Search

Objective Selected patients with large vessel occlusion (LVO) strokes can benefit from endovascular therapy (EVT). However, the effectiveness of EVT is largely dependent on how quickly the patient receives treatment. Recent technological developments have led to the first neurointerventional treatments using robotic assistance, opening up the possibility of performing remote stroke interventions. Existing telestroke networks provide acute stroke care, including remote administration of intravenous thrombolysis (IVT). Therefore, the introduction of remote EVT in distant stroke centers requires an adaptation of the existing telestroke networks. The aim of this work was to propose a framework for centers that are potential candidates for telerobotics according to the resources currently available in these centers. Methods In this paper, we highlight the future challenges for including remote robotics in telestroke networks. A literature review provides potential solutions. Results Existing telestroke networks need to determine which centers to prioritize for remote robotic technologies based on objective criteria and cost-effectiveness analysis. Organizational challenges include regional coordination and specific protocols. Technological challenges mainly concern telecommunication networks. Conclusions Specific adaptations will be necessary if regional telestroke networks are to include remote robotics. Some of these can already be put in place, which could greatly help the future implementation of the technology.

Some promoters, termed Epromoters, can display enhancer activity and regulate distal genes in their endogenous context. Here the authors report the broad involvement of Epromoters in the coordinated activation of interferon (IFN) response. They show activation of a number of IFN-inducible genes is a result of Epromoters regulating expression of an entire IFN response gene cluster.

Objectives: Mechanical thrombectomy (MT) is an effective treatment for acute ischemic stroke (AIS) caused by large vessel occlusion. Recanalization time is a key factor in the treatment of AIS. It has previously been suggested that intravenous thrombolysis (IVT) may be associated with a shorter recanalization time. The aim of our study was to investigate whether IVT or other factors could be associated with shorter or longer MT procedure times. Methods: We performed a retrospective analysis of a local cohort of patients treated by MT. We collected procedure time (puncture to recanalization and clot visualization to recanalization), demographic data, localization of the thrombus, antithrombotic treatment at arrival, IVT infusion, and stroke subtype at discharge according to the TOAST classification. We planned to analyze the full cohort and the successful revascularization subgroup. Results: There was no difference in procedure times between patients who received IVT and those who did not. In the successful revascularization subgroup, patients presenting with cardioembolic stroke had a significantly shorter time between clot visualizations and revascularization than the other patients (41 vs. 56 min, p = 0.024), but this was not the case in the full cohort. Also in the successful revascularization subgroup, the revascularization time was 76 vs. 61 min (p = 0.075) in patients presenting with tandem occlusion vs. the others, but there was no difference between these groups in the full cohort. Conclusions: There was no difference in terms of procedure times in patients treated by IVT and MT vs. patients treated by MT alone either in the full cohort or in the successful revascularization subgroup. The data from the successful revascularization subgroup may be useful for studying revascularization times, provided that data from procedures that were stopped prematurely by the operator due to the length of time since symptom onset is removed.

Background and PurposeThe presence of a Susceptibility Vessel Sign (SVS) in the acute phase of proximal occlusion ischemic stroke indicates the presence of deoxyhemoglobin in the thrombus. Thrombi composition changes over time. The aim of this study was to investigate whether the absence of SVS is associated with a shorter symptom onset to imaging time.MethodsWe retrospectively analyzed all patients referred for mechanical thrombectomy at Besançon University Hospital between 1 January 2015 and 31 December 2020 for whom readable T2*-weighted imaging was available. We compared patient characteristics according to the presence or absence of an SVS. We also studied the subgroup for whom the exact symptom onset time was known. We performed a univariate statistical analysis, then a multivariate analysis on the variables that were statistically significant in the univariate analysis.ResultsOf the 389 patients included, 309 (79.4%) were SVS+. We found no significant relationship between SVS– and the time between symptom onset and imaging in the whole cohort. In the multivariate analysis, SVS– was associated with anticoagulant treatment (p < 0.01), and SVS+ with age (p = 0.023) and carotid terminus occlusion (p = 0.042). In the known symptom onset subgroup, SVS– was significantly associated with a shorter symptom onset -imaging time (p < 0.001), and this was confirmed in the multivariate analysis (p = 0.011; OR 0.911; 95% CI [0.844; 0.972]).ConclusionIn the acute phase of proximal occlusion ischemic stroke, absence of SVS was associated with a shorter symptom onset–imaging time for patients with a known symptom onset time.

Background and Purpose: The aim of this study was to characterize neurological complications after flow diverter (FD) treatment on a long follow-up cohort and identify predictive factors associated with these complications.Methods: This study was conducted on a monocentric cohort of patients treated for intracranial aneurysms by FD.Results: Between September 2008 and July 2018, 413 patients were treated for 514 aneurysms: 18% of the patients presented with at least one neurological complication during a median follow-up of 446 days (IQR 186–1,210). Sixty-one patients presented with ischemic complications, 13 with hemorrhagic ones and 10 with compressive processes. Among 89 neurological complications 64.5% were peri-operative (occurring within the 30 days following the procedure) and 35.5% were delayed after 1 month.Conclusions: Overall, neurological complications after FD implantation were overrepresented by cerebrovascular ischemic events occurring during the peri-operative period, but also in a delayed manner after 1 year. Long-term follow-up is relevant after aneurysm intervention using FD.

Introduction Mechanical thrombectomy (MT) increases functional independence in patients with acute ischaemic stroke with anterior circulation large vessel occlusion (LVO), and the probability to achieve functional independence decreases by 20% for each 1-hour delay to reperfusion. Therefore, we aim to investigate whether direct angiosuite transfer (DAT) is superior to standard imaging/emergency department-based management in achieving 90-day functional independence in patients presenting with an acute severe neurological deficit likely due to LVO and requiring emergent treatment with MT.Methods and analysis DIRECT ANGIO (Effect of DIRECT transfer to ANGIOsuite on functional outcome in patient with severe acute stroke treated with thrombectomy: the randomised DIRECT ANGIO Trial) trial is an investigator-initiated, multicentre, prospective, randomised, open-label, blinded endpoint (PROBE) study. Eligibility requires a patient ≤75 years, pre-stroke modified Rankin Scale (mRS) 0–2, presenting an acute severe neurological deficit and admitted within 5 hours of symptoms onset in an endovascular-capable centre. A total of 208 patients are randomly allocated in a 1:1 ratio to DAT or standard management. The primary outcome is the rate of patients achieving a functional independence, assessed as mRS 0–2 at 90 days. Secondary endpoints include patients presenting confirmed LVO, patients eligible to intravenous thrombolysis alone, patients with intracerebral haemorrhage and stroke-mimics, intrahospital time metrics, early neurological improvement (reduction in National Institutes of Health Stroke Scale by ≥8 points or reaching 0–1 at 24 hours) and mRS overall distribution at 90 days and 12 months. Safety outcomes are death and intracerebral haemorrhage transformation. Medico-economics analyses include health-related quality of life and cost utility assessment.Ethics and dissemination The DIRECT ANGIO trial was approved by the ethics committee of Ile de France 1. Study began in April 2020. Results will be published in an international peer-reviewed medical journal.Trial registration number NCT03969511.

Intracranial hemorrhage is one of the most feared complications following brain infarct. Ischemic tissues have a natural tendency to bleed. Moreover, the first recanalization trials using intravenous thrombolysis have shown an increase in mild to severe intracranial hemorrhage. Symptomatic intracerebral hemorrhage is strongly associated with poor outcomes and is an important factor in recanalization decisions. Stroke physicians have to weigh the potential benefit of recanalization therapies, first, with different risks of intracranial hemorrhage described in randomized controlled trials, and second with numerous risk markers that have been found to be associated with intracranial hemorrhage in retrospective series. These decisions have become quite complex with different intravenous thrombolytics and mechanical thrombectomy. This review aims to outline some elements of the pathophysiological mechanisms and classifications, describe most of the risk factors identified for each reperfusion therapy, and finally suggest future research directions that could help physicians dealing with these complications.

Abstract Mercury (Hg) enrichments in sediments are increasingly used as tracer for distal volcanism in deep‐time investigations. The impact of changes in organic‐matter deposition and preservation on sedimentary Hg sequestration is, however, poorly understood. In this study, we evaluate the potential role of intense weathering and postdepositional organic‐matter degradation on the Hg/TOC proxy in sediments. For this, we investigate weathering profiles in organic‐rich sediments from lowermost Toarcian sediments (T‐OAE; Lafarge cement quarry, France) and organic‐rich deposits from the uppermost Cenomanian‐lowermost Turonian Bonarelli level (OAE2; Furlo and Monte Velo, Italy; Manilva and El Chorro, Spain). The comparison of Hg data along weathering profiles in lowermost Toarcian sediments indicates that recent intense oxidation of the originally organic‐rich deposits has removed up to 89% of the Hg signal. The organic‐rich sediments of the Furlo and Manilva sections are characterized by lower Hg/total organic carbon (TOC) ratios, which suggest important Hg scavenging by organic matter (OM) deposition. At the opposite, in equivalent successions, three significant positive Hg/TOC excursions persist at El Chorro and Monte Velo. These samples exhibit low Hydrogen Index (HI) values, which plot in the field of type‐III OM. This resulted from postdepositional degradation of marine OM type II to type III, which largely modified the amount and the quality of OM. Consequently, the recorded Hg/TOC ratios do not reflect original Hg drawdown but postdepositional oxidation, suggesting that extreme care is needed in the evaluation of the history of OM preservation when using Hg as a proxy for volcanic activity.

The Ikzf1 locus encodes the lymphoid specific transcription factor Ikaros, which plays an essential role in both T and B cell differentiation, while deregulation or mutation of IKZF1/Ikzf1 is involved in leukemia. Tissue-specific and cell identity genes are usually associated with clusters of enhancers, also called super-enhancers, which are believed to ensure proper regulation of gene expression throughout cell development and differentiation. Several potential regulatory regions have been identified in close proximity of Ikzf1, however, the full extent of the regulatory landscape of the Ikzf1 locus is not yet established. In this study, we combined epigenomics and transcription factor binding along with high-throughput enhancer assay and 4C-seq to prioritize an enhancer element located 120 kb upstream of the Ikzf1 gene. We found that deletion of the E120 enhancer resulted in a significant reduction of Ikzf1 mRNA. However, the epigenetic landscape and 3D topology of the locus were only slightly affected, highlighting the complexity of the regulatory landscape regulating the Ikzf1 locus.

Summary: Nuclear protein in testis (Nut) is a universal oncogenic driver in the highly aggressive NUT midline carcinoma, whose physiological function in male germ cells has been unclear. Here we show that expression of Nut is normally restricted to post-meiotic spermatogenic cells, where its presence triggers p300-dependent genome-wide histone H4 hyperacetylation, which is essential for the completion of histone-to-protamine exchange. Accordingly, the inactivation of Nut induces male sterility with spermatogenesis arrest at the histone-removal stage. Nut uses p300 and/or CBP to enhance acetylation of H4 at both K5 and K8, providing binding sites for the first bromodomain of Brdt, the testis-specific member of the BET family, which subsequently mediates genome-wide histone removal. Altogether, our data reveal the detailed molecular basis of the global histone hyperacetylation wave, which occurs before the final compaction of the male genome. : A transcription-independent histone hyperacetylation is associated with near-total histone replacement during mouse spermatogenesis. Shiota et al. show the oncogenic factor Nut is expressed in post-meiotic male germ cells, where it recruits p300 and/or CBP and enhances histone H4K5 and H4K8 acetylation, leading to histone-to-protamine replacement. Keywords: BRD4-NUT, protamines, transition proteins, histone variants, spermiogenesis, histone post-translational modifications, cancer testis, testis specific

The molecular basis of residual histone retention after the nearly genome-wide histone-to-protamine replacement during late spermatogenesis is a critical and open question. Our previous investigations showed that in postmeiotic male germ cells, the genome-scale incorporation of histone variants TH2B-H2A.L.2 allows a controlled replacement of histones by protamines to occur. Here, we highlight the intrinsic ability of H2A.L.2 to specifically target the pericentric regions of the genome and discuss why pericentric heterochromatin is a privileged site of histone retention in mature spermatozoa. We observed that the intranuclear localization of H2A.L.2 is controlled by its ability to bind RNA, as well as by an interplay between its RNA-binding activity and its tropism for pericentric heterochromatin. We identify the H2A.L.2 RNA-binding domain and demonstrate that in somatic cells, the replacement of H2A.L.2 RNA-binding motif enhances and stabilizes its pericentric localization, while the forced expression of RNA increases its homogenous nuclear distribution. Based on these data, we propose that the specific accumulation of RNA on pericentric regions combined with H2A.L.2 tropism for these regions are responsible for stabilizing H2A.L.2 on these regions in mature spermatozoa. This situation would favor histone retention on pericentric heterochromatin.