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In clinical practice, patients with a range of signs and symptoms suggestive of connective tissue disease, but who do not fulfil the classification criteria for a defined disease are often found. This condition is defined as “Undifferentiated Connective Tissue Disease” (UCTD). Most of the authors consider UCTD as a distinct clinical entity, generally stable during follow-up. Despite this, no mutual agreement regarding criteria for its diagnosis has been reached. The clinical, serological, therapeutical and evolutional patterns of 41 patients initially diagnosed as having early UCTD during a 3-year follow-up are described in this study. At the end of the observational period, 21% of the enrolled patients, followed throughout the follow-up, demonstrated clinical evolution to a defined connective tissue disease (CTD), whereas 52% of the observed subjects maintained an undifferentiated profile with variable clinical findings and presenting a generally stable disease over time. The remaining patients showed clinical improvement or complete regression of the symptoms associated with normalization of the inflammatory indexes. The role of therapy in these different clinical courses is discussed.

Abstract To determine whether abnormal casual blood pressure (BP) is associated with left ventricular (LV) abnormalities in children, 190 6- to 11-year-old children (77 girls, 113 boys) were studied at a school site in Naples, Italy, by limited echocardiography and bioelectric impedance to calculate fat-free body mass (FFM). Single-visit BP measurements (defined as casual BP) were high (based on the Italian tables of BP) in 34 children (18%; 9 girls, 25 boys; 133±8/81±10 mm Hg) and obesity was present in 44 (23%; 15 girls, 29 boys). Sex- and age-independent risk of high casual BP value was 2.9-fold (odds ratio) greater in obese than in normal-weight children (95% confidence interval, 1.3 to 6.5; P 2.7 or FFM) was higher and relative wall thickness increased in children with high casual BP (all P P P P r =−.62, SEE=3.8% and r =−.32, SEE=2.4% in normal children). Shortening as a percentage of predicted from wall stress was increased in children with high casual BP at the endocardial level ( P

We investigated several phenotypic and functional parameters of T cell-mediated immunity in a large series of common variable immunodeficiency (CVID) patients. We demonstrated that the vast majority of CVID patients presented multiple T cell abnormalities intimately related among them, the severity of which was reflected in a parallel loss of CD4+ naive T cells. A strong correlation between the number of CD4+ naive T cells and clinical features was observed, supporting the subgrouping of patients according to their number of naive CD4+ T lymphocytes. A reduced thymic output and disrupted CD4+ and CD8+ TCR repertoires paralleled the contraction of CD4+ naive T cell pools. The evaluation of activation markers and cytokine production indicated a strong T cell activation that was significantly related to the increased levels of T cell turnover and apoptosis. Finally, discrete genetic profiles could be demonstrated in groups of patients showing extremely diverse T cell subset composition and function. Naive CD4+ T cell levels were significantly associated with the switched memory B cell-based classification, although the concordance between the respective subgroups did not exceed 58.8%. In conclusion, our data highlight the key role played by the T cell compartment in the pathogenesis of CVID, pointing to the need to consider this aspect for classification of this disease.

BackgroundThe optimal therapeutic strategies for patients presenting with advanced disease at HIV-1 diagnosis are as yet incompletely defined.MethodsAll patients presenting at two outpatient clinics in 2000-2009 with an AIDS-defining clinical condition or a CD4+ T cell count < 200/μL at HIV-1 diagnosis were analyzed for the presence of combined immunovirological response, defined by the concomitant presence of an absolute number of CD4+ T cells > 200 cells/μL and a plasma HIV-1 RNA copy number < 50/mL after 12 months of HAART.ResultsAmong 102 evaluable patients, first-line regimens were protease inhibitors [PI]-based in 78 cases (77%) and efavirenz-based in 24 cases (23%). The overall response rate was 65% (95% CI: 55-74), with no differences by gender, age, nationality, route of transmission, hepatitis virus coinfections, presence of AIDS-defining clinical events, baseline HIV-1 viral load, or type of regimen (response rates with PI-based and efavirenz-based therapy: 63% and 71%, respectively, p = 0.474). Response rate was significantly better with higher baseline CD4+ T cell counts (78% with CD4+ ≥ 100/μL, compared to 50% with CD4+ < 100/μL; odds ratio: 3.5; 95% CI: 1.49-8.23, p = 0.003). Median time on first-line antiretroviral therapy was 24 months (interquartile range: 12-48). Switch to a second line treatment occurred in 57% of patients, mainly for simplification (57%), and was significantly more common with PI-based regimens [adjusted hazard ratios (AHR) with respect to efavirenz-based regimens: 3.88 for unboosted PIs (95% CI: 1.40-10.7, p = 0.009) and 4.21 for ritonavir-boosted PI (95%CI 1.7-10.4, p = 0.002)] and in older subjects (≥ 50 years) (AHR: 1.83; 95% CI: 1.02-3.31, p = 0.044). Overall mortality was low (3% after a median follow up of 48 months).ConclusionsOur data indicate that a favorable immunovirological response is possible in the majority of naive patients presenting at HIV-1 diagnosis with AIDS or low CD4+ T cell counts, and confirm that starting HAART with a more compromised immune system may be associated with a delayed and sometimes partial immune recovery. Simpler regimens may be preferable in this particular population.

Background Metastases are the major cause of cancer-related morbidity and mortality. By the time cancer cells detach from their primary site to eventually spread to distant sites, they need to acquire the ability to survive in non-adherent conditions and to proliferate within a new microenvironment in spite of stressing conditions that may severely constrain the metastatic process. In this study, we gained insight into the molecular mechanisms allowing cancer cells to survive and proliferate in an anchorage-independent manner, regardless of both tumor-intrinsic variables and nutrient culture conditions. Methods 3D spheroids derived from lung adenocarcinoma (LUAD) and breast cancer cells were cultured in either nutrient-rich or -restricted culture conditions. A multi-omics approach, including transcriptomics, proteomics, and metabolomics, was used to explore the molecular changes underlying the transition from 2D to 3D cultures. Small interfering RNA-mediated loss of function assays were used to validate the role of the identified differentially expressed genes and proteins in H460 and HCC827 LUAD as well as in MCF7 and T47D breast cancer cell lines. Results We found that the transition from 2D to 3D cultures of H460 and MCF7 cells is associated with significant changes in the expression of genes and proteins involved in metabolic reprogramming. In particular, we observed that 3D tumor spheroid growth implies the overexpression of ALDOC and ENO2 glycolytic enzymes concomitant with the enhanced consumption of glucose and fructose and the enhanced production of lactate. Transfection with siRNA against both ALDOC and ENO2 determined a significant reduction in lactate production and cell viability. Furthermore, both the number and size of spheroids produced by H460, HCC827, MCF7, and T47D cell lines were significantly reduced upon ALDOC and ENO2 knockdown. Conclusions Our results show that anchorage-independent survival and growth of cancer cells are supported by changes in genes and proteins that drive glucose metabolism towards an enhanced lactate production. Notably, this finding is valid regardless of the tumor type and nutrient environmental availability, thus suggesting the possible general involvement of this mechanism in cancer metastasis. The pan-cancer validation of this vulnerability could potentially help to slow or prevent cancer progression.

The aim of this work was to investigate the mechanisms of appearance and disappearance of the rigid amorphous fraction as well as its effects on the molecular mobility in a large panel of polyesters. Microstructural were performed to evaluate the effects of different chemical compositions and structures on the appearance and disappearance of the rigid amorphous fraction. These studies were carried out using different experimental techniques : modulated-temperature differential scanning calorimetry (MT-DSC), fast scanning calorimetry (FSC), dielectric relaxation spectroscopy (DRS) and X-ray diffraction (XRD). Fast scanning calorimetry proved to be a very efficient technique to obtain the temperature dependence of the melting enthalpy of the fully crystalline material, which then allows to get a better estimation of the rigid amorphous fraction in semi-crystalline samples. The microstructural studies showed that the chemical composition and structure have a strong effect on the appearance and disappearance of the rigid amorphous fraction. The whole set of experimental results also proved that by adjusting the chemical composition and structure,as well as the crystallization protocol, it is possible to obtain microstructures with different properties, which gives access to a wide range of applications.; L’objectif de ce travail était d’étudier les mécanismes de formation et de disparition de la fraction amorphe rigide ainsi que son impact sur la mobilité moléculaire d’un large panel de polyesters. Des études microstructurales ont été réalisées afin d’investiguer les effets de la composition et de la structure chimique sur la formation et la disparition de la fraction amorphe rigide dans différents systèmes polymères. Ces études ont été réalisées à l’aide de différentes techniques d’analyses : calorimétrie différentielle à balayage avec modulation en température (MT-DSC), calorimétrie à balayage rapide (FSC), spectroscopie diélectrique relaxationelle (DRS) et diffraction des rayons X (DRX). La calorimétrie à balayage rapide s’est montrée particulièrement intéressante pour étudier la dépendance en température de l’enthalpie de fusion des échantillons 100% cristallins, ce qui permet ensuite, d’obtenir une meilleure estimation de la quantité de fraction amorphe rigide dans les échantillons semi-cristallins. Les études microstructurales sur les différents polyesters ont ensuite montré que la composition et la structure chimique du polymère ont un effet significatif sur la formation et la disparition de la fraction amorphe rigide. Elles ont également prouvé qu’en ajustant la composition et la structure chimique, ainsi que le protocole de cristallisation, il est possible de créer des microstructures avec des propriétés diverses et variées augmentant ainsi le nombre d’applications.

This work explored for the first time some physical properties of a new generation of copolyesters obtained from physical mixtures of two isomers: 2,5-furandicarboxylic acid (2,5-FDCA) and 2,4-furandicarboxylic acid (2,4-FDCA). The 2,5-FDCA isomer is the most studied today because it is used to obtain Poly (Ethylene-2,5-Furanoate) (2,5-PEF), which is the best bio-based candidate to replace the giant of the plastic industry, Poly (Ethylene-Terephthalate) (PET). The 2,4-FDCA isomer has also been studied because it can be used to obtain Poly (Ethylene-2,4-Furanoate) (2,4-PEF), with an extremely slow kinetics of crystallization. It has been shown that the combination of these two isomers allows to obtain copolymers with adjusted and controlled properties. The dynamics of molecular relaxation in the amorphous phase, both localized and cooperative, have been studied over a wide range of frequencies and temperatures, according to approaches typically used to study glass-forming liquids. Then, the investigation was directed towards the influence of the position of the carbonyl group on the furan ring on the ability to crystallize and the kinetics of crystallization. Several experimental techniques have been used: differential scanning calorimetry (DSC), modulate-temperature differential scanning calorimetry (MT-DSC), dielectric relaxation spectroscopy (DRS) and measurement of thermos-stimulated depolarization currents (TSDC)., L'objectif de ce travail est d'explorer pour la première fois certaines propriétés physiques d'une nouvelle génération de copolyesters obtenus à partir d'un mélange physique de deux isomères : l’acide-2,5-furandicarboxylique (2,5-FDCA) et l’acide-2,4-furandicarboxylique (2,4-FDCA). L’isomère 2,5-FDCA est aujourd’hui le plus étudié, car il est utilisé pour obtenir le Poly(Ethylène-2,5-Furanoate) (2,5-PEF), qui est le meilleur candidat biosourcé pour remplacer le géant de l'industrie plastique, le Poly (Ethylène-Téréphtalate) (PET). Son isomère, le 2,4-FDCA, a aussi été étudié puisqu’il permet d’obtenir le Poly (Ethylène-2,4-Furanoate) (2,4-PEF), qui possède une cinétique de cristallisation extrêmement lente. Il a été montré que la combinaison de ces deux isomères permet d’obtenir des copolymères ayant des propriétés ajustées et contrôlées. Les dynamiques de relaxation moléculaire dans la phase amorphe, aussi bien localisées que coopératives, ont été étudiées dans une large gamme de fréquences et températures, selon les approches caractéristiques de l’étude des liquides formateurs de verre. Ensuite, l’étude a été orientée vers l'influence de la position du groupe carbonyle sur le furane sur l’aptitude à cristalliser et les cinétiques de cristallisation. Plusieurs techniques expérimentales ont été utilisées : calorimétrie différentielle à balayage (DSC), calorimétrie différentielle à balayage avec modulation de température (MT-DSC), spectroscopie de relaxation diélectrique (DRS) et mesure des courants de dépolarisation thermostimulés (TSDC).

La figura dell'eroe e del poeta nelle Argonautiche di Apollonio Rodio.