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Recently, neurorehabilitation that uses virtual reality systems is being applied in clinical settings to deal with issues such as phantom limb pain (PLP) as an alternative to mirror box therapy. One of the weak points of mirror box therapy is that the desired analgesia effect might not be confirmed in some patients. One hypothesis to explain this phenomenon is that the subjective sense of the length of a phantom limb is different from that of an intact limb. Since the gap between body representation in the brain and actual sensory feedback is considered one of the causes of PLP, different lengths of a subjective phantom limb are a serious problem for mirror box therapy and similar VR-based rehabilitation methods. We are thus developing a VR system that displays an avatar that has the same length as the subjective phantom limb. The purpose of the current study is to determine the feasibility of the VR system – specifically, whether it has enough effect on sense of agency (SoA) and sense of ownership (SoO) for healthy subjects – before conducting experiments for actual phantom limb patients. To this end, we developed a VR system in which a virtual avatar performs a motion identical to that of the subject by means of a motion capturing device (Kinect V2). The subject wears a 3D head mounted display (Oculus Rift DK2) to experience seeing through the eyes of the avatar. Six conditions of avatar representation were used: two appearances of a normal human arm and a robot arm and three lengths of the arm (short, medium, and long). The subject executes elbow flexion-extension movement of the right arm, which causes the same movement in the VR avatar’s arm. After the induction movement, the subjective sense of the length of the right arm is measured by a pointing gesture of the left hand. Twelve subjects participated in this experiment. Results showed that the subjective length of the arm was changed according to the length of the displayed arm in the VR environment. From the results of a questionnaire, we found that there is no negative effect on SoA. SoO when the subjects watch the natural human avatar is stronger than when the robot arm is shown. These results are positive, thus confirming the basic potential of the proposed VR system. In conclusion, the change of self-body appearance of a VR avatar has enough effect on subjective sense of arm length. Since the subjective sense of arm length is strongly related to body representation in the brain, we believe that the system can be a platform for research on embodied-brain science systems. [ABSTRACT FROM AUTHOR]

Aims: This study was performed to determine the short-term risk-benefit profiles of patients treated with oral antic- oagulation for acute ischemic stroke or transient ischemic attack using a multicenter, prospective registry. Methods: A total of 1137 patients (645 men, 77 ± 10 years old) with acute ischemic stroke/transient ischemic attack taking warfarin (662 patients) or non-vitamin K antagonist oral anticoagulants (dabigatran in 205, rivaroxaban in 245, apixaban in 25 patients) for nonvalvular atrial fibrillation who completed a three-month follow-up survey were studied. Choice of anticoagulants was not randomized. Primary outcome measures were stroke/systemic embolism and major bleeding. Results: Both warfarin and non-vitamin K antagonist oral anticoagulants were initiated within four days after stroke/ transient ischemic attack onset in the majority of cases. Non-vitamin K antagonist oral anticoagulant users had lower ischemia- and bleeding-risk indices (CHADS2, CHA2DS2-VASc, HAS-BLED) and milder strokes than warfarin users. The three-month cumulative rate of stroke/systemic embolism was 3.06% (95% CI 1.96%-4.74%) in warfarin users and 2.84% (1.65%-4.83%) in non-vitamin K antagonist oral anticoagulant users (adjusted HR 0.96, 95% CI 0.44-2.04). The rate of major bleeding was 2.61% (1.60%-4.22%) and 1.11% (0.14%-1.08%), respectively (HR 0.63, 0.19-1.78); that for intracranial hemorrhage was marginally significantly lower in non-vitamin K antagonist oral anticoagulant users (HR 0.17, 0.01-1.15). Major bleeding did not occur in non-vitamin K antagonist oral anticoagulant users with a CHADS2 score <4 or those with a discharge modified Rankin Scale score ≤2. Conclusions: Stroke or systemic embolism during the initial three-month anticoagulation period after stroke/transient ischemic attack was not frequent as compared to previous findings regardless of warfarin or non-vitamin K antagonist oral anticoagulants were used. Intracranial hemorrhage was relatively uncommon in non-vitamin K antagonist oral anticoagulant users, although treatment assignment was not randomized. Early initiation of non-vitamin K antagonist oral anticoagulants during the acute stage of stroke/transient ischemic attack in real-world clinical settings seems safe in bleeding-susceptible Japanese population. [ABSTRACT FROM AUTHOR]

Highlights: [•] The decomposition rate was significantly increased by the addition of oxygen. [•] The influence of DO concentration on selectivity for nitrite and nitrate was examined. [•] The selectivity for nitrite and nitrate was suppressed as the initial concentration of ammonia was increased. [ABSTRACT FROM AUTHOR]

Sordaricin derivatives possessing a cyclohexane ring appendage attached via an ether, thioether, amine, oxime, ester or amide linkage were synthesized and their antifungal activity was evaluated in vitro. Compounds containing a thioether bond or an oxime bond as a linkage exhibited potent MICs (≤0.125 μg/mL) against four Candida albicans strains including azole-low-susceptible strains. They were also active (MIC ≤0.125 μg/mL) against Candida glabrata. Their in vivo efficacy was confirmed in a murine intravenous infection model with Candida albicans. [Copyright &y& Elsevier]

The discovery of a novel class of state-dependent voltage-gated sodium channel (Na V )1.7 inhibitors is described. By the modification of amide or urethane bond in Na V 1.7 blocker III, structure-activity relationship studies that led to the identification of novel Na V 1.7 inhibitor 2i (DS01171986) were performed. Compound 2i exhibited state-dependent inhibition of Na V 1.7 without Na V 1.1, Na V 1.5 or human ether-a-go-go related gene (hERG) liabilities at concentrations up to 100 μM. Further biological profiling successfully revealed that 2i possessed potent analgesic properties in a murine model of neuropathic pain (ED 50 : 3.4 mg/kg) with an excellent central nervous system (CNS) safety margin (> 600 fold).

Background: The present study aimed to clarify the association between left atrial (LA) size and ischemic events after ischemic stroke or transient ischemic attack (TIA) in patients with nonvalvular atrial fibrillation (NVAF)., Methods: Acute ischemic stroke or TIA patients with NVAF were enrolled. LA size was classified into normal LA size, mild LA enlargement (LAE), moderate LAE, and severe LAE. The ischemic event was defined as ischemic stroke, TIA, carotid endarterectomy, carotid artery stenting, acute coronary syndrome or percutaneous coronary intervention, systemic embolism, aortic aneurysm rupture or dissection, peripheral artery disease requiring hospitalization, or venous thromboembolism., Results: A total of 1,043 patients (mean age, 78 years; 450 women) including 1,002 ischemic stroke and 41 TIA were analyzed. Of these, 351 patients (34%) had normal LA size, 298 (29%) had mild LAE, 198 (19%) had moderate LAE, and the remaining 196 (19%) had severe LAE. The median follow-up duration was 2.0 years (interquartile range, 0.9-2.1). During follow-up, 117 patients (11%) developed at least one ischemic event. The incidence rate of total ischemic events increased with increasing LA size. Severe LAE was independently associated with increased risk of ischemic events compared with normal LA size (multivariable-adjusted hazard ratio, 1.75; 95% confidence interval, 1.02-3.00)., Conclusion: Severe LAE was associated with increased risk of ischemic events after ischemic stroke or TIA in patients with NVAF., (© 2020 S. Karger AG, Basel.)

Background: We determined the 2-year long-term risk-benefit profile in patients with stroke or transient ischemic attack (TIA) receiving warfarin or direct oral anticoagulants (DOACs) for nonvalvular atrial fibrillation (NVAF) using a prospective, multicenter, observational registry in Japan.Methods and Results:NVAF patients within 7 days after onset of ischemic stroke/TIA were enrolled in 18 stroke centers. Outcome measures included ischemic and bleeding events and death in the 2-year follow-up period. We enrolled 1,116 patients taking either warfarin (650 patients) or DOACs (466 patients) at acute hospital discharge. DOAC users were younger and had lower National Institutes of Health Stroke Scale, CHADS 2 and discharge modified Rankin Scale scores than warfarin users (P<0.0001 each). Incidences of stroke/systemic embolism (adjusted hazard ratio, 1.07; 95% CI, 0.66-1.72), all ischemic events (1.13; 0.72-1.75), and ischemic stroke/TIA (1.58; 0.95-2.62) were similar between groups. Risks of intracranial hemorrhage (0.32; 0.09-0.97) and death (0.41; 0.26-0.63) were significantly lower for DOAC users. Infection was the leading cause of death, accounting for 40% of deaths among warfarin users., Conclusions: Stroke/TIA patients receiving DOACs for secondary prevention were younger and had lower stroke severity and risk indices than those receiving warfarin. Estimated cumulative incidences of stroke and systemic embolism within 2 years were similar between warfarin and DOACs users, but those of death and intracranial hemorrhage were significantly lower among DOAC users.

We report two patients of status epilepticus, in which detailed brain magnetic resonance image (MRI) studies were performed. In one patient apparent diffusion coefficient (ADC) increased in the right temporopareital regions in the acute phase. This patient finally has good clinical course without neurological deficits, and abnormal findings on MRI also disappeared. In another patient ADC increased in the similar regions in the acute phase, and an MRI demonstrated cortical laminar necrosis on T1-weighted scans in the same regions in the posticteric phase about 3 months later. The patient had a poorer prognosis with moderate dementia. It has been demonstrated that increased ADC reflects extracellular edema, while decreased ADC indicates cytotoxic edema. ADC mapping appears to be useful for predicting the reversibility of brain damages due to status epilepticus.