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This article presents a proposal for the implementation of the Grand Challenges Scholars Program (GCSP), created by the National Academy of Engineering, in an engineering teaching institution in Brazil. The GCSP focuses on teaching by soft skills and shows great intersection with the soft skills of Curricular Guidelines for engineering programs in Brazil. Besides this relation, it is clear that the use of active strategies for learning is a point of encounter between these two strategies and, in particular, the use of projects and PBL, can be the inducer for learning these strategies. The GCSP aims to build soft skills in their participating students by placing them in the face of major problems. This work involves the elaboration of a possible way of implementing the GCSP in an educational institution and, as a reference, the construction of a project in the area of Mechanical Engineering. The GCSP requires customization, hence each student receives individual guidance from a tutor who will shape the student`s path to optimize his performance in the program. The implementation of this new teaching approach becomes important, since, currently, the freshmen in university programs, in most cases, do not arrive with the experience in the job market that students of the past used to have. In that way, only the technical part of the academic training is not enough for the professional development of the student who is inserted in an increasingly competitive job market, requiring flexible and versatile engineers, capable of proposing solutions to the most diverse problems. The work is based on document analysis method and an recorded interview with a key person to implement this proposal.

BackgroundThe repeatome, the collection of repetitive DNA sequences represented by transposable elements (TEs) and tandemly repeated satellite DNA (satDNAs), is found in high proportion in organisms across the tree of life. Grasshoppers have large genomes (average 9 Gb), containing large amounts of repetitive DNA which has hampered progress in assembling reference genomes. Here we combined linked-read genomics with transcriptomics to assemble, characterize, and compare the structure of the repeatome and its contribution to genome evolution, in four chromosomal races of the morabine grasshopperVandiemenella viaticaspecies complex.ResultsWe obtained linked-read genome assemblies of 2.73-3.27 Gb from estimated genome sizes of 4.26-5.07 Gb DNA per haploid genome of the four chromosomal races ofV. viatica. These constitute the third largest insect genomes assembled so far (the largest being two locust grasshoppers). Combining complementary annotation tools and manual curation, we found a large diversity of TEs and satDNAs constituting 66 to 75 % per genome assembly. A comparison of sequence divergence within the TE classes revealed massive accumulation of recent TEs in all four races (314-463 Mb per assembly), indicating that their large genome size is likely due to similar rates of TE accumulation across the four races. Transcriptome sequencing showed more biased TE expression in reproductive tissues than somatic tissues, implying permissive transcription in gametogenesis. Out of 129 satDNA families, 102 satDNA families were shared among the four chromosomal races, which likely represent a repertoire of satDNA families in the ancestor of theV. viaticachromosomal races. Notably, 50 of these shared satDNA families underwent differential proliferation since the recent diversification of theV. viaticaspecies complex.ConclusionIn-depth annotation of the repeatome in morabine grasshoppers provided new insights into the genome evolution of Orthoptera. Our TEs analysis revealed a massive recent accumulation of TEs equivalent to the size of entireDrosophilagenomes, which likely explains the large genome sizes in grasshoppers. Although the TE and satDNA repertoires were rather similar between races, the patterns of TE expression and satDNA proliferation suggest rapid evolution of grasshopper genomes on recent timescales.

Made available in DSpace on 2020-12-12T00:07:54Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-08-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Background: Well studied in patients with ischemic stroke after reperfusion thera-pies (RT), hemorrhagic transformation (HT) is also common in patients not treated with RT and can lead to disability even in initially asymptomatic cases. The best predictors of HT in patients not treated with RT are not well established. Therefore, we aimed to identify predictors of HT in patients not submitted to RT and create a user-friendly predictive score (PROpHET). Material and Methods: Patients admitted to a Comprehensive Stroke Center from 2015 to 2017 were prospectively evaluated and randomly selected to the derivation cohort. A multivariable logistic regression modeling was built to produce a predictive grading score for HT. The external vali-dation was assessed using datasets from 7 Comprehensive Stroke Centers using the area under the receiver operating characteristic curve (AUROC). Results: In the derivation group, 448 patients were included in the final analysis. The validation group included 2,683 patients. The score derived from significant predictors of HT in the multivariate logistic regression analysis was male sex (1 point), ASPECTS = 180 mg/dL (1 point), cardioembolism (1 point) and lacunar syndrome (-3 points) as a protective factor. The grading score ranges from -3 to 7. A Score >= 3 had 78.2% sensitivity and 75% specificity, and AUROC of 0.82 for all cases of HT. In the validation cohort, our score had an AUROC of 0.83. Conclusions: The PROpHET is a simple, quick, cost-free, and easy-to-perform tool that allows risk stratification of HT in patients not submitted to RT. A cost-free computerized version of our score is available online with a user-friendly interface. Univ Fed Sao Paulo, Rua Napoleao Barros 715, Sao Paulo, SP, Brazil Columbia Univ, Doris & Stanley Tananbaum Stroke Ctr, Neurol Inst New York, 710 W 168th St,6TH Floor,NI 614, New York, NY 10032 USA Univ Fortaleza, Fortaleza, Cear, Brazil Hosp Geral Fortaleza, Fortaleza, Ceara, Brazil Univ Fed Ceara, Campus Quixada, Quixada, CE, Brazil Univ Fed Bahia, Salvador, BA, Brazil Univ Sao Paulo, Ribeirao Preto, Brazil Univ Estadual Paulista, Sao Paulo, Brazil Hosp Inst Neurol Curitiba, Curitiba, Parana, Brazil Hosp Geral Fortaleza, Rua Avila Goulart 900, Fortaleza, CE, Brazil Praca 15 Novembro SN, Salvador, BA, Brazil Hosp Clin, Floor 4th, Ribeirao Preto, SP, Brazil Av Prof Mario Rubens Guimaraes Montenegro, Botucatu, SP, Brazil R Jeremias Maciel Perretto 300, Curitiba, PR, Brazil Hosp Israelita Brasileiro Albert Einstein, Rua Albert Einstein 627, Sao Paulo, SP, Brazil Univ Estadual Paulista, Sao Paulo, Brazil

It is a broadly observed pattern that the non-recombining regions of sex-limited chromosomes (Y and W) accumulate more repeats than the rest of the genome, even in species like birds with a low genome-wide repeat content. Here, we show that in birds with highly heteromorphic sex chromosomes, the W chromosome has a transposable element (TE) density of greater than 55% compared to the genome-wide density of less than 10%, and contains over half of all full-length (thus potentially active) endogenous retroviruses (ERVs) of the entire genome. Using RNA-seq and protein mass spectrometry data, we were able to detect signatures of female-specific ERV expression. We hypothesize that the avian W chromosome acts as a refugium for active ERVs, probably leading to female-biased mutational load that may influence female physiology similar to the ‘toxic-Y’ effect in Drosophila males. Furthermore, Haldane's rule predicts that the heterogametic sex has reduced fertility in hybrids. We propose that the excess of W-linked active ERVs over the rest of the genome may be an additional explanatory variable for Haldane's rule, with consequences for genetic incompatibilities between species through TE/repressor mismatches in hybrids. Together, our results suggest that the sequence content of female-specific W chromosomes can have effects far beyond sex determination and gene dosage. This article is part of the theme issue ‘Challenging the paradigm in sex chromosome evolution: empirical and theoretical insights with a focus on vertebrates (Part II)’.

BackgroundAlthough the Head Positioning in acute Stroke Trial (HeadPoST) showed no effect of the flat head position (FP; vs sitting up head position (SUP)) on functional outcome, we hypothesised that it could still offer benefits if commenced early in those with acute ischaemic stroke (AIS) of at least moderate severity.MethodsSubgroup analysis of HeadPoST in participants with National Institutes of Health Stroke Scale (NIHSS) scores ≥7, ≥10 and ≥14, randomised to FP or SUP ResultsThere was no significant differential treatment effect in patient subgroups defined by increasing baseline NIHSS scores: adjusted OR and 95% CI for ordinal shift and binary (3–6) mRS scores: for NIHSS ≥7 (n=867) 0.92 (0.67 to 1.25) and 0.74 (0.52 to 1.04); NIHSS ≥ 10 (n=606) 0.80 (0.58 to 1.10) and 0.77 (0.49 to 1.19); NIHSS ≥14 (n=378) 0.82 (0.54 to 1.24) and 1.22 (0.69 to 2.14).ConclusionsEarly FP had no significant effect in patients with moderate–severe AIS.Trial registration numberNCT02162017.

Given their copy number differences and unique modes of inheritance, the evolved gene content and expression of sex chromosomes is unusual. In many organisms the X and Y chromosomes are inactivated in spermatocytes, possibly as a defense mechanism against insertions into unpaired chromatin. In addition to current sex chromosomes, Drosophila has a small gene-poor X-chromosome relic (4th) that re-acquired autosomal status. Here we use single cell RNA-Seq on fly larvae to demonstrate that the single X and pair of 4th chromosomes are specifically inactivated in primary spermatocytes, based on measuring all genes or a set of broadly expressed genes in testis we identified. In contrast, genes on the single Y chromosome become maximally active in primary spermatocytes. Reduced X transcript levels are due to failed activation of RNA-Polymerase-II by phosphorylation of Serine 2 and 5., Sex chromosome gene content and expression is unusual. Here the authors use single cell RNA-Seq on Drosophila larvae to demonstrate that the single X and pair of 4th chromosomes are specifically inactivated in primary spermatocytes, while genes on the single Y chromosome become maximally active in primary spermatocytes.

Background: The increasing demand and shortage of experts to evaluate and treat acute stroke patients has led to the development of remote communication tools to aid stroke management. We aimed to describe the experience of the Brazilian Stroke Network in the implementation of a telemedicine stroke program using a low-cost smartphone application system (JOIN App, Allm, Japan) for rapid sharing of clinical and neuroimaging patient data. Methods: We evaluated the initial experience of the telestroke program using a smartphone app measuring its feasibility, safety and speed in the acute stroke decision-making process, with a particular focus on intravenous thrombolysis. The App was implemented in hospitals without neurologists available for acute stroke evaluation and was connected with a stroke team to support the decision for thrombolysis. We analyzed the times of acute treatment and safety through the rate of symptomatic intracranial hemorrhage (sICH) in 24hours. The program was implemented as part of the partnership with the Angels Initiative in Brazil supported by Boehringer Ingelheim to improve stroke care across the globe. Results: The telestroke program started in May 2019 and since then 7 hospitals, in 5 Brazilian states, were included. Only 2 of these hospitals had previous experience with stroke thrombolysis. In all hospitals, the patients were assisted by emergency physicians with eventual support of local neurologists. The telestroke program was activated for 58 patients. The median age was 68yo (IQR58-72), 47% were female and the baseline NIHSS was 11 (IQR8-16). In 69% of the activation the diagnosis was ischemic stroke (IS), 7% hemorrhagic, 5% TIA and 28% other diagnosis. Thrombolysis was suggested in 48% of all evaluations (70% of IS patients). A total of 53% of IS were actually treated with thrombolys. The response-time of the stroke experts was 2.6 minutes (2-6), door-to-CT scan 20min (15-31) and door-needle time 59min (27-81). None of the patients had sICH. Conclusion: In a telestroke program using a smartphone App, thrombolysis performed by emergency physicians was feasible and safe. This mobile low cost technology can increase the possibility of patients with stroke to receive treatment in regions without neurologists across the globe.

Background and purpose: RESILIENT Trial was the first study in a developing country to demonstrate the benefit of mechanical thrombectomy (MT) in acute stroke patients. This economic evaluation aimed to access the cost-utility of MT under the perspective of the Brazilian Public Healthcare System. Methods: Analysis was based on a subset sample of the original study (151 of 221 patients) from 4 hospitals. We compared costs and utilities between MT plus standard care (n=78) vs. standard care alone (n=73). Direct medical costs were considered, and utilities were inputted according to each patient’s Utility-Weighted modified Rankin Score (UW-mRS). First-year survival was obtained from trial follow-up and modelled for a life-time horizon adjusted by National Mortality Data. Direct medical costs were converted to I$ using Purchasing Power Parity (PPP). A discount rate of 5% was used. Incremental cost-effectiveness ratio (ICER) is expressed in cost (I$) per Quality-Adjusted Life Year (QALY). Results: RESILIENT trial was stopped on its first interim analysis because of early efficacy. The incremental costs and QALYs gained with MT were estimated at I$ 8,369 and 0.75, respectively, compared with standard medical care, yielding an incremental cost-effectiveness ratio (ICER) of I$ 7,256 per QALY. Conclusion: The initially higher costs of MT were offset by the clear benefit of the intervention. RESILIENT trial demonstrated that such therapy is likely to be cost-effective despite the economical constraints in the Brazilian healthcare system.

Background: Mechanical thrombectomy (MT) in addition to intravenous thrombolysis (IVT) is now the recommended treatment for acute ischemic stroke (AIS) patients with large vessel occlusion (LVO). The positive trials also demonstrated that MT alone among patients ineligible for IVT is an effective therapy for AIS. Whether MT alone is as effective, worse, or better than pretreatment with IVT before MT among IVT-eligible AIS patients with LVO is debatable. We aimed to assess the effect of IVT on the clinical outcome of MT in the RESILIENT trial. Methods: RESILIENT was a randomized, prospective, multicenter, controlled trial evaluating the safety, efficacy, and cost-effectiveness of thrombectomy versus medical treatment alone. A total of 221 patient were enrolled. The trial showed a strong benefit to thrombectomy (90-day mRS ordinal shift, OR 95%CI). All eligible patients received intravenous tPA within the 4.5-hour-window. The primary end-point was the common odds ratio (cOR) of mRs at 90 days (shift analysis) and the main secondary endpoint was the rate of functional independence (mRS 0-2) at 90 days. Ordinal logistic and binary regression analyses with the use of intravenous tPA as an interaction term were performed with adjustments for potential confounders including age, baseline NIHSS score, occlusion site, IV tPA use and ASPECTS. A p value < 0.05 was considered statistically significant. Results: Among 221 randomized patients (median NIHSS, 18 IQR [14-21]), 155 (70%) were treated with IV tPA. The frequency of good recanalization (TICI 2b> ) and of hemorrhagic transformation was not affected by IVT. There was no significant difference in the treatment effect size across patients who received intravenous tPA versus those who did not in terms of overall functional disability (ordinal mRS shift: aOR: 2.63, 95%CI [1.48-4.69] vs. 1.54, 95%CI [0.63-3.74]; p=0.42) or functional independence (mRS 0-2: aOR: 3.06, 95%CI [1.37-6.48] vs. 1.71 95%CI [0.55-5.33], p=0.40) at 90 days. Conclusions: The large effect size of MT on LVO outcomes was not significantly affected by IVT. Further studies directly evaluating the role of IVT before MT are of utmost importance.

Background: Despite evidence supporting the overall efficacy of mechanical thrombectomy (MT) in acute ischemic stroke (AIS) due to large vessel occlusion (LVO) of the anterior circulation, it is unclear whether the treatment effect of MT differs by sex in different populations. We assessed the impact of sex differences in the treatment effect of MT in the RESILIENT trial. Methods: RESILIENT was a prospective, multicenter, randomized phase III trial that was designed to assess the safety, efficacy, and cost-effectiveness of mechanical thrombectomy as compared to medical treatment alone in patients treated under the less than ideal conditions typically found in the public healthcare system of a developing country. Results: Among 221 patients enrolled in the trial, 104 (47,1%) were female. Baseline characteristics were well balanced between sexes, except for a higher prevalence of hypertension (76% vs. 57.4%; p=0.004) and diabetes (34.3% vs. 21.7%; p=0.039) and a lower frequency of alcohol abuse (4% vs. 28.9%; p=0.001) in females. After adjustment for baseline characteristics, we found a significant interaction (p=0.026) between sex and the effect of MT with a lower efficacy of MT for functional independency at 90 days among women (aOR=1.13;95%CI:0.42-3.02) compared to men (aOR=4.78; 95%CI:1.88-12.15). Conclusions: In our study population of patients with AIS caused by LVO of the anterior circulation, women were less likely to benefit from MT than men. Further studies are necessary to investigate these findings.

Background: The RESILIENT randomized trial of endovascular therapy for anterior circulation stroke within 8 hours of symptom onset excluded subjects with poor collaterals. We analyzed the relationship of CTA collateral grade with respect to subsequent infarct growth over 24 hours, with and without revascularization. Methods: The independent RESILIENT imaging and angiography core lab scored baseline CTA Tan collateral grade (0-3) and CT ASPECTS scores at baseline and 24 hours in both arms. ASITN collateral grade (0-4) was adjudicated prior to revascularization in the interventional arm. Descriptive statistics, univariate, multivariate and ANOVA related CTA collateral grade with 24-hour infarct growth. Results: 210/221 (95%) subjects (median age 67 (53-76) years; 48% women) in RESILIENT had baseline single-phase CTA available to the core lab evaluation. CTA collateral grade was complete (grade 3) in 106 (50.5%), grade 2 (50-99%) in 68 (32.4%), grade 1 (1-49%) in 36 (17.1%), with no collaterals in 0. The extent of collaterals was more robust in the medical arm (55.0% grade 3, 31.4% grade 2, 13.3% grade 1) compared to the interventional arm (45.7% grade 3, 33.3% grade 2, 21.0% grade 1), although this finding was not statistically significant (p=0.11). In the interventional arm, the extent of CTA collaterals had a strong correlation with ASITN grade (ρ=0.59, p Conclusions: In RESILIENT, CTA collateral grade was linked with higher ASPECTS and less infarct growth over 24 hours. Despite more robust collaterals in the medical arm, greater infarct growth occurred without revascularization or endovascular therapy.

Background: Randomized trials performed in high income countries have shown similar effects of mechanical thrombectomy (MT) in elderly and non-elderly patients with large vessel ischemic strokes (LVO). We aimed to assess the effect of age on the clinical outcome of MT in RESILIENT (a randomized, prospective, multicenter, controlled, phase III, clinical trial with blinded outcome assessment performed in Brazil designed to assess the safety, efficacy, and cost-effectiveness of mechanical thrombectomy as compared to medical treatment alone). Methods: Patients were classified as elderly and non-elderly (≤ 70 vs. > 70 years). The end-points were the common odds ratio (cOR) of mRs (shift analysis) and the frequency of functional independence (mRS 0-2) at 90 days. Ordinal logistic regression analysis (unadjusted and adjusted for important potential confounders) with age group as an interaction term were performed. A p value < 0.05 was considered statistically significant. Results: Among 221 randomized patients (117- 52.9% males), 89 (40.2%) were classified as elderly. Age had an important effect modification of MT on the mRS shift analysis (elderly - cOR 1.20 95% CI [0.57-2.51] vs. non-elderly cOR 3.9, 95% CI [1.65-5.80], p-interaction = 0.003) and on the frequency of functional independence at 90 days (elderly - OR 0.92 95% CI [0.33 - 2.59] vs. non-elderly OR 3.56, 95% CI [1.64 - 7.75], p-interaction = 0.04). A similar effect modification was observed after adjusting for IV rt-PA, occlusion site, baseline NIHSS and ASPECTS on the mRS shift analysis (elderly - cOR 1.34, 95% CI [0.63 - 2.86] vs. non-elderly cOR 3.26, 95% CI [1.73 - 6.13], p-interaction = 0.06) and on the frequency of functional independence at 90 days (elderly - OR 1.08 95% CI [0.36 - 3.21] vs. non-elderly OR 4.26, 95% CI [1.85 - 9.82], p-interaction = 0.04) . Conclusion: The large effect size of MT on LVO outcomes is significantly diminished in the elderly population of patients treated under the less than ideal conditions typically found in the public healthcare system of a developing country.

Objective: To create an accurate and user-friendly pr edictive sc o re for he morrhagic t ransformation in patients not submitted to reperfusion therapies (PROpHET). Methods: We created a multivariable logistic regression model to assess the prediction of Hemorrhage Transformation (HT) for acute ischemic strokes not treated with reperfusion therapy. One point was assigned for each of gender, cardio-aortic embolism, hyperdense middle cerebral artery sign, leukoaraiosis, hyperglycemia, 2 points for ASPECTS ≤7, and -3 points for lacunar syndrome. Acute ischemic stroke patients admitted to the Fortaleza Comprehensive Stroke Center in Brazil from 2015 to 2017 were randomly selected to the derivation cohort. The validation cohort included similar, but not randomized, cases from 5 Brazilian and one American Comprehensive Stroke Centers. Symptomatic cases were defined as NIHSS ≥4 at 24 hours after the event. Results from the derivation and validation cohorts were assessed with the area under the receiver operating characteristic curve (AUC-ROC). Results: From 2,432 of acute ischemic stroke screened in Fortaleza, 448 were prospectively selected for the derivation cohort and a 7-day follow-up. From 1,847 not selected, 577 underwent reperfusion therapy, 734 were excluded due to inadequate imaging or refusal of consent, and 538 whose data were obtained retrospectively and were selected only for the validation cohort. A score ≥3 had 78% sensitivity and 75% specificity, AUC-ROC 0.82 for all cases of HT, Hosmer-Lemeshow 0.85, Brier Score 0.1, and AUC-ROC 0.83 for those with symptomatic HT. An AUC-ROC of 0.84 was found for the validation cohort of 1,910 from all 6 centers, and a score ≥3 was found in 65% of patients with HT against 11.3% of those without HT. In comparison with 8 published predictive scores of HT, PROpHET was the most accurate (p < 0.01). Conclusions: PROpHET offers a tool simple, quick and easy-to-perform to estimate risk stratification of HT in patients not submitted to RT. A digital version of PROpHET is available in www.score-prophet.com Classification of evidence: This study provides Class I evidence from prospective data acquisition.

Background: CT perfusion has been increasingly used as a selection tool in acute reperfusion therapies. However, it remains unknown whether its use is associated with a higher treatment benefit in patients undergoing thrombectomy. We sought to evaluate the interaction between imaging selection modalities and treatment effect in the RESILIENT Trial. Methods: RESILIENT was a randomized, prospective, multicenter, controlled trial evaluating the safety, efficacy, and cost-effectiveness of thrombectomy versus medical treatment alone in Brazil. A total of 221 patient were enrolled. The trial showed a strong benefit of thrombectomy (90-day mRS ordinal shift, OR 2.28 95%CI [1.41-3.70]; p=0.001). Key imaging selection criteria included ASPECTS ≥6 on non-contrast CT (NCCT) and the exclusion of malignant collateral profile on CT angiography. The use of automated CT perfusion software (RAPID, IschemaView) was optional but was made available in some centers with the pre-specified plan to compare imaging selection modalities. The primary end-point was the common odds ratio (cOR) of mRs at 90 days (shift analysis) and the main secondary endpoint was the rate of functional independence (mRS 0-2) at 90 days. Ordinal logistic and binary regression analyses with imaging selection modality (NCCT versus CTP) as an interaction term were performed with adjustments for potential confounders including age, baseline NIHSS score, occlusion site, IV tPA use and ASPECTS. A p value < 0.05 was considered statistically significant. Results: CTP was performed in 41% of the thrombectomy group and 45% in the control group. There was no significant difference in the treatment effect size for patients selected on the basis of NCCT and CTA only versus those submitted to CTP in terms of overall functional disability (ordinal mRS shift: aOR: 2.87, 95%CI [1.47-5.61] vs. 2.10, 95%CI [1.01-4.36]; p=0.390) or functional independence (mRS 0-2: aOR: 3.16, 95%CI [1.32-7.57] vs. 2.54 95%CI [0.86-7.49], p=0.40) at 90 days. Conclusion: In a randomized clinical trial of thrombectomy within 8 hours of stroke onset, there was no evidence of difference in the treatment effect size across patients selected with NCCT and CTA alone versus automated CT perfusion software.

Modernization in agriculture and crops produced for export crops strongly impact in rural areas. We preliminarily analyze changes in crop patterns and their potential impact on groundwater consumption in three municipalities in the state of Michoacan (western Mexico). Specifically, it examines the pressures exerted on the aquifer of a sub-basin of the Lerma River, and the conditions of an unequal distribution of hydric resources. From a geographic perspective, we use three variables to evaluate the pressure placed on hydric resources: the number of deep wells, their depth, and the volume of water authorized in concessions. This first approximation allowed us to visualize areas that are at risk for over-exploitation, an important advance, since few hydrological studies have been conducted on the level of hydraulic equilibrium of aquifers in Mexico. Finally, we also focused on the increase in well-drilling in the area around this aquifer in the Bajio michoacano .

The burden of stroke in Brazil, as in other developing countries, has considerably increased over the past years. With incidence rates ranging from 105 to 137 cases per 100 000 persons per year and mortality reaching 24%, stroke is a major public health issue in this continental country. Although most strokes in Brazil can be attributed to classic treatable cardiovascular risk factors, infectious diseases such as Chagas disease, arboviruses hemorrhagic fevers, neurocysticercosis, and malaria are also important risk factors. Socioeconomic disparities and population unawareness about stroke symptoms are great challenges in Brazil. There was an improvement in stroke awareness after the Brazilian Stroke Society and the World Stroke Organization launched several campaigns throughout the country. Another important step was taken in 2012, when the Brazilian Ministry of Health published the Brazilian National Stroke Act, including reimbursement for rtPA, creation of stroke centers qualified according to the hospital complexity, integration of the Brazilian Emergency Medical System, establishment of a budget for the rehabilitation system, and education and training of healthcare professionals and of the population. Since these measures, the number of stroke centers increased from 35 in 2008 to 149 in 2017 and stroke mortality in public stroke centers decreased from 17.9% in 2010 to 12.8% in 2014. Although much has improved, Brazil still has major social inequalities and further measures are needed to guarantee a high-quality stroke care.

Background: Mirror therapy (MT) is becoming an alternative rehabilitation strategy for various conditions, including stroke. Although recent studies suggest the positive benefit of MT in chronic stroke motor recovery, little is known about its neural mechanisms. Purpose: To identify functional brain changes induced by a single MT intervention in ischemic stroke survivors, assessed by both transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI). Materials and methods: TMS and fMRI were used to investigate 15 stroke survivors immediately before and after a single 30-min MT session. Results: We found statistically significant increase in post-MT motor evoked potential (MEP) amplitude (increased excitability) from the affected primary motor cortex (M1), when compared to pre-MT MEP. Post-MT fMRI maps were associated with a more organized and constrained pattern, with a more focal M1 activity within the affected hemisphere after MT, limited to the cortical area of hand representation. Furthermore, we find a change in the balance of M1 activity toward the affected hemisphere. In addition, significant correlation was found between decreased fMRI β-values and increased MEP amplitude post-MT, in the affected hemisphere. Conclusion: Our study suggests that a single MT intervention in stroke survivors is related to increased MEP of the affected limb, and a more constrained activity of the affected M1, as if activity had become more constrained and limited to the affected hemisphere.

Fil: Palacios Gimenez, Octavio M. Universidad Estatal Paulista Julio de Mesquita Filho. Instituto de Biociencias. Departamento de Biología; Brasil. Fil: Milani, Diogo. Universidad Estatal Paulista Julio de Mesquita Filho. Instituto de Biociencias. Departamento de Biología; Brasil. Fil: Lemos, Bernardo. Universidad de Harvard. Escuela de Salud Pública. Departamento de Salud Ambiental. Programa de Ciencias Fisiológicas Moleculares e Integrativas; Estados Unidos. Fil: Castillo, Elio Rodrigo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico (Nordeste). Instituto de Biología Subtropical; Argentina. Fil: Castillo, Elio Rodrigo Daniel. Universidad Nacional de Misiones. Facultad de Ciencias Exactas, Química y Naturales. Instituto de Biología Subtropical; Argentina. Fil: Marti, Dardo Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico (Nordeste). Instituto de Biología Subtropical; Argentina. Fil: Marti, Dardo Andrea Universidad Nacional de Misiones. Facultad de Ciencias Exactas, Química y Naturales. Instituto de Biología Subtropical; Argentina. Fil: Ramos, Erica. Universidad Estatal Paulista Julio de Mesquita Filho. Instituto de Biociencias. Departamento de Morfología; Brasil. Fil: Cabral De Mello, Diogo C. Universidad Estatal Paulista Julio de Mesquita Filho. Instituto de Biociencias. Departamento de Morfología; Brasil. Fil: Martins, Cesar. Universidad Estatal Paulista Julio de Mesquita Filho. Instituto de Biociencias. Departamento de Biología; Brasil. Background Neo-sex chromosome systems arose independently multiple times in evolution, presenting the remarkable characteristic of repetitive DNAs accumulation. Among grasshoppers, occurrence of neo-XY was repeatedly noticed in Melanoplinae. Here we analyzed the most abundant tandem repeats of R. bergii (2n = 22, neo-XY♂) using deep Illumina sequencing and graph-based clustering in order to address the neo-sex chromosomes evolution. Results The analyses revealed ten families of satDNAs comprising about ~1% of the male genome, which occupied mainly C-positive regions of autosomes. Regarding the sex chromosomes, satDNAs were recorded within centromeric or interstitial regions of the neo-X chromosome and four satDNAs occurred in the neo-Y, two of them being exclusive (Rber248 and Rber299). Using a combination of probes we uncovered five well-defined cytological variants for neo-Y, originated by multiple paracentric inversions and satDNA amplification, besides fragmented neo-Y. These neo-Y variants were distinct in frequency between embryos and adult males. Conclusions The genomic data together with cytogenetic mapping enabled us to better understand the neo-sex chromosome dynamics in grasshoppers, reinforcing differentiation of neo-X and neo-Y and revealing the occurrence of multiple additional rearrangements involved in the neo-Y evolution of R. bergii. We discussed the possible causes that led to differences in frequency for the neo-Y variants between embryos and adults. Finally we hypothesize about the role of DNA satellites in R. bergii as well as putative historical events involved in the evolution of the R. bergii neo-XY.

Made available in DSpace on 2018-12-11T16:53:11Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-04-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Satellite DNA (satDNA) is an abundant class of non-coding repetitive DNA that is preferentially found as tandemly repeated arrays in gene-poor heterochromatin but is also present in gene-rich euchromatin. Here, we used DNA- and RNA-seq from Gryllus assimilis to address the content and transcriptional patterns of satDNAs. We also mapped RNA-seq libraries for other Gryllus species against the satDNAs found in G. assimilis and G. bimaculatus genomes to investigate their evolutionary conservation and transcriptional profiles in Gryllus. Through DNA-seq read clustering analysis using RepeatExplorer, dotplots analysis and fluorescence in situ hybridization mapping, we found that â 1/44% of the G. assimilis genome is represented by 11 well-defined A + T-rich satDNA families. These are mainly located in heterochromatic areas, with some repeats able to form high-order repeat structures. By in silico transcriptional analysis we identified satDNAs that are conserved in Gryllus but differentially transcribed. The data regarding satDNA presence in G. assimilis genome were discussed in an evolutionary context, with transcriptional data enabling comparisons between sexes and across tissues when possible. We discuss hypotheses for the conservation and transcription of satDNAs in Gryllus, which might result from their role in sexual differentiation at the chromatin level, heterochromatin formation and centromeric function. Departamento de Biologia Instituto de Biociências/IB UNESP-Univ Estadual Paulista Program in Molecular and Integrative Physiological Sciences Department of Environmental Health Harvard University T. H. Chan School of Public Health Departamento de Biologia Instituto de Biociências/IB UNESP-Univ Estadual Paulista FAPESP: 2014/11763-8 FAPESP: 2015/16661-1

Background Intravenous thrombolysis (IVT) and endovascular therapy (EVT) were proven safe and effective for anterior circulation proximal occlusions. However, the most appropriate recanalization strategy in patients with acute basilar artery occlusion (BAO) is still controversial. This study aimed to assess outcomes of patients with BAO at an academic stroke center in Brazil. Methods This is a retrospective analysis of consecutive patients with BAO from a prospective stroke registry at Ribeirao Preto Medical School. Primary outcomes were mortality and favorable outcome (modified Rankin score [mRS] ≤3) at 90 days. After univariate analyses, multivariate logistic regressions were used to identify independent predictors of primary outcomes. Results Between August 2004 and December 2015, 63 (65% male) patients with BAO and median National Institutes of Health Stroke Scale (NIHSS) score of 31 (interquartile range: 19-36) were identified. Twenty-nine (46%) patients received no acute recanalization therapy, 15 (24%) received IVT, and 19 (30%) received EVT (68% treated with stent retrievers). Twenty-four (83%) patients treated conservatively died, and only 2 (7%) achieved an mRS less than or equal to 3. Among patients treated with acute recanalization therapies, 15 (44%) died, and 9 (26.5%) had a favorable outcome. On multivariate analysis, baseline systolic blood pressure (odds ratio [OR] = .97; 95% confidence interval [CI]: .95-0.99; P = .023), posterior circulation Alberta Stroke Program Early CT score (OR = .62; 95% CI: .41-0.94; P = .026), and successful recanalization (OR = .18; 95% CI: .04-0.71; P = .015) were independent predictors of lower mortality. Baseline NIHSS (OR = 1.40; 95% CI: 1.08-1.82; P = .012), prior use of statins (OR = .003; 95% CI: .001-0.28; P = .012), and successful recanalization (OR = .05; 95% CI: .001-0.27; P = .009) were independent predictors of favorable outcome. There was no significant difference between the IVT group and the EVT group on primary outcomes. Conclusions BAO is associated with high morbidity and mortality in Brazil. Access to acute recanalization therapies may decrease mortality in those patients.

Background and Purpose— Many patients receiving thrombolysis for acute ischemic stroke are on prior antiplatelet therapy (APT), which may increase symptomatic intracerebral hemorrhage risk. In a prespecified subgroup analysis, we report comparative effects of different doses of intravenous alteplase according to prior APT use among participants of the international multicenter ENCHANTED study (Enhanced Control of Hypertension and Thrombolysis Stroke Study). Methods— Among 3285 alteplase-treated patients (mean age, 66.6 years; 38% women) randomly assigned to low-dose (0.6 mg/kg) or standard-dose (0.9 mg/kg) intravenous alteplase within 4.5 hours of symptom onset, 752 (22.9%) reported prior APT use. Primary outcome at 90 days was the combined end point of death or disability (modified Rankin Scale [mRS] scores, 2–6). Other outcomes included mRS scores 3 to 6, ordinal mRS shift, and symptomatic intracerebral hemorrhage by various standard criteria. Results— There were no significant differences in outcome between patients with and without prior APT after adjustment for baseline characteristics and management factors during the first week; defined by mRS scores 2 to 6 (adjusted odds ratio [OR], 1.01; 95% confidence interval [CI], 0.81–1.26; P =0.953), 3 to 6 (OR, 0.95; 95% CI, 0.75–1.20; P =0.662), or ordinal mRS shift (OR, 1.03; 95% CI, 0.87–1.21; P =0.770). Alteplase-treated patients on prior APT had higher symptomatic intracerebral hemorrhage (OR, 1.82; 95% CI, 1.00–3.30; P =0.051) according to the safe implementation of thrombolysis in stroke-monitoring study definition. Although not significant ( P -trend, 0.053), low-dose alteplase tended to have better outcomes than standard-dose alteplase in those on prior APT compared with those not using APT (mRS scores of 2–6; OR, 0.84; 95% CI, 0.62–1.12 versus OR, 1.16; 95% CI, 0.99–1.36). Conclusions— Low-dose alteplase may improve outcomes in thrombolysis-treated acute ischemic stroke patients on prior APT, but this requires further evaluation in a randomized controlled trial. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01422616.