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Cognitive impairment in adult patients with moyamoya disease (MMD) is sometimes overlooked and can occur in patients with no ischemic or hemorrhagic lesions. Better profiling and reliable diagnostic methods that characterize the group and associate the impairments and pathology of MMD are required in order to deliver appropriate treatments and support. The potential of 123I-iomazenil single-photon emission computed tomography (SPECT) for this issue has been reported in some studies, but the universality of this method remains unclear. A multicenter study of adult patients (aged 18-60 years) with MMD who experienced difficulties in social lives despite normal activities of daily living was implemented to delineate the common characteristics of this group of patients. In this study, iomazenil SPECT, besides patient characteristics, cognitive functions, and conventional imaging, was acquired to examine whether this method is suitable as a universal diagnostic tool. A total of 36 patients from 12 institutes in Japan were included in this study. Domain scores of world health organization quality of life 26 indicated low self-rating in physical health and psychological domains. The percentages of patients who had

We investigated epidemiologic and molecular characteristics of healthcare-associated (HA) and community-associated (CA) Clostridioides difficile infection (CDI) among adult patients in Canadian Nosocomial Infection Surveillance Program hospitals during 2015–2019. The study encompassed 18,455 CDI cases, 13,735 (74.4%) HA and 4,720 (25.6%) CA. During 2015–2019, HA CDI rates decreased by 23.8%, whereas CA decreased by 18.8%. HA CDI was significantly associated with increased 30-day all-cause mortality as compared with CA CDI (p

Abstract Background Hashimoto’s disease has reportedly been associated with stroke; however, cerebrovascular morphology and clinical course remain poorly documented. The present study aimed to determine the angiographic features and clinical outcomes of intracranial arterial stenosis (IAS) associated with Hashimoto’s disease in a retrospective cohort. Methods Overall, 107 adult patients with IAS were screened for anti-thyroid antibodies; of these, 26 patients tested positive. The 42 affected hemispheres were classified into subgroups according to the steno-occlusion site and the development of abnormal collateral (moyamoya) vessels. These subgroups were dichotomized into moyamoya vessels positive (MM type) and negative (non-MM type). The initial presentation, IAS progression, and vascular events during the follow-up period were compared. Results The following sites of stenosis were identified: the bifurcation of the internal carotid artery in 11 (26.2%), M1 or A1 in 29 (69.0%), and more distal (M2-M4/A2-A4) in 2 (4.8%) hemispheres. Further, 17 hemispheres were categorized into the MM type and 25 were classified into the non-MM type. During the follow-up period (mean 2.5 years), IAS progression was identified in 8 (32%) hemispheres of the non-MM type and 0 (0%) hemispheres of the MM type (p = 0.041). Ischemic attacks occurred in 5 (20.0%) hemispheres of the non-MM type (4.6%/year) and 0 hemispheres of the MM type (p = 0.08). Further, 4 (23.5%) hemispheres of the MM type experienced intracerebral hemorrhage, whereas none of the non-MM type hemorrhaged (p = 0.012). Conclusions Hashimoto’s disease-associated IAS exhibits various angiographic morphologies, resulting in different clinical presentations. Screening for anti-thyroid antibodies and careful management based on vascular morphology appears important in adults with IAS.

Abstract Background 15O-oxygen inhalation PET is unique in its ability to provide fundamental information regarding cerebral hemodynamics and energy metabolism in man. However, the use of 15O-oxygen has been limited in a clinical environment largely attributed to logistical complexity, in relation to a long study period, and the need to produce and inhale three sets of radiopharmaceuticals. Despite the recent works that enabled shortening of the PET examination period, radiopharmaceutical production has still been a limiting factor. This study was aimed to evaluate a recently developed radiosynthesis/inhalation system that automatically supplies a series of 15O-labeled gaseous radiopharmaceuticals of C15O, 15O2, and C15O2 at short intervals. Methods The system consists of a radiosynthesizer which produces C15O, 15O2, and C15O2; an inhalation controller; and an inhalation/scavenging unit. All three parts are controlled by a common sequencer, enabling automated production and inhalation at intervals less than 4.5 min. The gas inhalation/scavenging unit controls to sequentially supply of qualified radiopharmaceuticals at given radioactivity for given periods at given intervals. The unit also scavenges effectively the non-inhaled radioactive gases. Performance and reproducibility are evaluated. Results Using an 15O-dedicated cyclotron with deuteron of 3.5 MeV at 40 μA, C15O, 15O2, and C15O2 were sequentially produced at a constant rate of 1400, 2400, and 2000 MBq/min, respectively. Each of radiopharmaceuticals were stably inhaled at

Background We aimed to improve the assessment quality of plaque vulnerability with combined use of magnetic resonance imaging and contrast‐enhanced ultrasound (CEUS). Methods and Results We prospectively enrolled 71 patients with internal carotid artery stenosis who underwent carotid endarterectomy and performed preoperative CEUS and magnetic resonance plaque imaging. We distinguished high–signal‐intensity plaques (HIPs) and non‐HIPs based on magnetization‐prepared rapid acquisition with gradient echo images. We graded them according to the CEUS contrast effect and compared the CEUS images with the carotid endarterectomy specimens. Among the 70 plaques, except 1 carotid endarterectomy tissue sample failure, 59 were classified as HIPs (43 symptomatic) and 11 were classified as non‐HIPs (5 symptomatic). Although the magnetization‐prepared rapid acquisition with gradient echo findings alone had no significant correlation with symptoms (P=0.07), concomitant use of magnetization‐prepared rapid acquisition with gradient echo and CEUS findings did show a significant correlation (P

Steroid-sensitive nephrotic syndrome (SRNS) can cause CKD and necessitate kidney transplant. Here the authors identify FAT1 mutations by homozygosity mapping and whole-exome sequencing in families with SRNS and provide functional mouse and zebrafish evidence that FAT1 is required for normal glomerular and tubular function and that FAT1 mutations can cause SRNS.

Compressed sensing (CS) reconstructions of under-sampled measurements generate missing data based on assumptions of image sparsity. Non-contrast time-of-flight MR angiography (TOF-MRA) is a good candidate for CS based acceleration, as MRA images feature bright trees of sparse vessels over a well-suppressed anatomical background signal. A short scan time derived from CS is beneficial for patients of moyamoya disease (MMD) because of the frequency of MR scans. The purpose of this study was to investigate the reliability of TOF-MRA with CS in the evaluation of MMD. Twenty-two patients were examined using TOF-MRA with CS (CS-TOF) and parallel imaging (PI-TOF). The acceleration factors were 3 (CS3) and 5 (CS5) for CS-TOF, and 3 (PI3) for PI-TOF. Two neuroradiologists evaluated the MMD grading according to stenosis/occlusion scores using the modified Houkin's system, and the visibility of moyamoya vessels (MMVs) using a 3-point scale. Concordance was calculated with Cohen's κ. The numbers of MMVs in the basal ganglia were compared using Bland-Altman analysis and Wilcoxon's signed-rank tests. MRA scan times were 4:07, 3:53, and 2:42 for PI3, CS3, and CS5, respectively. CS-reconstruction completed within 10 minutes. MMD grading and MMV visibility scales showed excellent correlation (κ > .966). Although the number of MMVs was significantly higher in CS3 than in PI3 (p < .0001) and CS5 (p < .0001), Bland-Altman analysis showed a good agreement between PI3, CS3, and CS5. Compressed sensing can accelerate TOF-MRA with improved visualization of small collaterals in equivalent time (CS3) or equivalent results in a shorter scan time (CS5).

Intracellular Ca2+ signaling regulates diverse functions of the nervous system. Many of these neuronal functions, including learning and memory, are regulated by neuronal calcium sensor-1 (NCS-1). However, the pathways by which NCS-1 regulates these functions remain poorly understood. Consistent with the findings of previous reports, we revealed that NCS-1 deficient (Ncs1-/-) mice exhibit impaired spatial learning and memory function in the Morris water maze test, although there was little change in their exercise activity, as determined via treadmill-analysis. Expression of brain-derived neurotrophic factor (BDNF; a key regulator of memory function) and dopamine was significantly reduced in the Ncs1-/- mouse brain, without changes in the levels of glial cell-line derived neurotrophic factor or nerve growth factor. Although there were no gross structural abnormalities in the hippocampi of Ncs1-/- mice, electron microscopy analysis revealed that the density of large dense core vesicles in CA1 presynaptic neurons, which release BDNF and dopamine, was decreased. Phosphorylation of Ca2+/calmodulin-dependent protein kinase II-α (CaMKII-α, which is known to trigger long-term potentiation and increase BDNF levels, was significantly reduced in the Ncs1-/- mouse brain. Furthermore, high voltage electric potential stimulation, which increases the levels of BDNF and promotes spatial learning, significantly increased the levels of NCS-1 concomitant with phosphorylated CaMKII-α in the hippocampus; suggesting a close relationship between NCS-1 and CaMKII-α. Our findings indicate that NCS-1 may regulate spatial learning and memory function at least in part through activation of CaMKII-α signaling, which may directly or indirectly increase BDNF production.

Moyamoya disease (MMD) is a chronic, progressive, cerebrovascular occlusive disease that causes abnormal enlargement of collateral pathways (moyamoya vessels) in the region of the basal ganglia and thalamus. Cerebral revascularization procedures remain the preferred treatment for patients with MMD, improving the compromised cerebral blood flow (CBF). However, voxel based analysis (VBA) of revascularization surgery for MMD based on data from pre- and postoperative data has not been established. The latest algorithm called as Diffeomorphic Anatomical Registration Through Exponentiated Lie Algebra (DARTEL) has been introduced for VBA as the function of statistical parametric mapping (SPM8), and improved registration has been achieved by SPM8 with DARTEL. In this study, VBA was conducted to evaluate pre- and postoperative single photon emission computed tomography (SPECT) images for MMD by SPM8 with DARTEL algorithm, and the results were compared with those from SPM8 without DARTEL (a conventional method). Thirty-two patients with MMD who underwent superficial temporal artery-middle cerebral artery (STA-MCA) bypass surgery as the first surgery were included and all patients underwent pre- and postoperative 3D T1-weighted imaging and SPECT. Pre- and postoperative SPECT images were registered to 3D T1-weighted images, then VBA was conducted. Postoperative SPECT showed more statistically increased CBF areas in the bypassed side cerebral hemisphere by using SPM8 with DARTEL (58,989 voxels; P

Background: Intracerebral hemorrhage (ICH) is one of the most serious complications in patients supported by a left ventricular assist device (LVAD). We evaluate the efficacy of prothrombin complex concentrate (PCC) for rapid reversal of warfarin-induced anticoagulation in this population. Methods: A total of 38 consecutive ICH events in patients supported by an LVAD between 1996 and 2007 were retrospectively reviewed. Fourteen ICH events were treated with fresh frozen plasma (FFP) (Group FFP) and 24 ICH events were treated with PCC (Group PCC). The efficacy and outcome of PCC administration versus FFP were evaluated. Results: The proportion of patients surviving after an ICH event was significantly smaller in Group FFP than Group PCC (35.7% vs. 75.0%, p < 0.05). None of the patients in Group FFP were able to undergo heart transplantation, whereas 21.4% patients in Group PCC successfully underwent heart transplantation. Conclusion: Patients on LVAD are in need for intensified anticoagulation and are at high risk of ICH; therefore, adequate use of PCC in the event of ICH could be of importance for survival and allow subsequent heart transplantation.

V1 and V2b interneurons (INs) are essential for the production of an alternating flexor–extensor motor output. Using a tripartite genetic system to selectively ablate either V1 or V2b INs in the caudal spinal cord and assess their specific functions in awake behaving animals, we find that V1 and V2b INs function in an opposing manner to control flexor–extensor-driven movements. Ablation of V1 INs results in limb hyperflexion, suggesting that V1 IN-derived inhibition is needed for proper extension movements of the limb. The loss of V2b INs results in hindlimb hyperextension and a delay in the transition from stance phase to swing phase, demonstrating V2b INs are required for the timely initiation and execution of limb flexion movements. Our findings also reveal a bias in the innervation of flexor- and extensor-related motor neurons by V1 and V2b INs that likely contributes to their differential actions on flexion–extension movements.

Clostridioides difficile is a major cause of infectious nosocomial diarrhea in high-income countries (1). Disease severity ranges from asymptomatic colonization to fulminant colitis, sometimes leading to colectomy and death (2). [...]

The Arase satellite observed the precipitation of monoenergetic electrons accelerated from a very high altitude above 32,000 km altitude on 16 September 2017. The event was selected in the period when the high‐angular resolution channel of the electron detector looked at pitch angles within ∼5° from the ambient magnetic field direction, and thereby was the first to examine the detailed distribution of electron flux near the energy‐dependent loss cone at such high altitudes. The potential energy below the satellite estimated from the observed energy‐dependence of the loss cone was consistent with the energy of the upgoing ion beams, indicating that ionospheric ions were accelerated by a lower‐altitude acceleration region. The accelerated electrons inside the loss cone carried a significant net field‐aligned current (FAC) density corresponding to ionospheric‐altitude FAC of up to ∼3μA/m2. Based on the anisotropy of the accelerated electrons, we estimated the height of the upper boundary of the acceleration region to be >∼2 RE above the satellite. The height distribution of the acceleration region below the satellite, estimated from the frequency of auroral kilometric radiation, was ∼4,000–13,000 km altitude, suggesting that the very‐high‐altitude acceleration region was separated from the lower acceleration region. Additionally, we observed time domain structure (TDS) electric fields on a subsecond time scale with a thin FAC indicated by magnetic deflections. Such a TDS may be generated by the formation of double layers in the magnetotail, and its potential drop could significantly contribute (∼40%–60%) to the parallel energization of precipitating auroral electrons. Plain Language Summary: The auroral arc is produced by electrons in the magnetosphere accelerated downward by a quasi‐static electric field. The region of the electric field, so called the auroral acceleration region, is typically located just above the ionosphere, at altitudes of a few thousand kilometers. However, recent studies have shown that it can be extended to altitudes higher than 30,000 km. The mechanism and impact of such a very‐high‐altitude acceleration region remain a mystery. The high‐angular resolution electron detector on board the Arase satellite successfully measured current and energy flows carried by the electron accelerated at the very‐high‐altitude acceleration region above the satellite altitude of 32,000 km. This acceleration at very‐high‐altitudes contributed significantly to the energy flow into the ionosphere. Based on the anisotropy of the accelerated electrons, the frequency of auroral kilometric radiation, and the presence of spiky electrostatic waves, we estimate that the very‐high‐altitude acceleration region was located more than 12,000 km above the satellite as a thin charge separation layer, apart from the acceleration region below the satellite. Our results suggest that localized electric fields at very high altitudes, which were not previously associated with the aurora, can energize auroral electrons and affect auroral visibility. Key Points: We comprehensively analyzed a very‐high‐altitude (>32,000 km) auroral acceleration eventNet precipitation of accelerated electrons significantly contributes to the field‐aligned current and energy flux into the ionosphereDouble layers in the magnetotail are possible candidates for very‐high‐altitude auroral accelerations [ABSTRACT FROM AUTHOR]

Maintenance hemodialysis (MHD) patients display reduced daily physical activity (DPA) and physical performance (PP). Previous studies did not differentiate the effects of kidney failure and MHD treatments from comorbidities as causes for reduced DPA and PP. In relatively healthy MHD patients and normal adults, we evaluated DPA and PP and examined relationships between DPA and PP and possible associations between anxiety or depression and DPA and PP. DPA, 6-minute walk distance (6-MWD), sit-to-stand (STS), and stair-climbing tests were measured in 72 MHD patients (40% diabetics) with limited comorbidities and 39 normal adults of similar age and gender mix. Anxiety and depression were measured by the Beck anxiety and depression inventories. DPA, time-averaged over 7 days, and all 3 PP tests were impaired in MHD patients, to about 60% to 70% of normal values (P < .0001 for each measurement). MHD patients spent more time sleeping or physically inactive (P < .0001) and less time in ≥ moderate activity (P < .0001). Adjusted DPA correlated with 6-MWD but not STS or stair-climbing. Anxiety and depression were identified in 43% and 33% of MHD patients and 2.5% and 5.1% of normals (P < .0001 for each comparison). Most of the impairment in DPA and PP tests were also observed in MHD patients without anxiety or depression. However, MHD patients with both anxiety and depression generally had the most impaired DPA and PP. In MHD patients, higher adjusted anxiety scores were correlated with impaired 6-MWD and STS, whereas adjusted average DPA was negatively correlated with depression (r = -0.33, P = .006) but not anxiety. DPA on the hemodialysis day (P = .01), day after dialysis (P = .03), and day 2 after dialysis (P = .03) each correlated negatively with degree of depression but not with anxiety. MHD patients displayed negative-adjusted correlations between anxiety and 6-MWD (P = .03) and STS (P = .04). In relatively healthy MHD patients, DPA and PP are substantially impaired and correlated with each other, even in patients without evidence for anxiety or depression. Anxiety and depression are common in MHD patients and are associated with further impairment in DPA and PP.

This is the first report of significant energization (up to 7,000 eV) of low‐energy He+ ions, which occurred simultaneously with H‐band electromagnetic ion cyclotron (EMIC) wave activity, in a direction mostly perpendicular to the ambient magnetic field. The event was detected by the Arase satellite in the dayside plasmatrough region off the magnetic equator on 15 May 2019. The peak energy of the He+ flux enhancements is mostly above 1,000 eV. At some interval, the He+ ions are energized up to ∼7,000 eV. The H‐band waves are excited in a frequency band between the local crossover and helium gyrofrequencies and are close to a linear polarization state with weakly left‐handed or right‐handed polarization. The normal angle of the waves exhibits significant variation between 0° and 80°, indicating a non‐parallel propagation. We run a hybrid code with parameters estimated from the Arase observations to examine the He+ energization. The simulations show that cold He+ ions are energized up to more than 1,000 eV, similar to the spacecraft observations. From the analysis of the simulated wave fields and cold plasma motions, we found that the ratio of the wave frequency to He+ gyrofrequency is a primary factor for transverse energization of cold He+ ions. As a consequence of the numerical analysis, we suggest that the significant transverse energization of He+ ions observed by Arase is attributed to H‐band EMIC waves excited near the local helium gyrofrequency. Key Points: Strong H‐band EMIC waves were detected in the dayside plasmatrough region off the magnetic equator by the Arase spacecraftThe H‐band waves energize cold He+ ions to levels above ∼1,000 eV in the direction perpendicular to the background magnetic fieldSimulation indicates that the ratio of the wave frequency to He+ gyrofrequency is a primary factor in the strong energization of He+ ions [ABSTRACT FROM AUTHOR]