O papel das proteínas da matriz extracelular e das metaloproteinases em carcinomas de cabeça e pescoço: uma atualização bibliográfica

Interações entre células neoplásicas e constituintes da matriz extracelular (MEC) interferem fortemente no desenvolvimento tumoral, incluindo os localizados em cabeça e pescoço, pois influenciam a proliferação e sobrevivência celular, bem como a sua capacidade de migrar do sítio primário para outros tecidos e formar metástases. Essa migração celular é facilitada pela destruição parcial da MEC, a qual é realizada pelas metaloproteinases (MMPs), que representam uma família de mais de vinte endopeptidases, com atividade controlada pela expressão de inibidores específicos (TIMPs). Diversos estudos utilizando-se de marcadores para constituintes da MEC bem como pelas MMPs têm fornecido informações adicionais sobre o diagnóstico e prognóstico em carcinomas de cabeça e pescoço. Nesta revisão consideraremos o papel da MEC e das MMPs na progressão desses tumores, enfatizando que não somente a degradação proteolítica está envolvida neste processo, como também interações entre vários constituintes da MEC fornecem substrato para regulação e crescimento destes tumores.

Avaliação de fatores demográficos e estadiamento clínico nos pacientes submetidos a resgate cirúrgico por carcinomas epidermóides de orofaringe

O tratamento clássico do carcinoma epidermóide das vias aéreas digestivas superiores (VADS) é a cirurgia, associada ou não à radioterapia pós-operatória. As recidivas loco-regionais constituem a principal falha no tratamento inicial e o diagnóstico precoce favorece a indicação de cirurgia de resgate. OBJETIVO: Análise descritiva dos dados demográficos e de estadiamento no resgate cirúrgico dos tumores de orofaringe. CASUÍSTICO E MÉTODOS: Estudo retrospectivo de 78 pacientes, submetidos à cirurgia em todos os casos e a radioterapia complementar em 37 destes. RESULTADOS: Predomínio do gênero masculino em 70 casos, com idade média de 54,2 anos e etnia branca em 54 pacientes. O pacientes foram estadiados em T3 e T4 em 38 casos. Dos 78 pacientes, 40 eram pescoço N0. Trinta e cinco pacientes desenvolveram recidiva loco-regional e à distância. Das recidivas loco-regionais, 17 deles foram submetidos ao resgate cirúrgico, sendo que 12 pacientes foram reestadiados na recidiva em T1; 2 em T2 e quanto ao N, 2 eram N2a e 2 eram N2b. A idade média dos pacientes submetidos ao resgate foi de 52,8 anos, com predomínio na etnia branca e gênero masculino. CONCLUSÃO: O resgate predominou em estádios I e II com controle da doença em 58,8%.

Valor prognóstico da correlação imunoistoquímica do Ki-67 e p53 em carcinomas epidermóides da laringe

Os fatores prognósticos histológicos podem colaborar para determinar a evolução desta neoplasia. OBJETIVO: Correlacionar a expressão imunoistoquímica do p53 e Ki-67 com idade, grau histológico, comprometimento de linfonodos e estadiamento patológico de pacientes com carcinomas epidermóides de laringe. MÉTODO: Foram avaliados trinta casos consecutivos de carcinomas epidermóides de laringe, submetidos à técnica de imunoistoquímica para verificar a expressão dos anticorpos p53 e Ki-67. RESULTADO: A idade média foi de 56,2 anos e a imunoexpressão dos marcadores foi mais observada no grupo com mais de 50 anos de idade, especialmente a do anticorpo Ki-67 (p=0,032). Não houve relação do p53 e Ki-67 com o comprometimento de linfonodos. O Ki-67 se expressou em 70% nos casos de alto grau histológico e 80% nos de baixo, enquanto o p53 em 70% apenas nos de alto grau. O estadiamento patológico mostrou que no grupo dos carcinomas avançados a expressão do p53 foi de 61,5%, enquanto o Ki-67 mostrou positividade para os casos precoces (100%) e avançados (73,1%). CONCLUSÃO: Não houve diferenças significantes entre a imunoexpressão do p53 e do Ki-67 em carcinomas epidermóides de laringe, exceto no grupo de pacientes com mais de 50 anos, onde a expressão do Ki-67 foi significativamente maior.

El efecto de la triple hélice en los resultados de innovación

La innovación está relacionada con el crecimiento de las economías y de las empresas, y en un entorno cambiante como el actual, se presenta como una herramienta fundamental para conseguir ventajas competitivas. Esta investigación tiene por objetivo analizar la relación existente entre la capacidad de innovación de las empresas y la obtención de información de las mismas a través de la cooperación con competidores, proveedores, Universidades y otras instituciones públicas (Triple Hélice). En primer lugar se desarrolla una revisión bibliográfica de los conceptos relacionados para posteriormente, a través del método de ecuaciones estructurales, dar respuesta y aceptar la hipótesis propuesta que pone de manifiesto la relación existente entre los resultados de innovación de las empresas y la información obtenida de la Triple Hélice. La investigación se realiza con una muestra de empresas españolas, encuestadas por el Instituto Nacional de Estadística (INE), durante los años 2008-2010.

Multi-stage evolution of a sub-aerial volcanic ridge over the last 1.3 Myr: S. Jorge Island, Azores Triple Junction

New K/Ar dating and geochemical analyses have been carried out on the WNW-ESE elongated oceanic island of S. Jorge to reconstruct the volcanic evolution of a linear ridge developed close to the Azores triple junction. We show that S. Jorge sub-aerial construction encompasses the last 1.3 Myr, a time interval far much longer than previously reported. The early development of the ridge involved a sub-aerial building phase exposed in the southeast end of the island and now constrained between 1.32 +/- 0.02 and 1.21 +/- 0.02 Ma. Basic lavas from this older stage are alkaline and enriched in incompatible elements, reflecting partial melting of an enriched mantle source. At least three differentiation cycles from alkaline basalts to mugearites are documented within this stage. The successive episodes of magma rising, storage and evolution suggest an intermittent reopening of the magma feeding system, possibly due to recurrent tensional or trans-tensional tectonic events. Present data show a gap in sub-aerial volcanism before a second main ongoing building phase starting at about 750 ka. Sub-aerial construction of the S. Jorge ridge migrated progressively towards the west, but involved several overlapping volcanic episodes constrained along the main WNW-ESE structural axis of the island. Malic magmas erupted during the second phase have been also generated by partial melting of an enriched mantle source. Trace element data suggest, however, variable and lower degrees of partial melting of a shallower mantle domain, which is interpreted as an increasing control of lithospheric deformation on the genesis and extraction of primitive melts during the last 750 kyr. The multi-stage development of the S. Jorge volcanic ridge over the last 1.3 Myr has most likely been greatly influenced by regional tectonics, controlled by deformation along the diffuse boundary between the Nubian and the Eurasian plates, and the increasing effect of sea-floor spreading at the Mid-Atlantic Ridge.

Negative modulation of human osteoclastogenesis by antiepileptic drugs

Bone is constantly being molded and shaped by the action of osteoclasts and osteoblasts. A proper equilibrium between both cell types metabolic activities is required to ensure an adequate skeletal tissue structure, and it involves resorption of old bone and formation of new bone tissue. It is reported that treatment with antiepileptic drugs (AEDs) can elicit alterations in skeletal structure, in particular in bone mineral density. Nevertheless, the knowledge regarding the effects of AEDs on bone cells are still scarce, particularly on osteoclastic behaviour. In this context, the aim of this study was to investigate the effects of five different AEDs on human osteoclastic cells. Osteoclastic cell cultures were established from precursor cells isolated from human peripheral blood, and were maintained in the absence (control) or in the presence of 10-8-10-4 M of different AEDs (valproate, carbamazepine, gabapentin, lamotrigine and topiramate). Cell cultures were characterized throughout a 21-day period for tartrate-resistant acid phosphatase (TRAP) activity, number of TRAP+ multinucleated cells, presence of cells with actin rings and expressing vitronectin and calcitonin receptors, and apoptosis rate. Also, the involvement of several signaling pathways on the cellular response was addressed. All the tested drugs were able to affect osteoclastic cell development, although with different profiles on their osteoclastogenic modulation properties. Globally, the tendency was to inhibit the process. Furthermore, the signaling pathways involved in the process also seemed to be differentially affected by the AEDs, suggesting that the different drugs may affect osteoclastogenesis through different mechanisms. In conclusion, the present study showed that the different AEDs had the ability to negatively modulate the osteoclastogenesis process, shedding new light towards a better understanding of how these drugs can affect bone tissue.

OsRMC, a negative regulator of salt stress response in rice, is regulated by two AP2/ERF transcription factors

High salinity causes remarkable losses in rice productivity worldwide mainly because it inhibits growth and reduces grain yield. To cope with environmental changes, plants evolved several adaptive mechanisms, which involve the regulation of many stress-responsive genes. Among these, we have chosen OsRMC to study its transcriptional regulation in rice seedlings subjected to high salinity. Its transcription was highly induced by salt treatment and showed a stress-dose-dependent pattern. OsRMC encodes a receptor-like kinase described as a negative regulator of salt stress responses in rice. To investigate how OsRMC is regulated in response to high salinity, a salt-induced rice cDNA expression library was constructed and subsequently screened using the yeast one-hybrid system and the OsRMC promoter as bait. Thereby, two transcription factors (TFs), OsEREBP1 and OsEREBP2, belonging to the AP2/ERF family were identified. Both TFs were shown to bind to the same GCC-like DNA motif in OsRMC promoter and to negatively regulate its gene expression. The identified TFs were characterized regarding their gene expression under different abiotic stress conditions. This study revealed that OsEREBP1 transcript level is not significantly affected by salt, ABA or severe cold (5 °C) and is only slightly regulated by drought and moderate cold. On the other hand, the OsEREBP2 transcript level increased after cold, ABA, drought and high salinity treatments, indicating that OsEREBP2 may play a central role mediating the response to different abiotic stresses. Gene expression analysis in rice varieties with contrasting salt tolerance further suggests that OsEREBP2 is involved in salt stress response in rice.

Framework de controlo de acessos para Triple-stores com interface Sail API

Grande parte dos triples-stores são open source e desenvolvidos em Java, disponibilizando interfaces standards e privadas de acesso. A grande maioria destes sistemas não dispõe de mecanismos de controlo de acessos nativos, o que dificulta ou impossibilita a sua adopção em ambientes em que a segurança dos factos é importante (e.g. ambiente empresarial). Complementarmente observa-se que o modelo de controlo de acesso a triplos e em particular a triplos descritos por ontologias não está standardizado nem sequer estabilizado, havendo diversos modelos de descrição e algoritmos de avaliação de permissões de acesso. O trabalho desenvolvido nesta tese/dissertação propõe um modelo e interface de controlo de acesso que permite e facilite a sua adopção por diferentes triple-stores já existentes e a integração dos triples-stores com outros sistemas já existentes na organização. Complementarmente, a plataforma de controlo de acesso não impõe qualquer modelo ou algoritmo de avaliação de permissões, mas pelo contrário permite a adopção de modelos e algoritmos distintos em função das necessidades ou desejos. Finalmente demonstra-se a aplicabilidade e validade do modelo e interface propostos, através da sua implementação e adopção ao triple-store SwiftOWLIM já existente, que não dispõe de mecanismo de controlo de acessos nativo.

Use of negative information in positioning and tracking algorithms

To avoid additional hardware deployment, indoor localization systems have to be designed in such a way that they rely on existing infrastructure only. Besides the processing of measurements between nodes, localization procedure can include the information of all available environment information. In order to enhance the performance of Wi-Fi based localization systems, the innovative solution presented in this paper considers also the negative information. An indoor tracking method inspired by Kalman filtering is also proposed.

Incremental yield of bronchial washing for diagnosing smear-negative pulmonary tuberculosis

OBJECTIVE To assess the increased diagnostic yield for pulmonary tuberculosis using bronchial washing cultures compared with sputum cultures. METHODS Study conducted with 61 adults in Lima, Peru, from January 2006 to December 2007. The yield of sputum cultures was compared with the yield of acid-fast bacilli smears and cultures of bronchial washing for diagnosing pulmonary tuberculosis in suspected cases of clinical tuberculosis with negative acid fast bacilli sputum smears. RESULTS Twenty seven (95%CI 32;58) of the cases were eventually diagnosed with smear-negative pulmonary tuberculosis. Bronchial washing samples detected 23 (95%CI 72;99) of the smear-negative pulmonary tuberculosis cases compared with 15 (95%CI 37;74) for sputum cultures (p = 0.02). The incremental diagnostic yield of acid fast bacilli smear and culture of bronchial washing specimens over sputum culture was 44% (95%CI 25;65). CONCLUSIONS In function of the epidemiological context and the resources available, bronchoscopy should be deployed as part of a comprehensive work up that optimizes smear-negative pulmonary tuberculosis diagnosis and minimizes risk and costs.

Predictors of infant positive, negative and self-direct coping during face to face still-face in a Portuguese preterm sample

Past studies found three types of infant coping behaviour during Face-to-Face Still-Face paradigm (FFSF): a Positive Other-Directed Coping; a Negative Other-Directed Coping and a Self-Directed Coping. In the present study, we investigated whether those types of coping styles are predicted by: infants’ physiological responses; maternal representations of their infant’s temperament; maternal interactive behaviour in free play; and infant birth and medical status. The sample consisted of 46, healthy, prematurely born infants and their mothers. At one month, infant heart rate was collected in basal. At three months old (corrected age), infant heart-rate was registered during FFSF episodes. Mothers described their infants’ temperament using a validated Portuguese temperament scale, at infants three months of corrected age. As well, maternal interactive behaviour was evaluated during a free play situation using CARE-Index. Our findings indicate that positive coping behaviours were correlated with gestational birth weight, heart rate (HR), gestational age, and maternal sensitivity in free play. Gestational age and maternal sensitivity predicted Positive Other-Direct Coping behaviours. Moreover, Positive Other-Direct coping was negatively correlated with HR during Still-Face Episode. Self-directed behaviours were correlated with HR during Still-Face Episode and Recover Episode and with maternal controlling/intrusive behaviour. However, only maternal behaviour predicted Self-direct coping. Early social responses seem to be affected by infants’ birth status and by maternal interactive behaviour. Therefore, internal and external factors together contribute to infant ability to cope and to re-engage after stressful social events.

Non-colorectal intestinal tract carcinomas in inflammatory bowel disease: results of the 3rd ECCO Pathogenesis Scientific Workshop (II)

Patients with inflammatory bowel diseases (IBD) have an excess risk of certain gastrointestinal cancers. Much work has focused on colon cancer in IBD patients, but comparatively less is known about other more rare cancers. The European Crohn's and Colitis Organization established a pathogenesis workshop to review what is known about these cancers and formulate proposals for future studies to address the most important knowledge gaps. This article reviews the current state of knowledge about small bowel adenocarcinoma, ileo-anal pouch and rectal cuff cancer, and anal/perianal fistula cancers in IBD patients.

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.

Detection of Toxoplasma gondii soluble antigen, SAG-1(p30), antibody and immune complex in the cerebrospinal fluid of HIV positive or negative individuals

Active infection by T. gondii was evaluated by immunoassay for soluble SAG-1 (p30), the major surface antigen from T. gondii, specific antibodies and immune complexes in human cerebrospinal fluid (CSF) samples. A total of 263 samples of CSF were collected from hospitalized patients presenting neurological disorders and analyzed for antibodies to HIV. Patients were divided into two groups: HIV positive (n = 96) or HIV negative (n =167). The results of the assays showed that 45% of all samples were positive for soluble SAG-1. Toxoplasma Ag/Ab immune complexes were detected in 19% of the CSF samples and 62% were positive for T. gondii- specific IgG. A combination of these assays in the presence of clinical findings consistent with active Toxoplasma infection may predict the presence of toxoplasmic encephalitis. Moreover, detection of soluble SAG-1 in the CSF of these individuals appears consistent with active infection.

Negative non-ground queries in well founded semantics

Dissertação apresentada na Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa para obtenção do grau de Mestre em Computational Logic