Complex networks and public funding: the case of the 2007-2013 Italian program

In this paper we apply techniques of complex network analysis to data sources representing public funding programs and discuss the importance of the considered indicators for program evaluation. Starting from the Open Data repository of the 2007-2013 Italian Program Programma Operativo Nazionale 'Ricerca e Competitivit\`a' (PON R&C), we build a set of data models and perform network analysis over them. We discuss the obtained experimental results outlining interesting new perspectives that emerge from the application of the proposed methods to the socio-economical evaluation of funded programs.Comment: 22 pages, 9 figure

Hyperhomocysteinemia as a Risk Factor and Potential Nutraceutical Target for Certain Pathologies

Hyperhomocysteinemia is recognized as a risk factor for several diseases, including cardiovascular and neurological conditions. Homocysteine (HCys) is a key metabolite involved in the biosynthesis and metabolism of methionine (Met), which plays a pivotal role in the physiological cell's life cycle. The biochemistry of Met is finely regulated by several enzymes that control HCys concentration. Indeed, balanced activity among the enzymes is essential for the cell's well-being, while its malfunction could raise HCys concentration which can lead to the onset of several pathological conditions. The HCys concentration increase seems to be caused mainly by the widely diffused polymorphisms of several enzymes. Nowadays, a blood test can easily detect elevated concentrations of HCys, referred to as Hyperhomocysteinemia (HHCys). Prolonged exposure to this condition can lead to the onset of cardiovascular disease and can lead to the development of atherosclerosis, stroke, inflammatory syndromes like osteoporosis and rheumatism, as well as neuronal pathologies including Alzheimer's and Parkinson's diseases. In this review, we analyzed the literature of several pathological conditions in which the molecular pathways of HHCys are involved. Interestingly, several observations indicate that the calibrated assumption of correct doses of vitamins such as folic acid, vitamin B6, vitamin B12, and betaine may control HHCys-related conditions

Structured headache services as the solution to the ill-health burden of headache. 2. Modelling effectiveness and cost-effectiveness of implementation in Europe: methodology

Background: Health economic evaluations support health-care decision-making by providing information on the costs and consequences of health interventions. No universally accepted methodology exists for modelling effectiveness and cost-effectiveness of interventions designed to close treatment gaps for headache disorders in countries of Europe (or elsewhere). Our aim here, within the European Brain Council’s Value-of-Treatment project, was to develop headache-type-specific analytical models to be applied to implementation of structured headache services in Europe as the health-care solution to headache. Methods: We developed three headache-type-specific decision-analytical models using the WHO-CHOICE framework and adapted these for three European Region country settings (Luxembourg, Russia and Spain), diverse in geographical location, population size, income level and health-care systems and for which we had population-based data. Each model compared current (suboptimal) care vs target care (delivered in accordance with the structured headache services model). Epidemiological and economic data were drawn from studies conducted by the Global Campaign against Headache; data on efficacy of treatments were taken from published randomized controlled trials; assumptions on uptake of treatments, and those made for Healthy Life Year (HLY) calculations and target-care benefits, were agreed with experts. We made annual and 5-year cost estimates from health-care provider (main analyses) and societal (secondary analyses) perspectives (2020 figures, euros). Results: The analytical models were successfully developed and applied to each country setting. Headache-related costs (including use of health-care resources and lost productivity) and health outcomes (HLYs) were mapped across populations. The same calculations were repeated for each alternative (current vs target care). Analyses of the differences in costs and health outcomes between alternatives and the incremental cost-effectiveness ratios are presented elsewhere. Conclusions: This study presents the first headache-type-specific analytical models to evaluate effectiveness and cost-effectiveness of implementing structured headache services in countries in the European Region. The models are robust, and can assist policy makers in allocating health budgets between interventions to maximize the health of populations

Structured headache services as the solution to the ill-health burden of headache. 3. Modelling effectiveness and cost-effectiveness of implementation in Europe: findings and conclusions

Background: There have been several calls for estimations of costs and consequences of headache interventions to inform European public-health policies. In a previous paper, in the absence of universally accepted methodology, we developed headache-type-specific analytical models to be applied to implementation of structured headache services in Europe as the health-care solution to headache. Here we apply this methodology and present the findings. Methods: Data sources were published evidence and expert opinions, including those from an earlier economic evaluation framework using the WHO-CHOICE model. We used three headache-type-specific analytical models, for migraine, tension-type-headache (TTH) and medication-overuse-headache (MOH). We considered three European Region case studies, from Luxembourg, Russia and Spain to include a range of health-care systems, comparing current (suboptimal) care versus target care (structured services implemented, with provider-training and consumer-education). We made annual and 5-year cost estimates from health-care provider and societal perspectives (2020 figures, euros). We expressed effectiveness as healthy life years (HLYs) gained, and cost-effectiveness as incremental cost-effectiveness-ratios (ICERs; cost to be invested/HLY gained). We applied WHO thresholds for cost-effectiveness. Results: The models demonstrated increased effectiveness, and cost-effectiveness (migraine) or cost saving (TTH, MOH) from the provider perspective over one and 5 years and consistently across the health-care systems and settings. From the societal perspective, we found structured headache services would be economically successful, not only delivering increased effectiveness but also cost saving across headache types and over time. The predicted magnitude of cost saving correlated positively with country wage levels. Lost productivity had a major impact on these estimates, but sensitivity analyses showed the intervention remained cost-effective across all models when we assumed that remedying disability would recover only 20% of lost productivity. Conclusions: This is the first study to propose a health-care solution for headache, in the form of structured headache services, and evaluate it economically in multiple settings. Despite numerous challenges, we demonstrated that economic evaluation of headache services, in terms of outcomes and costs, is feasible as well as necessary. Furthermore, it is strongly supportive of the proposed intervention, while its framework is general enough to be easily adapted and implemented across Europe

Inflammation and Neurotransmission of the Vescico-Uterine Space in Cesarean Sections:

Collagen IV and laminin play a key role in regulating stiffness, elasticity and flexibility of the vescico-uterine space (VUS) tissue. The neurotensin (NT), the neuropeptide tyrosine (NPY) and the protein gene product 9.5 (PGP 9.5) possessing vasorelaxation and tissue vascularization activities, play key roles in cervical ripening, scar innervations and pain control. We propose that the integrity of these substances in VUS tissue is compromised after Cesarean section (CS), since wound healing disturbances and pelvic pain, as well as pregnancy and delivery complications, are related with lower uterine segment dysfunctions after CS. Therefore, the contents of collagen IV, laminin, NT, NPY and PGP 9.5 nerve fibres from the VUS tissue samples obtained during the first CS and the repeated CS were comparatively studied. VUS specimens were collected from 104 patients during CS and evaluated by immunohistochemistry. Collagen IV and laminin were mostly found in the vascular membrane bounds and their images were quantitatively evaluated by Quantimet Leica analyzer software. Differences of collagen IV, laminin, NT, NPY and PGP 9.5 values in VUS tissue between the first CS and the repeat CS samples were calculated by Student's Mest. Reduced laminin and increased collagen IV values were observed in the VUS scar tissue after the repeated CS in comparison with those of VUS intact tissue obtained during the first CS. Significantly higher values of nerve fibres, containing NT, NPY and PGP 9.5 were registered in intact VUS tissue samples, respectively 5±0.7, 7±0.6 and 5±0.9 CU, than those of VUS scar tissue samples obtained during the repeated CS, respectively 3±0.6,2±0.4 and 3±0.7 CU (p<0.05). The authors observed increased collagen IV and reduced laminin values after the repeated CS which might be the key signs of inflammatory damage of VUS scar tissue by CS. These findings were strengthened by the registration of decreased NT, NPY and PGP 9.5 values in the same samples, which are important neurotransmitters and are responsible for optimal wound healing, pain control and lower uterine segment functions

Post-exposure rate of tuberculosis infection among health care workers measured with tuberculin skin test conversion after unprotected exposure to patients with pulmonary tuberculosis: 6-year experience in an Italian teaching hospital

BACKGROUND: This study assesses the risk of LTBI at our Hospital among HCWs who have been exposed to TB patients with a delayed diagnosis and respiratory protection measures were not implemented. METHODS: All HCWs exposed to a patient with cultural confirmed pulmonary TB and respiratory protection measures were not implemented were included. Data on TST results performed in the past (defined as T0) were recorded. TST was performed twice: first, immediately after exposure to an index patient (T1) and three months later (T2). The period of time between T0 and T1 was used to calculate he annual rate of tuberculosis infection (ARTI), while le period of time between T1 and T2 was used to calculate the post exposure annual rate of tuberculosis infection (PEARTI). RESULTS: Fourteen index patients were admitted; sputum smear was positive in 7 (58.3%), 4 (28.6%) were non-Italian born patients. 388 HCWs were exposed to index patients, a median of 27 (12-39) HCW per each index patient. One hundred eighty (46.4%) HCWs received BCG in the past. One hundred twenty two HCWs (31%) were TST positive at a previous routine screening and not evaluated in this subset. Among the remaining 255 HCWs with negative TST test in the past, TST at T1 was positive in 11 (4.3%). ARTI was 1.6 (95% CI 0.9-2.9) per 100 PY. TST at T2 was positive in 9 (3.7%) HCWs, that were TST negative at T1. PEARTI was 26 (95% CI 13.6-50) per 100 PY. At univariate analysis, older age was associated with post exposure latent tuberculosis infection (HR 1.12; 95% CI 1.03-1.22, p=0.01). CONCLUSIONS: PEARTI was considerably higher among HCWs exposed to index patients than ARTI. These data underscore the overwhelming importance of performing a rapid diagnosis, as well as implementing adequate respiratory protection measures when TB is suspected

Metalloproteinases in diabetics and nondiabetics during acute coronary syndromes and after 3 months

The authors hypothesized that matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1, and TIMP-2 would be abnormal in acute coronary syndromes (ACS). Forty-six diabetic and 78 nondiabetic patients during ACS and after 3 months were enrolled in this study. MMP-2, -9 and TIMP-1, -2 plasma levels were measured. Significant decrease of MMP-2, TIMP-1, and TIMP-2 plasma levels was observed in the nondiabetic group with ACS after 3 months compared to the baseline value. Significant decrease of MMP-2, MMP-9, TIMP-1, and TIMP-2 plasma levels was observed in the diabetic group with ACS after 3 months compared to the baseline value. MMP-9, TIMP-1, and TIMP-2 plasma levels were higher in diabetic patients during ACS compared to nondiabetic patients during ACS. TIMP-1 and TIMP-2 increases were observed in diabetic patients with ACS at 3 months compared to nondiabetic patients after ACS. MMPs and TIMP-1 and -2 plasma levels were alterated in nondiabetic and diabetic patients during ACS and after 3 months, which may reflect abnormal extracellular matrix metabolism in diabetes during and after acute event

Nef-specific CD45RA+ CD8+ T cells secreting MIP-1β but not IFN-γ are associated with nonprogressive HIV-1 infection

<p>Abstract</p> <p>Background</p> <p>Long-term survival of HIV-1 infected individuals is usually achieved by continuous administration of combination antiretroviral therapy (ART). An exception to this scenario is represented by HIV-1 infected nonprogressors (NP) which maintain relatively high circulating CD4+ T cells without clinical symptoms for several years in the absence of ART. Several lines of evidence indicate an important role of the T-cell response in the modulation of HIV-1 infection during the acute and chronic phase of the disease.</p> <p>Results</p> <p>We analyzed the functional and the differentiation phenotype of Nef- and Tat-specific CD8+ T cells in a cohort of HIV-1 infected NP in comparison to progressors, ART-treated seropositive individuals and individuals undergoing a single cycle of ART interruption. We observed that a distinctive feature of NP is the presence of Nef-specific CD45RA+ CD8+ T cells secreting MIP-1beta but not IFN-gamma. This population was present in 7 out of 11 NP. CD45RA+ IFN-gamma^negMIP-1beta+ CD8+ T cells were not detected in HIV-1 infected individuals under ART or withdrawing from ART and experiencing a rebounding viral replication. In addition, we detected Nef-specific CD45RA+ IFN-gamma^negMIP-1beta+ CD8+ T cells in only 1 out of 10 HIV-1 infected individuals with untreated progressive disease.</p> <p>Conclusion</p> <p>The novel antigen-specific CD45RA+ IFN-gamma^negMIP-1beta+ CD8+ T cell population represents a new candidate marker of long-term natural control of HIV-1 disease progression and a relevant functional T-cell subset in the evaluation of the immune responses induced by candidate HIV-1 vaccines.</p

Ultrastructural features of human sperm cells cryopreserved by different methods

Cryopreservation of human spermatozoa has been recognized as a key strategy for management of male fertility. Nevertheless, current protocols of sperm freezing are neither optimal nor standardized between different labs (1). In this study we compare the ultrastructural features of human normospermic sperm samples (according to WHO parameters 2010) from 5 different freezing techniques in order to identify the best methods of cryopreservation. After informed con- sent, 21 normospermic patients (from the Medically Assisted Procreation PMA Center of the Fondazione IRCCS Policlinico San Matteo in Pavia) were recruited and both traditional and improved analysis of sperm quality were applied, in order to define critical steps of cryopreservation. Cryopreservation of human spermatozoa has been related to decreased motility associated with impaired velocity and viability of sperm pre-freeze and post-thaw. For all applied methods there was a significant reduction of progressive and total motility (P) as a result of freezing. To investigate ultrastructural details, 5 additional cryopreserved samples by the best two freezing methods were analyzed with elec- tron microscopy (TEM). Preliminary data showed the minimal differences between the protocols, with a large number of queues detached and large quantities of cyto- plasmic debris after of the first protocol. Spermatozoa appear to be better preserved in the second analyzed method, despite both procedures induced deteriorations at ultrastructural level (2). Other non-routine analysis will be performed to determine whether the cooling time to +4°C may affect the procedure; Comet Assay (to assess the degree of sperm DNA fragmentation) (3) and flow cytometry (to study light scat- ters patterns and membrane integrity) (4) will be applied