Kennedysmart6930

This scientific statement is endorsed by European Academy of Neurology (EAN). This article is protected by copyright. All rights reserved.BACKGROUND AND PURPOSE Cancer is a frequent finding in ischaemic stroke patients. The frequency of cancer amongst participants in the NAVIGATE ESUS randomized trial and the distribution of outcome events during treatment with aspirin and rivaroxaban were investigated. METHODS Trial participation required a recent embolic stroke of undetermined source. Patients' history of cancer was recorded at the time of study entry. During a mean follow-up of 11 months, the effects of aspirin and rivaroxaban treatment on recurrent ischaemic stroke, major bleeding and all-cause mortality were compared between patients with cancer and patients without cancer. RESULTS Amongst 7213 randomized patients, 543 (7.5%) had cancer. Of all patients, 3609 were randomized to rivaroxaban [254 (7.0%) with cancer] and 3604 patients to aspirin [289 (8.0%) with cancer]. The annual rate of recurrent ischaemic stroke was 4.5% in non-cancer patients in the rivaroxaban arm and 4.6% in the aspirin arm [hazard ratio (HR) 0.98, 95% confidence interval (CI) 0.78-1.24]. In cancer patients, the rate of recurrent ischaemic stroke was 7.7% in the rivaroxaban arm and 5.4% in the aspirin arm (HR 1.43, 95% CI 0.71-2.87). Amongst cancer patients, the annual rate of major bleeds was non-significantly higher for rivaroxaban than aspirin (2.9% vs. 1.1%; HR 2.57, 95% CI 0.67-9.96; P for interaction 0.95). All-cause mortality was similar in both groups. CONCLUSIONS Our exploratory analyses show that patients with embolic stroke of undetermined source and a history of cancer had similar rates of recurrent ischaemic strokes and all-cause mortality during aspirin and rivaroxaban treatments and that aspirin appeared safer than rivaroxaban in cancer patients regarding major bleeds. www.clinicaltrials.gov (NCT02313909). © 2020 European Academy of Neurology.Pre-targeted strategies combine high specificity of macromolecules such as antibodies for target binding and rapid clearance of small molecular ligands to image target molecules. However, pre-targeted imaging of the activity of enzymes has not been described likely due to the lack of a mechanism to retain the injected substrate in the first step for subsequent labeling. Here we report the use of  two   bioorthogonal reactions-the condensation reaction of aromatic nitriles and aminothiols, and the  inverse-electron demand Deals-Alder reaction (IEDDA) between tetrazine and trans-cyclooctene (TCO) -to develop a novel strategy for pre-targeted imaging of the activity of proteases.  The substrate  probe bearing TCO (TCO-C-SNAT4) can be selectively activated by an enzyme target (e.g. caspase-3/7), which triggers macrocyclization and subsequent in situ self-assembly into nanoaggregates retained at the target site. Our results show that tetrazine-imaging tag conjugate is able to label TCO in the nanoaggregates to generate selective signal retention for imaging in vitro, in cells and in mice. Due to the decoupling of enzyme activation and imaging tag immobilization, TCO-C-SNAT4 can be repetitively injected to generate and accumulate more TCO-nanoaggregates for click labeling. This strategy should be particularly attractive for imaging the activity of enzymes with slow kinetics using short-lived radioisotopes. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Drought extent and severity have increased and are predicted to continue to increase in many parts of the world. Understanding tree vulnerability to drought at both individual and species levels is key to ongoing forest management and preparation for future transitions in community composition. The influence of subsurface hydrologic processes is particularly important in water-limited ecosystems, and is an under-studied aspect of tree drought vulnerability. With California's 2013-2016 extraordinary drought as a natural experiment, we studied four co-occurring woodland tree species, blue oak (Quercus douglasii), valley oak (Quercus lobata), grey pine (Pinus sabiniana), and California juniper (Juniperus californica), examining drought vulnerability as a function of climate, lithology and hydrology using regional aerial dieback surveys and site scale field surveys. We found that in addition to climatic drought severity (i.e. rainfall), subsurface processes explained variation in drought vulnerability within and change. This article is protected by copyright. All rights reserved.BACKGROUND Mutations in the BICD2 gene cause autosomal dominant lower extremity-predominant spinal muscular atrophy 2A (SMALED2A), a condition that is associated with a specific pattern of thigh and calf muscle involvement when studied by Magnetic Resonance Imaging (MRI). Patients may present minor clinical sensory impairment, however objective sensory involvement has yet to be demonstrated. METHODS We collected clinical data from 11 patients from five different families carrying mutations in BICD2. Genetic diagnosis was achieved using gene panel testing and skin biopsies were taken from two patients to study the Epidermal Nerve Fiber Density (ENFD). RESULTS In the studied patients, three new pathogenic mutations were detected as well as the already defined pathogenic p.Ser107Leu mutation. The most frequent clinical picture was characterized by lower limb weakness in combination with foot deformities. One patient manifested clinical and electrophysiological sensory impairment, and the ENFD study of another patient revealed the existence of a small fiber neuropathy. Muscle MRI showed a common pattern of fat deposition including selective involvement of gluteus medius and minimus at the pelvic level, the anterior compartment of the thigh, and the posterior compartment of the calf, with only mild or no involvement of the intrinsic foot muscles. CONCLUSIONS We report three new pathogenic mutations in the BICD2 gene. Muscle MRI confirms the existence of a selective pattern of thigh and leg muscle involvement in SMALED2A, providing additional information regarding pelvic and foot muscles. read more Moreover, our results raise the possibility of sensory involvement in the disease. This article is protected by copyright. All rights reserved.