Delay-induced amplitude death in multiplex oscillator network with frequency-mismatched layers.

The present paper analytically investigates the stability of amplitude death in a multiplex Stuart-Landau oscillator network with a delayed interlayer connection. The network consists of two frequency-mismatched layers, and all oscillators in each layer have identical frequencies. We show that, if the matrices describing the network topologies of each layer commute, then the characteristic equation governing the stability can be reduced to a simple form. This form reveals that the stability of amplitude death in the multiplex network is equally or more conservative than that in a pair of frequency-mismatched oscillators coupled by a delayed connection. In addition, we provide a procedure for designing the delayed interlayer connection such that amplitude death is stable for any commuting matrices and for any intralayer coupling strength. These analytical results are verified through numerical examples. Moreover, we numerically discuss the results for the case in which the commutative property does not hold.

Amyloid Beta Is Internalized via Macropinocytosis, an HSPG- and Lipid Raft-Dependent and Rac1-Mediated Process.

Intracellular amyloid ß peptide (Aß) accumulation has drawn attention in relation to the pathophysiology of Alzheimer's disease in addition to its extracellular deposition as senile plaque. Cellular uptake of extracellular Aß is one of the possible mechanisms by which intracellular Aß deposits form. Given the relevance of Aß inside cells, it is important to understand the mechanism by which it is taken up by them. In this study, we elucidated that Neuro2A and SH-SY5Y cells internalize specifically oligomerized Aß in a time- and dose-dependent manner. The depletion of plasma membrane cholesterol with methyl-ß-cyclodextrin or treatment with trypsin diminished the internalization of oAß, suggesting that the oAß uptake might be both a lipid raft-dependent and heparan sulfate proteoglycan-mediated process. Treatment with a macropinocytosis inhibitor (ethylisopropyl amiloride and wortmannin) also drastically reduced the uptake of oligomer-Aß (oAß). oAß-treated cells exhibited an increase in Rac1 activity, indicating that macropinocytosis induced by oAß is regulated by these small GTPases. These findings suggest that macropinocytosis is a major endocytic route through which oAß42 enters cells.

Diffusion-Weighted Imaging Hyperintensities in Acute and Subacute-Phase Intracerebral Hemorrhage.

OBJECTIVE: Diffusion-weighted imaging hyperintensities are observed in intracerebral hemorrhage patients at times and might be associated with unfavorable functional outcomes. However, the suitable time to evaluate diffusion-weighted imaging hyperintensities to influence stroke outcome remains unclear. This study investigated the associations between acute and sub-acute diffusion-weighted imaging hyperintensities and functional outcomes among patients with acute intracerebral hemorrhage. METHODS: Diffusion-weighted imaging hyperintensities were evaluated within 24 h (acute phase) and at 14 ± 5 days (sub-acute phase). An unfavorable functional outcome was a score of 5-6 on the modified Rankin Scale at 3 months. RESULTS: Among 268 intracerebral hemorrhage patients, diffusion-weighted imaging hyperintensities in the acute phase were observed in 32 (11.9%). Among 227 patients who underwent a second magnetic resonance imaging in the sub-acute phase, diffusion-weighted imaging hyperintensities were observed in 57 (25.1%). Multivariable analysis revealed that the baseline intracerebral hemorrhage volume, history of stroke, and severe white matter lesions were associated with sub-acute diffusion-weighted imaging hyperintensities. The patients with unfavorable outcomes (n = 37) had a higher frequency of sub-acute diffusion-weighted imaging hyperintensities than those without (n = 190) (51.4% vs. 20.0%, P < 0.001); the frequencies of acute diffusion-weighted imaging hyperintensities were not significantly different between the groups (13.5% vs. 10.0%, P = 0.559). Sub-acute diffusion-weighted imaging hyperintensities were independently associated with unfavorable outcomes after adjusting for confounding factors (Odds Ratio, 3.35, 95% CI 1.20-9.35, P = 0.021). CONCLUSION: The rate of sub-acute diffusion-weighted imaging hyperintensities was higher than acute diffusion-weighted imaging hyperintensities among acute intracerebral hemorrhage patients and likely to be associated with unfavorable outcomes.

Effects of frequency mismatch on amplitude death in delay-coupled oscillators.

The present paper analytically reveals the effects of frequency mismatch on the stability of an equilibrium point within a pair of Stuart-Landau oscillators coupled by a delay connection. By analyzing the roots of the characteristic function governing the stability, we find that there exist four types of boundary curves of stability in a coupling parameters space. These four types depend only on the frequency mismatch. The analytical results allow us to design coupling parameters and frequency mismatch such that the equilibrium point is locally stable. We show that, if we choose appropriate frequency mismatches and delay times, then it is possible to induce amplitude death with strong stability, even by weak coupling. In addition, we show that parts of these analytical results are valid for oscillator networks with complete bipartite topologies.

Characteristics and Prognostic Factors of Swallowing Dysfunction in Patients with Lateral Medullary Infarction.

OBJECTIVES: Lateral medullary infarction mainly impairs the pharyngeal phase of swallowing. We aimed to investigate the utility of the assessment tools of swallowing function in patients with lateral medullary infarction and to determine the factors that could predict the outcomes of swallowing function. MATERIALS AND METHODS: 15 patients with lateral medullary infarction who were admitted to Suiseikai Kajikawa Hospital between August 1, 2016, and March 31, 2020 (age 62.7 ± 14.8 years, 5 women) were enrolled in this prospective study. The diagnosis was made using brain magnetic resonance imaging. We analyzed the factors associated with severe swallowing dysfunction, which was defined as the necessity for tube feeding on the 90th day from admission, with multiple logistic regression analysis. RESULTS: Multivariate analyses identified the repetitive saliva swallowing test, modified water swallowing test, and vertical spread of stroke lesions as independent significant factors affecting severe swallowing dysfunction (p = 0.002, 0.016, and 0.011, respectively). The sub-scores of the pharyngeal phase of the Mann Assessment of Swallowing Ability were also significantly associated with severe swallowing dysfunction (p < 0.001). However, tongue pressure, severe passage pattern abnormality on videofluoroscopic examination, and vertebral artery dissection were not significantly associated with swallowing dysfunction. CONCLUSIONS: Since lateral medullary infarction presents with swallowing dysfunction mainly in the pharyngeal phase, tools that can be used to evaluate the pharyngeal phase of swallowing, such as repetitive saliva swallowing test and modified water swallowing test, are moreuseful than tongue pressure measurement.

Zonisamide can ameliorate the voltage-dependence alteration of the T-type calcium channel CaV3.1 caused by a mutation responsible for spinocerebellar ataxia.

Spinocerebellar ataxia (SCA) 42 is caused by a mutation in CACNA1G, which encodes the low voltage-gated calcium channel CaV3.1 (T-type). Patients with SCA42 exhibit a pure form of cerebellar ataxia. We encountered a patient with the p.Arg1715His mutation, suffering from intractable resting tremor, particularly head tremor. This symptom improved with the administration of low-dose of zonisamide (ZNS), a T-type calcium channel blocker effective for treating Parkinson's disease and epilepsy. Previous electrophysiological studies showed that the voltage dependence of this mutant CaV3.1 was shifted toward the positive potential. This abnormal shift was considered a factor related to disease onset and symptoms. In this study, we performed whole-cell recordings of GFP-expressing HEK293T cells that expressed wild-type or mutant CaV3.1 and investigated the changes in the abnormal shift of voltage dependence of the mutant CaV3.1. The results showed that ZNS in an amount equivalent to the patient's internal dose significantly ameliorated the abnormal shift in the mutant CaV3.1, giving values close to those in the wild-type. On the other hand, ZNS did not affect the voltage dependence of wild-type CaV3.1. Because CaV3.1 is known to be involved in tremogenesis, modulation of the voltage dependence of mutant CaV3.1 by ZNS might have contributed to improvement in the intractable tremor of our patient with SCA42. Moreover, efonidipine, another T-type calcium channel blocker, had no effect on tremors in our patient with SCA42 and did not improve the abnormal shift in the voltage dependence of the mutant CaV3.1. This indicates that ZNS is distinct from other T-type calcium channel blockers in terms of modulation of the voltage dependence of the mutant CaV3.1.

Amplitude suppression of oscillators with delay connections and slow switching topology.

The present paper shows that the amplitudes of oscillators in delay-coupled oscillator networks can be suppressed by switching the network topology at a rate much lower than the oscillator frequencies. The mechanism of suppression was clarified numerically, and a procedure for determining the connection parameters to induce suppression is presented. The analytical and numerical results were obtained with Stuart-Landau oscillators and were experimentally validated using double-scroll chaotic circuits.

Identification and functional characterization of novel mutations including frameshift mutation in exon 4 of CSF1R in patients with adult-onset leukoencephalopathy with axonal spheroids and pigmented glia.

OBJECTIVE: Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is caused by mutations in CSF1R. Pathogenic mutations in exons 12-22 including coding sequence of the tyrosine kinase domain (TKD) of CSF1R were previously identified. We aimed to identify CSF1R mutations in patients who were clinically suspected of having ALSP and to determine the pathogenicity of novel CSF1R variants. METHODS: Sixty-one patients who fulfilled the diagnostic criteria of ALSP were included in this study. Genetic analysis of CSF1R was performed for all the coding exons. The haploinsufficiency of CSF1R was examined for frameshift mutations by RT-PCR. Ligand-dependent autophosphorylation of CSF1R was examined in cells expressing CSF1R mutants. RESULTS: We identified ten variants in CSF1R including two novel frameshift, five novel missense, and two known missense mutations as well as one known missense variant. Eight mutations were located in TKD. One frameshift mutation (p.Pro104LeufsTer8) and one missense variant (p.His362Arg) were located in the extracellular domain. RT-PCR analysis revealed that the frameshift mutation of p.Pro104LeufsTer8 caused nonsense-mediated mRNA decay. Functional assay revealed that none of the mutations within TKD showed autophosphorylation of CSF1R. The p.His362Arg variant located in the extracellular domain showed comparable autophosphorylation of CSF1R to the wild type, suggesting that this variant is not likely pathogenic. CONCLUSIONS: The detection of the CSF1R mutation outside of the region-encoding TKD may extend the genetic spectrum of ALSP with CSF1R mutations. Mutational analysis of all the coding exons of CSF1R should be considered for patients clinically suspected of having ALSP.

Stabilization of a spatially uniform steady state in two systems exhibiting Turing patterns.

This paper deals with the stabilization of a spatially uniform steady state in two coupled one-dimensional reaction-diffusion systems with Turing instability. This stabilization corresponds to amplitude death that occurs in a coupled system with Turing instability. Stability analysis of the steady state shows that stabilization does not occur if the two reaction-diffusion systems are identical. We derive a sufficient condition for the steady state to be stable for any length of system and any boundary conditions. Our analytical results are supported with numerical examples.

[Reversible cerebral vasoconstriction syndrome: a clinical study of 11 cases].

This study reports eleven cases of reversible cerebral vasospasm syndrome (RCVS). Of the 11 patients, two were males and nine were females, with the average age of 47.9 ± 14.1 years. Many of these patients were young. The rates of severe, intractable and pulsative headache, generalized convulsions, and motor hemiparesis were 64%, 27%, and 36%, respectively. As complications of intracerebral lesions in the early stage of disease onset, convexal subarachnoid hemorrhage, lobar intracerebral hemorrhage, and posterior reversible encephalopathy syndrome were observed in 63%, 9%, and 45% of cases, respectively. Cerebral infarction occurred in 45% of cases at around 1-3 weeks after onset. Improvement of cerebral vasoconstriction was recognized in several cases from about the first month of onset. The post-partum period, migraine, transfusion, rapid amelioration for anemia, renal failure, bathing, and cerebrovascular dissection were suspected as disease triggers. Abnormally high blood pressure at onset was confirmed in 55% of cases. It is important to analyze the pathophysiology of RCVS associated with these triggers from the viewpoint of the breakdown of the blood-brain barrier.

System identification of propagating wave segments in excitable media and its application to advanced control.

The present paper proposes a scheme for controlling wave segments in excitable media. This scheme consists of two phases: in the first phase, a simple mathematical model for wave segments is derived using only the time series data of input and output signals for the media; in the second phase, the model derived in the first phase is used in an advanced control technique. We demonstrate with numerical simulations of the Oregonator model that this scheme performs better than a conventional control scheme.

[Trigeminal Herpes Zoster Presenting with High-intensity Signals for the Spinal Trigeminal Nucleus and Tract on Diffusion-weighted Image: A Case Report of Stroke Mimic].

A 50-year-old woman was admitted to our hospital with dysesthesia on the right upper portion of her face and a headache. Diffusion-weighted brain magnetic resonance imaging (MRI) revealed high-intensity signals in the dorsolateral portion of the medulla oblongata. She was diagnosed with lateral medullary infarction and was intravenously treated with sodium ozagrel. On the second day of hospitalization, she had nausea and vomiting and showed nystagmus to all directions, suggesting damage to the vestibular nucleus. These manifestations coincided with partial symptoms of lateral medullary syndrome. On the third day of hospitalization, a rash appeared on the region of skin innervated by the first and second branches of the right trigeminal nerve. A reevaluation of the MRI findings indicated the presence of a lesion of the right spinal trigeminal nucleus and tract. She was treated with acyclovir for 14 days, and was discharged without any residual symptoms. Varicella zoster virus-DNA was detected in her cerebrospinal fluid. This disease mimics the presentation of a stroke and is important for differential diagnosis. (Received August 1, 2017; Accepted September 14, 2017; Published February 1, 2018).

Amplitude death in a pair of one-dimensional complex Ginzburg-Landau systems coupled by diffusive connections.

This paper shows that, in a pair of one-dimensional complex Ginzburg-Landau (CGL) systems, diffusive connections can induce amplitude death. Stability analysis of a spatially uniform steady state in coupled CGL systems reveals that amplitude death never occurs in a pair of identical CGL systems coupled by no-delay connection, but can occur in the case of delay connection. Moreover, amplitude death never occurs in coupled identical CGL systems with zero nominal frequency. Based on these analytical results, we propose a procedure for designing the connection delay time and the coupling strength to induce spatial-robust stabilization, that is, a stabilization of the steady state for any system size and any boundary condition. Numerical simulations are performed to confirm the analytical results.

Ability of the Ankle Brachial Index and Brachial-Ankle Pulse Wave Velocity to Predict the 3-Month Outcome in Patients with Non-Cardioembolic Stroke.

AIM: Both the ankle brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV) are surrogates for atherosclerosis. In this study, we aimed to evaluate the ability of ABI and baPWV to predict stroke outcome in patients with first-ever non-cardioembolic stroke. METHODS: This study included consecutive patients with first-ever non-cardioembolic stroke admitted within 1 week after onset to Ota Memorial Hospital between January 2011 and December 2013. Baseline characteristics and National Institutes of Health stroke scale scores at admission were noted. ABI and baPWV were evaluated within 5 days of admission. The patients were categorized according to ABI (cut-off 0.9) and baPWV (cut-off 1870 cm/s) determined using the receiver operation curve for poor outcome. Clinical outcomes were defined based on the modified Rankin scale (mRS) scores 3 months after stroke onset as good (0 and 1) or poor (2-6). RESULTS: A total of 861 patients were available for evaluation. ABI ＜0.9 and baPWV ＞1870 cm/s were associated with poor outcome in the univariate analysis (p＜0.001 and p＜0.001, respectively). After adjusting for factors that showed differences between groups, ABI ＜0.9 was associated with poor outcome. Among patients with ABI ≥ 0.9, higher baPWV showed a slight association with poor outcome after adjustment [odds ratio 1.46 (95% CI 0.95-2.27)]. CONCLUSION: Our study suggests that the stroke outcome can be predicted using ABI and to an extent using baPWV when ABI ≥ 0.9 in patients with non-cardioembolic stroke.

Proportional-integral control of propagating wave segments in excitable media.

Numerical simulations are performed to demonstrate that proportional-integral control, one of the most commonly used feedback schemes in control engineering, can stabilize propagating wave segments in excitable media to a desired size. The proportional-integral controller measures the size of a wave segment and applies a spatially uniform signal to the medium. This controller has the following features: difficult trial-and-error adjustment is not necessary, wave segments can be stabilized to different sizes without readjusting the controller, and the wave segment size can be maintained even in media having position-dependent parameters.

Acute encephalopathy due to angel's trumpet intoxication: A case report and literature review.

We report two cases (a married couple) of intoxication due to angel's trumpet ingestion. Case 1: A 71-year-old woman was found lying unconscious on the sofa at home and was brought to our hospital by ambulance. She showed mydriatic anisocoria, and an intracerebral lesion was suspected. However, the brain magnetic resonance imaging showed no abnormal lesion and acute encephalopathy of unknown cause was diagnosed. Case 2: A 68-year-old man (husband of the patient of Case 1) showed alteration of consciousness with agitation and was admitted to our hospital on the next day. He also had slight mydriasis. As his manifestations were similar to those of his wife, we studied their medical history again. We found that they mistook the roots of angel's trumpet for burdock and cooked and ate them. This intoxication causes characteristic encephalopathy with altered consciousness and mydriasis. In the case of anisocoria or mild mydriasis, the diagnosis is difficult sometimes. The intoxication occurred within a family; this was a clue to the correct diagnosis. Severe cases exhibit pyramidal signs and symptoms or convulsion, and deaths have been reported. Angel's trumpet intoxication is an important neurological emergency.

Ischemic Stroke Mortality Is More Strongly Associated with Anemia on Admission Than with Underweight Status.

BACKGROUND: Underweight patients have recently been reported as a group with a high risk of poststroke death. Anemia also increases mortality rates in stroke patients. However, the causal associations between body weight and anemia resulting in stroke-related death remain unclear. We examined the association of weight status and hemoglobin levels with 3-month mortality after ischemic stroke. METHODS: The study enrolled all consecutive patients with acute ischemic stroke and no history of stroke admitted to our hospital between January 2010 and December 2013. The patients were categorized into 4 body mass index (BMI) categories (underweight, normal-weight, overweight, and obese). Anemia was evaluated according to the World Health Organization criteria (men, <13 g/dL; women, <12 g/dL). RESULTS: A total of 1733 acute ischemic stroke patients (149 underweight, BMI < 18.5 kg/m2; 1076 normal-weight, BMI = 18.5-24.9 kg/m2; 436 overweight, BMI = 25-29.9 kg/m2; and 72 obese, BMI > 30 kg/m2) were included. Death within 3 months occurred in 65 patients (underweight, 10.1%; normal-weight, 3.4%; overweight, 2.3%; and obese, 5.6%). Compared to nonanemic patients, those with anemia (n = 329, 19.0%) had lower BMI (21.8 kg/m2 versus 23.7 kg/m2, P <.001) and higher mortality rates (9.1% versus 2.5%, P <.001). Underweight status was associated with 3-month mortality after adjusting for age, sex, comorbidities, and initial stroke severity. However, in the models that included laboratory findings, it was anemia status (odds ratio, 2.81; 95% confidence interval, 1.46-5.43), not underweight status, that was independently associated with 3-month mortality. CONCLUSION: Anemia on admission was associated with stroke mortality independent of underweight status.

Carotid Artery Dissection and Ischemic Stroke Originating from Localized Aortic Arch Dissection.

Aortic dissection is an infrequent but important cause of acute ischemic stroke (AIS), and must not be overlooked because of a possible worse outcome, especially with the use of an intravenous recombinant tissue plasminogen activator. We report a case of left carotid artery dissection and AIS originating from localized aortic arch dissection, pathologically caused by cystic medial necrosis in the tunica media.

Dynamical behavior and peak power reduction in a pair of energy storage oscillators coupled by delayed power price.

This paper investigates dynamics of a management system for controlling a pair of energy storages. The system involves the following two characteristics: each storage behaves in a manner that reduces the number of charge noncharge cycles and begins to be charged when the price of power is lower than a particular price threshold. The price is proportional to the past total power flow from a power grid to all storages. A peak of the total power flow occurs when these storages are charged simultaneously. From the viewpoint of nonlinear dynamics, the energy storages can be considered as relaxation oscillators coupled by a delay connection. Our analytical results suggest that the peak can be reduced by inducing an antiphase synchronization in coupled oscillators. We confirm these analytical results through numerical simulations. In addition, we numerically investigate the dynamical behavior in 10 storages and find that time delay in the connection is important in reducing the peak.