Serum anti-Müllerian hormone is lower in patients with multiple radioiodine dose for treatment of pediatric thyroid cancer.

Introduction: Treatment of patients with pediatric differentiated thyroid cancer (DTC) often involves radioiodine (RAI), which is associated with increased risks of short- and long-term adverse outcomes. The impact of RAI treatment on the female reproductive system remains uncertain. Anti-Müllerian hormone (AMH) is a marker of ovarian reserve and is related to fertility. Objective: The aim was to analyze the association between RAI and serum AMH level in women treated with RAI. Methods: We evaluated women with pediatric DTC treated with RAI at the age of ≤19 years. Serum AMH was measured. Results: The study included 47 patients with a mean age of 25.1 years (12.4-50.8) at AMH measurement and follow-up of 11.8 ± 8.4 years. The mean RAI administered was 235 mCi (30-1150). Sixteen (34%) received multiple RAI doses (471 ± 215 mCi). Mean AMH level was 2.49 ng/mL (0.01-7.81); the level was 1.57 ng/mL (0.01-7.81) after multiple RAI doses and 2.99 ng/mL (0.01-6.63) after a single RAI dose (P = 0.01). Patients who received a cumulative RAI lower than 200 mCi had higher AMH levels (2.23 ng/mL, 0.39-7.81) than those who received more (1.0 ng/mL, 0.01-6.63; P = 0.02). In patients with similar cumulative RAI activities, administration of multiple RAI doses was significantly and independently associated with AMH level lower than the reference range for age (HR: 5.9, 1.55-52.2, P = 0.014) after age adjustments. Conclusion: Levels of AMH were lower after multiple RAI doses, especially after a cumulative RAI dose above 200 mCi. More studies are needed to clarify the impact of RAI on fertility considering its cumulative activity and treatment strategy.

Stimulated thyroglobulin and diagnostic 131-iodine whole-body scan as a predictor of distant metastasis and association with response to treatment in pediatric thyroid cancer patients.

INTRODUCTION: Differentiated thyroid carcinoma (DTC) is a rare oncological disease in the pediatric population, presenting with a more aggressive form. Stimulated thyroglobulin (sTg) and the 131-iodine whole-body scans (WBSs) are known adult markers related to the presence of distant metastasis. Little is known about their roles in the pediatric population. PURPOSE: To evaluate sTg levels and diagnostic WBS (DxWBS) as predictors of distant metastasis after thyroidectomy and to correlate with the response to treatment at the end of follow-up in pediatric DTC. MATERIALS AND METHODS: Patients under 19 years old diagnosed with DTC from 1980 to 2022 were retrospectively evaluated. sTg values and WBS were assessed after thyroidectomy and prior radioiodine treatment (RIT) and correlated with the possibility of finding distant metastasis and response to treatment at the end of follow-up. RESULTS: In a total of 142 patients with a median age of 14.6 (4-18) years who were followed for 9.5 ± 7.2 years and classified according to the ATA risk of recurrence as low (28%), intermediate (16%), and high risk (56%), 127 patients had their sTg evaluated. A sTg value of 21.7 ng/dl yielded a sensitivity of 88% compared to 30% for DxWBS in predicting distant metastasis. Specificity was 60% and 100% respectively. 42% of patients obtained discordant results between DxWBS and RxWBS. In high-risk patients, sTg levels were particularly able to differentiate those who would have distant metastasis with better diagnostic accuracy than the WBSs. CONCLUSIONS: The sTg level had better performance in detecting distant metastases in pediatric DTC than the DxWBS. DxWBS's low performance suggests that caution should be taken in interpreting their findings in terms of the underdiagnosis for metastatic disease, especially when the sTg level already suggests distant disease.

Neutrophil-to-lymphocyte ratio as an independent factor for worse prognosis in radioiodine refractory thyroid cancer patients.

PURPOSE: This study aimed to evaluate neutrophil to lymphocyte ratio (NLR) as a laboratory biomarker in radioactive iodine-refractory (RAIR) locally advanced and/or metastatic differentiated thyroid cancer (DTC) and determine its correlation with overall survival (OS). METHODS: We retrospectively included 172 patients with locally advanced and/or metastatic RAIR DTC admitted between 1993 and 2021 at INCA. Age at diagnosis, histology, presence of distant metastasis (DM), DM site, neutrophil-to- lymphocyte ratio (NLR), imaging studies such as PET/CT results, progression free survival (PFS) and overall survival (OS) data were analyzed. NLR was calculated at the time of locally advanced and/or metastatic disease diagnosis and the cutoff value was 3. Survival curves were established using the Kaplan-Meier method. The confidence interval is 95%, and a p-value of less than 0.05 was considered statistically significant RESULTS: Out of 172 patients, 106 were locally advanced, and 150 presented DM at some point during follow-up. Regarding NLR data, 35 had NLR over 3 and 137 had NLR under 3. Higher NLR at was associated with shorter OS (6 vs. 10; p = 0.05) and with highest SUV on FDG PET-CT (15.9 vs. 7.7, p = 0.013). We found no association between higher NLR and age at diagnosis, DM or final status. CONCLUSION: NLR higher than 3 at the time of locally advanced and/or metastatic disease diagnosis is an independent fator for shorter OS in RAIR DTC patients. Noteworthy higher NLR was also associated with highest SUV on FDG PET-CT in this population.

Types of analysis of validation studies in nursing: scoping review / Tipos de análisis de los estudios de validación de enfermería: scoping review / Tipos de análises dos estudos de validação na enfermagem: scoping review

Objective. To identify and map the types of analysis in nursing validation studies.Methods. This is a scoping review with collection carried out in July 2020. The following data extraction indicators were considered: year of publication, country of origin, type of study, level of evidence, scientific references for validation and types of analyses. Data were collected in the following bases: U.S. National Library of Medicine, Cumulative Index to Nursing and Allied Health Literature, SCOPUS, COCHRANE, Web of Science, PsycInfo, Latin American and Caribbean Literature in Health Sciences, CAPES Theses and Dissertation Portal, Education Resources Information Center, The National Library of Australia's Trobe, Academic Archive Online, DART-Europe E-Theses Portal, Electronic Theses Online Service, Open Access Scientific Repository of Portugal, National ETD Portal, Theses Canada, Theses and dissertations from Latin America. Results. The reviewsample consisted of 881 studies, with a predominance of articles (841; 95.5%), with a prevalence of publications in 2019 (152; 17.2%), of Brazilian origin (377; 42.8%), of the methodological study type (352; 39.9%). Polit and Beck stood out as the methodological reference (207; 23.5%) and Cronbach's Alpha (421; 47.8%) as the statistical test. Regarding the type of analysis, the exploratory factor analysis and the content validation index stood out. Conclusion. The use of at least one method of analysis was evident in more than half of the studies, which implied the need to carry out several statistical tests in order to evaluate the validation of the instrument used and show its reliability.

Objetivo. Identificar y mapear los tipos de análisis de los estudios de validación de enfermería. Métodos. Esta es una revisión de alcance, con recolección realizada en julio de 2020. Se consideraron los siguientes indicadores para la extracción de datos: año de publicación, país de origen, tipo de estudio, nivel de evidencia, referencias científicas para la validación y tipos de análisis. Los datos se recolectaron en las siguientes bases: U.S. National Library of Medicine, Cumulative Index to Nursing and Allied Health Literature, SCOPUS, COCHRANE, Web of Science, PsycInfo, Latin American and Caribbean Literature in Health Sciences, CAPES Theses and Dissertation Portal, Education Resources Information Center, The National Library of Australia's Trobe, Academic Archive Online, DART-Europe E-Theses Portal, Electronic Theses Online Service, Open Access Scientific Repository of Portugal, National ETD Portal, Theses Canada y Tesis y disertaciones de América Latina. Resultados. La muestra la constituyeron 881 estudios, con predominio de artículos (841; 95.5%), con una frecuencia mayor de publicaciones en 2019 (152; 17.2%), de origen brasileño (377; 42.8%), del tipo de estudio metodológico. (352; 39.9%). Polit y Beck se destacaron como referencia metodológica (207; 23.5%) y el Alpha de Cronbach (421; 47.8%) como prueba estadística. En cuanto al tipo de análisis, se destacó el análisis factorial exploratorio y el índice de validación de contenido. Conclusión. En más de la mitad de los estudios fue evidente la utilización de, al menos, un método de análisis, lo que implicó la necesidad de realizar varias pruebas estadísticas con el fin de evaluar la validación del instrumento empleado y mostrar su fiabilidad.

Objetivo. Identificar e mapear os tipos de análises dos estudos de validação em enfermagem. Métodos. Trata-se de uma scoping review, com coleta realizada em julho de 2020. Considerou-se como indicadores de extração de dados: ano de publicação, país de origem, tipo de estudo, nível de evidência, os referenciais científicos para validação e os tipos de análises. Os dados foram coletados nas bases: U.S. National Library of Medicine,Cumulative Index to Nursing and Allied Health Literature, SCOPUS, COCHRANE, Web of Science, PsycInfo,Literatura Latino-Americana e do Caribe em Ciências da Saúde, Portal de Teses e Dissertações da CAPES, Education Resources Information Center, The National Library of Australia's Trobe, Academic Archive Online, DART-Europe E-Theses Portal, Electronic Theses Online Service, Repositório Científico de Acesso Aberto de Portugal, National ETD Portal, Theses Canada, Teses e dissertações da América latina. Resultados. A amostra foi de 881 estudos, com predomínio de artigos (841; 95.5%), com prevalência de publicações em 2019 (152; 17.2%), de origem brasileira (377; 42.8%), do tipo estudo metodológico (352; 39.9%). Sobressaiu-se Polit e Beck como referencial metodológico (207; 23.5%) e Alfa de Cronbach (421; 47.8%) como teste estatístico. Em relação ao tipo de análise destacou-se a análise fatorial exploratória e o índice de validação de conteúdo. Conclusão. Em mais da metade dos estudos ficou evidente a utilização de pelo menos um método de análise, o que implicou a necessidade de realização de diversos testes estatísticos para avaliar a validade do instrumento utilizado e mostrar sua confiabilidade.

FAIR Genomes metadata schema promoting Next Generation Sequencing data reuse in Dutch healthcare and research.

The genomes of thousands of individuals are profiled within Dutch healthcare and research each year. However, this valuable genomic data, associated clinical data and consent are captured in different ways and stored across many systems and organizations. This makes it difficult to discover rare disease patients, reuse data for personalized medicine and establish research cohorts based on specific parameters. FAIR Genomes aims to enable NGS data reuse by developing metadata standards for the data descriptions needed to FAIRify genomic data while also addressing ELSI issues. We developed a semantic schema of essential data elements harmonized with international FAIR initiatives. The FAIR Genomes schema v1.1 contains 110 elements in 9 modules. It reuses common ontologies such as NCIT, DUO and EDAM, only introducing new terms when necessary. The schema is represented by a YAML file that can be transformed into templates for data entry software (EDC) and programmatic interfaces (JSON, RDF) to ease genomic data sharing in research and healthcare. The schema, documentation and MOLGENIS reference implementation are available at https://fairgenomes.org .

Types of analysis of validation studies in nursing: scoping review.

OBJECTIVES: To identify and map the types of analysis in nursing validation studies. METHODS: This is a scoping review with collection carried out in July 2020. The following data extraction indicators were considered: year of publication, country of origin, type of study, level of evidence, scientific references for validation and types of analyses. Data were collected in the following bases: U.S. National Library of Medicine, Cumulative Index to Nursing and Allied Health Literature, SCOPUS, COCHRANE, Web of Science, PSYCHINFO, Latin American and Caribbean Literature in Health Sciences, CAPES Theses and Dissertation Portal, Education Resources Information Center, The National Library of Australia's Trobe, Academic Archive Online, DART-Europe E-Theses Portal, Electronic Theses Online Service, Open Access Scientific Repository of Portugal, National ETD Portal, Theses Canada, Theses and dissertations from Latin America. RESULTS: The sample consisted of 881 studies, with a predominance of articles (841; 95.5%), with a prevalence of publications in 2019 (152;17.2%), of Brazilian origin (377; 42.8%), of the methodological study type (352; 39.9%). Polit and Beck stood out as the methodological reference (207; 23.5%) and Cronbach's Alpha (421; 47.8%) as the statistical test. Regarding the type of analysis, the exploratory factor analysis and the content validation index stood out. CONCLUSIONS: The use of at least one method of analysis was evident in more than half of the studies, which implied the need to carry out several statistical tests in order to evaluate the validation of the instrument used and show its reliability.

Diagnostic Failure Rate in Detecting Perilunate Carpal Fractures and Dislocations Using Plain Wrist X-Rays.

Objectives The present study aimed to evaluate the diagnostic failure rate in detecting perilunate fractures and dislocations using plain wrist radiographs by orthopedists and orthopedic residents. A secondary objective was to identify possible groups with a greater or lesser chance of establishing a correct diagnosis. Methods An online questionnaire was sent to several orthopedists through e-mail, social networks, and smartphone-based communication applications to assess the rate of diagnostic failure in detecting perilunate fractures and dislocations using plain radiographs. Results A total of 511 responses was obtained, with a diagnostic error rate of 8.81% for simple dislocations and 1.76% for trans-scaphoid perilunate fractures. Group stratification showed that residents presented the highest error rates in simple perilunate dislocations (23.91%), whereas hand surgeons presented the lowest error rates (1.74%). Conclusion Compared with the literature, the failure rates found were lower, suggesting that plain radiography is effective and that the error rate may not be as high as reported.

Prognostic factors in patients with advanced differentiated thyroid cancer treated with multikinase inhibitors - a single Brazilian center experience.

OBJECTIVE: The aim of this study was to describe the real-world experience multikinase inhibitors (MKI) in the treatment advanced differentiated thyroid carcinoma (DTC) refractory to radioactive iodine (RAIR) therapy. METHODS: We reviewed the records of all patients with MKI-treated DTC from 2010 to 2018. Progression free survival (PFS), response rates (RR) and adverse events (AE) profiles were assessed. Clinical parameters were compared between groups with different outcomes (disease progression and death) to identify possible prognostic factors and benefit from treatment. RESULTS: Forty-four patients received MKI for progressive RAIR DTC. Median PFS was 24 months (10.2-37.7) and median overall survival (OS) was 31 months. Best overall response was complete response in one patient (4.5%), partial response in nine (20.4%), stable disease in twenty-two (50%), and progressive disease (PD) in twelve (27.3%). Seventy-two point 7 percent patients had clinical benefit and AE were mild in most cases (82.7%). Progressive patients were more likely to have FDG positive target lesion than those who did not progress (p = 0.033) and higher maximum SUV on target lesions (p = 0.042). Presence of lung-only metastasis and lower thyroglobulin (Tg) during treatment was associated with stable disease (p = 0.015 and 0,049, respectively). Patients with shorter survival had larger primary tumor size (p = 0.015) and higher maximum SUV on target lesions (p = 0.023). CONCLUSION: Our findings demonstrate safety and effectiveness of MKI in patients with advanced RAIR DTC. We were able to identify as possible prognostic markers of better outcomes: absence of FDG uptake on target lesions, lower maximum SUV on PET-CT, presence of lung-only metastasis and lower Tg during treatment.

Role of nicergoline in corneal wound healing in diabetic rats.

BACKGROUND: To investigate the effect of nicergoline on the rate of complete corneal ulcer reepithelialization (CCUR) in diabetic rats with diabetic keratopathy. METHODS: Forty-eight streptozotocin-induced diabetic rats were randomly divided into two groups. The experimental group (n = 24) received nicergoline (10 mg.kg- 1.day- 1), while the control group (n = 24) received a placebo. A corneal epithelial defect was induced using a corneal diamond burr, and defect area was compared at time points of 0, 12, 24, 48 and 72 h after the injury using image analysis software. The probability of CCUR within 72 h was assessed using the Kaplan-Meier survival analysis log-rank test. RESULTS: When compared, 4 of the 24 rats (17%) in the placebo group and 12 of the 24 rats (50%) in the nicergoline group were found to have CCUR within 72 h (log-rank = 0.027). Cox regression analysis found no effect of the covariates blood glucose (P = 0.601) or weight (P = 0.322) on the corneal reepithelialization (survival) curve. CONCLUSIONS: Nicergoline increased wound healing rates relative to placebo and may therefore be investigated as a treatment option in diabetic keratopathy.

High thyroglobulin and negative whole-body scan: no long-term benefit of empiric radioiodine therapy.

PURPOSE: Around 10-27% of patients will present elevated thyroglobulin (Tg) levels and negative diagnostic whole-body scan (dxWBS) during differentiated thyroid cancer (DTC) follow-up. Empiric radioactive iodine (RAI) therapy in this context is controversial due to the lack of good quality studies in the context. The main purpose of this study is to compare long-term response to therapy status and overall survival between empiric RAI treated and untreated DTC patients. METHODS: A retrospective study comparing differentiated thyroid cancer patients with negative diagnostic whole-body scan and elevated thyroglobulin levels submitted or not to empiric radioactive iodine therapy in a thyroid cancer referral center. The main outcome measures were ATA Response to Therapy Stratification at 6-12 months after RAI ablative dose, at 6-18 months after negative dxWBS and last follow-up visits. RESULTS: Overall, 120 DTC patients with stimulated Tg >10 ng/ml and negative dxWBS were included in this study. Overall, 53 patients were submitted to empiric RAI and 67 were in the control group. No difference was observed in ATA Response to Therapy Stratification after RAI ablation or at the end of follow-up between groups. Also, no difference was found in terms of Tg changes response. After more than 10 years of follow-up, 17 patients died (13 from treated and 4 from untreated group). CONCLUSIONS: Empiric RAI treatment was not associated with better long-term ATA response to therapy status or overall survival.

Spray-Dried Yerba Mate Extract Capsules: Clinical Evaluation and Antioxidant Potential in Healthy Individuals.

The aim of the present study was to evaluate the clinical effects and antioxidant potential of spray-dried yerba mate extract (SDME) capsules in healthy individuals. Fourteen healthy volunteers consumed three capsules of SDME three times daily. Measurements were carried out at the baseline and after 7, 30, and 60 days of SDME capsules intake. Electrocardiogram, hematological, urinary, and biochemical parameters analyzed remained within the normal values during all the study. SDME capsules ingestion increased significantly serum antioxidant capacity (after 7 and 30 days) and reduced glutathione values (after 7 and 60 days), and the superoxide dismutase (after 7, 30, and 60 days), catalase (after 7 and 30 days), and paraoxonase-1 activities (after 7 days); and decreased lipid hydroperoxides (after 30 and 60 days) and thiobarbituric acid reactive substances levels (after 7 and 30 days). No change was observed for glutathione peroxidase activity after SDME capsules intake. The present study showed that SDME capsules ingestion by healthy individuals did not promote clinical changes and promoted an increase of antioxidant biomarkers with a concomitant decrease of lipid peroxidation biomarkers in a short and prolonged manner.

Beneficial effects of inoculation of growth-promoting bacteria in strawberry.

Plant growth-promoting bacteria have been highlighted by their potential for application in plant production, allowing the reduction of the use of fertilizers and pesticides, which is due to the ability to stimulate the growth of plants by nitrogen-fixation and production of phytohormones, such as indole-3-acetic acid (IAA). The objective of this study was to verify the potential of plant growth promotion of 25 wild isolates from the Agricultural Microbiology Culture Collection of the Federal University of Lavras (CCMA-UFLA) through the evaluation of the biological nitrogen-fixation capacity and the production of IAA. In addition, the growth of three selected strains inoculated on roots of strawberry seedlings in greenhouse conditions was evaluated. The experiment was conducted in a completely randomized design (CRD), with an 8 × 2 factorial schemes involving eight combinations of bacteria: alone, in pairs and threes, plus the control without inoculation. Two fertilizer levels were used (0% and 50% of nitrogen), totaling 16 treatments with eight replicates each. After 75 days, variables such as root length, root dry weight, aerial part length, aerial part dry weight, leaf number, total dry mass and ultrastructural analysis of the inoculated and uninoculated roots, were evaluated. The results showed that the strawberry crop responded positively to inoculation with the three bacteria combined Azospirillum brasilense (Ab-V5) + Burkholderia cepacia (CCMA 0056) + Enterobacter cloacae (CCMA 1285) compared to the uninoculated controls. More expressive responses in terms of plant growth were observed in relation to the combined inoculation of the three bacterial strains plus fertilizer application with 50% of nitrogen.

Assessing the effectiveness of nutrition interventions implemented among US college students to promote healthy behaviors: A systematic review.

BACKGROUND:: Nutrition interventions are used to increase knowledge, change attitudes and beliefs about healthy eating, to increase skills, and promote healthy eating. AIMS:: To review the effectiveness of published nutrition interventions implemented among college students to promote healthy behaviors. METHODS:: The authors explored multiple electronic databases, such as ERIC, Science Direct, and EBSCOhost. Search criteria included nutritional interventions implemented among students attending US colleges, written in English, and published in peer-reviewed journals between 2000 and 2015. The authors conducted a systematic search of 1413 articles, and an in-depth review of 30 articles. The authors evaluated the following: (a) participants; (b) research design; (c) assessment instruments; (d) outcome measures; (e) results; and (f) methodological issues. RESULTS:: Short-term interventions showed promise in promoting positive dietary changes, which can serve as a protective factor for developing overweight and obesity. Methodological issues related to lack of comparison groups and minimal long-term follow-up do not allow researchers to determine if the interventions were the cause of the change, or if these changes are sustained over time. Studies that have a comparison group, use visual displays, or have longer durations, may maximize outcomes, improving long-term effects. CONCLUSIONS:: Nutrition interventions can effectively change dietary habits among college students. This can lead to healthy weight management and reduce the risk for overweight and obesity. Future research should consider the highlighted methodological issues to improve the quality of nutrition interventions.

TERTp mutation is associated with a shorter progression free survival in patients with aggressive histology subtypes of follicular-cell derived thyroid carcinoma.

PURPOSE: Evaluate the impact of TERTp mutation on the outcomes after initial treatment of 45 patients with thyroid carcinomas derived from follicular cells (TCDFC) with aggressive histology, in which the role of this mutation is not yet well defined. METHODS: Analysis of the presence of TERTp (-124C > T and -146C > T), BRAF (V600E), and NRAS (Q 61R) mutations by Sanger sequencing and analysis of their correlation with the patient's outcomes. RESULTS: Forty-five patients with aggressive histopathologic variants were included in the study. Of these, 68.9% had aggressive variants of papillary thyroid cancer (PTC), 22.2% had poorly differentiated thyroid carcinoma (PDTC)/insular carcinoma, and 8.9% had invasive follicular thyroid cancer (FTC) with Hurthle cell features (Hurthle cell carcinoma). Lymph node metastases were present in 46.7% and distant metastases in 54.6%. The response to the initial therapy was excellent in 45.5% and structurally incomplete in 50%. During the follow-up period (median of 56 months; 5-360 months), 47.7% presented with disease progression and 17.8% experienced disease-related death. In 53.3% of the cases at least one molecular alteration (TERTp in 33.4%, BRAF in 24.5%, RAS in 8.9%) was detected. In the multivariate analysis, TERTp mutation was the factor associated with the highest risk (6 times) of having structural disease after initial therapy (p = 0.01), followed by vascular invasion (p = 0.02), gross extrathyroidal extension (ETE) (p = 0.02) and distant metastasis (p = 0.04). Regarding mutational status, only TERTp mutation was associated with disease progression, and diminished disease progression-free survival (PFS). The presence of distant metastasis, vascular invasion and gross ETE were significantly associated with the risk of disease progression. CONCLUSIONS: TERTp mutation appears be an indicator of both persistence and progression of structural disease after initial therapy in aggressive variants of TCDFC, and associates with a shorter progression free survival regardless of the therapy employed.

Temporal arachnoid cysts: are they congenital?

CASE REPORT: The authors report two cases of arachnoid cysts (ACs) neither detected during pregnancy nor shortly after birth when newborns underwent CT scan evaluation after birth head trauma. ACs were diagnosed at 10 months and 6 years, respectively. The first one becomes symptomatic, and the other one was incidentally found during a head trauma investigation. DISCUSSION: These cases give support for the postnatal pathogenesis for some of the assumed congenital ACs. We collected data from the literature that supports the acquired hypothesis for ACs.

Geographical Analysis for Detecting High-Risk Areas for Bovine/Human Rabies Transmitted by the Common Hematophagous Bat in the Amazon Region, Brazil.

BACKGROUND: The common hematophagous bat, Desmodus rotundus, is one of the main wild reservoirs of rabies virus in several regions in Latin America. New production practices and changed land use have provided environmental features that have been very favorable for D. rotundus bat populations, making this species the main transmitter of rabies in the cycle that involves humans and herbivores. In the Amazon region, these features include a mosaic of environmental, social, and economic components, which together creates areas with different levels of risk for human and bovine infections, as presented in this work in the eastern Brazilian Amazon. METHODOLOGY: We geo-referenced a total of 175 cases of rabies, of which 88% occurred in bovines and 12% in humans, respectively, and related these cases to a number of different geographical and biological variables. The spatial distribution was analyzed using the Kernel function, while the association with independent variables was assessed using a multi-criterion Analytical Hierarchy Process (AHP) technique. FINDINGS: The spatiotemporal analysis of the occurrence of rabies in bovines and humans found reduction in the number of cases in the eastern state of Pará, where no more cases were recorded in humans, whereas high infection rates were recorded in bovines in the northeastern part of the state, and low rates in the southeast. The areas of highest risk for bovine rabies are found in the proximity of rivers and highways. In the case of human rabies, the highest concentration of high-risk areas was found where the highway network coincides with high densities of rural and indigenous populations. CONCLUSION: The high-risk areas for human and bovine rabies are patchily distributed, and related to extensive deforested areas, large herds of cattle, and the presence of highways. These findings provide an important database for the generation of epidemiological models that could support the development of effective prevention measures and controls.

Immunohistochemical expression of cyclin D1 is higher in supratentorial ependymomas and predicts relapses in gross total resection cases.

Ependymomas are tumors of the CNS. Although cyclin D1 overexpression has been related to several cancers, its prognostic value in ependymomas has not yet been fully established. We evaluated cyclin D1 expression by an immunohistochemistry analysis of 149 samples of ependymomas, including some relapses, corresponding to 121 patients. Eighty-one patients were adults, 60 were intracranial cases and 92 tumors were grade II. Gross total resection (GTR) was achieved in 62% of cases, and relapse was confirmed in 41.4% of cases. Cyclin D1 protein expression was analyzed by immunohistochemistry and scored with a labeling index (LI) calculated as the percentage of positively stained cells by intensity. We also analyzed expression of CCND1 and NOTCH1 in 33 samples of ependymoma by quantitative real-time PCR. A correlation between cyclin D1 LI score and anaplastic cases (P < 0.001), supratentorial location (P < 0.001) and age (P = 0.001) were observed. A stratified analysis demonstrated that cyclin D1 protein expression was strong in tumors with a supratentorial location, independent of the histological grade or age. Relapse was more frequent in cases with a higher cyclin D1 LI score (P = 0.046), and correlation with progression-free survival was observed in cases with GTR (P = 0.002). Only spinal canal tumor location and GTR were suggestive markers of PFS in multivarite analyses. Higher expression levels were observed in anaplastic cases for CCND1 (P = 0.002), in supratentorial cases for CCND1 (P = 0.008) and NOTCH1 (P = 0.011). There were correlations between the cyclin D1 mRNA and protein expression levels (P < 0.0001) and between CCND1 and NOTCH1 expression levels (P = 0.003). Higher cyclin D1 LI was predominant in supratentorial location and predict relapse in GTR cases. Cyclin D1 could be used as an immunohistochemical marker to guide follow-up and treatment in these cases.

Enhancing vascular relaxing effects of nitric oxide-donor ruthenium complexes.

Ruthenium-derived complexes have emerged as new nitric oxide (NO) donors that may help circumvent the NO deficiency that impairs vasodilation. NO in vessels can be produced by the endothelial cells and/or released by NO donors. NO interacts with soluble guanylyl-cyclase to produce cGMP to activate the kinase-G pathway. As a result, conductance arteries, veins and resistance arteries dilate, whereas the cytosolic Ca(2+) levels in the smooth muscle cells decrease. NO also reacts with oxygen or the superoxide anion, to generate reactive oxygen species that modulate NO-induced vasodilation. In this article, we focus on NO production by NO synthase and discuss the vascular changes taking place during hypertension originating from endothelial dysfunction. We will describe how the NO released from ruthenium-derived complexes enhances the vascular effects arising from failed NO generation or lack of NO bioavailability. In addition, how ruthenium-derived NO donors induce the hypotensive effect by vasodilation is also discussed.

Phylogeography of the dark fruit-eating bat Artibeus obscurus in the Brazilian Amazon.

Artibeus obscurus (Mammalia: Chiroptera) is endemic to South America, being found in at least 18 Brazilian states. Recent studies revealed that different populations of this genus present distinct phylogeographic patterns; however, very little is known on the population genetics structure of A. obscurus in the Amazon rainforest. Here, using a fragment (1010bp) of the mitochondrial gene cytochrome b from 87 samples, we investigated patterns of genetic divergence among populations of A. obscurus from different locations in the Brazilian Amazon rainforest and compared them with other Brazilian and South American regions. Analysis of molecular variance (AMOVA), fixation index (Fst) analysis, and phylogeographic patterns showed divergence between two major monophyletic groups, each one corresponding to a geographic region associated with the Atlantic and Amazon forest biomes. The Atlantic forest clusters formed a monophyletic group with a high bootstrap support and a fragmented distribution that follows the pattern predicted by the Refuge Theory. On the other hand, a different scenario was observed for the Amazon forest, where no fragmentation was identified. The AMOVA results revealed a significant geographic heterogeneity in the distribution of genetic variation, with 70% found within populations across the studied populations (Fst values ranging from 0.05864 to 0.09673; φST = 0.55). The intrapopulational analysis revealed that one population (Bragança) showed significant evidence of population expansion, with the formation of 2 distinct phylogroups, suggesting the occurrence of a subspecies or at least a different population in this region. These results also suggest considerable heterogeneity for A. obscurus in the Amazon region.

Yerba mate (Ilex paraguariensis) enhances the gene modulation and activity of paraoxonase-2: in vitro and in vivo studies.

OBJECTIVE: Paraoxonase-2 (PON-2) is an intracellular antioxidant enzyme that can be modulated by polyphenols. The aim of this study was to verify whether yerba mate (Ilex paraguariensis), a plant species rich in phenolic compounds, modulates gene expression and the activity of PON-2 in macrophages in vitro and in monocytes from peripheral blood and monocyte-derived macrophages obtained after the ingestion of green or roasted yerba mate infusions by healthy subjects. METHODS: THP-1 macrophages were incubated with increasing amounts of yerba mate extracts or chlorogenic and caffeic acids (1-10 µmol/L). The in vivo effects of yerba mate or water (control) intakes were evaluated acutely (2 h after ingestion) and in the short term (after daily ingestion for 7 d) in 20 healthy women. RESULTS: In general, there was no difference between the two kinds of yerba mate studied. Yerba mate extracts or chlorogenic acid at 1 and 3 µmol/L increased PON-2 relative gene expression in THP-1 macrophages (P < 0.05), whereas higher concentrations (5 and 10 µmol/L) increased the activity only. Caffeic acid induced PON-2 activity only. The acute ingestion of yerba mate infusions increased relative gene expression and PON-2 activity in monocytes (P < 0.05), whereas the consumption of yerba mate for 7 d increased PON-2 relative gene expression (P < 0.05) and had a tendency to increase PON-2 activity in monocytes and monocyte-derived macrophages. CONCLUSION: It is suggested that green or roasted yerba mate modulates positively the mRNA relative expression and activity of the PON-2 enzyme in monocytes and macrophages, which may prevent cellular oxidative stress.