Health Care Financing Reforms in Italy: Projects of Jefferson\u27s Center for Research in Medical Education and Health Care

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RELATIONSHIP AMONG SYMPTOMS SCORE,PROSTATE VOLUME AND URINARY FLOW RATES IN 543 PATIENTS WITH AND WIHTOUT BPH

BACKGROUND. Studies on the relationship among symptom score, urinary flow rate, and prostate volume in men with lower urinary tract symptoms (LUTS) continue to be of great interest. METHODS. A total of 2,418 men, aged 30-86 years, agreed to participate in an interview and to complete a questionnaire regarding voiding patterns. All subjects answering positively to one or more of the questions were submitted to a diagnostic assessment, based on the algorithm outlined by the guidelines of the International Consultation on Benign Prostatic Hyperplasia (BPH). Five hundred forty-three out of the 2,418 participants (22.45%) were evaluated. At the end of the diagnostic evaluation, 400 men with LUTS but without concomitant conditions (except BPH) known to interfere with normal voiding were selected. Descriptive statistics were used to characterize age, symptom score (International Prostate Symptom Score), prostate volume, and urinary flow rate distribution in these patients. Correlations among the aforementioned parameters were evaluated by means of a multivariate, multiple linear regression and logistic regression model. RESULTS. As reported in other studies, only weak or modest correlations were found. Moreover, the 400 cases were classified according to four age decades. The decrease in peak and mean flow rate per decade of age was similar (0.5 and 0.4 ml/sec); the increase in prostate volume and in total symptom score per decade was 3.3 cc and 0.6, respectively. In patients less than 50 years old, most of the correlations were stronger than those observed in the entire population of 400 men (age and prostate volume, c.c. 0.2864; age and peak flow rate, c.c. -0.2689; age and mean flow rate, c.c. -0.3034). However, symptom score continued to be weakly correlated with age and prostate volume (c.c. 0.0498 and 0.1966, respectively). In the last part of the study, men were assigned to different treatment strategies. Patients who were assigned to surgical treatment had higher prostate volume and IPSS and lower urinary flow rate than those assigned to nonsurgical treatment. CONCLUSIONS. We believe that the reason for the weak statistical association frequently reported in the literature is mainly the urology clinic-based population from which the patient samples were drawn. Data emerging from this analysis support the hypothesis that age is one of the principal factors influencing the relationship among symptom score, urinary flow rate, and prostate volume. (C) 1998 Wiley-Liss, Inc

Agronomic, nutritional and nutraceutical aspects of durum wheat (Triticum durum Desf.) cultivars under low input agricultural management

Among cereals, durum wheat has a central role in the Italian diet and economy, where there is a historical tradition of pasta making. In the present study, we evaluated the nutrient and nutraceutical properties of 2 old and 6 modern durum wheat varieties grown under low input agricultural management. Considering the lack of available data on the adaptability of existing durum wheat varieties to the low input and organic sectors, the research aimed at providing a complete description of the investigated genotypes, considering the agronomic performance as well as the nutrient and phytochemical composition. The experimental trials were carried out at the same location (Bologna, Northern Italy) for two consecutive growing seasons (2006/2007, 2007/2008). No clear distinction between old and modern varieties was observed in terms of grain yield (mean values ranging from 2.5 to 4.0 t/ha), highlighting that the divergence in productivity, normally found between dwarf and non-dwarf genotypes, is strongly reduced when they are cropped under low input management. All durum wheat varieties presented high protein levels and, in addition, provided remarkable amounts of phytochemicals such as dietary fibre, polyphenols, flavonoids and carotenoids. Some of the investigated genotypes, such as Senatore Cappelli, Solex, Svevo and Orobel, emerged with intriguing nutritional and phytochemical profiles, with the highest levels of dietary fibre and antioxidant compounds. The study provided the basis for further investigations into the adaptability of the durum wheat genotypes to low input management, for the selection of genotypes characterised by higher yield and valuable nutrient and nutraceutical quality

Beneficial effects of curtailing immune susceptibility in an Alzheimer's disease model

Background Currently, there are no effective therapeutic options for Alzheimer's disease, the most common, multifactorial form of dementia, characterized by anomalous amyloid accumulation in the brain. Growing evidence points to neuroinflammation as a major promoter of AD. We have previously shown that the proinflammatory cytokine TNFSF10 fuels AD neuroinflammation, and that its immunoneutralization results in improved cognition in the 3xTg-AD mouse. Methods Here, we hypothesize that inflammatory hallmarks of AD might parallel with central and peripheral immune response dysfunction. To verify such hypothesis, we used a triple transgenic mouse model of AD. 3xTg-AD mice were treated for 12 months with an anti-TNFSF10 antibody, and thereafter immune/inflammatory markers including COX2, iNOS, IL-1 beta and TNF-alpha, CD3, GITR, and FoxP3 (markers of regulatory T cells) were measured in the spleen as well as in the hippocampus. Results Spleens displayed accumulation of amyloid-beta(1-42) (A beta(1-42)), as well as high expression of Treg cell markers FoxP3 and GITR, in parallel with the increased levels of inflammatory markers COX2, iNOS, IL-1 beta and TNF-alpha, and blunted IL-10 expression. Moreover, CD3 expression was increased in the hippocampus, consistently with FoxP3 and GITR. After chronic treatment of 3xTg-AD mice with an anti-TNFSF10 antibody, splenic FoxP3, GITR, and the above-mentioned inflammatory markers expression was restored to basal levels, while expression of IL-10 was increased. A similar picture was observed in the hippocampus. Such improvement of peripheral and CNS inflammatory/immune response was associated with decreased microglial activity in terms of TNF alpha production, as well as decreased expression of both amyloid and phosphorylated tau protein in the hippocampus of treated 3xTg-AD mice. Interestingly, we also reported an increased expression of both CD3 and FoxP3, in sections from human AD brain. Conclusions We suggest that neuroinflammation in the brain of 3xTg-AD mice triggered by TNFSF10 might result in a more general overshooting of the immune response. Treatment with an anti-TNFSF10 antibody blunted inflammatory processes both in the spleen and hippocampus. These data confirm the detrimental role of TNFSF10 in neurodegeneration, and corroborate the hypothesis of the anti-TNFSF10 strategy as a potential treatment to improve outcomes in AD

Role of extracellular microvesicles in celiac disease as potential pathogenetic agents and biomarkers of intestinal inflammation

BACKGROUND AND AIM: Celiac Disease (CD) is a chronic intestinal disease caused by the ingestion of gluten. Microvesicles (MVs) belong to a heterogeneous population, released by cells both in homeostasis and pathological conditions. MVs can be considered mediators of inflammation and potential biomarkers. The aim of this study is: 1) to evaluate the possible role of MVs in the propagation of inflammation in CD, using MVs purified by supernatant of duodenal biopsies from CD patients; 2) to identify potential biomarkers by proteomic analysis of pasma-derived MVs from CD patients. MATERIAL AND METHODS: MVs were isolated by molecular exclusion chromatography and ultracentrifugation respectively from plasma and culture supernatant of duodenal biopsies of 10 active CD, 5 remission CD and 6 controls. Proteomic analysis of plasma-derived MVs was performed by mass spectrometry. The possible effects of duodenal-derived MVs on confluent Caco-2 cells were evaluated by measuring Transepithelial Electrical Resistance (TEER) and analyzing the expression of actin, tissue transglutaminase (TG2) and Zonula Occludens-1 (ZO-1). The dosage of IL-8 in the Caco-2 culture supernatant was carried out by ELISA test. The statistical analysis of the data obtained was performed using the Student's t-test. RESULTS: The proteomic analysis of circulating MVs showed 8 proteins from desmosome and cytoskeleton (desmoglein-1 and gamma-enteric actin) associated with the active phase of the disease. Caco-2 cells, treated with the MVs purified from the duodenal biopsies of active CD patients showed: 1) rearrangement of actin filaments; 2) increased expression of TG2; 3) decreased expression of the ZO-1 protein, although an alteration of intestinal permeability was not observed. The analysis of Caco-2 cell supernatants showed a statistically significant increase in IL-8 (p <0.05), in the presence of MVs isolated from biopsies of active CD patients, compared to remission CD patients and controls. CONCLUSIONS: MVs isolated from plasma of active CD patients could represent potential diagnostic and prognostic biomarkers. Although they don’t induce changes in intestinal permeability, MVs could contribute to inflammatory cascade increasing IL-8 production

Baseline Predictors of the Long-Term Insufficient Biochemical Response in Patients with Autoimmune Hepatitis: A Single Center Experience

The treatment response criteria in autoimmune hepatitis (AIH) have been recently updated. This study aimed to assess treatment responses in 39 (16 males) patients with AIH confirmed by histology. Prednisone added to azathioprine or mycophenolate was the most frequent first-line treatment. Serum alanine aminotransferase (ALT) levels were periodically checked for a median of 45 months. Eight (20.5%) patients presented 4 weeks non-response (NR). Baseline lower multiples of ALT above the upper normal limit (UNL) (p = 0.005), Ishak liver fibrosis score > 3 (p = 0.029), and less frequent confluent necrosis > 2 (p 100 strongly predicted CBR failure (p = 0.003) at a follow-up greater than 12 months. In conclusion, the absence of cirrhosis and a ≥50% UNL decrease in serum ALT levels were independent predictors for CBR. A baseline GLUCRE score may help identify patients maintaining longer CBR

The mirna content of exosomes released from the glioma microenvironment can affect malignant progression

Low-grade gliomas (LGG) are infiltrative primary brain tumors that in 70% of the cases undergo anaplastic transformation, deeply affecting prognosis. However, the timing of progression is heterogeneous. Recently, the tumor microenvironment (TME) has gained much attention either as prognostic factor or therapeutic target. Through the release of extracellular vesicles, the TME contributes to tumor progression by transferring bioactive molecules such as microRNA. The aim of the study was to take advantage of glioma-associated stem cells (GASC), an in vitro model of the glioma microenvironment endowed with a prognostic significance, and their released exosomes, to investigate the possible role of exosome miRNAs in favoring the anaplastic transformation of LGG. Therefore, by deep sequencing, we analyzed and compared the miRNA profile of GASC and exosomes obtained from LGG patients characterized by different prognosis. Results showed that exosomes presented a different signature, when compared to their cellular counterpart and that, although sharing several miRNAs, exosomes of patients with a bad prognosis, selectively expressed some miRNAs possibly responsible for the more aggressive phenotype. These findings get insights into the value of TME and exosomes as potential biomarkers for precision medicine approaches aimed at improving LGG prognostic stratification and therapeutic strategies