Reproductive outcomes in an area adjacent to a petrochemical plant in southern Brazil

OBJECTIVE: To evaluate possible adverse reproductive outcomes in an area adjacent to a petrochemical plant in southern Brazil. METHODS: A review of 17,113 birth records of the main hospital of the municipality of Montenegro, southern Brazil, from 1983 to 1998 was carried out. Three groups of cases were selected: (1) newborns with major congenital malformations; (2) newborns with low birth weight (<2,500 g); and (3) stillborns (>500 g). A control was assigned to each case. Controls were the first newborns weighing > or = 2,500 g without malformations and of case-matching sex. Mother's residence during pregnancy was used as an exposure parameter. Statistical analyses were performed using Chi-square test or Fisher test, odds ratio, 0.05 significance level, and 95% confidence interval. RESULTS: For unadjusted analysis, it was found a correlation between low birth weight and geographical proximity of mother's residence to the petrochemical plant (OR = 1.66; 95% CI = 1.01--2.72) or residence on the way of preferential wind direction (OR = 1.62; 95% CI = 1.03--2.56). When other covariates were added in the conditional logistic regression (maternal smoking habits, chronic disease and age), there was no association. CONCLUSIONS: Despite final results were negative, low birth weight could be a good parameter of environmental contamination and should be closely monitored in the studied area.

Temporal variation in reproductive phenology of Patella spp.: past and present.

World Congress of Malacology, Universidade dos Açores, Ponta Delgada, 21-28 de julho.

Reproductive dynamics of Sterna hirundinacea Lesson, 1831 in Ilha dos Cardos, Santa Catarina, Brazil

In this work, we intend to describe the reproductive dynamics of Sterna hirundinacea in an island fromSouth Brazil.We studied the reproductive biology of this species in its natural environment and provide data on their growth, survival, and reproductive success in Ilha dosCardos, SantaCatarina, South Brazil. Samplingswere carried out daily on the island throughout the reproductive seasons of 2003, 2005, and 2006 and the different stages of development of the chicks were characterized according to age, length of the beak, and plumage characteristics.We provide a basic equation Lm = 167.91 (1 – e −0.062t−(−0.23)) to determine the approximate age of individuals using their body mass. The main cause of chick mortality on the island was natural (63.17% in 2003, 81.41% in 2005, and 79.96% in 2006), whereas predation contributed to mortality in a proportion of 38.83% in 2003, 18.59% in 2005, and 20.04% in 2006.The absence in the area of the chicks’ main predator, Kelp gull (Larus dominicanus), the large number of chicks that reached the final stages of development, and their reproductive success demonstrate that Ilha dos Cardos is an important breeding site for the species in southern Brazil.

Pittosporum Undulatum and Hedychium Gardnerianum: nutritive value and secondary metabolites on cattle reproductive performances

Hedychium gardnerianum (HG) and Pittospporum undulatum (PU) are invasive plants all over the world, being in the Azores supplied to cattle on periods of shortage food. As these plants produce secondary metabolites, including a diverse range of phytochemicals compounds, the aim of the presente study is to identify how these metabolites can be related to animal’s reproductive performances. For such purpose, plants were harvested on winter, compounds extracted by method of decoction and analysed by combination of liquid chromatography and mass spectrometry as well as highperformance liquid chromatography. For nutritive evaluations, Van Soest and Weende methodologies were used. In HG quercetin-3, 4'-di-O-betaglucopyranoside, myricetin rhamnoside, quercetin rhamnoside, and gibberellin A1 and A8 were identified, while for PU were found cafeic acid derivatives, including dicaffeoylquinic acid and caffeoylquinic acid. In nutritional terms, these plants can be considered as poor, presenting percentages of dry matter (DM%) of 16.34% and 40.39%, respectively for HG and PU. Values for ash 10.4%, crude protein (CP) 7.75%, neutral detergent fiber (NDF) 64.5, acid detergent fiber (ADF) 34.69%, acid detergent lignin (ADL) 3.47% and ether extract (EE) 2.03% were found for HG. For PU values were ash 6.64%, CP 6.11%, NDF 43.84%, acid ADF 35.57%, ADL 3.56% and EE 2.71%. This study clearly indicated that, besides their low nutritive values, these plants can be used to feed ruminants, especially when pasture lacks. Nevertheless, as some compounds, namely the caffeoylquinic and dicaffeoylquinic acids, are known to be associated to physiological reproductive mechanisms, one could speculate that these compounds can be directly or indirectly associated to reproductive performances in bovine fed with these plants.

Gender and reproductive autonomy : are there second-class citizens in Europe?

EUROPEAN MASTER’S DEGREE IN HUMAN RIGHTS AND DEMOCRATISATION Academic Year 2007/2008

Immunohistochemical molecular phenotypes of gastric cancer based on SOX2 and CDX2 predict patient outcome

Background Gastric cancer remains a serious health concern worldwide. Patients would greatly benefit from the discovery of new biomarkers that predict outcome more accurately and allow better treatment and follow-up decisions. Here, we used a retrospective, observational study to assess the expression and prognostic value of the transcription factors SOX2 and CDX2 in gastric cancer. Methods SOX2, CDX2, MUC5AC and MUC2 expression were assessed in 201 gastric tumors by immunohistochemistry. SOX2 and CDX2 expression were crossed with clinicopathological and follow-up data to determine their impact on tumor behavior and outcome. Moreover, SOX2 locus copy number status was assessed by FISH (N = 21) and Copy Number Variation Assay (N = 62). Results SOX2 was expressed in 52% of the gastric tumors and was significantly associated with male gender, T stage and N stage. Moreover, SOX2 expression predicted poorer patient survival, and the combination with CDX2 defined two molecular phenotypes, SOX2+CDX2- versus SOX2-CDX2+, that predict the worst and the best long-term patients’ outcome. These profiles combined with clinicopathological parameters stratify the prognosis of patients with intestinal and expanding tumors and in those without signs of venous invasion. Finally, SOX2 locus copy number gains were found in 93% of the samples reaching the amplification threshold in 14% and significantly associating with protein expression. Conclusions We showed, for the first time, that SOX2 combined with CDX2 expression profile in gastric cancer segregate patients into different prognostic groups, complementing the clinicopathological information. We further demonstrate a molecular mechanism for SOX2 expression in a subset of gastric cancer cases.

TERT Promoter Mutations Are a Major Indicator of Poor Outcome in Differentiated Thyroid Carcinomas

Context: Telomerase promoter mutations (TERT) were recently described in follicular cell-derived thyroid carcinomas (FCDTC) and seem to be more prevalent in aggressive cancers. Objectives: We aimed to evaluate the frequency of TERT promoter mutations in thyroid lesions and to investigate the prognostic significance of such mutations in a large cohort of patients with differentiated thyroid carcinomas (DTCs). Design: This was a retrospective observational study. Setting and Patients: We studied 647 tumors and tumor-like lesions. A total of 469 patients with FCDTC treated and followed in five university hospitals were included. Mean follow-up (±SD) was 7.8 ± 5.8 years. Main Outcome Measures: Predictive value of TERT promoter mutations for distant metastasization, disease persistence at the end of follow-up, and disease-specific mortality. Results: TERT promoter mutations were found in 7.5% of papillary carcinomas (PTCs), 17.1% of follicular carcinomas, 29.0% of poorly differentiated carcinomas, and 33.3% of anaplastic thyroid carcinomas. Patients with TERT-mutated tumors were older (P < .001) and had larger tumors (P = .002). In DTCs, TERT promoter mutations were significantly associated with distant metastases (P < .001) and higher stage (P < .001). Patients with DTC harboring TERT promoter mutations were submitted to more radioiodine treatments (P = .009) with higher cumulative dose (P = .004) and to more treatment modalities (P = .001). At the end of follow-up, patients with TERT-mutated DTCs were more prone to have persistent disease (P = .001). TERT promoter mutations were significantly associated with disease-specific mortality [in the whole FCDTC (P < .001)] in DTCs (P < .001), PTCs (P = .001), and follicular carcinomas (P < .001). After adjusting for age at diagnosis and gender, the hazard ratio was 10.35 (95% confidence interval 2.01–53.24; P = .005) in DTC and 23.81 (95% confidence interval 1.36–415.76; P = .03) in PTCs. Conclusions: TERT promoter mutations are an indicator of clinically aggressive tumors, being correlated with worse outcome and disease-specific mortality in DTC. TERT promoter mutations have an independent prognostic value in DTC and, notably, in PTC.

The role of functional polymorphisms in immune response genes as biomarkers of BCG Immunotherapy outcome in bladder cancer: Establishment of a predictive profile in a Southern Europe population

OBJECTIVE: To evaluate the predictive value of genetic polymorphisms in the context of BCG immunotherapy outcome and create a predictive profile that may allow discriminating the risk of recurrence. MATERIAL AND METHODS: In a dataset of 204 patients treated with BCG, we evaluate 42 genetic polymorphisms in 38 genes involved in the BCG mechanism of action, using Sequenom MassARRAY technology. Stepwise multivariate Cox Regression was used for data mining. RESULTS: In agreement with previous studies we observed that gender, age, tumor multiplicity and treatment scheme were associated with BCG failure. Using stepwise multivariate Cox Regression analysis we propose the first predictive profile of BCG immunotherapy outcome and a risk score based on polymorphisms in immune system molecules (SNPs in TNFA-1031T/C (rs1799964), IL2RA rs2104286 T/C, IL17A-197G/A (rs2275913), IL17RA-809A/G (rs4819554), IL18R1 rs3771171 T/C, ICAM1 K469E (rs5498), FASL-844T/C (rs763110) and TRAILR1-397T/G (rs79037040) in association with clinicopathological variables. This risk score allows the categorization of patients into risk groups: patients within the Low Risk group have a 90% chance of successful treatment, whereas patients in the High Risk group present 75% chance of recurrence after BCG treatment. CONCLUSION: We have established the first predictive score of BCG immunotherapy outcome combining clinicopathological characteristics and a panel of genetic polymorphisms. Further studies using an independent cohort are warranted. Moreover, the inclusion of other biomarkers may help to improve the proposed model.

Sex Determination and Female Reproductive Development in the Genus Schistosoma: A Review

Parasites of the genus Schistosoma were among the first metazoans to develop separate sexes, which is chromosomally determined in the fertilized egg. Despite the occurrence of specific sex chromosomes, the females of most Schistosomatidae species do not complete their somatic development and reach no sexual maturity without the presence of males. Indeed, the most controversial and at the same time most fascinating aspect about the sexual development of Schistosoma females lies on discover the nature of the stimulus produced by males that triggers and controls this process. Although the nature of the stimulus (physical or chemical) is a source of controversy, there is agreement that mating is a necessary requirement for maturation to occur and for migration of the female to a definitive final site of residence in the vascular system of the vertebrate host. It has also been proposed that the stimulus is not species-specific and, in some cases, not even genus-specific. Despite a vast literature on the subject, the process or processes underlying the meeting of males and females in the circulatory system have not been determined and as yet no consensus exists about the nature of the stimulus that triggers and maintains female development. In the studies about their role, Schistosoma males have been considered, at times pejoratively, the brother, the muscles or even the liver of females. Indeed, it still remains to be determined whether the stimulus responsible for female maturation involves the transfer of hormones, nutrients, neuromediators, mere tactile stimulation or a combination of chemotactic and thigmotactic factors

Hepatitis C viral load does not predict disease outcome: going beyond numbers

The analysis of 58 patients with chronic hepatitis C without cirrhosis and treated with interferon-alpha demonstrated that hepatitis C viral (HCV) load does not correlate with the histological evolution of the disease (p = 0.6559 for architectural alterations and p = 0.6271 for the histological activity index). Therefore, the use of viral RNA quantification as an evolutive predictor or determinant of the severity of hepatitis C is incorrect and of relative value. A review of the literature provided fundamental and interdependent HCV (genotype, heterogeneity and mutants, specific proteins), host (sex, age, weight, etc) and treatment variables (dosage, time of treatment, type of interferon) within the broader context of viral kinetics, interferon-mediated immunological response (in addition to natural immunity against HCV) and the role of interferon as a modulator of fibrogenesis. Therefore, viral load implies much more than numbers and the correct interpretation of these data should consider a broader context depending on multiple factors that are more complex than the simple value obtained upon quantification.

The influence of the human genome on chronic viral hepatitis outcome

The mechanisms that determine viral clearance or viral persistence in chronic viral hepatitis have yet to be identified. Recent advances in molecular genetics have permitted the detection of variations in immune response, often associated with polymorphism in the human genome. Differences in host susceptibility to infectious disease and disease severity cannot be attributed solely to the virulence of microbial agents. Several recent advances concerning the influence of human genes in chronic viral hepatitis B and C are discussed in this article: a) the associations between human leukocyte antigen polymorphism and viral hepatic disease susceptibility or resistance; b) protective alleles influencing hepatitis B virus (HBV) and hepatitis C virus (HCV) evolution; c) prejudicial alleles influencing HBV and HCV; d) candidate genes associated with HBV and HCV evolution; d) other genetic factors that may contribute to chronic hepatitis C evolution (genes influencing hepatic stellate cells, TGF-beta1 and TNF-alpha production, hepatic iron deposits and angiotensin II production, among others). Recent discoveries regarding genetic associations with chronic viral hepatitis may provide clues to understanding the development of end-stage complications such as cirrhosis or hepatocellular carcinoma. In the near future, analysis of the human genome will allow the elucidation of both the natural course of viral hepatitis and its response to therapy.

Paracoccidioidomycosis in children: clinical presentation, follow-up and outcome

From February, 1981 to May, 2001, 63 children under 15 y old (ages 2 - 15 y, median = 8 y, mean ± 1 SD = 8 ± 3 y) presenting 70 episodes of Paracoccidioidomycosis were admitted. The main clinical manifestations and laboratory features observed upon admission were: lymph node enlargement (87.1%), fever (75.7%), weakness (48.6%), pallor (41.4%), hepatomegaly (40%), splenomegaly (35.7%), anemia (90%), hypergammaglobulinemia (88.5%), eosinophilia (75.5%) and hypoalbuminemia (72.5%). Moderate to severe malnutrition was detected in 35.7% of the episodes (Gomez's criterion). Radiographic and technetium studies showed bone lesions in 20 of the episodes, most of them being multiple lytic lesions, involving both long (70%) and plain bones (30%). First line treatment consisted of an association of sulfametoxazole-trimethoprin, which was used, exclusively, in 50 episodes. Follow-up of hemoglobin levels, number of eosinophils in the peripheral blood, albumin and gammaglobulin serum levels revealed significant sequential improvement one and six months after hospital admission, being quite useful to evaluate treatment effectiveness. Six patients died (9.3%) and four developed sequelae (6.3%) . In conclusion, the juvenile and disseminated forms can be observed in about 70% of the episodes of PCM occurring in children younger than 15 y old, most of them presenting with a febrile lymphoproliferative syndrome associated to anemia, eosinophilia and hypergammaglobulinemia.

Primary Antiphospholipid Syndrome: Pregnancy Outcome in a Portuguese Population

Introduction:Women with antiphospholipid syndrome(APS) may suffer from recurrent miscarriage, fetal death, fetal growth restriction (FGR), pre-eclampsia, placental abruption, premature delivery and thrombosis. Treatment with aspirin and low molecular weight heparin (LMWH) combined with close maternal-fetal surveillance can change these outcomes. Objective: To assess maternal and perinatal outcome in a cohort of Portuguese women with primary APS. Patients and Methods: A retrospective analysis of 51 women with primary APS followed in our institution (January 1994 to December 2007). Forty one(80.4%) had past pregnancy morbidity and 35.3%(n=18) suffered previous thrombotic events. In their past they had a total of 116 pregnancies of which only 13.79 % resulted in live births. Forty four patients had positive anticardiolipin antibodies and 33 lupus anticoagulant. All women received treatment with low dose aspirin and LMWH. Results: There were a total of 67 gestations (66 single and one multiple). The live birth rate was 85.1%(57/67) with 10 pregnancy failures: seven in the first and second trimesters, one late fetal death and two medical terminations of pregnancy (one APS related). Mean (± SD) birth weight was 2837 ± 812 g and mean gestational age 37 ± 3.3 weeks. There were nine cases of FGR and 13 hypertensive complications(4 HELLP syndromes). 54.4% of the patients delivered by caesarean section. Conclusions: In our cohort, early treatment with aspirin and LMWH combined with close maternal-fetal surveillance was associated with a very high chance of a live newborn.

Impact of Donor and Recipient Cytokine Genotypes on Renal Allograft Outcome

Allelic differences in gene promoter or codifying regions have been described to affect regulation of gene expression, consequently increasing or decreasing cytokine production and signal transduction responses to a given stimulus. This observation has been reported for interleukin (IL)-10 (-1082 A/G; -819/-592 CT/CA), transforming growth factor (TGF)-beta (codon 10 C/T, codon 25 G/C), tumor necrosis factor (TNF)-alpha (-308 G/A), TNF-beta (+252 A/G), interferon (IFN)-gamma (+874 T/A), IL-6 (-174 G/C), and IL-4R alpha (+1902 G/A). To evaluate the influence of these cytokine genotypes on the development of acute or chronic rejection, we correlated the genotypes of both kidney graft recipients and cadaver donors with the clinical outcome. Kidney recipients had 5 years follow-up, at least 2 HLA-DRB compatibilities, and a maximum of 25% anti-HLA pretransplantation sensitization. The clinical outcomes were grouped as follows: stable functioning graft (NR, n = 35); acute rejection episodes (AR, n = 31); and chronic rejection (CR, n = 31). The cytokine genotype polymorphisms were defined using PCR-SSP typing. A statistical analysis showed a significant prevalence of recipient IL-10 -819/-592 genotype among CR individuals; whereas among donors, the TGF-beta codon 10 CT genotype was significantly associated with the AR cohort and the IL-6 -174 CC genotype with CR. Other albeit not significant observations included a strong predisposition of recipient TGF-beta codon 10 CT genotype with CR, and TNF-beta 252 AA with AR. A low frequency of TNF-alpha -308 AA genotype also was observed among recipients and donors who showed poor allograft outcomes.

Clinical Outcome and Morphologic Analysis after Endovascular Aneurysm Repair Using the Excluder Endograft

OBJECTIVE: Long-term follow-up after endovascular aneurysm repair (EVAR) is very scarce, and doubt remains regarding the durability of these procedures. We designed a retrospective cohort study to assess long-term clinical outcome and morphologic changes in patients with abdominal aortic aneurysms (AAAs) treated by EVAR using the Excluder endoprosthesis (W. L. Gore and Associates, Flagstaff, Ariz). METHODS: From 2000 to 2007, 179 patients underwent EVAR in a tertiary institution. Clinical data were retrieved from a prospective database. All patients treated with the Excluder endoprosthesis were included. Computed tomography angiography (CTA) scans were retrospectively analyzed preoperatively, at 30 days, and at the last follow-up using dedicated tridimensional reconstruction software. For patients with complications, all remaining CTAs were also analyzed. The primary end point was clinical success. Secondary end points were freedom from reintervention, sac growth, types I and III endoleak, migration, conversion to open repair, and AAA-related death or rupture. Neck dilatation, renal function, and overall survival were also analyzed. RESULTS: Included were 144 patients (88.2% men; mean age, 71.6 years). Aneurysms were ruptured in 4.9%. American Society of Anesthesiologists classification was III/IV in 61.8%. No patients were lost during a median follow-up of 5.0 years (interquartile range, 3.1-6.4; maximum, 11.2 years). Two patients died of medical complications ≤ 30 days after EVAR. The estimated primary clinical success rates at 5 and 10 years were 63.5% and 41.1%, and secondary clinical success rates were 78.3% and 58.3%, respectively. Sac growth was observed in 37 of 142 patients (26.1%). Cox regression showed type I endoleak during follow-up (hazard ratio, 3.74; P = .008), original design model (hazard ratio, 3.85; P = .001), and preoperative neck diameter (1.27 per mm increase, P = .006) were determinants of sac growth. Secondary interventions were required in 32 patients (22.5%). The estimated 10-year rate of AAA-related death or rupture was 2.1%. Overall life expectancy after AAA repair was 6.8 years. CONCLUSIONS: EVAR using the Excluder endoprosthesis provides a safe and lasting treatment for AAA, despite the need for maintained surveillance and secondary interventions. At up to 11 years, the risk of AAA-related death or postimplantation rupture is remarkably low. The incidences of postimplantation sac growth and secondary intervention were greatly reduced after the introduction of the low-permeability design in 2004.