142 research outputs found
Contributi e prospettive della formazione manageriale in SanitĂ
2013 - 2014The research project explores the theme of management education in healthcare in the regional context Campano referring to its strategic role in a perspective of change and management innovation to ensure performance improvement in health care.
In the Campania Region, the PRS track the educational goals of the health system and defines the extremely important management training to achieve the desired organizational change... [edited by author]XIII n.s
The Development of a Decision Support System for Wellbeing in the Danube River Basin
The aims of the project are to develop a decision-making support tool – DeWOS; and to establish a
permanent users network using a spin-off company, which will enable international cooperation and implementation
of the software. DeWOS will encompass all existing relevant data on factors affecting
wellbeing: environmental (water, air, soil, food quality and quantity), social-demographic (education,
prosperity, migration, tourism and mobility, health services, safety) and economic factors (employment,
industry, agriculture). The tool will provide a reliable valuation of the degree of wellbeing in the Danube
River Basin enabling policy makers (from the municipality to the national level) and other stakeholders
to assess the current wellbeing situation and simulate possible scenarios along with the feasibility and
impacts of possible interventions
Antioxidant, Nutraceutical Properties, and Fluorescence Spectral Profiles of Bee Pollen Samples from Different Botanical Origins
Bee pollen is made by honey bees (Apis Mellifera) from the pollen of plants and flowers and represents an apiary product enriched in essential amino acids, polyphenols, omega-3, and omega-6 fatty acids. This study investigated the botanical origin, micronutrient profile, and antioxidant activity of bee pollen samples (n = 10) harvested in Lucca and Massa Carrara (Tuscany, Italy) between 2016 and 2017. The palynological analysis showed that bee pollen samples were composed of nine botanical families. Front-face fluorescence spectroscopy was performed on bee pollen samples in bulk, without any treatment, and in ethanol extracts to determine the characteristic fluorescent profile and, to identify the main chemical compounds with biological activity. The main chemical compounds detected were polyphenols (mainly flavonoids and phenolic acids), hydro-soluble vitamins (B2, B3, B6, and B9), amino acids, and pigments. Furthermore, the antioxidant activity was investigated, and one of the two Viburnum pollens resulted in the highest polyphenols and flavonoids content (20.15 ± 0.15 mg GAE/g fw and 23.46 ± 0.08 mg CE/g fw, respectively). However, Prunus and Eucalyptus families showed the highest in vitro (190.27 ± 8.30 µmol Fe2+/g) and ex vivo (54.61 ± 8.51 CAA unit) antioxidant capacity, respectively. These results suggested that Tuscan bee pollen, depending on the botanical family, is rich in essential nutrients and potential nutraceutical product
Performance of Different Analytical Software Packages in Quantification of DNA Methylation by Pyrosequencing
BACKGROUND:Pyrosequencing has emerged as an alternative method of nucleic acid sequencing, well suited for many applications which aim to characterize single nucleotide polymorphisms, mutations, microbial types and CpG methylation in the target DNA. The commercially available pyrosequencing systems can harbor two different types of software which allow analysis in AQ or CpG mode, respectively, both widely employed for DNA methylation analysis. OBJECTIVE:Aim of the study was to assess the performance for DNA methylation analysis at CpG sites of the two pyrosequencing software which allow analysis in AQ or CpG mode, respectively. Despite CpG mode having been specifically generated for CpG methylation quantification, many investigations on this topic have been carried out with AQ mode. As proof of equivalent performance of the two software for this type of analysis is not available, the focus of this paper was to evaluate if the two modes currently used for CpG methylation assessment by pyrosequencing may give overlapping results. METHODS:We compared the performance of the two software in quantifying DNA methylation in the promoter of selected genes (GSTP1, MGMT, LINE-1) by testing two case series which include DNA from paraffin embedded prostate cancer tissues (PC study, N = 36) and DNA from blood fractions of healthy people (DD study, N = 28), respectively. RESULTS:We found discrepancy in the two pyrosequencing software-based quality assignment of DNA methylation assays. Compared to the software for analysis in the AQ mode, less permissive criteria are supported by the Pyro Q-CpG software, which enables analysis in CpG mode. CpG mode warns the operators about potential unsatisfactory performance of the assay and ensures a more accurate quantitative evaluation of DNA methylation at CpG sites. CONCLUSION:The implementation of CpG mode is strongly advisable in order to improve the reliability of the methylation analysis results achievable by pyrosequencing
SMYD1 and G6PD modulation are critical events for miR-206-mediated differentiation of rhabdomyosarcoma
Rhadomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood. RMS cells resemble fetal myoblasts but are unable to complete myogenic differentiation. In previous work we showed that miR-206, which is low in RMS, when induced in RMS cells promotes the resumption of differentiation by modulating more than 700 genes. To better define the pathways involved in the conversion of RMS cells into their differentiated counterpart, we focused on 2 miR-206 effectors emerged from the microarray analysis, SMYD1 and G6PD. SMYD1, one of the most highly upregulated genes, is a H3K4 histone methyltransferase. Here we show that SMYD1 silencing does not interfere with the proliferative block or with the loss anchorage independence imposed by miR-206, but severely impairs differentiation of ERMS, ARMS, and myogenic cells. Thus SMYD1 is essential for the activation of muscle genes. Conversely, among the downregulated genes, we found G6PD, the enzyme catalyzing the rate-limiting step of the pentose phosphate shunt. In this work, we confirmed that G6PD is a direct target of miR-206. Moreover, we showed that G6PD silencing in ERMS cells impairs proliferation and soft agar growth. However, G6PD overexpression does not interfere with the pro-differentiating effect of miR-206, suggesting that G6PD downmodulation contributes to - but is not an absolute requirement for - the tumor suppressive potential of miR-206. Targeting cancer metabolism may enhance differentiation. However, therapeutic inhibition of G6PD is encumbered by side effects. As an alternative, we used DCA in combination with miR-206 to increase the flux of pyruvate into the mitochondrion by reactivating PDH. DCA enhanced the inhibition of RMS cell growth induced by miR-206, and sustained it upon miR-206 de-induction. Altogether these results link miR-206 to epigenetic and metabolic reprogramming, and suggest that it may be worth combining differentiation-inducing with metabolism-directed approaches
GDF15 Plasma Level Is Inversely Associated With Level of Physical Activity and Correlates With Markers of Inflammation and Muscle Weakness
Growth differentiation factor 15 (GDF15) is a stress molecule produced in response to
mitochondrial, metabolic and inflammatory stress with a number of beneficial effects on
metabolism. However, at the level of skeletal muscle it is still unclear whether GDF15 is
beneficial or detrimental. The aim of the study was to analyse the levels of circulating
GDF15 in people of different age, characterized by different level of physical activity
and to seek for correlation with hematological parameters related to inflammation. The
plasma concentration of GDF15 was determined in a total of 228 subjects in the age
range from 18 to 83 years. These subjects were recruited and divided into three different
groups based on the level of physical activity: inactive patients with lower limb mobility
impairment, active subjects represented by amateur endurance cyclists, and healthy
controls taken from the general population. Cyclists were sampled before and after
a strenuous physical bout (long distance cycling race). The plasma levels of GDF15
increase with age and are inversely associated with active lifestyle. In particular, at any
age, circulating GDF15 is significantly higher in inactive patients and significantly lower in
active people, such as cyclists before the race, with respect to control subjects. However,
the strenuous physical exercise causes in cyclists a dramatic increase of GDF15 plasma
levels, that after the race are similar to that of patients. Moreover, GDF15 plasma levels
significantly correlate with quadriceps torque in patients and with the number of total
leukocytes, neutrophils and lymphocytes in both cyclists (before and after race) and
patients. Taken together, our data indicate that GDF15 is associated with decreased
muscle performance and increased inflammation
Temozolomide as salvage treatment for recurrent intracranial ependymomas of the adult: a retrospective study
BACKGROUND: Few data are available on temozolomide (TMZ) in ependymomas. We investigated the response, survival, and correlation with MGMT promoter methylation in a cohort of patients with adult intracranial ependymoma receiving TMZ as salvage therapy after failure of surgery and radiotherapy. PATIENTS AND METHODS: We retrieved clinical information from the institutional database and follow-up visits, and response to TMZ on MRI was evaluated according to the MacDonald criteria. RESULTS: Eighteen patients (median age, 42 y), with either WHO grade III (10) or grade II (8) ependymoma were evaluable. Tumor location at diagnosis was supratentorial in 11 patients and infratentorial in 7. Progression before TMZ was local in 11 patients, local and spinal in 6 patients, and spinal only in one patient. A median of 8 cycles of TMZ (1–24) was administered. Response to TMZ consisted of complete response (CR) in one (5%) patient, partial response (PR) in 3 (17%) patients, stable disease (SD) in 7 (39%) patients, and progressive disease (PD) in 7 (39%) patients. Maximum response occurred after 3, 10, 14, and 15 cycles, respectively, with neurological improvement in 2 patients. All 4 responding patients were chemotherapy naïve. Both anaplastic (2) and grade II (2) tumors responded. Median progression-free survival and overall survival were 9.69 months (95% CI, 3.22–30.98) and 30.55 months (95% CI, 12.85–52.17), respectively. MGMT methylation was available in 11 patients and was not correlated with response or outcome. CONCLUSION: TMZ has a role in recurrent chemo-naïve adult patients with intracranial ependymoma, regardless of tumor grade and MGMT methylation. We suggest that, after failure of surgery and radiotherapy, TMZ should be considered as a possible first-line treatment for recurrent ependymoma
Case–control study of HLA-G promoter methylation status, HPV infection and cervical neoplasia in Curitiba, Brazil: a pilot analysis
BACKGROUND: The causal association between persistent human papillomavirus (HPV) infection and cervical cancer has been established, but the mechanisms that favor HPV persistence in cervical cells are still unknown. The diminished capability of the immune system to control and resolve HPV infection is one of several hypotheses. The tolerogenic protein HLA-G has shown aberrant expression in a variety of cancers, which has been suggested as a mechanism for tumor escape from immunosurveillance. In the present study we evaluate the role of epigenetic modification (promoter de-methylation) of the HLA-G gene on susceptibility to HPV infection and development of high-grade cervical lesions. METHODS: A case–control study was carried out in Curitiba, Brazil, between February and June 2010. A total of 789 women aged 15–47 years were recruited: 510 controls with normal cervical cytology, and 279 cases with histologically confirmed cervical intraepithelial neoplasia grade 2 (CIN2, N = 150) or grade 3 (CIN3, N = 129). All women were administered a questionnaire by interview, which collected information on demographic and lifestyle factors, and a cervical sample was collected. HPV DNA detection was performed by GP5+/GP6+ primer-mediated PCR. HPV-positive samples were genotyped by multiplex PCR. A pilot analysis of HLA-G promoter methylation was carried out in a subset of the study population (96 cases and 76 controls) by pyrosequencing. HLA-G methylation and HPV infection status of cases and controls were compared, and confounding factors were computed by t Student and non-parametric Wilcoxon tests. Comparison of HLA-G methylation between cases and controls was assessed by the Bonferroni correction. The association of HLA-G methylation with CIN2/3 was evaluated by logistic regression. RESULTS: HPV prevalence was 19.6% in controls and 94.3% in CIN2/3 cases. HPV16, 31, 33, 35 and 18 were the most prevalent types. Methylation analysis of seven CpGs in the HLA-G promoter did not reveal any spontaneous de-methylation events in CIN2/3 cases (mean proportion of methylation: 75.8%) with respect to controls (mean 73.7%; odds ratio 1.01, 95% confidence interval 0.96, 1.07). CONCLUSIONS: This study did not support the hypothesis that spontaneous de-methylation events in the HLA-G promoter play a primary role in promoting escape from immunosurveillance in the development of precancerous cervical lesions
- …