56 research outputs found
La documentazione scritta e la valutazione del potenziale archeologico: il caso dell'Inchiesta Jacini
No full textNew locus for autosomal dominant high myopia maps to the long arm of chromosome 17
No full textPURPOSE. To map the gene(s) associated with autosomal dominant (AD) high-grade myopia. METHODS. A multigeneration English/Canadian family with AD severe myopia was ascertained. Myopes were healthy, with no clinical evidence of syndromic disease, anterior segment abnormalities, or glaucoma. The family contained 22 participating members (12 affected). The average age of diagnosis of myopia was 8.9 years (range, birth to 11 years). The average refractive error for affected adults was -13.925 D (range, -5.50 to -50.00). Microsatellite markers for genotyping were used to assess linkage to several candidate loci, including three previously identified AD high-myopia loci on 18p11.31, 12q22q23, and 7q36. Syndromic myopia linkage was excluded by using intragenic or flanking markers for Stickler syndrome types 1, 2, and 2B; Marfan syndrome; Ehlers-Danlos syndrome type 4; and juvenile glaucoma. A full genome screening was performed, with 327 microsatellite markers spaced by 5 to 10 cM. Two-point linkage was analyzed using the FASTLINK program run at 90% penetrance and a myopia gene frequency of 0.0133. RESULTS. Linkage to all candidate loci was excluded. The genome screening yielded a maximum two-point lod score of 3.17 at θ = 0 with microsatellite marker D17S1604. Fine mapping and haplotype analysis defined the critical interval of 7.71 cM at 17q21-22. CONCLUSIONS. A novel putative disease locus for AD high-grade myopia has been identified and provides additional support for genetic heterogeneity for this disorder
An experimental, theoretical and numerical investigation of shape memory polymers
No full textThe present paper deals with the experimental analysis, constitutive modeling and numerical simulation of a class of polymers, exhibiting shape memory effects. We first present and discuss the results of an experimental traction-shrinkage campaign on semi-crystalline shape memory polymers, particularly, on low-density and high-density polyethylene-based polymers. Then, we develop a new one-dimensional phenomenological constitutive model, based on the so-called phase transition approach and formulated in a finite strain framework, in order to reproduce experimental observations. The model is treated through a numerical procedure, consisting in the replacement of the classical set of Kuhn-Tucker inequality conditions by the Fischer-Burmeister complementarity function. Numerical predictions reveal that the model is able to describe qualitative aspects of material behavior, involving both orientation and thermal retraction, as well as to predict experimental orientation processes for semi-crystalline polyethylene-based polymers with different densities
Circulating Endothelial Stem Cells in Age-Matched Smokers with or without Mild-to-Moderate Pulmonary Emphysema
No full textPrevious studies have suggested a role for an increased apoptosis of the endothelial cells in the pulmonary capillaries of the alveolar septa in the pathogenesis of pulmonary emphysema. In animal models, circulating endothelial stem cells may contribute to the repair of lung damage. It is unknown if a decrease in the blood of these cells may contribute to the pathogenesis of pulmonary emphysema in humans. The aim of our study was to investigate by flow cytometry the number of total (CD34+) and endothelial stem (triple positive for CD34+/CD133/VEGF-R2) cells in the peripheral venous blood of age-matched smokers with or without pulmonary emphysema. The presence and the severity of pulmonary emphysema was determined using HRCT of the chest with density mask and the NETT score (0 to 4; NEJM 2001). All the subjects were free from concomitant diseases or drugs able to interfere with the number of circulating stem cells. Venous blood samples from 37 subjects (mean age: 66.8±1.4, 25M/12F, mean 33.11±3.2 pack-years, 12 current and 25 ex-smokers) were obtained. Their mean HRCT NETT score is 1.7±0.4.
Twenty-two subjects (59.5%) had chronic airflow obstruction (mean post-bronchodilator FEV1/FVC ratio=56.8%±2.7) whereas 39.5% (n=15) had normal lung function (FEV1/FVC ratio=77.1%±1.4).
We found a significant correlation between the absolute number of circulating CD34+ cells and the absolute number of circulating endothelial stem cells (r=0.593, p<0.0001). Also there was a significant correlation between the percentage of circulating endothelial stem cells and the number of pack-years smoked (r=0.42, p<0.05). No correlation was found between total and endothelial stem cells number and HRCT score of pulmonary emphysema or lung function data. These data suggest that the number of circulating endothelial stem cells is not related to pulmonary emphysema severity
Modulation of soluble receptor for advanced glycation end products isoforms and advanced glycation end products in long-living individuals
No full textBackground: Circulating levels of soluble receptor for advanced glycation end products (sRAGE) and advanced glycation end products (AGEs) correlate with aging/cardiovascular risk, which is delayed in long-living individuals (LLIs). AGEs/sRAGE isoforms (cleaved RAGE [cRAGE] and secretory RAGE [esRAGE]) ratio is a valuable marker for disease risk. Results: We evaluated circulating sRAGE isoforms, and AGEs in LLIs (n = 95; 90-105 years) and controls (n = 94; 11-89 years). cRAGE decreased with age in controls and further declined in LLIs. esRAGE increased in LLIs. AGEs rose with age in controls and decreased in LLIs that were characterized by a lower AGEs/sRAGE ratio. Notably, cRAGE and AGE/esRAGE ratio better discriminated controls from LLIs. Conclusion: circulating cRAGE could be considered a reliable marker of chronological age while esRAGE a protective factor for longevity. Aging is the major risk factor for disease development. Long-living individuals (LLIs) are subjects older than 90 years that represent an invaluable model to study mechanisms underpinning longevity and healthy aging. Circulating levels of soluble receptor for advanced glycation end products (sRAGE) change with aging and can forecast the cardiovascular risk, which is reduced in centenarians. sRAGE is composed of two isoforms, the cleaved RAGE (cRAGE) and the secretory RAGE (esRAGE), that are known to inhibit the oxidative stress and inflammatory activities of their ligands such the advanced glycation end products (AGEs). In this study, we measured the plasmatic levels of both sRAGE isoforms and AGEs in LLIs (90-105 years) and control subjects (11-89 years). We found that cRAGE decreases with age in controls and LLIs. esRAGE increases in LLIs and AGEs increase in controls with age but decrease in LLIs. AGEs/esRAGE ratio and cRAGE were able to discriminate controls from LLIs. Hence, LLIs are characterized by a lower AGEs/sRAGE ratio, due to esRAGE increase and AGEs reduction that may explain their reduced cardiovascular and metabolic risk. Besides, circulating cRAGE could be considered a reliable marker of chronological age, while esRAGE a protective factor associated with longevity
Simplification to TDF+FTC fixed dose combination shows improved immunological response, adherence and patient-related outcomes while maintaining virological efficacy (the MULTIFACTORS Back Study)
No full textAim of this study was to assess the efficacy, adherence and patient-related outcomes of a simplification strategy in patients switching from a stable regimen containing tenofovir and lamivudine to fixed dose combination with tenofovir + emtricitabine
Cardiometabolic risk is unraveled by color Doppler ultrasound of the clitoral and uterine arteries in women consulting for sexual symptoms
No full textFemale sexual dysfunction (FSD) may be a mirror of a poor cardiometabolic state. In a small pilot study enrolling 71 women with FSD, we previously demonstrated that clitoral Pulsatility Index (PI) evaluated by using color Doppler ultrasound (CDU), reflecting vascular resistance, was associated with cardiometabolic risk factors. Data on uterine CDU in this context are lacking. First, to confirm previously reported data on the direct association between clitoral PI and cardiometabolic risk factors on a larger study population of women consulting for sexual symptoms; second, to investigate eventual similar correlations between cardiometabolic risk factors and CDU parameters of the uterine artery. We also ascertained whether uterine artery PI, similarly to what had previously been observed for clitoral artery PI, was directly related to body image uneasiness and psychopathological symptoms, assessed by validated questionnaires. N = 230 women consulting our clinic for sexual symptoms were examined with clitoral CDU and blood sampling and were asked to fill out the Female Sexual Function Index, the Middlesex Hospital Questionnaire (MHQ) and the Body Uneasiness Test (BUT). In a subgroup of women (n = 164), we also performed transvaginal CDU with measurement of uterine artery parameters. At multivariate analysis, we found a direct association between clitoral PI and body mass index (BMI) (p = 0.004), waist circumference (WC) (p = 0.004), triglycerides (p = 0.006), insulin (p = 0.029) and HOMA-IR (p = 0.009). Furthermore, a correlation between obesity and Metabolic Syndrome (MetS) and a higher clitoral PI was observed (p = 0.003 and p = 0.012, respectively). Clitoral PI was also correlated with MHQ-S (p = 0.010), a scale exploring somatized anxiety symptoms, and BUT-B Positive Symptom Distress Index (p = 0.010), a measure of body image concerns. Similarly, when investigating the uterine artery, we were able to demonstrate an association between its PI and BMI (p < 0.0001), WC (p = 0.001), insulin (p = 0.006), glycated haemoglobin (p = < 0.0001), and HOMA-IR (p = 0.009). Women diagnosed with obesity and MetS showed significantly higher uterine PI values vs. those without obesity or MetS (p = 0.001 and p = 0.004, respectively). Finally, uterine PI was associated with BUT-A Global Severity Index (p < 0.0001) and with several other BUT-A subdomains. Vascular resistance of clitoral and uterine arteries is associated with cardiometabolic risk factors and body image concerns in women consulting for sexual symptoms. If further confirmed in different populations, our data could suggest CDU, a common examination method, as a useful tool for an identification—and possible correction—of cardiometabolic risk factors
Et toutesfoiz je contredictz ! La celebrazione delle martiri nei mystères agiografici di S. Barbara e di S. Margherita
No full textInternational audienc
Et toutesfoiz je contredictz ! La celebrazione delle martiri nei mystères agiografici di S. Barbara e di S. Margherita
No full textInternational audienc
Cateslytin and Chromofungin, two CgA derived peptides actors of the immune and cardiac systems
No full textLa CgA est une pro-hormone stockée dans les granules de sécrétion et elle subit une maturation protéolytique conduisant à la formation d’un très grand nombre de peptides dérivés. La Chromofungine (Chr: CgA47-66) et la Cateslytine (Ctl: CgA344–358) possèdent des propriétés antimicrobiennes. Staphylococcus aureus est un pathogène très virulent qui provoque un très grand nombre de graves infections cliniques et il représente une des causes principales des infections nosocomiales et la destruction du tissu endocardiaque après implantation de valve cardiaque. La première partie de l’étude nous avons montré que la Chr induise un effet inotropique négatif sans changement de la pression coronarienne. L’activation de la voie de signalisation AKT/eNOS/cGMP/PKG est responsable de cet effet de Chr. Nous avons aussi montré que Chr agit comme un agent de post-conditionnement contre les effets négatifs de l’ischémie/reperfusion, a responsables de cette cardio-protection impliquent les cascades de signalisation PI3K, RISK, MitoKATP et miRNA-21. Dans le but d’élaborer un nouveau revêtement de valves cardiaques le peptide D*T*Ctl se révèle intéressant dans des conditions non oxydantes car (1) il présente une activité antimicrobienne contre S. aureus; (2) en présence de S. aureus il permet par clivage protéolytique de libérer le peptide Ctl actif. Une première expérience réalisée in vivo a montré le rôle de Ctl pour combattre l’infection à S. aureus au niveau systémique et au niveau cardiaque, mais aussi assurer la protection du myocarde.CgA is a pro-hormone costored in secretory granules and numerous cleavage products of this protein have been identified. Chromofungin (Chr: CgA47-66) and Cateslytin (Ctl: CgA344–358) are peptides that display antimicrobial activities.Staphylococcus aureus is an opportunistic pathogen and the leading cause of a wide range of severe clinical infections and one of the most important cause of hospital-acquired infections and leading infective cause of destruction of endocardial tissue after implantation of prosthetic heart valve. The first part of the study, we found that Chr induced negative inotropic effects without changing coronary pressure. The AKT/eNOS/cGMP/PKG pathway mediated this action. We also found that Chr acted as a postconditioning agent against ischemia/reperfusion damages. Cardioprotection involved PI3K, RISK pathway, MitoKATPand miRNA-21. In order to develop a new coating of cardiac valves, the peptide D*T *Ctl proves to be useful under non-oxidizing conditions because (1) it exhibits antimicrobial activity against S. aureus; (2) in the presence of S. aureus, it allows proteolytic cleavage to release the active Ct1 peptide.In the last part of this thesis we showed in vivo the antibacterial role of Ctl against S. aureus infection at the systemic and cardiac levels, but also its cardioprotective action
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