Water-related diseases outbreaks reported in Italy.

Water related disease outbreak (WRDO) statistics in Italy from 1998 to 2005 have been discussed in this paper. The true incidence of WRDO is not reflected in the National Surveillance System (NSS), although this study has provided information on pathogens associated to different water sources, incidence in Regions and inadequacy of regulations. 192 outbreaks and 2546 cases of WRD were reported to the NSS, an average of 318 cases per year. Cases were associated to shellfish (58.79%), drinking water (39.94%) and agricultural products (1.25%). WRDs have been detected in 76% of Regions: central and southern Regions showed lower percentage of cases (35.4%) due to under-reporting. Most of WRD cases in the North were related to drinking water; WRDs in marine coastal Regions were mostly related to shellfish. 49% of Districts (Province) notified WRDs, including only 101 Municipalities. Pathogenic microorganisms were identified in a few cases from clinical investigations. They included enteric viruses, Norwalk viruses, Salmonella, Shigella, Giardia and Campylobacter. There is the need to improve the existing NSS in relation to WRDs. An adequate WRDs Surveillance System should be based on connection between health and environmental authorities, priority pathogens and critical areas identification, response capability and contingency plans

Coperture vaccinali in Italia e valutazione dell’attuazione del PNPV 2012-2014

INTRODUZIONE Il Piano Nazionale di Prevenzione vaccinale (PNPV 2012-2014) è stato emanato nel 2012 dal Ministero della Salute e dalla Conferenza Stato-Regioni con l’obiettivo di armonizzare le strategie di immunizzazione in tutto il Paese e di assicurare un accesso equo alla prevenzione delle malattie infettive a tutti i cittadini. Il Piano definisce gli standard di immunizzazione ai quali tutte le Regioni si sono impegnate ad aderire. OBIETTIVO A più di tre anni dall’approvazione e nell’imminenza dell’uscita del nuovo Piano, obiettivo del nostro studio è stato quello di: i)riassumere i contenuti del PNPV 2012-2014, ii) descriverne le declinazioni regionali e iii) presentare i più aggiornati dati di copertura, evidenziando gli obiettivi raggiunti e le criticità riscontrate. RISULTATI Dall’analisi dei dati raccolti dal Ministero della Salute emergono il calo delle coperture in quasi tutte le Regioni per le vaccinazioni dell’infanzia e nella popolazione anziana per il vaccino antinfluenzale; promettenti dati preliminari circa l’introduzione delle vaccinazioni antimeningococco e antipneumococco nelle schedule regionali, e coperture in aumento per tutte le coorti invitate alla vaccinazione anti-HPV - benché al di sotto dei target stabiliti nel Piano. CONCLUSIONI I nostri dati sottolineano che gli obiettivi del PNPV 2012-2014 sono stati raggiunti solo parzialmente a causa di diversi fattori, in particolare l’incremento dell’esitazione sui vaccini. Maggiori sforzi sono necessari per promuovere l’immunizzazione. Il nuovo Piano dovrà considerare i nuovi vaccini e l’estensione dell’offerta di quelli esistenti che già sono stati introdotti in alcune Regioni alla luce delle nuove evidenze scientifiche disponibili. Inoltre, interventi di informazione e comunicazione di provata efficacia dovranno essere realizzati per fronteggiare il fenomeno della esitazione sui vaccini e garantire il raggiungimento degli standard di copertura

Vaccine coverage in Italy and assessment of the 2012-2014 National Immunization Prevention Plan

BACKGROUND: In 2012, the ItalianMinistry of Health issued the National Immunization Prevention Plan (Piano Nazionale Prevenzione Vaccinale, or PNPV 2012-2014), with the aim of harmonizing immunization strategies across the country and ensuring equitable access to infectious disease prevention to all citizens. The Plan defines the immunization standards all regions should comply with. OBJECTIVE AND METHODS: As new evidence has accumulated in the field of immunization, and the new National Immunization Prevention Plan is about to be launched, the aim of the current study is to: i. present immunization coverage data (2000-2014) for 14 vaccines included in the PNPV to be offered to the general population, ii. assess to what extent the PNPV coverage targets and objectives have been met, and iii. report on how the PNPV was transposed into regional immunization programs. Data are also available for the eight regions that piloted varicella immunization. RESULTS: The 2012-2014 PNPV first introduced a "lifecourse" approach to vaccination at the institutional level, and has been a milestone for prevention in the Italian health policy agenda. However, infant vaccine coverage rates have been decreasing over the last years, as has influenza immunization in the elderly. HPV vaccine coverage has been increasing for all birth cohorts, but is still far below the targets set in the Plan. Promising preliminary data show that pneumococcal and meningococcal C conjugate vaccines were well introduced in regional immunization schedules. CONCLUSION: The 2012-2014 PNPV objectives have only been partially met, due to several factors, in particular increase in vaccine hesitancy. Strengthened efforts are needed to promote immunization. The new National Immunization Prevention Plan should introduce new vaccines and extend immunization programs to other target populations on the basis of the most recent scientific evidence available. It is of crucial importance that interventions of proven efficacy be planned and implemented to contrast the growing phenomenon of vaccine hesitancy and ultimately increase immunization uptake

Specific gene expression signatures induced by the multiple oncogenic alterations that occur within the PTEN/PI3K/AKT pathway in lung cancer

Hyperactivation of the phosphatydil-inositol-3' phosphate kinase (PI3K)/AKT pathway is observed in most NSCLCs, promoting proliferation, migration, invasion and resistance to therapy. AKT can be activated through several mechanisms that include loss of the negative regulator PTEN, activating mutations of the catalytic subunit of PI3K (PIK3CA) and/or mutations of AKT1 itself. However, number and identity of downstream targets of activated PI3K/AKT pathway are poorly defined. To identify the genes that are targets of constitutive PI3K/AKT signalling in lung cancer cells, we performed a comparative transcriptomic analysis of human lung epithelial cells (BEAS-2B) expressing active mutant AKT1 (AKT1-E17K), active mutant PIK3CA (PIK3CA-E545K) or that are silenced for PTEN. We found that, altogether, aberrant PI3K/AKT signalling in lung epithelial cells regulated the expression of 1,960/20,436 genes (9%), though only 30 differentially expressed genes (DEGs) (15 up-regulated, 12 down-regulated and 3 discordant) out of 20,436 that were common among BEAS-AKT1-E17K, BEAS-PIK3CA-E545K and BEAS-shPTEN cells (0.1%). Conversely, DEGs specific for mutant AKT1 were 133 (85 up-regulated; 48 down-regulated), DEGs specific for mutant PIK3CA were 502 (280 up-regulated; 222 down-regulated) and DEGs specific for PTEN loss were 1549 (799 up-regulated, 750 down-regulated). The results obtained from array analysis were confirmed by quantitative RT-PCR on selected up-and down-regulated genes (n = 10). Treatment of BEAS-C cells and the corresponding derivatives with pharmacological inhibitors of AKT (MK2206) or PI3K (LY294002) further validated the significance of our findings. Moreover, mRNA expression of selected DEGs (SGK1, IGFBP3, PEG10, GDF15, PTGES, S100P, respectively) correlated with the activation status of the PI3K/AKT pathway assessed by S473 phosphorylation in NSCLC cell lines (n = 6). Finally, we made use of Ingenuity Pathway Analysis (IPA) to investigate the relevant BioFunctions enriched by the costitutive activation of AKT1-, PI3K-or PTEN-dependent signalling in lung epithelial cells. Expectedly, the analysis of the DEGs common to all three alterations highlighted a group of BioFunctions that included Cell Proliferation of tumor cell lines (14 DEGs), Invasion of cells (10 DEGs) and Migration of tumour cell lines (10 DEGs), with a common core of 5 genes (ATF3, CDKN1A, GDF15, HBEGF and LCN2) that likely represent downstream effectors of the pro-oncogenic activities of PI3K/AKT signalling. Conversely, IPA analysis of exclusive DEGs led to the identification of different downstream effectors that are modulated by mutant AKT1 (TGFBR2, CTSZ, EMP1), mutant PIK3CA (CCND2, CDK2, IGFBP2, TRIB1) and PTEN loss (ASNS, FHL2). These findings not only shed light on the molecular mechanisms that are activated by aberrant signalling through the PI3K/AKT pathway in lung epithelial cells, but also contribute to the identification of previously unrecognised molecules whose regulation takes part in the development of lung cancer

Bergamot polyphenol fraction prevents nonalcoholic fatty liver disease via stimulation of lipophagy in cafeteria diet-induced rat model of metabolic syndrome

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in industrialized countries. Defective autophagy of lipid droplets (LDs) in hepatocytes, also known as lipophagy, has recently been identified as a possible pathophysiological mechanism of NAFLD. Experimental and epidemiological evidence suggests that dietary polyphenols may prevent NAFLD. To address this hypothesis and analyze the underlying mechanisms, we supplemented bergamot polyphenol fraction (BPF) to cafeteria (CAF) diet-fed rats, a good model for pediatric metabolic syndrome and NAFLD. BPF treatment (50 mg/kg/day supplemented with drinking water, 3 months) potently counteracted the pathogenic increase of serum triglycerides and had moderate effects on blood glucose and obesity in this animal model. Importantly, BPF strongly reduced hepatic steatosis as documented by a significant decrease in total lipid content (-41.3% \ub1 12% S.E.M.), ultrasound examination and histological analysis of liver sections. The morphometric analysis of oil-red stained sections confirmed a dramatic reduction in LDs parameters such as total LD area (48.5% \ub1 15% S.E.M.) in hepatocytes from CAF+BPF rats. BPF-treated livers showed increased levels of LC3 and Beclin 1 and reduction of SQSTM1/p62, suggesting autophagy stimulation. Consistent with BPF stimulation of lipophagy, higher levels of LC3II were found in the LD subcellular fractions of BPF-expose livers. This study demonstrates that the liver and its lipid metabolism are the main targets of bergamot flavonoids, supporting the concept that supplementation of BPF is an effective strategy to prevent NAFLD

Aberrant signaling through the HER2-ERK1/2 pathway is predictive of reduced disease-free and overall survival in early stage non-small cell lung cancer (NSCLC) patients

Background: Purpose of this study was to evaluate the contribution of the Extracellular-regulated protein kinase (ERK)-1/2 pathway to oncogenic signaling elicited by the tyrosine kinase receptor HER2 in Non-Small Cell Lung Cancer (NSCLC) and to assess the prognostic value of these oncoproteins in NSCLC patients. Methods: Immunohistochemistry was performed to determine expression and activation of HER2 and ERK1/2 (detected by phosphorylation of Y1248 and T202/Y204, respectively) using Tissue Micro Arrays (TMA) containing matched normal and neoplastic tissues from 132 NSCLC patients. Survival analysis was carried out using the Kaplan-Meier method. Univariate and multivariate analysis were used to evaluate the prognostic value of pERK1/2, pHER2 and a combination thereof with clinical-pathological parameters such as age, lymph node status (N), size (T), stage (TNM) and grade. Results: We found that HER2 was overexpressed in 33/120 (27%) and activated in 41/114 (36%) cases; ERK1/2 was activated in 44/102 (43%) cases. A direct association was found between pERK1/2 and pHER2 (23/41; p=0.038). In addition, patients positive for pERK1/2 and for both pHER2 and pERK1/2 showed significantly worse overall survival (OS) and disease-free survival (DFS) compared with negative patients. Univariate and multivariate analysis of patients' survival revealed that positivity for pHER2-pERK1/2 and for pERK1/2 alone were independent prognostic factors of poor survival in NSCLC patients. In particular, this association was significantly important for DFS in stage I+II patients. Conclusion: This study provides evidence that activated ERK1/2 and/or the combined activation of HER2 and ERK1/2 are good indicators of poor prognosis in NSCLC patients, not only in unselected patients but also in early stage disease

Exclusive DEGs showing the highest values of fold change specific for PTEN loss.

<p>Exclusive DEGs showing the highest values of fold change specific for PTEN loss.</p

Array analysis of genes regulated by the PI3K/AKT pathway in lung epithelial cells.

<p>(A) Heatmap representation of expression values of DEGs comparing BEAS-AKT1-E17K, BEAS-PIK3CA-E545K and BEAS-shPTEN to BEAS-C control cells. Hierarchical clustering analysis was perfomed with Euclidean metric distance and Ward’s linkage rule. (B) The Venn diagram shows the number of common, specific and exclusive DEGs.</p

Comparison analysis of Diseases and Bio Functions enriched in BEAS-2B cells expressing constitutively active PIK3CA, AKT1 or interfered for PTEN.

<p>IPA heatmap displays the top three Disease and Biofunctions enriched by DEGs that are common among BEAS-AKT1-E17K, BEAS-PIK3CA-E545K and BEAS-shPTEN cells (commons, rightmost column) or that are exclusive for each cell line (AKT1, PIK3CA, shPTEN). Diseases and Bio Functions were sorted for p-value, from the most significant (violet) to the least significant (white) values.</p

Validation of array results by quantitative RT-PCR analysis.

<p><b>(A)</b> Analysis of 10 representative DEGs in BEAS-C and derivatives. Bars are mean ± SD of 4 independent experiments performed in triplicate. Statistical analysis was performed by One-way ANOVA test and Dunnett's test for each gene, p-values as indicated.</p