Pancreatic cancer clusters and arsenic-contaminated drinking water wells in Florida

This is the final version of the article. Available from BioMed Central via the DOI in this record.BACKGROUND: We sought to identify high-risk areas of pancreatic cancer incidence, and determine if clusters of persons diagnosed with pancreatic cancer were more likely to be located near arsenic-contaminated drinking water wells. METHODS: A total of 5,707 arsenic samples were collected from December 2000 to May 2008 by the Florida Department of Health, representing more than 5,000 individual privately owned wells. During that period, 0.010 ppm (10 ppb) or greater arsenic levels in private well water were considered as the threshold based on standard of United States Environmental Protection Agency (EPA). Spatial modeling was applied to pancreatic cancer cases diagnosed between 1998-2002 in Florida (n = 11,405). Multivariable logistic regression was used to determine if sociodemographic indicators, smoking history, and proximity to arsenic-contaminated well sites were associated with residence at the time of pancreatic cancer diagnosis occurring within versus outside a cluster. RESULTS: Spatial modeling identified 16 clusters in which 22.6% of all pancreatic cancer cases were located. Cases living within 1 mile of known arsenic-contaminated wells were significantly more likely to be diagnosed within a cluster of pancreatic cancers relative to cases living more than 3 miles from known sites (odds ratio = 2.1 [95% CI = 1.9, 2.4]). CONCLUSIONS: Exposure to arsenic-contaminated drinking water wells may be associated with an increased risk of pancreatic cancer. However, case-control studies are needed in order to confirm the findings of this ecological analysis. These cluster areas may be appropriate to evaluate pancreatic cancer risk factors, and to perform targeted screening and prevention studies.The project was supported by grants from the James and Esther King Biomedical Research Foundation (#06TSP); the Bankhead-Coley Cancer Research Program (#1BG06-341963, #08BN-03), the Florida Department of Health (FDOH); the CDC National Program of Cancer Registries (CDC NPCR); and the European Union ERDF funding (University of Exeter)

Dose-dependent effects of Allopurinol on human foreskin fibroblast cell and human umbilical vein endothelial cell under hypoxia

Allopurinol, an inhibitor of xanthine oxidase, has been used in clinical trials of patients with cardiovascular and chronic kidney disease. These are two pathologies with extensive links to hypoxia and activation of the transcription factor hypoxia inducible factor (HIF) family. Here we analysed the effects of allopurinol treatment in two different cellular models, and their response to hypoxia. We explored the dose-dependent effect of allopurinol on Human Foreskin Fibroblasts (HFF) and Human Umbilical Vein Endothelial Cells (HUVEC) under hypoxia and normoxia. Under normoxia and hypoxia, high dose allopurinol reduced the accumulation of HIF-1α protein in HFF and HUVEC cells. Allopurinol had only marginal effects on HIF-1α mRNA level in both cellular systems. Interestingly, allopurinol effects over the HIF system were independent of prolyl-hydroxylase activity. Finally, allopurinol treatment reduced angiogenesis traits in HUVEC cells in an in vitro model. Taken together these results indicate that high doses of allopurinol inhibits the HIF system and pro-angiogenic traits in cells

The Portuguese Severe Asthma Registry: Development, Features, and Data Sharing Policies

The Portuguese Severe Asthma Registry (Registo de Asma Grave Portugal, RAG) was developed by an open collaborative network of asthma specialists. RAG collects data from adults and pediatric severe asthma patients that despite treatment optimization and adequate management of comorbidities require step 4/5 treatment according to GINA recommendations. In this paper, we describe the development and implementation of RAG, its features, and data sharing policies. The contents and structure of RAG were defined in a multistep consensus process. A pilot version was pretested and iteratively improved. The selection of data elements for RAG considered other severe asthma registries, aiming at characterizing the patient's clinical status whilst avoiding overloading the standard workflow of the clinical appointment. Features of RAG include automatic assessment of eligibility, easy data input, and exportable data in natural language that can be pasted directly in patients' electronic health record and security features to enable data sharing (among researchers and with other international databases) without compromising patients' confidentiality. RAG is a national web-based disease registry of severe asthma patients, available at asmagrave.pt. It allows prospective clinical data collection, promotes standardized care and collaborative clinical research, and may contribute to inform evidence-based healthcare policies for severe asthma.info:eu-repo/semantics/publishedVersio

Determination and Validation of Nimesulide in Pharmaceutical Formulation by Near Infrared Spectroscopy

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)The determination of nimesulide in pharmaceutical formulation in the range of 10.38 to 39.47% m/m using near infrared spectroscopy and multivariate calibration based on partial least squares (PLS) and net analyte signal (NAS) was studied and validated by establishing its figures of merit. Suitable results were obtained, with limit of detection of 0.61%, limit quantification of 2.03%, accuracy estimated as root mean square error of prediction (RMSEP) of 1.05%, mean selectivity of 0.006, sensitivity of 0.004%, inverse analytical sensitivity of (0.20%)(-1) and signal-to-noise ratio of 181. In addition, it was obtained relative errors lower than 10% that are acceptable values for quality control of this drug. These results indicate that the proposed method can be used in pharmaceutical industries as an alternative to standard analytical procedures.211019291936Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)International Institute of Pharmaceutical Researches (IIPF)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Angeítis primaria del sistema nervioso central: una forma de presentación poco habitual

INTRODUCTION: Primary angiitis of the central nervous system (CNS) is a rare disease. Clinical signs and symptoms include headache and cognitive disorders associated to multifocal neurological deficits. A definitive diagnosis can only be achieved by means of a cerebromeningeal biopsy. CASE REPORT: We describe the case of a 15-year-old male who first reported lower back pain and progressive paresis of the right lower limb, later followed by laterocollis on the right side. Magnetic resonance (MR) scanning of the brain and spinal cord revealed a pseudotumoral lesion in the right cerebellum and two lesions in the spinal cord. Dexamethasone was administered and surgical resection of the cerebellar lesion was performed. Following surgery, the patient received corticoid treatment with progressive withdrawal. Full clinical recovery of the patient was achieved. A year later, the same patient was admitted to hospital again because of headaches and diplopia. A new MR brain scan showed a right frontotemporal lesion. Dexamethasone was administered and the patient recovered. Thirteen months later, he reported dysarthria and right-side hemiparesis. An MR brain scan revealed the presence of a number of bilateral lesions in the white matter. Results of a lumbar puncture showed lymphocytic pleocytosis and raised protein levels in cerebrospinal fluid. The laminae from the cerebromeningeal biopsy were reviewed and the results confirmed the hypothetical diagnosis of angiitis of the CNS. Treatment was established with intravenous cyclophosphamide in association with oral prednisone. CONCLUSIONS: Primary angiitis of the CNS is an infrequent disease and its pathogenesis remains unknown. The definitive diagnosis of these patients is histological. It courses spontaneously and generally has a fatal outcome. Treatment, which consists in an association of cyclophosphamide and prednisone, must be started as early as possible

Age differences in the use of implicit visual cues in a response time task

Background: Many activities require a complex interrelationship between a performer and stimuli available in the environment without explicit perception, but many aspects regarding developmental changes in the use of implicit cues remain unknown. Aim: To investigate the use of implicit visual precueing presented at different time intervals in children, adolescents, and adults. Method: Seventy-two people, male and female, constituted four age groups: 8-, 10- and 12-year-olds and adults. Participants performed 32 trials, four-choice-time task across four conditions: no precue and a 43 ms centralized dot appearing in the stimulus circle at 43, 86 or 129 ms prior the stimulus. Response times were obtained for each trial and pooled into each condition. Results: Response times for 8-year-olds were longer than for 12-year-olds and adults and for 10-year-olds were longer than for adults. Response times were longer in the no precue condition compared to when precues were presented at 86 and 129 ms before the stimulus. Response times were longer when precue was presented at 43 ms compared presented at 129 ms before the stimulus. Interpretation: Implicit precues reduce response time in children, adolescents and adults, but young children benefit less from implicit precues than adolescents and adults.</jats:p

Effects of physical exercise in biochemical parameters and dorsolateral prostate lesions: data from a rat model of prostate cancer

Background: Prostate cancer (PCa) is among the most prevalent cancers worldwide. Physical exercise is widely recognized due to its beneficial effects. This study aimed to evaluate the effects of physical exercise on biochemical pa- rameters and in dorsolateral prostate lesions in a rat model of PCa. Materials and Methods: Ninety-five male Wistar Unilever rats were randomly divided into eight groups sacrificed at 35 (groups I) or 61 weeks of age (groups II): control sedentary groups (Cont+Sed I (n = 10); Cont+Sed II (n = 10)); induced sedentary group (PCa+Sed I (n = 10); PCa+Sed II (n = 15)); control exercised groups (Cont+EX I (n = 10); Cont+EX II (n = 10)) and induced exercised groups (PCa+EX I (n = 10); PCa+EX II (n = 20)). All procedures were approved (DGAV, no. 021326). Animals from exercised groups started the exer- cise program in a treadmill at 8 weeks of age, for 28 weeks or 53 weeks. The animals were trained 5 days/week, 60 min per day. Prostate lesions were induced at 12 weeks of age, with sequential administration of flutamide, testosterone propion- ate and N-methyl-N-nitrosourea, and subcutaneous implants of crystalline testosterone. Animals were sacrificed at 35 or 61 weeks of age. Peripheral blood of all animals was col- lected by intracardiac puncture. A complete necropsy was performed. The dorsolateral prostate tissues sections were processed for histological analysis. Data were analysed using SPSS 25. p 0.05). Dorsolateral prostate lesions were classified as dysplasia, prostatic intraep- ithelial neoplasia (PIN) and microinvasive carcinoma. The number of prostate lesions was higher in animals from groups II than in those from groups I, mainly in PCa+Sed II animals when compared with PCa+Sed I (p 0.05). Conclusions: Overall, the animals sacrificed at 61 weeks of age developed more dorsolateral prostate lesions than ani- mals sacrificed at 35 weeks of age, which may be related to a longer testosterone exposure

Parameter estimation of the kinetic α-Pinene isomerization model using the MCSfilter algorithm

This paper aims to illustrate the application of a derivative-free multistart algorithm with coordinate search filter, designated as the MCSFilter algorithm. The problem used in this study is the parameter estimation problem of the kinetic α -pinene isomerization model. This is a well known nonlinear optimization problem (NLP) that has been investigated as a case study for performance testing of most derivative based methods proposed in the literature. Since the MCSFilter algorithm features a stochastic component, it was run ten times to solve the NLP problem. The optimization problem was successfully solved in all the runs and the optimal solution demonstrates that the MCSFilter provides a good quality solution.(undefined)info:eu-repo/semantics/publishedVersio