Invecchiamento, immigrazione, economia

Analisi e interpretazione economica e sociologica della evoluzione demografica in Italia, anche in chiave comparativa. Valutazione degli effetti economici e finanziari dell'invecchiamento della popolazione e dell'immigrazione. Evoluzione demografica e sostenibilit\ue0 del debito pubblico: previsione dei futuri andamenti. Politiche pubbliche per la famiglia e politiche dell'immigrazione

New Baryons in the Delta eta and Delta omega Channels

The decays of excited nonstrange baryons into the final states Delta eta and Delta omega are examined in a relativized quark pair creation model. The wavefunctions and parameters of the model are fixed by previous calculations of N pi and N pi pi, etc., decays through various quasi-two body channels including N eta and N omega. Our results show that the combination of thresholds just below the region of interest and the isospin selectivity of these channels should allow the discovery of several new baryons in such experiments.Comment: 10 pages, RevTe

Advances in targeted Alpha therapy for prostate cancer

BACKGROUND: Amongst therapeutic radiopharmaceuticals, targeted alpha therapy (TαT) can deliver potent and local radiation selectively to cancer cells as well as the tumor microenvironment and thereby control cancer while minimizing toxicity. DESIGN: In this review, we discuss the history, progress, and future potential of TαT in the treatment of prostate cancer, including dosimetry-individualized treatment planning, combinations with small-molecule therapies, and conjugation to molecules directed against antigens expressed by prostate cancer cells, such as prostate-specific membrane antigen (PSMA) or components of the tumor microenvironment. RESULTS: A clinical proof of concept that TαT is efficacious in treating bone-metastatic castration-resistant prostate cancer has been demonstrated by radium-223 via improved overall survival and long-term safety/tolerability in the phase III ALSYMPCA trial. Dosimetry calculation and pharmacokinetic measurements of TαT provide the potential for optimization and individualized treatment planning for a precision medicine-based cancer management paradigm. The ability to combine TαTs with other agents, including chemotherapy, androgen receptor (AR)-targeting agents, DNA repair inhibitors, and immuno-oncology agents, is under investigation. Currently, TαTs that specifically target prostate cancer cells expressing PSMA represents a promising therapeutic approach. Both PSMA-targeted actinium-225 and thorium-227 conjugates are under investigation. CONCLUSIONS: The described clinical benefit, safety and tolerability of radium-223 and the recent progress in TαT trial development suggest that TαT occupies an important new role in prostate cancer treatment. Ongoing studies with newer dosimetry methods, PSMA targeting, and novel approaches to combination therapies should expand the utility of TαT in prostate cancer treatment

T cell-mediated oral tolerance is intact in germ-free mice

Commensal enteric bacteria stimulate innate immune cells and increase numbers of lamina propria and mesenteric lymph node (MLN) T and B lymphocytes. However, the influence of luminal bacteria on acquired immune function is not understood fully. We investigated the effects of intestinal bacterial colonization on T cell tolerogenic responses to oral antigen compared to systemic immunization. Lymphocytes specific for ovalbumin–T cell receptor (OVA–TCR Tg+) were transplanted into germ-free (GF) or specific pathogen-free (SPF) BALB/c mice. Recipient mice were fed OVA or immunized subcutaneously with OVA peptide (323–339) in complete Freund's adjuvant (CFA). Although the efficiency of transfer was less in GF recipients, similar proportions of cells from draining peripheral lymph node (LN) or MLN were proliferating 3–4 days later in vivo in GF and SPF mice. In separate experiments, mice were fed tolerogenic doses of OVA and then challenged with an immunogenic dose of OVA 4 days later. Ten days after immunization, lymphocytes were restimulated with OVA in vitro to assess antigen-specific proliferative responses. At both high and low doses of OVA, cells from both SPF and GF mice fed OVA prior to immunization had decreased proliferation compared to cells from control SPF or GF mice. In addition, secretion of interferon (IFN)-γ and interleukin (IL)-10 by OVA–TCR Tg+ lymphocytes was reduced in both SPF and GF mice fed OVA compared to control SPF or GF mice. Unlike previous reports indicating defective humoral responses to oral antigen in GF mice, our results indicate that commensal enteric bacteria do not enhance the induction of acquired, antigen-specific T cell tolerance to oral OVA

Is the abundance of Faecalibacterium prausnitzii relevant to Crohn's disease?

Reports that bacteria within the Firmicutes phylum, especially the species Faecalibacterium prausnitzii, are less abundant in Crohn’s disease (CD) patients and supernatants from cultures of this bacterium are anti-inflammatory prompted the investigation of the possible correlations between the abundance of F.prausnitzii and the response to treatment in patients with gut diseases and healthy controls. In a randomized, double-blind trial, faeces were collected from healthy volunteers, and from patients with active CD, ulcerative colitis (UC) and irritable bowel syndrome before and after treatment. The levels of F. prausnitzii DNA in faecal suspensions were determined by PCR. Treatment by an elemental diet was effective, resulting in decreases in both the Harvey and Bradshaw index (P<0.001) and the concentrations of serum C-reactive protein (P<0.05). The total levels of F. prausnitzii in faecal samples from CD patients at presentation were lower than those in the other groups both before and after the treatment. There was no correlation between F. prausnitzii abundance and the severity of CD before treatment. Clinical improvement unexpectedly correlated with a significant decrease in the abundance of F. prausnitzii, especially the A2-165 subgroup (P<0.05). Our data suggest that a paucity of F. prausnitzii in the gastrointestinal microbial communities is likely to be a minor aetiological factor in CD: recovery following elemental diet is attributed to lower levels of gut flora

Classification of the severity of diabetic neuropathy: a new approach taking uncertainties into account using fuzzy logic

OBJECTIVE: This study proposes a new approach that considers uncertainty in predicting and quantifying the presence and severity of diabetic peripheral neuropathy. METHODS: A rule-based fuzzy expert system was designed by four experts in diabetic neuropathy. The model variables were used to classify neuropathy in diabetic patients, defining it as mild, moderate, or severe. System performance was evaluated by means of the Kappa agreement measure, comparing the results of the model with those generated by the experts in an assessment of 50 patients. Accuracy was evaluated by an ROC curve analysis obtained based on 50 other cases; the results of those clinical assessments were considered to be the gold standard. RESULTS: According to the Kappa analysis, the model was in moderate agreement with expert opinions. The ROC analysis (evaluation of accuracy) determined an area under the curve equal to 0.91, demonstrating very good consistency in classifying patients with diabetic neuropathy. CONCLUSION: The model efficiently classified diabetic patients with different degrees of neuropathy severity. In addition, the model provides a way to quantify diabetic neuropathy severity and allows a more accurate patient condition assessment

Influence of Crohn’s disease related polymorphisms in innate immune function on ileal microbiome

We have previously identified NOD2 genotype and inflammatory bowel diseases (IBD) phenotype, as associated with shifts in the ileal microbiome (“dysbiosis”) in a patient cohort. Here we report an integrative analysis of an expanded number of Crohn's disease (CD) related genetic defects in innate immune function (NOD2, ATG16L1, IRGM, CARD9, XBP1, ORMDL3) and composition of the ileal microbiome by combining the initial patient cohort (Batch 1, 2005–2010, n = 165) with a second consecutive patient cohort (Batch 2, 2010–2012, n = 118). These combined patient cohorts were composed of three non-overlapping phenotypes: 1.) 106 ileal CD subjects undergoing initial ileocolic resection for diseased ileum, 2.) 88 IBD colitis subjects without ileal disease (predominantly ulcerative colitis but also Crohn’s colitis and indeterminate colitis, and 3.) 89 non-IBD subjects. Significant differences (FDR C. difficile infection, and NOD2 genotype on ileal dysbiosis in the expanded analysis. The relative abundance of the Proteobacteria phylum was positively associated with ileal CD and colitis phenotypes, but negatively associated with NOD2R genotype. Additional associations with ORMDL3 and XBP1 were detected at the phylum/subphylum level. IBD medications, such as immunomodulators and anti-TNFα agents, may have a beneficial effect on reversing dysbiosis associated with the IBD phenotype. Exploratory analysis comparing microbial composition of the disease unaffected region of the resected ileum between 27 ileal CD patients who subsequently developed endoscopic recurrence within 6–12 months versus 34 patients who did not, suggested that microbial biomarkers in the resected specimen helped stratify patients with respect to risk of post-surgical recurrence.</div