Does the evidence about health risks associated with nitrate ingestion warrant an increase of the nitrate standard for drinking water?

Several authors have suggested that it is safe to raise the health standard for nitrate in drinking water, and save money on measures associated with nitrate pollution of drinking water resources. The major argument has been that the epidemiologic evidence for acute and chronic health effects related to drinking water nitrate at concentrations near the health standard is inconclusive. With respect to the chronic effects, the argument was motivated by the absence of evidence for adverse health effects related to ingestion of nitrate from dietary sources. An interdisciplinary discussion of these arguments led to three important observations. First, there have been only a few well-designed epidemiologic studies that evaluated ingestion of nitrate in drinking water and risk of specific cancers or adverse reproductive outcomes among potentially susceptible subgroups likely to have elevated endogenous nitrosation. Positive associations have been observed for some but not all health outcomes evaluated. Second, the epidemiologic studies of cancer do not support an association between ingestion of dietary nitrate (vegetables) and an increased risk of cancer, because intake of dietary nitrate is associated with intake of antioxidants and other beneficial phytochemicals. Third, 2–3 % of the population in Western Europe and the US could be exposed to nitrate levels in drinking water exceeding the WHO standard of 50 mg/l nitrate, particularly those living in rural areas. The health losses due to this exposure cannot be estimated. Therefore, we conclude that it is not possible to weigh the costs and benefits from changing the nitrate standard for drinking water and groundwater resources by considering the potential consequences for human health and by considering the potential savings due to reduced costs for nitrate removal and prevention of nitrate pollution

Prostate cancer-derived urine exosomes: a novel approach to biomarkers for prostate cancer

Herein, we describe a novel approach in the search for prostate cancer biomarkers, which relies on the transcriptome within tumour exosomes. As a proof-of-concept, we show the presence of two known prostate cancer biomarkers, PCA-3 and TMPRSS2:ERG the in exosomes isolated from urine of patients, showing the potential for diagnosis and monitoring cancer patients status

Suitable reference genes for real-time PCR in human HBV-related hepatocellular carcinoma with different clinical prognoses

<p>Abstract</p> <p>Background</p> <p>Housekeeping genes are routinely used as endogenous references to account for experimental differences in gene expression assays. However, recent reports show that they could be de-regulated in different diseases, model animals, or even under varied experimental conditions, which may lead to unreliable results and consequently misinterpretations. This study focused on the selection of suitable reference genes for quantitative PCR in human hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) with different clinical outcomes.</p> <p>Methods</p> <p>We evaluated 6 commonly used housekeeping genes' expression levels in 108 HBV-related HCCs' matched tumor and non-tomor tissue samples with different clinical outcomes and 26 normal liver specimens by real-time PCR. The expression stability of the 6 genes was compared using the software programs geNorm and NormFinder. To show the impact of reference genes on data analysis, we took PGK1 as a target gene normalized by each reference gene, and performed one-way ANOVA and the equivalence test.</p> <p>Results</p> <p>With the geNorm and NormFinder software programs, analysis of TBP and HPRT1 showed the best stability in all tissue samples, while 18s and ACTB were less stable. When 18s or ACTB was used for normalization, no significant difference of PGK1 expression (p > 0.05) was found among HCC tissues with and without metastasis, and normal liver specimens; however, dramatically differences (p < 0.001) were observed when either TBP or the combination of TBP and HPRT1 were selected as reference genes.</p> <p>Conclusion</p> <p>TBP and HPRT1 are the most reliable reference genes for q-PCR normalization in HBV-related HCC specimens. However, the well-used ACTB and 18S are not suitable, which actually lead to the misinterpretation of the results in gene expression analysis.</p

Suitable reference genes for real-time PCR in human HBV-related hepatocellular carcinoma with different clinical prognoses

<p>Abstract</p> <p>Background</p> <p>Housekeeping genes are routinely used as endogenous references to account for experimental differences in gene expression assays. However, recent reports show that they could be de-regulated in different diseases, model animals, or even under varied experimental conditions, which may lead to unreliable results and consequently misinterpretations. This study focused on the selection of suitable reference genes for quantitative PCR in human hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) with different clinical outcomes.</p> <p>Methods</p> <p>We evaluated 6 commonly used housekeeping genes' expression levels in 108 HBV-related HCCs' matched tumor and non-tomor tissue samples with different clinical outcomes and 26 normal liver specimens by real-time PCR. The expression stability of the 6 genes was compared using the software programs geNorm and NormFinder. To show the impact of reference genes on data analysis, we took PGK1 as a target gene normalized by each reference gene, and performed one-way ANOVA and the equivalence test.</p> <p>Results</p> <p>With the geNorm and NormFinder software programs, analysis of TBP and HPRT1 showed the best stability in all tissue samples, while 18s and ACTB were less stable. When 18s or ACTB was used for normalization, no significant difference of PGK1 expression (p > 0.05) was found among HCC tissues with and without metastasis, and normal liver specimens; however, dramatically differences (p < 0.001) were observed when either TBP or the combination of TBP and HPRT1 were selected as reference genes.</p> <p>Conclusion</p> <p>TBP and HPRT1 are the most reliable reference genes for q-PCR normalization in HBV-related HCC specimens. However, the well-used ACTB and 18S are not suitable, which actually lead to the misinterpretation of the results in gene expression analysis.</p

Identification of field caught Anopheles gambiae s.s. and Anopheles arabiensis by TaqMan single nucleotide polymorphism genotyping

BACKGROUND: Identification of Anopheles gambiae s.s. and Anopheles arabiensis from field-collected Anopheles gambiae s.l. is often necessary in basic and applied research, and in operational control programmes. The currently accepted method involves use of standard polymerase chain reaction amplification of ribosomal DNA (rDNA) from the 3' 28S to 5' intergenic spacer region of the genome, and visual confirmation of amplicons of predicted size on agarose gels, after electrophoresis. This report describes development and evaluation of an automated, quantitative PCR method based upon TaqMan™ single nucleotide polymorphism (SNP) genotyping. METHODS: Standard PCR, and TaqMan SNP genotyping with newly designed primers and fluorophore-labeled probes hybridizing to sequences of complementary rDNA specific for either An. gambiae s.s. or An. arabiensis, were conducted in three experiments involving field-collected An. gambiae s.l. from western Kenya, and defined laboratory strains. DNA extraction was from a single leg, sonicated for five minutes in buffer in wells of 96-well PCR plates. RESULTS: TaqMan SNP genotyping showed a reaction success rate, sensitivity, and species specificity comparable to that of standard PCR. In an extensive field study, only 29 of 3,041 (0.95%) were determined to be hybrids by TaqMan (i.e., having rDNA sequences from both species), however, all but one were An. arabiensis by standard PCR, suggesting an acceptably low (ca. 1%) error rate for TaqMan genotyping in mistakenly identifying species hybrids. CONCLUSION: TaqMan SNP genotyping proved to be a sensitive and rapid method for identification of An. gambiae s.l. and An. arabiensis, with a high success rate, specific results, and congruence with the standard PCR method

Cognitive Behavioral Therapy versus Short Psychodynamic Supportive Psychotherapy in the outpatient treatment of depression: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Previous research has shown that Short Psychodynamic Supportive Psychotherapy (SPSP) is an effective alternative to pharmacotherapy and combined treatment (SPSP and pharmacotherapy) in the treatment of depressed outpatients. The question remains, however, how Short Psychodynamic Supportive Psychotherapy compares with other established psychotherapy methods. The present study compares Short Psychodynamic Supportive Psychotherapy to the evidence-based Cognitive Behavioral Therapy in terms of acceptability, feasibility, and efficacy in the outpatient treatment of depression. Moreover, this study aims to identify clinical predictors that can distinguish patients who may benefit from either of these treatments in particular. This article outlines the study protocol. The results of the study, which is being currently carried out, will be presented as soon as they are available.</p> <p>Methods/Design</p> <p>Adult outpatients with a main diagnosis of major depressive disorder or depressive disorder not otherwise specified according to DSM-IV criteria and mild to severe depressive symptoms (<it>Hamilton Depression Rating Scale </it>score ≥ 14) are randomly allocated to Short Psychodynamic Supportive Psychotherapy or Cognitive Behavioral Therapy. Both treatments are individual psychotherapies consisting of 16 sessions within 22 weeks. Assessments take place at baseline (week 0), during the treatment period (week 5 and 10) and at treatment termination (week 22). In addition, a follow-up assessment takes place one year after treatment start (week 52). Primary outcome measures are the number of patients refusing treatment (acceptability); the number of patients terminating treatment prematurely (feasibility); and the severity of depressive symptoms (efficacy) according to an independent rater, the clinician and the patient. Secondary outcome measures include general psychopathology, general psychotherapy outcome, pain, health-related quality of life, and cost-effectiveness. Clinical predictors of treatment outcome include demographic variables, psychiatric symptoms, cognitive and psychological patient characteristics and the quality of the therapeutic relationship.</p> <p>Discussion</p> <p>This study evaluates Short Psychodynamic Supportive Psychotherapy as a treatment for depressed outpatients by comparing it to the established evidence-based treatment Cognitive Behavioral Therapy. Specific strengths of this study include its strong external validity and the clinical relevance of its research aims. Limitations of the study are discussed.</p> <p>Trial registration</p> <p>Current Controlled Trails ISRCTN31263312</p

Estimation of incidence and social cost of colon cancer due to nitrate in drinking water in the EU: a tentative cost-benefit assessment

<p>Abstract</p> <p>Background</p> <p>Presently, health costs associated with nitrate in drinking water are uncertain and not quantified. This limits proper evaluation of current policies and measures for solving or preventing nitrate pollution of drinking water resources. The cost for society associated with nitrate is also relevant for integrated assessment of EU nitrogen policies taking a perspective of welfare optimization. The overarching question is at which nitrogen mitigation level the social cost of measures, including their consequence for availability of food and energy, matches the social benefit of these measures for human health and biodiversity.</p> <p>Methods</p> <p>Epidemiological studies suggest colon cancer to be possibly associated with nitrate in drinking water. In this study risk increase for colon cancer is based on a case-control study for Iowa, which is extrapolated to assess the social cost for 11 EU member states by using data on cancer incidence, nitrogen leaching and drinking water supply in the EU. Health costs are provisionally compared with nitrate mitigation costs and social benefits of fertilizer use.</p> <p>Results</p> <p>For above median meat consumption the risk of colon cancer doubles when exposed to drinking water exceeding 25 mg/L of nitrate (NO₃) for more than ten years. We estimate the associated increase of incidence of colon cancer from nitrate contamination of groundwater based drinking water in EU11 at 3%. This corresponds to a population-averaged health loss of 2.9 euro per capita or 0.7 euro per kg of nitrate-N leaching from fertilizer.</p> <p>Conclusions</p> <p>Our cost estimates indicate that current measures to prevent exceedance of 50 mg/L NO₃are probably beneficial for society and that a stricter nitrate limit and additional measures may be justified. The present assessment of social cost is uncertain because it considers only one type of cancer, it is based on one epidemiological study in Iowa, and involves various assumptions regarding exposure. Our results highlight the need for improved epidemiological studies.</p