The University of Naples Federico II is a university located in Naples, Italy. It was founded in 1224 and is organized into 13 faculties. It is the world's oldest state university and one of the oldest academic institutions in continuous operation. The university is named after its founder Frederick II. Wikipedia.
Cooper D.S.,Johns Hopkins University |
Biondi B.,University of Naples Federico II
The Lancet | Year: 2012
Subclinical thyroid diseases - subclinical hyperthyroidism and subclinical hypothyroidism - are common clinical entities that encompass mild degrees of thyroid dysfunction. The clinical significance of mild thyroid overactivity and underactivity is uncertain, which has led to controversy over the appropriateness of diagnostic testing and possible treatment. In this Seminar, we discuss the definition, epidemiology, differential diagnoses, risks of progression to overt thyroid disease, potential effects on various health outcomes, and management of subclinical hyperthyroidism and subclinical hypothyroidism. Treatment recommendations are based on the degree to which thyroid-stimulating hormone concentrations have deviated from normal and underlying comorbidities. Large-scale randomised trials are urgently needed to inform how to best care for individuals with subclinical thyroid disease. © 2012 Elsevier Ltd.
Parenti G.,University of Naples Federico II
Molecular Therapy | Year: 2014
Enzyme replacement therapy is currently the only approved treatment for Pompe disease, due to acid α-glucosidase deficiency. Clinical efficacy of this approach is variable, and more effective therapies are needed. We showed in preclinical studies that chaperones stabilize the recombinant enzyme used for enzyme replacement therapy. Here, we evaluated the effects of a combination of enzyme therapy and a chaperone on α-glucosidase activity in Pompe disease patients. α-Glucosidase activity was analyzed by tandem-mass spectrometry in dried blood spots from patients treated with enzyme replacement therapy, either alone or in combination with the chaperone N-butyldeoxynojirimycin given at the time of the enzyme infusion. Thirteen patients with different presentations (3 infantile-onset, 10 late-onset) were enrolled. In 11 patients, the combination treatment resulted in α-glucosidase activities greater than 1.85-fold the activities with enzyme replacement therapy alone. In the whole patient population, α-glucosidase activity was significantly increased at 12 hours (2.19-fold, P = 0.002), 24 hours (6.07-fold, P = 0.001), and 36 hours (3.95-fold, P = 0.003). The areas under the curve were also significantly increased (6.78-fold, P = 0.002). These results suggest improved stability of recombinant α-glucosidase in blood in the presence of the chaperone.Molecular Therapy (2014); doi:10.1038/mt.2014.138.
Andolfo I.,University of Naples Federico II
Blood | Year: 2013
Autosomal dominant dehydrated hereditary stomatocytosis (DHSt) usually presents as a compensated hemolytic anemia with macrocytosis and abnormally shaped red blood cells (RBCs). DHSt is part of a pleiotropic syndrome that may also exhibit pseudohyperkalemia and perinatal edema. We identified PIEZO1 as the disease gene for pleiotropic DHSt in a large kindred by exome sequencing analysis within the previously mapped 16q23-q24 interval. In 26 affected individuals among 7 multigenerational DHSt families with the pleiotropic syndrome, 11 heterozygous PIEZO1 missense mutations cosegregated with disease. PIEZO1 is expressed in the plasma membranes of RBCs and its messenger RNA, and protein levels increase during in vitro erythroid differentiation of CD34(+) cells. PIEZO1 is also expressed in liver and bone marrow during human and mouse development. We suggest for the first time a correlation between a PIEZO1 mutation and perinatal edema. DHSt patient red cells with the R2456H mutation exhibit increased ion-channel activity. Functional studies of PIEZO1 mutant R2488Q expressed in Xenopus oocytes demonstrated changes in ion-channel activity consistent with the altered cation content of DHSt patient red cells. Our findings provide direct evidence that R2456H and R2488Q mutations in PIEZO1 alter mechanosensitive channel regulation, leading to increased cation transport in erythroid cells.
Marotti De Sciarra F.,University of Naples Federico II
International Journal of Plasticity | Year: 2012
In this paper a thermodynamically consistent theory of elastoplasticity coupled with nonlocal damage in the strain space is presented. The theory is developed in the framework of the generalized standard material and the constitutive model is identified by the specification of the dissipation and of the internal energy depending on total and plastic strain, kinematic internal variables, nonlocal relaxation stress and entropy. Coupling between plasticity and nonlocal damage is achieved by using a plastic-damage dissipation which can be split in two parts. One damage dissipation occurs independent of plastic behavior while the other one is coupled with plasticity. The former dissipation occurs in both the elastic and plastic behaviors. Further the local uniqueness conditions of the considered model are studied. The structural model is then addressed and variational formulations with different combinations of local and nonlocal state variables are provided. Finally the general model governed by a single dissipation is specialized to a simplified model which is defined by two dissipations which are, in turn, equivalent to define a yield function and a nonlocal damage loading function. Two examples of the application of the theory are then provided in which no mesh dependence is apparent. © 2012 Elsevier Ltd. All rights reserved.
Lavecchia A.,University of Naples Federico II
Drug Discovery Today | Year: 2015
During the past decade, virtual screening (VS) has evolved from traditional similarity searching, which utilizes single reference compounds, into an advanced application domain for data mining and machine-learning approaches, which require large and representative training-set compounds to learn robust decision rules the explosive growth in the amount of public domain-available chemical and biological data has generated huge effort to design, analyze, and apply novel learning methodologies. Here, I focus on machine-learning techniques within the context of ligand-based VS (LBVS). In addition, I analyze several relevant VS studies from recent publications, providing a detailed view of the current state-of-the-art in this field and highlighting not only the problematic issues, but also the successes and opportunities for further advances. © 2014 Elsevier Ltd. All rights reserved.