Melusin gene (ITGB1BP2) nucleotide variations study in hypertensive and cardiopathic patients

<p>Abstract</p> <p>Background</p> <p>Melusin is a muscle specific signaling protein, required for compensatory hypertrophy response in pressure-overloaded heart. The role of Melusin in heart function has been established both by loss and gain of function experiments in murine models. With the aim of verifying the hypothesis of a potential role of the Melusin encoding gene, <it>ITGB1BP2</it>, in the modification of the clinical phenotype of human cardiomyopathies, we screened the <it>ITGB1BP2 </it>gene looking for genetic variations possibly associated to the pathological phenotype in three selected groups of patients affected by hypertension and dilated or hypertrophic cardiomyopathy</p> <p>Methods</p> <p>We analyzed <it>ITGB1BP2 </it>by direct sequencing of the 11 coding exons and intron flanking sequences in 928 subjects, including 656 hypertensive or cardiopathic patients and 272 healthy individuals.</p> <p>Results</p> <p>Only three nucleotide variations were found in patients of three distinct families: a C>T missense substitution at position 37 of exon 1 causing an amino acid change from His-13 to Tyr in the protein primary sequence, a duplication (IVS6+12_18dupTTTTGAG) near the 5'donor splice site of intron 6, and a silent 843C>T substitution in exon 11.</p> <p>Conclusions</p> <p>The three variations of the <it>ITGB1BP2 </it>gene have been detected in families of patients affected either by hypertension or primary hypertrophic cardiomyopathy; however, a clear genotype/phenotype correlation was not evident. Preliminary functional results and bioinformatic analysis seem to exclude a role for IVS6+12_18dupTTTTGAG and 843C>T in affecting splicing mechanism.</p> <p>Our analysis revealed an extremely low number of variations in the <it>ITGB1BP2 </it>gene in nearly 1000 hypertensive/cardiopathic and healthy individuals, thus suggesting a high degree of conservation of the melusin gene within the populations analyzed.</p

I.S.Mu.L.T - Rotator cuff tears guidelines

Despite the high level achieved in the field of shoulder surgery, a global consensus on rotator cuff tears management is lacking. This work is divided into two main sessions: in the first, we set questions about hot topics involved in the rotator cuff tears, from the etiopathogenesis to the surgical treatment. In the second, we answered these questions by mentioning Evidence Based Medicine. The aim of the present work is to provide easily accessible guidelines: they could be considered as recommendations for a good clinical practice developed through a process of systematic review of the literature and expert opinion, in order to improve the quality of care and rationalize the use of resources

Economic consequences of investing in anti-HCV antiviral treatment from the Italian NHS perspective : a real-world-based analysis of PITER data

OBJECTIVE: We estimated the cost consequence of Italian National Health System (NHS) investment in direct-acting antiviral (DAA) therapy according to hepatitis C virus (HCV) treatment access policies in Italy. METHODS: A multistate, 20-year time horizon Markov model of HCV liver disease progression was developed. Fibrosis stage, age and genotype distributions were derived from the Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. The treatment efficacy, disease progression probabilities and direct costs in each health state were obtained from the literature. The break-even point in time (BPT) was defined as the period of time required for the cumulative costs saved to recover the Italian NHS investment in DAA treatment. Three different PITER enrolment periods, which covered the full DAA access evolution in Italy, were considered. RESULTS: The disease stages of 2657 patients who consecutively underwent DAA therapy from January 2015 to December 2017 at 30 PITER clinical centres were standardized for 1000 patients. The investment in DAAs was considered to equal €25 million, €15 million, and €9 million in 2015, 2016, and 2017, respectively. For patients treated in 2015, the BPT was not achieved, because of the disease severity of the treated patients and high DAA prices. For 2016 and 2017, the estimated BPTs were 6.6 and 6.2 years, respectively. The total cost savings after 20 years were €50.13 and €55.50 million for 1000 patients treated in 2016 and 2017, respectively. CONCLUSIONS: This study may be a useful tool for public decision makers to understand how HCV clinical and epidemiological profiles influence the economic burden of HCV

L'Italia come modello per l'Europa e per il mondo nelle politiche sanitarie per il trattamento dell'epatite cronica da HCV

The World Health Organization foresees the elimination of HCV infection by 2030. In light of this and the curre nt, nearly worldwide, restriction in direct-acting agents (DAA) accessibility due to their high price, we aimed to evaluate the cost-effectiveness of two alternative DAA treatment policies: Policy 1 (universal): treat all patients, regardless of the fibrosis stage; Policy 2 (prioritized): treat only priori tized patients and delay treatment of the remaining patients until reaching stage F3. T he model was based on patient’s data from the PITER cohort. We demonstrated that extending HC V treatment of patients in any fibrosis stage improves health outcomes and is cost-effective

Le “riforme strutturali” del mercato del lavoro: promesse politiche ed evidenze empiriche

Una proposta di dialogo tra economisti e giuristi ispirata a una rassegna delle evidenze empiriche sugli effetti delle politiche di deregolamentazione del mercato del lavoro

Fault detection in dielectric grid scattering

The problem of diagnosing a grid of small (in terms of the probing wavelength) dielectric scatterers is considered. The aim is to detect and locate possible defects occurring within a known grid when one (or more) scatterer is removed/missing (fault). The study is developed for the canonical case of a TM scalar two-dimensional geometry with the scatterers consisting of dielectric cylinders of small circular cross section. The scattering by a fault is modeled by relaying only to a priori information about the complete grid which leads to a numerically effective inversion procedures as the bulk of the numerical effort is to be done only once. Inversion is achieved by a truncated singular value decomposition scheme and results are provided in terms of closed form expressions for the probability of detection and of false alarm. This allows us to foreseen the achievable performance and to highlight the role of scattering configuration parameters. Numerical examples are also enclosed to corroborate theoretical outcomes. The case of two or more faults is considered as well. For such a case it is numerically shown that detection method still works well even though multiple scattering (occurring between faults) is neglected

Dagli slogan alle evidenze: una rassegna sugli effetti delle deregolamentazioni del lavoro

none3nomixedEmiliano Brancaccio, Nadia Garbellini, Raffaele GiammettiBrancaccio, Emiliano; Garbellini, Nadia; Giammetti, Raffael

Neoclassical influences in agent-based literature: A systematic review

Several studies highlight that the method and the object of analysis of Agent-Based models are in various respects in stark contrast to the prevailing neoclassical paradigm and therefore should be included in the traditions of alternative economic thought. In this paper, however, we show that distinctive features of the neoclassical theory can be found in most of the AB literature. Through a systematic review of most cited academic papers published in the period 1996–2019 and dedicated to Agent-Based models, we show that a “neoclassical influence” can be detected in 61% of papers, while only 39% do not have links with the mainstream neoclassical approach. We also note that after the “great recession” started in 2008 the neoclassical influences on AB literature decline to a significant extent