Functional differences in human aortic valve interstitial cells from patients with varying calcific aortic valve disease.

Calcific aortic valve disease (CAVD) is characterized by progressive stiffening of aortic valve (AV) tissues, inducing stenosis and insufficiency. Bicuspid aortic valve (BAV) is a common congenital defect in which the AV has two leaflets rather than three, with BAV patients developing CAVD decades years earlier than in the general population. Current treatment for CAVD remains surgical replacement with its continued durability problems, as there are no pharmaceutical therapies or other alternative treatments available.

Implications of Bicuspid Aortic Valve Disease and Aortic Stenosis/Insufficiency as Risk Factors for Thoracic Aortic Aneurysm.

Bicuspid Aortic Valves (BAV) are associated with an increased incidence of thoracic aortic aneurysms (TAA). TAA are a common aortic pathology characterized by enlargement of the aortic root and/or ascending aorta, and may become life threatening when left untreated. Typically occurring as the sole pathology in a patient, TAA are largely asymptomatic.

Decreased serotonin transporter activity in the mitral valve contributes to progression of degenerative mitral regurgitation.

Degenerative mitral valve (MV) regurgitation (MR) is a highly prevalent heart disease that requires surgery in severe cases. Here, we show that a decrease in the activity of the serotonin transporter (SERT) accelerates MV remodeling and progression to MR. Through studies of a population of patients with MR, we show that selective serotonin reuptake inhibitor (SSRI) use and promoter polymorphism 5-HTTLPR LL genotype were associated with MV surgery at younger age.

Cardiometabolic profiles in children and adults with overweight and obesity and down syndrome.

Individuals with Down syndrome (DS) are at increased risk for being overweight/obese, but the associated cardiometabolic risk (CR) is not clear. Cross-sectional anthropometric and clinical laboratory data from a multi-site, international cohort of individuals with DS were analyzed to determine cardiometabolic risk by reporting observed distributions of cardiometabolic biomarkers in overweight/obese individuals with DS throughout the lifespan. Descriptive statistics and regression analyses by age categories determined the distributive percentiles for cardiometabolic biomarkers and tested for adiposity as a predictor of CR.

Safety and Long-Term Immunogenicity of BNT162b2 Vaccine in Individuals with Down Syndrome.

We aimed to evaluate the safety and immunogenicity of the BNT162b2 vaccine in young people with Down syndrome (DS), and to compare their humoral immune response with those of the healthy controls (HC). Individuals with DS and HC received the BNT162b2 vaccine. Longitudinal blood samples were collected on the day of vaccination, twenty-one days after the first dose, seven days after the second dose, and six months after the first dose.

LPHN2 inhibits vascular permeability by differential control of endothelial cell adhesion.

Dynamic modulation of endothelial cell-to-cell and cell-to-extracellular matrix (ECM) adhesion is essential for blood vessel patterning and functioning. Yet the molecular mechanisms involved in this process have not been completely deciphered. We identify the adhesion G protein-coupled receptor (ADGR) Latrophilin 2 (LPHN2) as a novel determinant of endothelial cell (EC) adhesion and barrier function.

Altered Responsiveness to TGFβ and BMP and Increased CD45+ Cell Presence in Mitral Valves Are Unique Features of Ischemic Mitral Regurgitation.

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Management of pediatric post-infectious neurological syndromes.

Background: Post-Infectious Neurological Syndromes (PINS) are heterogeneous neurological disorders with post or para-infectious onset. PINS diagnosis is complex, mainly related to the absence of any recognized guidelines and a univocal definition.

Aim Of The Study: To elaborate a diagnostic guide for PINS.

Distinct retrograde microtubule motor sets drive early and late endosome transport.

Although subcellular positioning of endosomes significantly impacts on their functions, the molecular mechanisms governing the different steady-state distribution of early endosomes (EEs) and late endosomes (LEs)/lysosomes (LYs) in peripheral and perinuclear eukaryotic cell areas, respectively, are still unsolved. We unveil that such differences arise because, while LE retrograde transport depends on the dynein microtubule (MT) motor only, the one of EEs requires the cooperative antagonism of dynein and kinesin-14 KIFC1, a MT minus end-directed motor involved in cancer progression. Mechanistically, the Ser-x-Ile-Pro (SxIP) motif-mediated interaction of the endoplasmic reticulum transmembrane protein stromal interaction molecule 1 (STIM1) with the MT plus end-binding protein 1 (EB1) promotes its association with the p150Glued subunit of the dynein activator complex dynactin and the distinct location of EEs and LEs/LYs.

Pertussis in early life: underdiagnosed, severe, and risky disease. A seven-year experience in a pediatric tertiary-care hospital.

Aim: Pertussis continues to be a common worldwide infection in pediatric and adult populations.We aimed to study epidemiological and clinical characteristics of infants and children admitted for pertussis to a tertiary-care hospital and to investigate the risk factors for pediatric intensive care unit (PICU) admission.

Materials And Methods: With a retrospective study, we analyzed all medical reports of patients admitted to Bambino Gesù Children's Hospital in Rome from January 2011 to December 2018 with a diagnosis of pertussis.

PNPLA3 gene polymorphism is associated with liver steatosis in children with Down syndrome.

Background And Aims: We previously demonstrated that children with Down syndrome (DS) exhibited a greater risk of steatosis than the general pediatric population. This trend was independent of obese phenotype, thus suggesting a role of genetic predisposition. Therefore, we investigated the prevalence of non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS) in function of genetic susceptibility and adipocytokine levels in children with DS.

Effects of Pidotimod on recurrent respiratory infections in children with Down syndrome: a retrospective Italian study.

Background: Children with Down syndrome (DS) show a high susceptibility to recurrent infections (RI), caused by immune defects and abnormalities of the airways. Our goal was to investigate the effects of Pidotimod on RI prevention in children with DS, comparing immune and clinical parameters before (T0) and after (T1) the treatment with Pidotimod.

Methods: The study was conducted at the Down syndrome outpatient Center of Bambino Gesù Children's Hospital, in Rome.

Complications and risk factors for severe outcome in children with measles.

Objective And Design: Risk factors for severe measles are poorly investigated in high-income countries. The Italian Society for Paediatric Infectious Diseases conducted a retrospective study in children hospitalised for measles from January 2016 to August 2017 to investigate the risk factors for severe outcome defined by the presence of long-lasting sequelae, need of intensive care or death.

Results: Nineteen hospitals enrolled 249 children (median age 14.

Active prophylaxis for respiratory syncytial virus: current knowledge and future perspectives.

Respiratory syncytial virus (RSV) is the most common respiratory pathogen in infants and young children but represents also an important cause of morbidity in adults, particularly in the elderly and immunocompromised persons. Despite its global impact on human health, no effective treatment is available except for supportive care and no safe vaccine has been licensed yet. Vaccine development has been hindered by several factors including vaccine enhanced disease associated with formalin-inactivated RSV vaccine, ethical concerns and lack of consensus concerning the most appropriate target antigen.

Scurvy: still a threat in the well-fed first world?

We report three cases of scurvy in previously healthy children referred to us for leg pain and refusal to walk. All children had no significant medical history, symptoms had started months before and subtly advanced. Two of them presented with gingival hyperplasia and petechiae, another one reported night sweats and gingival bleeding in the past few weeks.

A rationally designed NRP1-independent superagonist SEMA3A mutant is an effective anticancer agent.

Vascular normalizing strategies, aimed at ameliorating blood vessel perfusion and lessening tissue hypoxia, are treatments that may improve the outcome of cancer patients. Secreted class 3 semaphorins (SEMA3), which are thought to directly bind neuropilin (NRP) co-receptors that, in turn, associate with and elicit plexin (PLXN) receptor signaling, are effective normalizing agents of the cancer vasculature. Yet, SEMA3A was also reported to trigger adverse side effects via NRP1.

[Vaccination in childhood: how to protect the "unprotectable"?].

The failure of immunization coverage is the primary reason for the transmission and the spread of the diseases in young infants not eligible for vaccination because of age and in immunocompromised individuals. In both these categories measles, pertussis and varicella could be devastating. Pertussis, measles and varicella in the first year of life are responsible to the ED admission, the hospitalization and, exceptionally, the death.

Nonalcoholic Fatty Liver Disease in Italian Children with Down Syndrome: Prevalence and Correlation with Obesity-Related Features.

Objective: To assess the prevalence of overweight/obesity in a cohort of Italian children with Down syndrome (DS) and to investigate the correlation of both obesity and DS with nonalcoholic fatty liver disease (NAFLD).

Study Design: We enrolled 280 children with DS (age range 5-18 years), who were referred to the DS outpatient clinic of the Bambino Gesù Children's Hospital in Rome. For all children, we collected the clinical history and measured anthropometric variables.

TRPM8 inhibits endothelial cell migration via a non-channel function by trapping the small GTPase Rap1.

Endothelial cell adhesion and migration are critical steps of the angiogenic process, whose dysfunction is associated with tumor growth and metastasis. The TRPM8 channel has recently been proposed to play a protective role in prostate cancer by impairing cell motility. However, the mechanisms by which it could influence vascular behavior are unknown.

Hospital-acquired rotavirus and norovirus acute gastroenteritis in a pediatric unit, in 2014-2015.

The occurrence of hospital-acquired acute gastroenteritis (AGE) is a major concern for public health. RotavirusA (RVA) and norovirus (NoV) are common causes of viral AGE in the pediatric population, and their role in nosocomial infections has been proven, remaining poorly investigated. To investigate RVA and NoV in hospital-acquired AGE, 55 stool samples from children with nosocomial AGE were collected between May 2014 and May 2015.

Fatal varicella pneumonia in an unvaccinated child with Down Syndrome: a case report.

Background: Varicella is an acute infectious disease common during childhood. It has mostly an uncomplicated course in early childhood. Neverthless, it may result in severe complications, especially in particular age groups and clinical conditions.

An Electrical Impedance-Based Method for Quantitative Real-Time Analysis of Semaphorin-Elicited Endothelial Cell Collapse.

Semaphorins (SEMA) are chemorepulsive guidance cues that, acting through plexin receptors, inhibit integrin-mediated cell adhesion to the extracellular matrix. The ensuing cell retraction and collapse is a key biological event downstream of SEMA/plexin signaling that is however hard to precisely quantify. Here, we describe a quantitative approach that allows monitoring over time the evolution of SEMA3E/plexin D1-elicited endothelial cell collapse.

Lipid profiles in a large cohort of Italian children with Down syndrome.

Objectives: Results of epidemiological studies of lipid profiles in individuals with Down Syndrome (DS) in different settings showed discordant results but laboratory norms for this population has been lacking. The aim of our study is to evaluate lipid profiles in a large population of Italian children with DS.

Methods: Lipid profiles of 357 patients with diagnosis of DS were recorded.