Clinical follow up is scheduled at baseline, 1, 6, and 12 months after randomization. All clinical outcomes are recorded following the Valve Academic Research Consortium 2 criteria. Discussion The QUALITY-AVR trial aims to test the hypothesis that ministernotomy improves quality of life, satisfaction and clinical outcomes in patients referred for isolated aortic valve replacement. Statistically significant differences favouring ministernotomy could modify the surgical “gold standard” for aortic stenosis surgery, and subsequently the need to change the control group in transcatheter aortic valve implantation trials. Recruitment started on 18 March 2016. In November 2017, 75 patients were enrolled. Trial registration ClinicalTrials.gov , NCT02726087 . Registered on 13 March 2016.

Background Although recent studies indicate that epicardial adipose tissue expresses brown fat-like genes, such as PGC1α, UCP1 and PRDM16, the association of these genes with type 2 diabetes mellitus (DM2) in coronary artery disease (CAD) remains unknown. Methods PGC1α, UCP1, and PRDM16 mRNAs expression levels were measured by real-time PCR in epicardial and thoracic subcutaneous adipose tissue from 44 CAD patients (22 with DM2 [CAD-DM2] and 22 without DM2 [CAD-NDM2]) and 23 non-CAD patients (NCAD). Results The CAD-DM2 patients had significantly lower PGC1α and UCP1 expression in epicardial adipose tissue than the CAD-NDM2 and NCAD patients. However, PGC1α and UCP1 mRNA trended upward in subcutaneous adipose tissue from CAD-DM2 patients. At multiple regression analysis, age, body mass index, left ventricular ejection fraction, UCP1 expression of epicardial adipose tissue and diabetes came out to be independent predictors of PGC1α levels. Epicardial adipose tissue PGC1α expression was dependent on the number of injured coronary arteries and logistic regression analysis showed that PGC1α expression in epicardial adipose tissue could exert a protective effect against coronary lesions. Conclusions DM2 is associated with decreased expression of PGC1α and UCP1 mRNA in epicardial adipose tissue of patients with CAD, likely reflecting a loss of brown-like fat features. Decreased expression of PGC1α in human epicardial adipose tissue is associated with higher prevalence of coronary lesions.

Mental health issues among young university students have increased in recent years, driven by academic stress and sedentary lifestyles. The YoungFitT Project aims to explore well-being strategies and the psychobiological mechanisms behind their effects on university students. The project includes two studies: the first evaluates the effectiveness of High-Intensity Functional Training (HIFT), Mindfulness-Based Stress Reduction (MBSR), and Qigong (QG) on psychological well-being and cognitive functions, and also explores whether socio-demographic, mental (mindful thinking, sleep quality), physical (physical fitness, physical activity), physiological (heart rate variability), and biological (microbiota) factors mediate or moderate intervention effects on university students. Given that immersive virtual reality (VR) can enhance adherence and provide additional benefits, the second study will explore the feasibility and efficacy of HIFT-VR, MBSR-VR, and QG-VR on university students' psychological well-being and cognitive functions. Two mixed-methods randomized controlled trials will be conducted. In Study 1, participants will be randomly assigned to one of three groups (HIFT, MBSR, QG) using a 1:1:1 ratio. Psychological, cognitive, physical, physiological, and biological measures will be evaluated two weeks before and after the interventions. The interventions include three weekly sessions for 12 weeks. Subsequently, a follow-up will be conducted 12 weeks after the intervention to assess psychological well-being. Study 2 is a proof-of-concept study in which VR interventions will be co-designed with input from university students and professionals. Twelve participants from each study will also complete semi-structured interviews to explore their experiences and perceived impact. The proposed interventions are expected to produce differential effects on psychological well-being and cognitive function. VR environments may enhance adherence and offer added benefits over conventional training. Findings will inform effective, personalized strategies for the mental and physical health of university youth. www.ClinicalTrials.gov, identifier NCT06406283; Registration date: 2024/05/06.

Stroke survivors experience a wide range of physical, cognitive, and emotional challenges. In the MindFit Project, a randomized clinical trial, 141 chronic stroke patients were divided into three groups: mindfulness-based stress reduction (MBSR) with computerized cognitive training (CCT), physical exercise (PE) with CCT, and CCT alone. The interventions were conducted remotely over 12 weeks, including online group and individual sessions. This exploratory nested qualitative study aimed to investigate chronic stroke survivors’ experiences, opinions, and perceived changes due to the interventions within the MindFit Project. The secondary objective was to describe the broader experience of their recovery journey. Twenty-seven participants were recruited through purposive sampling and engaged in semi-structured one-on-one interviews. Twelve received MBSR+CCT, nine received PE+CCT, and six received CCT-only. The interviews were recorded, transcribed, and analyzed using thematic analysis. Participants shared insights into their lives after stroke, including emotional and physical challenges, coping mechanisms, and the impact of societal perceptions. The interventions were generally positively valued, with MBSR aiding in emotional regulation, PE enhancing physical capabilities, and CCT improving cognition. The group setting provided valuable peer support and motivation, although some participants noted challenges owing to the heterogeneity. The telematic format was also appreciated for its accessibility, although it posed challenges to personal interaction and intervention supervision. Our study emphasizes the complexity of stroke recovery and the importance of holistic, patient-centered rehabilitation approaches. It also highlights the value of combining physical and non-physical interventions in a group setting, along with the potential of remote platforms to enhance the accessibility of rehabilitation programs. These findings generate hypotheses for future randomized clinical trials aimed at improving post-stroke recovery. •Qualitative study in a randomized trial shows stroke's multifaceted impact.•Mindfulness improves emotional regulation and post-stroke living.•Physical exercise increases autonomy and reduces the fear of falling.•Computerized cognitive training boosts cognition and daily routines.•Online group-based treatments can enhance accessibility and effectiveness.

Behavioral interventions have shown promising neuroprotective effects, but the cascade of molecular, brain and behavioral changes involved in these benefits remains poorly understood. Projecte Moviment is a 12-week (5 days per week – 45 min per day) multi-domain, single-blind, proof-of-concept randomized controlled trial examining the cognitive effect and underlying mechanisms of an aerobic exercise (AE), computerized cognitive training (CCT) and a combined (COMB) groups compared to a waitlist control group. Adherence was >80% for 82/109 participants recruited (62% female; age = 58.38 ± 5.47). In this study we report intervention-related changes in plasma biomarkers (BDNF, TNF-α, HGF, ICAM-1, SDF1-α) and structural-MRI (brain volume) and how they related to changes in physical activity and individual variables (age and sex) and their potential role as mediators in the cognitive changes. Our results show that although there were no significant changes in molecular biomarker concentrations in any intervention group, changes in ICAM-1 and SDF1-α were negatively associated with changes in physical activity outcomes in AE and COMB groups. Brain volume changes were found in the CCT showing a significant increase in precuneus volume. Sex moderated the brain volume change in the AE and COMB groups. Changes in molecular biomarkers and brain volumes did not significantly mediate the cognitive-related benefits found previously for any group. This study shows crucial initial molecular and brain volume changes related to lifestyle interventions at early stages and highlights the value of examining activity parameters, individual difference characteristics and using a multi-level analysis approach to address these questions.

Sex hormones’ and menstrual cycle’s effects on cognitive performance remain unclear. This study examined cognitive differences between women across menstrual cycle phases, sex differences between women and men, and hormone–cognition associations. In total, 71 healthy young adults, aged 20–36 (42 women, 29 men), completed standardised cognitive tests measuring attention, processing speed, working memory, and visuospatial abilities. Women were tested twice: during menstrual (low-oestradiol) and pre-ovulatory (high-oestradiol) phases; men once. Hormone levels (oestradiol, progesterone, testosterone) were measured in blood samples via electrochemiluminescence immunoassay (ECLIA). Two analytical strategies were used: (1) within-subject analysis comparing women between phases, and (2) between-group comparison across three groups—women in menstrual phase, pre-ovulatory phase, and men. Women performed better during pre-ovulatory versus menstrual phase in working memory (Digit span forward: p = 0.04; Digit span backwards max: p = 0.02) and attention switching (Trail Making Test B: p = 0.01). Sex differences in processing speed were observed only during the menstrual phase (Trail Making Test A: p = 0.03; Stroop B: p = 0.04), but not in the pre-ovulatory phase. Positive correlations between oestradiol/progesterone and cognitive performance were found in men, while complex bidirectional relationships emerged in women during the menstrual phase only. Testosterone showed no significant correlations. These findings highlight hormonal status effects on cognitive sex differences.

Background Large-artery intracranial atherosclerosis may be the most frequent cause of ischemic stroke worldwide. Traditional approaches have attempted to target the disease when it is already symptomatic. However, early detection of intracranial atherosclerosis may allow therapeutic intervention while the disease is still asymptomatic. The prevalence and natural history of asymptomatic intracranial atherosclerosis in Caucasians remain unclear. The aims of the Barcelona- AS ymptomatic I ntracranial A therosclerosis (ASIA) study are (1) to determine the prevalence of ASIA in a moderate-high vascular risk population, (2) to study its prognostic impact on the risk of suffering future major ischemic events, and (3) to identify predictors of the development, progression and clinical expression of this condition. Methods/Design Cross-over and cohort, population-based study. A randomly selected representative sample of 1,503 subjects with a mild-moderate-high vascular risk (as defined by a REGICOR score ≥ 5%) and with neither a history of cerebrovascular nor ischemic heart disease will be studied. At baseline, all individuals will undergo extracranial and transcranial Color-Coded Duplex (TCCD) ultrasound examinations to detect presence and severity of extra and intracranial atherosclerosis. Intracranial stenoses will be assessed by magnetic resonance angiography (MRA). Clinical and demographic variables will be recorded and blood samples will be drawn to investigate clinical, biological and genetic factors associated with the presence of ASIA. A long-term clinical and sonographic follow-up will be conducted thereafter to identify predictors of disease progression and of incident vascular events. Discussion The Barcelona-ASIA is a population-based study aiming to evaluate the prevalence and clinical importance of asymptomatic intracranial large-artery atherosclerosis in Caucasians. The ASIA project may provide a unique scientific resource to better understand the dynamics of intracranial atherosclerosis from its early stages and to identify new potential therapeutic targets for this condition.

The primary goal of this study was to determine the incidence of post-traumatic ventriculomegaly (Evans' index > or = 0.30) in 95 head-injured patients with a Glasgow Coma Scale (GCS) score of < or =13 at admission. Additional objectives were to determine the relationship between an increase in ventricular size and several clinical and radiological features and outcome. A planimetric study was carried out in the sequential control computed tomography (CT) scans of 34 moderately head-injured (GCS 9-13) and 61 severely head-injured (GCS 3-8) patients with a minimum follow-up of 2 months. Between two and six CT scans were evaluated in each patient. The presence of subarachnoid hemorrhage (SAH) was registered. Evans' index was determined in all CT scans. In the final CT scan of each patient, ventricular size was related to the admission GCS score, age, the presence of SAH in the initial CT scans, type of brain lesion (classified according to the final diagnosis in the Traumatic Coma Data Bank classification), and outcome. Ventriculomegaly was found in 39.3% of patients with severe head injury and in 27.3% of those with a moderate head injury. Increased ventricular size was evident 4 weeks after injury in 57.6% and 2 months after injury in 69.7%. No relationship was found between post-traumatic ventriculomegaly and age, initial GCS score, the presence of SAH, or type of lesion (focal or diffuse). Post-traumatic ventriculomegaly was significantly correlated with outcome. Post-traumatic ventriculomegaly is a frequent and early finding in patients with moderate or severe traumatic brain injury.

Background: Although exercise is known to have a neuroprotective effect in aging, the mediators underlying the exercise-cognition association remain poorly understood. In this paper we aimed to study the molecular, brain, and behavioral changes related to physical activity and their potential role as mediators. Methods: We obtained demographic, physical activity outcomes [sportive physical activity and cardiorespiratory fitness (CRF)], plasma biomarkers (TNF-α, ICAM-1, HGF, SDF1-α, and BDNF), structural-MRI (brain volume areas), psychological and sleep health (mood, depressive and distress symptoms, and sleep quality), and multi-domain cognitive data from 115 adults aged 50–70 years. We conducted linear regression models and mediation analyses stratifying results by sex in a final sample of 104 individuals [65 women (age = 56.75 ± 4.96) and 39 men (age = 58.59 ± 5.86)]. Results: Women engaging in greater amounts of exercising showed lower TNF-α levels and greater dorsolateral prefrontal cortex and temporal lobe volumes. Men engaging in greater amounts of exercise showed greater temporal lobe volumes. CRF levels were not related to any of the analyzed outcomes in women but in men higher CRF was associated with lower TNF-α, HGF and ventricle volumes, greater volume of temporal and parietal lobes and fewer depressive symptoms and better mood. In men, reduced TNF-α and HGF levels mediated brain and cognitive CRF-related benefits. Conclusion: Our results show that exercise is a promising approach for influencing inflammation and brain volume and also contributes to ongoing discussions about the physiological mediators for the association between CRF and cognition in men.