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Although some sex differences in stroke have been reported, differences in the effects of antiplatelet therapy for secondary stroke prevention have not been clarified.In the Cilostazol Stroke Prevention Study combination trial, patients with high-risk, non-cardioembolic ischemic stroke between 8 and 180 days after onset treated with aspirin or clopidogrel alone were recruited and randomly assigned to receive either monotherapy or dual antiplatelet therapy (DAPT) using cilostazol and followed up for 0.5-3.5 years. The primary efficacy outcome was recurrence of ischemic stroke. The safety outcome was severe or life-threatening hemorrhage. Outcomes were analyzed by sex.A total of 1,320 male patients and 558 female patients were included. The male patients had more risk factors than the female patients. In male patients, the primary endpoint occurred at a rate of 2.0 per 100-patient years in the DAPT group and 5.1 per 100 patient-years in the monotherapy group (hazard ratio (HR), 0.40; 95% confidence interval (CI), 0.23-0.68). In male patients, DAPT prolonged the time to recurrent stroke by 4.02-fold (95% CI, 1.63-9.96) compared with monotherapy. In female patients, the average annual event rates were 2.7 per 100 patient-years in the DAPT group and 3.3 per 100 patient-years in the monotherapy group (HR, 0.82; 95% CI, 0.37-1.84). Safety outcomes did not differ significantly in both male and female patients.Long-term DAPT using cilostazol reduced the recurrence of ischemic stroke and prolonged the recurrence-free time in male patients, but not in female patients.

Supplemental Digital Content is available in the text., Background and Purpose: Although dual antiplatelet therapy (DAPT) with aspirin and clopidogrel reduces the recurrence of ischemic stroke while significantly increasing the bleeding events compared with monotherapy, the CSPS.com trial (Cilostazol Stroke Prevention Study combination) showed that DAPT using cilostazol was more effective without the bleeding risk. In the CSPS.com trial, aspirin or clopidogrel was used as the underlying antiplatelet drug. The effectiveness and safety of each combination were examined and clarified. Methods: In the CSPS.com trial, a multicenter, open-label, randomized controlled study, patients with high-risk, noncardioembolic ischemic stroke 8 to 180 days after onset treated with aspirin or clopidogrel alone at the discretion of the physician in charge were recruited. Patients were randomly assigned to receive either monotherapy or DAPT using cilostazol and followed for 0.5 to 3.5 years. The primary efficacy outcome was first recurrence of ischemic stroke. The safety outcome was severe or life-threatening bleeding. The analysis was based on the underlying antiplatelet agents. Results: A total of 763 patients taking aspirin and 1116 taking clopidogrel were included in the intention-to-treat analysis. Although the clopidogrel group had more risk factors than the aspirin group, the primary efficacy outcome and safety outcome did not differ significantly between the 2 groups. In the aspirin group, the primary efficacy outcome and safety outcome did not differ significantly between the DAPT group and the aspirin-monotherapy group. In the clopidogrel group, the primary end point occurred at a rate of 2.31 per 100 patient-years in the DAPT group and 5.19 per 100 patient-years in the clopidogrel-monotherapy group (hazard ratio, 0.447 [95% CI, 0.258–0.774]). Safety outcome did not differ significantly between groups (0.51 per 100 patient-years versus 0.71 per 100 patient-years, respectively; hazard ratio, 0.730 [95% CI, 0.206–2.588]). Conclusions: The combination of cilostazol and clopidogrel significantly reduced the recurrence of ischemic stroke without increasing the bleeding risk in noncardioembolic, high-risk patients. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01995370. URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000012180.

Ground-based light detection and ranging (LiDAR) is becoming increasingly popular as an alternative means to conventional forest inventory methods. By gauging the distances to multiple points on the surrounding object surfaces, LiDAR acquires 3D point clouds from which tree sizes and spatial distributions can be rapidly estimated. However, the high cost and specialized skills associated with LiDAR technologies have put them out of reach for many potential users.We here introduce ForestScanner, a free, mobile application that allows LiDAR-based forest inventories by means of iPhone or iPad with a built-in LiDAR sensor. ForestScanner does not require any manual analysis of 3D point clouds. As the user scans trees with an iPhone/iPad, ForestScanner estimates the stem diameters and spatial coordinates based on real-time instance segmentation and circle fitting. The users can visualize, check, and share the scanning results in situ.By using ForestScanner, we measured the stem diameters and spatial coordinates of 672 trees within a 1 ha plot in 1 h 39 min with an iPhone and in 1 h 38 min with an iPad (diameter ≥5 cm; detection rate = 100%). The diameters measured by ForestScanner and a diameter tape were in good agreement; R2=0.963 for iPhone and R2=0.961 for iPad. ForestScanner and a conventional surveying system showed almost identical results for tree mapping (assessed by the spatial distances among trees within 0.04 ha subplots); Mantel R2=0.999 for both iPhone and iPad. ForestScanner reduced the person-hours required for measuring diameters to 25.7%, mapping trees to 9.3%, and doing both to 6.8% of the person-hours taken using a dimeter tape and the conventional surveying system.Our results indicate that ForestScanner enables cost-, labor-, and time-efficient forest inventories. The application can increase the accessibility to LiDAR for non-experts (e.g., students, citizen scientists) and enhance resource assessments and biodiversity monitoring in forests worldwide.

An 82-year-old man presented with subacute bilateral lower limb paralysis, deep sensory disturbance, and vesico-rectal disturbance. MRI of the spinal cord revealed a large gray matter-dominant lesion extending from the medulla oblongata to the lower thoracic spinal cord. The patient was treated with steroid-pulse therapy for myelitis, but without symptomatic improvement. A spinal cord biopsy was performed for treatment-resistant myelopathy, and histopathology revealed a diffuse large B-cell lymphoma, that was diagnosed as a primary intramedullary spinal cord lymphoma because systemic examination didn't show any other findings suggestive of malignant lymphoma. A spinal cord biopsy is necessary for the definitive diagnosis of this disease, but in the case of poor response to treatment and a progressive course, intramedullary malignant lymphoma should be considered if there is a persistent elevation of CSF IL-10 or a prolonged contrast effect.

Background Long‐term benefit of dual antiplatelet therapy (DAPT) over single antiplatelet therapy (SAPT) for the prevention of recurrent stroke has not been established in patients with intracranial arterial stenosis. We compared the efficacy and safety of DAPT with cilostazol and clopidogrel or aspirin to those of SAPT with clopidogrel or aspirin in patients with intracranial arterial stenosis, who were recruited to the Cilostazol Stroke Prevention Study for Antiplatelet Combination trial, a randomized controlled trial in high‐risk Japanese patients with ischemic stroke. Methods and Results We compared the vascular and hemorrhagic events between DAPT and SAPT in patients with ischemic stroke and symptomatic or asymptomatic intracranial arterial stenosis of at least 50% in a major intracranial artery. Patients were placed in two groups: 275 were assigned to receive DAPT and 272 patients SAPT. The risks of ischemic stroke (hazard ratio [HR], 0.47; 95% CI, 0.23–0.95); and composite of stroke, myocardial infarction, and vascular death (HR, 0.48; 95% CI, 0.26–0.91) were lower in DAPT than SAPT, whereas the risk of severe or life‐threatening bleeding (HR, 0.72; 95% CI, 0.12–4.30) did not differ between the 2 treatment groups. Conclusions DAPT using cilostazol was superior to SAPT with clopidogrel or aspirin for the prevention of recurrent stroke and vascular events without increasing bleeding risk among patients with intracranial arterial stenosis after stroke. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01995370.

Background and ObjectivesLong-term treatment with the combination of cilostazol with aspirin or clopidogrel showed a lower risk of stroke recurrence compared to aspirin or clopidogrel alone after high-risk noncardioembolic ischemic stroke in a randomized trial. We aimed to determine whether the effect of the dual medication compared to monotherapy on risk of recurrent ischemic stroke differs according to timing of starting medication after stroke onset.MethodsIn a subanalysis of the randomized controlled trial, patients between 8 and 180 days after stroke onset were randomly assigned to receive aspirin or clopidogrel alone or a combination of cilostazol with aspirin or clopidogrel. They were divided into 3 groups according to the timing of starting trial treatment: between 8 and 14 days after stroke onset (8–14 days group), between 15 and 28 days after stroke onset (15–28 days group), and between 29 and 180 days after stroke onset (29–180 days group). The primary efficacy outcome was the first recurrence of ischemic stroke. Safety outcomes included severe or life-threatening bleeding.ResultsOf 1,879 patients, 498 belonged to the 8–14 days group, 467 to the 15–28 days group, and 914 to the 29–180 days group. There was a significant treatment-by-subgroup interaction for the recurrence of ischemic stroke between trial treatment and trichotomized groups. The recurrence of ischemic stroke was less common with dual therapy than with monotherapy in the 15–28 days group (annualized rate 1.5% vs 4.9%, respectively; adjusted hazard ratio 0.34 [95% CI 0.12–0.95]) and the 29–180 days group (1.9% vs 4.4%, respectively; 0.27 [0.12–0.63]) and similarly common in the 8–14 days group (4.5% for both; 1.02 [0.51–2.04]). Severe or life-threatening bleeding occurred similarly between patients on dual therapy and those on monotherapy in any of the trichotomized groups (crude hazard ratio 0.22 [95% CI 0.03–1.88] in the 8–14 days group, 1.07 [0.15–7.60] in the 15–28 days group, and 0.76 [0.24–2.39] in the 29–180 days group).DiscussionLong-term dual antiplatelet therapy using cilostazol starting 15–180 days after stroke onset, compared to therapy started 8–14 days after onset, was more effective for secondary stroke prevention than monotherapy without increasing hemorrhage risk.Trial Registration InformationClinicalTrials.gov NCT01995370; UMIN Clinical Trials Registry 000012180.Classification of EvidenceThis study provides Class II evidence that for patients with acute noncardioembolic stroke taking either aspirin or clopidogrel, the addition of cilostazol 15–180 days after stroke onset decreases the risk of recurrent ischemic stroke.

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Although dual antiplatelet therapy with aspirin and clopidogrel reduces early recurrence of ischaemic stroke, with long-term use this type of therapy is no longer effective and the risk of bleeding increases. Given that cilostazol prevents stroke recurrence without increasing the incidence of serious bleeding compared with aspirin, we aimed to establish whether dual antiplatelet therapy involving cilostazol is safe and appropriate for long-term use.In a multicentre, open-label, randomised controlled trial across 292 hospitals in Japan, patients with high-risk non-cardioembolic ischaemic stroke identified on MRI were randomly assigned to two groups in a 1:1 ratio to receive monotherapy with either oral aspirin (81 or 100 mg, once per day) or clopidogrel (50 or 75 mg, once per day) alone, or a combination of cilostazol (100 mg, twice per day) with aspirin or clopidogrel. Randomisation was done centrally (using block randomisation with a block size of six per each participating hospital) through a web-based registration system and was done by EPS Corporation. The patients were required to have at least 50% stenosis of a major intracranial or extracranial artery or two or more of the vascular risk factors. Trial medication was continued for half a year or longer, for a maximum of 3·5 years. The primary efficacy outcome was the rate of first recurrence of symptomatic ischaemic stroke. Safety outcomes were severe or life-threatening bleeding; any adverse events; serious adverse events; and any bleeding events. Efficacy analyses were done in the intention-to-treat population and safety analyses were done in the as-treated population. This trial was registered with ClinicalTrials.gov (number NCT01995370) and UMIN Clinical Trials Registry (number 000012180).Participants were recruited from Dec 13, 2013, to March 31, 2017. 932 patients assigned to the dual therapy group and 947 patients assigned to the monotherapy group were included in the intention-to-treat analysis. The trial was stopped after the enrolment of 1884 patients of an anticipated 4000 patients because of the delay in recruitment. Ischaemic stroke recurred in 29 (3%) of 932 patients (annualised rate 2·2%) on dual therapy including cilostazol and 64 (7%) of 947 patients (annualised rate 4·5%) on monotherapy during a median 1·4 years follow-up (hazard ratio [HR] 0·49, 95% CI 0·31-0·76, p=0·0010). Severe or life-threatening bleeding occurred in eight patients (annualised rate 0·6%) on dual therapy and 13 patients (annualised rate 0·9%) on monotherapy (HR 0·66, 95% CI 0·27-1·60, p=0·35). Occurrence of any type of adverse event was similar between the groups (255 [28%] of 910 patients in the dual therapy group vs 219 [24%] of 921 patients in the monotherapy group); as was occurrence of serious adverse events (87 [10%] vs 142 [15%]) and bleeding events (38 [4%] vs 33 [4%]). Gastrointestinal bleeding, which affected nine (1%) of 910 patients in the monotherapy group and nine (1%) of 921 patients in the dual therapy group, was the most common type of bleeding.The combination of cilostazol with aspirin or clopidogrel had a reduced incidence of ischaemic stroke recurrence and a similar risk of severe or life-threatening bleeding compared with treatment with aspirin or clopidogrel alone in patients at high risk for recurrent ischaemic stroke.Otsuka Pharmaceutical.

Tumor emboli due to a sarcoma are usually confirmed by an autopsy or operative findings. A sarcoma embolus in an acute stroke patient is rare. We herein report a 37-year-old man with acute stroke caused by internal carotid artery occlusion who underwent embolectomy. A histopathological analysis of an embolus obtained with a mechanical retriever device was diagnosed as undifferentiated sarcoma. This is the first case of extracardiac sarcoma extraction via mechanical retrieval performed during intervention for acute ischemic stroke. A histopathologic evaluation with embolectomy is important for diagnosing tumor emboli.

A 64-year-old man was diagnosed with spinal and bulbar muscular atrophy (SBMA) in 2014, and began gait training with the hybrid assistive limb (HAL) in 2017. We conducted 2 courses of HAL-based gait training and temporary improvement was confirmed both before and after intervention based on evaluation of the 2-minute walking distance, walking speed, and the Timed Up and Go test. HAL-based gait training may be effective for improving and maintaining walking ability in SBMA. However, long-term observation of this patient will be performed.

Hypothalamic orexin-containing neurons are activated by CO2 and contribute to hypercapnic ventilatory activation. However, their role in oxygen-related regulation of breathing is not well defined. In this study, we examined whether an experimental model mimicking apnea-induced repetitive hypoxemia (intermittent hypoxia [IH]) activates orexin-containing neurons. Mice were exposed to IH (5 × 5 min at 10% O2), intermittent hyperoxia (IO; 5 × 5 min at 50% O2), sustained hypoxia (SH; 25 min at 10% O2), or sham stimulation. Their brains were examined using double immunohistochemical staining for orexin and c-Fos. The results indicated that IH (25.8 ± 3.0%), but not SH (9.0 ± 1.5%) activated orexin-containing neurons when compared to IO (5.5 ± 0.6%) and sham stimulation (5.9 ± 1.4%). These results correlate with those of our previous work showing that IH-induced respiratory long-term facilitation is dependent on orexin-containing neurons. Taken together, orexin contributes to repetitive hypoxia-induced respiratory activation and the hypoxic activation of orexin-containing neurons is pattern dependent.

A 78-year old woman who presented with akinetic mutism was admitted to our hospital. Brain MRI showed multifocal increased T

Introduction Therapeutic strategies for pancreatic trauma vary greatly depending on its severity. Surgical intervention is recommended in cases of severe pancreatic injuries for which standard therapy is not advised. We present a two-step treatment method for severe pancreatic injury using an endoscopic ultrasound (EUS)-guided transgastric internal stent. Clinical case A 50 year-old male with blunt abdominal trauma sustained in a traffic accident was transported with vital signs indicating shock and CT findings of complete transection of the proximal pancreas and a huge haematoma. A life-saving primary emergency damage control operation was performed. A secondary EUS-guided transgastric internal stent was placed into the pancreatic fluid collection on post-operative day 8 (POD 8). The pancreatic juice secreted from the transected pancreatic tail eventually flowed along the internal stent and emptied completely into the stomach. The patient did not display prognostic symptoms at discharge. Discussion EUS-guided transgastric internal stenting is currently considered the first line of therapy for pancreatic pseudocysts. It is recommended that pseudocyst drainage occur at least four weeks or more after its formation. In this severe case of blunt pancreatic trauma, the primary damage control operation saved the patient's life. Following primary surgery, a secondary early operation involved insertion of an EUS-guided transgastric internal stent into the collection of pancreatic juice secreted from the transected pancreatic tail, which allowed complete recovery without surgical extraction or reconstruction of the pancreatic tail. Conclusion In cases of severe pancreatic trauma, practitioners should consider the value of early EUS-guided transgastric internal stenting.

Background: Dementia is a new focus of research on improved treatment for Parkinson's disease (PD). In 2007, a screening tool for PD dementia (PD-D) was developed by the Movement Disorder Society (Level I testing), which still requires verification by a large population study. Methods: We conducted a cross-sectional and multicenter study including 13 institutions administering the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) to 304 PD patients (mean age: 70.6 ± 8.3 years; mean Hoehn and Yahr stage: 2.7 ± 0.7). Results: In all, 34.5% of the patients had MMSE scores Conclusions: Level I testing with administration of the MMSE and MoCA is a practical and efficient screening tool for PD-D. However, the phonemic fluency and pentagon copying tests should be replaced by more specific/sensitive ones when screening for PD-D.

Background and Aim The Montreal Cognitive Assessment (MoCA) is the most suitable measure for screening cognitive impairment in Parkinson's disease (PD). However, the utility of the MoCA has not been documented sufficiently, especially in Asian populations. The present multicenter study included a large number of Japanese patients, and compared Mini-Mental State Examination (MMSE) and MoCA scores in PD patients. Methods We carried out a cross-sectional study. Idiopathic PD patients (n = 304; age 70.6 ± 8.3 years (mean ± SD); disease duration 6.6 ± 5.1 years; Hoehn and Yahr stage 2.7 ± 0.7) were registered at 13 participating hospitals, and their clinical/neurological/cognitive features were examined using Japanese versions of the MMSE and MoCA. Results The MMSE and MoCA scores were 26.3 ± 3.6 (range 12–30) and 20.9 ± 5.0 (range 5–30), respectively, and showed a strong correlation (R2 = 0.74, P

In this study, 2 methods of DNA extraction were evaluated for use in conjunction with the screening system Rapid Foodborne Bacterial Screening 24 (RFBS24), which employs multiplex real-time SYBR Green polymerase chain reaction (SG-PCR) and can simultaneously detect 24 target genes of foodborne pathogens in fecal DNA samples. The QIAamp DNA Stool mini kit (Qkit) and Ultra Clean Fecal DNA Isolation Kit (Ukit) were used for bacterial DNA extraction from fecal samples artificially inoculated with Clostridium perfringens, Staphylococcus aureus, Salmonella Typhimurium, and Campylobacter jejuni. SG-PCR and simplex real-time quantitative PCR (S-qPCR) analyses revealed higher copy numbers (8-234 times) of DNA in samples obtained using Ukit compared with those obtained using Qkit, resulting in lower cycle threshold values for the Ukit samples of the 4 bacteria on SG-PCR analysis. Fecal DNA samples from patients infected during foodborne outbreaks of Salmonella and Campylobacter were also prepared by Qkit and Ukit methods and subjected to RFBS24 analyses. Higher numbers of RFBS24 bacterial target genes were detected in DNA samples obtained using Ukit compared with those obtained using Qkit. Thus, the higher DNA extraction efficiency of the Ukit method compared with Qkit renders the former more useful in achieving improved detection rates of these 4 bacteria in fecal samples using SG-PCR.

The aim of the present study was to investigate whether changes in hepatic oxygenation can be detected by time-resolved spectroscopy (TRS) placed on the skin surface above the liver. METHODS: With approval of the local Hospital Ethics Committee and informed consent, six healthy volunteers aged 28.8 (25–36) years, and five patients with chronic renal failure aged 70.6 (58–81) years were studied. In six healthy volunteers, following echography, TRS (TRS-10, Hamamatsu Photonics K.K., Hamamatsu, Japan) probes consisting of a near-infrared light (at 760, 800, 835 nm) emitter and a receiver optode, were placed 4 cm apart on the abdominal skin surface above the liver or at least 10 cm distant from the liver. In five patients with chronic renal failure, following echography, TRS probes were placed 4 cm apart on the skin surface above the liver during hemodialysis (HD). RESULTS: In six healthy volunteers, the values of abdominal total hemoglobin concentration (tHb) were significantly higher in the liver area than in the other area (80.6 ± 26.81 vs 44.6 ± 23.1 μM, p = 0.0017), while the value of abdominal SO2 in the liver area was nearly the same as that in the other area (71.5 ± 3.6 vs 73.6 ± 4.6 %, p = 0.19). The values of mean optical pathlength and scattering coefficient (μ′s) at 800 nm in the liver area were significantly different from those in the other area (21.3 ± 4.9 vs 29.2 ± 5 cm, p = 0.0004, and 7.97 ± 1.14 vs 9.02 ± 0.51 cm−1, p = 0.015). One of five patients with chronic renal failure complained of severe abdominal pain during HD, and abdominal SO2 decreased from 53 to 22 %; however, pain relief occurred following cessation of HD, and SO2 recovered to the baseline level. CONCLUSIONS: Our data suggest that the optical properties of the liver may be measured by the TRS placed on the skin surface, and the hepatic oxygenation may act as a non-invasive monitoring for early detection of intestinal ischemia.

Discriminating Escherichia albertii from other Enterobacteriaceae is difficult. Systematic analyses showed that E. albertii represents a substantial portion of strains currently identified as eae-positive Escherichia coli and includes Shiga toxin 2f-producing strains. Because E. albertii possesses the eae gene, many strains might have been misidentified as enterohemorrhagic or enteropathogenic E. coli.

REM sleep behavior disorder (RBD) is known to be observed more frequently in patients with an α-synucleinopathy such as Parkinson’s disease (PD) than in the general population. The precise prevalence of RBD in Japanese PD patients is not known. Therefore, we investigated the prevalence and the clinical characteristics of patients with RBD in a large population of Japanese patients with PD. We investigated various clinical features and employed the Japanese version of the RBD screening questionnaire on 469 non-demented Japanese PD patients in this multicenter study. Probable or possible RBD was detected in 146 patients (31.1%) and was significantly associated with longer PD duration, higher Hoehn and Yahr stage, higher Unified Parkinson’s Disease Rating Scale part III subscale (7 items), more motor fluctuations, and a higher levodopa-equivalent daily dose (p

Objective: The aim of this work was to investigate the prevalence of camptocormia and the clinical characteristics of patients with camptocormia in a large population of PD patients. Background: Although camptocormia has been recognized as a prominent phenomenon in PD, the previous epidemiological reports were limited, especially in terms of sample size. Methods: We evaluated 531 PD patients (disease duration: 7.0 ± 5.5 years, mean ± standard deviation). We examined their clinical features and the prevalence of camptocormia. Results: Camptocormia was detected in 22 patients (4.1%) and found in patients who were older and had more severe motor symptoms and a higher levodopa (L-dopa) dose (P < 0.05), compared to the patients without camptocormia. Patients with camptocormia showed significantly higher frequencies of autonomic symptoms, such as constipation and urinary incontinence (P < 0.05). Conclusions: Camptocormia is uncommon in PD and is associated with disease severity, higher L-dopa dose and higher frequencies of autonomic symptoms. © 2011 Movement Disorder Society

Here, we developed a new version of our original screening system (Rapid Foodborne Bacterial Screening 24; RFBS24), which can simultaneously detect 24 genes of foodborne pathogens in fecal DNA samples. This new version (RFBS24 ver. 5) detected all known stx2 subtypes, enterotoxigenic Escherichia coli (STh genotype), and Vibrio parahaemolyticus (trh2), which were not detected by the original RFBS24 assay. The detection limits of RFBS24 ver. 5 were approximately 5.6 × 10(-2)-5.6 × 10(-5) (ng DNA)/reaction, significantly lower (10- to 100-fold) than those of the original RFBS24 for the 22 target genes analyzed here. We also tested the new assay on fecal DNA samples from patients infected with Salmonella, Campylobacter, or enterohemorrhagic E. coli. The number of bacterial target genes detected by RFBS24 ver. 5 was greater than that detected by RFBS24. RFBS24 ver. 5 combined with an Ultra Clean Fecal DNA Isolation Kit showed adequate performance (sensitivity and specificity 89% and 100%, respectively, for Salmonella spp. and 100% and 83%, respectively, for Campylobacter jejuni) in terms of rapid detection of a causative pathogen during foodborne-illness outbreaks. Thus, RFBS24 ver. 5 is more useful than the previous assay system for detection of foodborne pathogens and offers quick simultaneous analysis of many targets and thus facilitates rapid dissemination of information to public health officials.

We report here a case of diffuse Lewy body disease with the A53T mutation in the alpha-synuclein gene. The proband presented at the age of 41 years with parkinsonism that was poorly responsive to levodopa. She subsequently developed cognitive impairment and moderate dementia, and died at the age of 50. Her father, paternal grandfather and uncle were all reported to have suffered from Parkinson's disease. Staining of tissue sections from the proband's brain with hematoxylin-eosin and alpha-synuclein antibodies showed small numbers of Lewy bodies in a few brain regions. This contrasted with large numbers of Lewy neurites and neuroaxonal spheroids in many brain regions. By electron microscopy, Lewy neurites consisted of abnormal filaments and dense granular material. Isolated filaments resembled those previously described in idiopathic Parkinson's disease and dementia with Lewy bodies. They were decorated by antibodies specific for the N and C termini of alpha-synuclein, indicating the presence of the full-length protein. Nucleus accumbens and the lower layers in limbic areas of the cerebral cortex showed prominent vacuolation, with frequent clustering of microvacuoles around Lewy neurites. Nerve cell loss was most extensive in dorsal motor nucleus of the vagus nerve, substantia nigra and nucleus basalis of Meynert. Neurofibrillary tangles and senile plaques were not observed. However, in several brain regions, a few widely scattered tau-positive nerve cell bodies and neurites were present. By electron microscopy, Alzheimer-type paired helical and straight filaments were seen.

Stress is defined as a state of disharmony or threatened homeostasis. The purpose of the present study was conducted to reveal the effect of intensive training as rangers of Japan Ground Self Defence Force (JGSDF), which would be a strong stressor, on the level of neurotransmitters related with endogenous control of pain. Subjects were seven uniformed members (aged 19–21 years old) who underwent ranger training in the 8th Division of the JGSDF. Before and after the 40 days hard training, the levels of serotonin, β-endorphin and three fractions of catecholamine in plasma were routinely measured. The levels of serotonin, β-endorphin, noradrenaline and dopamine were significantly increased after the ranger training. A close relationship between the changes in skin pain threshold previously reported and the present levels of serotonin, β-endorphin, noradrenaline and dopamine was observed in four of the seven rangers. These findings suggest that the intensive training changes level of some endogenous transmitters which might be related with stress-induced analgesia through descending control of pain. Copyright © 2004 John Wiley & Sons, Ltd.

Saliva can be considered a mirror of the body, reflecting its general conditions. The present study was conducted to identify the changes in specific neurotransmitter and prekallikrein levels in saliva and the correlations between changes in neuroendocrine factors in plasma and saliva after intensive physical training of rangers of Japan Ground Self Defence Force (JGSDF). The subjects were 14 young uniformed males (aged 20–26 years old) who underwent ranger training under the control of the 4th Division of the JGSDF. Before training began and after 30 days of hard training, the levels of prekallikrein, β-endorphin, serotonin, noradrenaline and dopamine in saliva and plasma were routinely measured. The level of prekallikrein in saliva was significantly increased after training, and the level of β-endorphin in saliva showed an upward trend after the training. The level of prekallikrein in plasma showed a significant decrease after the training, while the level of β-endorphin was unchanged. Average concentrations of values in serotonin, noradrenaline and dopamine in plasma were significantly increased after the training. These findings suggest that the comparison of levels of prekallikrein and β-endorphin in saliva and plasma may give useful insights for the estimation of stress-induced analgesia. Copyright © 2004 John Wiley & Sons, Ltd.

Pain sensation usually depends on psychological factors such as motivational and emotional state. The purpose of the present study was to reveal the effect of intensive training as rangers of Japan Ground Self Defence Force (JGSDF), which would be a strong stressor, on the pain threshold in human skin and tooth. Participants were seven uniformed members (aged 19–21 years old) who underwent ranger training in the 8th Division of the JGSDF. Before and after their hard training for 40 days, both skin and tooth pain threshold were measured. We selected five skin sites for pain test using a von Fray type filament. To measure tooth pain threshold, four teeth were selected and a conventional electric pulp tester was used. The threshold values in the skin were significantly increased after ranger training. However, the increase of tooth pain threshold was not clearly observed at each tooth tested. A close relationship between the changes in skin and tooth pain threshold was observed in two of the seven subjects. The present study indicates that intensive training can evoke analgesic effects which are thought to be stress-induced analgesia. Copyright © 2003 John Wiley & Sons, Ltd.

Objectives: To study the proportion and characteristics of potential candidates for the intravenous administration of tissue plasminogen activator (IV-tPA) among patients with cerebral infarction in a Japanese emergency department (ED). Methods: A retrospective observational study was performed using patients who had been transported by ambulance between August 1988 and April 2000 to an urban ED of a university hospital located in the Tokyo metropolitan area. Potential candidates for IV-tPA were identified using the criteria of the National Institute of Neurological Disorders and Stroke (NINDS) study. Results: Of all 30,064 patients transported by ambulance, 526 were diagnosed as having cerebral infarction. Among them, 190 patients arrived at the ED within two hours of symptom onset (early ED arrivers). In comparison of their demographics with late ED arrivers (n = 319), atrial fibrillation, male gender, and consciousness disturbance were related with early ED arrivers, while aging and diabetes were related with late ED arrivers. As to the stroke subtype, patients with an embolic infarction accounted for 76.8% among early ED arrivers. Application of exclusion criteria identified 114 patients, who were suitable for the thrombolysis treatment, indicating that the proportion of potential IV-tPA candidates was 21.7% among all cerebral infarction patients and 0.38% among all ED patients. Conclusions: The number of potential IV-tPA candidates among patients transported to the ED by ambulance in Japan was substantial, where the proportion of embolic infarction cases was extremely high.

We discuss the color-superconductivity and its effect on the cooling behavior of strange quark stars. The neutrino emissivity and specific heat of quark matter are calculated within the BCS theory. In the superconducting phase, the emissivity decreases and causes suppression of the cooling rate. It is shown that the phase transition leads to a sudden discontinuous suppression of the cooling rate in cooperation with the specific heat., Comment: 7 pages, 3 figures

We have developed a 1/2.3-in. 10.3 mega pixel back-illuminated CMOS image sensor utilizing serial multiple sampling. This sensor achieves an RMS random noise of 1.3e− and row temporal noise (RTN) of 0.19e−. Serial multiple sampling is realized with a column inline averaging technique without the need for additional processing circuitry. Pixel readout is accomplished utilizing a 4-shared-pixel floating diffusion (FD) boost-driving architecture. RTN caused by column parallel readout was analyzed considering the transfer function at the system level and the developed model was verified by measurement data taken at each sampling time. This model demonstrates the RTN improvement of −1.6 dB in a parallel multiple readout architecture.

In this article, we review the potential complications of spinal instrumentation discussing various types of postoperative complications. Surgical implants in spinal surgeries are used to stabilize the spine, replace the defective parts and maintain anatomic reduction. Internal spinal instrumentation has undergone considerable advances during the last century. However, the spinal instrumentation is an invasive surgery, and postoperative complications occur frequently after the spinal deformity surgery. Elderly patients, who may have many histories of medical complications and osteoporosis, have a higher complication rate. Pulmonary complications are the most common life-threatening postoperative complications. The acute onset of neurologic symptoms in the immediate postoperative period should arouse clinical suspicion about the possible formation of a hematoma. Such occurrences require urgent surgical decompression. Better recognition of postoperative risk factors and early detection of urgent signs may lead to decrease complication rates and may improve outcomes. Although the latest monitoring system is very useful we should recognize that the observation of the patients by the five senses is the most important way to detect the postoperative medical complications early.

It was believed that food poisoning in Osaka in 2000 was due to small amounts of staphylococcal enterotoxin A (SEA) in reconstituted milk. Results of this study clearly indicate that SEH was also present in the raw material of reconstituted milk, indicating that the food poisoning was caused by multiple staphylococcal enterotoxins.

It is known that patients with severe head injury experience marked hypercoagulability and excessive hyperfibrinolysis due to the release of tissue factors from injured cerebral parenchyma.We retrospectively evaluated the usefulness of tranexamic acid (TA) in patients with single, severe head trauma, who showed a Glasgow coma scale (GCS) 8 or D-dimeor = 20 microg ml-1. Twenty-five patients receiving TA [TA (+) ] were given the agent 2 g taking 30 minutes soon after their visit. Those not receiving TA [TA (--)] were 25 consecutive patients who met the criteria before the initiation of treatment with TA.The mortality rate was 4% in TA (+) and 24% in TA (-), significantly lower than in the former. The prognosis showed a tendency to improve in TA (+), but without significant differences between the groups. D-dimer was compared between the groups with a favorable prognosis in TA (+) and those in TA (-), its value was significantly higher in the former (60+/-56 microg ml-1) than the latter (28 +/- 27 microg ml-1) group. In addition, no thrombotic complications occurred in the former.Patients with severe head injury receiving TA showed a significantly better mortality rate without complications suggesting its usefulness.

posterior DMN connectivity normalized in the middle and posterior cingulate gyri but remained in the precuneus and retrosplenial cortex after adjusting for global cortical PiB retention in DLB. Conclusions: Patients with DLB are characterized by increases in the anterior DMN and decreases in the posterior DMN and PVN. This reciprocal change in the anterior and posterior DMN identified in patients with DLB closely resemble the DMN changes observed in AD. Although As load modifies the decreases in the middle and posterior cingulate regions in the posterior DMN, connectivity abnormalities in DLB persist even after controlling for As load. The pattern of posterior DMN and PVN connectivity decreases sparing the middle and posterior cingulate gyri after adjusting for As load is consistent with the pattern of regional hypometabolism typically observed in DLB.

This multicenter cross-sectional study aimed to investigate the clinical features and varieties of non-motor fluctuation in Parkinson's disease (PD).To identify motor and non-motor fluctuation, we employed the wearing-off questionnaire of 19 symptoms (WOQ-19) in 464 PD patients. We compared the frequency of levodopa-related fluctuation as identified by the WOQ-19 with recognition by neurologists. We compared patients with both motor and non-motor fluctuations with those who only had motor fluctuations. Non-motor fluctuations were separated into psychiatric, autonomic, and sensory categories for further analysis.The patients' average age was 70.8 ± 8.4 years (mean ± SD) and disease duration was 6.6 ± 5.0 years. The frequency of motor fluctuations was 69% and for non-motor fluctuation 40%. Fifty-three percent of patients with motor fluctuations also had non-motor fluctuations, whereas 93% of patients with non-motor fluctuations also had motor fluctuations. The WOQ-19 showed a sensitivity of 82% but a specificity of only 40%. The patients with both non-motor and motor fluctuations exhibited more severe motor symptoms, more non-motor symptoms and higher levodopa daily doses (p0.05). Patients had significantly higher fluctuation rates if they had psychiatric (49%) and sensory (45%) symptoms than patients with autonomic symptoms (32%, p0.01). Forty-eight percent of patients with non-motor fluctuations exhibited more than one type of non-motor fluctuation.Forty percent of PD patients presented with non-motor fluctuations, and almost half of these exhibited more than one type. Appropriate recognition of levodopa-related fluctuations, both motor and non-motor, can lead to treatment modifications in PD patients.

Disaster medicine is a special field of medicine which is required at unexpected times under poor medical circumstances, such as the transport of several patients at once, complex information and lack of medical staff. In order to provide accurate diagnostic information under such poor medical conditions, it is necessary to establish a well-considered and functional system to prevent malpractice in a serial process from the identification of each patient to blood sampling, its analysis and reporting, and in the process of blood transfusion, as a typical example. We have established a diagnostic system based on a manual focusing on rapidity of procedures and prevention of malpractice consisting of a distinction between priority analysis (for blood gas and blood type) and secondary analysis, the development of a blood typing method, adoption of blood sampling with heparin and so on. On the basis of the characteristics of disaster medicine, we stressed the minimization of analytical items and simplification of analytical procedures as much as possible. In order to utilize this system effectively in a disaster, it is essential to implement periodic training and revision.

Escherichia coli was isolated from wild and captive Japanese macaques (Macaca fuscata) to investigate the risk of zoonotic infections and the prevalence of antimicrobial-resistant Escherichia coli in the wild macaque population in Shimokita Peninsula, a rural area of Japan. We collected 265 fresh fecal samples from wild macaques and 20 samples from captive macaques in 2005 and 2006 for E. coli isolation. The predominant isolates were characterized by serotyping, virulence gene profiling, plasmid profiling, pulsed-field gel electrophoresis (PFGE), and microbial sensitivity tests. In total, 248 E. coli strains were isolated from 159 fecal samples from wild macaques, and 42 E. coli were isolated from 17 samples from captive macaques. None of the virulence genes eae, stx, elt, and est were detected in any of the isolates. The relatedness between wild- and captive-derived isolates was low by serotyping, PFGE, and plasmid profiling. Serotypes O8:H6, O8:H34, O8:H42, O8:HUT, O103:H27, O103:HNM, and OUT:H27 were found in wild macaque feces; serotypes O157:H42 and O119:H21 were recovered from captive macaques. O-and H-serotypes of the 26 isolates were not typed by commercial typing antisera and were named OUT and HUT, respectively. Twenty-eight isolates had no flagellar antigen, and their H-serotypes were named HNM. Similarity of PFGE patterns between wild-derived isolates and captive-derived isolates was

This paper presents a 1/2.3-inch 10.3Mpixel Back-Illuminated (BI) CMOS image sensor that targets both digital still camera (DSC) and high-definition camcorder applications. These applications require high-pixel-count, high-sensitivity, high saturation signal, low noise and high-speed imaging for image quality [1]. The sensor is scaled down to get a higher resolution due to higher pixel count. Several approaches such as a Cu process to reduce the pixel height and inner micro-lenses to gather rays of incident light have been proposed to overcome electro-optical challenges [2–4]. The BI process has been reported as one of the most promising technologies to improve optical performance [5,9]. This BI image sensor includes a 10b/12b analog-to-digital converter (ADC), an internal phase-locked loop (PLL) and a 10b serial LVDS interface to enable a data-rate up to 576MHz.