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Grasshoppers in the genus Ronderosia (divergence time

Progress in precision medicine is being achieved through the design of clinical trials that use genetic biomarkers to guide stratification of patients and assignation to treatment or control groups. Genetic analysis of biomarkers is, therefore, essential to complete their objectives, and this involves the study of biological samples from donor patients that have been recruited according to criteria previously established in the design of the clinical trial. Nevertheless, it is becoming very common that, in the solicitation of biological samples, purposes that are beyond the objectives of the stated therapeutic trial research are introduced, like the development of ill-explained exploratory studies or the use in unspecified future research. In the digital era, the sequencing of patients’ DNA needs to be considered as a serious security matter, not only for the patients, but also for their relatives. Genetic information may be easily stored, even forever, in digital files. This engenders a permanent risk of being stolen or misused in many ways. Furthermore, re-identification of sample donors is technically feasible through their genetic data. For these reasons, genetic analysis of samples collected in clinical trials should be restricted to the accomplishment of their main objectives or well justified goals.

Introduction: Poststroke apathy (PSA) is a common neuropsychiatric disorder that may affect up to 30% of stroke patients. Despite the difficulties of investigating this condition (overlapping with depression, heterogeneity of diagnostic criteria, a small number of studies), some recent diffusion tensor imaging studies have suggested that widespread microstructural white matter (WM) disruption plays a key role in the development of PSA. Therefore, we intended to investigate this hypothesis by evaluating the relationship between WM hyperintensities (WMH) and apathy in patients with cerebrovascular disease. Methods: We studied patients with apathy (n = 7), depression (n = 13), comorbid apathy and depression (n = 13), and controls (n = 20), and we investigated the variables associated with the volume of WMH measured by an automated brain MRI segmentation software. Results: The overall prevalence of PSA was 37.7% (pure and comorbid). Patients with apathy presented a higher volume of WMH in comparison to controls. Mini-Mental State Examination (MMSE), NPI-A, and the number of cerebral microbleeds were the only variables associated with WMH. Conversely, NPI-D did not correlate to WMH. Discussion/Conclusion: This is an exploratory study that supports the view of PSA as a distinct syndrome from PSD mediated mainly by diffuse white matter hyperintensities, which suggests that WM disruption is an important pathway to the development of apathy in stroke patients.

Introduction The benefits of mechanical thrombectomy in the treatment of patients with acute stroke due to large vessel occlusions (LVOs) have been extensively demonstrated by randomized trials and registries in developed countries. However, data on thrombectomy outside controlled trials are scarce in developing countries. The aim of this study was to assess the safety and efficacy, and to investigate the predictors for good and poor outcomes of thrombectomy for treatment of AIS due to anterior circulation LVOs in Brazil. Materials and Methods This was a single center registry of thrombectomy in the treatment of stroke caused by anterior circulation LVOs. Between 2011 and 2019, a total of 565 patients were included. Results the mean baseline NIHSS score on admission was 17.2. The average baseline ASPECTS was 8, and 91.0% of patients scored ≥6. Half of the patients received intravenous thrombolysis. The mean time from symptom onset to arterial puncture was 296.4 minutes. The mean procedure time was 61.4 minutes. The rates of the main outcomes were recanalization (TICI 2b-3) 85.6%, symptomatic intracranial hemorrhage (sICH) 8,1%, good clinical outcome (mRS=0-2) 43,5%, and mortality 22.1% at three months. Conclusions This study demonstrates the efficacy and safety of mechanical thrombectomy for treatment of patients with AIS of the anterior circulation in real-life conditions under limited facilities and resources. The results of the present study were relatively similar to those of large trials and population registers of developed countries.

BackgroundThere is increasing evidence from pathology and neuroimaging suggesting that the structural abnormalities which characterize leukoaraiosis are present within regions of normal-appearing white matter. In this study, we aimed to verify whether signal intensity on FLAIR imaging in normal-appearing white matter is related to the leukoaraiosis burden.MethodsWe performed a cross-sectional study of adult patients admitted with a diagnosis of acute ischemic stroke or transient ischemic attack. Leukoaraiosis was segmented using a semi-automated method involving manual outlining and signal thresholding. White matter regions were segmented based on the probabilistic tissue maps from the International Consortium for Brain Mapping 152 atlas. Also, white matter was further segmented based on voxel-distance from leukoaraiosis borders. Normalized mean FLAIR signal intensity on normal-appearing white matter (NAWMM) was used as a dependent variable in univariate and multivariate statistical analysis, and leukoaraiosis volume quartiles (LKAV) and clinical data as independent variables.ResultsOne-hundred consecutive patients were selected for analysis (53% female, mean age 68 years). NAWMMwas higher in the vicinity of leukoaraiosis and progressively lower at increasing distances from leukoaraiosis. NAWMMwas independently associated with leukoaraiosis volume. In voxels in the vicinity of leukoaraiosis borders, there was a linear association between LKAVand NAWMM(B=0.03;PMamong patients in the second and third quartiles, and lower in the first and fourth quartiles (B=-0.21 for the second order term;PM.ConclusionsOur results show that normal-appearing white matter exhibits subtle signal intensity changes that are related to leukoaraiosis burden. The neuroimaging signature of these subtle changes suggests that they might not be a milder form of leukoaraiosis, but rather rather reflect widespread etiopathogenic processes underlying small-vessel disease and thus, leukoaraiosis development.

Background: Intensive blood pressure lowering may adversely affect evolving cerebral ischaemia. We aimed to determine whether intensive blood pressure lowering altered the size of cerebral infarction in the 2196 patients who participated in the Enhanced Control of Hypertension and Thrombolysis Stroke Study, an international randomised controlled trial of intensive (systolic target 130–140 mm Hg within 1 h; maintained for 72 h) or guideline-recommended (systolic target 150 mm Hg) after thrombolysis treatment for acute ischaemic stroke between March 3, 2012 and April 30, 2018. Methods: All available brain imaging were analysed centrally by expert readers. Log-linear regression was used to determine the effects of intensive blood pressure lowering on the size of cerebral infarction, with adjustment for potential confounders. The primary analysis pertained to follow-up computerised tomography (CT) scans done between 24 and 36 h. Sensitivity analysis were undertaken in patients with only a follow-up magnetic resonance imaging (MRI) and either MRI or CT at 24–36 h, and in patients with any brain imaging done at any time during follow-up. This trial is registered with ClinicalTrials.gov, number NCT01422616. Findings: There were 1477 (67.3%) patients (mean age 67.7 [12.1] y; male 60%, Asian 65%) with available follow-up brain imaging for analysis, including 635 patients with a CT done at 24–36 h. Mean achieved systolic blood pressures over 1–24 h were 141 mm Hg and 149 mm Hg in the intensive group and guideline group, respectively. There was no effect of intensive blood pressure lowering on the median size (ml) of cerebral infarction on follow-up CT at 24–36 h (0.3 [IQR 0.0–16.6] in the intensive group and 0.9 [0.0–12.5] in the guideline group; log Δmean −0.17, 95% CI −0.78 to 0.43). The results were consistent in sensitivity and subgroup analyses. Interpretation: Intensive blood pressure lowering treatment to a systolic target

Introduction: Cerebral small vessel disease (cSVD) involves a myriad of pathogenic mechanisms affecting small vessels of the brain, leading to a significant impact on motor and cognitive functions, and it is the main cause of Vascular cognitive impairment (VCI). The endothelial glycocalyx (EG), the layer lining the vascular endothelium, has a pivotal player in maintaining the proper function of neurovascular unit, and its degradation may be involved in VCI due to cSVD. Objectives: to investigate the relationship between markers of EG damage and VCI related to cSVD. Methods: Cross-sectional study based on clinical data and serum samples for the quantification of EG damage markers (syndecan-1, hyaluran) of VCI related to cSVD patients and of a control group derived from a dataset of healthy workers from the same institution. We used an automatic logarithm for segmentation and volumetric evaluation of white matter lesions on brain MRI of the patients. Logistic regression models and c-statistics were used to identify the independent variables related to VCI and investigate the accuracy of syndecan-1 to detect VCI. We studied the association of thebiomarkers and MoCA scores, index of independence in activities of daily living and whitematter lesion burden respectively. Results: Between July 2019 and March 2020, we studied 22 patients with VCI associated with cSVD and compared them with a dataset of 22 healthy workers from the same institution. Patients with VCI were older, had a higher prevalence of diabetesmellitus and hypertension, had a worse index of independence for daily activities, and higherlevels of syndecan-1 (78,4 vs 24; p < 0,01). There was no difference in hyaluran levels between both groups. In multivariate analysis, only age (OR 1,35;CI 1,04 - 1,76; p = 0,02) and syndecan-1 levels (OR 1,08;CI 1,01 - 1,15;p = 0,01) related to VCI. The ROC curve ofsyndecan-1 levels to predict VCI had a area under de curve of 0,78 (CI 0,64 - 0,92) and there was a correlation between syndecan-1 levels and MoCA scores (rho = - 0,34;p = 0,02). There were no correlations between syndecan-1 and hyaluran levels and index of independence and white matter lesion burden respectively. Conclusions: Syndecan-1, but not hyaluran, is a potential biomarker for VCI associated with cSVD.

Background The RESILIENT trial demonstrated the clinical benefit of mechanical thrombectomy in patients presenting acute ischemic stroke secondary to anterior circulation large vessel occlusion in Brazil. Aims This economic evaluation aims to assess the cost-utility of mechanical thrombectomy in the RESILIENT trial from a public healthcare perspective. Methods A cost-utility analysis was applied to compare mechanical thrombectomy plus standard medical care (n = 78) vs. standard medical care alone (n = 73), from a subset sample of the RESILIENT trial (151 of 221 patients). Real-world direct costs were considered, and utilities were imputed according to the Utility-Weighted modified Rankin Score. A Markov model was structured, and probabilistic and deterministic sensitivity analyses were performed to evaluate the robustness of results. Results The incremental costs and quality-adjusted life years gained with mechanical thrombectomy plus standard medical care were estimated at Int$ 7440 and 1.04, respectively, compared to standard medical care alone, yielding an incremental cost-effectiveness ratio of Int$ 7153 per quality-adjusted life year. The deterministic sensitivity analysis demonstrated that mRS-6 costs of the first year most affected the incremental cost-effectiveness ratio. After 1000 simulations, most of results were below the cost-effective threshold. Conclusions The intervention's clear long-term benefits offset the initially higher costs of mechanical thrombectomy in the Brazilian public healthcare system. Such therapy is likely to be cost-effective and these results were crucial to incorporate mechanical thrombectomy in the Brazilian public stroke centers.

Disk solids are critical in many planet formation processes, however, their effect on planet migration remains largely unexplored. Here we assess for the first time this important issue by building on the systematic measurements of dust torques on an embedded planet by Benitez-Llambay & Pessah (2018). Adopting standard models for the gaseous disk and its solid content, we quantify the impact of the dust torque for a wide range of conditions describing the disk/planet system. We show that the total torque can be positive and revert inward planet migration for planetary cores with $M_{\rm p} \lesssim 10 M_\oplus$. We compute formation tracks for low-mass embryos for conditions usually invoked when modeling planet formation processes. Our most important conclusion is that dust torques can have a significant impact on the migration and formation history of planetary embryos. The most important implications of our findings are: $\it{i})$ For nominal dust-to-gas mass ratios $\epsilon \simeq 0.01$, low-mass planets migrate outwards beyond the water ice-line if most of the mass in solids is in particles with Stokes numbers St $\simeq 0.1$. $\it{ii})$. For $\epsilon \gtrsim 0.02-0.05$, solids with small Stokes numbers, St $\simeq 0.01$, can play a dominant role if most of the mass is in those particles. $\it{iii})$ Dust torques have the potential to enable low-mass planetary cores formed in the inner disk to migrate outwards and act as the seed for massive planets at distances of tens of au., Comment: Paper submitted to ApJ after minor corrections required. Feedback from the community is welcome

We revisit asteroseismology with quadrupolar wI modes and present universal relationships for its fundamental and first overtone. In contrast to relationships proposed in the literature, our universal relationships are capable of including slow stable hybrid stars that appear when considering slow sharp hadron-quark phase transitions. We show that, if the frequency and damping time of the fundamental mode of a given pulsating object are measured, its mass, radius, and dimensionless tidal deformability can be inferred. Moreover, we show that the errors of such estimates are smaller than a few percent for the mass and radius. For the dimensionless tidal deformability, the errors are -- for compact objects with $M\gtrsim 1.4\,M_\odot$ -- in general smaller than ~100%. Comparison with previous universal relationships shows that the ones proposed in this work produce better estimates of the mass and radius of totally stable compact objects., Accepted to be published in the MNRAS

Transcranial color-coded Doppler (TCCD) is an ultrasonographic technique used to obtain and evaluate images of the cerebral parenchyma and to assess blood flow velocities of the intracranial vessels. One of the major limitations of TCCD is the failure to insonate through the transtemporal window, which occurs in about 5%-44% of patients. Temporal bone thickness has been strongly associated with transtemporal window failure (TWF). The aims of the study were to evaluate the association between TWF on TCCD and radiologic findings on computed tomography of the skull along with the demographic characteristics of patients with acute stroke or transient ischemic attack (TIA), and to propose a classification for transcranial window quality (TWQ) on B-mode scan of TCCD. A total of 187 consecutive patients with acute stroke or TIA were included. Among them, 21.9% had TWF and 34.8% had TWQ categorized as insufficient on B-mode scan of TCCD. On logistic regression, age (odds ratio [OR] = 1.07, 95% confidence interval [CI]: 1.03-1.12, p0.001), female sex (OR = 5.99, 95% CI: 2.09-17.16, p = 0.001), pneumatized temporal bone (OR = 7.90, 95% CI: 1.95-32.03, p = 0.004) and temporal bone thickness (OR = 3.04, 95% CI: 1.73-5.35, p0.001) were independent predictors of TWF, even after adjusting for confounders. These findings may help to select patients in whom echogenic contrast or even other imaging methods could be used to assess intracranial vessels.

Background: Simulations are becoming widely used in medical education, but there is little evidence of their effectiveness on neurocritical care. Because acute stroke is a neurological emergency demanding prompt attention, it is a promising candidate for simulation training. Objective: To assess the impact of a stroke realistic simulation course on clinicians’ self-perception of confidence in the management of acute stroke. Methods: We conducted a controlled, before-after study. For our intervention, 17 healthcare professionals participated in a stroke realistic simulation course. As controls, participants were chosen from a convenience sample of attendees to the courses Emergency Neurologic Life Support (ENLS) (18 participants) and Neurosonology (20 participants). All participants responded pre- and post-test questionnaires evaluating their self-perception of confidence in acute stroke care, ranging from 10 to 50 points. We evaluated the variation between pre- and post-test results to assess the change on trainees’ self-perception of confidence in the management of acute stroke. Multivariate analysis was performed to control for potential confounders. Results: Forty-six (83.63%) subjects completed both questionnaires. The post-test scores were higher than those from the pretests in the stroke realistic simulation course group [pretest median (interquartile range - IQR): 41.5 (36.7-46.5) and post-test median (IQR): 47 (44.7-48); p=0.033], but not in the neurosonology [pretest median (IQR): 46 (44-47) and post-test median (IQR): 46 (44-47); p=0.739] or the ENLS [pretest median (IQR): 46.5 (39-48.2), post-test median (IQR): 47 (40.2-49); p=0.317] groups. Results were maintained after adjustment for covariates. Conclusions: This stroke realistic simulation course was associated with an improvement on trainees’ self-perception of confidence in providing acute stroke care. RESUMO Introdução: Simulações são amplamente utilizadas na educação médica, mas há pouca evidência de sua eficácia no tratamento de pacientes neurocríticos. Como o acidente vascular cerebral agudo (AVC) é uma patologia que requer atendimento imediato, o uso de simulação pode ser uma ferramenta útil no treinamento do manejo desses pacientes. Objetivo: Avaliar o impacto do uso de simulação realística na autopercepção de segurança no atendimento a pacientes vítimas de AVC agudo. Métodos: Estudo antes-depois controlado. No grupo da intervenção, 17 profissionais da área de saúde participaram de um curso de simulação realística de atendimento a pacientes com AVC. Como controles, os participantes foram escolhidos a partir de uma amostra de conveniência composta por 18 participantes do curso Emergency Neurologic Life Support (ENLS) e 20 participantes de um curso de Neurossonologia. Foram respondidos questionários antes e após o curso para avaliar a autopercepção de segurança no atendimento a pacientes vítimas de AVC agudo, variando de 10 a 50 pontos. Foi avaliada a variação entre os resultados pré- e pós-teste, para avaliar a mudança na autopercepção de confiança do trainee no manejo do AVC agudo. Análise multivariada foi realizada para controlar possíveis fatores de confusão. Resultados: Quarenta e seis (83,63%) participantes responderam aos questionários. A pontuação no questionário pós-curso foi maior do que a obtida no questionário pré-curso no grupo de participantes do curso de simulação realística em AVC [mediana do questionário pré-curso: 41,5 (36,7-46,5) e mediana do questionário pós-curso: 47,0 (44,7-48,0); p=0,033]. Essa diferença não foi observada no curso de Neurossonologia [mediana pré-curso (IQR): 46,0 (44,0-47,00), mediana pós-curso (IQR): 46,0 (44,0-47,0); p=0,739] nem no ENLS [mediana pré-curso (IQR): 46,5 (39,0-48,2) mediana pós-curso (IQR): 47,0 (40,2-49,0); p=0,317]. Esses resultados persistiram após ajuste das variáveis. Conclusão: O curso de simulação realística em AVC foi associado a um aumento na autopercepção de segurança dos participantes em atender pacientes vítimas de AVC agudo.

Limited data exist on the optimum level of SBP in thrombolyzed patients with acute ischemic stroke (AIS). We aimed to determine the effects of intensive blood pressure (BP) lowering, specifically in patients with severe AIS who participated in the international, Enhanced Control of Hypertension and Thrombolysis Stroke Study.Prespecificed subgroup analyzes of the BP arm of Enhanced Control of Hypertension and Thrombolysis Stroke Study, a multicenter, partial-factorial, open, blinded outcome assessed trial, in which 2227 thrombolysis-eligible and treated AIS patients with elevated SBP (150 mmHg) were randomized to intensive (target 130-140 mmHg) or guideline-recommended (180 mmHg) BP management. Severe stroke was defined by computed tomography or magnetic resonance angiogram confirmation of large-vessel occlusion, receipt of endovascular therapy, final diagnosis of large artery atheromatous disease, or high (10) baseline neurological scores on the National Institutes of Health Stroke Scale. The primary efficacy outcome was death or any disability (modified Rankin scale scores 2-6). The key safety outcome was intracranial hemorrhage (ICH). Treatment effects estimated in logistic regression models are reported as odds ratios (ORs) with 95% confidence intervals (CIs).There were 1311 patients [mean age 67 years; 37% female; median baseline National Institutes of Health Stroke Scale of 11 (range 6.0-15.0)] with severe AIS. Overall, there was no significant difference in the primary outcome of death or disability. However, intensive BP lowering significantly increased mortality (OR 1.52, 95% CI 1.09-2.13; P = 0.014) compared with guideline BP lowering, despite significantly lowering clinician-reported ICH (OR 0.63, 95% CI 0.43-0.92; P = 0.016).Intensive BP lowering is associated with increased mortality in patients with severe AIS despite lowering the risk of ICH. Further randomized trials are required to provide reliable evidence over the optimum SBP target in the most serious type of AIS.ClinicalTrials.gov Identifier: NCT01422616.

Improving the readout for arterial spin labeling with multiple post-labeling delays (multi-PLD ASL) through a flip angle (FA) sweep towards increasing contrast-to-noise ratio for long PLD images. Images were acquired from 20 healthy subjects and 14 patients with severe, asymptomatic carotid artery stenosis (ACAS) in a 3T MRI scanner. Multi-PLD ASL images with conventional and proposed (FA sweep) readouts were acquired. For patients, magnetic resonance angiography was used to validate the multi-PLD ASL results. Perfusion values were calculated for brain regions irrigated by the main cerebral arteries and compared by analysis of variance. For healthy subjects, better contrast was obtained for long PLDs when using the proposed multi-PLD method compared to the conventional. For both methods, no hemispheric difference of perfusion was observed. For patients, the proposed method facilitated the observation of delayed tissue perfusion, which was not visible for long PLD using the conventional multi-PLD ASL. We successfully assessed brain perfusion of patients with asymptomatic CAS using multi-PLD ASL with FA sweep. We were able to show subtle individual differences. Moreover, prolonged arterial transit time in patients was observed, although they were considered asymptomatic, suggesting that it may not be an adequate term to characterize them.

O Brasil é um país emergente com crescente desenvolvimento econômico nos últimos 20 anos e com a sétima economia mais rica do mundo. No entanto, o ranking do Brasil no Índice de Desenvolvimento Humano das Nações Unidas (79ª posição, com base em dados de 2014) é paradoxalmente baixo em comparação com seu status econômico. As dimensões continentais do Brasil ampliam as desigualdades entre suas regiões, e a Amazônia é a área menos desenvolvida do país. Neste artigo, discutimos algumas das razões para a escassez de neurologistas na Amazônia brasileira. Além disso, discutimos possíveis novas estratégias para diminuir essas desigualdades em saúde pública em um futuro próximo.

Made available in DSpace on 2020-12-12T01:26:10Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-09-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) A common characteristic of sex chromosomes is the accumulation of repetitive DNA, which accounts for their diversification and degeneration. In grasshoppers, the X0 sex-determining system in males is considered ancestral. However, in some species, derived variants like neo-XY in males evolved several times independently by Robertsonian translocation. This is the case of Ronderosia bergii, in which further large pericentromeric inversion in the neo-Y also took place, making this species particularly interesting for investigating sex chromosome evolution. Here, we characterized the satellite DNAs (satDNAs) and transposable elements (TEs) of the species to investigate the quantitative differences in repeat composition between male and female genomes putatively associated with sex chromosomes. We found a total of 53 satDNA families and 56 families of TEs. The satDNAs were 13.5% more abundant in males than in females, while TEs were just 1.02% more abundant in females. These results imply differential amplification of satDNAs on neo-Y chromosome and a minor role of TEs in sex chromosome differentiation. We showed highly differentiated neo-XY sex chromosomes owing to major amplification of satDNAs in neo-Y. Furthermore, chromosomal mapping of satDNAs suggests high turnover of neo-sex chromosomes in R. bergii at the intrapopulation level, caused by multiple paracentric inversions, amplifications, and transpositions. Finally, the species is an example of the action of repetitive DNAs in the generation of variability for sex chromosomes after the suppression of recombination, and helps understand sex chromosome evolution at the intrapopulation level. Departamento de Biologia Geral e Aplicada UNESP-Univ Estadual Paulista Instituto de Biociências/IB Department of Organismal Biology Uppsala University Evolutionary Biology Centre Department of Ecology and Genetics Uppsala University Evolutionary Biology Centre Departamento de Biologia Geral e Aplicada UNESP-Univ Estadual Paulista Instituto de Biociências/IB

According to previous epidemiological studies, we can reduce the thickness of epicardial fat and improve cardiovascular risk factors through exercise, and the changes may depend on the form of exercise. We systemically reviewed published studies that evaluated exercise intervention on epicardial adipose tissue (EAT) levels. We included randomized controlled trials (RCTs) comparing one exercise with another exercise or diet for the treatment to reduce EAT. We used fixed effects models for meta-analyses; effects of exercise on outcomes were described as mean differences (MD) or standardized difference of means (SMD) was used, their 95% confidence intervals (CI). Five RCTs were included (n = 299), 156 in exercise group and 143 in the control. In comparison to the control group, exercise significantly reduced EAT (SMD − 0.57, 95%CI − 0.97 to − 0.18) and waist circumference (MD − 2.95 cm, 95%CI − 4.93 to − 0.97). Exercise did not have an effect on BMI (MD − 0.23 kg/m2, 95%CI − 0.73 to 0.27), weight (MD − 0.06 kg, 95%CI − 1.46 to 1.34), or HDL (SMD 0.26, 95%CI − 0.06 to 0.57).VO2 was significantly increased by exercise (SMD 1.58, 95%CI 1.17 to 1.99). Risk of bias was high for 3 studies, and GRADE quality of evidence was very low to moderate. Exercise reduced epicardial adipose tissue and waist circumference, and did not have effect on weight, BMI, or HDL. Newer trials with better design and methods are necessary to improve the quality of the evidence. PROSPERO registration number (CRD42018096581)

Satellite DNA (satDNA) is an abundant class of tandemly repeated noncoding sequences, showing high rate of change in sequence, abundance, and physical location. However, the mechanisms promoting these changes are still controversial. The library model was put forward to explain the conservation of some satDNAs for long periods, predicting that related species share a common collection of satDNAs, which mostly experience quantitative changes. Here, we tested the library model by analyzing three satDNAs in ten species of Schistocerca grasshoppers. This group represents a valuable material because it diversified during the last 7.9 Myr across the American continent from the African desert locust (Schistocerca gregaria), and this thus illuminates the direction of evolutionary changes. By combining bioinformatic and cytogenetic, we tested whether these three satDNA families found in S. gregaria are also present in nine American species, and whether differential gains and/or losses have occurred in the lineages. We found that the three satDNAs are present in all species but display remarkable interspecies differences in their abundance and sequences while being highly consistent with genus phylogeny. The number of chromosomal loci where satDNA is present was also consistent with phylogeny for two satDNA families but not for the other. Our results suggest eminently chance events for satDNA evolution. Several evolutionary trends clearly imply either massive amplifications or contractions, thus closely fitting the library model prediction that changes are mostly quantitative. Finally, we found that satDNA amplifications or contractions may influence the evolution of monomer consensus sequences and by chance playing a major role in driftlike dynamics. Fil: Palacios-Gimenez, Octavio M.. Uppsala Universitet; Suecia Fil: Milani, Diogo. Universidade Estadual Paulista Julio de Mesquita Filho; Brasil Fil: Song, Hojun. Texas A&M University; Estados Unidos Fil: Marti, Dardo Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas | Universidad Nacional de Misiones. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas; Argentina Fil: López-León, Maria D.. Universidad de Granada; España Fil: Ruiz-Ruano, Francisco J.. Uppsala Universitet; Suecia Fil: Camacho, Juan Pedro M.. Universidad de Granada; España Fil: Cabral-de-Mello, Diogo C.. Universidade Estadual Paulista Julio de Mesquita Filho; Brasil

Made available in DSpace on 2020-12-12T01:56:44Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-12-01 Introduction: The presence of microembolic signals (MES) during the acute phase of stroke is poorly understood, and its role and clinical application in relation to risk stratification and prognosis in patients remain uncertain. We assessed the prevalence of spontaneous MES in acute stroke and their relationship with risk stratification, stroke recurrence, morbidity, and mortality. Patients and methods: This was a prospective cohort study conducted in the Stroke Unit. The MES presence was evaluated by transcranial Doppler (TCD) in patients with ischemic stroke within 48 h. The outcomes (risk stratification, morbidity, mortality, and recurrence of a stroke) were followed up for 6 months. The relationship between risk stratification and MES was obtained by odds ratios and that between MES and stroke recurrence, morbidity, and mortality using multiple logistic regression; considering statistical significance at P < 0.05. Results: Of the 111 patients studied, 70 were men (63.1%) and 90 were white (81.1%), with a median age of 68 years. The MES frequency was 7%. There was a significant relationship between MES and symptomatic carotid disease (OR = 22.7; 95% CI 4.1–125.7; P < 0.001), a shorter time to monitoring (OR = 12.4; 95% CI 1.4–105.4; P = 0.02), and stroke recurrence (OR = 16.83; 95% CI 2.01–141; P =.009). Discussion: It was observed that the stroke recurrence adjusted for prior stroke was higher and earlier among patients with MES detection. In conclusion, MES demonstrated a significant correlation with symptomatic carotid disease and a shorter DELAY until monitoring, and could be a predictor for the early recurrence of stroke in the long term. Department of Neurology Psychology and Psychiatry Botucatu Medical School UNESP–Univ Estadual Paulista, Campus de Botucatu, Distrito de Rubião Jr, s/n Department of Applied Physical Therapy Institute of Health Sciences UFTM–Univ Federal do Triângulo Mineiro Department of Internal Medicine Botucatu Medical School UNESP–Univ Estadual Paulista Department of Tropical Diseases and Imaging Diagnosis Botucatu Medical School UNESP–Univ Estadual Paulista Department of Surgery and Orthopedics Botucatu Medical School UNESP–Univ Estadual Paulista Department of Neuroscience and Behavior Ribeirão Preto School of Medicine USP–Univ São Paulo Department of Neurology Psychology and Psychiatry Botucatu Medical School UNESP–Univ Estadual Paulista, Campus de Botucatu, Distrito de Rubião Jr, s/n Department of Internal Medicine Botucatu Medical School UNESP–Univ Estadual Paulista Department of Tropical Diseases and Imaging Diagnosis Botucatu Medical School UNESP–Univ Estadual Paulista Department of Surgery and Orthopedics Botucatu Medical School UNESP–Univ Estadual Paulista

Cerebral small vessel disease (cSVD), a common cause of stroke and dementia, is traditionally considered the small vessel equivalent of large artery occlusion or rupture that leads to cortical and subcortical brain damage. Microvessel endothelial dysfunction can also contribute to it. Brain imaging, including MRI, is useful to show the presence of lesions of several types, although the association between conventional MRI measures and clinical features of cSVD is not always concordant. We assessed the additional contribution of contrast-agent-free, state-of-the-art MRI techniques such as arterial spin labeling (ASL), diffusion tensor imaging, functional MRI, and intravoxel incoherent motion (IVIM) applied to cSVD in the existing literature. We performed a review following the PICO Worksheet and Search Strategy, including original papers in English, published between 2000 and 2022. For each MRI method, we extracted information about their contributions, in addition to those established with traditional MRI methods and related information about the origins, pathology, markers, and clinical outcomes in cSVD. This paper presents the first part of the review, which includes 37 studies focusing on ASL, IVIM, and cerebrovascular reactivity (CVR) measures. In general, they have shown that, in addition to white matter hyperintensities, alterations in other neuroimaging parameters such as blood flow and CVR also indicate the presence of cSVD. Such quantitative parameters were also related to cSVD risk factors. Therefore, they are promising, noninvasive tools to explore questions that have not yet been clarified about this clinical condition. However, protocol standardization is essential to increase their clinical use.

Cerebral small vessel disease (cSVD) has been widely studied using conventional magnetic resonance imaging (MRI) methods, although the association between MRI findings and clinical features of cSVD is not always concordant. We assessed the additional contribution of contrast agent-free, state-of-the-art MRI techniques, particularly diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI), to understand brain damage and structural and functional connectivity impairment related to cSVD. We performed a review following the PICOS worksheet and Search Strategy, including 152 original papers in English, published from 2000 to 2022. For each MRI method, we extracted information about their contributions regarding the origins, pathology, markers, and clinical outcomes in cSVD. In general, DTI studies have shown that changes in mean, radial, and axial diffusivity measures are related to the presence of cSVD. In addition to the classical deficit in executive functions and processing speed, fMRI studies indicate connectivity dysfunctions in other domains, such as sensorimotor, memory, and attention. Neuroimaging metrics have been correlated with the diagnosis, prognosis, and rehabilitation of patients with cSVD. In short, the application of contrast agent-free, state-of-the-art MRI techniques has provided a complete picture of cSVD markers and tools to explore questions that have not yet been clarified about this clinical condition. Longitudinal studies are desirable to look for causal relationships between image biomarkers and clinical outcomes.

This is the 2021 edition of the Cardiovascular Statistics – Brazil , a multi-institutional effort to periodically provide updated information on the epidemiology of heart diseases and stroke in Brazil. The report incorporates official statistics provided by the Brazilian Ministry of Health and other government agencies, by the GBD project led by the IHME of the University of Washington, as well as data generated by other sources and scientific studies, such as cohorts and registries, on CVDs and their risk factors. The document is directed to researchers, clinicians, patients, healthcare policy makers, media professionals, the public, and others who seek comprehensive national data available on heart disease and stroke.

Multi-messenger astronomy with gravitational waves is a blooming area whose limits are not clear. After the first detection of binary black hole merger and the famous event GW170817 and its electromagnetic counterpart, the compact-object astrophysical community is starting to grasp the physical implications of such event and trying to improve numerical models to compare with future observations. Moreover, recent detections made by the NICER collaboration increased the tension between several theoretical models used to describe matter in the inner core of compact objects. In this paper, we focus on quadrupolar purely spacetime wI-modes of oscillating compact objects described using a wide range of hybrid equations of state able to include several theoretical possibilities of exotic matter in the inner core of such stars. We study the case in which a sharp first order hadron-quark phase transition occurs and explore the scenarios of rapid and slow phase conversions at the interface. We put special attention on the validity of universal relationships for the oscillation frequency and damping time that might help unravel the mysteries hidden at the inner cores of compact objects. We show that, within the slow conversion regime where extended branches of hybrid stars appear, universal relationships for wI-modes proposed in the literature do not hold., Comment: 17 pages, 11 figures. Accepted for publication in PRD

Celiac disease (CD) is a genetically predisposed, T cell-mediated and autoimmune-like disorder caused by dietary exposure to the storage proteins of wheat and related cereals. A gluten-free diet (GFD) is the only treatment available for CD. The celiac immune response mediated by CD4+ T-cells can be assessed with a short-term oral gluten challenge. This study aimed to determine whether the consumption of bread made using flour from a low-gluten RNAi wheat line (named E82) can activate the immune response in DQ2.5-positive patients with CD after a blind crossover challenge. The experimental protocol included assessing IFN-γ production by peripheral blood mononuclear cells (PBMCs), evaluating gastrointestinal symptoms, and measuring gluten immunogenic peptides (GIP) in stool samples. The response of PBMCs was not significant to gliadin and the 33-mer peptide after E82 bread consumption. In contrast, PBMCs reacted significantly to Standard bread. This lack of immune response is correlated with the fact that, after E82 bread consumption, stool samples from patients with CD showed very low levels of GIP, and the symptoms were comparable to those of the GFD. This pilot study provides evidence that bread from RNAi E82 flour does not elicit an immune response after a short-term oral challenge and could help manage GFD in patients with CD., This research was funded by The Spanish Ministry of Science and Innovation, Agencia Estatal de Investigación (Project PID2019-110847RB-I00), Consejería de Transformación Económica, Industria, Conocimiento y Universidades, Junta de Andalucía (Project P20_01005), and “ERDF A way of making Europe”, by the “European Union”.

Ischemic stroke is a leading cause of morbidity and mortality worldwide. Embolic stroke of undetermined source has been recently proposed to categorize nonlacunar ischemic strokes without confirmed etiology after adequate investigation with a likely embolic stroke mechanism. A strategy of empirical anticoagulation for embolic stroke of undetermined source patients is attractive but may only be beneficial in a select subset of patients. Strategies which would help identify the subset of embolic stroke of undetermined source patients most likely to have cardioembolic origin of stroke, and hence benefit from anticoagulation, are needed. This article will review current evidence which may be useful in the development of a risk stratification approach based on arrhythmia monitoring, cardiac imaging, and clinical risk stratification. This approach may be beneficial in clinical practice in improving patient outcomes and reducing stroke recurrence in this population; however, further work is required with active trials underway.

Made available in DSpace on 2022-04-29T08:37:33Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-12-01 In Acridoidea grasshoppers, chromosomal rearrangements are frequently found as deviations from the standard acrocentric karyotype (2n = 23♂/24♀, FN = 23♂/24♀) in either phylogenetically unrelated species or shared by closely related ones, i.e. genus. In the South American subfamily Ommexechinae, most of the species show a unique karyotype (2n = 23♂/24♀, FN = 25♂/26♀) owing to the occurrence of a large autosomal pair (L1) with submetacentric morphology. In the early 1960s, Alejo Mesa proposed the hypothesis of an ancestral pericentric inversion to explain this karyotype variation. Furthermore, in Ommexechinae, extra chromosomal rearrangements (e.g. centric fusions) are recorded between the ancestral X chromosome and autosomes that originated the so-called neo-sex chromosomes. However, the evolutionary significance of the pericentric inversions and centric fusions in Ommexechinae remains poorly explored. Aiming for a better understanding of chromosomal evolution in Ommexechinae, we performed a detailed cytogenetic analysis in five species. Our findings support the hypothesis about the occurrence of an early pericentric inversion in the ancestor of Ommexechinae. Moreover, our results show a complex karyotype diversification pattern due to several chromosome rearrangements, variations in heterochromatin and repetitive DNA dynamics. Finally, the chromosomal mapping of U2 snDNA in L1 provided new insights about the morphological evolution of this autosomal pair and revealed unnoticed chromosome reorganizations. Laboratorio de Genética Evolutiva Dr. Claudio J. Bidau. Instituto de Biología Subtropical (IBS) CONICET-UNaM. FCEQyN, Posadas, Misiones Departamento de Genética e Biologia Evolutiva Instituto de Biociências Universidade de São Paulo (USP) São Paulo Departamento de Biologia Geral e Aplicada Universidade Estadual Paulista (UNESP) Instituto de Biociências/IB, Rio Claro Department of Organismal Biology-Systematic Biology Program Evolutionary Biology Centre Uppsala University Departamento de Biologia Geral e Aplicada Universidade Estadual Paulista (UNESP) Instituto de Biociências/IB, Rio Claro

BackgroundDuring the COVID-19 pandemic, decreased volumes of stroke admissions and mechanical thrombectomy were reported. The study's objective was to examine whether subarachnoid haemorrhage (SAH) hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines.MethodsWe conducted a cross-sectional, retrospective, observational study across 6 continents, 37 countries and 140 comprehensive stroke centres. Patients with the diagnosis of SAH, aneurysmal SAH, ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases, 10th Revision, codes. The 3-month cumulative volume, monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before (1 year and immediately before) and during the pandemic, defined as 1 March-31 May 2020. The prior 1-year control period (1 March-31 May 2019) was obtained to account for seasonal variation.FindingsThere was a significant decline in SAH hospitalisations, with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic, representing a relative decline of 22.5% (95% CI -24.3% to -20.7%, p

Background and Purpose: In thrombolysis-eligible patients with acute ischemic stroke, there is uncertainty over the most appropriate systolic blood pressure (SBP) lowering profile that provides an optimal balance of potential benefit (functional recovery) and harm (intracranial hemorrhage). We aimed to determine relationships of SBP parameters and outcomes in thrombolyzed acute ischemic stroke patients. Methods: Post hoc analyzes of the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study), a partial-factorial trial of thrombolysis-eligible and treated acute ischemic stroke patients with high SBP (150–180 mm Hg) assigned to low-dose (0.6 mg/kg) or standard-dose (0.9 mg/kg) alteplase and intensive (target SBP, 130–140 mm Hg) or guideline-recommended (target SBP Results: Among 4511 included participants (mean age 67 years, 38% female, 65% Asian) lower attained SBP and smaller SBP variability were associated with favorable shift on the modified Rankin Scale (per 10 mm Hg increase: odds ratio, 0.76 [95% CI, 0.71–0.82]; P P =0.025) respectively, but not for magnitude of SBP reduction (0.98, [0.93–1.04]; P =0.564). Odds of intracranial hemorrhage was associated with higher attained SBP and greater SBP variability (1.18 [1.06–1.31]; P =0.002 and 1.34 [1.11–1.62]; P =0.002) but not with magnitude of SBP reduction (1.05 [0.98–1.14]; P =0.184). Conclusions: Attaining early and consistent low levels in SBP Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01422616.

Made available in DSpace on 2022-04-28T19:41:07Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-08-01 National Science Foundation Multigene families are essential components of eukaryotic genomes and play key roles either structurally and functionally. Their modes of evolution remain elusive even in the era of genomics, because multiple multigene family sequences coexist in genomes, particularly in large repetitive genomes. Here, we investigate how the multigene families 18S rDNA, U2 snDNA, and H3 histone evolved in 10 species of Schistocerca grasshoppers with very large and repeat-enriched genomes. Using sequenced genomes and fluorescence in situ hybridization mapping, we find substantial differences between species, including the number of chromosomal clusters, changes in sequence abundance and nucleotide composition, pseudogenization, and association with transposable elements (TEs). The intragenomic analysis of Schistocerca gregaria using long-read sequencing and genome assembly unveils conservation for H3 histone and recurrent pseudogenization for 18S rDNA and U2 snDNA, likely promoted by association with TEs and sequence truncation. Remarkably, TEs were frequently associated with truncated copies, were also among the most abundant in the genome, and revealed signatures of recent activity. Our findings suggest a combined effect of concerted and birth-and-death models driving the evolution of multigene families in Schistocerca over the last 8 million years, and the occurrence of intra- and interchromosomal rearrangements shaping their chromosomal distribution. Despite the conserved karyotype in Schistocerca, our analysis highlights the extensive reorganization of repetitive DNAs in Schistocerca, contributing to the advance of comparative genomics for this important grasshopper genus. Departamento de Biologia Geral e Aplicada UNESP – Univ Estadual Paulista Instituto de Biociências/IB Department of Entomology Texas A&M University Department of Organismal Biology – Systematic Biology Evolutionary Biology Centre Uppsala University Population Ecology Group Institute of Ecology and Evolution Friedrich Schiller University Jena Departamento de Biologia Geral e Aplicada UNESP – Univ Estadual Paulista Instituto de Biociências/IB National Science Foundation: IOS-1253493

Objective: Uncertainty exists over the prognostic significance of low arterial oxygen saturation (SaO(2)) in acute stroke. We aimed to determine the strength of association of SaO(2) and adverse outcomes among participants of the international Head Positioning in acute Stroke Trial (HeadPoST). Methods: Post-hoc analyzes of HeadPoST, a pragmatic cluster-crossover randomized trial of lying flat versus sitting up head positioning in 11,093 patients (age >= 18 years) with acute stroke at 114 hospitals in 9 countries during 2015-2016. Associations of the lowest recorded SaO(2) level, as a continuous measure and as a cut-point for desaturation (SaO(2)

ObjectiveCardioembolic (CE) stroke carries significant morbidity and mortality. Left atrial (LA) size has been associated with CE risk. We hypothesised that differential LA remodelling impacts on pathophysiological mechanism of major CE strokes.MethodsA cohort of consecutive patients hospitalised with ischaemic stroke, classified into CE versus non-CE strokes using the Causative Classification System for Ischaemic Stroke were enrolled. LA shape and remodelling was characterised by assessing differences in maximal LA cross-sectional area (LA-CSA) in a cohort of 40 prospectively recruited patients with ischaemic stroke using three-dimensional (3D) echocardiography. Flow velocity profiles were measured in spherical versus ellipsoidal in vitro models to determine if LA shape influences flow dynamics. Two-dimensional (2D) LA-CSA was subsequently derived from standard echocardiographic views and compared with 3D LA-CSA.ResultsA total of 1023 patients with ischaemic stroke were included, 230 (22.5%) of them were classified as major CE. The mean age was 68±16 years, and 464 (45%) were women. The 2D calculated LA-CSA correlated strongly with the LA-CSA measured by 3D in both end-systole and end-diastole. In vitro flow models showed shape-related differences in mid-level flow velocity profiles. Increased LA-CSA was associated with major CE stroke (adjusted relative risk 1.10, 95% CI 1.04 to 1.16; p2DS2-VASc score. Specifically, the inclusion of LA-CSA in a model with traditional risk factors for CE stroke resulted in significant improvement in model performance with the net reclassification improvement of 0.346 (95% CI 0.189 to 0.501; p=0.00001) and the integrated discrimination improvement of 0.013 (95% CI 0.003 to 0.024; p=0.0119).ConclusionsLA-CSA is a marker of adverse LA shape associated with CE stroke, reflecting importance of differential LA remodelling, not simply LA size, in the mechanism of CE risk.

The corneal reflex assesses the integrity of the trigeminal and facial cranial nerves. This brainstem reflex is fundamental in neuroprognostication after cardiac arrest and in brain death determination. We sought to investigate corneal reflex testing methods among neurologists and general critical care providers in the context of neuroprognostication following cardiac arrest. This is an international cross-sectional study disseminated to members of the Neurocritical Care Society, Society of Critical Care Medicine, and American Academy of Neurology. We utilized an open Web-based survey (Qualtrics®, Provo, UT, USA) to disseminate 26 questions regarding neuroprognostication practices following cardiac arrest, in which 3 questions pertained to corneal reflex testing. Descriptive statistical measures were used, and subgroup analyses performed between neurologists and non-neurologists. Questions were not mandatory; therefore, the percentages were relative to the number of respondents for each question. There were 959 respondents in total. Physicians comprised 85.1% of practitioners (762 out of 895), of which 55% (419) identified themselves as non-neurologists and 45% (343) as neurologists. Among physicians, 85.9% (608 out of 708) deemed corneal reflex relevant for prognostication following cardiac arrest (neurologists 84.4% versus non-neurologists 87.0%). A variety of techniques were employed for corneal reflex testing, the most common being “light cotton touch” (59.2%), followed by “cotton-tipped applicator with pressure” (23.9%), “saline or water squirt” (15.9%), and “puff of air” (1.0%). There were no significant differences in the methods for testing between neurologists and non-neurologists (p = 0.52). The location of stimulus application was variable, and 26.1% of physicians (148/567) apply the stimulus on the temporal conjunctiva rather than on the cornea itself. Corneal reflex testing remains a cornerstone of the coma exam and is commonly used in neuroprognostication of unconscious cardiac arrest survivors and in brain death determination. A wide variability of techniques is noted among practitioners, including some that may provide suboptimal stimulation of corneal nerve endings. Imprecise testing in this setting may lead to inaccuracies in critical settings, which carries significant consequences such as guiding decisions of care limitations, misdiagnosis of brain death, and loss of public trust.

Introduction: The damage in the endothelium and the neurovascular unit appears to play a key role in the pathogenesis of vascular cognitive impairment (VCI). Although there have been many advances in understanding the physiopathology of this disease, several questions remain unanswered. The association with other degenerative diseases and the heterogeneity of its clinical spectrum establish a diagnostic problem, compromising a better comprehension of the pathology and halting the development of effective treatments. The investigation of biomarkers is an important movement to the development of novel explicative models and treatment targets involved in VCI. Methods: We searched MEDLINE considering the original research based on VCI biomarkers in the past 20 years, following prespecified selection criteria, data extraction, and qualitative synthesis. Results: We reviewed 42 articles: 16 investigated plasma markers, 17 analyzed neuropathological markers, 4 studied CSF markers, 4 evaluated neuroimaging markers (ultrasound and MRI), and 1 used peripheral Doppler perfusion imaging. Conclusions: The biomarkers in these studies suggest an intrinsic relationship between endothelial dysfunction and VCI. Nonetheless, there is still a need for identification of a distinctive set of markers that can integrate the clinical approach of VCI, improve diagnostic accuracy, and support the discovery of alternative therapies.

Introduction The benefits of thrombectomy for occlusion of M2 segments remain controversial. The aim of this study is to assess thrombectomy’s efficacy and safety in patients with M2 segment occlusion and associations between occlusion sites and anatomic variations of M1 division. Materials and methods A prospective series of 30 patients with acute ischemic stroke (AIS) resulting from M2 segment occlusion of the middle cerebral artery (MCA) who underwent thrombectomy was analyzed. The primary endpoint was assessed by the Extended Treatment in Cerebral Infarction scale (eTICI). The secondary endpoints were the incidence of symptomatic hemorrhagic transformation (sICH), mortality and good functional outcome at three months. Results The mean patient age was 69.2 years. The mean National Institutes Health Stroke Scale score (NIHSS) upon hospital admission was 16. The recanalization rates were eTICI 2b/3 in 90% and 2c/3 in 60% of the patients. Total recanalization of the M2 branch was achieved in 53% of patients. sICH incidence was 6.6%, the mortality rate was 30%, and a good functional outcome (mRS ≤2) was observed in 50% of the patients. Twenty-seven patients (90%) had a dominant M2 branch and all were occluded. Regarding the site of M2 occlusions, 74% of patients had proximal M2 occlusions. Conclusions Thrombectomy appears to be a safe and effective method for the treatment of acute M2 segment occlusions of the MCA. Most of the cases had a dominant M2 branch, and all of them were occluded. Larger studies are needed to verify the benefits of thrombectomy for different settings of M2 occlusions.

Background Randomized controlled trials provide high-level evidence, but the necessity to include selected patients may limit the generalisability of their results. Methods Comparisons were made of baseline and outcome data between patients with acute ischemic stroke (AIS) recruited into the alteplase-dose arm of the international, multi-center, Enhanced Control of Hypertension and Thrombolysis Stroke study (ENCHANTED) in the United Kingdom (UK), and alteplase-treated AIS patients registered in the UK Sentinel Stroke National Audit Programme (SSNAP) registry, over the study period June 2012 to October 2015. Results There were 770 AIS patients (41.2% female; mean age 72 years) included in ENCHANTED at sites in England and Wales, which was 19.5% of alteplase-treated AIS patients registered in the SSNAP registry. Trial participants were significantly older, had lower baseline neurological severity, less likely Asian, and had more premorbid symptoms, hypertension and atrial fibrillation. Although ENCHANTED participants had higher rates of symptomatic intracerebral hemorrhage than those in SSNAP, there were no differences in onset-to-treatment time, levels of disability (assessed by the modified Rankin scale) at hospital discharge, and mortality over 90 days between groups. Conclusions Despite the high level of participation, equipoise over the dose of alteplase among UK clinician investigators favored the inclusion of older, frailer, milder AIS patients in the ENCHANTED trial. Clinical trial registration Clinical Trial Registration-URL: http://www.clinicaltrials.gov . Unique identifier: NCT01422616

The Head Positioning in Acute Stroke Trial (HeadPoST) is a pragmatic, international, cluster crossover randomized trial of 11,093 patients with acute stroke assigned to a lying-flat (0°) or sitting-up (head elevated ≥30°) position. This post hoc analysis aimed to determine the association between blood pressure variability (BPV) and outcomes for patients from a wide range of international clinical settings and how the association was modified by randomized head position. BPV was defined according to the standard criteria, with the key parameter considered the coefficient of variation (CV) of systolic BP (SBP) over 24 h. Outcome was ordinal 90-day Modified Rankin Scale (mRS) score. The association was analyzed by ordinal, logistic regression, hierarchical, mixed models with fixed intervention (lying flat vs. sitting up), and fixed period, random cluster, and random cluster-period, effects. Nine thousand one hundred and fifty six (8324 acute ischemic stroke and 817 intracerebral hemorrhage; mean age 68.1 years; 39.2% women) were included in the analysis. CV of SBP had a significant linear association with unfavorable shift of mRS at 90 days (adjusted odds ratio 1.06, 95% confidence interval 1.02–1.11; P = 0.01). There was no heterogeneity of the association by randomized head positioning. In addition, CV of diastolic BP (DBP) (1.08, 1.03–1.12; P = 0.001) over 24 h post stroke was significantly associated with 3-month poor outcome. The association was more apparent in sitting-up position (1.12, 1.06–1.19) compared with lying-flat position (1.03, 0.98–1.09) (P interaction = 0.005). BPV was associated with adverse stroke outcome, and the magnitude of the association was greater with sitting-up head positioning in terms of DBP variability.

Since neuronal activity is coupled with neurovascular activity, we aimed to analyze the cerebral blood flow hemodynamics during and following high-definition transcranial direct current stimulation (HD-tDCS). We assessed the mean middle cerebral artery blood flow velocity (MCA-BFv) bilaterally using transcranial doppler ultrasound, during and after HD-tDCS, in eleven right-handed healthy adult participants (6 women, 5 men; mean age 31 ± 5.6 years old), with no evidence of brain or cardiovascular dysfunction. The HD-tDCS electrode montage was centered over the right temporo-parietal junction. The stimulation protocol comprised 3 blocks of 2 min at each current intensity (1, 2, and 3 mA) and an inter-stimulus interval of 5 min between blocks. Participants received three electrical stimulation conditions (anode center, cathode center, and sham) on three different days, with an interval of at least 24 h. Stimulation was well tolerated across HD-tDCS conditions tested, and the volunteers reported no significant discomfort related to stimulation. There was no significant difference in the right or the left MCA-BFv during or after the stimulation protocol across all stimulation conditions. We conclude that at a range of intensities, vascular reaction assessed using middle cerebral artery blood flow is not significantly altered during or after HD-tDCS both locally and remotely, which provides further evidence for the safety of HD-tDCS.

Neurofibromatosis type 1 (NF1) predisposes to the development of dermal and plexiform neurofibromas and serum of NF1 patients stimulates neurofibroma proliferation in vitro. This study aimed to determine whether, in NF1 patients, serum levels of midkine (MK) and fibroblast growth factor 2 (FGF2) were associated with the number and/or type of neurofibromas. In addition, their concentrations were correlated with serum levels of dehydroepiandrosterone sulfate (DHEAS), a neurosteroid secreted by the peripheral nervous system. We performed a case control-study and measured, by ELISA assay, serum concentrations of MK, FGF2, and DHEAS in 20 NF1 patients and 30 controls. We found increased serum levels of MK and FGF2 in NF1 patients between 30 and 50 years old. Their concentrations were significantly higher in NF1 patients with plexiform neurofibromas than in controls (P=0.003 for MK and P=0.008 for FGF2). As an underlying hormonal regulation was suspected, DHEAS serum levels were measured but no difference was observed between patients and controls. We also observed a strong association between MK and FGF2 levels (P=0.0001) in NF1 patients and controls. In conclusion, we point out MK and FGF2 as biomarkers for plexiform neurofibroma in NF1 patients. As both growth factors are estrogen-responsive genes and neurofibromin is a co-repressor of estrogen receptor alpha activity, we suggest that the increased serum levels of MK and FGF2 observed in NF1 patients might be due to estradiol hypersensitivity.

To test the hypothesis that high speciation rate in groups is coupled with high rate of karyotype evolution but also that younger groups having a higher rate of karyotypic diversity, I estimated rates of speciation and rates of karyotype evolution in 1,177 species belonging to 26 families in the insect order Orthoptera. Rates of karyotype evolution were estimated using the diploid number and the number of chromosome arms (fundamental number) from published karyotypes of Orthoptera. Rates of speciation were quantified considering the number of species examined karyotypically in each family, the most recent common ancestor of each family and the information about extinction rate. The rate of speciation was strongly correlated with rate of karyotype evolution and the average rates of speciation was nearly ~177 times higher than the background rate estimated for Orthoptera based on acoustic communication using phylogenomic data, as well as 8.4 and 35.6 times higher than the estimated speciation rate in vertebrates and bivalve mollusks respectively, indicating that Orthoptera has evolved very fast at chromosomal level. The findings supported the hypothesis of a high speciation rate in lineages with high rate of chromosomal evolution but there were not evidences that younger groups tended to have higher rate of karyotypic diversity. Furthermore, rates of karyotype evolution most closely fitted the punctuational evolutionary model indicating the existence of long periods of stasis of karyotype change with most karyotype change occurring quickly over short evolutionary times. I discussed genetic drift, divergent selection and meiotic drive as potential biological mechanisms to explain karyotype evolution allowing or impeding for the fixation of chromosomal rearrangements and in turn speciation in orthopterans lineages.

Communication is a factor that can influence the success of projects, especially when several partners are involved and their joint action is necessary to achieve results. The implementation of a curricular change is one of those situations, because it is planned by curriculum managers, but will have as a final focus the work done by the students, who are the agents in the learning process and will make use of the experiences and strategies created for the curricula. Although the curricula are created based on the needs raised with students and teachers, their implementation requires a clear communication of objectives, teaching and assessment strategies, in addition to constant monitoring throughout the process, so that any adjustments can be made quickly, correcting the route in case of failures. This communication should ensure consensus on the purposes and engagement in the learning activities. Five years after the start of the implementation of a curricular proposal in an engineering school, which introduced the use of projects in parallel to the course subjects, two surveys were carried out, one with teachers and the other with students, and both showed the existence of doubts about the purpose of the changes introduced, which can be attributed to ineffective communication. The curricular change is consolidated and is valued by both teachers and students, however better results could have been achieved if there was better communication, which would make the experience more successful and, even, making the participants the best disseminators of this experience. This work analyses the communication aspects of this curriculum, based on the data from the two surveys, to identify problems and suggest actions. &nbsp

Objective: Limited data exist on the optimum level of systolic blood pressure (BP) in thrombolyzed patients with acute ischemic stroke (AIS). We aimed to determine the effects of intensive BP lowering, specifically in patients with severe AIS who participated in the international, Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). Methods: Pre-specificed subgroup analyzes of the BP arm of ENCHANTED, a multicenter, partial-factorial, open, blinded outcome assessed trial, in which 2227 thrombolysis-eligible and treated AIS patients with elevated systolic BP (>150 mmHg) were randomized to intensive (target 130-140 mmHg) or guideline-recommended (10) baseline neurological scores on the National Institutes of Health Stroke Scale (NIHSS). The primary efficacy outcome was death or any disability (modified Rankin scale [mRS] scores 2-6). The key safety outcome was intracranial hemorrhage (ICH). Treatment effects estimated in logistic regression models are reported as odds ratios with 95% confidence intervals (CIs). Results: There were 1,311 patients (mean age 67 years; 37% female; median baseline NIHSS of 11 [range 6.0-15.0]) with severe AIS. Overall, there was no significant difference in the primary outcome of death or disability. However, intensive BP lowering significantly increased mortality (odds ratio 1.52, 95% CI 1.09-2.13; P=0.014) compared to guideline BP lowering, despite significantly lowering clinician-reported ICH (odds ratio 0.63, 95% CI 0.43-0.92; P=0.016). Conclusion: Intensive BP lowering is associated with increased mortality in patients with severe AIS despite lowering the risk of ICH. Further randomized trials are required to provide reliable evidence over the optimum systolic BP target in the most serious type of AIS. Trial Registration: ClinicalTrials.gov Identifier: NCT01422616

COVID-19 may be associated with neurologic complications. Patients with COVID-19 may develop an acute inflammatory painful polyradiculoneuritis that seems to respond to intravenous human immunoglobulin.

Background RESILIENT is a prospective, multicenter, randomized phase III trial to test 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. Methods Subjects must fulfill the following main inclusion criteria: symptom onset ≤8 h, age ≥18 years, baseline NIHSS ≥8, evidence of intracranial ICA or proximal MCA (M1 segment) occlusion, ASPECTS ≥6 on CT or >5 on DWI-MRI and be either ineligible for or unresponsive to intravenous alteplase. The primary end-point is the distribution of disability levels (on the modified Rankin Scale, mRS) at 90 days under the intention-to-treat principle. Randomization Randomization is performed under a minimization process using age, baseline NIHSS, intravenous alteplase use, occlusion site and center. Design The trial is designed with an expectation of a 10% difference in the proportion of favorable outcome (mRS 0–2 at 90 days) common odds ratio of 1.615. Primary outcome Projected sample size is 690 subjects with pre-planned interim analyses at 174, 346, and 518 subjects. Secondary outcomes Secondary end-points include: 90-day functional independence (mRS ≤2), mRS shift stratified for treatment with IV rt-PA at 90 days, infarct volume on 24 h CT or MRI, early dramatic response (NIHSS 0–2 or improvement ≥8 points) at 24 h, vessel recanalization evaluated by CTA or MRA at 24 h, and the post-procedure rate of successful reperfusion (defined as a modified Treatment in Cerebral Infarction 2b or greater). Safety variables are mortality at 90 days, symptomatic intracranial hemorrhage at 24 h and procedure-related complications.