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Abstracts from the 8th International Conference on cGMP Generators, Effectors and Therapeutic Implications
No full textThis work was supported by a restricted research grant of Bayer AG
Areas with evidence of equity and their progress on mortality from tuberculosis in an endemic municipality of southeast Brazil
No full textAbstract\ud
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Background\ud
In Brazil, people still fall ill and die from tuberculosis (TB), and this can be explained by the significant impasse in the equity of distribution of therapeutic resources to the population as a whole. The aim was to identify geographical areas which have shown progress in terms of equity (of income, schooling and urban occupancy) and test its effect on mortality from TB in a municipality of southeast Brazil.\ud
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Methods\ud
It is an ecological study considering TB as the basic cause for deaths registered between 2006 and 2013 on the Mortality Information System and other variables obtained through the Demographic Census of the Brazilian Institute of Geography and Statistics (2010). The geographical area for analysis comprised the areas of coverage of the health services. Social indicators have been constructed through the Principal Component Analysis (PCA). The cases were geocoded and the annual mortality rate from TB was calculated with smoothing using the local empirical Bayesian method. Multiple linear regression was then performed. There was confirmation of the existence of spatial dependence of residue through the application of the Global Moran I test, and application of the Models with Global Spatial Effects, to identify the best standard of spatial regression.\ud
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Results\ud
The mortality rates ranged from 0.00 to 2.8 deaths per 100,000 people, per year. In the PCA, three indicators were constructed, and designated as indicators of income, social inequality, and social equity. In multiple linear regression, the indicator of social equity was statistically significant (P < 0.0001) but had a negative association, an adjusted R2 of 28.36% and with spatial dependence (Moran I = 0.21, P = 0.003455). The best model to deal with existing spatial dependence was the Spatial Lag Model.\ud
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Conclusions\ud
The better social conditions have shown progress in reducing mortality from TB, thereby reinforcing the achievement of Sustainable Development Goals. In addition, cartography was also applied, which can be replicated in other scenarios throughout the world, using a scope distinct from that of works traditionally produced in that it places the emphasis on social equity.The authors received financial support from the National Scientific and\ud
Technological Development Council, São Paulo Research Foundation and\ud
Coordination of Improvement of Higher Level Personnel for the\ud
implementation the study.\ud
MY received financial assistance from São Paulo Research Foundation (Process\ud
number: 2011/22834–5) and Coordination of Improvement of Higher Level\ud
Personnel (Programa Nacional de Pós Doutorado/Capes - PNPD).\ud
RAA received financial assistance from the National Council for Scientific and\ud
Technological Development as a researcher (Process number: 305,236/2015–6)\ud
and from the São Paulo Research Foundation (Process: 2015/17586–3).\ud
The funders had no role in any part of the study design, data collection or\ud
analysis, in the decision to to implement the smoothing process provided by\ud
the use of the local empirical Bayesian model, which smooths the gross\ud
rates by applying weighted averages, resulting in a corrected and more\ud
stable rate, considering not only the information of the area, but also those\ud
of its neighborhood’. At this stage, we used the Terraview 4.2.2 and ArcGis\ud
10.2 software packages for the preparation of the chropleth maps.\ud
Publish, or in the preparation of the manuscript.\ud
Website:\ud
http://cnpq.br/ (National Council for Scientific and Technological Development)\ud
http://www.fapesp.br/en/ (São Paulo Research Foundation)\ud
http://www.capes.gov.br/ (Coordination of Improvement of Higher Level\ud
Personnel
Phylogeography of Nasutitermes corniger (Isoptera: Termitidae) in the Neotropical Region
No full textAbstract\ud
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Background\ud
The Neotropical Region is known for its biodiversity and ranks third in number of known termite species. However, biogeographic and phylogeographic information of termites of this region is limited compared to other world geographic regions. Nasutitermes corniger is widely distributed in the region and is of considerable economic importance. The goal of this study was to describe the phylogeography of N. corniger in the Neotropical Region, to better understand its evolutionary processes.\ud
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Results\ud
The sampled populations of N. corniger showed high genetic variation. Results indicated strong geographic structure among N. corniger populations, with most haplotypes not broadly shared among separated locations. Phylogeographic analyses showed a dispersal route for N. corniger from Central America into South America via the Isthmus of Panama, with subsequent dispersal through the highlands east of the Andes and into eastern regions of the continent. The majority of haplotypes were limited in distribution to proximal regions, corresponding to particular biomes (Atlantic Forest, Amazonia, Chaco, Cerrado and Caatinga).\ud
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Conclusions\ud
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Nasutitermes corniger is suggested to be a good model for biogeographic and phylogeographic studies in the Neotropical Region. This study clarified the phylogeographic history of N. corniger and can contribute to the understanding of biogeographic dispersion processes in the Neotropical Region.CAPES: scholarship to AFS; CNPq (Proc. 308,227/2013–0): award of a grant to EMC; FAPESP (Proc.13/20068–9): financial support. All these funding bodies were essential for the financing of samples collection and laboratory procedures
Educational program promoting regular physical exercise improves functional capacity and daily living physical activity in subjects with knee osteoarthritis
No full textAbstract\ud
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Background\ud
Physical exercise and educational programs promote several benefits for patients with knee osteoarthritis (OA). However, little is known about the effects of educational programs promoting the regular practice of physical exercise. The purpose of the present study was to assess the effect of an interdisciplinary educational program, emphasizing the recommendation for regular practice of physical exercise, on functional capacity and daily living physical activity in individuals with knee OA.\ud
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Methods\ud
Two hundred and thirty-nine individuals (50 men) with an established diagnosis of knee OA (degree I to IV in the Kelgreen and Lawrence scale) were randomly allocated into a multidisciplinary educational program (EDU; n = 112) or control group (CON; n = 127). Functional capacity (sit and reach, 6-min walking test (6MWT), timed up and down stairs test, timed up and go test (TUGT), and five times sit-to-stand test (FTSST)) and daily living physical activity (IPAQ, short version) were measured before, during (6 months) and after 12 months of follow-up.\ud
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Results\ud
Body mass index reduced significantly (P < 0.05) after 6 months, and remained reduced after 12-month of follow-up in EDU, but not in CON. EDU group improved (P < 0.05) timed up and down stairs (19%), TUGT (32.5%) and FTSST (30%) performance after 6 months of follow-up, which remained improved after 12 months of follow-up. Functional capacity did not change in CON, excepted for the timed up and down stairs performance that increased after 6 months (12%, P < 0.05), but returned to levels similar to baseline after 12 months of follow-up. There was also an increase (P < 0.05) in the prevalence of active and very active individuals, as well as a reduction (P < 0.05) in the prevalence of sedentary individuals in EDU group during follow-up. There were no significant changes on sit and reach and 6MWT performance during follow-up in both groups.\ud
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Conclusions\ud
The results suggest that an educational program emphasizing the recommendation for regular practice of physical exercise may be an effective tool for improving functional capacity and daily physical activity in individuals with knee OA.\ud
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Trial registration\ud
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NCT 02335034\ud
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, December 22, 2014.This work is part of José M. Rodrigues da Silva’s Master of Sciences\ud
dissertation under the guidance of Dr. Emmanuel G. Ciolac. This study was\ud
only possible because of the efforts of secretaries Suellen Lima and Natalia\ud
Borges and support from TRB Pharma, which together with the Department\ud
of Orthopedics and Traumatology at the Hospital das Clínicas at FMUSP and\ud
Professor Olavo Pires de Camargo, made the PARQVE project and this\ud
prospective study possible. We also thank Fundação de Amparo à Pesquisa\ud
do Estado de São Paulo (FAPESP) and Comissão de Aperfeiçoamento de\ud
Pessoal de Nível Superior (CAPES) for the constant support to our research in\ud
Brazil
A web-based information system for a regional public mental healthcare service network in Brazil
No full textAbstract\ud
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Background\ud
Regional networking between services that provide mental health care in Brazil’s decentralized public health system is challenging, partly due to the simultaneous existence of services managed by municipal and state authorities and a lack of efficient and transparent mechanisms for continuous and updated communication between them. Since 2011, the Ribeirao Preto Medical School and the XIII Regional Health Department of the Sao Paulo state, Brazil, have been developing and implementing a web-based information system to facilitate an integrated care throughout a public regional mental health care network.\ud
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Case presentation\ud
After a profound on-site analysis, the structure of the network was identified and a web-based information system for psychiatric admissions and discharges was developed and implemented using a socio-technical approach. An information technology team liaised with mental health professionals, health-service managers, municipal and state health secretariats and judicial authorities. Primary care, specialized community services, general emergency and psychiatric wards services, that comprise the regional mental healthcare network, were identified and the system flow was delineated. The web-based system overcame the fragmentation of the healthcare system and addressed service specific needs, enabling: detailed patient information sharing; active coordination of the processes of psychiatric admissions and discharges; real-time monitoring; the patients’ status reports; the evaluation of the performance of each service and the whole network. During a 2-year period of operation, it registered 137 services, 480 health care professionals and 4271 patients, with a mean number of 2835 accesses per month. To date the system is successfully operating and further expanding.\ud
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Conclusion\ud
We have successfully developed and implemented an acceptable, useful and transparent web-based information system for a regional mental healthcare service network in a medium-income country with a decentralized public health system. Systematic collaboration between an information technology team and a wide range of stakeholders is essential for the system development and implementation.This study was funded by the ‘Conselho Nacional de Desenvolvimento Cientí‑\ud
fico e Tecnológico’ (CNPq) and ‘Coordenação de Aperfeiçoamento de Pessoal\ud
de Nível Superior’ (CAPES)—Science Without Borders Programme
GBS-based single dosage markers for linkage and QTL mapping allow gene mining for yield-related traits in sugarcane
No full textAbstract\ud
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Background\ud
Sugarcane (Saccharum spp.) is predominantly an autopolyploid plant with a variable ploidy level, frequent aneuploidy and a large genome that hampers investigation of its organization. Genetic architecture studies are important for identifying genomic regions associated with traits of interest. However, due to the genetic complexity of sugarcane, the practical applications of genomic tools have been notably delayed in this crop, in contrast to other crops that have already advanced to marker-assisted selection (MAS) and genomic selection. High-throughput next-generation sequencing (NGS) technologies have opened new opportunities for discovering molecular markers, especially single nucleotide polymorphisms (SNPs) and insertion-deletion (indels), at the genome-wide level. The objectives of this study were to (i) establish a pipeline for identifying variants from genotyping-by-sequencing (GBS) data in sugarcane, (ii) construct an integrated genetic map with GBS-based markers plus target region amplification polymorphisms and microsatellites, (iii) detect QTLs related to yield component traits, and (iv) perform annotation of the sequences that originated the associated markers with mapped QTLs to search putative candidate genes.\ud
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Results\ud
We used four pseudo-references to align the GBS reads. Depending on the reference, from 3,433 to 15,906 high-quality markers were discovered, and half of them segregated as single-dose markers (SDMs) on average. In addition to 7,049 non-redundant SDMs from GBS, 629 gel-based markers were used in a subsequent linkage analysis. Of 7,678 SDMs, 993 were mapped. These markers were distributed throughout 223 linkage groups, which were clustered in 18 homo(eo)logous groups (HGs), with a cumulative map length of 3,682.04 cM and an average marker density of 3.70 cM. We performed QTL mapping of four traits and found seven QTLs. Our results suggest the presence of a stable QTL across locations. Furthermore, QTLs to soluble solid content (BRIX) and fiber content (FIB) traits had markers linked to putative candidate genes.\ud
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Conclusions\ud
This study is the first to report the use of GBS for large-scale variant discovery and genotyping of a mapping population in sugarcane, providing several insights regarding the use of NGS data in a polyploid, non-model species. The use of GBS generated a large number of markers and still enabled ploidy and allelic dosage estimation. Moreover, we were able to identify seven QTLs, two of which had great potential for validation and future use for molecular breeding in sugarcane.This work was supported by grants from the FINEP (Finaciadora de Estudos\ud
e Projetos), FAPESP (Fundação de Amparo à Pesquisa de São Paulo,\ud
08/52197-4) and INCT-Bioetanol (Instituto Nacional de Ciência e Tecnologia\ud
do Bioetanol, FAPESP 08/57908-6 and CNPq, Conselho Nacional de\ud
Desenvolvimento Científico e Tecnológico, 574002/2008-1). TWAB,\ud
GSP, MCM, EAC and CBCS received doctoral fellowships from FAPESP\ud
(10/50091-4, 12/25236-4, 10/50549-0, 10/50031-1 and 12/11109-0, respectively).\ud
COA received a doctoral fellowship from the CNPq. FZB received a master’s\ud
fellowship from CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível\ud
Superior). APS and AAFG received research fellowships from CNPq
Wing variation in Culex nigripalpus (Diptera: Culicidae) in urban parks
No full textAbstract\ud
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Background\ud
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Culex nigripalpus has a wide geographical distribution and is found in North and South America. Females are considered primary vectors for several arboviruses, including Saint Louis encephalitis virus, Venezuelan equine encephalitis virus and Eastern equine encephalitis virus, as well as a potential vector of West Nile virus. In view of the epidemiological importance of this mosquito and its high abundance, this study sought to investigate wing variation in Cx. nigripalpus populations from urban parks in the city of São Paulo, Brazil.\ud
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Methods\ud
Female mosquitoes were collected in seven urban parks in the city of São Paulo between 2011 and 2013. Eighteen landmark coordinates from the right wing of each female mosquito were digitized, and the dissimilarities between populations were assessed by canonical variate analysis and cross-validated reclassification and by constructing a Neighbor-Joining (NJ) tree based on Mahalanobis distances. The centroid size was calculated to determine mean wing size in each population.\ud
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Results\ud
Canonical variate analysis based on fixed landmarks of the wing revealed a pattern of segregation between urban and sylvatic Cx. nigripalpus, a similar result to that revealed by the NJ tree topology, in which the population from Shangrilá Park segregated into a distinct branch separate from the other more urban populations.\ud
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Conclusion\ud
Environmental heterogeneity may be affecting the wing shape variation of Cx. nigripalpus populations.This study was supported by the State of São Paulo Research Foundation\ud
(FAPESP), grant 2013/15313–4. GCC is the recipient of a PhD fellowship,\ud
grant 2013/18965–2. FAPESP had no role in the design of the study and\ud
collection, analysis, and interpretation of data and in writing the manuscript
Methodological quality and transparency of clinical practice guidelines for the pharmacological treatment of non-communicable diseases using the AGREE II instrument: a systematic review protocol
No full textAbstract\ud
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Background\ud
Non-communicable diseases (NCDs) are the leading cause of death worldwide. Clinical practice guidelines (CPGs) constitute an important tool for the promotion of evidence-based health, which may improve healthcare outcomes for individuals with NCDs. Studies have shown that many CPGs have poor or moderate quality. Therefore, the aim of the proposed study is to systematically identify and appraise CPGs for pharmacological treatment of the most prevalent NCDs in primary care.\ud
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Methods\ud
A comprehensive literature search will be conducted in the following databases: MEDLINE, Embase and Cochrane Library. Twelve databases specific to CPGs will also be searched. Three appraisers will assess the quality of the CPGs using the Appraisal of Guidelines Research and Evaluation (AGREE) Instrument, version II. The AGREE II results will be checked for discrepancies. Differences between scores equal than or greater to 2 will be considered discrepant and the appraisers will decide the final score by consensus. If no consensus is reached, a fourth appraiser will decide the score. According to the AGREE II User’s Manual, the six domains of the instrument are independent. Thus, each domain score will be calculated by the sum of the individual item scores and scaling the total as a percentage of the maximum possible score for the domain.\ud
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Discussion\ud
The AGREE II instrument will be applied to evaluate the quality of CPGs and contribute to enhance the discussion and development of guidelines of high quality. The findings will be submitted for publication in high-impact, peer-reviewed scientific journals and will also be disseminated at international conferences.\ud
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Systematic review registration\ud
PROSPERO \ud
CRD42016043364This work is supported by the Brazilian National Council for Scientific and\ud
Technological Development (CNPq, process number 164700/2015–3). The\ud
funding source did not influence the content of this study
MicroRNA-195 acts as an anti-proliferative miRNA in human melanoma cells by targeting Prohibitin 1
No full textAbstract
Background
Melanoma is the most lethal type of skin cancer. Since chemoresistance is a significant barrier, identification of regulators affecting chemosensitivity is necessary in order to create new forms of intervention. Prohibitin 1 (PHB1) can act as anti-apoptotic or tumor suppressor molecule, depending on its subcellular localization. Our recent data shown that accumulation of PHB1 protects melanoma cells from chemotherapy-induced cell death. Lacking of post-transcriptional regulation of PHB1 could explain this accumulation. Interestingly, most of melanoma patients have down-regulation of microRNA-195. Here, we investigate the role of miR-195, its impact on PHB1 expression, and on chemosensitivity in melanoma cells.
Methods
TCGA-RNAseq data obtained from 341 melanoma patient samples as well as a panel of melanoma cell lines were used in an expression correlation analysis between PHB1 and predicted miRNAs. miR-195 impact on PHB1 mRNA and protein levels and relevance of this regulation were investigated in UACC-62 and SK-MEL-5 melanoma lines by RT-qPCR and western blot, luciferase reporter and genetic rescue experiments. Cell proliferation, cell-cycle analysis and caspase 3/7 assay were performed to investigate the potential action of miR-195 as chemosensitizer in melanoma cells treated with cisplatin and temozolomide.
Results
Analysis of the TCGA-RNAseq revealed a significant negative correlation (Pearson) between miR-195 and PHB1 expression. Moreover, RT-qPCR data showed that miR-195 is down-regulated while PHB1 is up-regulated in a collection of melanoma cells. We demonstrated that miR-195 regulates PHB1 directly by RT-qPCR and western blot in melanoma cells and luciferase assays. To establish PHB1 as a relevant target of miR-195, we conducted rescue experiments in which we showed that PHB1 transgenic expression could antagonize the suppressive effect miR-195 on the proliferation of melanoma cells. Finally, transfection experiments combined with drug treatments performed in the UACC-62 and SK-MEL-5 melanoma cells corroborated miR-195 as potential anti-proliferative agent, with potential impact in sensitization of melanoma cell death.
Conclusions
This study support the role of miR-195 as anti-proliferative miRNA via targeting of PHB1 in melanoma cells