Antenatal Glucocorticoid Administration Promotes Cardiac Structure and Energy Metabolism Maturation in Preterm Fetuses.

Although the rate of preterm birth has increased in recent decades, a number of preterm infants have escaped death due to improvements in perinatal and neonatal care. Antenatal glucocorticoid (GC) therapy has significantly contributed to progression in lung maturation; however, its potential effects on other organs remain controversial. Furthermore, the effects of antenatal GC therapy on the fetal heart show both pros and cons. Translational research in animal models indicates that constant fetal exposure to antenatal GC administration is sufficient for lung maturation. We have established a premature fetal rat model to investigate immature cardiopulmonary functions in the lungs and heart, including the effects of antenatal GC administration. In this review, we explain the mechanisms of antenatal GC actions on the heart in the fetus compared to those in the neonate. Antenatal GCs may contribute to premature heart maturation by accelerating cardiomyocyte proliferation, angiogenesis, energy production, and sarcoplasmic reticulum function. Additionally, this review specifically focuses on fetal heart growth with antenatal GC administration in experimental animal models. Moreover, knowledge regarding antenatal GC administration in experimental animal models can be coupled with that from developmental biology, with the potential for the generation of functional cells and tissues that could be used for regenerative medical purposes in the future.

[A case of meningoencephalitis that developed during nivolumab use].

A 72-year-old woman developed a fever and consciousness disturbance after completing 8 courses of nivolumab for lung adenocarcinoma. A cerebrospinal fluid test showed an increased cell count, but bacterial culture, herpes simplex virus-polymerase chain reaction, acid-fast staining, and cytology were negative; serum paraneoplastic syndrome-related antibody was also negative. Serum and cerebrospinal fluid specimens were positive for anti-glutamate receptor (GluR) antibody, and fluid-attenuated inversion recovery images on head magnetic resonance imaging showed a high signal intensity at the right parietal lobe. The condition was determined to be immune-mediated encephalitis, and pulse steroid therapy was performed. The symptoms promptly improved after treatment. The patient in the present case was anti-GluR antibody-positive but was determined to have nivolumab-related encephalitis based on the clinical course. The use of immune checkpoint inhibitors has become widespread in recent years, although it can occasionally lead to encephalitis. We herein report our experience with immune checkpoint inhibitor-related encephalitis, which is seldom reported in Japan.

Exposure of immature rat heart to antenatal glucocorticoid results in cardiac proliferation.

BACKGROUND: ATP synthesis and cardiac contraction-related protein production are accelerated in the immature fetal heart by antenatal glucocorticoids (GC). This study investigated the structural maturity of the myocardium and underlying signal pathway associated with cardiac growth in fetal rats that received antenatal GC. METHODS AND RESULTS: Dexamethasone (DEX) was given to pregnant rats for 2 days from day 17 or day 19 of gestation, and the hearts of 19 and 21 day fetuses and 1-day-old neonates were analyzed. Although irregular myofibril orientation was observed morphologically in 19 day fetal hearts, the myofibril components were organized in fetuses after DEX. The cross-sectional area of the myocardium and Ki-67-positive cells were significantly increased in fetal DEX groups, suggesting that cardiac enlargement resulted from myocyte proliferation. Glycogen synthase kinase-3ß (GSK-3ß) protein was significantly decreased in fetal DEX groups. ß-Catenin and vascular endothelial growth factor protein were also significantly increased. Furthermore, increased cardiomyocyte proliferation appeared to be mediated by GC receptors after culture with DEX in vitro. CONCLUSIONS: Antenatal DEX induces structural maturity accompanying cardiomyocyte proliferation in the premature fetal rat heart, and GSK-3ß and ß-catenin are thought to contribute to cardiac growth.

A single auditory tone alters the perception of multiple visual events.

We aimed to show that a single auditory tone crossmodally affects multiple visual events using a multiple stream/bounce display (SBD), consisting of two disk pairs moving toward each other at equal speeds, coinciding, and then moving apart in a two-dimensional (2-D) display. The temporal offsets were manipulated between the coincidences of the disk pairs (0 to ±240 ms) by staggering motion onset between the pairs. A tone was presented at the coincidence timing of one of the disk pairs on half of the trials. Participants judged whether the disks in each of two pairs appeared to stream through or bounce off each other. Results show that a tone presented at either of the disk pairs' coincidence points promoted bouncing percepts in both disk pairs compared to no-tone trials. Perceived bouncing persisted in the disk-pair whose coincidence was offset 60 ms before and up to more than 120 ms after the audiovisual coincidence timing of the other disk-pair. The temporal window of bounce promotion was comparable to that obtained with a conventional SBD. The interaction of a single auditory event and multiple visual events was also modulated by the kind of experimental task (the stream/bounce or simultaneity judgments). These findings suggest that, using a single auditory cue, the perceptual system resolves the ambiguity of the motion of multiple disk pairs presented within the conventional temporal window of crossmodal interaction.

Specific needs for telestroke networks for thrombolytic therapy in Japan.

The concept of telestroke networks has been proposed to overcome regional disparities in stroke treatment. Such networks do not yet operate in Japan. We aimed to determine the specific needs for telestroke networks and to estimate the effects on the number of thrombolytic therapies. Five of the 47 Japanese prefectures with various population densities to estimate the nationwide effect of telestroke networks were selected. The questionnaire survey was administered at hospitals in these prefectures that are authorized to admit patients with acute stroke. Low-volume hospitals that annually treated fewer than 12 patients with acute stroke had never used tissue plasminogen activator (tPA). The number of days when telestroke support might have been needed varied depending on the size of the population aged 65 years or older within a 30-minute-driving-time area of a hospital and the annual number of patients treated within 3 hours of onset. The geographic information system analysis showed that .6%-8.3% of the population lived in areas where they could not reach a hospital for acute stroke treatment within 60 minutes. If 24/7 full telestroke support was introduced to the existing hospitals, 6.8-69.3 more patients could be treated by intravenous (IV) tPA annually. These numbers exceeded the estimated annual increases of .8-13.7 more patients if a drip-and-ship telestroke network was introduced into an underserved area outside the 60-minute-driving-time area. This study uncovered that many Japanese stroke hospitals, especially low-volume facilities located in rural areas, do not perform IV tPA therapy in 24/7 fashion and telestroke support to these hospitals may be highly effective compared with the drip-and-ship network in an underserved area.

Impact of life and family background on delayed presentation to hospital in acute stroke.

The over-65 population stands at 29 million, more than 20% of the total population in Japan. This is the highest rate in the world. One-person households and older couple households will be increasing. The aim of the present study was to identify whether life and family background are significant factors for delayed presentation to hospital after stroke onset. A total of 253 patients (mean age, 70.7 ± 13.2 years) with stroke was examined. Patients who presented to hospital within 3 hours of onset were categorized as the early presentation group, and the other patients were categorized as the late presentation group. Life and family background were classified into 3 categories, namely 1-person households, 2-person households, and patients living with 3 or more persons. Two-person households were further subdivided by the age of family members. Multivariate logistic regression analysis demonstrated that 1-person households (odds ratio [OR]: 2.980, 95% confidence interval [CI]: 1.108-8.011) and 2-person households with individuals 65 years and older (OR: 3.059, 95% CI: 1.297-7.217) were significant independent factors for delayed presentation, in addition to stroke subtype, time of stroke onset, and route of admission. Onset-to-door time in patients with night-time onset was significantly different among different types of households. Significant delay was demonstrated in 2-person households with 2 individuals 65 years and older compared with that in patients living with 3 or more persons (P = .038). Our findings show that delayed presentation to hospital is more likely in stroke patients living in an elderly couple household, especially those with evening onset in an aging society.

Use of the Superficialized Brachial Artery as Vascular Access for a Patient with Myasthenia Gravis with a Frequent Need for Plasmapheresis.

A 41-year-old woman diagnosed with seronegative myasthenia gravis struggled to maintain remission for a decade, facing crises every 3 months for several years. After repeated apheresis using a non-tunneled non-cuffed central venous dialysis catheter (NTNCC), complications such as catheter-related thrombus in the internal jugular veins and morbid obesity from steroids made the insertion of NTNCC increasingly difficult, leading to consideration of an alternative permanent vascular access (VA) approach. Thus, we created a subcutaneously superficialized brachial artery as the VA, which allowed the patient to undergo safe and uninterrupted apheresis therapy.

Association between inflammatory biomarkers and progression of intracranial large artery stenosis after ischemic stroke.

BACKGROUND: Proinflammatory state has been implicated as a pathogenetic mechanism in the progression of intracranial large artery atherosclerosis (ILA). High levels of inflammatory biomarkers in healthy populations and in patients with acute stroke or acute coronary syndrome are known to be associated with subsequent stroke events. This study investigated the relationship between circulating biomarkers measured early after stroke onset and future ILA progression. METHODS: In 48 patients with acute ischemic stroke, high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), IL-18, tumor necrosis factor-α, matrix metalloproteinase (MMP)-2 and MMP-9 were measured within 48 hours after onset. Baseline severity and ILA progression were assessed by serial magnetic resonance angiography (MRA). The median follow-up period for MRA was 3.1 years. Hazard ratio (HR) was calculated using the Cox proportional hazard model adjusted for traditional risk factors, and accuracy of predicted ILA progression was analyzed by receiver operating characteristic (ROC) curve analysis. RESULTS: ILA progression was observed in 6 of 48 patients (12.5%). After adjusting for age, sex, and presence of hypertension, baseline ILA severity score (HR 2.814; 95% confidence interval [CI] 1.172-6.754) and IL-6 (HR 1.215; 95% CI 1.002-1.473) were significantly associated with ILA progression. Area under the ROC curve (AUC) for prediction of ILA progression by traditional risks, baseline ILA severity score and IL-6, was 0.647. When IL-6 was removed from this model, AUC remained at 0.631. CONCLUSIONS: In addition to traditional risk factors and baseline radiologic findings, circulating levels of IL-6 measured soon after stroke onset are associated with future ILA progression.

Auditory transients do not affect visual sensitivity in discriminating between objective streaming and bouncing events.

With few exceptions, the sound-induced bias toward bouncing characteristic of the stream/bounce effect has been demonstrated via subjective responses, leaving open the question whether perceptual factors, decisional factors, or some combination of the two underlie the illusion. We addressed this issue directly, using a novel stimulus and signal detection theory to independently characterize observers' sensitivity (d') and criterion (c) when discriminating between objective streaming and bouncing events in the presence or absence of a brief sound at the point of coincidence. We first confirmed that sound-induced motion reversals persist despite rendering the targets visually distinguishable by differences in texture density. Sound-induced bouncing persisted for targets differing by as many as nine just-noticeable-differences (JNDs). We then exploited this finding in our signal detection paradigm in which observers discriminated between objective streaming and bouncing events. We failed to find any difference in sensitivity (d') between sound and no-sound conditions, but we did observe a significantly more liberal criterion (c) in the sound condition than the no-sound condition. The results suggest that the auditory-induced bias toward bouncing in this context is attributable to a sound-induced shift in criterion implicating decisional processes rather than perceptual processes determining responses to these displays.

Effects of edaravone, a free radical scavenger, on serum levels of inflammatory biomarkers in acute brain infarction.

The potent free radical scavenger edavarone is widely used in Japan to treat acute ischemic stroke within 24 hours after onset. Recent experimental studies have shown that edavarone alleviates blood-brain barrier disruption in conjunction with suppression of the inflammatory reaction in acute brain ischemia. We investigated the effects of edaravone on circulating inflammatory biomarkers in patients with ischemic stroke. Patients with acute ischemic stroke admitted 12-36 hours after onset of symptoms were prospectively enrolled. Intravenous edaravone at 60 mg/day for 14 days was administered to patients admitted 12-24 hours after symptom onset (edaravone group; n = 29). Patients admitted 24-36 hours after onset served as controls (control group; n = 34). Venous blood samples were obtained on admission and at 48 hours, 7 days, and 14 days after symptom onset. Serum concentrations of high-sensitivity C-reactive protein, interleukin (IL)-6, IL-10, IL-18, tumor necrosis factor α, matrix metalloproteinase (MMP)-2, and MMP-9 were measured. General linear models were used to compare changes in concentrations of these biomarkers over time between the groups. In the control group, the mean MMP-9 concentration increased gradually from 3.857 ± 1.880 ng/mL to 4.538 ± 1.966 ng/mL over the 14-day period (P = .027, one-way repeated-measures analysis of variance [ANOVA]), but the edavarone group demonstrated no such increase (P = .564). A significant group-time interaction was demonstrated only for MMP-9 (P = .029, two-way repeated-measures ANOVA), and no significant differences in other biomarkers were seen between groups. Our data indicate that edaravone suppresses serum MMP-9 level in patients with acute ischemic stroke. Further studies with a larger sample size are needed to explore the relationship between circulating MMP-9 level and the protective effect of edaravone.

Body Pitch Together With Translational Body Motion Biases the Subjective Haptic Vertical.

Accurate perception of verticality is critical for postural maintenance and successful physical interaction with the world. Although previous research has examined the independent influences of body orientation and self-motion under well-controlled laboratory conditions, these factors are constantly changing and interacting in the real world. In this study, we examine the subjective haptic vertical in a real-world scenario. Here, we report a bias of verticality perception in a field experiment on the Hong Kong Peak Tram as participants traveled on a slope ranging from 6° to 26°. Mean subjective haptic vertical (SHV) increased with slope by as much as 15°, regardless of whether the eyes were open (Experiment 1) or closed (Experiment 2). Shifting the body pitch by a fixed degree in an effort to compensate for the mountain slope failed to reduce the verticality bias (Experiment 3). These manipulations separately rule out visual and vestibular inputs about absolute body pitch as contributors to our observed bias. Observations collected on a tram traveling on level ground (Experiment 4A) or in a static dental chair with a range of inclinations similar to those encountered on the mountain tram (Experiment 4B) showed no significant deviation of the subjective vertical from gravity. We conclude that the SHV error is due to a combination of large, dynamic body pitch and translational motion. These observations made in a real-world scenario represent an incentive to neuroscientists and aviation experts alike for studying perceived verticality under field conditions and raising awareness of dangerous misperceptions of verticality when body pitch and translational self-motion come together.

A case of autoimmune encephalitis with involuntary movements as the first symptom and suspected association with mumps virus infection.

This case involved a 72-year-old woman. From the day after mitral annuloplasty, a fever over 37°C and ballismus-like involuntary movements of the right upper and lower limbs appeared. A few month later, involuntary movements spread throughout the body, and she developed impairment of consciousness and difficulty speaking and eating. Levels of protein in cerebrospinal fluid were high. Positive results were seen for serum mumps immunoglobulin G and M antibody. Because steroid pulse therapy proved effective, we suspected autoimmune encephalitis associated with mumps virus infection.

The Utility of Automated ASPECTS in Acute Ischemic Stroke for Intravenous Recombinant Tissue Plasminogen Activator (IV-rtPA) Therapy.

PURPOSE: This study aimed to investigate the accuracy and clinical significance of an artificial intelligence (AI)-based automated Alberta Stroke Program Early Computed Tomography (ASPECT) scoring software of head CT for the indication of intravenous recombinant tissue plasminogen activator (rt-PA) therapy. METHODS: This study included two populations of acute ischemic stroke: one comprised patients who had undergone head CT within 48 h of presentation (Population #1, n = 448), while the other included patients within 4.5 h from onset (Population #2, n = 132). The primary endpoint was the concordance rate of ASPECTS of the neurologists and AI software against the benchmark score. The secondary endpoints were to validate the accuracy of the neurologist and AI software in assessing the ability to rule out extensive infarction (ASPECTS of 0-5) in population #2. RESULTS: The reading accuracy of AI software was comparable to that of the board-certified vascular neurologists. The detection rate of cardiogenic cerebral embolism was better than that of atherothrombotic cerebral infarction. By excluding extensive infarction, AI-software showed a higher specificity and equivalent sensitivity compared to those of experts. CONCLUSIONS: The AI software for ASPECTS showed convincing agreement with expert evaluation and would be supportive in determining the indications of intravenous rt-PA therapy.

[Effects of early statin treatment on inflammatory biomarkers and clinical deterioration in patients with acute ischemic stroke].

We prospectively studied the effects of early statin treatment on stroke-induced changes in the levels of inflammatory biomarkers. Patients admitted within 48 hours after the onset of ischemic stroke were enrolled. They were divided into 2 groups according to their lipid profiles and history of statin treatment. In patients who had received statin treatment prior to admission and those who had abnormal lipid profiles on admission, daily treatment with 10 mg atorvastatin was initiated within 48 hours after the onset of stroke (Statin group; n = 45). In patients who had normal lipid profiles on admission, statin was not administered for at least 2 weeks after admission (Non-Statin group; n = 101). The serum concentrations of interleukin (IL)-6, IL-10, IL-18, matrix metalloproteinase (MMP)-2, MMP-9, and high sensitive C-reactive protein were measured on days 1, 3, 7, and 14. In percentage changes in serially measured circulating IL-6 levels, a significant interaction between group and repeated measures (group X time factor) was demonstrated (p = 0.047). Frequency of neurological deterioration episodes (NIHSS score > or = 2) during 14 days after admission was lower in the Statin group than in the Non-Statin group, however the difference did not reach statistically significant level (7.9% vs 20.2%, p = 0.118). The initiation of usual dose of atorvastatin early after the onset of ischemic stroke significantly decreased the elevation of IL-6 and may protect against the early neurological deterioration. Circulating levels of IL-6 may be one of the candidates for monitoring the acute effects of statin. Further studies wherein IL-6 levels are monitored in larger samples would be feasible for investigating the effect of early treatment with usual dose of atorvastatin on the functional outcome.

[A case of nasal discharge resulting in recurrent bacterial meningitis].

A 47-year-old man who was previously hospitalized three times due to bacterial meningitis experienced a headache and posterior neck pain in May. He was admitted to our hospital because of a fever 3 h later. He was fully conscious and febrile, with a headache and signs of meningeal irritation. A cerebrospinal fluid examination showed an increased number of cells with polynuclear cell predominance and decreased glucose levels, leading to the diagnosis of bacterial meningitis. Steroid and antibiotic treatment was initiated, at which time, large amounts of nasal discharge were observed. Cisternal scintigraphy was performed, and cerebrospinal fluid was detected in the nasal discharge. The cause was idiopathic, and endoscopic repair was performed. The nasal fluid leakage was suggested to be the cause of the recurrent bacterial meningitis in this case.