“ESPORTE E CULTURA: MOVIMENTO E CRIAÇÃO” Apresentação esquematizada de um exemplo de formação artístico-pedagógica na Escola Superior de Esportes de Colônia: Teatro de movimento/Jogo-Música-Dança, uma área de estudos interdisciplinar no curso de graduação

É possível criar ligações entre esporte e arte de diversas formas, entendendo-se esporte de maneira ampla e diversificada e definido como uma área do movimento, em suas possíveis manifestações, uma área abrangente da cultura do movimento, com interesses e manifestações da cultura lúdica, expressiva, esportiva e da saúde e não apenas no âmbito das disciplinas esportivas específicas e suas técnicas de movimento

Autonomic reactions and peri-interventional alterations in body weight as potential supplementary outcome parameters for thromboembolic stroke in rats

BACKGROUND: Since several neuroprotectives failed to reproduce promising preclinical results under clinical conditions, efforts emerged to implement clinically relevant endpoints in animal stroke studies. Thereby, insufficient attention was given on autonomic reactions due to experimental stroke, although clinical trials reported on high functional and prognostic impact. This study focused on autonomic consequences and body weight changes in a translational relevant stroke model and investigated interrelations to different outcome measurements. METHODS: Forty-eight rats underwent thromboembolic middle cerebral artery occlusion (MCAO) while recording heart rate (HR) and mean arterial pressure (MAP). After assessing early functional impairment (Menzies score), animals were assigned to control procedure or potentially neuroprotective treatment with normobaric (NBO) or hyperbaric oxygen (HBO). Four or 24 hours after ischemia onset, functional impairment was re-assessed and FITC-albumin administered intravenously obtaining leakage-related blood–brain barrier (BBB) impairment. Body weight was documented prior to MCAO and 4 or 24 hours after ischemia onset. RESULTS: During MCAO, HR was found to increase significantly while MAP decreased. The amount of changes in HR was positively correlated with early functional impairment (P = 0.001): Severely affected animals provided an increase of 15.2 compared to 0.8 beats/minute in rats with low impairment (P = 0.048). Regarding body weight, a decrease of 9.4% within 24 hours after MCAO occurred, but treatment-specific alterations showed no significant correlations with respective functional or BBB impairment. CONCLUSIONS: Future studies should routinely include autonomic parameters to allow inter-group comparisons and better understanding of autonomic reactions due to experimental stroke. Prospectively, autonomic consequences might represent a useful outcome parameter enhancing the methodological spectrum of preclinical stroke studies

Performance of Automated Attenuation Measurements at Identifying Large Vessel Occlusion Stroke on CT Angiography

PURPOSE Computed tomography angiography (CTA) is routinely used to detect large-vessel occlusion (LVO) in patients with suspected acute ischemic stroke; however, visual analysis is time consuming and prone to error. To evaluate solutions to support imaging triage, we tested performance of automated analysis of CTA source images (CTASI) at identifying patients with LVO. METHODS Stroke patients with LVO were selected from a prospectively acquired cohort. A control group was selected from consecutive patients with clinically suspected stroke without signs of ischemia on CT perfusion (CTP) or infarct on follow-up. Software-based automated segmentation and Hounsfield unit (HU) measurements were performed on CTASI for all regions of the Alberta Stroke Program Early CT score (ASPECTS). We derived different parameters from raw measurements and analyzed their performance to identify patients with LVO using receiver operating characteristic curve analysis. RESULTS The retrospective analysis included 145 patients, 79 patients with LVO stroke and 66 patients without stroke. The parameters hemispheric asymmetry ratio (AR), ratio between highest and lowest regional AR and M2-territory AR produced area under the curve (AUC) values from 0.95-0.97 (all p < 0.001) for detecting presence of LVO in the total population. Resulting sensitivity (sens)/specificity (spec) defined by the Youden index were 0.87/0.97-0.99. Maximum sens/spec defined by the specificity threshold ≥0.70 were 0.91-0.96/0.77-0.83. Performance in a~small number of patients with isolated M2 occlusion was lower (AUC: 0.72-0.85). CONCLUSION Automated attenuation measurements on CTASI identify proximal LVO stroke patients with high sensitivity and specificity. This technique can aid in accurate and timely patient selection for thrombectomy, especially in primary stroke centers without CTP capacity

Incremental Value of Computed Tomography Perfusion for Final Infarct Prediction in Acute Ischemic Cerebellar Stroke

Background The diagnosis of ischemic cerebellar stroke is challenging because of nonspecific symptoms and very limited accuracy of commonly applied computed tomography (CT) imaging. Advances in CT perfusion imaging provide increasing value in the detection of posterior circulation stroke, but the prognostic value remains unclear. We aimed to identify imaging parameters that predict morphologic outcome in cerebellar stroke patients using advanced CT including whole‐brain CT perfusion (WB‐CTP). Methods and Results We selected all subjects with cerebellar WB‐CTP perfusion deficits and follow‐up‐confirmed cerebellar infarction from a consecutive cohort with suspected stroke who underwent WB‐CTP. Posterior‐circulation‐Acute‐Stroke‐Prognosis‐Early‐CT‐Score (pc‐ASPECTS) was determined on noncontrast CT, CT angiography source images, and on parametric WB‐CTP maps. Cerebellar perfusion deficit volumes on all maps and the final infarction volume on follow‐up imaging were quantified. Uni‐ and multivariate regression analyses were performed. Sixty patients fulfilled the inclusion criteria. pc‐ASPECTS on CT angiography source images (ß, −9.239; 95% CI, −14.220 to −4.259; P0.05). Conclusions In contrast to noncontrast CT and CT angiography, WB‐CTP imaging contains prognostic information for morphologic outcome in patients with acute cerebellar stroke

CT after interhospital transfer in acute ischemic stroke: Imaging findings and impact of prior intravenous contrast administration

Objectives: Large vessel occlusion (LVO) stroke patients routinely undergo interhospital transfer to endovascular thrombectomy capable centers. Imaging is often repeated with residual intravenous (IV) iodine contrast at post-transfer assessment. We determined imaging findings and the impact of residual contrast on secondary imaging. Anterior circulation LVO stroke patients were selected out of a consecutive cohort. Directly admitted patients were contrast naïve, and transferred patients had previously received IV iodine contrast for stroke assessment at the referring hospital. Two independent readers rated the visibility of residual contrast on non-contrast computed tomography (CT) after transfer and assessed the hyperdense vessel sign. Multivariate linear regression analysis was used to investigate the association of the Alberta Stroke Program Early CT score (ASPECTS) with prior contrast administration, time from symptom onset (TFSO), and CTP ischemic core volume in both directly admitted and transferred patients. Results: We included 161 patients, with 62 (39%) transferred and 99 (62%) directly admitted patients. Compared between these groups, transferred patients had a longer TFSO-to-imaging at our institution (median: 212 vs. 75 min, p < 0.001) and lower ASPECTS (median: 8 vs. 9, p < 0.001). Regression analysis presented an independent association of ASPECTS with prior contrast administration (β = −0.25, p = 0.004) but not with TFSO (β = −0.03, p = 0.65). Intergroup comparison between transferred and directly admitted patients pointed toward a stronger association between ASPECTS and CTP ischemic core volume in transferred patients (β = −0.39 vs. β = −0.58, p = 0.06). Detectability of the hyperdense vessel sign was substantially lower after transfer (66 vs. 10%, p < 0.001). Conclusion: Imaging alterations due to residual IV contrast are frequent in clinical practice and render the hyperdense vessel sign largely indetectable. Larger studies are needed to clarify the influence on the association between ASPECTS and ischemic core

Functional redundancy between RAP1 isoforms in murine platelet production and function

RAP GTPases, important regulators of cellular adhesion, are abundant signaling molecules in the platelet/megakaryocytic lineage. However, mice lacking the predominant isoform, RAP1B, display a partial platelet integrin activation defect and have a normal platelet count, suggesting the existence of a RAP1-independent pathway to integrin activation in platelets and a negligible role for RAP GTPases in megakaryocyte biology. To determine the importance of individual RAP isoforms on platelet production and on platelet activation at sites of mechanical injury or vascular leakage, we conditionally deleted Rap1a and/or Rap1b in the megakaryocytic lineage (mKO). Interestingly, Rap1a/b-mKO mice displayed a marked macrothrombocytopenia due to impaired pro- platelet formation by megakaryocytes. In platelets, RAP isoforms had both redundant and isoform-ˇspecific functions. Deletion of RAP1B, but not RAP1A, significantly reduced α- granule secretion and activation of the cytoskeleton regulator RAC1. Both isoforms significantly contributed to thromboxane A2 generation and the inside-out activation of platelet integrins. Combined deficiency of RAP1A and RAP1B markedly impaired platelet aggregation, spreading and clot retraction. Consistently, thrombus formation in physiological flow conditions was abolished in Rap1a/b-mKO, but not Rap1a-mKO or Rap1b-mKO platelets. Rap1a/b-mKO mice were strongly protected from experimental thrombosis and exhibited a severe defect in hemostasis after mechanical injury. Surprisingly, Rap1a/b-mKO platelets were indistinguishable from controls in their ability to prevent blood-lymphatic mixing during development and hemorrhage at sites of inflammation. In summary, our studies demonstrate an essential role for RAP1 signaling in platelet integrin activation and a critical role in platelet production. While important for hemostatic/thrombotic plug formation, platelet RAP1 signaling is dispensable for vascular integrity during development and inflammation

A Phase Ib/II, open-label, multicenter study of INC280 (capmatinib) alone and in combination with buparlisib (BKM120) in adult patients with recurrent glioblastoma

Purpose: To estimate the maximum tolerated dose (MTD) and/or identify the recommended Phase II dose (RP2D) for combined INC280 and buparlisib in patients with recurrent glioblastoma with homozygous phosphatase and tensin homolog (PTEN) deletion, mutation or protein loss. Methods: This multicenter, open-label, Phase Ib/II study included adult patients with glioblastoma with mesenchymal-epithelial transcription factor (c-Met) amplification. In Phase Ib, patients received INC280 as capsules or tablets in combination with buparlisib. In Phase II, patients received INC280 only. Response was assessed centrally using Response Assessment in Neuro-Oncology response criteria for high-grade gliomas. All adverse events (AEs) were recorded and graded. Results: 33 patients entered Phase Ib, 32 with altered PTEN. RP2D was not declared due to potential drug–drug interactions, which may have resulted in lack of efficacy; thus, Phase II, including 10 patients, was continued with INC280 monotherapy only. Best response was stable disease in 30% of patients. In the selected patient population, enrollment was halted due to limited activity with INC280 monotherapy. In Phase Ib, the most common treatment-related AEs were fatigue (36.4%), nausea (30.3%) and increased alanine aminotransferase (30.3%). MTD was identified at INC280 Tab 300 mg twice daily + buparlisib 80 mg once daily. In Phase II, the most common AEs were headache (40.0%), constipation (30.0%), fatigue (30.0%) and increased lipase (30.0%). Conclusion: The combination of INC280/buparlisib resulted in no clear activity in patients with recurrent PTEN-deficient glioblastoma. More stringent molecular selection strategies might produce better outcomes. Trial registration: NCT01870726

On a theorem of Deaconescu

. Consider finite groups having all nontrivial elements of prime order as a subclass of CN--groups in which the centralizers of all nontrivial elements are nilpotent. Then we give in generalization of a Theorem of Deaconescu [2] necessary and sufficient conditions to be such a group. 1 Introduction Let CP 1 , CP and CN be the class of finite groups in which the centralizers of all nontrivial elements contain only elements of prime order, of prime power order and are nilpotent, respectively. Clearly CP 1 ae CP ae CN , and CP 1 , CP consists of exactly those groups having all nontrivial elements of prime order and prime power order, respectively. Deaconescu [2] had shown Theorem 1 Let G be a CP 1 --group. Then one of the following cases occurs: I: G is a p--group of exponent p: II: (a) jGj = p a q; 3 p ! q; a 3; jF (G)j = p a\Gamma1 ; jG : G 0 j = p: (b) jGj = p a q; 3 p; q; a 1; jF (G)j = jG 0 j = p a : (c) jGj = 2 a p; p 3; a 2; jF (G)j = jG 0 j = 2 a : (d..

Promiscuous Defluorinating Enoyl-CoA Hydratases/Hydrolases Allow for Complete Anaerobic Degradation of 2-Fluorobenzoate

Biodegradation of the environmentally hazardous fluoroaromatics has mainly been associated with oxygenase-dependent defluorination reactions. Only very recently a novel mode of oxygen-independent defluorination was identified for the complete degradation of para-substituted fluoroaromatics in the denitrifying Thauera aromatica: a promiscuous class I benzoyl-coenzyme A (BzCoA) reductase (BCR) catalyzed the ATP-dependent defluorination of 4-F-BzCoA to BzCoA. Here, we studied the unknown enzymatic defluorination during the complete degradation of 2-F-benzoate to CO2 and HF. We demonstrate that after activation of 2-F-benzoate by a promiscuous AMP-forming benzoate-CoA ligase, the 2-F-BzCoA formed is subsequently dearomatized by BCR to a mixture of 2-F- and 6-F-cyclohexa-1,5-diene-1-carboxyl-CoA (2-F-/6-F-1,5-dienoyl-CoA). This finding indicates that BCR is not involved in C–F-bond cleavage during growth with 2-F-benzoate. Instead, we identified defluorination of the two isomers by enoyl-CoA hydratases/hydrolases involved in down-stream reactions of the BzCoA degradation pathway. (i) The 1,5-dienoyl-CoA hydratase hydrated the F-1,5-dienoyl-CoA isomers to a mixture of the stable 2-F-6-OH-1-enoyl-CoA and the unstable α-fluorohydrin 6-F-6-OH-1-enoyl-CoA; the latter spontaneously decomposed to HF and 6-oxo-cyclohex-1-enoyl-CoA (6-oxo-1-enoyl-CoA), a common intermediate of the BzCoA degradation pathway. (ii) 6-Oxo-1-enoyl-CoA hydrolase/hydratase catalyzed the defluorination of 2-F-6-OH-1-enoyl-CoA to 2-oxo-6-OH-1-enoyl-CoA and HF again via water addition to an F-enoyl-CoA functionality. Based on these in vitro results, we demonstrate a previously overseen capability of 2-F-benzoate degradation for many but not all tested facultatively and obligately anaerobic bacteria that degrade aromatic compounds via the BzCoA degradation pathway. In conclusion, the newly identified enzymatic defluorination by enoyl-CoA hydratases via α-fluorohydrin formation represents an abundant, physiologically relevant principle of enzymatic defluorination