Macrophages as biomarkers in BCG treatment response in bladder cancer

Bladder cancer is a common urologic cancer and the majority has origin in the urothelium. Patients with intermediate and high risk of recurrence/progression bladder cancer are treated with intravesical instillation with Bacillus Calmette-Guérin, however, approximately 30% of patients do not respond to treatment. At the moment, there are no accepted biomarkers do predict treatment outcome and an early identification of patients better served by alternative therapeutics. The treatment initiates a cascade of cytokines responsible by recruiting macrophages to the tumor site that have been shown to influence treatment outcome. Effective BCG therapy needs precise activation of the Th1 immune pathway associated with M1 polarized macrophages. However, tumor-associated macrophages (TAMs) often assume an immunoregulatory M2 phenotype, either immunosuppressive or angiogenic, that interfere in different ways with the BCG induced antitumor immune response. The M2 macrophage is influenced by different microenvironments in the stroma and the tumor. In particular, the degree of hypoxia in the tumors is responsible by the recruitment and differentiation of macrophages into the M2 angiogenic phenotype, suggested to be associated with the response to treatment. Nevertheless, neither the macrophage phenotypes present nor the influence of localization and hypoxia have been addressed in previous studies. Therefore, this work devoted to study the influence of TAMs, in particular of the M2 phenotype taking into account their localization (stroma or tumor) and the degree of hypoxia in the tumor (low or high) in BCG treatment outcome. The study included 99 bladder cancer patients treated with BCG. Tumors resected prior to treatment were evaluated using immunohistochemistry for CD68 and CD163 antigens, which identify a lineage macrophage marker and a M2-polarized specific cell surface receptor, respectively. Tumor hypoxia was evaluated based on HIF-1α expression. As a main finding it was observed that a high predominance of CD163+ macrophage counts in the stroma of tumors under low hypoxia was associated with BCG immunotherapy failure, possibly due to its immunosuppressive phenotype. This study further reinforces the importance the tumor microenvironment in the modulation of BCG responses.

Phonological and articulation treatment approaches in Portuguese children with speech and language impairments: a randomized controlled intervention study

Background: In Portugal, the routine clinical practice of speech and language therapists (SLTs) in treating children with all types of speech sound disorder (SSD) continues to be articulation therapy (AT). There is limited use of phonological therapy (PT) or phonological awareness training in Portugal. Additionally, at an international level there is a focus on collecting information on and differentiating between the effectiveness of PT and AT for children with different types of phonologically based SSD, as well as on the role of phonological awareness in remediating SSD. It is important to collect more evidence for the most effective and efficient type of intervention approach for different SSDs and for these data to be collected from diverse linguistic and cultural perspectives. Aims: To evaluate the effectiveness of a PT and AT approach for treatment of 14 Portuguese children, aged 4.0–6.7 years, with a phonologically based SSD. Methods & Procedures: The children were randomly assigned to one of the two treatment approaches (seven children in each group). All children were treated by the same SLT, blind to the aims of the study, over three blocks of a total of 25 weekly sessions of intervention. Outcome measures of phonological ability (percentage of consonants correct (PCC), percentage occurrence of different phonological processes and phonetic inventory) were taken before and after intervention. A qualitative assessment of intervention effectiveness from the perspective of the parents of participants was included. Outcomes & Results: Both treatments were effective in improving the participants’ speech, with the children receiving PT showing a more significant improvement in PCC score than those receiving the AT. Children in the PT group also showed greater generalization to untreated words than those receiving AT. Parents reported both intervention approaches to be as effective in improving their children’s speech. Conclusions & Implications: The PT (combination of expressive phonological tasks, phonological awareness, listening and discrimination activities) proved to be an effective integrated method of improving phonological SSD in children. These findings provide some evidence for Portuguese SLTs to employ PT with children with phonologically based SSD

Hearing evaluation of portuguese school communities: school‑based audiology and hearing screening

Introduction: Hearing loss h sone raised impact in the development and academic progress of a child. In several developed countries, early detection is part of the national health plan through universal neonatal hearing screening (UNHS) and also with school hearing screening programs (SHSP), but only a few have published national data and revised protocols. Currently in Portugal, the UNHS is implemented in the main district hospitals but not the SHPS, as well we still do not make use of concrete data nor publication of studies on the national reality. Objectives: The incidence of the hearing loss and of otological problems was studied in school communities in the north of the country with 2550 participants between 3 and 17 years old. Methods: Statistical data collected within the schools with a standard auditory hearing screening protocol. All participants were evaluated with the same protocol, an audiological anamnesis, otoscopy and audiometric exam screening (500, 1000, 2000 and 4000 Hz) were fulfilled. Results: Different otological problems were identified and the audiometric screening exam counted auditory thresholds that outpointed uni and bilateral hearing loss in about 5.7% of the cases. Conclusions: The study has demonstrated that auditory school screening should take place as early as possible and be part of the primary health care to identify and direct children to appropriate rehabilitation, education and attendance. Thus, reducing high costs with late treatment.

Demand for and availability of online support to stop smoking

OBJECTIVES: Estimate the frequency of online searches on the topic of smoking and analyze the quality of online resources available to smokers interested in giving up smoking. METHODS: Search engines were used to revise searches and online resources related to stopping smoking in Brazil in 2010. The number of searches was determined using analytical tools available on Google Ads; the number and type of sites were determined by replicating the search patterns of internet users. The sites were classified according to content (advertising, library of articles and other). The quality of the sites was analyzed using the Smoking Treatment Scale- Content (STS-C) and the Smoking Treatment Scale - Rating (STS-R). RESULTS: A total of 642,446 searches was carried out. Around a third of the 113 sites encountered were of the 'library' type, i.e. they only contained articles, followed by sites containing clinical advertising (18.6) and professional education (10.6). Thirteen of the sites offered advice on quitting directed at smokers. The majority of the sites did not contain evidence-based information, were not interactive and did not have the possibility of communicating with users after the first contact. Other limitations we came across were a lack of financial disclosure as well as no guarantee of privacy concerning information obtained and no distinction made between editorial content and advertisements. CONCLUSIONS: There is a disparity between the high demand for online support in giving up smoking and the scarcity of quality online resources for smokers. It is necessary to develop interactive, customized online resources based on evidence and random clinical testing in order to improve the support available to Brazilian smokers.

A web-based tool to evaluate the iterative processes of direct search methods

Constrained and unconstrained Nonlinear Optimization Problems often appear in many engineering areas. In some of these cases it is not possible to use derivative based optimization methods because the objective function is not known or it is too complex or the objective function is non-smooth. In these cases derivative based methods cannot be used and Direct Search Methods might be the most suitable optimization methods. An Application Programming Interface (API) including some of these methods was implemented using Java Technology. This API can be accessed either by applications running in the same computer where it is installed or, it can be remotely accessed through a LAN or the Internet, using webservices. From the engineering point of view, the information needed from the API is the solution for the provided problem. On the other hand, from the optimization methods researchers’ point of view, not only the solution for the problem is needed. Also additional information about the iterative process is useful, such as: the number of iterations; the value of the solution at each iteration; the stopping criteria, etc. In this paper are presented the features added to the API to allow users to access to the iterative process data.

Spatial analysis of the tuberculosis treatment dropout, Buenos Aires, Argentina

OBJECTIVE Identify spatial distribution patterns of the proportion of nonadherence to tuberculosis treatment and its associated factors.METHODS We conducted an ecological study based on secondary and primary data from municipalities of the metropolitan area of Buenos Aires, Argentina. An exploratory analysis of the characteristics of the area and the distributions of the cases included in the sample (proportion of nonadherence) was also carried out along with a multifactor analysis by linear regression. The variables related to the characteristics of the population, residences and families were analyzed.RESULTS Areas with higher proportion of the population without social security benefits (p = 0.007) and of households with unsatisfied basic needs had a higher risk of nonadherence (p = 0.032). In addition, the proportion of nonadherence was higher in areas with the highest proportion of households with no public transportation within 300 meters (p = 0.070).CONCLUSIONS We found a risk area for the nonadherence to treatment characterized by a population living in poverty, with precarious jobs and difficult access to public transportation.

Reconfigurable weblabs based on the IEEE1451 Std

Technology plays a double role in Education: it can act as a facilitator in the teaching/learning process and it can be the very subject of that process in Science & Engineering courses. This is especially true when students perform laboratory activities where they interact with equipment and objects under experimentation. In this context, technology can also play a facilitator role if it allows students to perform experiments in a remote fashion, through the Internet, in a so-called weblab or remote laboratory. No doubt, the Internet has been revolutionizing the educational process in many aspects, and it can be stated that remote laboratories are just an angle of that on-going revolution. As any other educational tool or resource, the i) pedagogical approach and the ii) technology used in the development of a remote laboratory can dictate its general success or its ephemeral existence. By pedagogical approach we consider the way remote experiments address the process by which students acquire experimental skills and link experimental results to theoretical concepts. In respect to technology, we discuss different specification and implementation alternatives, to show the case where the adoption of a family of standards would positively contribute to a larger acceptance and utilization of remote laboratories, and also to a wider collaboration in their development.

Severity of malocclusion in adolescents: populational-based study in the north of Minas Gerais, Brazil

ABSTRACT OBJECTIVE To identify the factors associated with severity of malocclusion in a population of adolescents. METHODS In this cross-sectional population-based study, the sample size (n = 761) was calculated considering a prevalence of malocclusion of 50.0%, with a 95% confidence level and a 5.0% precision level. The study adopted correction for the effect of delineation (deff = 2), and a 20.0% increase to offset losses and refusals. Multistage probability cluster sampling was adopted. Trained and calibrated professionals performed the intraoral examinations and interviews in households. The dependent variable (severity of malocclusion) was assessed using the Dental Aesthetic Index (DAI). The independent variables were grouped into five blocks: demographic characteristics, socioeconomic condition, use of dental services, health-related behavior and oral health subjective conditions. The ordinal logistic regression model was used to identify the factors associated with severity of malocclusion. RESULTS We interviewed and examined 736 adolescents (91.5% response rate), 69.9% of whom showed no abnormalities or slight malocclusion. Defined malocclusion was observed in 17.8% of the adolescents, being severe or very severe in 12.6%, with pressing or essential need of orthodontic treatment. The probabilities of greater severity of malocclusion were higher among adolescents who self-reported as black, indigenous, pardo or yellow, with lower per capita income, having harmful oral habits, negative perception of their appearance and perception of social relationship affected by oral health. CONCLUSIONS Severe or very severe malocclusion was more prevalent among socially disadvantaged adolescents, with reported harmful habits and perception of compromised esthetics and social relationships. Given that malocclusion can interfere with the self-esteem of adolescents, it is essential to improve public policy for the inclusion of orthodontic treatment among health care provided to this segment of the population, particularly among those of lower socioeconomic status.

Survey on the clinical trial results achieved in Brazil comparing praziquantel and oxamniquine in the treatment of mansoni schistosomiasis

A random, double-blind, parallel group clinical trial program was carried out to compare praziquantel, a recently developed anti-helmintic drug, and oxamniquine, an already established agent for treating mansoni schistosomiasis. Both drugs were administered orally as a single dose, on the average, praziquantel 55 mg/kg and oxamniquine 16 mg/kg BWT. The diagnosis and the parasitological follow-up lasting for a minimum of six months, were based on stool examinations according to Kato/Katz technique. A patient was considered cured if all results were negative and if he had performed at least three post-treatment controls, each one comprising three stool examinations. The finding of a single S. mansoni egg in any stool examination indicated, a therapeutical failure. A total of 267, cases were treated with praziquantel and 272 with oxamniquine. The two groups were homogeneous in regard to patients, age, clinical form of the disease, risk of reinfection and worm burden, relevant factors in the therapeutical response. The incidence and severity of untoward, effects were similar in both groups but abdominal distress and diarrhoea were more frequently reported under praziquantel and dizzines under oxamniquine (p < 0.05). In the former group a marked urticariform reaction was observed whereas in the latter one patient presented convulsion. The laboratory work-up. failed to disclose any significant alteration although the AST, ALT and y-GT mean values revealed a tendence to increase on the 7th day after oxamniquine intake. The overall parasitological cure rates were 75.5% (139/ 184) with praziquantel and 69.8% (134/192) with oxamniquine (p > 0.05). Amongst the noncured aptients a reduction of 88.6% and 74.6% in the mean number of eggs/g of feces Was seen following the treatment with praziquantel and oxamniquine, respectively (p < 0.05). In conclusion, in spite of their different chemical, pharmacological and toxicological profiles as well as mechanisms-of-action, inclusively praziquantel already had proved to be 100% active against S. mansoni strains resistant to oxamniquine, both drugs showed comparable tolerance and therapeutical efficacy.

Treatment of patients with Schistosomiasis mansoni: a double blind clinical trial comparing praziquantel with oxamniquine

A double-blind clinical trial involving 120 patients with chronic schistosomiasis was carried out to compare the tolerability and efficacy of praziquantel and oxamniquine. The patients were randomly allocated into two groups. One was treated with praziquantel, 55 mg/kg of body weight CBWT), and the other one with oxamniquine, 15mg/kg bwt, administered in a single oral dose. The diagnosis and the parasitological follow-up was based on stool examinations by quantitative Kato-Katz method and on rectal biopsies. Side-effects — mainly dizziness, sleepness, abdominal distress, headache, nausea and diarrhea — were observed in 87% of the cases. Their incidence, intensity and duration were similar for both drugs but abdominal pain was significantly more frequent after praziquantel intake and severe dizziness was more commonly reported after oxamniquine. A significant increase of alanine-aminotransferase and y-glutamyltransferase was found with the latter drug and of total bilirubin with the former one. A total of 48 patients treated with praziquantel and 46 with oxamniquine completed with negative findings the required three post-treatment parasitological controls — three slides of each stool sample on the first, third and sixth month. The achieved cure rates were 79.2% and 84.8%, respectively, a difference without statistical significance. The non-cured cases showed a mean reduction in the number of eggs per gram of feces of 93.5% after praziquantel and of 84.1% after oxamniquine. This diference also was not significant. Five patients retreated with praziquantel were cured but only one out of three treated a second time with oxamniquine. These findings show that both drugs — despite their different chemical structures, pharmacological properties and mechanisms-of-action — induce similar side-effects as well as a comparable therapeutical efficacy, in agreement with the results reported from analogous investigations.

Therapeutical evaluation of different dose regimens of praziquantel in schistosomiasis mansoni, based on the quantitative oogram technique

A clinical trial involving 80 patients of both sexes, from ages 15 to 55, with chronic intestinal or hepatointestinal schistosomiasis mansoni, was carried out to evaluate the therapeutical efficacy of different dose regimens of praziquantel. The patients were randomly allocated into four groups with an equal number of cases and were then treated with one of the following dosages: 60 mg/kg for 1 day; 60 mg/kg daily for 2 days; 60 mg/kg daily for 3 days; and 30 mg/kg daily for 6 days. The assessment of parasitological cure was based on the quantitative oogram technique through rectal mucosa biopsies which were undertaken prior to, as well as, 1,2,4 and 6 months post-treatment. Concurrently, stool examinations according to the qualitative Hoffman, Pons & Janer (HPJ) and the quantitative Kato-Katz (K-K) methods were also performed. The best tolerability was observed with 30 mg/kg daily for 6 days whereas the highest incidence of side-effects (mainly dizziness and nausea) was found with 60 mg/kg daily for 3 days. No serious adverse drug reaction has occurred. The achieved cure rates were: 25% with 60 mg/kg for 1 day; 60% with 60 mg/kg daily for 2 days; 89.5% with 60 mg/kg daily for 3 days; and 90% with 30 mg/kg daily for 6 days. At the same time there has been a downfall of 64%, 73%, 87% and 84% respectively, in the median number of viable S. mansoni ova per gram of tissue. Thus, a very clear direct correlation between dose and effect could be seen. The corresponding cure rates according to stool examinations by HPJ were 39%, 80%, 100% and 95%; by K-K 89%, 100%, 100% and 100%. This discrepancy in results amongst the three parasitological methods is certainly due to their unequal accuracy. In fact, when the number of viable eggs per gram of tissue fell below 5,000 the difference in the percentage of false negative findings between HPJ (28%) and K-K (80%) became significative. When this number dropped to less than 2,000 the percentage of false negative results obtained with HPJ (49%) turned significant in relation to the oogram as well. In conclusion, it has been proven that praziquantel is a highly efficacious agent against S. mansoni infections. If administered at a total dose of 180 mg/kg divided into either 3 or 6 days, it yields a 90% cure rate. Possibly, one could reach 100% by increasing the total dose to 240 mg/kg. Furthermore, it was confirmed that the quantitative oogram technique is the most reliable parasitological method when evaluating the efficacy of new drugs in schistosomiasis mansoni.

Contributo das tecnologias de informação na gestão do regime terapêutico no diabético

A diabetes é a doença do seculo XXI, atinge mais de um milhão de portugueses cada vez mais jovens em idades trabalhadoras, e já custa mais de 1% do PIB, além dos enormes danos que pode causar às pessoas e à sociedade. Segundo o Relatório Anual do Observatório Nacional da Diabetes, em 2011, cerca de um quarto da população portuguesa integrada no escalão etário dos 60 aos 79 tem Diabetes. Um estudo realizado pelo Lisbon Internet and Networks Institute (LINI), em 2010, diz-nos que “a internet é um recurso para a informação e educação para a saúde”. Em 2010 49% dos lares portugueses possuem acesso à internet e 44% da população é utilizadora (acréscimo significativo relativamente aos 29% em 2003). Destes, dois terços têm entre os 15 e os 24 anos. Os idosos representam 1,6%, dos quais os reformados e pensionistas representam 5%, as domésticas representam 11% e os trabalhadores manuais 22%, sendo estes os menos utilizadores. Um terço da restante população procura informação sobre saúde semanalmente, cerca de 16%. Face à atual conjuntura económica, com restrições orçamentais, nomeadamente na área da saúde, devem-se encontrar meios para prevenir e lidar com a Diabetes numa perspetiva de custo-benefício, isto porque a Diabetes pode reduzir as oportunidades de emprego e de aprendizagem. O atual diretor da Organização para a Cooperação e Desenvolvimento Económico (OCDE) Yyes Leterme diz que “Prevenir e tratar a Diabetes e as suas complicações custa cerca de 90 mil milhões de euros anualmente na Europa”. Atualmente, não é muito utilizado nem explorado o potencial das tecnologias de informação e as ferramentas web ao serviço da saúde, quer por profissionais de saúde, quer por utentes na gestão ao regime terapêutico na doença crónica, mais precisamente na gestão adequada da Diabetes. Potenciar uma visão integrada dos diferentes recursos de comunicação e a sua utilização conjugada com a promoção da saúde e prevenção da doença poderá enfatizar em termos de eficácia e eficiência a minimização de recursos das organizações de saúde e promover a gestão adequada da Diabetes. Tendo por base esta problemática, este estudo pretende abordar e refletir o possível contributo das tecnologias de informação e das ferramentas web na gestão adequada ao regime terapêutico da Diabetes.

New recycling approaches for thermoset polymeric composite wastes – an experimental study on polyester based concrete materials filled with fibre reinforced plastic recyclates

In this study, a new waste management solution for thermoset glass fibre reinforced polymer (GFRP) based products was assessed. Mechanical recycling approach, with reduction of GFRP waste to powdered and fibrous materials was applied, and the prospective added-value of obtained recyclates was experimentally investigated as raw material for polyester based mortars. Different GFRP waste admixed mortar formulations were analyzed varying the content, between 4% up to 12% in weight, of GFRP powder and fibre mix waste. The effect of incorporation of a silane coupling agent was also assessed. Design of experiments and data treatment was accomplished through implementation of full factorial design and analysis of variance ANOVA. Added value of potential recycling solution was assessed by means of flexural and compressive loading capacity of GFRP waste admixed mortars with regard to unmodified polymer mortars. The key findings of this study showed a viable technological option for improving the quality of polyester based mortars and highlight a potential cost-effective waste management solution for thermoset composite materials in the production of sustainable concrete-polymer based products.

Mining social individuals movements and friends based on mobile devices

Trabalho de Projeto realizado para obtenção do grau de Mestre em Engenharia Informática e de Computadores

Reinfection after treatment of schistosomiasis: environment or "predisposition"?

Although very efficient for the control of morbidity due to S. mansoni in individual patients, chemotherapy has not proven successful in the management of transmission within hyperendemic areas when used alone, even if repeated at short intervals. Consequently, a great deal of effort has been expended toward immunologic investigation and development of a specific vaccine. Based upon a study of a group of children (5-14 years) from the state of Alagoas, the author demonstrates that the outcome one year after chemotherapy depends essentially on the "risk rating" of the area of domicile. A regression analysis did not reveal significant correlation to neither age, sex or initial egg counts. Although the study was not designed to reveal individual variations in the immune status, it is postulated that putative differences in genetic make-up are irrelevant in terms of large-scale intervention. Since morbidity due to S. mansoni has substantially declined during the last two or three decades, a control policy based on vaccination can only be justified if high levels of protective immunity can be attained. At any rate, such a vaccine will have to be administered in early childhood (preferably below the age of three). It can also be demonstrated that immunization in adolescence or adulthood serves no purpose whatsoever. The author is convinced that environmental intervention, usually dismissed as unrealistic in terms of the developing countries, is not only feasible, if done on a selective basis, but prioritary.