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Referral gynecological ambulatory clinic: principal diagnosis and distribution in health services
No full textAbstract\ud
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Background\ud
The association between gynecological diagnoses and their distribution in the health sectors provides benefits in the field of women’s health promotion and in medical and interdisciplinary education, along with rationalization according to level of care complexity. Thus, the objective is analyze the clinical-demographic characteristics, main diagnoses in gynecological ambulatory care, and their distribution in health services.\ud
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Method\ud
This is a research project of retrospective audit study design with a chart review of data from 428 women treated at University Ambulatory Clinic of Women’s Health, the facility in gynecology and training for Family and Community Medical Residents, São Paulo, Brazil, from 2012 to 2014. Clinical and demographic information, gynecological diagnoses (International Classification of Diseases), and distribution of health services (primary, secondary, and tertiary) were described.\ud
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Results\ud
The female patients present non-inflammatory disorders of the female genital tract (81.07%, n = 347) and diseases of the urinary system (22.66%, n = 97) among the gynecological diagnoses. The chances of having benign breast disease and non-inflammatory disorders of the female genital tract during the reproductive period corresponds to being 3.61 (CI 1.00–16.29) and 2.56 times (CI 1.58–4.16) higher, respectively, than during the non-reproductive period. The non-inflammatory disorders of the female genital tract (93.33%, n = 28) are most related to the tertiary sector. The distribution in health services was the following: 71.30% (n = 305) in the primary sector, 21.70% (n = 93) in the secondary sector and 7% (n = 30) in the tertiary sector.\ud
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Conclusion\ud
The studied women presented non-inflammatory disorders of the female genital tract and diseases of the urinary system as determined by gynecological diagnoses. Low-assistance complexity followed in most cases
Nc886 is epigenetically repressed in prostate cancer and acts as a tumor suppressor through the inhibition of cell growth
No full textAbstract\ud
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Background\ud
Nc886 is a 102 bp non-coding RNA transcript initially classified as a microRNA precursor (Pre-miR-886), later as a divergent homologue of the vault RNAs (vtRNA 2–1) and more recently as a novel type of RNA (nc886). Although nc886/vtRNA2–1/Pre-miR-886 identity is still controversial, it was shown to be epigenetically controlled, presenting both tumor suppressor and oncogenic function in different cancers. Here, we study for the first time the role of nc886 in prostate cancer.\ud
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Methods\ud
Nc886 promoter methylation status and its correlation with patient clinical parameters or DNMTs levels were evaluated in TCGA and specific GEO prostate tissue datasets. Nc886 level was measured by RT-qPCR to compare normal/neoplastic prostate cells from radical prostatectomies and cell lines, and to assess nc886 response to demethylating agents. The effect of nc886 recovery in cell proliferation (in vitro and in vivo) and invasion (in vitro) was evaluated using lentiviral transduced DU145 and LNCaP cell lines. The association between the expression of nc886 and selected genes was analyzed in the TCGA-PRAD cohort.\ud
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Results\ud
Nc886 promoter methylation increases in tumor vs. normal prostate tissue, as well as in metastatic vs. normal prostate tissue. Additionally, nc886 promoter methylation correlates with prostate cancer clinical staging, including biochemical recurrence, Clinical T-value and Gleason score. Nc886 transcript is downregulated in tumor vs. normal tissue -in agreement with its promoter methylation status- and increases upon demethylating treatment. In functional studies, the overexpression of nc886 in the LNCaP and DU145 cell line leads to a decreased in vitro cell proliferation and invasion, as well as a reduced in vivo cell growth in NUDE-mice tumor xenografts. Finally, nc886 expression associates with the prostate cancer cell cycle progression gene signature in TCGA-PRAD.\ud
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Conclusions\ud
Our data suggest a tumor suppressor role for nc886 in the prostate, whose expression is epigenetically silenced in cancer leading to an increase in cell proliferation and invasion. Nc886 might hold clinical value in prostate cancer due to its association with clinical parameters and with a clinically validated gene signature.This study was funded by Comisión Honoraria de Lucha contra el Cáncer (CHLC), Agencia Nacional de Investigación e Innovación (ANII), Comisión Sectorial de Investigación Científica (CSIC) and Programa de Desarrollo de las Ciencias Básicas (PEDECIBA) from Uruguay
Chromosomal microarray analysis in the genetic evaluation of 279 patients with syndromic obesity
No full textAbstract\ud
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Background\ud
Syndromic obesity is an umbrella term used to describe cases where obesity occurs with additional phenotypes. It often arises as part of a distinct genetic syndrome with Prader-Willi syndrome being a classical example. These rare forms of obesity provide a unique source for identifying obesity-related genetic changes. Chromosomal microarray analysis (CMA) has allowed the characterization of new genetic forms of syndromic obesity, which are due to copy number variants (CNVs); however, CMA in large cohorts requires more study. The aim of this study was to characterize the CNVs detected by CMA in 279 patients with a syndromic obesity phenotype.\ud
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Results\ud
Pathogenic CNVs were detected in 61 patients (22%) and, among them, 35 had overlapping/recurrent CNVs. Genomic imbalance disorders known to cause syndromic obesity were found in 8.2% of cases, most commonly deletions of 1p36, 2q37 and 17p11.2 (5.4%), and we also detected deletions at 1p21.3, 2p25.3, 6q16, 9q34, 16p11.2 distal and proximal, as well as an unbalanced translocation resulting in duplication of the GNB3 gene responsible for a syndromic for of childhood obesity. Deletions of 9p terminal and 22q11.2 proximal/distal were found in 1% and 3% of cases, respectively. They thus emerge as being new putative obesity-susceptibility loci. We found additional CNVs in our study that overlapped with CNVs previously reported in cases of syndromic obesity, including a new case of 13q34 deletion (CHAMP1), bringing to 7 the number of patients in whom such defects have been described in association with obesity. Our findings implicate many genes previously associated with obesity (e.g. PTBP2, TMEM18, MYT1L, POU3F2, SIM1, SH2B1), and also identified other potentially relevant candidates including TAS1R3, ALOX5AP, and GAS6.\ud
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Conclusion\ud
Understanding the genetics of obesity has proven difficult, and considerable insight has been obtained from the study of genomic disorders with obesity associated as part of the phenotype. In our study, CNVs known to be causal for syndromic obesity were detected in 8.2% of patients, but we provide evidence for a genetic basis of obesity in as many as 14% of cases. Overall, our results underscore the genetic heterogeneity in syndromic forms of obesity, which imposes a substantial challenge for diagnosis.This study was supported by The State of São Paulo Research Foundation,\ud
FAPESP (09/52523–1 to C.S.D.), The Centers for Research, Innovation and Diffusion, CEPID-FAPESP (1998/14254–2), and The National Council for Scientific and Technological Development, CNPq (304381/2007–1 to C.P.K.)
Modulation of pro-apoptotic effects and mitochondrial potential on B16F10 cells by DODAC/PHO-S liposomes
No full textAbstract\ud
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Objective\ud
We aimed to evaluate the potential of DODAC/PHO-S liposomes on the modulation of the expression of pro-apoptotic proteins, loss of lysosomal integrity and the mitochondrial electrical potential, compared with phosphoethanolamine.\ud
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Results\ud
The results of this study demonstrate that DODAC/PHO-S liposomes have exhibited broad cytotoxic potential in B16F10 murine melanoma cells, with significantly greater proportions than treatment with PHO-S. The treatment with the DODAC/PHO-S 2.0 mM liposomal formulation was more efficient in decreasing mitochondrial electrical potential at the same concentrations and treatment time than PHO-S The liposomal formulation DODAC/PHO-S (2.0 mM) was more efficient to promote morphological changes in the cells, without presenting intact lysosomes, at the same time of treatment and concentration as PHO-S Our results demonstrated that the liposomal formulation increased DR4 receptor expression and activated caspases 8 and 3, resulting in the release of cytochrome c in B16F10 tumour cells, when compared to treatment with PHO-S The data obtained prove that the use of DODAC as carrier can maximize the cytotoxic effects of PHO-S This was demonstrated by the translocation of cytochrome c to the cytoplasm and activation of caspase-3 and 8, decreasing the mitochondrial electrical potential and generating morphological changes, in B16F10 cells.This study was funded by Sao Paulo Research Foundation, process number: 2015/02,950- 1
Probiotic supplementation in dental caries: is it possible to replace conventional treatment?
No full textAbstract\ud
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Background\ud
Probiotic supplementation alters oral microbiota composition and could reduce the risk or treat oral cavity diseases, such as dental caries, which are considered a public health problem.\ud
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Aim\ud
To summarize the therapeutic effects of probiotics in caries and to verify whether this intervention is capable of replacing conventional treatment in human beings.\ud
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Methods\ud
The search of the studies was carried out in the PubMed database in October 2017, without limiting the publication period. The keyword combination used was “Probiotics” and “Dental caries.” Forty-two original articles that evaluated the effect of probiotic supplementation on caries treatment in humans were included in the study.\ud
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Results\ud
Most of the studies evaluated bacteria of the genus Lactobacillus. The main therapeutic effects are related to the reduction of the Streptococcus mutans oral count, increased Lactobacillus oral count, and reduction in the incidence of caries. Evidence on the therapeutic effects of the Bifidobacterium and Streptococcus genres is scarce and conflicting, making it difficult to recommend them for use in clinical practice. Only a few studies administered probiotics without conventional treatments, such as fluoride. Although probiotic supplementation presented interesting properties, the therapeutic effects are more pronounced when probiotic and fluoride are applied together.\ud
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Conclusion\ud
Probiotics, especially of the Lactobacillus genus, can be used as adjuvants, but cannot replace the conventional treatments of caries.The authors would like to thank The São Paulo Research Foundation (FAPESP\ud
2016/04910-0 and 2016/11360-6), the Brazilian National Council for Scientific\ud
and Technological Development (CNPq) (154403/2016-4), and the Coordination\ud
for the Improvement of Higher Education Personnel (CAPES) for the\ud
financial support
Increased levels of cyclin D1 negatively impacts on acute lymphoblastic leukemia overall survival
No full textAbstract\ud
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Background\ud
Cyclin D1 is a protein essential for transition from G1 to S phase during cell cycle progression, which has an oncogenic potential and is highly expressed in several human malignancies. However, in view of the heterogeneity of the findings in the literature, the prognostic value of cyclin D1 expression still needs to be validated in different cohorts of adult acute lymphoblastic leukemia (ALL) patients.\ud
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Methods\ud
Bone marrow samples from 13 healthy donors and 45 adult patients with acute lymphoblastic leukemia were included. Cyclin D1 gene expression was evaluated by quantitative PCR. For statistical analysis, Mann–Whitney test, Fisher’s exact test, Chi-squared test and Cox regression were used, as appropriate. All p values were two-sided with a significance level of 5%.\ud
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Results\ud
Cyclin D1 mRNA levels were similar between primary cells from ALL patients and healthy donors. In ALL patients, high cyclin D1 expression was associated with older age at the diagnosis, presence of BCR-ABL1, and lower white blood cell counts. Importantly, increased cyclin D1 expression was an independent factor that predicted worse overall survival in our adult ALL cohort.\ud
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Conclusion\ud
Increased levels of cyclin D1 negatively impacted on ALL survival outcome, suggesting that this gene is involved in the malignant phenotype of ALL.This work was supported by Conselho Nacional de Desenvolvimento\ud
Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de\ud
Pessoal de Nível Superior (CAPES) and Fundação de Amparo à Pesquisa do\ud
Estado de São Paulo ; grant #2013/26213-0 and # 2013/08135-2, São Paulo\ud
Research Foundation (FAPESP)
Genomic positional conservation identifies topological anchor point RNAs linked to developmental loci
No full textAbstract\ud
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Background\ud
The mammalian genome is transcribed into large numbers of long noncoding RNAs (lncRNAs), but the definition of functional lncRNA groups has proven difficult, partly due to their low sequence conservation and lack of identified shared properties. Here we consider promoter conservation and positional conservation as indicators of functional commonality.\ud
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Results\ud
We identify 665 conserved lncRNA promoters in mouse and human that are preserved in genomic position relative to orthologous coding genes. These positionally conserved lncRNA genes are primarily associated with developmental transcription factor loci with which they are coexpressed in a tissue-specific manner. Over half of positionally conserved RNAs in this set are linked to chromatin organization structures, overlapping binding sites for the CTCF chromatin organiser and located at chromatin loop anchor points and borders of topologically associating domains (TADs). We define these RNAs as topological anchor point RNAs (tapRNAs). Characterization of these noncoding RNAs and their associated coding genes shows that they are functionally connected: they regulate each other’s expression and influence the metastatic phenotype of cancer cells in vitro in a similar fashion. Furthermore, we find that tapRNAs contain conserved sequence domains that are enriched in motifs for zinc finger domain-containing RNA-binding proteins and transcription factors, whose binding sites are found mutated in cancers.\ud
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Conclusions\ud
This work leverages positional conservation to identify lncRNAs with potential importance in genome organization, development and disease. The evidence that many developmental transcription factors are physically and functionally connected to lncRNAs represents an exciting stepping-stone to further our understanding of genome regulation.This work was funded by programme grants from Cancer Research UK (C6/A18796) and European Research Council CRIPTON Grant (268569), and supported by a University of Cambridge and FAPESP grant (2014/50308–4) and Institutional funding by a Wellcome Trust Core Grant (092096) and Cancer Research UK Grant (C6946/A14492). VMC was supported by a PAI-CONICYT grant (PAI79170021) and a FONDECYT-CONICYT grant (11161020)
The role of networks in technological capability: a technology-based companies perspective
No full textAbstract\ud
This study examined the influence of networks on the development of technological capabilities of 90 technology-based companies (TBCs) graduated by Brazilian incubators. The relational-based view theoretically supported the study. The data were processed via Structural Equation Modeling (SEM). A model with three hypotheses was tested. Two hypotheses were validated, proving that technological and financial networks built by those firms with external agents explained 70.6% of their capacity to innovate. The insertion into technology networks of licensing, universities, suppliers, and consulting shows that the TBCs are making use of relationships of high technical content, which is expected according to previous literature. As for the financial networks, it was observed that the insertion into networks of venture capital and economic subvention demonstrates that the innovation ecosystem presents advancements in the well-known challenge of financial support for technology-based startups. A third hypothesis was not validated, which provides another important finding: the planning effort presented a negative relationship on the technological capability, but a positive relationship on the insertion into relationship networks. This means that only direct planning is not able to support technological capabilities. In other words, planning is more effective when indirectly applied to relational resources of technical and financial networks, rather than when directly applied to technological capabilities. The insertion into technical and financial networks, in turn, positively affects the TBC’s innovation capability. Results demonstrate that this change in planning focus, from inside to outside of the company, could improve technological capabilities in R&D, patent, people, and products. Future studies could investigate the entrepreneur’s competencies in managing networks and further understanding of how networks could be constructed through formal and informal cooperation
Pulmonary interstitial emphysema in fatal asthma: case report and histopathological review
No full textAbstract\ud
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Background\ud
Mortality related to asthma has decreased worldwide since the introduction of inhaled corticosteroid therapy in the past decades. However, there are still some asthma fatalities identified mainly in populations with less access to regular treatment. Pulmonary interstitial emphysema due to alveolar rupture has been rarely described as a complication of an acute severe asthma attack, and its identification in pathological analysis can be difficult. Previous studies reported the association of pulmonary interstitial emphysema and bronchial ductal gland ectasia in asthma.\ud
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Case presentation\ud
We present the case of a 42-year- old man that died due to a fatal asthma attack. Postmortem computed tomography revealed the unusual finding of acute Pulmonary Interstitial Emphysema, confirmed by pathological analysis. We reviewed 28 cases of fatal asthma tissue and identified the presence of pulmonary interstitial emphysema in 10% of the cases.\ud
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Conclusions\ud
Postmortem computed tomography is a useful complimentary diagnostic tool for autopsies. Pulmonary Interstitial Emphysema in acute exacerbations of asthma seems to be more frequent than reported. Alveolar hyperdistension and bronchial duct gland ectasia causing tissue rupture are possible mechanisms involved in the formation of Pulmonary Interstitial Emphysema. The clinical impact of Pulmonary Interstitial Emphysema in asthma is unknown.São Paulo Research Foundation (FAPESP), National Council for Scientific and\ud
Technological Development (CNPq)
EX-MET study: exercise in prevention on of metabolic syndrome – a randomized multicenter trial: rational and design
No full textAbstract\ud
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Background\ud
Metabolic syndrome substantially increases risk of cardiovascular events. It is therefore imperative to develop or optimize ways to prevent or attenuate this condition. Exercise training has been long recognized as a corner-stone therapy for reducing individual cardiovascular risk factors constituting the metabolic syndrome. However, the optimal exercise dose and its feasibility in a real world setting has yet to be established.\ud
The primary objective of this randomized trial is to investigate the effects of different volumes of aerobic interval training (AIT) compared to the current exercise guideline of moderate-intensity continuous training (MICT) on the composite number of cardiovascular disease risk factors constituting the metabolic syndrome after a 16 week, 1-year, and 3-year follow-up.\ud
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Methods\ud
This is a randomized international multi-center trial including men and women aged ≥30 years diagnosed with the metabolic syndrome according to the International Diabetes Federation criteria. Recruitment began in August 2012 and concluded in December 2016. This trial consists of supervised and unsupervised phases to evaluate the efficacy and feasibility of different exercise doses on the metabolic syndrome in a real world setting. This study aims to include and randomize 465 participants to 3 years of one of the following training groups: i) 3 times/week of 4 × 4 min AIT at 85–95% peak heart rate (HRpeak); ii) 3 times/week of 1 × 4 min AIT at 85–95% HRpeak; or iii) 5–7 times/week of ≥30 min MICT at 60–70% HRpeak. Clinical examinations, physical tests and questionnaires are administered to all participants during all testing time points (baseline, 16 weeks and after 1-, and 3-years).\ud
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Discussion\ud
This multi-center international trial indeed aims to ease the burden in healthcare/economic cost arising from treating end-stage CVD related conditions such as stroke and myocardial infarction, that could eventually emerge from the metabolic syndrome condition.\ud
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Trial registration\ud
Clinical registration number: \ud
NCT01676870\ud
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, ClinicalTrials.gov (August 31, 2012).The study received two peer – review funding’s from the Joint Research\ud
Committee between St. Olavs Hospital and the Faculty of Medicine and\ud
Health sciences, Norwegian University of Science and Technology (NTNU