Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection: The STOP-CAD Study.

BACKGROUND: Small, randomized trials of patients with cervical artery dissection showed conflicting results regarding optimal stroke prevention strategies. We aimed to compare outcomes in patients with cervical artery dissection treated with antiplatelets versus anticoagulation. METHODS: This is a multicenter observational retrospective international study (16 countries, 63 sites) that included patients with cervical artery dissection without major trauma. The exposure was antithrombotic treatment type (anticoagulation versus antiplatelets), and outcomes were subsequent ischemic stroke and major hemorrhage (intracranial or extracranial hemorrhage). We used adjusted Cox regression with inverse probability of treatment weighting to determine associations between anticoagulation and study outcomes within 30 and 180 days. The main analysis used an as-treated crossover approach and only included outcomes occurring with the above treatments. RESULTS: The study included 3636 patients (402 [11.1%] received exclusively anticoagulation and 2453 [67.5%] received exclusively antiplatelets). By day 180, there were 162 new ischemic strokes (4.4%) and 28 major hemorrhages (0.8%); 87.0% of ischemic strokes occurred by day 30. In adjusted Cox regression with inverse probability of treatment weighting, compared with antiplatelet therapy, anticoagulation was associated with a nonsignificantly lower risk of subsequent ischemic stroke by day 30 (adjusted hazard ratio [HR], 0.71 [95% CI, 0.45-1.12]; P=0.145) and by day 180 (adjusted HR, 0.80 [95% CI, 0.28-2.24]; P=0.670). Anticoagulation therapy was not associated with a higher risk of major hemorrhage by day 30 (adjusted HR, 1.39 [95% CI, 0.35-5.45]; P=0.637) but was by day 180 (adjusted HR, 5.56 [95% CI, 1.53-20.13]; P=0.009). In interaction analyses, patients with occlusive dissection had significantly lower ischemic stroke risk with anticoagulation (adjusted HR, 0.40 [95% CI, 0.18-0.88]; Pinteraction=0.009). CONCLUSIONS: Our study does not rule out the benefit of anticoagulation in reducing ischemic stroke risk, particularly in patients with occlusive dissection. If anticoagulation is chosen, it seems reasonable to switch to antiplatelet therapy before 180 days to lower the risk of major bleeding. Large prospective studies are needed to validate our findings.

Study of Rivaroxaban for Cerebral Venous Thrombosis: A Randomized Controlled Feasibility Trial Comparing Anticoagulation With Rivaroxaban to Standard-of-Care in Symptomatic Cerebral Venous Thrombosis.

BACKGROUND: Emerging data suggest that direct oral anticoagulants may be a suitable choice for anticoagulation for cerebral venous thrombosis (CVT). However, conducting high-quality trials in CVT is challenging as it is a rare disease with low rates of adverse outcomes such as major bleeding and functional dependence. To facilitate the design of future CVT trials, SECRET (Study of Rivaroxaban for Cerebral Venous Thrombosis) assessed (1) the feasibility of recruitment, (2) the safety of rivaroxaban compared with standard-of-care anticoagulation, and (3) patient-centered functional outcomes. METHODS: This was a phase II, prospective, open-label blinded-end point 1:1 randomized trial conducted at 12 Canadian centers. Participants were aged ≥18 years, within 14 days of a new diagnosis of symptomatic CVT, and suitable for oral anticoagulation; they were randomized to receive rivaroxaban 20 mg daily, or standard-of-care anticoagulation (warfarin, target international normalized ratio, 2.0-3.0, or low-molecular-weight heparin) for 180 days, with optional extension up to 365 days. Primary outcomes were annual rate of recruitment (feasibility); and a composite of symptomatic intracranial hemorrhage, major extracranial hemorrhage, or mortality at 180 days (safety). Secondary outcomes included recurrent venous thromboembolism, recanalization, clinically relevant nonmajor bleeding, and functional and patient-reported outcomes (modified Rankin Scale, quality of life, headache, mood, fatigue, and cognition) at days 180 and 365. RESULTS: Fifty-five participants were randomized. The rate of recruitment was 21.3 participants/year; 57% of eligible candidates consented. Median age was 48.0 years (interquartile range, 38.5-73.2); 66% were female. There was 1 primary event (symptomatic intracranial hemorrhage), 2 clinically relevant nonmajor bleeding events, and 1 recurrent CVT by day 180, all in the rivaroxaban group. All participants in both arms had at least partial recanalization by day 180. At enrollment, both groups on average reported reduced quality of life, low mood, fatigue, and headache with impaired cognitive performance. All metrics improved markedly by day 180. CONCLUSIONS: Recruitment targets were reached, but many eligible participants declined randomization. There were numerically more bleeding events in patients taking rivaroxaban compared with control, but rates of bleeding and recurrent venous thromboembolism were low overall and in keeping with previous studies. Participants had symptoms affecting their well-being at enrollment but improved over time. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03178864.

Microbe-Assisted Nanocomposite Anodes for Aqueous Li-Ion Batteries.

With the rapid increase in the use of lithium-ion batteries (LIBs), the development of safe LIBs has become an important social issue. Replacing flammable organic liquid electrolytes in current LIBs with water can be an alternative route to resolve this safety concern. The water-in-salt (WIS) electrolytes received great attention as next-generation electrolytes due to their large electrochemical stability window. However, their high cathodic limit remains as a challenge, impeding the use of low-potential anodes. Here, we report the first biodirected synthesis of carbonaceous layers on anodes to use them as interlayers that prevent a direct contact of water molecules to anode particles. High-aspect ratio microbes are utilized as precursors of carbonaceous layers on TiO2 nanoparticles (m-TiO2) to enhance the conductivity and to reduce the electrolysis of WIS electrolytes. We selected the cylindrical shape of microbes that offers geometric diversity, providing us a toolkit to investigate the effect of microbe length in forming the network in binary composites and their impacts on the battery performance with WIS electrolytes. Using microbes with varying aspect ratios, the optimal microbe size to maximize the battery performance is determined. The effects of storage time on microbe size are also studied. Compared to uncoated TiO2 anodes, m-TiO2 exhibited 49% higher capacity at the 40th cycle and enhanced the cycle life close to anodes made with a conventional carbon precursor while using an 11% less amount of carbon. We performed density functional theory calculations to unravel the underlying mechanism of the performance improvement using microbe-derived carbon layers. Computational results show that high amounts of pyridinic nitrogen present in the peptide bonds in microbes are expected to slow down the water diffusion. Our findings provide key insights into the design of an interlayer for WIS anodes and open an avenue to fabricate energy storage materials using biomaterials.

Experience-Dependent Changes in Myelin Basic Protein Expression in Adult Visual and Somatosensory Cortex.

An experience-driven increase in oligodendrocytes and myelin in the somatosensory cortex (S1) has emerged as a new marker of adult cortical plasticity. That finding contrasts with the view that myelin is a structural brake on plasticity, and that contributes to ending the critical period (CP) in the visual cortex (V1). Despite the evidence that myelin-derived signaling acts to end CP in V1, there is no information about myelin changes during adult plasticity in V1. To address this, we quantified the effect of three manipulations that drive adult plasticity (monocular deprivation (MD), fluoxetine treatment or the combination of MD and fluoxetine) on the expression of myelin basic protein (MBP) in adult rat V1. In tandem, we validated that environmental enrichment (EE) increased cortical myelin by measuring MBP in adult S1. For comparison with the MBP measurements, three plasticity markers were also quantified, the spine markers drebrin E and drebrin A, and a plasticity maintenance marker Ube3A. First, we confirmed that EE increased MBP in S1. Next, that expression of the plasticity markers was affected in S1 by EE and in V1 by the visual manipulations. Finally, we found that after adult MD, MBP increased in the non-deprived V1 hemisphere, but it decreased in the deprived hemisphere, and those changes were not influenced by fluoxetine. Together, the findings suggest that modulation of myelin expression in adult V1 may reflect the levels of visually driven activity rather than synaptic plasticity caused by adult plasticity.