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Objective Dementia with Lewy bodies (DLB) is the second-most common form of neurodegenerative dementia after Alzheimer's disease (AD). Falls are a vital prognostic factor in patients with dementia and are a characteristic feature of DLB. This study investigated the screening potential of the fall risk evaluation for DLB and compared it with that of AD to facilitate an accurate diagnosis. Methods We enrolled patients diagnosed with DLB (n = 410) and AD (n = 2,683) and categorized the participants into 3 groups depending on their physical ability, age, cognitive function, and fall events. Using the Fall Risk Index-21 (FRI-21) questionnaire, we evaluated and comparatively analyzed the fall risk between DLB and AD patients in three defined groups of participants. Results The FRI-21 score was significantly higher in DLB patients than in AD patients in every group. Using this score, we were able to distinguish between DLB and AD patients in each group. Among the three groups, the group with a young age, relatively mild cognitive dysfunction, and no fall events exhibited the best specificity for DLB (0.895). Conclusions The FRI-21 is a useful tool for screening for DLB and differentiating it from AD. This questionnaire can be used at a relatively early stage of the disease in young patients with mild cognitive dysfunction and no history of falling. These preliminary results need to be validated in an interventional study to evaluate the effectiveness of rehabilitative measures and daily environmental changes carried out to prevent falls using this tool.

Total internal reflection is an optical imaging technique for nanoparticle tracking and observation employing the scattered light from an evanescent field near the interface or reference surface. Generally, the nanoparticle behavior is the three-dimensional Brownian motion in an aqueous medium. The motion can be traced by an optical microscopy, but it cannot be traced by an electron microscopy technique. In the three-dimensional nanoparticle moving position, the X and Y positions are parallel to the surface, which can be traced by the general microscopy techniques. However, the height position Z of a nanoparticle perpendicular to the surface could not be traced without the longitudinal scanning method. Here, a novel method is proposed to investigate the 3D position of nanoparticles by applying multi-wavelength evanescent fields microscopy, which has a high spatial resolution in the Z-direction without longitudinal scanning. This paper focuses on the verification of measurement in the Z-direction. A piezoelectric actuator was employed to control the nanoparticle displacement in height Z. Standard polystyrene 100 nm particles were randomly adhered on a spherical tip that connected with the piezoelectric actuator. The spherical tip was essentially made from an optical adhesive (n = 1.348) with a refractive index close to the water for decreasing the unnecessary signal from the tip-self during nanoparticle observation in the water. The proposed method could obtain the multi-wavelength scattering lights from the observed nanoparticles by an 8-bit color camera with higher than 50 frames per second recording to investigate the 3D nanoscale tracking. The X and Y positions of nanoparticles were determined by the centroid of the scattering light intensities. The height Z was determined from the logarithm ratios between the detected scattering light intensities of both wavelengths. The measurement repeatability of the absolute difference in height between nanoparticles could be measured less than ±16 nm by using the proposed method. The penetration height measurability range was approximated at 250 nm from the reference surface.

Background To assess the health care burden of elderly patients with heart failure (HF) in an aging Japanese community-based hospital, we investigated the outcomes of cardiac rehabilitation. Methods and Results We enrolled all patients with HF aged ≥65 years admitted to 3 hospitals in the Niigata Prefecture. We prospectively collected data on their hospital stays and for 2 years postdischarge. The cohort comprised 617 patients (46.5% men; mean age 84.7 years), 76.2% of whom were aged ≥80 years. Among these patients, 15.6% were nursing home residents, 57.7% required long-term care insurance, only 37.6% could walk unaided at the time of admission, and 70.5% required cardiac rehabilitation; age had no significant rehabilitative effect on the degree of improvement in activities of daily living (ADLs). Two years postdischarge, all-cause mortality, and HF rehospitalization were 41.1% and 38.6%, respectively. The ADL score at discharge was an independent prognostic factor for mortality. The incidence of mortality and rehospitalization was lower in elderly patients with preserved ADLs at discharge. Conclusions Elderly patients with HF in our super-aged society were mainly octogenarians who required disease management and personalized care support. Although their ADL scores increased with comprehensive cardiac rehabilitation, improved scores at discharge were closely associated with prognosis.

Factors causing atrial tachyarrhythmia recurrence after catheter ablation (CA) of atrial fibrillation (AF) remain undetermined. This study aimed to investigate the effect of nocturnal hypoxemia on the recurrence of atrial tachyarrhythmia after CA of AF. Among 594 patients with AF who underwent an ambulatory sleep study at the National Cerebral and Cardiovascular Center, Suita, Osaka, Japan (2014–2019), 365 underwent CA of AF; 290 patients who underwent CA were followed up for > 3 months. Multivariate Cox regression analysis was used to calculate hazard ratios (HRs) using clinical variables, to identify the independent predictors of atrial tachyarrhythmia recurrence after the final CA. Atrial tachyarrhythmia recurred in 45 of 290 (15.5%) patients during the median follow-up period of 479 days (interquartile range 225–1002). On the performing multivariate analysis of the data of patients who did not receive continuous positive airway pressure (CPAP), severe nocturnal hypoxemia [defined as the percentage of sleep time spent with SaO2 of

Sleep disturbances are among the common nonmotor symptoms in patients with Parkinson’s disease (PD). Sleep can be disrupted by nocturnal motor and nonmotor symptoms and other comorbid sleep disorders. Rapid eye movement sleep behavior disorder (RBD) causes sleep-related injury, has important clinical implications as a harbinger of PD and predicts a progressive clinical phenotype. Restless legs syndrome (RLS) and its related symptoms can impair sleep initiation. Excessive daytime sleepiness (EDS) is a refractory problem affecting patients’ daytime activities. In particular, during the COVID-19 era, special attention should be paid to monitoring sleep problems, as infection-prevention procedures for COVID-19 can affect patients’ motor symptoms, psychiatric symptoms and sleep. Therefore, screening for and managing sleep problems is important in clinical practice, and the maintenance of good sleep conditions may improve the quality of life of PD patients. This narrative review focused on the literature published in the past 10 years, providing a current update of various sleep disturbances in PD patients and their management, including RBD, RLS, EDS, sleep apnea and circadian abnormalities.

Background: The coronavirus disease 2019 (COVID-19) pandemic has negatively affected the mental health of the general population. Objective: We investigated the determinants of quality of life (QOL) in Parkinson’s disease (PD) patients during the COVID-19 pandemic. Methods: Impacts of lifestyle changes due to the COVID-19 pandemic on 100 patients with PD and their caregivers/spouses were assessed. The Hospital Anxiety and Depression Scale was used to assess anxiety and depression. The physical component summary (PCS) and mental component summary (MCS) scores of the short form (SF)-8 were used to evaluate health-related QOL. Results: Regarding health-related QOL, physical function, role physical, general health, vitality and the PCS score were significantly worse in PD patients than in caregivers. Worsening of PD-related symptoms, increased stress, and decreased physical activity were observed in 29.0%, 37.0% and 44.0% of PD patients, respectively. Sixteen patients (16.0%) experienced problems with hospital access, but none reported medication shortages. Strong concerns about COVID-19 were reported by 47.0% of caregivers and 50.0% of PD patients. In PD patients, increased gait disturbance and rigidity, disease severity, smoking, the levodopa equivalent dose and decreased body weight predicted a worse PCS score; anxiety, depression, female sex, stress and long disease duration predicted a worse MCS score. In caregivers, age and smoking contributed to a worse PCS score; depression, stress and worsening patient mood contributed to a worse MCS score. Conclusion: We report the negative impacts of the COVID-19 pandemic on health-related QOL and its determinants in PD patients and their caregivers.

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., The patient presented with delayed and transient short‐term memory impairment due to glyphosate medication. MRI showed bilateral medial temporal lobe and hippocampal swelling and high signal on T2‐weighted images, high signal in the right predominant insular cortex on diffusion‐weighted images, and high signal in the hippocampus and insular cortex on T2FLAIR.

Purpose Tissue engineering of esophagus is required for management of long-gap esophageal atresia (LGEA). Collagenous connective tissue membranes fabricated by in-body tissue architecture (iBTA), called biosheets, can repair esophageal defects and generate tissues similar to native esophagus. However, iBTA requires second-stage surgery because of heterotopic preparation of biosheets. Our aim was to develop orthotopic iBTA for primary engineering of the esophagus by interposing a tubular mold to the esophageal defect. Method The cervical esophagus of six rats was transected. An acrylic tube (internal diameter 2.6 mm, length 7.0 mm) was inserted and fixed between the ends of the upper and lower esophagus, and a 3 mm-long esophageal defect was created. Four weeks later, the rats were sacrificed for histological analysis. Results Postoperatively the rats could intake liquid food. After four weeks, the esophageal defects were filled with regenerated tissues. Histologically the new esophageal walls stained positive for collagen type I. The inner surfaces were covered with stratified squamous epithelium that expressed pan-cytokeratin. In only one of six rats, regeneration of muscular-like tissue was suggested by positive immunohistochemical staining for desmin. Conclusion Orthotopic iBTA can regenerate a substitute esophagus with esophageal epithelium and collagenous wall. This technique may be a novel treatment for esophageal atresia with gaps of various lengths including LGEA.

Atrial tachycardia (AT) and atrial fibrillation (AF) commonly occur after cardiac surgeries (CSs). This study investigated the mechanisms and long-term outcomes of AT and AF ablation after various Maze procedures, particularly whether atrial tachyarrhythmias after the Maze procedure occur due to gaps in the Maze lines. We analyzed 37 consecutive cases with atrial tachyarrhythmias after the Maze procedures and concomitant CSs between 2007 and 2019. Fifty-nine atrial tachyarrhythmias were induced in 37 consecutive cases, and 49 of those atrial tachyarrhythmias were mappable ATs. Forty ATs were related to the Maze procedures in the 49 mappable ATs (81.6%). All 37 consecutive cases had residual electrical conductions (gaps) in the Maze lines (88 gaps; 2.4 ± 1.2 gaps/patient). Forty of 88 gaps (45.5%) were associated with gap-related ATs. The common ATs in this study were 1. peri-mitral atrial flutter due to gaps at pulmonary vein isolation (PVI) line to mitral valve annulus (MVA) (20 cases), and 2. peri-tricuspid atrial flutter due to gaps at right atrial incision to the tricuspid valve annulus (TVA) (10 cases). Forty-seven of 49 ATs (95.9%) were successfully ablated at the first session, and there were no complications. The mean follow-up period after ablation was 3.6 ± 3.2 (median, 2.1; interquartile range, 0.89-6.84) years. The Kaplan-Meier analysis of freedom from recurrent atrial tachyarrhythmias after Maze procedure was 82.7% at 1-year follow-up and 75.5% at 4-year follow-up after a single procedure. Reentry was the main mechanism of ATs after Maze procedures and concomitant CSs, and ATs were largely related to the gaps on the Maze lines between the PVI line and the MVA or those on the lines between right atrial incision to the TVA. Long-term follow-up data suggest that catheter ablation of atrial tachyarrhythmias after various Maze procedures is effective and safe.

Background Pancreatic trauma is reportedly associated with high morbidity and mortality. Main pancreatic duct (MPD) injury is critical for treatment. Methods As a study project of the Japanese Society for Abdominal Emergency Medicine (JSAEM), we collected the data of 163 patients with pancreatic trauma who were diagnosed and treated at JSAEM board‐certified hospitals from 2006 to 2016. Clinical backgrounds, diagnostic approaches, management strategies, and outcomes were evaluated. Results Sixty‐four patients (39%) were diagnosed as having pancreatic trauma with MPD injury that resulted in 3% mortality. Blunt trauma and isolated pancreatic injury were independent factors predicting MPD injury. Nine of 11 patients with MPD injury who were initially treated nonoperatively had serious clinical sequelae and five (45%) required surgery as a secondary treatment. Among all cases, the detectability of MPD injury of endoscopic retrograde pancreatography (ERP) was superior to that of other imaging modalities (CT or MRI), with higher sensitivity and specificity (sensitivity = 0.96; specificity = 1.0). Conclusions Acceptable outcomes were observed in pancreatic trauma patients with MPD injury. Nonoperative management should be carefully selected for MPD injury. ERP is recommended to be performed in patients with suspected MPD injury and stable hemodynamics., Highlight Ando and colleagues analyzed data from 163 patients with pancreatic trauma in a nationwide multicenter study. They found that serum amylase and C‐reactive protein levels were significantly higher in patients with main pancreatic duct injuries, indicating that endoscopic retrograde pancreatography was the most accurate imaging modality for assessing pancreatic duct injury.

Purpose Oral adverse events, such as dental inflammation with exacerbation, are stressful and lead to poor nutrition in patients undergoing cancer therapy. Thus, the prediction of risk factors for dental inflammation with exacerbation is important before cancer therapy is initiated. We hypothesized that, during cancer therapy (DIECT), fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) imaging could be useful to predict dental inflammation with exacerbation. Methods We enrolled 124 patients who underwent FDG-PET/CT for diagnostic staging before cancer treatment. We then assessed DIECT outcomes after basic perioperative oral treatment. Moreover, we evaluated clinical parameters, therapeutic strategies, periodontal examination (probing depth (PD) and bleeding on probing (BOP)), dental imaging, and FDG-PET/CT imaging results of patients with and without DIECT. Furthermore, PET/CT images were assessed as per the FDG accumulation of the dental lesion (PAD) grading system. Results Univariate analysis demonstrated significant differences in age, periodontal examination (PD and BOP), and PAD grade between patients with and without DIECT. Furthermore, multivariate logistic regression analysis identified independent predictive factors for a positive periodontal examination (PD) (odds ratio (OR) 5.9, 95% confidence interval (CI) 1.8–19.7; P = 0.004) and PAD grade (OR 11.6, 95% CI 3.2–41.2; P = 0.0002). In patients with cancer, PAD grade using FDG-PET/CT imaging was an independent and informative risk factor for DIECT. Conclusion Our results suggested that, for patients with DIECT, periodontal examination and PAD grade were independent predictive factors. Hence, regardless of the presence or absence of any lesion on dental imaging, PAD grade might be an additional tool, in addition to periodontal examination that potentially improves oral care management.

[Purpose] To clarify the relationship between changes in deoxygenated hemoglobin level due to cycling exercise and body composition in healthy participants with unilateral lower-limb obstruction. [Participants and Methods] The height, weight, body mass index, and body composition (skeletal muscle mass, body water content, and body fat percentage) of nine healthy males were measured along with the anaerobic threshold. The protocol consisted of 7 minutes of rest followed by 4 minutes of cycling exercise (anaerobic threshold level) with unilateral lower extremity occlusion. After exercise, ischemia was released, and the participants was allowed rest for 5 minutes. Deoxygenated hemoglobin levels before and after the exercise and the relationship between the level of variation and each index were examined. [Results] Body water content and skeletal muscle mass showed a significant negative correlation with changes in deoxygenated hemoglobin level; however, no correlation was found for the other indices. Body water content and skeletal muscle mass were found to be significantly positively correlated. they showed a significant positive correlation with deoxygenated hemoglobin levels. [Conclusion] Our study indicates that body water content and skeletal muscle mass play a significant role in the recovery of blood flow following exercise.

We describe an autopsied patient with familial parkinsonism and unclassified four repeat-tau (4R-tau) aggregation. She presented with bradykinesia, truncal dystonia, and mild amnesia at the age of 61 and then exhibited body weight loss (15 kg over 8 months), sleep disturbances, and progressive respiratory failure with CO2 narcosis. She died of respiratory failure at the age of 62, 14 months after disease onset. Her brother also showed parkinsonism at the age of 58 and suddenly died 6 months later. Postmortem examination revealed 4R-tau aggregation, which was characterized by neuronal globose-type tangles or pretangles, bush-like or miscellaneous astrocytic inclusions, and coiled bodies. The temporal tip, the striatum, the substantia nigra, the tegmentum of the midbrain, the medullary reticular formation, and the spinal cord were severely involved with tau aggregation. Argyrophilic grains and ballooned neurons were also found in the medial temporal structures, however, extensions of the 4R-aggregations in the case were clearly broader than those of the argyrophilic grains. Western blot analysis of sarkosyl-insoluble fractions from brain lysates revealed prominent bands of tau at both 33 kDa and 37 kDa. Genetic examinations did not reveal any known pathogenic mutations in MAPT, DCTN-1, PSEN-1, or familial or young-onset parkinsonism-related genes. The clinical manifestations, pathologic findings, and biochemical properties of aggregated tau in our patient cannot be explained by argyrophilic grain disease or other known 4R-tauopathies alone. Our results further extend the clinical and neuropathologic spectra of 4R-tauopathy.

Aim: This study aimed to compare the surgical outcomes of patients with the intermediate-type imperforate anus who underwent laparoscopically assisted anorectoplasty (LAARP; L group) with those of ...

The present study aimed to survey the prevalence of prodromal symptoms of Parkinson’s disease (PD) in Japanese health checkup examinees, for identifying at-risk subjects. We conducted a questionnaire survey of annual health checkup examinees without neurological symptoms using the following self-reported questionnaires: Japanese version of the Scale for Outcomes in Parkinson’s disease for Autonomic Symptoms (SCOPA-AUT); Self-administered Odor Question (SAOQ); REM Sleep Behavior Disorder Screening Scale (RBDSQ); Beck Depression Inventory-Second Edition (BDI-II); Epworth Sleepiness Scale (ESS); and Physical Activity Scale for the Elderly (PASE). The presence of prodromal symptoms was determined using the 90th percentile threshold of each questionnaire. Subjects ≥ 50 years of age with ≥ 2 core prodromal symptoms (dysautonomia, hyposmia, and RBD), were classified as at risk. Between March 2017 and March 2018, 4,953 participants sufficiently answered the questionnaires. Among 2,726 subjects ≥ 50 years of age, 155 were classified as at risk. These subjects had worse values of BDI-II (12.0 ± 8.3 vs. 4.4 ± 3.8, p

Clinical features and imaging findings of maxillo-mandibular actinomycosis are similar to those of intraosseous carcinoma. The purpose of this study is to clarify the characteristics of the imaging findings for screening of maxillo-mandibular actinomycosis using CT and PET. Reports on maxillo-mandibular actinomycosis published between 1997 and 2016 were searched in PubMed using “actinomycosis,” “maxilla,” and “mandibular” as keywords. Ten cases suspected to have malignant tumors on diagnostic imaging findings were selected. In addition, three patients who visited Gunma University Hospital were also included. The 13 total cases were subjected to a pooled analysis of diagnostic screening of maxillo-mandibular actinomycosis using CT, 18F-FDG-PET/CT (FDG-PET/CT) and 18F-α-methyl tyrosine PET/CT (FAMT-PET/CT). Additionally, cases of intraosseous carcinoma were analyzed as comparative controls to investigate the difference between maxillo-mandibular actinomycosis and intraosseous carcinoma on CT imaging. CT images of the 13 cases with maxillo-mandibular actinomycosis were investigated; spotty-type bone resorption was observed in 66.7% (8/12). Moreover, FDG-PET/CT showed abnormal accumulation, but FAMT-PET/CT showed no apparent abnormal accumulation. Clinical and imaging findings of maxillo-mandibular actinomycosis are similar to those of intraosseous carcinoma. Differential diagnostic screening can confirm spotty-type bone resorption in cortical bone with CT and specific accumulation in malignant tumors with FAMT-PET/CT. This screening facilitates the rapid implementation of therapeutic interventions.

Purpose To enhance the utility of acceleration time (AcT) in the diagnosis of internal carotid artery (ICA) stenosis, we assessed the value of AcT measurements with different waveform patterns. Methods Ninety-three patients with acute atherothrombotic cerebral infarction were enrolled, and they underwent both carotid ultrasonography and digital subtraction angiography (DSA). AcT was determined by a conventional procedure (using the first peak point or the bending point) and the peak systolic velocity (PSV) procedure. The AcT ratio was calculated as (AcT of ICA)/(AcT of the ipsilateral common carotid artery). We evaluated the correlation of stenosis rate as assessed by the North American Symptomatic Carotid Endarterectomy Trial method using DSA (DSA-NASCET) with the AcT of ICA (ICA-AcT), the AcT ratio measured by the conventional procedure (conventional AcT ratio), and the AcT ratio measured by the PSV procedure (PSV AcT ratio). The area under receiver operating characteristic curves (AUC) for DSA-NASCET was calculated based on the ICA-AcT and AcT ratio. Results Forty-five vessels had 50% or greater ICA stenosis. DSA-NASCET was positively correlated with the conventional AcT ratio (r = 0.723), conventional ICA-AcT (r = 0.638), and PSV AcT ratio (r = 0.245). The corresponding AUCs for ICA stenosis ≥ 50% were 0.971, 0.886, and 0.572, respectively. Conclusion We demonstrated the usefulness of the conventional procedure for diagnosing stenosis of ICA origin using AcT and showed that the AcT ratio was a more beneficial parameter than AcT.

Background An early clinical differentiation between Parkinson's disease (PD) and multiple system atrophy (MSA) or progressive supranuclear palsy (PSP) remains a challenge. The purpose of this study was to evaluate the usefulness of the combination use of midbrain-to-pontine ratio (M/P ratio) from magnetic resonance imaging (MRI) with cardiac 123I-metaiodobenzylguanidine (MIBG) uptake for differentiating PD from MSA and PSP. Methods Ninety-six parkinsonian patients (70 PD, aged 68.5 ± 9.5 years; 16 MSA, aged 67.9 ± 7.5 years; 10 PSP, aged 70.4 ± 9.4 years) who underwent MRI and cardiac MIBG scintigraphy were included in this study. Receiver operating characteristic (ROC) curve analysis was used to assess the sensitivity and specificity for distinguishing PD from MSA and PSP patients. The diagnostic accuracy of these tests was also assessed among patients at the early disease stage (defined as patients with a disease duration of 3 years or less). Results The individual diagnostic sensitivity of the M/P ratio and cardiac MIBG scintigraphy was 87.1% and 67.1% in PD vs. MSA and 78.6% and 67.1% in PD vs. PSP, respectively. The diagnostic specificity of the M/P ratio and cardiac MIBG scintigraphy was 56.3% and 100% in PD vs. MSA and 70.0% and 90% in PD vs. PSP, respectively. With the optimal cutoff values, at least one positive result (either the M/P ratio or cardiac MIBG revealed abnormalities) improved sensitivity (95.7%) without decrease of specificity (56.3%) in PD vs. MSA, as well as in PD vs. PSP (100% sensitivity, 70.0% specificity). In contrast, both positive results of two tests had good specificity but low sensitivity in PD vs. MSA (60.0% sensitivity and 100% specificity) and in PD vs. PSP (47.1% sensitivity and 90% specificity). Similar trends were observed in early-stage patients. Conclusion Although M/P ratio alone was potentially useful for distinguishing PD from MSA or PSP, the combined use with cardiac MIBG scintigraphy can further improve the diagnostic accuracy of PD from MSA or PSP.

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

Background: Alzheimer’s disease (AD) is conceptualized as a biological continuum encompassing the preclinical (clinically asymptomatic but with evidence of AD pathology) and clinical (symptomatic) phases. Objective: Using 18F-THK5351 as a tracer that binds to both tau and monoamine oxidase B (MAO-B), we investigated the changes in 18F-THK5351 accumulation patterns in AD continuum individuals with positive amyloid PET consisting of cognitively normal individuals (CNp), amnestic mild cognitive impairment (aMCI), and AD and cognitively normal individuals (CNn) with negative amyloid PET. Methods: We studied 69 individuals (32 CNn, 11 CNp, 9 aMCI, and 17 AD) with structural magnetic resonance imaging, 11C-Pittsburgh compound-B (PIB) and 18F-THK5351 PET, and neuropsychological assessment. 18F-THK5351 accumulation was evaluated with visual analysis, voxel-based analysis and combined region of interest (ROI)-based analysis corresponding to Braak neurofibrillary tangle stage. Results: On visual analysis, 18F-THK5351 accumulation was increased with stage progression in the AD continuum. On voxel-based analysis, there was no statistical difference in 18F-THK5351 accumulation between CNp and CNn. However, a slight increase of the bilateral posterior cingulate gyrus in aMCI and definite increase of the bilateral parietal temporal association area and posterior cingulate gyrus/precuneus in AD were detected compared with CNn. On ROI-based analyses, 18F-THK5351 accumulation correlated positively with supratentorial 11C-PIB accumulation and negatively with the hippocampal volume and neuropsychological assessment. Conclusion: The AD continuum showed an increase in 18F-THK5351 with stage progression, suggesting that 18F-THK5351 has the potential to visualize the severity of tau deposition and neurodegeneration in accordance with the AD continuum.

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.

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.

Objectives To assess the impacts of social situation changes due to the coronavirus disease 2019 (COVID-19) pandemic on headache-related disability and other symptoms in patients with migraine in Japan. Methods We conducted a multicentre, cross-sectional study including 659 outpatients with migraine diagnosed by headache specialists. The participants were asked about the impacts of the first wave of the COVID-19 pandemic on headache-related disability, headache days, headache intensity, stress, physical activity, hospital access and their work and home lives. For headache-related disability, the total Migraine Disability Assessment (MIDAS) score and part A and B scores were analysed. Multivariate stepwise linear regression analysis was performed to identify the clinical predictors of changes in the total MIDAS score before and during the COVID-19 pandemic. Logistic regression analysis was performed to determine the factors related to new-onset headache during the COVID-19 pandemic. Results Finally, 606 migraine patients (73 M/533 F; age, 45.2 ± 12.0 years) were included in the study, excluding those with incomplete data. Increased stress, substantial concern about COVID-19 and negative impacts of the first wave of the COVID-19 pandemic on daily life were reported in 56.8 %, 55.1 and 45.0 % of the participants, respectively. The total MIDAS and A and B scores did not significantly change after the first wave of the COVID-19 pandemic. New-onset headache, which was observed in 95 patients (15.7 %), was associated with younger age and worsened mood and sleep in the logistic regression analysis. The multivariate stepwise linear regression analysis of changes in the total MIDAS score before and during the first wave of COVID-19 pandemic identified worsened sleep, increased acute medication use, increased stress, medication shortages, comorbidities, the absence of an aura and new-onset headache were determinants of an increased total MIDAS score during the first wave of the COVID-19 pandemic. Conclusions In this multicentre study, clinical factors relevant to headache-related disability, such as new-onset headache, stress and sleep disturbances, were identified, highlighting the importance of symptom management in migraine patients during the first wave of the COVID-19 pandemic.

Background & Aims: The purpose of this study is to identify the clinical and immunohistological factors that inhibit bone healing after extirpation of extensive radicular cysts and endodontic microsurgery-microscopic apicoectomy, and utilize these factors as predictors of treatment outcome. Methods: Endodontic microsurgery-microscopic apicoectomy was performed in 26 patients. Outcomes were evaluated based on clinical signs and radiographs. Expression levels of cytokines (IL-1β, TNF-α, RANKL) in the cyst epithelium and subepithelial connective tissue were also investigated. Results: The success rate was 88.5%. The radiological reduction rate was ≥75% in 16 patients (good bone healing) and

Spinal and bulbar muscular atrophy (SBMA) is a progressive hereditary neuromuscular disease caused by the testosterone-dependent accumulation of pathogenic polyglutamine-expanded androgen receptor protein. A 41-year-old man with SBMA received the androgen deprivation agent leuprorelin acetate for 7 years in clinical trials and underwent castration following the trial. Suppression of testosterone levels for 14 years resulted in a slower disease progression, as measured prospectively with quantitative measurements, than the historical control data reported in previous studies. This suggests that long-term androgen deprivation delays disease progression in SBMA.

Introduction Despite an urgent need for developing remedial measures against dementia, no disease-modifying drugs have been developed. Efficient protocols for participant recruitment need to be established for conducting clinical trials. To meet this need, a large-scale online registry system, the Integrated Registry of Orange Plan (IROOP®), was created for healthy individuals. Although the risk factors for dementia have been discussed in our previous studies for a short interval of 6 months, some factors remain controversial. The present study aimed to explore factors affecting longitudinal changes in cognitive function for a longer interval of 18 months using the IROOP® data. Methods This study assessed the longitudinal changes in the collated data for predicting the risk of dementia and included 473 individuals (175 men and 298 women; mean age 59.6 ± 10.1 years) registered in the IROOP® between July 5, 2016 and January 15, 2018 who completed the initial questionnaire and brief assessment of cognitive function (Mild Cognitive Impairment Screen) at baseline and the regular questionnaire and the Mild Cognitive Impairment Screen at least once after baseline. Statistical analyses were performed using IBM SPSS, version 23.0, for Windows for demographic data and the MIXED procedure in SAS, version 9.4, for the linear mixed-effect model. In each analysis, the statistical significance level was set at P, Highlights • Mood consistently influences on longitudinal changes of cognitive function. • Sleep is also an important factor for maintaining cognitive function. • Given the multifactorial etiology of dementia, multidomain prevention is required.

Cleaning process is indispensable in Post chemical mechanical polishing (Post-CMP) to remove the abrasive nano-particles remaining on the polished wafer surface. There are two main types of the cleaning process. One is contact cleaning with polyvinyl alcohol (PVA) sponge brush scrubbing, and the other is non-contact cleaning enforced with mega sonic by piezoelectric unit or dual (gas-liquid phase spray) jet cleaning. We have been focusing on the phenomenon of PVA brush contact cleaning process. Generally, cleaning phenomenon is considered as abrasive nano-particle behaviors, which are removed from a wafer surface and occasionally reattach to the surface or still stay on the surface to be a residual contamination. However, these contaminations on a wafer surface are usually inspected before and after cleaning process, not during the cleaning process. Hence, we have been duplicated experimental cleaning process of thin film material on a silica glass surface, and have also been proposing a real time observing method to inspect the removal of abrasive nano-particle behaviors during the cleaning process. Because these behaviors occur in a few hundred nm range from the wafer surface. Therefore, an evanescent light that localizes on the surface being cleaned in range of a few hundred nm can be applied to limitedly optically illuminate to observe either abrasive nano-particle behaviors or PVA brush movement. By this optical illumination, the contaminated nano-particles and/or PVA brush existing in an evanescent field will scatter their evanescent field to be the propagating light, which can reach to a camera in a microscopy to visualize the brush scrubbing cleaning phenomenon (figure(a)). However, both scattering lights from PVA brush and nano-particles are same wavelength of illuminated laser. In this paper, 100±20 nm fluorescence silica-nano-particles were employed to identify the contaminated silica particles by fluorescent wavelength (λ=600 nm) that different from the illuminated laser wavelength (λ=450 nm). A typical result of optical method is shown in figure(b). A silica particle that was already adhered on a glass surface was removed by sliding of PVA brush in pure water. Evidently, fluorescence scattering light (red light intensity : λ=600 nm) and PVA brush scattering light (blue light intensity : λ=450 nm) could be distinguished in the recorded phenomenon in rate of 120 frame per second by a RGB color camera. Before coming of PVA brush, 100 nm silica particle already adhered on a glass surface. Next, PVA brush moved with a sliding speed of 2.5 mm per second by a rotation motor. Where the sliding speed was calculated by distance of PVA brush movement during 1/120 s (≈8.3 ms). Then, 100 nm silica particle was removed from surface after 33.3 ms as quantitatively shown in figure(c). These results imply that nano-particle was removing away at the same time during the attachment of PVA brush to the nano-particle or the approach near to the nano-particle. By using evanescent field and fluorescent nano-particle, we can observe nanoscale cleaning phenomenon during PVA brush scrubbing in real time. Figure 1

Background We investigated serum insulin-like growth factor (IGF)-1 levels in patients with neurodegenerative diseases and correlated these levels with clinical parameters. Methods One hundred and fifty-six patients with neurodegenerative diseases were included in this study, and serum IGF-1 levels were determined. Results Serum IGF-1 levels (mean ± standard error) were not significantly different among the patients with different neurodegenerative diseases: Parkinson's disease (PD; n = 73), 112.1 ± 5.1 ng/mL; progressive supranuclear palsy (n = 15), 102.9 ± 8.3 ng/mL; multiple system atrophy (n = 22), 103.1 ± 37.6 ng/mL; Alzheimer's disease (AD; n = 18), 102.2 ± 9.4 ng/mL; amyotrophic lateral sclerosis (n = 6), 105.5 ± 27.4 ng/mL; dementia with Lewy bodies (n = 14), 82.4 ± 7.4 ng/mL; frontotemporal dementia (n = 6), 90.0 ± 17.0 ng/mL; and corticobasal syndrome (n = 2), 118.0 ± 14.0 ng/mL. In patients with PD, serum IGF-1 levels were negatively correlated with age and modified Rankin scale (mRS) scores and positively correlated with the striatal dopamine transporter-specific binding ratio and the frontal assessment battery score. In patients with AD, serum IGF-1 levels were negatively correlated with age, disease duration, and mRS scores. Conclusion We found correlations of serum IGF-1 levels with frontal lobe and striatal dopaminergic function and disability in PD patients and with disability in AD patients. The usefulness of measuring serum IGF-1 levels for monitoring disease progression in neurodegenerative diseases requires further studies.

A 33-year-old man presented with slowly progressive weakness in the lower extremities over 8 years. At the age of 16 years, the elevation of serum creatine kinase level was detected. Physical examination revealed scapular winging, exaggerated lumbar lordosis and tendoachilles contracture. Gowers sign was positive and proximal dominant limb weakness was noted. Hypertrophy was observed in the upper limbs such as the biceps brachii and forearm flexor muscles. Muscle biopsy showed distinct differences in size of muscle fibers and regenerating and necrotic muscle fibers. A histological study revealed decreased calpain3 expression. Gene analysis of CAPN3 revealed two known gene mutations, leading to a diagnosis of calpainopathy (limb girdle muscular dystrophy 2A; LGMD2A). We here report our patient to discuss findings of upper limb hypertrophy, which are frequently missed compared to the lower limb, but important clinical findings.

Background: Minimally invasive Maze procedure via right mini-thoracotomy approach is reportedly a promising option for paroxysmal and non-paroxysmal atrial fibrillation (AF), although it is not widely performed. This study aimed to validate feasibility and safety of minimally invasive stand-alone Maze procedure in an institutional first case series. Methods: This study enrolled an institutional consecutive series of 20 cases who underwent minimally invasive Maze procedure between November 2018 and January 2021. Concomitant tricuspid annuloplasty was performed in five cases who showed moderate tricuspid regurgitation preoperatively. Results: Minimally invasive Maze procedure using cryo-energy source was successfully accomplished with sinus rhythm being restored at the intensive care unit entry in all cases without conversion to the sternotomy approach. All cases were discharged home, while one case was complicated with stroke postoperatively. Nineteen cases (95%) showed sinus rhythm at the last follow-up, whereas one case, who had large left atrium, showed recurrent persistent AF despite optimum medical therapy. Catheter ablations were performed for residual conductions at box lesions and/or mitral/tricuspid isthmus in three cases, who showed medically refractory atrial tachycardia post-Maze procedure. Consequently, these three cases showed sinus rhythm restoration at the last follow-up Conclusions: Minimally invasive stand-alone Maze procedure with or without tricuspid annuloplasty was feasible and safe for AF in the institutional first case series. Catheter ablations for recurrent AF post-Maze procedure would be warranted.

Background: Heatstroke is a life-threatening disease that causes body fluid loss and electrolyte abnormalities due to exposure to high ambient temperature (AT) and relative humidity (RH). Recently, global warming has increased the number of heatstroke patients worldwide. Aquaporin 1 (AQP1) is a water-selective protein that plays an important role in water homeostasis. However, the role of AQP1 in heatstroke has not been elucidated yet. Therefore, in this study, we examined the role of endothelial AQP1 using Tie2-Cre/LNL-AQP1 double transgenic (dTG) mice with an upregulation of aqp1 on endothelial cells. Methods: Tie2-Cre/LNL-AQP1 dTG mice were generated by breeding CAG-LNL(STOP)-AQP1 Tg and Tie2-Cre Tg mice. The transgenes were evaluated in the brain because brain vessels do not express aqp1. For production of experimental heatstroke, the mice were kept in a heatstroke chamber that was pre-heated at 41 °C AT and >99% RH for 1 h, and the blood, brain, kidney, and liver were collected 24 h later. Blood samples were analyzed for biochemical parameters such as electrolytes and tissue damage markers, and the organs were examined via morphological and immunohistological (3-nitrotyrosine (3-NT), AQP1, and Iba-1) staining. Results: Although no difference was observed in aqp1 expression in the whole brain, aqp1 was detected only in Tie2-Cre/LNL-AQP1 dTG mice after capillary deprivation. Moreover, AQP1 immunostaining also revealed immunoreaction in blood vessels. After heat exposure, electrolyte abnormalities were observed in both the wild and Tie2-Cre/LNL-AQP1 dTG mice compared to non-heat stroke wild mice. Hepatic damage markers, aspartate aminotransferase and alanine aminotransferase, were increased, and serum lactate dehydrogenase levels were significantly higher in Tie2-Cre/LNL-AQP1 dTG mice than in wild mice. Hematoxylin-eosin staining and 3-NT immunoreactivity in the liver also supported hepatic damage. Moreover, the number of hepatic vasculature adherent Iba-1 positive cells was significantly higher in Tie2-Cre/LNL-AQP1 dTG mice than in wild mice. Conclusions: In the present study, for the first time, we suggested that endothelial AQP1 contributes to hepatic damage after heatstroke.

Background: Secretory carcinoma (SC) is a malignancy of the salivary glands, which is similar to SC of the breast in terms of its association with neurotrophic tyrosine receptor kinase (NTRK) fusion-positive gene. SC is a recently described salivary gland tumor, and there are few reports describing oral minor salivary gland-derived SC. We reported two cases of SC in the oral cavity and reviewed the literature.Case presentation: The patients included a 65-year-old Japanese woman presented with a mass of the upper lip and an 84-year-old Japanese man presented with a mass on the buccal mucosa, respectively. Diagnosis was based on histomorphological and immunohistochemical findings and identification of a specific translocation of the ETS variant 6-neurotrophic receptor tyrosine kinase 3 (ETV6-NTRK3) gene fusion. Case 1 was finally diagnosed using reverse transcription-polymerase chain reaction using formalin-fixed paraffin-embedded tissue samples, while case 2 was diagnosed using fluorescence in situ hybridization analysis. Conclusion: It is highly likely for many cases of SC to be initially diagnosed as acinic cell carcinoma (AciCC) owing to their similar histological findings. The treatment strategy for minor salivary gland-originated SC is the same as that for AciCC, but SC is often highly malignant and involves a high risk of cervical lymph node metastasis. Making an accurate diagnosis in cooperation with pathologists and confirming the presence of the ETV6-NTRK3 fusion gene using genetic analysis is important.

Displaced rib fractures can injure intercostal vessels leading to chest wall hematomas. As the bleeding occurs within the vessel, compression of the vessel wall helps in preventing further bleeding. Therefore, chest wall hematomas rarely result in shock. A thin 78-year-old man transferred to the emergency department with complaints of left dorsal pain due to an injury. He had a history of hypertension and aorta dissection. He arrived at the ED in a state of shock and presented with a large left dorsal wall mass. Subsequent imaging using computed tomography angiography revealed a large hyperdense hematoma at the left dorsal-flank wall along with rib fracture (11th intercostal artery). Moreover, a large fusiform aneurysm was detected from the abdominal aorta to the iliac arteries. Extravasation of the contrast agent was detected at the branch of the 11th intercostal artery, and hence, embolization was performed. The dermis, which comprises collagen and elastin fibers, plays an important role in vessel compression to prevent bleeding. The aortic media also comprises collagen and elastin fibers. Cell turnover, loss of collagen, and excessive elastolysis are associated with the formation of abdominal aortic aneurysms. The systemic degeneration of connecting tissue (collagen and elastin fiber) appears to be progress in patients with an aortic aneurysms and history of aortic dissection compared with other healthy older individuals. Physicians should be cognizant of the potential unexpected large hematoma complications if a risk of systemic connecting tissue degradation exists, as seen in patients with aortic aneurysm or aortic dissection.

Background: We hypothesized that rotigotine may have a positive effect on cognitive function in patients with Parkinson’s disease (PD) by improving daytime motor function and nighttime sleep status due to its 24-hour sustained properties.Methods: We evaluated the effect of rotigotine on motor symptoms, cognitive function, daytime sleepiness, sleep disturbances, and motor symptoms in 10 PD patients with sleep disturbances, defined as a PD Sleep Scale (PDSS)-2 score of ≥ 15, in a single-center, 3-month open-label study. Participants received 24 mg/24 h (patch content: 4.5-9 mg) rotigotine for a 3-month period. At baseline and 3 months, patients were evaluated on the Movement Disorder Society Revision of the Unified PD Rating Scale (MDS-UPDRS) parts III and IV and cognitive assessments, such as the Mini-Mental State Examination (MMSE), frontal assessment battery (FAB) and Montreal Cognitive Assessment (MoCA). The Epworth Sleepiness Scale (ESS) and PDSS-2 were administered at baseline and at 1 month, 2 months and 3 months.Results: At 3 months, MDS-UPDRS part III (-10.7, pConclusion: Our preliminary findings suggest that low-dose rotigotine could improve motor symptoms, sleep disturbance, and cognitive function without worsening daytime sleepiness in patients with PD.

Background Rapid eye movement sleep behavior disorder (RBD) and olfactory dysfunction are useful for early diagnosis of Parkinson’s disease (PD). RBD and severe olfactory dysfunction are also regarded as risk factors for cognitive impairment in PD. This study aimed to assess the associations between RBD, olfactory function, and clinical symptoms in patients with PD. Methods The participants were 404 patients with non-demented PD. Probable RBD (pRBD) was determined using the Japanese version of the RBD screening questionnaire (RBDSQ-J) and the RBD Single-Question Screen (RBD1Q). Olfactory function was evaluated using the odor identification test for Japanese. Clinical symptoms were evaluated using the Movement Disorder Society Revision of the Unified PD Rating Scale (MDS-UPDRS) parts I–IV. Results In total, 134 (33.2%) patients indicated a history of pRBD as determined by the RBD1Q and 136 (33.7%) by the RBDSQ-J based on a cutoff value of 6 points. Moreover, 101 patients were diagnosed as pRBD by both questionnaires, 35 by the RBDSQ-J only, and 33 by the RBD1Q only. The MDS-UPDRS parts I–III scores were significantly higher and disease duration significantly longer in the pRBD group. pRBD was significantly associated with male gender and the MDS-UPDRS part I score. The olfactory identification function was significantly reduced in the pRBD group. Conclusions About 33% of the patients with PD had pRBD based on the questionnaires, and both motor and non-motor functions were significantly decreased in these patients. These results suggest that more extensive degeneration occurred in patients with non-demented PD with RBD.

Background. The role of central sensitization in refractory pain-related diseases has not yet been clarified. Methods. We performed a multicenter case-controlled study including 551 patients with various neurological, psychological, and pain disorders and 5,188 healthy controls to investigate the impact of central sensitization in these patients. Symptoms related to central sensitization syndrome (CSS) were assessed by the Central Sensitization Inventory (CSI) parts A and B. Patients were categorized into 5 groups based on CSI-A scores from subclinical to extreme. The Brief Pain Inventory (BPI), addressing pain severity and pain interference with daily activities, and the Patient Health Questionnaire (PHQ)-9, assessing depressive symptoms, were also administered. Results. CSI-A scores and CSI-B disease numbers were significantly greater in patients than in controls ( p < 0.001 ). Medium effect sizes (r = 0.37) for CSI-A scores and large effect sizes (r = 0.64) for CSI-B disease numbers were found between patients and control groups. Compared with the CSI-A subclinical group, the CSI-A mild, moderate, severe, and extreme groups had significantly higher BPI pain interference and severity scores, PHQ-9 scores, and CSS-related disease numbers based on ANCOVA. Greater CSI-B numbers resulted in higher CSI-A scores ( p < 0.001 ) and a higher odds ratio ( p for trend