Thrombophilia screening: An artificial neural network approach

Thrombotic disorders have severe consequences for the patients and for the society in general, being one of the main causes of death. These facts reveal that it is extremely important to be preventive; being aware of how probable is to have that kind of syndrome. Indeed, this work will focus on the development of a decision support system that will cater for an individual risk evaluation with respect to the surge of thrombotic complaints. The Knowledge Representation and Reasoning procedures used will be based on an extension to the Logic Programming language, allowing the handling of incomplete and/or default data. The computational framework in place will be centered on Artificial Neural Networks.

In vitro screening of Amazonian plants for hemolytic activity and inhibition of platelet aggregation in human blood

In the present study, different aerial parts from twelve Amazonian plant species found in the National Institute for Amazon Research's (INPA's) Adolpho Ducke Forest Reserve (in Manaus, Amazonas, Brazil) were collected. Separate portions of dried, ground plant materials were extracted with water (by infusion), methanol and chloroform (by continuous liquid-solid extraction) and solvents were removed first by rotary evaporation, and finally by freeze-drying which yielded a total of seventy-one freeze-dried extracts for evaluation. These extracts were evaluated initially at concentrations of 500 and 100 µg/mL for in vitro hemolytic activity and in vitro inhibition of platelet aggregation in human blood, respectively. Sixteen extracts (23 % of all extracts tested, 42 % of all plant species), representing the following plants: Chaunochiton kappleri (Olacaceae), Diclinanona calycina (Annonaceae), Paypayrola grandiflora (Violaceae), Pleurisanthes parviflora (Icacinaceae), Sarcaulus brasiliensis (Sapotaceae), exhibited significant inhibitory activity towards human platelet aggregation. A group of extracts with antiplatelet aggregation activity having no in vitro hemolytic activity has therefore been identified. Three extracts (4 %), all derived from Elaeoluma nuda (Sapotaceae), exhibited hemolytic activity. None of the plant species in this study has known use in traditional medicine. So, these data serve as a baseline or minimum of antiplatelet and hemolytic activities (and potential usefulness) of non-medicinal plants from the Amazon forest. Finally, in general, these are the first data on hemolytic and inhibitory activity on platelet aggregation for the genera which these plant species represent.

Search for massive, long-lived particles using multitrack displaced vertices or displaced lepton pairs in pp collisions at s =8TeV with the ATLAS detector

Many extensions of the Standard Model posit the existence of heavy particles with long lifetimes. This article presents the results of a search for events containing at least one long-lived particle that decays at a significant distance from its production point into two leptons or into five or more charged particles. This analysis uses a data sample of proton-proton collisions at s√ = 8 TeV corresponding to an integrated luminosity of 20.3 fb−1 collected in 2012 by the ATLAS detector operating at the Large Hadron Collider. No events are observed in any of the signal regions, and limits are set on model parameters within supersymmetric scenarios involving R-parity violation, split supersymmetry, and gauge mediation. In some of the search channels, the trigger and search strategy are based only on the decay products of individual long-lived particles, irrespective of the rest of the event. In these cases, the provided limits can easily be reinterpreted in different scenarios.

The contribution of phenolic acids to the anti-inflammatory activity of mushrooms: Screening in phenolic extracts, individual parent molecules and synthesized glucuronated and methylated derivatives

In the present study, the ethanolic extracts of fourteen edible mushrooms were investigated for their anti-inflammatory potential in LPS (lipopolysaccharide) activated RAW 264.7 macrophages. Furthermore the extracts were chemically characterized in terms of phenolic acids and related compounds. The identified molecules (p-hydroxybenzoic, p-coumaric and cinnamic acids) and their glucuronated and methylated derivatives obtained by chemical synthesis were also evaluated for the same bioactivity, in order to establish structure-activity relationships and to comprehend the effects of in vivo metabolism reactions in the activity of the compounds. The extracts of Pleurotus ostreatus, Macrolepiota procera, Boletus impolitus and Agaricus bisporus revealed the strongest anti-inflammatory potential (EC50 values 96 ± 1 to 190 ± 6 µg/mL, and also the highest concentration of cinnamic acid (656 to 156 µg/g), which was also the individual compound with the highest anti-inflammatory activity. The derivatives of p-coumaric acid revealed the strongest properties, specially the derivative methylated in the carboxylic group (CoA-M1) that exhibited similar activity to the one showed by dexamethaxone used as anti-inflammatory standard; by contrast, the derivatives of p-hydroxybenzoic revealed the lowest inhibition of NO production. All in all, whereas the conjugation reactions change the chemical structure of phenolic acids and may increase or decrease their activity, the glucuronated and methylated derivatives of the studied compounds are still displaying anti-inflammatory activity.

Human papillomavirus (HPV) screening and cervical cancer burden. A Brazilian perspective

This review tackles the issues related to disease burden caused by cervical cancer (CC) and its precursor (CIN) lesions in Brazil. A special focus is given to new technologies with potential to interfere with the development of CC by reducing the high-risk human papillomavirus (hr-HPV)-induced lesions that remain a major public health burden in all developing countries where organized screening programs do not exist. Globally, 85 % of all incident CC and 50 % of CC deaths occur in the developing countries. Unfortunately, most regions of Brazil still demonstrate high mortality rates, ranking CC as the second most common cancer among Brazilian women. Recently, CC screening programs have been tailored in the country to enable early detection of CC precursor lesions and thereby reduce cancer mortality. A combination of HPV testing with liquid-based cytology (LBC) seems to be a promising new approach in CC screening, with high expectation to offer an adequate control of CC burden in this country.

HPV DNA testing with cytology triage in cervical cancer screening: Influence of revealing HPV infection status

BACKGROUND: Knowledge of cervical human papillomavirus (HPV) status might influence a cytotechnician's assessment of cellular abnormalities. The authors compared original cytotechnicians' Papanicolaou (Pap) readings for which HPV status was concealed with Pap rereads for which HPV status was revealed separately for 3 screening populations. METHODS: Previously collected cervical Pap smears and clinical data were obtained from the Canadian Cervical Cancer Screening Trial (study A), the Democratic Republic of Congo Community-Based Screening Study (study B), and the Brazilian Investigation into Nutrition and Cervical Cancer Prevention (study C). Smears were reread with knowledge of HPV status for all HPV-positive women as well as a sample of HPV-negative women. Diagnostic performance of Pap cytology was compared between original readings and rereads. RESULTS: A total of 1767 Pap tests were reread. Among 915 rereads for HPV-positive women, the contrast between "revealed" and "concealed" Pap readings demonstrated revisions from negative to positive results for 109 women (cutoff was atypical squamous cells of undetermined significance or worse) and 124 women (cutoff was low-grade squamous intraepithelial lesions [LSIL] or worse). For a disease threshold of cervical intraepithelial neoplasia of grade 2 or worse, specificity significantly declined at the atypical squamous cells of undetermined significance cutoff for studies A (86.6% to 75.3%) and C (42.5% to 15.5%), and at the LSIL cutoff for study C (61.9% to 37.6%). Sensitivity remained nearly unchanged between readings, except in study C, in which reread performance was superior (91.3% vs 71.9% for the LSIL cutoff). CONCLUSIONS: A reduction in the diagnostic accuracy of Pap cytology was observed when revealing patients' cervical HPV status, possibly due to a heightened awareness of potential abnormalities, which led to more false-positive results. Cancer (Cancer Cytopathol) 2015. (c) 2015 American Cancer Society.

Historical analysis of the Brazilian cervical cancer screening program from 2006 to 2013: a time for reflection

BACKGROUND: The Cervical Cancer Database of the Brazilian National Health Service (SISCOLO) contains information regarding all cervical cytological tests and, if properly explored, can be used as a tool for monitoring and managing the cervical cancer screening program. The aim of this study was to perform a historical analysis of the cervical cancer screening program in Brazil from 2006 to 2013. MATERIAL AND METHODS: The data necessary to calculate quality indicators were obtained from the SISCOLO, a Brazilian health system tool. Joinpoint analysis was used to calculate the annual percentage change. RESULTS: We observed important trends showing decreased rates of low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL) and an increased rate of rejected exams from 2009 to 2013. The index of positivity was maintained at levels below those indicated by international standards; very low frequencies of unsatisfactory cases were observed over the study period, which partially contradicts the low rate of positive cases. The number of positive cytological diagnoses was below that expected, considering that developed countries with low frequencies of cervical cancer detect more lesions annually. CONCLUSIONS: The evolution of indicators from 2006 to 2013 suggests that actions must be taken to improve the effectiveness of cervical cancer control in Brazil.

A novel hanging spherical drop system for the generation of cellular spheroids and high throughput combinatorial drug screening

We propose a novel hanging spherical drop system for anchoring arrays of droplets of cell suspension based on the use of biomimetic superhydrophobic flat substrates, with controlled positional adhesion and minimum contact with a solid substrate. By facing down the platform, it was possible to generate independent spheroid bodies in a high throughput manner, in order to mimic in vivo tumour models on the lab-on-chip scale. To validate this system for drug screening purposes, the toxicity of the anti-cancer drug doxorubicin in cell spheroids was tested and compared to cells in 2D culture. The advantages presented by this platform, such as feasibility of the system and the ability to control the size uniformity of the spheroid, emphasize its potential to be used as a new low cost toolbox for high-throughput drug screening and in cell or tissue engineering.

Endomyocardial fibrosis associated with massive calcification of the left ventricle

This is the report of a rare case of endomyocardial fibrosis associated with massive calcification of the left ventricle in a male patient with dyspnea on great exertion, which began 5 years earlier and rapidly evolved. Due to lack of information and the absence of clinical signs that could characterize impairment of other organs, the case was initially managed as a disease with a pulmonary origin. With the evolution of the disease and in the presence of radiological images of heterogeneous opacification in the projection of the left ventricle, the diagnostic hypothesis of endomyocardial disease was established. This hypothesis was later confirmed on chest computed tomography. The patient died on the 16th day of the hospital stay, probably because of lack of myocardial reserve, with clinical findings of refractory heart failure, possibly aggravated by pulmonary infection. This shows that a rare disease such as endomyocardial fibrosis associated with massive calcification of the left ventricle may be suspected on a simple chest X-ray and confirmed by computed tomography.

Zebrafish embryos as in vivo model for toxicity evaluation: screening of nanoparticle formulations DODAB:MO and DODAC:MO

Dissertação de mestrado em Molecular Genetics

Screening for depression and anxiety disorders from pregnancy to postpartum with the EPDS and STAI

The Edinburgh Postnatal Depression Scale (EPDS) and the State Anxiety Inventory (STAI-S) are widely used self-report measures that still need to be further validated for the perinatal period. The aim of this study was to examine the screening performance of the EPDS and the STAI-S in detecting depressive and anxiety disorders at pregnancy and postpartum. Women screening positive on EPDS (EPDS ≥ 9) or STAI-S (STAI-S ≥ 45) during pregnancy (n = 90), as well as matched controls (n = 58) were selected from a larger study. At 3 months postpartum, 99 of these women were reassessed. At a second stage, women were administered a clinical interview to establish a DSM-IV-TR diagnosis. Receiver operator characteristics (ROC) analysis yielded areas under the curve higher than .80 and .70 for EPDS and STAI-S, respectively. EPDS and STAI-S optimal cut-offs were found to be lower at postpartum (EDPS = 7; STAI-S = 34) than during pregnancy (EPDS = 9; STAI-S = 40). EPDS and STAI-S are reasonably valid screening tools during pregnancy and the postpartum.

Desarrollos estadísticos para el procesamiento de información genómica masiva en agro-biotecnología. Statistical developments for processing massive genomic information in agro-biotechnology.

Nuevas biotecnologías, como los marcadores de la molécula de ADN, permiten caracterizar el genoma vegetal. El uso de la información genómica producida para cientos o miles de posiciones cromosómicas permite identificar genotipos superiores en menos tiempo que el requerido por la selección fenotípica tradicional. La mayoría de los caracteres de las especies vegetales cultivadas de importancia agronómica y económica, son controlados por poli-genes causantes de un fenotipo con variación continua, altamente afectados por el ambiente. Su herencia es compleja ya que resulta de la interacción entre genes, del mismo o distinto cromosoma, y de la interacción del genotipo con el ambiente, dificultando la selección. Estas biotecnologías producen bases de datos con gran cantidad de información y estructuras complejas de correlación que requieren de métodos y modelos biométricos específicos para su procesamiento. Los modelos estadísticos focalizados en explicar el fenotipo a partir de información genómica masiva requieren la estimación de un gran número de parámetros. No existen métodos, dentro de la estadística paramétrica capaces de abordar este problema eficientemente. Además los modelos deben contemplar no-aditividades (interacciones) entre efectos génicos y de éstos con el ambiente que son también dificiles de manejar desde la concepción paramétrica. Se hipotetiza que el análisis de la asociación entre caracteres fenotípicos y genotipos moleculares, caracterizados por abundante información genómica, podría realizarse eficientemente en el contexto de los modelos mixtos semiparamétricos y/o de métodos no-paramétricos basados en técnicas de aprendizaje automático. El objetivo de este proyecto es desarrollar nuevos métodos para análisis de datos que permitan el uso eficiente de información genómica masiva en evaluaciones genéticas de interés agro-biotecnológico. Los objetivos específicos incluyen la comparación, respecto a propiedades estadísticas y computacionales, de estrategias analíticas paramétricas con estrategias semiparamétricas y no-paramétricas. Se trabajará con aproximaciones por regresión del análisis de loci de caracteres cuantitativos bajo distintas estrategias y escenarios (reales y simulados) con distinto volúmenes de datos de marcadores moleculares. En el área paramétrica se pondrá especial énfasis en modelos mixtos, mientras que en el área no paramétrica se evaluarán algoritmos de redes neuronales, máquinas de soporte vectorial, filtros multivariados, suavizados del tipo LOESS y métodos basados en núcleos de reciente aparición. La propuesta semiparamétrica se basará en una estrategia de análisis en dos etapas orientadas a: 1) reducir la dimensionalidad de los datos genómicos y 2) modelar el fenotipo introduciendo sólo las señales moleculares más significativas. Con este trabajo se espera poner a disposición de investigadores de nuestro medio, nuevas herramientas y procedimientos de análisis que permitan maximizar la eficiencia en el uso de los recursos asignados a la masiva captura de datos genómicos y su aplicación en desarrollos agro-biotecnológicos.

Screening for Fabry Disease in Left Ventricular Hypertrophy: Documentation of a Novel Mutation

AbstractBackground:Fabry disease is a lysosomal storage disease caused by enzyme α-galactosidase A deficiency as a result of mutations in the GLA gene. Cardiac involvement is characterized by progressive left ventricular hypertrophy.Objective:To estimate the prevalence of Fabry disease in a population with left ventricular hypertrophy.Methods:The patients were assessed for the presence of left ventricular hypertrophy defined as a left ventricular mass index ≥ 96 g/m2 for women or ≥ 116 g/m2 for men. Severe aortic stenosis and arterial hypertension with mild left ventricular hypertrophy were exclusion criteria. All patients included were assessed for enzyme α-galactosidase A activity using dry spot testing. Genetic study was performed whenever the enzyme activity was decreased.Results:A total of 47 patients with a mean left ventricular mass index of 141.1 g/m2 (± 28.5; 99.2 to 228.5 g/m2] were included. Most of the patients were females (51.1%). Nine (19.1%) showed decreased α-galactosidase A activity, but only one positive genetic test − [GLA] c.785G>T; p.W262L (exon 5), a mutation not previously described in the literature. This clinical investigation was able to establish the association between the mutation and the clinical presentation.Conclusion:In a population of patients with left ventricular hypertrophy, we documented a Fabry disease prevalence of 2.1%. This novel case was defined in the sequence of a mutation of unknown meaning in the GLA gene with further pathogenicity study. Thus, this study permitted the definition of a novel causal mutation for Fabry disease - [GLA] c.785G>T; p.W262L (exon 5).

Screening primary-care patients forgoing health care for economic reasons.

BACKGROUND: Growing social inequities have made it important for general practitioners to verify if patients can afford treatment and procedures. Incorporating social conditions into clinical decision-making allows general practitioners to address mismatches between patients' health-care needs and financial resources. OBJECTIVES: Identify a screening question to, indirectly, rule out patients' social risk of forgoing health care for economic reasons, and estimate prevalence of forgoing health care and the influence of physicians' attitudes toward deprivation. DESIGN: Multicenter cross-sectional survey. PARTICIPANTS: Forty-seven general practitioners working in the French-speaking part of Switzerland enrolled a random sample of patients attending their private practices. MAIN MEASURES: Patients who had forgone health care were defined as those reporting a household member (including themselves) having forgone treatment for economic reasons during the previous 12 months, through a self-administered questionnaire. Patients were also asked about education and income levels, self-perceived social position, and deprivation levels. KEY RESULTS: Overall, 2,026 patients were included in the analysis; 10.7% (CI95% 9.4-12.1) reported a member of their household to have forgone health care during the 12 previous months. The question "Did you have difficulties paying your household bills during the last 12 months" performed better in identifying patients at risk of forgoing health care than a combination of four objective measures of socio-economic status (gender, age, education level, and income) (R(2) = 0.184 vs. 0.083). This question effectively ruled out that patients had forgone health care, with a negative predictive value of 96%. Furthermore, for physicians who felt powerless in the face of deprivation, we observed an increase in the odds of patients forgoing health care of 1.5 times. CONCLUSION: General practitioners should systematically evaluate the socio-economic status of their patients. Asking patients whether they experience any difficulties in paying their bills is an effective means of identifying patients who might forgo health care.