Remission of Kimura disease with carotid hypervascularization after cyclosporine treatment

No abstract available

PINK1 homozygous W437X mutation in a patient with apparent dominant transmission of parkinsonism.

We analyzed the PINK1 gene in 58 patients with early-onset Parkinsonism and detected the homozygous mutation W437X in 1 patient. The clinical phenotype was characterized by early onset (22 years of age), good re- sponse to levodopa, early fluctuations and dyskinesias, and psychiatric symptoms. The mother, heterozygote for W437X mutation, was affected by Parkinson’s disease and 3 further relatives were reported affected, according to an autosomal dominant transmission

Chronic heart failure is characterized by altered mitochondrial function and structure in circulating leucocytes

Oxidative stress is currently viewed as a key factor in the genesis and progression of Heart Failure (HF). The aim of this study was to characterize the mitochondrial changes linked to oxidative stress generation in circulating peripheral blood mononuclear cells isolated from chronic HF patients (HF_PBMCs) in order to highlight the involvement of mitochondrial dysfunction in the pathophysiology of HF. To assess the production of reactive oxygen species (ROS), mitochondrial function and ultrastructure and the mitophagic flux in circulating PBMCs we enrolled 15 patients with HF and a control group of ten healthy subjects. The HF_PBMCs showed a mitochondrial population consisting of damaged and less functional organelles responsible of higher superoxide anion production both at baseline and under in vitro stress conditions, with evidence of cellular apoptosis. Although the mitophagic flux at baseline was enhanced in HF_PBMCs at level similar to those that could be achieved in control PBMCs only under inflammatory stress conditions, the activation of mitophagy was unable to preserve a proper mitochondrial dynamics upon stress stimuli in HF. In summary, circulating HF_PBMCs show structural and functional derangements of mitochondria with overproduction of reactive oxidant species. This mitochondrial failure sustains a leucocyte dysfunctional status in the blood that may contribute to development and persistence of stress conditions within the cardiovascular system in HF

Lung Ultrasonography May Provide an Indirect Estimation of Lung Porosity and Airspace Geometry

Background: Echographic vertical artifacts (B-lines) in chest ultrasonography have often been associated with pathological patterns. A scientifically sound explanation of these artifacts has not yet been proposed. Objectives: The 'spongy' nature of the lung in its liquid and solid components and the changes that take place in peripheral airspace (PAS) geometry might be the key point to understanding these phenomena. Methods: Six excised right rabbit lungs were obtained. Each lung underwent direct ultrasound evaluation in two different conditions: at complete tissue elastic recoil volume and at pulmonary expansion volume achieved by applying a constant positive pressure of 12 cm H2O. Lung volumes and densities were reported in both conditions. Histological examination was performed on three naturally collapsed lungs and on three lungs under positive pressure inflation after having been fixed in formalin solution. Results: Mean volumes of naturally collapsed lungs and fixed expanded lungs were 11.2 ± 0.36 and 44.83 ± 3.03 ml, respectively. Mean densities were 0.622 ± 0.016 and 0.155 ± 0.007 g/ml, respectively. Ultrasound evaluation of collapsed lungs showed dense vertical artifacts and a 'white lung' pattern, while the evaluation of expanded lungs showed hyperechoic line and horizontal artifacts of reflection. Histological evaluation showed a different PAS geometry in collapsed lungs caused by alveolar size reduction and shape changes with unfolded and closed units modifying the peripheral porosity of the frothy nature of the lung. Conclusions: Airspace geometry, frothy nature and porosity are the determinants of the different behavior of ultrasound interacting with the subpleural lung parenchyma. Chest ultrasound may thus be interpreted as an indirect 'estimator' of lung porosity

Obstructive sleep apnea and heart disease: the biomarkers point of view.

Obstructive sleep apnea syndrome (OSAS) is a highly prevalent disorder. Important risk factors for this disease are represented by obesity, male gender, smoking, some endocrinological disturbances, alcohol intake, use of benzodiazepines, and craniofacial alterations. It is well known that OSAS is a frequent comorbidity as well as a relevant risk factor for cardiovascular diseases (CVD), especially in patients with hypertension, coronary artery disease (CAD), arrhythmias, and heart failure. Furthermore, therapy with continuous positive airway pressure devices (CPAP) has been shown to significantly reduce the incidence of serious cardiovascular consequences. Interactions between OSAS and the cardiovascular system (CVS) can eventually result mainly in coronary atherosclerosis. These two conditions are connected by a complex biomarkers network. An extensive overview of these pathways could be helpful to better understand the causes of cardiovascular impairment in patients with OSAS

Neuronopathic Gaucher disease models reveal defects in cell growth promoted by Hippo pathway activation

Gaucher Disease (GD), the most common lysosomal disorder, arises from mutations in the GBA1 gene and is characterized by a wide spectrum of phenotypes, ranging from mild hematological and visceral involvement to severe neurological disease. Neuronopathic patients display dramatic neuronal loss and increased neuroinflammation, whose molecular basis are still unclear. Using a combination of Drosophila dGBA1b loss-of-function models and GD patient-derived iPSCs differentiated towards neuronal precursors and mature neurons we showed that different GD- tissues and neuronal cells display an impairment of growth mechanisms with an increased cell death and reduced proliferation. These phenotypes are coupled with the downregulation of several Hippo transcriptional targets, mainly involved in cells and tissue growth, and YAP exclusion from nuclei. Interestingly, Hippo knock-down in the GBA-KO flies rescues the proliferative defect, suggesting that targeting the Hippo pathway can be a promising therapeutic approach to neuronopathic GD.A combination of Drosophila dGBA1b loss-of-function models and Gaucher Disease (GD) patient-derived iPSCs reveals an impairment in GD neuronal cell growth and that Hippo pathway hyperactivation contributes to the impairment