New perspectives for pharmacological chaperoning treatment in methylmalonic aciduria cblB type

Methylmalonic aciduria cblB type (MMA cblB) is caused by the impairment of ATP:cob(I)alamin adenosyltransferase (ATR), the enzyme responsible for the synthesis of adenosylcobalamin (AdoCbl) from cob(I)alamin. No definitive treatment is available for patients with this condition and novel therapeutic strategies are therefore much needed. Recently, we described a proof-of-concept regarding the use of pharmacological chaperones as a treatment. This work describes the effect of two potential pharmacological chaperones - compound V (N-{[(4-chlorophenyl)carbamothioyl]amino}-2-phenylacetamide) and compound VI (4-(4-(4-fluorophenyl)-5-methyl-1H-pyrazol-3-yl)benzene-1,3-diol) - on six ATR mutants, including the most common, p.Arg186Trp. Comprehensive functional analysis identified destabilizing (p.Arg186Gln, p.Arg190Cys, p.Arg190His, p.Arg191Gln and p.Glu193Lys) and oligomerization (p.Arg186Trp and p.Arg191Gln) mutations. In a cellular model overexpressing the destabilizing/oligomerization mutations, compounds V and VI had a positive effect on the stability and activity of all ATR variants. When provided in combination with hydroxocobalamin a more positive effect was obtained than with the compounds alone, even in mutations previously described as B12 non-responsive. In addition, a normal oligomerization profile was recovered after treatment of the p.Arg186Trp mutant with both compounds. These promising results confirm MMA cblB type as a conformational disorder and hence, pharmacological chaperones as a new therapeutic option alone or in combination with hydroxocobalamin for many patients with MMA cblBThis work was supported by Instituto de Salud Carlos III and (grant PI13/01239) plus grants from the Fundación Isabel Gemio and Obra Social de La Caixa to BP; the Research Council of Norway [nr. 185181 to AM], The KG Jebsen Foundation, and NovoSeeds (Novo Nordisk). AG was supported by a Ramón y Cajal grant from the Ministerio de Ciencia y Tecnología. This work was supported also by the European Regional Development Fund (PI13/01239

System of Web-Based Electronic Medical Record

Nowadays, the information systems are considered a tool to make-decision support in several areas. One of the applications of this system could be in the development of a web-based Electronic Medical Record. The attention to standards, naming, accurate measuring and the system security in the sense of information privacy are fundamental elements in the development of a web-based electronic medical record. Therefore, based on the solidarity and maturity of web applications, this work presents a solution that could supply the construction of electronic medical records by the internet. Recently, in the Brazilian market there have been few successful initiatives. Taking this into account, this work proposes the use of proven software development methodologies. How a study case was used the tengiology and vascular surgery. Currently the medical consultation processes of the angiology and vascular surgery specialties are operated manually. The final product provides automatization of these procedures

Web platform using digital image processing and geographic information system tools : a Brazilian case study on dengue

Background: Dengue fever is endemic in Asia, the Americas, the East of the Mediterranean and the Western Pacific. According to the World Health Organization, it is one of the diseases of greatest impact on health, affecting millions of people each year worldwide. A fast detection of increases in populations of the transmitting vector, the Aedes aegypti mosquito, is essential to avoid dengue outbreaks. Unfortunately, in several countries, such as Brazil, the current methods for detecting populations changes and disseminating this information are too slow to allow efficient allocation of resources to fight outbreaks. To reduce the delay in providing the information regarding A. aegypti population changes, we propose, develop, and evaluate a system for counting the eggs found in special traps and to provide the collected data using a web structure with geographical location resources. Methods: One of the most useful tools for the detection and surveillance of arthropods is the ovitrap, a special trap built to collect the mosquito eggs. This allows for an egg counting process, which is still usually performed manually, in countries such as Brazil. We implement and evaluate a novel system for automatically counting the eggs found in the ovitraps’ cardboards. The system we propose is based on digital image processing (DIP) techniques, as well as a Web based Semi-Automatic Counting System (SCSA-WEB). All data collected are geographically referenced in a geographic information system (GIS) and made available on a Web platform. The work was developed in Gama’s administrative region, in Brasília/Brazil, with the aid of the Environmental Surveillance Directory (DIVAL-Gama) and Brasília’s Board of Health (SSDF), in partnership with the University of Brasília (UnB). The system was built based on a field survey carried out during three months and provided by health professionals. These professionals provided 84 cardboards from 84 ovitraps, sized 15 × 5 cm. In developing the system, we conducted the following steps: i. Obtain images from the eggs on an ovitrap’s cardboards, with a microscope. ii. Apply a proposed image-processing-based semi-automatic counting system. The system we developed uses the Java programming language and the Java Server Faces technology. This is a framework suite for web applications development. This approach will allow a simple migration to any Operating System platform and future applications on mobile devices. iii. Collect and store all data into a Database (DB) and then georeference them in a GIS. The Database Management System used to develop the DB is based on PostgreSQL. The GIS will assist in the visualization and spatial analysis of digital maps, allowing the location of Dengue outbreaks in the region of study. This will also facilitate the planning, analysis, and evaluation of temporal and spatial epidemiology, as required by the Brazilian Health Care Control Center. iv. Deploy the SCSA-WEB, DB and GIS on a single Web platform. Results: The statistical results obtained by DIP were satisfactory when compared with the SCSA-WEB’s semi-automated eggs count. The results also indicate that the time spent in manual counting has being considerably reduced when using our fully automated DIP algorithm and semi-automated SCSA-WEB. The developed georeferencing Web platform proves to be of great support for future visualization with statistical and trace analysis of the disease. Conclusions: The analyses suggest the efficiency of our algorithm for automatic eggs counting, in terms of expediting the work of the laboratory technician, reducing considerably its time and error counting rates. We believe that this kind of integrated platform and tools can simplify the decision making process of the Brazilian Health Care Control Center

Biocides used as additives to biodiesels and their risks to the environment and public health : a review

One of the advantages of using biodiesel and its blends with diesel oil is the lower levels of emissions of particulate matter, sulfur dioxide, carbon monoxide, among others, making it less harmful to the environment and to humans. However, this biofuel is susceptible to microbial contamination and biodeterioration. In this sense, studies on the use of effective low toxicity biocides are being carried out, and this work aims to present the latest information (2008–2018) available in the scientific databases, on the use of biocides in biodiesel, mainly concerning their toxicity to the environment and public health. The results showed that in relation to the control of microbial contamination, the current scenario is limited, with seven publications, in which the most studied additives were isothiazolinones, oxazolidines, thiocyanates, morpholines, oxaborinanes, thiocarbamates and phenolic antioxidants. Studies regarding direct experiments with humans have not been found, showing the need for more studies in this area, since the potential growth of biodiesel production and consumption in the world is evident. Thus, there are need for more studies on antimicrobial products for use in biodiesel, with good broad-spectrum activity (bactericidal and fungicidal), and further toxicological tests to ensure no or little impact on the environment

Comparison between observed children's tooth brushing habits and those reported by mothers

<p>Abstract</p> <p>Background</p> <p>Information bias can occur in epidemiological studies and compromise scientific outcomes, especially when evaluating information given by a patient regarding their own health. The oral habits of children reported by their mothers are commonly used to evaluate tooth brushing practices and to estimate fluoride intake by children. The aim of the present study was to compare observed tooth-brushing habits of young children using fluoridated toothpaste with those reported by mothers.</p> <p>Methods</p> <p>A sample of 201 mothers and their children (aged 24-48 months) from Montes Claros, Brazil, took part in a cross-sectional study. At day-care centres, the mothers answered a self-administered questionnaire on their child's tooth-brushing habits. The structured questionnaire had six items with two to three possible answers. An appointment was then made with each mother/child pair at day-care centres. The participants were asked to demonstrate the tooth-brushing practice as usually performed at home. A trained examiner observed and documented the procedure. Observed tooth brushing and that reported by mothers were compared for overall agreement using Cohen's Kappa coefficient and the McNemar test.</p> <p>Results</p> <p>Cohen's Kappa values comparing mothers' reports and tooth brushing observed by the examiner ranged from poor-to-good (0.00-0.75). There were statistically significant differences between observed tooth brushing habits and those reported by mothers (p < 0.001). When observed by the examiner, the frequencies of dentifrice dispersed on all bristles (35.9%), children who brushed their teeth alone (33.8%) and those who did not rinse their mouths during brushing (42.0%) were higher than those reported by the mothers (12.1%, 18.9% and 6.5%, respectively; p < 0.001).</p> <p>Conclusions</p> <p>In general, there was low agreement between observed tooth brushing and mothers' reports. Moreover, the different methods of estimation resulted in differences in the frequencies of tooth brushing habits, indicative of reporting bias. Data regarding children's tooth-brushing habits as reported by mothers should be considered with caution in epidemiological surveys on fluoridated dentifrice use and the risk of dental fluorosis.</p

Cooperation of Symbolic and Connectionist Expert System Techniques to Overcome Difficulties

A new methodology for developing Expert System (ES) is presented in this paper. It has learning ability to extract knowledge by a simple knowledge base using the learning by examples paradigm. The choice of a simple knowledge base was motivated by the fact that, in this case, it is easier to have consistence in putting together the several pieces of knowledge. So, the problems attached with knowledge elicitation phase are simplified. Th