Aminotransferase trends in propionic acidemia.

Propionic acidemia is a metabolic condition with multiple serious acute and chronic presentations that require strict monitoring. Literature on liver function abnormalities in propionic acidemia is scarce, and the mechanism of liver impairment in this condition remains unclear. Currently, there is no indication for liver-function tests during follow-up and their clinical or prognostic utility is unknown. This study aimed to determine aminotransferase trends in individuals with propionic acidemia at a single institution. We retrospectively evaluated and classified the aminotransferases of 12 patients with propionic acidemia during hospital admissions and routine office visits. The present findings suggest that aminotransferase elevations are very common in this population and can persist beyond acute illness. During hospitalization events, aminotransferases were not a predictor of severity, duration of stay, and readmission within 1 month. Understanding aminotransferase trends in these patients will help clinicians make decisions in the acute setting and potentially in the follow-up of new therapies.

A Shift in Pathotype Diversity and Complexity of Phytophthora sojae in Brazil.

Soybean root and stem rot caused by the oomycete Phytophthora sojae is a destructive disease worldwide that can affect plants at any growth stage. The use of resistant cultivars is the most effective method of controlling the disease. Therefore, monitoring changes in the population of P. sojae regarding the dynamics of avirulence genes capable of overcoming resistance genes (Rps) is important to reduce yield losses and to enhance the effectiveness of the Rps genes. Forty isolates of P. sojae sampled from a region of high incidence of soybean root and stem rot in Brazil were characterized using 14 soybean differentials, and 28 pathotypes were identified. Compared with a study conducted a decade ago, there was a major shift in pathotype diversity and complexity toward both higher numbers of different pathotypes and of avirulence genes in a given individual in the current population of P. sojae. Breeding programs aiming at developing soybean cultivars with resistance to root and stem rot should consider the high variability in the population of P. sojae and seek for strategic deployment of genes and germplasm.

Mapping the distribution of mercury (II) chloride in zebrafish organs by benchtop micro-energy dispersive X-ray fluorescence: A proof of concept.

BACKGROUND: Mercury (Hg) is a globally ubiquitous pollutant and one of the most dangerous metal contaminants, which presents a high risk of bioaccumulation in living organisms. In this study, we mapped the distribution of Hg and other trace elements in zebrafish (Danio rerio), which were exposed to mercury (II) chloride in order to assess its toxicity, bioaccumulation and distribution in fish organs. METHODS: Adult zebrafish were exposed for 7 days to different concentrations of mercury (II) chloride and the elemental distribution was obtained through the micro-energy dispersive X-ray fluorescence technique (µ-EDXRF). RESULTS: The results showed that Hg levels, measured in fish tissues, were indicative of bioaccumulation within some of its organs (e.g. visceral mass, gills), and that the physiological processes of accumulation were highly dose-dependent. In addition, the results showed higher concentrations of Hg in the gills. Moreover, other trace elements (e.g. Fe, Cu and Zn) levels were not altered after fish exposure to mercury(II) chloride. CONCLUSION: The µ-EDXRF results were assessed along with the determination of some oxidative stress biomarkers (e.g. antioxidant enzymes) to understand the effects behind the Hg bioaccumulation and toxicity. These results suggest that the metabolic changes in zebrafish due to the exposure to Hg are consistent with oxidative stress.

The CHEK2 Variant C.349A>G Is Associated with Prostate Cancer Risk and Carriers Share a Common Ancestor.

The identification of recurrent founder variants in cancer predisposing genes may have important implications for implementing cost-effective targeted genetic screening strategies. In this study, we evaluated the prevalence and relative risk of the CHEK2 recurrent variant c.349A>G in a series of 462 Portuguese patients with early-onset and/or familial/hereditary prostate cancer (PrCa), as well as in the large multicentre PRACTICAL case-control study comprising 55,162 prostate cancer cases and 36,147 controls. Additionally, we investigated the potential shared ancestry of the carriers by performing identity-by-descent, haplotype and age estimation analyses using high-density SNP data from 70 variant carriers belonging to 11 different populations included in the PRACTICAL consortium. The CHEK2 missense variant c.349A>G was found significantly associated with an increased risk for PrCa (OR 1.9; 95% CI: 1.1-3.2). A shared haplotype flanking the variant in all carriers was identified, strongly suggesting a common founder of European origin. Additionally, using two independent statistical algorithms, implemented by DMLE+2.3 and ESTIAGE, we were able to estimate the age of the variant between 2300 and 3125 years. By extending the haplotype analysis to 14 additional carrier families, a shared core haplotype was revealed among all carriers matching the conserved region previously identified in the high-density SNP analysis. These findings are consistent with CHEK2 c.349A>G being a founder variant associated with increased PrCa risk, suggesting its potential usefulness for cost-effective targeted genetic screening in PrCa families.

Absorption Mode Spectral Processing Improves Data Quality of Natural Organic Matter Analysis by Fourier-Transform Ion Cyclotron Resonance Mass Spectrometry.

Natural organic matter (NOM) plays an important role in elemental cycles and ecology. Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) is an ultrahigh resolution technique used to molecularly resolve the complexity of NOM mixtures. However, even the very high mass resolution of FT-ICR-MS may result in multiple formula assignments to peaks in an NOM spectrum, especially at the high mass-to-charge ratio (m/z). The absorption mode is one option to process raw FT-ICR-MS data that can further increase the resolution of the peaks and has not been widely applied in NOM studies. In this study, we show the advantages of using the absorption mode for the analysis of NOM samples using a reference sample (Suwannee River fulvic acid). The absorption mode increased the precision of peak detection as well as the number (+23%) and accuracy of formula assignment (by 28%) when compared to the magnitude mode, besides achieving three times higher resolution. The results presented here highlight the potential to reduce the error threshold used during molecular formula assignment. In conclusion, the absorption mode shows advantages in the processing of NOM samples and other complex mixtures and should be promoted in the NOM community.

Cancer Prognosis Defined by the Combined Analysis of 8q, PTEN and ERG.

Overtreatment is a major concern in men diagnosed with prostate cancer. The aim of this study was to evaluate the combined prognostic role of three frequent molecular alterations in prostate cancer, namely relative 8q gain, ERG overexpression, and loss of PTEN expression, in a series of 136 patients with prostate cancer treated with prostatectomy and with a long follow-up. Fluorescent in situ hybridization was used to detect the relative copy number of 8q and immunohistochemistry was used for quantitative assessment of ERG and PTEN expression. During a median follow-up period of 117.8 months, 66 (49%) patients had disease recurrence. Relative 8q gain, ERG overexpression, and loss of PTEN expression were observed in 18%, 56%, and 33% of the cases, respectively. No association with patient recurrence-free survival was found for relative 8q gain or ERG overexpression on their own, whereas loss of PTEN expression was associated with worse recurrence-free survival (P=.006). Interestingly, in the subgroup of patients with normal PTEN expression, we found that the combined relative 8q gain/ERG overexpression is associated with high risk of recurrence (P=.008), suggesting that alternative mechanisms exist for progression into clinically aggressive disease. Additionally, in intermediate-risk patients with normal PTEN expression in their tumors, the combination of 8q gain/ERG overexpression was associated with a poor recurrence-free survival (P<.001), thus indicating independent prognostic value. This study shows that the combined analysis of 8q, ERG and PTEN contributes to an improved clinical outcome stratification of prostate cancer patients treated with radical prostatectomy.

NCOA2 is a candidate target gene of 8q gain associated with clinically aggressive prostate cancer.

Prostate carcinomas harboring 8q gains are associated with poor clinical outcome, but the target genes of this genomic alteration remain to be unveiled. In this study, we aimed to identify potential 8q target genes associated with clinically aggressive prostate cancer (PCa) using fluorescence in situ hybridization (FISH), genome-wide mRNA expression, and protein expression analyses. Using FISH, we first characterized the relative copy number of 8q (assessed with MYC flanking probes) of a series of 50 radical prostatectomy specimens, with available global gene expression data and typed for E26 transformation specific (ETS) rearrangements, and then compared the gene expression profile of PCa subsets with and without 8q24 gain using Significance Analysis of Microarrays. In the subset of tumors with ERG fusion genes (ERG+), five genes were identified as significantly overexpressed (false discovery rate [FDR], ≤ 5%) in tumors with relative 8q24 gain, namely VN1R1, ZNF417, CDON, IKZF2, and NCOA2. Of these, only NCOA2 is located in 8q (8q13.3), showing a statistically higher mRNA expression in the subgroup with relative 8q gain, both in the ERG+ subgroup and in the whole series (P = 0.000152 and P = 0.008, respectively). Combining all the cases with NCOA2 overexpression, either at the mRNA or at the protein level, we identified a group of tumors with NCOA2 copy-number increase, independently of ETS status and relative 8q24 gain. Furthermore, for the first time, we detected a structural rearrangement involving NCOA2 in PCa. These findings warrant further studies with larger series to evaluate if NCOA2 relative copy-number gain presents prognostic value independently of the well-established poor prognosis associated with MYC relative copy-number gain.

Health risks caused by short term exposure to ultrafine particles generated by residential wood combustion: a case study of Temuco, Chile.

Temuco is one of the most highly wood smoke polluted cities in Chile; however, there is scarce evidence of respiratory morbidity due to fine particulate matter. We aimed to estimate the relationship between daily concentration of ultrafine particles (UFP), with an aerodynamic diameter ≤ 0.1 µm, and outpatient visits for respiratory illness at medical care centers of Temuco, Chile, from August the 20th, 2009 to June the 30th, 2011. The Air Pollution Health Effects European Approach (APHEA2) protocol was followed, and a multivariate semi-parametric Poisson regression model was fitted with GAM techniques using R-Project statistical package; controlling for trend, seasonality, and confounders. The daily UFP were measured by a MOUDI NR-110 sampler. We found that results of the statistical analyses show significant associations between UFP and respiratory outpatient visits, with the elderly (population ≥ 65 years), being the group that presented the greatest risk. An interquartile increase of 4.73 µg/m(3) in UFP (lag 5 days) was associated with respiratory outpatient visits with a relative risk (RR) of 1.1458 [95% CI (1.0497-1.2507)] for the elderly. These results show novel findings regarding the relevance of daily UFP concentrations and health risk, especially for susceptible population in a wood smoke polluted city.

Measuring the relationship of quality of life and health status, including tumor burden, symptoms, and biochemical measures in patients with neuroendocrine tumors.

The measurement of health-related quality of life (HRQOL) has become essential for evaluating the impact of neuroendocrine tumors (NETs) on symptoms and social, emotional, psychological, and physical functioning of patients who harbor these tumors. This article describes instruments that have been developed to capture the spectrum of symptoms and the impact of the disease on their overall well-being. The authors discuss the importance of adequate sensitivity, specificity, and reproducibility and the value of psychometric factor analysis to explore the domains that embrace the manifestations of these tumors as well as aspects of the instruments that reflect tumor burden, biochemical, and hormonal status.

Biochemical testing for neuroendocrine tumors.

In this review, we focus on the use of biochemical markers for the diagnosis of neuroendocrine tumors and exclusion of conditions that masquerade as neuroendocrine tumors. In addition, we outline the use of biochemical markers for follow-up, response to intervention, and determination of prognosis. Previous publications have focused only on markers specific to certain tumor types, but the uniqueness of this chapter is that it presents a new approach ranging from biochemical markers that relate to symptoms to the use of markers that facilitate decision making with regard to optimizing the choices of therapy from the complex arrays of intervention, The sequence of presentation in this chapter is first to provide the usual view, that is, biochemical markers of each tumor type and thereafter the diagnosis of the underlying condition or exclusion thereof and finally the algorithm for their use from the clinical presentation to the suspected diagnosis and the biochemical markers to monitor progression and therapeutic choice. There is also a specific description of the properties of the most important biochemical markers and 2 complications, bone metastasis and carcinoid heart disease, from the biochemical point of view.

Development of the Norfolk quality of life tool for assessing patients with neuroendocrine tumors.

OBJECTIVE: To develop a disease-specific questionnaire for identifying domains having the greatest impact on the quality of life (QOL) of patients with neuroendocrine tumors (NETS). METHODS: Patient responses to clinical interviews provided an 80-item initial pool for the development of the QOL-NET. The Delphi panel reviewed the items for content validity; the patient focus group reviewed the items for content/readability. Domains were derived from analysis of224 questionnaire responses. After principal components analysis, a scree plot suggested 7 domains. Exploratory factor analysis with forced 7-factor varimax rotation determined an ideal structure. Reliability/reproducibility was determined by test/retest 4 to 6 weeks apart. Logistic regression determined each domain score. RESULTS: All 7 domains exhibited strong internal consistency (Cronbach alpha = 0.86-0.97). Physical functioning contributed 40% of the total QOL score, followed by flushing, gastrointestinal symptoms, respiratory, cardiovascular, depression, and attitude domains. Most items loaded 0.40 or higher. No significant differences in test and retest scores. The mean values for the total QOL and 4 of 7 factor scores were significantly higher (P < 0.05) for NETS than controls: sensitivity was 71.4% and specificity was 69.6% to discriminate the NETS from the controls. CONCLUSIONS: We developed a 7-domain tool to determine QOL in NETS. Strong internal consistency exists within each domain of the QOL-NET. The QOL-NET is reliable and reproducible but weakly identifies NETS. Physical functioning is a greatest contributor to QOL impairment in NETS.

Particulate air pollution and health effects for cardiovascular and respiratory causes in Temuco, Chile: a wood-smoke-polluted urban area.

Temuco is one of the most highly wood-smoke-polluted cities in the world. Its population in 2004 was 340,000 inhabitants with 1587 annual deaths, of which 24% were due to cardiovascular and 11% to respiratory causes. For hospital admissions, cardiovascular diseases represented 6% and respiratory diseases 13%. Emergency room visits for acute respiratory infections represented 28%. The objective of the study presented here was to determine the relationship between air pollution from particulate matter less than or equal to 10 microm in aerodynamic diameter (PM10; mostly PM2.5, or particulate matter <2.5 microm in aerodynamic diameter) and health effects measured as the daily number of deaths, hospital admissions, and emergency room visits for cardiovascular, respiratory, and acute respiratory infection (ARI) diseases. The Air Pollution Health Effects European Approach (APHEA2) protocol was followed, and a multivariate Poisson regression model was fitted, controlling for trend, seasonality, and confounders for Temuco during 1998-2006. The results show that PM10 had a significant association with daily mortality and morbidity, with the elderly (population >65 yr of age) being the group that presented the greatest risk. The relative risk for respiratory causes, with an increase of 100 microg/m3 of PM10, was 1.163 with a 95% confidence interval (CI) of 1.057-1.279 for mortality, 1.137 (CI 1.096-1.178) for hospital admissions, and 1.162 for ARI (CI 1.144-1.181). There is evidence in Temuco of positive relationships between ambient particulate levels and mortality, hospital admissions, and ARI for cardiovascular and respiratory diseases. These results are consistent with those of comparable studies in other similar cities where wood smoke is the most important air pollution problem.