Search

Abstract Sublingual immunotherapy (SLIT) has received considerable attention as a method for allergen immunotherapy (AIT). However, the mechanism of SLIT, especially its timing, has not been thoroughly investigated. We evaluated therapeutic and prophylactic SLIT in an allergic airway inflammation model and evaluated their efficacies. Mice were intranasally exposed to Dermatophagoides farinae (Der f) extract and received SLIT before (prophylactic model) and after (therapeutic model) intranasal exposure of Der f. We investigated airway responsiveness, airway inflammation, allergen-specific antibodies, lung histology and single-cell RNA sequencing (scRNA-seq) and T-cell receptor sequencing were also investigated. SLIT in the therapeutic model was effective; however, the effects of SLIT in the prophylactic model were stronger and immune tolerance was maintained for three months. ScRNA-seq of lung CD4+CD25+ T cells revealed that the expansion of induced T regulatory (iTreg) cells was greater in the prophylactic model than that in the therapeutic model. Additionally, the TCR repertoire of iTregs from the prophylactic model was abundant, sharing many clones with the TCR repertoire of effector T cells. These data suggest that the prophylactic model of AIT is extremely effective and persistent, and may respond to allergen diversity, and provide evidence for the clinical recommendation of preventive AIT.

In this study, we analyzed the effects of motorcycle riders' emotional states and human characteristics on their lane change behavior. As a result, we confirmed that motorcycle riders tend to change lanes when the valence level of Russell's emotion model is negative, even in risky situations with small time to collision (TTC) with the following vehicle in the adjacent lane. We also clarified indicators of human characteristics related to the lane change behavior of motorcycle riders. Finally, we constructed a model to estimate the lane change probability of a motorcycle rider using their emotional states, human characteristics, and surrounding vehicle information based on logistic regression analysis in order to propose a cooperative Human-Machine Interface (HMI) for two-wheeled and four-wheeled vehicles.

Abstract Background Extracorporeal membrane oxygenation (ECMO) can provide temporary circulatory support and vital organ oxygenation and is potentially useful as a bridge therapy in some trauma cases. We aimed to demonstrate the characteristics and outcomes of patients with trauma treated with veno-arterial ECMO (V-A ECMO) using data from a Japanese nationwide trauma registry. Methods This retrospective descriptive study analyzed data from the Japan Trauma Data Bank between January 2019 and December 2021. Patients with severe trauma (injury severity score [ISS] ≥ 9) and treated using V-A ECMO were assessed. Results Among the 72,439 patients with severe trauma, 51 received V-A ECMO. Sixteen patients (31.3%) survived until hospital discharge. On hospital arrival, six (37.5%) survivors and 15 (42.9%) non-survivors experienced cardiac arrest. The median ISS for the survivor and non-survivor group was 25 (range, 25–39) and 25 (range, 17–33), respectively. Thoracic trauma was the most common type of trauma in both groups. In the non-survivor group, open-chest cardiopulmonary resuscitation, aortic cross-clamping, and resuscitative endovascular balloon occlusion of the aorta were performed in 10 (28.6%), 5 (14.3%), and 4 (11.4%) patients, respectively. However, these procedures were not performed in the survivor group. Peripheral oxygen saturation tended to be lower in the survivor group both before and upon arrival at the hospital. Conclusions The results of this study suggest the potential benefit of V-A ECMO in some challenging trauma cases. Further studies are warranted to assess the indications for V-A ECMO in patients with trauma.

We studied the traffic flow management on highway main line to assist drivers in merging using CACC (Cooperative Adaptive Cruise Control) vehicles which can adjust vehicle speed and time-headway based on control target from out-car via wide-area or narrow-area communication. By conducting platoon simulations to clarify the effect of CACC control on traffic flow under various vehicle and driver types by combining control target (speed or time-headway) and control trigger (time or position), we found that speed management based on narrow area communication (i.e., position triggering) is most effective to manage the traffic flow before and after merging sections in a quick and stable manner even at relatively low CACC ratio. The study also revealed the problems that the time-headway adjustment results in excessive speed changes and that time triggered speed management can cause irregular speed fluctuations. These findings are useful in providing driving assistance by controlling traffic flow stably, and we will realize desirable merging assistance to drivers in the future.

Abstract Comorbid Alzheimer’s disease (AD) neuropathology is common in Lewy body disease (LBD); however, AD comorbidity in the prodromal phase of LBD remains unclear. This study investigated AD comorbidity in the prodromal and symptomatic phases of LBD by analyzing plasma biomarkers in patients with Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) and individuals at risk of LBD (NaT-PROBE cohort). Patients with PD (PD group, n = 84) and DLB (DLB group, n = 16) and individuals with LBD with ≥ 2 (high-risk group, n = 82) and without (low-risk group, n = 37) prodromal symptoms were enrolled. Plasma amyloid-beta (Aβ) composite was measured using immunoprecipitation-mass spectrometry assays. Plasma phosphorylated tau 181 (p-tau181), neurofilament light chain (NfL), and alpha-synuclein (aSyn) were measured using a single-molecule array. Plasma p-tau181 levels were higher in the PD and DLB groups than in the low-risk group. Aβ composite level was higher in the DLB group than in the high-risk group. AD-related biomarker levels were not elevated in the high-risk group. NfL levels were higher in the high-risk, PD, and DLB groups than in the low-risk group. In the PD group, Aβ composite was associated with cognitive function, p-tau181 with motor function and non-motor symptoms, and NfL with cognitive and motor functions and non-motor symptoms. In the high-risk group, NfL was associated with metaiodobenzylguanidine scintigraphy abnormalities. The PD and DLB groups exhibited comorbid AD neuropathology, though not in the prodromal phase. Elevated plasma NfL levels, even without elevated AD-related plasma biomarker levels, may indicate aSyn-induced neurodegeneration in the LBD prodromal phase.

Abstract Recently, calcitonin gene‐related peptide (CGRP) monoclonal antibodies (mAbs) have become available as a prophylactic treatment for migraine and have shown high efficacy and safety in clinical practice. CGRP mAbs have been reported to be effective not only for migraine but also for other comorbidities, such as psychiatric complications in patients with migraine. However, there are no reports examining the effect of CGRP mAbs on dystonia. We treated a patient with comorbid migraine and focal task‐specific dystonia (writer's cramp) with a CGRP mAb (erenumab) because of an increase in monthly migraine days despite the addition of migraine prophylaxis. In this patient, erenumab treatment for 3 months led to improvements in symptoms of both focal dystonia and migraine, suggesting a role for CGRP in the pathophysiology of both conditions.

Abstract Background Resuscitative endovascular balloon occlusion of the aorta (REBOA) has been used to control massive hemorrhages. Although there is no consensus on the efficacy of REBOA, it remains an option as a bridging therapy in non-trauma centers where trauma surgeons are not available. To better understand the current landscape of REBOA application, we examined changes in its usage, target population, and treatment outcomes in Japan, where immediate hemostasis procedures sometimes cannot be performed. Methods This retrospective observational study used the Japan Trauma Data Bank data. All cases in which REBOA was performed between January 2004 and December 2021 were included. The primary outcome was the in-hospital mortality rate. We analyzed mortality trends over time according to the number of cases, number of centers, severity of injury, and overall and subgroup mortality associated with REBOA usage. We performed a logistic analysis of mortality trends over time, adjusting for probability of survival based on the trauma and injury severity score. Results Overall, 2557 patients were treated with REBOA and were deemed eligible for inclusion. The median age of the participants was 55 years, and male patients constituted 65.3% of the study population. Blunt trauma accounted for approximately 93.0% of the cases. The number of cases and facilities that used REBOA increased until 2019. While the injury severity score and revised trauma score did not change throughout the observation period, the hospital mortality rate decreased from 91.3 to 50.9%. The REBOA group without severe head or spine injuries showed greater improvement in mortality than the all-patient group using REBOA and all-trauma patient group. The greatest improvement in mortality was observed in patients with systolic blood pressure ≥ 80 mmHg. The adjusted odds ratios for hospital mortality steadily declined, even after adjusting for the probability of survival. Conclusions While there was no significant change in patient severity, mortality of patients treated with REBOA decreased over time. Further research is required to determine the reasons for these improvements in trauma care.

A 60-year-old woman with a history of neurofibromatosis type 1, who was admitted with pulmonary hypertension, developed buttock pain and anemia, and contrast-enhanced computed tomography showed a large subcutaneous hematoma with minimal active extravasation. Angiography of the bilateral internal iliac arteries revealed diffuse, irregular blood vessels without extravasation. As the exact bleeding site could not be identified, the patient was managed conservatively. However, the patient's symptoms and anemia worsened the following day. Repeat angiography revealed two pseudoaneurysms in the right inferior gluteal artery, which were embolized using n-butyl-2-cyanoacrylate. Nonetheless, the patient's anemia further worsened the following day. Repeat contrast-enhanced CT revealed another site of extravasation in the enlarging hematoma, but no extravasation was observed on the subsequent angiography. Owing to the worsening anemia and enlarging hematoma, proximal embolization of the irregular bilateral inferior gluteal arteries was performed using gelatin sponge particles. The patient's anemia and symptoms improved. Vasculopathy associated with neurofibromatosis type 1 is rare, with an incidence of approximately 3%. In patients with neurofibromatosis type 1, the blood vessels become fragile because of tunica media thinning and elastic-lamina rupture. Histopathologically, neurofibromatosis type 1-associated vasculopathy is characterized by a mixture of normal and abnormal vessels. Abnormally fragile blood vessels may repeatedly rupture followed by physiological hemostasis, which may explain the diagnostic and therapeutic challenges during angiography in this case. In patients with neurofibromatosis type 1 with acute bleeding, irregular vessels without active extravasation on angiography may be indicated for embolization.

Abstract Background Anti-calcitonin gene-related peptide monoclonal antibodies (CGRPmAbs) have greatly changed migraine treatment options. In Japan, although CGRPmAb guidelines (≥ 4 monthly migraine days (MMDs) and ≥ 1 previous preventive failure) are well-acknowledged, the actual use of CGRPmAbs and the circumstances of the related headache care are unknown. Methods We conducted an online survey of Japanese Headache Society members, inquiring about the physicians' experience with CGRPmAbs and how they make decisions related to their use. Results Of the 397 respondents, 320 had prescribed CGRPmAbs. The threshold number of previous preventive failures for recommending a CGRPmAb was two for the majority of the respondents (n = 170, 54.5%), followed by one (n = 64, 20.5%). The MMD threshold was ≥ 4 for 71 respondents (22.8%), ≥ 6 for 68 (21.8%), ≥ 8 for 76 (24.4%), and ≥ 10 for 81 (26.0%). The respondents tended to assess treatment efficacy after 3 months (episodic migraine: n = 217, 69.6%, chronic migraine: n = 188, 60.3%). The cost of CGRPmAbs was described by many respondents in two questions: (i) any request for a CGRPmAb (27.7%), and (ii) the most frequently reported reason for responders to discontinue CGRPmAbs (24.4%). Conclusions Most of the respondents recommended CGRPmAbs to patients with ≥ 2 preventive failures, followed by ≥ 1. The MMD threshold ranged mostly from ≥ 4 to ≥ 10. The concern for costs was raised as a major limiting factor for prescribing CGRPmAbs.

Introduction: Isolated h-type tracheoesophageal fistula (H-TEF) without esophageal discontinuity is rare and poses challenges in selecting a surgical approach due to the height of the fistula within the thoracic cavity. Case presentation: A female neonate was born prematurely at 31 weeks of gestation with a weight of 1200 g. She was intubated at birth due to respiratory distress. She was later diagnosed with CHARGE syndrome. Nasogastric tube feedings were initiated shortly after birth. Air bubbles could be seen coming out the nasogastric tube, which were suspicious for a tracheoesophageal fistula (TEF). A contrast esophagogram confirmed an h-type TEF at the level of the second thoracic vertebral body. When the patient was five months old and had a weight of 3 Kg, she was taken to the operating room for a thoracoscopic repair of the TEF. She was placed in complete left lateral position. Four 5-mm ports were placed in the right hemithorax. The right vagus nerve was identified. We first created a pleural flap with the mediastinal pleura. Blunt dissection of the esophagus and the trachea allowed clear identification of the TEF. A vessel loop was placed around the TEF. The TEF was divided. The esophageal end the tracheal sides of the TEF were closed with interrupted stitches. The pleural flap was interposed between the two stumps. The operation took 238 minutes. The postoperative period was uneventful, and she had no recurrence of the TEF. She underwent a tracheostomy one month later, and a laparoscopic fundoplication three months after that. She was discharged home at one year of age. Conclusion: Thoracoscopy appears to be a suitable approach for the repair of high thoracic h-type TEF.

Motorcycle assistance systems have been an increasing focus of research in recent years to promote safer riding practices and mitigate motorcycle-related accidents. While there is substantial interest in evaluating the beneficial aspect of these systems in improving driving safety, it is equally essential to clarify their unintended adverse effects on riders' driving behaviors and the overall interaction between riders and such systems. In this study, we designed alert and continuous real-time feedback HMIs that convey information about lateral deviation from the lane center based on our previous research results. Experiments were then conducted on a riding simulator to investigate whether variations in information presentation could alter rider-system interaction and ultimately affect riding performance. Fifteen young motorcyclists (mean age = 22.1 ± 1.87 years) were exposed to dummy and risky scenarios at uncontrolled intersections while interacting with alerting or real-time feedback systems separately. A path model was constructed, and the impacts of HMIs on riders' reaction time, information observation time, weighted workload, and risk of collision were clarified. Cluster analysis was subsequently utilized to categorize participants into confident and methodical riders, predicated upon their riding styles. Independent t-tests revealed that, except for Obs-time, there were no significant differences between confident and methodical riders in RT and TTCmin when using an alert HMI. However, when real-time feedback was displayed, significant differences were found for TTCmin and Obs-time. In general, participants exhibited superior performance with the Alert HMI, characterized by a shorter RT (1 second), longer TTCmin (0.79 seconds), reduced information observation time (0.42 seconds), and lower perceived workload compared to when real-time feedback was used. The authors believe that this research will contribute to the development of more effective and rider-centric HMI designs.

Objective To develop a new method of evaluating swallowing behaviour. Methods Sixty-nine healthy participants were divided into a younger (16 males and 16 females, mean age 39.09 ± 12.16 years) and older (18 males and 19 females, mean age 71.43 ± 5.50 years) group. The participants ingested water and yoghurt twice (directed and free swallowing) at rest and after performing simple daily life tasks (calculation and exercise). To measure swallowing frequency, we employed a smartphone-based, portable and neck-worn swallowing-sound-monitoring device. This device monitors swallowing behaviour continuously by collecting biological sounds from the neck without imposing behavioural restrictions. A neural network model of swallowing sound identification by deep learning was used for the subsequent evaluation. This device was used to obtain two types of saliva-swallowing sounds associated with different ingestants, at rest and after performing a stimulating task. Furthermore, we assessed the associated subjective psychological states. Results The younger group showed a higher directed swallowing frequency (for both water and yoghurt) than the older group did. Regarding the type of ingestant, the swallowing frequency for yoghurt was higher during free swallowing in both the young and the older groups. ‘Feeling calm’ was reported significantly more often in the older group after swallowing yoghurt following exercise. Conclusions Swallowing status in daily life was measured non-invasively using a wearable mobile device. It is important to consider the type of ingestant, daily living activities, and age when assessing swallowing.

Study region: Kamikochi area in the Japanese Northern Alps Study focus: For mountains with high precipitation and hydraulic gradients, understanding the hydrologic cycle is important for disaster prevention (i.e., floods and landslides) and water resource management. Mountainous regions with an Asian monsoon climate have higher precipitation than other parts of the world, and the runoff processes that accompany significant precipitation remain largely unresolved. We conducted hydrological observations to clarify the runoff process in mountainous regions with an Asian monsoon climate using the difference in runoff characteristics between mountain-block and floodplain springs in the Kamikochi area. New hydrological insight into the region: Hydrological observations and analysis under dry/wet conditions have revealed that the floodplain spring has a higher seasonally variable water temperature than the mountain-block spring. Under steady-state conditions, mountain-block groundwater has a larger discharge and helps maintain the baseflow. During precipitation events, the mountain-block spring exhibits a more pronounced increase in runoff than the floodplain spring under wet conditions. This is because the latter interacts with the mainstream through permeable sand/gravel beds, whereas the former is pushed out of the bedrock by precipitation. Thus, the hydrologic cycle in mountainous regions with an Asian monsoon climate is driven by the supply of high-potential mountain-block groundwater to the valley floor. Mountain-block groundwater not only maintains the baseflow but also drives the hydrologic cycle system in mountainous regions.

Abstract Background This study aimed to establish a systematic method for diagnosing atrioventricular nodal reentrant tachycardia (AVNRT) with a bystander concealed nodoventricular pathway (cNVP). Methods We analyzed 13 cases of AVNRT with a bystander cNVP, 11 connected to the slow pathway (cNVP‐SP) and two to the fast pathway (cNVP‐FP), along with two cases of cNVP‐related orthodromic reciprocating tachycardia (ORT). Results The diagnostic process was summarized in three steps. Step 1 was identification of the presence of an accessory pathway by resetting the tachycardia with delay (n = 9) and termination without atrial capture (n = 4) immediately after delivery of a His‐refractory premature ventricular contraction (PVC). Step 2 was exclusion of ORT by atrio‐His block during the tachycardia (n = 4), disappearance of the reset phenomenon after the early PVC (n = 7), or dissociation of His from the tachycardia during ventricular overdrive pacing (n = 1). Moreover, tachycardia reset/termination without the atrial capture (n = 2/2) 1 cycle after the His‐refractory PVC was specifically diagnostic. Exceptionally, the disappearance of the reset phenomenon was also observed in the two cNVP‐ORTs. Step 3 was verification of the AVN as the cNVP insertion site, evidenced by an atrial reset/block preceding the His reset/block in fast–slow AVNRT with a cNVP‐SP and slow–fast AVNRT with a cNVP‐FP or His reset preceding the atrial reset in slow–fast AVNRT with a cNVP‐SP. Conclusion AVNRT with a bystander cNVP can be diagnosed in the three steps with few exceptions. Notably, tachycardia reset/termination without atrial capture one cycle after delivery of a His‐refractory PVC is specifically diagnostic.

Abstract Introduction A higher levodopa dose is a risk factor for motor complications in Parkinson’s disease (PD). Istradefylline (IST) is used as adjunctive treatment to levodopa in PD patients with off episodes, but its impact on levodopa dose titration remains unclear. The objective of this study was to investigate the effect of IST on levodopa dose escalation in PD patients with wearing-off. Methods This was a multicenter, open-label, randomized, parallel-group controlled study (ISTRA ADJUST PD) in which PD patients experiencing wearing-off (n = 114) who were receiving levodopa 300–400 mg/day were randomized to receive IST or no IST (control). Levodopa dose was escalated according to clinical severity. The primary endpoint was cumulative additional levodopa dose, and secondary endpoints were changes in symptom rating scales, motor activity determined by a wearable device, and safety outcomes. Results The cumulative additional levodopa dose throughout 37 weeks and dose increase over 36 weeks were significantly lower in the IST group than in the control group (both p

Objective To examine the association between the mobilization level during intensive care unit (ICU) admission and independence in activity of daily living (ADL), defined as Barthel Index (BI)≥70. Methods This was a post-hoc analysis of the EMPICS study involving nine hospitals. Consecutive patients who spend >48 hours in the ICU were eligible for inclusion. Mobilization was performed at each hospital according to the shared protocol and the highest ICU mobility score (IMS) during the ICU stay, baseline characteristics, and BI at hospital discharge. Multiple logistic regression analysis, adjusted for baseline characteristics, was used to deter-mine the association between the highest IMS (using the receiver operating characteristic [ROC]) and ADL. Results Of the 203 patients, 143 were assigned to the ADL independence group and 60 to the ADL dependence group. The highest IMS score was significantly higher in the ADL independence group than in the dependence group and was a predictor of ADL independence at hospital discharge (odds ratio, 1.22; 95% confidence interval, 1.07–1.38; adjusted p=0.002). The ROC cutoff value for the highest IMS was 6 (specificity, 0.67; sensitivity, 0.70; area under the curve, 0.69). Conclusion These results indicate that, in patients who were in the ICU for more than 48 hours, that patients with good function in the ICU also exhibit good function upon discharge. However, prospective, multicenter trials are needed to confirm this conclusion.

Heatstroke induces fluid loss and electrolyte abnormalities owing to high ambient temperature (AT) and relative humidity (RH). Aquaporin 1 (AQP1) is a key protein for water homeostasis; however, its role in heatstroke remains unclear. This study examines endothelial AQP1 in Tie2-Cre/LNL-AQP1 double transgenic (dTG) mice with upregulated Aqp1 in endothelial cells. For experimental heatstroke, mice were exposed to 41 °C AT and >99% RH. Blood, brain, kidney, and liver samples were collected 24 h later. Blood was analyzed for electrolytes and tissue damage markers, and organs were examined using morphological and immunohistological staining for 3-nitrotyrosine (3-NT), AQP1, and Iba-1. No difference in Aqp1 expression was observed in the whole brain; however, it was detected in dTG mice after capillary deprivation. AQP1 immunostaining revealed immunoreaction in blood vessels. After heat exposure, wild-type and dTG mice showed electrolyte abnormalities compared with non-heatstroke wild-type mice. Hepatic damage markers were significantly higher in dTG mice than in wild-type mice. Hematoxylin–eosin staining and 3-NT immunoreactivity in the liver indicated hepatic damage. The number of Iba-1-positive cells adherent to hepatic vasculature was significantly higher in dTG mice than in wild-type mice. This study is the first to suggest that endothelial AQP1 contributes to hepatic damage after heatstroke.

A 79-year-old man was admitted for 2 weeks of dizziness, followed by diplopia, involuntary movement and progressive gait disturbances. Neurologic examination revealed horizontal and vertical gaze paresis, bilateral choreiform movement with orofacial dyskinesia, and limb/truncal ataxia. MRI revealed fluid-attenuated inversion recovery image-hyperintense signal abnormalities in the dorsal midbrain, pontine and medulla. Within another few days, the patient developed type II acute respiratory failure requiring artificial invasive ventilation. Because autoimmune encephalitis was suspected, he received intravenous immunoglobulin therapy followed by intravenous methylprednisolone, but only his ophthalmoplegia improved minimally. Serological tests were positive for anti-Ri onconeural antibodies. CT-guided mediastinal lymph node biopsy was performed and revealed small cell lung carcinoma. We report the rare manifestation of anti-Ri antibody-associated paraneoplastic neurological syndrome (PNS), and this case can alert us to the importance of respiratory management in this diverse neurologic disease. Furthermore, PNSs positive for anti-Ri antibodies should be added to the list of differential diagnoses of chorea with orofacial dyskinesia.

Objective To investigate the effect on early mobilization in patients undergoing extra-corporeal membrane oxygenation (ECMO) and acute blood purification therapy in the intensive care unit (ICU). Methods We conducted this multicenter retrospective cohort study by collecting data from six ICUs in Japan. Consecutive patients who were admitted to the ICU, aged ≥18 years, and received mechanical ventilation for >48 hours were eligible. The analyzed were divided into two groups: ECMO/blood purification or control group. Clinical outcomes; time to first mobilization, number of total ICU rehabilitations, mean and highest ICU mobility scale (IMS); and daily barrier changes were also investigated. Results A total of 204 patients were included in the analysis, 43 in the ECMO/blood purification group and 161 in the control group. In comparison of clinical outcome, the ECMO/blood purification group had a significantly longer time to first mobilization: ECMO/blood purification group 6 vs. control group 4 (p=0.003), higher number of total ICU rehabilitations: 6 vs. 5 (p=0.042), lower mean: 0 vs. 1 (p=0.043) and highest IMS: 2 vs. 3 (p=0.039) during ICU stay. Circulatory factor were most frequently described as barriers to early mobilization on days 1 (51%), 2 (47%), and 3 (26%). On days 4 to 7, the most frequently described barrier was consciousness factors (21%, 16%, 19%, and 21%, respectively) Conclusion The results of this study comparing the ECMO/blood purification group and the untreated group in the ICU showed that the ECMO/blood purification group had significantly longer days to mobilization and significantly lower mean and highest IMS.

ObjectiveSleep disturbances are common in migraine patients and affect quality of life. Central sensitization (CS) is likely to play a role in the increased severity and chronicity of migraine. We hypothesized that the number of comorbid sleep problems would affect headache-related disability through the effects of central sensitization (CS).MethodsWe performed a cross-sectional study including 215 consecutive patients with migraine. Insomnia was defined as a Pittsburgh Sleep Quality Index (PSQI) global score greater than 5. Probable REM sleep behavior disorder (pRBD) was defined as an RBD screening score of 5 or greater. Excessive daytime sleepiness (EDS) was defined as an Epworth Sleepiness Scale score of 10 or higher. Suspected sleep apnea (SA) was defined as patients with snoring or sleep apnea witnessed 3 or more nights a week. CS was assessed by the Central Sensitization Inventory (CSI).ResultsRestless legs syndrome, insomnia, EDS, SA and pRBD were observed in 25.6%, 71.6%, 34.4%, 10.2%, and 21.4%, respectively, of the patients. At least one sleep problem was present in 87.0% of the patients. According to the results of the multinomial logistic regression analysis with no sleep problems as a reference, after we corrected for adjustment factors, the Migraine Disability Assessment (MIDAS) score significantly increased when three or more comorbid sleep problems were present. According to our mediation analysis, an increased number of sleep problems had a direct effect on the MIDAS score after we adjusted for other variables, and the CSI score was indirectly involved in this association.ConclusionThe present study showed an association between migraine-related disability and the burden of multiple sleep problems, which was partially mediated by CS.

Background: Real-world evidence of erenumab effectiveness in migraine patients in Asia with various comorbidities and multiple previous medication failures is still limited. Methods: A 6-month single-center cohort study of 45 patients with episodic or chronic migraine (CM) treated with erenumab was conducted. In the cohort, 60.0% were switching from other calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs), and 66.7% had ≥4 prophylaxis failures. The change in monthly migraine days (MMDs) from baseline and percentages of responders after treatment were calculated. Weekly migraine days (WMDs) were obtained at baseline and at months 1, 2 and 3 and were compared between weeks 2 and 4. Results: In total, 36%, 47%, and 63% of patients had a ≥30% response at 1, 3, and 6 months, respectively. The cumulative percentage of patients achieving a ≥30% response over 6 months was 85%. Early responders (average ≥ 30% response at 1–3 months) accounted for 37.8%, 55.6%, and 25.9% of the total, CGRP mAb-naïve, and CGRP mAb-switching groups, respectively. Late responders (average

Background: In Japan, pollinosis caused by the Japanese cypress (JCy) Chamaecyparis obtusa is among the very common seasonal allergies. In JCy pollinosis, Cha o 1 is the first major allergen, and Cha o 2 is the second major allergen. Recently, Cha o 3 was identified as a new JCy pollen allergen in JCy pollinosis. However, the relative contribution of Cha o 3 to JCy pollinosis compared with that of Cha o 1 and that of Cha o 2 has not been fully elucidated. Objective: This study aimed to clarify the allergenicity of Cha o 3 compared with that of Cha o 1 and Cha o 2 in JCy pollinosis. Methods: We recruited 27 patients with JCy pollinosis and performed the basophil activation test (BAT) with native (n) Cha o 1, Cha o 2, and Cha o 3 purified from JCy pollen. In addition, we a performed JCy-specific IgE suppression test. Results: In the BAT, 26 of 27 patients (96%) and 18 of 27 patients (67%) showed positive basophil activation in response to n Cha o 1 and n Cha o 2, respectively, as judged by CD203c expression. Little CD203c expression in response to n Cha o 3 was seen. The presence of n Cha o 3 marginally reduced the titer levels of JCy-specific IgE. Conclusion: Cha o 3 showed little ability to activate basophils and suppress JCy-specific IgE titers compared with Cha o 1 or Cha o 2 in patients with JCy pollinosis. Thus, Cha o 3 may not be a major allergen in JCy pollinosis.

Visual hallucinations (VHs) are perceptions of objects or events in the absence of the sensory stimulation that would normally support such perceptions. Although all VHs share this core characteristic, there are substantial phenomenological differences between VHs that have different aetiologies, such as those arising from Neurodegenerative conditions, visual loss, or psychedelic compounds. Here, we examine the potential mechanistic basis of these differences by leveraging recent advances in visualising the learned representations of a coupled classifier and generative deep neural network—an approach we call ‘computational (neuro)phenomenology’. Examining three aetiologically distinct populations in which VHs occur—Neurodegenerative conditions (Parkinson’s Disease and Lewy Body Dementia), visual loss (Charles Bonnet Syndrome, CBS), and psychedelics—we identified three dimensions relevant to distinguishing these classes of VHs: realism (veridicality), dependence on sensory input (spontaneity), and complexity. By selectively tuning the parameters of the visualisation algorithm to reflect influence along each of these phenomenological dimensions we were able to generate ‘synthetic VHs’ that were characteristic of the VHs experienced by each aetiology. We verified the validity of this approach experimentally in two studies that examined the phenomenology of VHs in Neurodegenerative and CBS patients, and in people with recent psychedelic experience. These studies confirmed the existence of phenomenological differences across these three dimensions between groups, and crucially, found that the appropriate synthetic VHs were rated as being representative of each group’s hallucinatory phenomenology. Together, our findings highlight the phenomenological diversity of VHs associated with distinct causal factors and demonstrate how a neural network model of visual phenomenology can successfully capture the distinctive visual characteristics of hallucinatory experience.

Abstract Individuals with prodromal symptoms of Lewy body disease (LBD), such as rapid eye movement sleep behavior disorder (RBD), often showed imaging defects similar to patients with Parkinson’s disease and dementia with Lewy bodies. We examined dopamine transporter (DaT) single-photon-emission computed tomography (SPECT) and metaiodobenzylguanidine (MIBG) scintigraphy in 69 high-risk subjects with ≥2 prodromal symptoms (dysautonomia, hyposmia, and probable RBD) and 32 low-risk subjects without prodromal symptoms, whom were identified through a questionnaire survey of health checkup examinees. The high-risk subjects had significantly worse scores on Stroop test, line orientation test, and the Odor Stick Identification Test for Japanese than the low-risk subjects. The prevalence of abnormalities on DaT-SPECT was higher in the high-risk group than in the low-risk group (24.6% vs. 6.3%, p = 0.030). A decreased uptake on DaT-SPECT was associated with motor impairment, and MIBG scintigraphy defects were associated with hyposmia. The simultaneous evaluation of DaT-SPECT and MIBG scintigraphy may capture a wide range of individuals with prodromal LBD.

Objective: To determine the rate of wearing-off effects of monthly and quarterly dosing of fremanezumab based on real-world data. Methods: We conducted an observational, single-center cohort study including 101 high-frequency episodic migraine or chronic migraine patients receiving fremanezumab over a 9-month observation period. Weekly migraine days (WMDs) were assessed by headache diaries. Regarding monthly dosing, comparisons of WMDs were performed between week (W) 1–2 and W3–4 and between W2 and W4 in months 3, 6 and 9. Regarding quarterly dosing, comparisons of WMDs were performed between W1–2 and W11–12 and between W2 and W12 in the first, second and third quarters. Wearing-off effects were defined as a >1 day increase in WMDs at any of the 3 time points. Results: There was no increase in mean WMDs at the end or the second half of the week in the monthly and quarterly dosing groups over 9 months. Wearing-off effects occurred in 6.7–11.7% of the 60 patients in the monthly dosing group and 9.8% of the 41 patients in the quarterly dosing group. Conclusion: Our findings of a low incidence of wearing-off effects support the sustainability of the effect of fremanezumab as headache prophylaxis.

ObjectiveParkinson’s disease (PD) is characterized by various non-motor symptoms (NMS), such as constipation, olfactory disturbance, sleep disturbance, mental disorders, and motor symptoms. This study aimed to investigate factors associated with NMS in patients with PD.MethodsSymptoms of PD were evaluated using the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Parts I–IV. NMS was assessed using the MDS-UPDRS Part I (self-assessment of NMS) and rapid eye movement sleep behavior disorder (RBD) questionnaires. Patients were categorized by age into

This study focused on demonstrating how to design riding behavior-based collision avoidance systems (RB-CAWS). Statistical and machine learning algorithms were adopted and analyzed previously collected data from the riding simulator-based experiments. The experiments involved 23 participants who completed a 20 km course under four driving conditions, including high and low arousal and positive and negative valence emotional states. Our analysis started by implementing structural equation modeling (SEM) to examine the relationship between riding behaviors measured by speed variability and lateral instability and how these factors influence riding performance. Results revealed that lateral instability strongly affects riding performance. The average lateral deviation from the center of the lane (DCavg) and rolling entropy (RE) were clarified as more influential riding behaviors. Next, using the decision tree (DT) algorithm, significant thresholds for DCavg and RE were determined as 0.302m and 0.019, respectively. The neural network (NN) algorithm was also adopted and defined 0.5 as the optimal threshold value at a combined risk level. We compared the models based on their collision prediction accuracy and found that the DT model performed better with an accuracy rate of 80% compared to the NN model's accuracy rate of 76%. Using the identified thresholds, we highlighted potential warning systems and provided a framework for developing an RB-CAWS that integrates SEM and DT analysis techniques. This study can benefit researchers of motorcyclists' riding behavior and designers of advanced rider assistance systems (ARAS).

Key Clinical Message Even if cardiac rhythm deteriorated to asystole in the clinical course of fulminant myocarditis, cardiac function may recover, and the patient may be discharged without brain damage, if circulation could be maintained by appropriate mechanical cardiac supports. Abstract A 69‐year‐old man was diagnosed with fulminant myocarditis with circulatory collapse. His cardiac rhythm deteriorated to asystole on the second day; however, circulatory status was maintained through extracorporeal membrane oxygenation and intra‐aortic balloon pumping. After 38 h‐lasting asystole, his heart resumed beating. He was discharged without neurological deficits on Day 25.

Heat stroke may cause multi-organ dysfunction and death. Some patients with neurological abnormalities in the acute phase have neurological sequelae, particularly cerebellar ataxia, in the recovery phase. However, there is no method to predict the neurological prognosis, and the usefulness of imaging has not yet been established. We report the case of an 86-year-old woman with dementia brought to our emergency department in a coma and hyperthermia. The patient was diagnosed with heat stroke and promptly treated in the ICU but remained unconscious. The patient gained consciousness on day 19, but difficulty with stillness associated with cerebellar ataxia in her right upper extremity became apparent. On day 1, head magnetic resonance imaging (MRI) showed no obvious abnormality. However, on day 6, high-signal areas, suggestive of edema, were seen in the bilateral cerebellar hemispheres. Single-photon emission computed tomography (SPECT) on day 9 revealed significant hypoperfusion in the right cerebellum. These changes improved at the time of hospital discharge. This was a case of persistent cerebellar ataxia due to heat stroke, in which imaging findings improved over time. In most cases, MRI findings do not match clinical symptoms. However, the low cerebral blood flow in the early SPECT images was consistent with the clinical symptoms. MRI may not be a prognostic indicator; however, SPECT images may be useful for predicting sequelae.

BackgroundThe effectiveness of fremanezumab in treating migraine has been demonstrated in randomized controlled trials. However, real-world study results are still limited.MethodsWe conducted a single-center, observational study that included patients with episodic migraine (EM) and chronic migraine (CM) who received fremanezumab monthly or quarterly over 6-month periods. The primary outcome of this study was to evaluate changes in monthly migraine days (MMD) and responder achievement after treatment with fremanezumab. The secondary aim was to characterize the predictors of responder at 6 months. We also evaluated the effectiveness of fremanezumab in the patients who switched from other calcitonin gene-related peptide (CGRP) monoclonal antibodies, and compared the effectiveness of fremanezumab between the monthly and quarterly dosing groups. One hundred twenty-seven patients with migraine (age, 45.2 ± 12.6 years; 96 women) who received at least one dose of fremanezumab with ≥3 months of follow-up were included. The number of MMD was assessed by headache diary.ResultsThe changes in MMD from baseline at 1, 3, and 6 months were −6.1 ± 4.7, −7.7 ± 4.4, and − 8.5 ± 4.5 days in the total cohort, respectively (p

Hyperuricemia often accompanies hypertension, diabetes, dyslipidemia, metabolic syndrome, and chronic renal disease; it is also closely related to cardiovascular disease. Moreover, several epidemiological studies have linked hyperuricemia and ischemic stroke. However, uric acid may also have neuroprotective effects because of its antioxidant properties. An association between low uric acid levels and neurodegenerative diseases has been suggested, which may be attributed to diminished neuroprotective effects as a result of reduced uric acid. This review will focus on the relationship between uric acid and various neurological diseases including stroke, neuroimmune diseases, and neurodegenerative diseases. When considering both the risk and pathogenesis of neurological diseases, it is important to consider the conflicting dual nature of uric acid as both a vascular risk factor and a neuroprotective factor. This dual nature of uric acid is important because it may help to elucidate the biological role of uric acid in various neurological diseases and provide new insights into the etiology and treatment of these diseases.

Abstract Global warming increases heatstroke incidence. After heatstroke, patients exhibit neurological symptoms, suggesting cerebellar damage. However, the potential long-term adverse outcomes are poorly understood. We studied the cerebellum after heatstroke in mouse heatstroke models. In this study, motor coordination disorder significantly appeared 3 weeks after heatstroke and gradually improved to some extent. Although white matter demyelination was detected at 1 and 3 weeks after heatstroke in the cerebellum, it was not found in the corpus callosum. The Purkinje cell numbers significantly decreased at 1, 3, and 9 weeks after heatstroke. The intensity of synaptophysin and postsynaptic density-95 temporarily appeared to attenuate at 3 weeks after heatstroke; however, both appeared to intensify at 9 weeks after heatstroke. Motor coordination loss occurred a few weeks after heatstroke and recovered to some extent. Late-onset motor impairment was suggested to be caused by cerebellar dysfunctions morphologically assessed by myelin staining of cerebellar white matter and immunostaining of Purkinje cells with pre- and postsynaptic markers. Purkinje cell number did not recover for 9 weeks; other factors, including motor coordination, partially recovered, probably by synaptic reconstruction, residual Purkinje cells, and other cerebellar white matter remyelination. These phenomena were associated with late-onset neurological deficits and recovery after heatstroke.

BackgroundSleep disturbances and excessive daytime sleepiness (EDS) are common non-motor symptoms in patients with Parkinson's disease (PD). The purpose of this study was to identify the contributors to sleep disturbances, including insomnia, restless legs syndrome, rapid eye movement sleep behavior disorder (RBD), sleep-disordered breathing, nocturnal akinesia and EDS, in patients with PD.MethodsWe conducted a cross-sectional study including 128 consecutive Japanese patients with PD. Sleep disturbances and EDS were defined as a PD Sleep Scale-2 (PDSS-2) total score ≥15 and an Epworth Sleepiness Scale (ESS) score >10, respectively. The patients were divided into four groups according to the presence or absence of sleep disturbances and EDS. We evaluated the disease severity, motor symptoms, cognition, olfactory test, the Scales for Outcomes in PD-Autonomic dysfunction (SCOPA-AUT), the Beck Depression Inventory-II (BDI-II), and the RBD Screening Questionnaire Japanese version (RBDSQ-J).ResultsOf 128 patients, 64 had neither EDS nor sleep disturbances, 29 had sleep disturbances without EDS, 14 had EDS without sleep disturbances, and 21 had both EDS and sleep disturbances. Patients with sleep disturbances had higher BDI-II scores than those without sleep disturbances. Probable RBD was more frequent in patients with both sleep disturbances and EDS than in those with neither EDS nor sleep disturbances. The SCOPA-AUT score was lower in patients with neither EDS nor sleep disturbances than in patients in the other three groups. Using multivariable logistic regression analysis with neither sleep disturbances nor EDS as a reference group, that the SCOPA-AUT score was an independent contributor to sleep disturbances (adjusted OR, 1.192; 95% CI, 1.065–1.333; P = 0.002) or EDS (OR, 1.245; 95% CI, 1.087–1.424; P = 0.001) and that the BDI-II (OR, 1.121; 95% CI, 1.021–1.230; P = 0.016) and RBDSQ-J scores (OR, 1.235; 95% CI, 1.007–1.516; P = 0.043) as well as the SCOPA-AUT score (OR, 1.137; 95% CI, 1.006–1.285; P = 0.040) were independent contributors to both sleep disturbances and EDS.ConclusionsAutonomic symptoms were associated with patients with sleep disturbances or EDS, and depressive and RBD symptoms in addition to autonomic symptoms were associated with patients with both sleep disturbances and EDS.

Abstract Background Patients with antibodies against leucine-rich glioma-inactivated 1 (LGI1) present with limbic encephalitis, which is clinically characterized by a subacute disturbance of memory and behavior, often experience seizures. Most patients have a monophasic course, often with hyponatremia. Case presentation Herein, we report a 67-year-old Japanese male presenting with involuntary neck movement, abnormal behavior and apraxia. He was disoriented to time and place and occasionally unable to follow directions. Laboratory tests revealed the patient had hyponatremia (131 mEq/L). Cerebrospinal fluid (CSF) analysis showed that the cell count (1/μL) and protein content (33 mg/dL) were in the normal ranges. Electroencephalography showed transient theta bursts in the right frontal lobe. Magnetic resonance imaging (MRI) of the brain demonstrated hyperintensities in the medial temporal lobe and basal forebrain on fluid-attenuated inversion recovery (FLAIR) without gadolinium enhancement. Anti-voltage-gated potassium channel (Anti-VGKC) complex antibodies were below the reference level for limbic encephalitis. Although the diagnosis was unknown, intravenous methylprednisolone therapy was effective. Three years later, the patient began to speak incoherently and became disoriented to time. FLAIR MRI of the brain revealed recurrence in the left medial temporal lobe. The patient’s serum sodium level was 131 mEq/L. After intravenous methylprednisolone therapy, he regained alertness. A CSF sample stored at the time of the first attack was assayed and the patient was found to be LGI1-positive and CASPR-2-negative, and the diagnosis of anti-LGI1 encephalitis was made. Conclusions Monitoring serum sodium levels and the preserved samples from the first episode were useful for diagnosis.

Abstract Background Levodopa remains the most effective symptomatic treatment for Parkinson’s disease (PD) more than 50 years after its clinical introduction. However, the onset of motor complications can limit pharmacological intervention with levodopa, which can be a challenge when treating PD patients. Clinical data suggest using the lowest possible levodopa dose to balance the risk/benefit. Istradefylline, an adenosine A2A receptor antagonist indicated as an adjunctive treatment to levodopa-containing preparations in PD patients experiencing wearing off, is currently available in Japan and the US. Preclinical and preliminary clinical data suggested that adjunctive istradefylline may provide sustained antiparkinsonian benefits without a levodopa dose increase; however, available data on the impact of istradefylline on levodopa dose titration are limited. The ISTRA ADJUST PD study will evaluate the effect of adjunctive istradefylline on levodopa dosage titration in PD patients. Methods This 37-week, multicenter, randomized, open-label, parallel-group controlled study in PD patients aged 30–84 years who are experiencing the wearing-off phenomenon despite receiving levodopa-containing medications ≥ 3 times daily (daily dose 300–400 mg) began in February 2019 and will continue until February 2022. Enrollment is planned to attain 100 evaluable patients for the efficacy analyses. Patients will receive adjunctive istradefylline (20 mg/day, increasing to 40 mg/day) or the control in a 1:1 ratio, stratified by age, levodopa equivalent dose, and presence/absence of dyskinesia. During the study, the levodopa dose will be increased according to symptom severity. The primary study endpoint is the comparison of the cumulative additional dose of levodopa-containing medications during the treatment period between the adjunctive istradefylline and control groups. Secondary endpoints include changes in efficacy rating scales and safety outcomes. Discussion This study aims to clarify whether adjunctive istradefylline can reduce the cumulative additional dose of levodopa-containing medications in PD patients experiencing the wearing-off phenomenon, and lower the risk of levodopa-associated complications. It is anticipated that data from ISTRA ADJUST PD will help inform future clinical decision-making for patients with PD in the real-world setting. Trial registration Japan Registry of Clinical Trials, jRCTs031180248 ; registered 12 March 2019.

Abstract Background Sick sinus syndrome (SSS) is known to occur due to lesions in the medulla oblongata. Although medullary lesions have occurred in patients with neuromyelitis optica spectrum disorder (NMOSD), there are few reports of SSS associated with NMOSD. We report a patient with NMOSD who developed refractory nausea, vomiting and SSS as the initial manifestation. Case presentation A 77-year-old female developed refractory nausea and frequent episodes of syncope. The patient was diagnosed with SSS because sinus pauses lasting five to six seconds were observed, and pacemaker implantation was performed. Two months later, she was referred to our hospital because of limb weakness and sensory impairment that progressed over a month. The patient was confirmed to have muscle weakness; manual muscle testing revealed grade 4 in the upper extremities and grade 3 in the lower extremities. Tendon reflexes were diminished, while no pathological reflexes were present. Thermal and pain sensations were impaired in the upper and lower extremities, and vibration sensation was impaired in both lower extremities. Bladder and rectal disturbances were also noted. Optic neuritis was not detected. T2-weighted magnetic resonance imaging (MRI) showed high-intensity lesions in the dorsal part of the medulla oblongata and C3–6 cervical cord. Her serum was positive for antibodies against aquaporin 4, and a diagnosis of NMOSD was made. She was treated with two courses of an intravenous methylprednisolone pulse and one course of plasma exchange. Then, she was transferred to another hospital for rehabilitation. Conclusions Because SSS is a life-threatening complication, clinicians should be aware of the possibility that medullary lesions in NMOSD can cause SSS as the initial manifestation.

Abstract Background Fibrous sclerosing tumours and hypertrophic lesions in IgG4-related disease (IgG4-RD) are formed in various organs throughout the body, but disease in the oral region is not included among individual organ manifestations. We report a case of ossifying fibrous epulis that developed from the gingiva, as an instance of IgG4-RD. Case presentation A 60-year-old Japanese man visited the Department of Oral and Maxillofacial Surgery, Gunma University Hospital, with a chief complaint of swelling of the left mandibular gingiva. A 65 mm × 45 mm pedunculated tumour was observed. The bilateral submandibular lymph nodes were enlarged. The intraoperative pathological diagnosis of the enlarged cervical lymph nodes was inflammation. Based on this diagnosis, surgical excision was limited to the intraoral tumour, which was subsequently pathologically diagnosed as ossifying fibrous epulis. Histopathologically, the ossifying fibrous epulis exhibited increased levels of fibroblasts and collagen fibres, as well as infiltration by numerous plasma cells. The IgG4/IgG cell ratio was > 40%. Serologic analysis revealed hyper-IgG4-emia (> 135 mg/dL). The patient met the comprehensive clinical diagnosis criteria and the American College of Rheumatology and European League Against Rheumatism classification criteria for IgG4-RD. Based on these criteria, we diagnosed the ossifying fibrous epulis in our patient as an IgG4-related disease. A pathological diagnosis of IgG4-related lymphadenopathy was established for the cervical lymph nodes. Concomitant clinical findings were consistent with type II IgG4-related lymphadenopathy. Conclusions A routine serological test may be needed in cases with marked fibrous changes (such as epulis) in the oral cavity and plasma cells, accompanied by tumour formation, to determine the possibility of individual-organ manifestations of IgG4-related disease.

Abstract Background As the prognosis of esophageal cancer surgery has improved, reports on postoperative complications of gastric tubes have increased. Among them, gastric tube ulcer perforation is infrequent but often severe and difficult to treat. Case Presentation A 73‐year‐old man had undergone thoracoscopic subtotal esophagectomy and laparoscopic‐assisted gastric tube reconstruction via the retrosternal route for thoracic esophageal cancer 8 years previously. He was transferred to our hospital with a diagnosis of gastric tube ulcer perforation, penetrating the pericardium. Emergency surgery was performed to remove the gastric tube, followed by immediate reconstruction by right colon interposition. The patient was discharged on postoperative day 142. Conclusion We report a rare complication of gastric tube ulcer perforation, penetrating the pericardium, after esophagectomy for esophageal cancer. It was successfully treated with appropriate surgical management.

Abstract We report the case of a 33‐year‐old man with a self‐inflicted neck wound with severe hypopharynx injury, and hemorrhagic shock, which was well managed by a trauma surgeon trained in esophageal surgery. Training in cervical lymph node dissection for esophageal cancer could be useful in the management of penetrating neck injuries.

Posttraumatic subcutaneous emphysema, which can be benign and noninfectious, is associated with necrotizing fasciitis. Rarely, extensive emphysema occurs after a minor traumatic injury. A 23-year-old man came to our hospital with extensive emphysema, ranging from the left hand to the axilla, after a minor injury. Necrotizing fasciitis was suspected. Based on the blood and imaging tests, necrotizing fasciitis was not actively suspected. He was admitted and observed for one day, and he was discharged the following day. The mechanism by which air can enter through a small injury is unclear, but the one-way ball-valve mechanism is the most commonly proposed explanation. The nontraumatic causes of non-infectious subcutaneous emphysema include insect bites, skin biopsies, and the use of shock absorbers. Since it developed from a minor wound, other mechanisms, aside from the one-way ball-valve, were possibly involved. Based on the imaging results of this case, the air was predominantly distributed in the subcutaneous tissue along the neurovascular bundle. The relatively sparse tissue likely caused the extensive subcutaneous emphysema. While evaluating post-traumatic subcutaneous emphysema, benign and noninfectious cases should be differentiated to prevent unnecessary therapeutic intervention.

As mountainous areas provide abundant water resources to lower elevations, and alpine zones are major recharge areas for water resources, it is important to understand water storage and discharge processes in these zones. Regarding water storage, sedimentary structures (e.g., talus and moraines) in alpine zones function as aquifers. However, the functions of vegetation, thought to contribute to water recharge and storage in forested watersheds, have rarely been investigated. Accordingly, we evaluated the influence of alpine vegetation on water storage processes in alpine zones. Two intensive field surveys were conducted on August 17 and October 5, 2019, in the alpine headwaters of Mt. Norikura in the Northern Japan Alps. Chemical analyses were conducted of rainwater, snowmelt water, and runoff water from bare and vegetated catchments. From the results, a two-component separation was conducted to calculate the contributions of precipitation and groundwater components to runoff water. Our results implied that runoff water from vegetated catchments was in contact with the regolith for longer, with the contribution of groundwater being higher in this runoff water. Moreover, the groundwater component contribution tended to increase as the ratio of vegetation area to bare area in each catchment increased, suggesting a higher water storage function for vegetated areas. In other words, the subsurface water flow should be slower in vegetated areas due to the presence of vegetated soils compared to bare areas where coarse-grained sediments are dominant. Accordingly, the alpine vegetated area has a higher water storage function than the alpine bare area.

Abstract A cross-sectional study of 21,665 Japanese residents was performed to investigate the prevalence of central sensitization syndromes (CSS). CSS were assessed using the Central Sensitization Inventory (CSI-A). CSS were defined as a CSI-A score of 40 or higher. Age, sex, district, 10 CSS-related diseases (CSI-B), lifestyle, and mental factors were rated in a self-reported survey. The prevalence of CSS and its relationship with potential factors were examined by sex using descriptive and logistic regression models. The prevalence of CSS was 4.2% in all participants and was significantly higher in women (4.9%) than in men (2.7%). Adjusted odds ratios correlated with CSS for an age of 80–97 years versus 60–79 years (2.07 and 2.89), one or more CSI-B diseases (3.58 and 3.51), few sleeping hours (2.18 and 1.98), high perceived stress (5.00 and 4.91), low (2.94 and 2.71) and high (0.45 and 0.66) resilience versus moderate resilience, and exercise habits (0.68 and 0.55) in men and women (all P

Abstract Aim Glyphosate‐containing herbicides are less toxic than paraquat and are one of the most widely used herbicides today. Case presentation We report a case of ingestion of a pesticide containing glyphosate in a suicide attempt. The patient was admitted to the psychiatric department because of persistent suicidal thoughts. He suffered from short‐term memory impairment on day 3. Magnetic resonance imaging (MRI) showed swelling in the bilateral medial temporal lobes and hippocampi and high signal on T2‐weighted images. Gradually, the patient's cognitive impairments improved, and he was discharged on day 33. Conclusion A physician should examine the patient with the possibility of glyphosate encephalopathy in mind.

In critically ill patients requiring intensive care, increased oxidative stress plays an important role in pathogenesis. Sedatives are widely used for sedation in many of these patients. Some sedatives are known antioxidants. However, no studies have evaluated the direct scavenging activity of various sedative agents on different free radicals. This study aimed to determine whether common sedatives (propofol, thiopental, and dexmedetomidine (DEX)) have direct free radical scavenging activity against various free radicals using in vitro electron spin resonance. Superoxide, hydroxyl radical, singlet oxygen, and nitric oxide (NO) direct scavenging activities were measured. All sedatives scavenged different types of free radicals. DEX, a new sedative, also scavenged hydroxyl radicals. Thiopental scavenged all types of free radicals, including NO, whereas propofol did not scavenge superoxide radicals. In this retrospective analysis, we observed changes in oxidative antioxidant markers following the administration of thiopental in patients with severe head trauma. We identified the direct radical-scavenging activity of various sedatives used in clinical settings. Furthermore, we reported a representative case of traumatic brain injury wherein thiopental administration dramatically affected oxidative-stress-related biomarkers. This study suggests that, in the future, sedatives containing thiopental may be redeveloped as an antioxidant therapy through further clinical research.

Redox-active organic materials have emerged as promising alternatives to inorganic electrode materials in electrochemical devices owing to advantages such as low cost and flexible design. However, the kinetics of their electrochemical reactions are typically slow due to the slow diffusion of organic materials dissolved in the electrolyte. Generally, peak separation of the redox reaction is observed (mass-transfer-controlled system), while no peak separation is obtained when the active molecules, such as high surface carbon material, are adsorbed onto the electrode material (adsorption-controlled system). Aromatic compounds confined in activated carbon (AC) micropores exhibit an adsorption-controlled reaction, improving the reaction kinetics. To elucidate this behavior, a well-defined and accurate understanding of the pore geometry is required. Although various synthetic techniques have been used to tune the micropore size, these afford different surface properties. This study reports an approach to achieve an adsorption-controlled redox reaction of quinone-based molecules and a tool to analyze their reaction environment. AC micropores sized

Abstract Objective Sensory hypersensitivities such as photophobia, phonophobia, and osmophobia are common in patients with migraine. We investigated the burden of these multiple sensory hypersensitivities in migraine. Methods In this cross-sectional study, 187 consecutive patients with migraine (26 men/161 women; age, 45.9 ± 13.2 years) were included. Sensory hypersensitivity symptoms such as photo−/phono−/osmophobia and accompanying symptoms were determined by neurologists in interviews. The Migraine Disability Assessment (MIDAS) was used to assess headache-related disability. The Kessler Psychological Distress Scale (K6) was also administered. Results Photophobia, phonophobia and osmophobia were observed in 75.4%, 76.5% and 55.1% of the patients with migraine, respectively. A significant overlap in sensory hypersensitivities (photo−/phono−/osmophobia) was found; the proportions of patients with 2 and 3 coexisting sensory hypersensitivities were 33.2% and 41.7%, respectively. The MIDAS score was higher in those with 3 sensory hypersensitivity symptoms than in those with 0 to 2 sensory hypersensitivity symptoms. A generalized linear model with ordinal logistic regression analysis revealed that multiple sensory hypersensitivities, younger age, more migraine days per month, and a higher K6 score were significantly related to the higher MIDAS score. Conclusion Our study showed that sensory hypersensitivities commonly occur and overlap in patients with migraine and that multiple sensory hypersensitivity symptoms have a significant impact on headache-related disability.

Abstract Background Neurolymphomatosis (NL) is a rare manifestation of malignant lymphoma that shows selective infiltration to the peripheral nervous system primarily or secondarily. We report a patient with secondary NL caused by germinal center B-cell (GCB)-type diffuse large B-cell lymphoma (DLBCL) who showed selective infiltration of the lumbar plexus to the spinal cord and massive nerve enlargement resulting in severe pain. Case presentation A 72-year-old female exhibited asymmetric motor and sensory impairments and pain in the lower limbs that progressed for five months. Magnetic resonance imaging (MRI) showed an enlarged lumbar plexus, which continued to the cauda equina via the L3 and L4 spinal nerves. Her symptoms gradually worsened. Ten months after the onset of symptoms, the enlarged cauda equina filled the spinal canal space, and the spinal cord was swollen. A cauda equina biopsy was performed, and she was diagnosed with GCB-type DLBCL with CD10 positivity. The primary tumor was found in a mammary cyst. The autopsy study did not show apparent infiltration, except in the nervous system. Conclusions Although there are many neurologic phenotypes of malignant lymphoma, the association between the cytological characteristics of lymphoma and the neurological phenotypes is still unclear. Several reports of CD10-positive secondary NL are available, whereas peripheral or central nervous tissue origin lymphoma cases are mostly negative for CD10. CD10 staining may be useful for distinguishing primary NL from secondary NL. NL often has a strong organotropism for peripheral nervous tissue, which makes early diagnosis challenging.