Effect of Outdoor Cycling, Virtual and Enhanced Reality Indoor Cycling on Heart Rate, Motivation, Enjoyment and Intention to Perform Green Exercise in Healthy Adults.

Despite the benefits of physical activity (PA), Italy ranks low in leisure-time PA among European countries. Integrating virtual (VR)/enhanced (ER) reality with exercise equipment could boost PA engagement. Limited studies have explored how VR/ER-integrated cycling activity, compared to outdoor settings, influences PA among university students.

Sex and gender specific pitfalls and challenges in cardiac rehabilitation: a working hypothesis towards better inclusivity in cardiac rehabilitation programmes.

Notwithstanding its acknowledged pivotal role for cardiovascular prevention, cardiac rehabilitation (CR) is still largely under prescribed, in almost 25% of patients owing an indication for. In addition, when considering differences concerning the two sexes, female individuals are underrepresented in CR programmes with lower referral rates, participation, and completion as compared to male counterpart. This picture becomes even more tangled with reference to gender, a complex socio-cultural construct characterized by four domains (gender identity, relation, role, and institutionalized gender).

Lipid-lowering therapy in patients with coronary heart disease: an Italian real-life survey. Results from the Survey on Risk FactOrs and CardiovascuLar secondary prEvention and drug strategieS (SOFOCLES) in Italy.

In patients at high cardiovascular risk, a low-density lipoprotein cholesterol (LDL-C) reduction of ≥50% from baseline and an LDL-C goal of <70 mg/dL (or <55 mg/dL in very high-risk patients) are recommended. Multiple registry and retrospective studies have shown that patients with high atherosclerotic cardiovascular risk often do not reach the targets defined by the European Society of Cardiology guidelines as a result of suboptimal management of LDL-C. Here, we report the data on lipid-lowering therapy and lipid targets from the Survey on Risk FactOrs and CardiovascuLar secondary prEvention and drug strategieS (SOFOCLES), an observational, prospective study designed to collect data on patients with ischemic heart disease treated at cardiac outpatient clinics across the Italian national territory.

Tracing the invisible mutant ADNP protein in Helsmoortel-Van der Aa syndrome patients.

Heterozygous de novo mutations in the Activity-Dependent Neuroprotective Homeobox (ADNP) gene underlie Helsmoortel-Van der Aa syndrome (HVDAS). Most of these mutations are situated in the last exon and we previously demonstrated escape from nonsense-mediated decay by detecting mutant ADNP mRNA in patient blood. In this study, wild-type and ADNP mutants are investigated at the protein level and therefore optimal detection of the protein is required.

YY1 mutations disrupt corticogenesis through a cell-type specific rewiring of cell-autonomous and non-cell-autonomous transcriptional programs.

Germline mutations of YY1 cause Gabriele-de Vries syndrome (GADEVS), a neurodevelopmental disorder featuring intellectual disability and a wide range of systemic manifestations. To dissect the cellular and molecular mechanisms underlying GADEVS, we combined large-scale imaging, single-cell multiomics and gene regulatory network reconstruction in 2D and 3D patient-derived physiopathologically relevant cell lineages. YY1 haploinsufficiency causes a pervasive alteration of cell type specific transcriptional networks, disrupting corticogenesis at the level of neural progenitors and terminally differentiated neurons, including cytoarchitectural defects reminiscent of GADEVS clinical features.

Benchmarking brain organoid recapitulation of fetal corticogenesis.

Brain organoids are becoming increasingly relevant to dissect the molecular mechanisms underlying psychiatric and neurological conditions. The in vitro recapitulation of key features of human brain development affords the unique opportunity of investigating the developmental antecedents of neuropsychiatric conditions in the context of the actual patients' genetic backgrounds. Specifically, multiple strategies of brain organoid (BO) differentiation have enabled the investigation of human cerebral corticogenesis in vitro with increasing accuracy.

[Substance abuse and cardiovascular risk: cocaine].

Cocaine abuse is widely increasing, especially in younger individuals. Cocaine is a major cause of chest pain and acute coronary syndrome and is the leading cause for drug abuse-related visits to emergency departments, most of which are due to cardiovascular complaints. Cocaine use, especially long-term, is associated with an increased risk of all-cause mortality, and with several significant, life-threatening cardiovascular diseases although the multifactorial underlying cellular and molecular pathophysiological mechanisms of acute and chronic cocaine cardiotoxicity are not well established due to limited studies.

Dynamics of CTCF- and cohesin-mediated chromatin looping revealed by live-cell imaging.

Animal genomes are folded into loops and topologically associating domains (TADs) by CTCF and loop-extruding cohesins, but the live dynamics of loop formation and stability remain unknown. Here, we directly visualized chromatin looping at the TAD in mouse embryonic stem cells using super-resolution live-cell imaging and quantified looping dynamics by Bayesian inference. Unexpectedly, the loop was both rare and dynamic, with a looped fraction of approximately 3 to 6.

CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories.

Mutations in the chromodomain helicase DNA-binding 8 (CHD8) gene are a frequent cause of autism spectrum disorder (ASD). While its phenotypic spectrum often encompasses macrocephaly, implicating cortical abnormalities, how CHD8 haploinsufficiency affects neurodevelopmental is unclear. Here, employing human cerebral organoids, we find that CHD8 haploinsufficiency disrupted neurodevelopmental trajectories with an accelerated and delayed generation of, respectively, inhibitory and excitatory neurons that yields, at days 60 and 120, symmetrically opposite expansions in their proportions.

Imbalanced autophagy causes synaptic deficits in a human model for neurodevelopmental disorders.

Macroautophagy (hereafter referred to as autophagy) is a finely tuned process of programmed degradation and recycling of proteins and cellular components, which is crucial in neuronal function and synaptic integrity. Mounting evidence implicates chromatin remodeling in fine-tuning autophagy pathways. However, this epigenetic regulation is poorly understood in neurons.

Tracking and interpreting long-range chromatin interactions with super-resolution live-cell imaging.

Mammalian genomes are organized and regulated through long-range chromatin interactions. Structural loops formed by CCCTC-binding factor (CTCF) and cohesin fold the genome into domains, while enhancers interact with promoters across vast genomic distances to regulate gene expression. Although genomics and fixed-cell imaging approaches help illuminate many aspects of chromatin interactions, temporal information is usually lost.

High-throughput screening identifies histone deacetylase inhibitors that modulate GTF2I expression in 7q11.23 microduplication autism spectrum disorder patient-derived cortical neurons.

Background: Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental condition affecting almost 1% of children, and represents a major unmet medical need with no effective drug treatment available. Duplication at 7q11.23 (7Dup), encompassing 26-28 genes, is one of the best characterized ASD-causing copy number variations and offers unique translational opportunities, because the hemideletion of the same interval causes Williams-Beuren syndrome (WBS), a condition defined by hypersociability and language strengths, thereby providing a unique reference to validate treatments for the ASD symptoms.

KMT2B and Neuronal Transdifferentiation: Bridging Basic Chromatin Mechanisms to Disease Actionability.

The role of epigenetic regulators in the process of neuronal transdifferentiation was until recently largely uncharacterized, despite their key role in the physiological processes of neural fate acquisition and maintenance. In this commentary, we describe the main findings of our recent paper "KMT2B is selectively required for neuronal transdifferentiation, and its loss exposes dystonia candidate genes," where we investigated the role of this histone H3K4 methyltransferase during mouse embryonic fibroblasts (MEFs) to induced neuronal cells (iNs) direct conversion. Indeed, MEFs, transduced with three neuronal-specific transcription factors (TFs), , and , show lower transdifferentiation efficiency, defective iN maturation, and augmented alternative cell fates acquisition, with respect to controls.

From enhanceropathies to the epigenetic manifold underlying human cognition.

A vast portion of intellectual disability and autism spectrum disorders is genetically caused by mutations in chromatin modulators. These proteins play key roles in development and are also highly expressed in the adult brain. Specifically, the pivotal role of chromatin regulation in transcription has placed enhancers at the core of neurodevelopmental disorders (NDDs) studies, ushering in the coining of the term enhanceropathies.

The chromatin basis of neurodevelopmental disorders: Rethinking dysfunction along the molecular and temporal axes.

The complexity of the human brain emerges from a long and finely tuned developmental process orchestrated by the crosstalk between genome and environment. Vis à vis other species, the human brain displays unique functional and morphological features that result from this extensive developmental process that is, unsurprisingly, highly vulnerable to both genetically and environmentally induced alterations. One of the most striking outcomes of the recent surge of sequencing-based studies on neurodevelopmental disorders (NDDs) is the emergence of chromatin regulation as one of the two domains most affected by causative mutations or Copy Number Variations besides synaptic function, whose involvement had been largely predicted for obvious reasons.

ANMCO/SIC Consensus Document: cardiology networks for outpatient heart failure care.

Changing demographics and an increasing burden of multiple chronic comorbidities in Western countries dictate refocusing of heart failure (HF) services from acute in-hospital care to better support the long inter-critical out-of- hospital phases of HF. In Italy, as well as in other countries, needs of the HF population are not adequately addressed by current HF outpatient services, as documented by differences in age, gender, comorbidities and recommended therapies between patients discharged for acute hospitalized HF and those followed-up at HF clinics. The Italian Working Group on Heart Failure has drafted a guidance document for the organisation of a national HF care network.

YY1 Haploinsufficiency Causes an Intellectual Disability Syndrome Featuring Transcriptional and Chromatin Dysfunction.

Yin and yang 1 (YY1) is a well-known zinc-finger transcription factor with crucial roles in normal development and malignancy. YY1 acts both as a repressor and as an activator of gene expression. We have identified 23 individuals with de novo mutations or deletions of YY1 and phenotypic features that define a syndrome of cognitive impairment, behavioral alterations, intrauterine growth restriction, feeding problems, and various congenital malformations.

[ANMCO/SIC Consensus document: The heart failure network: organization of outpatient care].

Changing demographics and an increasing burden of multiple chronic comorbidities in western countries dictate refocusing of heart failure (HF) services from acute in-hospital care to better support the long inter-critical out-of-hospital phases of HF. The needs of the HF population are not adequately addressed by current HF outpatient services, as documented by differences in age, gender, comorbidities and recommended therapies between patients discharged for hospitalized HF and those followed up at HF clinics.The Working Group on Heart Failure of the Italian Association of Hospital Cardiologists (ANMCO) has drafted a consensus document for the organization of a national HF care network.

Germline mutations in DNA repair genes may predict neoadjuvant therapy response in triple negative breast patients.

Triple negative breast cancers (TNBCs) represent about 15-20% of all breast cancer cases and are characterized by a complex molecular heterogeneity. Some TNBCs exhibit clinical and pathological properties similar to BRCA-mutated tumors, without actually bearing a mutation in BRCA genes. This "BRCAness" phenotype may be explained by germline mutations in other genes involved in DNA repair.

[The Italian Survey on Cardiac Rehabilitation - 2013 (ISYDE.13-Directory): national availability and organization of cardiac rehabilitation facilities].

Background: The Italian Association for Cardiovascular Prevention, Rehabilitation and Epidemiology (GICR-IACPR) and the Italian Society of Cardiologists of Accredited Hospitals (SICOA) developed the ISYDE.13 survey with the purpose to take a detailed snapshot of number, distribution, facilities, staffing levels, organization, and program details of cardiac rehabilitation (CR) units in Italy.

Methods: The study was carried out using a web-based questionnaire running on the GICR-IACPR website for 4 weeks from September 2 to 29, 2013.

[The Health Department of Sicily "Regional recommendations for hospital discharge and communication with patients after admission due to a cardiologic event" decree].

Mortality and rehospitalizations still remain high after discharge for an acute cardiologic event. In this context, hospital discharge represents a potential pitfall for heart disease patients. In the setting of care transitions, the discharge letter is the main instrument of communication between hospital and primary care.

Lower extremities peripheral arterial disease among patients admitted to cardiac rehabilitation: the THINKPAD registry.

Background/objectives: Lower extremities peripheral arterial disease (LE-PAD) across the wide range of conditions for Cardiac Rehabilitation (CR) is poorly understood. The "ATHerosclerosis of the lower extremIties as a liNKed comorbidity in Patients Admitted for carDiac rehabilitation" (THINKPAD) registry explored LE-PAD in CR patients in terms of prevalence and interventions delivered.

Methods: Multicenter, consecutive case series of 1506 patients discharged from 16 CR Units in Italy from May 1 to June 30, 2012.