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Narrow band imaging versus lugol chromoendoscopy to diagnose squamous cell carcinoma of the esophagus: a systematic review and meta-analysis
No full textAbstract\ud
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Background\ud
In the early stage esophageal cancer, changes in the mucosa are subtle and pass unnoticed in endoscopic examinations using white light. To increase sensitivity, chromoscopy with Lugol’s solution has been used. Technological advancements have led to the emergence of virtual methods of endoscopic chromoscopy, including narrow band imaging (NBI). NBI enhances the relief of the mucosa and the underlying vascular pattern, providing greater convenience without the risks inherent to the use of vital dye. The purpose of this systematic review and meta-analysis was to evaluate the ability of NBI to diagnose squamous cell carcinoma of the esophagus and to compare it to chromoscopy with Lugol’s solution.\ud
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Methods\ud
This systematic review included all studies comparing the diagnostic accuracy of NBI and Lugol chromoendoscopy performed to identify high-grade dysplasia and/or squamous cell carcinoma in the esophagus. In the meta-analysis, we calculated and demonstrated sensitivity, specificity, and positive and negative likelihood values in forest plots. We also determined summary receiver operating characteristic (sROC) curves and estimates of the areas under the curves for both per-patient and per-lesion analysis.\ud
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Results\ud
The initial search identified 7079 articles. Of these, 18 studies were included in the systematic review and 12 were used in the meta-analysis, for a total of 1911 patients. In per-patient and per-lesion analysis, the sensitivity, specificity, and positive and negative likelihood values for Lugol chromoendoscopy were 92% and 98, 82 and 37%, 5.42 and 1.4, and 0.13 and 0.39, respectively, and for NBI were 88 and 94%, 88 and 65%, 8.32 and 2.62, and 0.16 and 0.12, respectively. There was a statistically significant difference in only specificity values, in which case NBI was superior to Lugol chromoendoscopy in both analyses. In the per-patient analysis, the area under the sROC curve for Lugol chromoendoscopy was 0.9559. In the case of NBI, this value was 0.9611; in the per-lesion analysis, this number was 0.9685 and 0.9587, respectively.\ud
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Conclusions\ud
NBI was adequate in evaluating the esophagus in order to diagnose high-grade dysplasia and squamous cell carcinoma. In the differentiation of those disorders from other esophageal mucosa alterations, the NBI was shown to be superior than Lugol
Development of a low-cost cellulase production process using Trichoderma reesei for Brazilian biorefineries
No full textAbstract\ud
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Background\ud
During the past few years, the first industrial-scale cellulosic ethanol plants have been inaugurated. Although the performance of the commercial cellulase enzymes used in this process has greatly improved over the past decade, cellulases still represent a very significant operational cost. Depending on the region, transport of cellulases from a central production facility to a biorefinery may significantly add to enzyme cost. The aim of the present study was to develop a simple, cost-efficient cellulase production process that could be employed locally at a Brazilian sugarcane biorefinery.\ud
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Results\ud
Our work focused on two main topics: growth medium formulation and strain improvement. We evaluated several Brazilian low-cost industrial residues for their potential in cellulase production. Among the solid residues evaluated, soybean hulls were found to display clearly the most desirable characteristics. We engineered a Trichoderma reesei strain to secrete cellulase in the presence of repressing sugars, enabling the use of sugarcane molasses as an additional carbon source. In addition, we added a heterologous β-glucosidase to improve the performance of the produced enzymes in hydrolysis. Finally, the addition of an invertase gene from Aspegillus niger into our strain allowed it to consume sucrose from sugarcane molasses directly. Preliminary cost analysis showed that the overall process can provide for very low-cost enzyme with good hydrolysis performance on industrially pre-treated sugarcane straw.\ud
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Conclusions\ud
In this study, we showed that with relatively few genetic modifications and the right growth medium it is possible to produce considerable amounts of well-performing cellulase at very low cost in Brazil using T. reesei. With further enhancements and optimization, such a system could provide a viable alternative to delivered commercial cellulases.This work was financed by the FINEP grant 03.13.0105.00 “Produção de etanol\ud
da biomassa de cana-de-açúcar, com produção de enzimas on-site e fermen‑\ud
tação de açúcares C5”
Impact of menopause and diabetes on atherogenic lipid profile: is it worth to analyse lipoprotein subfractions to assess cardiovascular risk in women?
No full textAbstract\ud
Cardiovascular disease is the leading cause of death in women at advanced age, who are affected a decade later compared to men. Cardiovascular risk factors in women are not properly investigated nor treated and events are frequently lethal. Both menopause and type 2 diabetes substantially increase cardiovascular risk in the female sex, promoting modifications on lipid metabolism and circulating lipoproteins. Lipoprotein subfractions suffer a shift after menopause towards a more atherogenic lipid profile, consisted of hypertriglyceridemia, lower levels of both total high density lipoprotein (HDL) and its subfraction HDL2, but also higher levels of HDL3 and small low-density lipoprotein particles. This review discusses the impact of diabetes and menopause to the lipid profile, challenges in lipoprotein subfractions determination and their potential contribution to the cardiovascular risk assessment in women. It is still unclear whether lipoprotein subfraction changes are a major driver of cardiometabolic risk and which modifications are predominant. Prospective trials with larger samples, methodological standardizations and pharmacological approaches are needed to clarify the role of lipoprotein subfractions determination on cardiovascular risk prediction and intervention planning in postmenopausal women, with or without DM
Engagement of cellular prion protein with the co-chaperone Hsp70/90 organizing protein regulates the proliferation of glioblastoma stem-like cells
No full textAbstract\ud
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Background\ud
Glioblastoma (GBM), a highly aggressive brain tumor, contains a subpopulation of glioblastoma stem-like cells (GSCs) that play roles in tumor maintenance, invasion, and therapeutic resistance. GSCs are therefore a promising target for GBM treatment. Our group identified the cellular prion protein (PrPC) and its partner, the co-chaperone Hsp70/90 organizing protein (HOP), as potential target candidates due to their role in GBM tumorigenesis and in neural stem cell maintenance.\ud
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Methods\ud
GSCs expressing different levels of PrPC were cultured as neurospheres with growth factors, and characterized with stem cells markers and adhesion molecules markers through immunofluorescence and flow cytometry. We than evaluated GSC self-renewal and proliferation by clonal density assays and BrdU incorporation, respectively, in front of recombinant HOP treatment, combined or not with a HOP peptide which mimics the PrPC binding site. Stable silencing of HOP was also performed in parental and/or PrPC-depleted cell populations, and proliferation in vitro and tumor growth in vivo were evaluated. Migration assays were performed on laminin-1 pre-coated glass.\ud
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Results\ud
We observed that, when GBM cells are cultured as neurospheres, they express specific stemness markers such as CD133, CD15, Oct4, and SOX2; PrPC is upregulated compared to monolayer culture and co-localizes with CD133. PrPC silencing downregulates the expression of molecules associated with cancer stem cells, upregulates markers of cell differentiation and affects GSC self-renewal, pointing to a pivotal role for PrPC in the maintenance of GSCs. Exogenous HOP treatment increases proliferation and self-renewal of GSCs in a PrPC-dependent manner while HOP knockdown disturbs the proliferation process. In vivo, PrPC and/or HOP knockdown potently inhibits the growth of subcutaneously implanted glioblastoma cells. In addition, disruption of the PrPC-HOP complex by a HOP peptide, which mimics the PrPC binding site, affects GSC self-renewal and proliferation indicating that the HOP-PrPC complex is required for GSC stemness. Furthermore, PrPC-depleted GSCs downregulate cell adhesion-related proteins and impair cell migration indicating a putative role for PrPC in the cell surface stability of cell adhesion molecules and GBM cell invasiveness, respectively.\ud
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Conclusions\ud
In conclusion, our results show that the modulation of HOP-PrPC engagement or the decrease of PrPC and HOP expression may represent a potential therapeutic intervention in GBM, regulating glioblastoma stem-like cell self-renewal, proliferation, and migration.Fundação de Amparo à pesquisa do Estado de São Paulo (2013/19860-0 to\ud
RPI; 2009/14027-2 to VRM; 2011/13906-2 to MHL; and 2015/04122-9 to MBP),\ud
Conselho Nacional de Desenvolvimento Científico e Tecnológico (467566/\ud
2014-3 to VRM and TGS), and Coordenação de Aperfeiçoamento de Pessoal\ud
de Nível Superior (Institutional Scholarship to RPI)
Daily activity patterns influence retinal morphology, signatures of selection, and spectral tuning of opsin genes in colubrid snakes
No full textAbstract\ud
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Background\ud
Morphological divergences of snake retinal structure point to complex evolutionary processes and adaptations. The Colubridae family has a remarkable variety of retinal structure that can range from all-cone and all-rod to duplex (cone/rod) retinas. To explore whether nocturnal versus diurnal activity is responsible for constraints on molecular evolution and plays a role in visual opsin spectral tuning of colubrids, we carried out molecular evolution analyses of the visual opsin genes LWS, RH1, and SWS1 from 17 species and performed morphological analyses.\ud
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Results\ud
Phylogenetic reconstructions of the RH1 and LWS recovered major clades characterized by primarily diurnal or primarily nocturnal activity patterns, in contrast with the topology for SWS1, which is very similar to the species tree. We found stronger signals of purifying selection along diurnal and nocturnal lineages for RH1 and SWS1, respectively. A blue-shift of the RH1 spectral peak is associated with diurnal habits. Spectral tuning of cone opsins did not differ among diurnal and nocturnal species. Retinas of nocturnal colubrids had many rows of photoreceptor nuclei, with large numbers of rods, labeled by wheat germ agglutinin (WGA), and two types of cones: large cones sensitive to long/medium wavelengths (L/M) and small cones sensitive to ultra-violet/violet wavelengths (UV/VS). In contrast, retinas of diurnal species had only one row of photoreceptor nuclei, with four types of cones: large and double L/M cones, small UV/VS cones, and a second group of small cones, labeled by WGA.\ud
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Conclusions\ud
For LWS gene, selection tests did not confirm different constraints related to activity pattern. For SWS1, stronger purifying selection in nocturnal lineages indicates divergent evolutionary pressures related to the activity pattern, and the importance of the short wavelength sensitivity at low light condition. Activity pattern has a clear influence on the signatures of selection and spectral tuning of RH1, with stronger purifying selection in diurnal lineages, which indicates selective pressure to preserve rhodopsin structure and function in pure-cone retinas. We suggest that the presence of four cone types in primarily diurnal colubrids might be related to the gain of color discrimination capacity.This work was funded by the Foundation of Research Support in the State of\ud
São Paulo (FAPESP), with fellowships to EH (PhD 2010/51670–8; post-doc\ud
2014/25743–9), DMOB (postdoc 2011/17423–6) and research grants to DFV\ud
(Projeto Temático 2008/58731–2; 2014/26818–2 and Projeto Regular 2009/\ud
06026–6); and by CONICYT, Fondecyt 3,160,328 to EYS-V. DFV is a CNPq 1 A\ud
Productivity Fellow. The funders had no role in study design, data collection\ud
and analysis, decision to publish, or preparation of the manuscript
Pre-travel malaria chemoprophylaxis counselling in a public travel medicine clinic in São Paulo, Brazil
No full textAbstract\ud
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Background\ud
Malaria is one of the most prevalent parasitic diseases in the world and represents a threat to travellers visiting endemic areas. Chemoprophylaxis is the prevention measure used in travel medicine, avoiding clinical manifestations and protecting against the development of severe disease and death.\ud
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Methods\ud
Retrospective and descriptive analysis of malaria prevention data in travellers was recorded from a travel medicine clinic in São Paulo, Brazil, between January 2006 and December 2010. All the medical records of travellers, who had travelled to areas with risk of disease transmission, including Brazil, were analysed. Demographic characteristics of travellers, travel details and recommendations for preventing malaria were also seen.\ud
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Results\ud
During the study period, 2836 pre-travel consultations were carried out on 2744 individuals (92 were consulted twice). The most common reasons for travelling were tourism and work. The most common destinations were Africa (24.5%), Europe (21.2%), Asia (16.6%) and locations within Brazil (14.9%). In general prophylaxis against malaria was recommended in 10.3% of all the consultations. African destinations vs Asian, Brazilian and other destinations and length of stay ≤30 days were independently associated with the higher odds of chemoprophylaxis recommendation after the logistic regression.\ud
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Conclusion\ud
The prophylaxis against malaria was recommended in 10.3% of the consultations. The authors believe that a coherent measure of malaria prevention in Brazil and for international travellers would be to recommend for all parts of the North Brazil, avoidance of mosquito bites and immediate consultation of a physician in case of fever during or after the journey is recommended
Polymorphisms in PPARG and APOE: relationships with lipid profile of adolescents with cardiovascular risk factors
No full textAbstract\ud
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Background\ud
Cardiovascular diseases constitute the main death cause worldwide resulting from a combination of genetic and lifestyle factors, and the prevalence among younger individuals has increased. It is important to early identify changes in lipid profile and the influence of genetic variations in specific genes on the individual patterns of lipid profile. Thus, the aim of this study was to verify the relationship of polymorphisms in PPAR-gamma gene (PPARG − rs1801282 − Pro12Ala) and in apolipoprotein E gene (APOE − rs429358 + rs7412, determinants of the APOE2, APOE3, or APOE4 genotypes) with lipid profile of adolescents under cardiovascular risk factors.\ud
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Methods\ud
This was a cross-sectional study with 115 adolescents aged 10–19 years, which presented cardiovascular risk factors. The students were evaluated regarding socioeconomic, anthropometric, biochemical, genetic, and dietetic variables. Student’s t test or Mann-Whitney test were applied to the analysis of the genotypes. Multiple linear regression analysis was performed to determine the variables that most influenced the lipid profile.\ud
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Results\ud
Adolescents carrying PPARG Ala allele showed higher serum triglycerides (p = 0.0423) and very low-density lipoprotein (p = 0.0410) levels when compared to those carrying the wild genotype. For the APOE polymorphism, it was observed a trend of higher triglycerides (p = 0.0712) and very low-density lipoprotein (p = 0.0758) levels in the adolescents carrying the E4 allele when compared to those who did not carry this allele.\ud
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Conclusion\ud
The polymorphisms PPARG rs1801282 and APOE rs429358 + rs7412 seem to be related to the development of lipid profile alterations in adolescents.This study was funded by Fundação de Amparo à Pesquisa do Estado de\ud
Goiás, process number 201210267001116
Comparative muscle transcriptome associated with carcass traits of Nellore cattle
No full textAbstract\ud
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Background\ud
Commercial cuts yield is an important trait for beef production, which affects the final value of the products, but its direct determination is a challenging procedure to be implemented in practice. The measurement of ribeye area (REA) and backfat thickness (BFT) can be used as indirect measures of meat yield. REA and BFT are important traits studied in beef cattle due to their strong implication in technological (carcass yield) and nutritional characteristics of meat products, like the degree of muscularity and total body fat. Thus, the aim of this work was to study the Longissimus dorsi muscle transcriptome of Nellore cattle, associated with REA and BFT, to find differentially expressed (DE) genes, metabolic pathways, and biological processes that may regulate these traits.\ud
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Results\ud
By comparing the gene expression level between groups with extreme genomic estimated breeding values (GEBV), 101 DE genes for REA and 18 for BFT (false discovery rate, FDR 10%) were identified. Functional enrichment analysis for REA identified two KEGG pathways, MAPK (Mitogen-Activated Protein Kinase) signaling pathway and endocytosis pathway, and three biological processes, response to endoplasmic reticulum stress, cellular protein modification process, and macromolecule modification. The MAPK pathway is responsible for fundamental cellular processes, such as growth, differentiation, and hypertrophy. For BFT, 18 biological processes were found to be altered and grouped into 8 clusters of semantically similar terms. The DE genes identified in the biological processes for BFT were ACHE, SRD5A1, RSAD2 and RSPO3. RSAD2 has been previously shown to be associated with lipid droplet content and lipid biosynthesis.\ud
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Conclusion\ud
In this study, we identified genes, metabolic pathways, and biological processes, involved in differentiation, proliferation, protein turnover, hypertrophy, as well as adipogenesis and lipid biosynthesis related to REA and BFT. These results enlighten some of the molecular processes involved in muscle and fat deposition, which are economically important carcass traits for beef production.This study was conducted with funding from Embrapa (Macroprograma 1,\ud
01/2005) and FAPESP (process number 2012/23638–8). LCAR and LLC were granted CNPq fellowships
26th Annual Computational Neuroscience Meeting (CNS*2017): Part 2
No full textResearch supported by FAPESP 2015/50122-0 and DFG-GRTK 1740/2. RP and AR are also part of the Research, Innovation and Dissemination Center for Neuromathematics FAPESP grant (2013/07699-0). RP is supported by a FAPESP scholarship (2013/25667-8). ACR is partially supported by a CNPq fellowship (grant 306251/2014-0)