Water safety plans by utilities: a review of research on implementation

Water supply is essential to public health, quality of life, environmental protection, economic activity, and sustainable development. In this context, it is imperative to assure the continuous improvement of all processes and practices conducive to guarantee water quality and safety. Water Safety Plans (WSPs) by water utilities are an important public policy tool to accomplish these goals. This manuscript reviews the international evidence of the adoption and implementation of water safety planning and reports the current situation in Portugal, as part of the necessary adjustment of the national legal framework to the publication of the Directive (EU) 2015/1787, October 6th, on water quality for human consumption. The aim is to draw lessons from several successful WSP experiments around the world and extract lessons from these cases when drafting new legislation in Portugal and elsewhere. Findings suggest there are four critical dimensions and key elements of success in developing and implementing WSPs: leadership commitment, technical knowledge, governance, and interagency collaboration.This research is partially supported by the “Programa Operacional da Região Norte”, NORTE2020, in the context of project NORTE-01-0145-FEDER-000037 (SmartEGOV) and by the Portuguese Science and Technology Foundation (Fundação para a Ciência e Tecnologia) [Grant No. PEst-OE/CJP/UI0758/2014]

Plasma haptoglobin and immunoglobulins as diagnostic indicators of deoxynivalenol intoxication

This study aimed to discover potential biomarkers for dioxynivalenol (DON) intoxication. B6C3F1 male mice were orally exposed to 0.83, 2.5 and 7.5 mg/kg body weight (bw) DON for 8 days and the differential protein expressions in their blood plasma were determined by SELDI - Time-of-Flight/Mass Spectrometry (TOF/MS) and the immunoglobulins (Igs) G, A, M and E in the serum were investigated. 11.7 kDa protein was significantly highly expressed according to DON administration and this protein was purified by employing a methyl ceramic HyperD F column with using optimization buffer for adsorption and desorption. The purified protein was identified as a haptoglobin precursor by peptide mapping with using LC/Q-TOF/MS and MALDI-TOF/MS and this was confirmed by western blotting and ELISA. IgG and IgM in serum were decreased in a dose-dependent manner and IgA was decreased at 7.5 mg/kg bw DON administration, but the IgE level was not changed. To compare the expressions of haptoglobin and the Igs patterns between aflatoxin B1 (AFB1), zearalenone (ZEA) and DON intoxications, rats were orally administered with AFB1 1.0, ZEA 240 and DON 7.5 mg/kg bw for 8 days. Haptoglobin was increased only at DON 7.5 mg/kg bw, while it was slightly decreased at ZEA 240 mg/kg bw and it was not detected at all at AFB1 1.0 mg/kg bw. IgG and IgA were decreased by DON, but IgG, IgA, IgM and IgE were all increased by AFB1. No changes were observed by ZEA administration. These results show that plasma haptoglobin could be a diagnostic biomarker for DON intoxication when this is combined with examining the serum Igs

Potential Tumor Suppressor NESG1 as an Unfavorable Prognosis Factor in Nasopharyngeal Carcinoma

BACKGROUND:Recently we identified nasopharyngeal epithelium specific protein 1 (NESG1) as a potential tumor suppressor in nasopharyngeal carcinoma (NPC). The purpose of this study is to investigate the involvement of NESG1 in tumor progression and prognosis of human NPC. METHODOLOGY/PRINCIPAL FINDINGS:NESG1 protein expression in NPC was examined. Survival analysis was performed using Kaplan-Meier method. The effect of NESG1 on cell proliferation, migration, and invasion were also investigated. RESULTS:NESG1 expression was downregulated in atypical hyperplasia and NPC samples compared to normal and squamous nasopharynx tissues. Reduced protein expression was negatively associated with the status of NPC progression. Patients with lower NESG1 expression had a shorter overall survival and disease-free time than did patients with higher NESG1 expression. Multivariate analysis suggested NESG1 expression as an independent prognostic indicator for NPC patient survival. Proliferation, migration, and invasion ability were significantly increased in cell lines following lentiviral-mediated shRNA suppression of NESG1 expression. Microarray analysis indicated that NESG1 participated in multiple pathways, including MAPK signaling and cell cycle regulation. Finally, DNA methylation microarray examination revealed a lack of hypermethylation at the NESG1 promoter, suggesting other mechanisms are involved in suppressing NESG1 expression in NPC. CONCLUSION:Our studies are the first to demonstrate that decreased NESG1 expression is an unfavorable prognostic factor for NPC

Hospitalizations for acetaminophen overdose: a Canadian population-based study from 1995 to 2004

<p>Abstract</p> <p>Background</p> <p>Acetaminophen overdose (AO) is the most common cause of acute liver failure. We examined temporal trends and sociodemographic risk factors for AO in a large Canadian health region.</p> <p>Methods</p> <p>1,543 patients hospitalized for AO in the Calgary Health Region (population ~1.1 million) between 1995 and 2004 were identified using administrative data.</p> <p>Results</p> <p>The age/sex-adjusted hospitalization rate decreased by 41% from 19.6 per 100,000 population in 1995 to 12.1 per 100,000 in 2004 (<it>P </it>< 0.0005). This decline was greater in females than males (46% vs. 29%). Whereas rates fell 46% in individuals under 50 years, a 50% increase was seen in those ≥ 50 years. Hospitalization rates for intentional overdoses fell from 16.6 per 100,000 in 1995 to 8.6 per 100,000 in 2004 (2004 vs. 1995: rate ratio [RR] 0.49; <it>P </it>< 0.0005). Accidental overdoses decreased between 1995 and 2002, but increased to above baseline levels by 2004 (2004 vs. 1995: RR 1.24;<it>P </it>< 0.0005). Risk factors for AO included female sex (RR 2.19; <it>P </it>< 0.0005), Aboriginal status (RR 4.04; <it>P </it>< 0.0005), and receipt of social assistance (RR 5.15; <it>P </it>< 0.0005).</p> <p>Conclusion</p> <p>Hospitalization rates for AO, particularly intentional ingestions, have fallen in our Canadian health region between 1995 and 2004. Young patients, especially females, Aboriginals, and recipients of social assistance, are at highest risk.</p

Haptoglobin phenotype is not a predictor of recurrence free survival in high-risk primary breast cancer patients

Contains fulltext : 70104tjan-heijnen.pdf (publisher's version ) (Open Access)BACKGROUND: Better breast cancer prognostication may improve selection of patients for adjuvant therapy. We conducted a retrospective follow-up study in which we investigated sera of high-risk primary breast cancer patients, to search for proteins predictive of recurrence free survival. METHODS: Two sample sets of high-risk primary breast cancer patients participating in a randomised national trial investigating the effectiveness of high-dose chemotherapy were analysed. Sera in set I (n = 63) were analysed by surface enhanced laser desorption ionisation time-of-flight mass spectrometry (SELDI-TOF MS) for biomarker finding. Initial results were validated by analysis of sample set II (n = 371), using one-dimensional gel-electrophoresis. RESULTS: In sample set I, the expression of a peak at mass-to-charge ratio 9198 (relative intensity 20), identified as haptoglobin (Hp) alpha-1 chain, was strongly associated with recurrence free survival (global Log-rank test; p = 0.0014). Haptoglobin is present in three distinct phenotypes (Hp 1-1, Hp 2-1, and Hp 2-2), of which only individuals with phenotype Hp 1-1 or Hp 2-1 express the haptoglobin alpha-1 chain. As the expression of the haptoglobin alpha-1 chain, determined by SELDI-TOF MS, corresponds to the phenotype, initial results were validated by haptoglobin phenotyping of the independent sample set II by native one-dimensional gel-electrophoresis. With the Hp 1-1 phenotype as the reference category, the univariate hazard ratio for recurrence was 0.87 (95% CI: 0.56 - 1.34, p = 0.5221) and 1.03 (95% CI: 0.65 - 1.64, p = 0.8966) for the Hp 2-1 and Hp 2-2 phenotypes, respectively, in sample set II. CONCLUSION: In contrast to our initial results, the haptoglobin phenotype was not identified as a predictor of recurrence free survival in high-risk primary breast cancer in our validation set. Our initial observation in the discovery set was probably the result of a type I error (i.e. false positive). This study illustrates the importance of validation in obtaining the true clinical applicability of a potential biomarker

HIV Restriction by APOBEC3 in Humanized Mice

Innate immune restriction factors represent important specialized barriers to zoonotic transmission of viruses. Significant consideration has been given to their possible use for therapeutic benefit. The apolipoprotein B mRNA editing enzyme catalytic polypeptide 3 (APOBEC3) family of cytidine deaminases are potent immune defense molecules capable of efficiently restricting endogenous retroelements as well as a broad range of viruses including Human Immunodeficiency virus (HIV), Hepatitis B virus (HBV), Human Papilloma virus (HPV), and Human T Cell Leukemia virus (HTLV). The best characterized members of this family are APOBEC3G (A3G) and APOBEC3F (A3F) and their restriction of HIV. HIV has evolved to counteract these powerful restriction factors by encoding an accessory gene designated viral infectivity factor (vif). Here we demonstrate that APOBEC3 efficiently restricts CCR5-tropic HIV in the absence of Vif. However, our results also show that CXCR4-tropic HIV can escape from APOBEC3 restriction and replicate in vivo independent of Vif. Molecular analysis identified thymocytes as cells with reduced A3G and A3F expression. Direct injection of vif-defective HIV into the thymus resulted in viral replication and dissemination detected by plasma viral load analysis; however, vif-defective viruses remained sensitive to APOBEC3 restriction as extensive G to A mutation was observed in proviral DNA recovered from other organs. Remarkably, HIV replication persisted despite the inability of HIV to develop resistance to APOBEC3 in the absence of Vif. Our results provide novel insight into a highly specific subset of cells that potentially circumvent the action of APOBEC3; however our results also demonstrate the massive inactivation of CCR5-tropic HIV in the absence of Vif