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Background: The Scoliosis Research Society-30 (SRS-30) is a questionnaire that was originally developed from the SRS-22r questionnaire and is used to evaluate adolescent idiopathic scoliosis (AIS). It comprises two sections, with Section 1 containing 22 items related to the SRS-22r questionnaire and 1 item regarding self-image and Section 2 containing 7 items specifically related to postoperative status. The SRS-30 has been also found useful in evaluating spinal disorders or deformity in adults. However, the Japanese version of the SRS-30 (Japanese SRS-30) has been validated for adolescent idiopathic scoliosis, but not for adult spinal deformity (ASD). This study aimed to assess the internal consistency and external validity of the Japanese SRS-30 for ASD., Methods: Of the 30 questions on the SRS-30, 8 questions added from the SRS-22r were translated and back-translated to create the Japanese SRS-30. The Japanese SRS-30 was used to survey patients with ASD who underwent corrective fusion surgery within 1 postoperative year. The internal consistency of the responses was evaluated using Cronbach α coefficient. Additionally, we performed Spearman correlation analysis of the Oswestry Disability Index (ODI) and SRS-22r with the Japanese SRS-30., Results: We included 120 patients (20 males and 100 females; mean age at surgery, 53.3 years). The mean preoperative Cobb angle, sagittal vertical axis, and pelvic incidence minus lumbar lordosis were 36.9°, 81.8 mm, and 24.0°, respectively. The Cronbach α coefficient for the overall SRS-30 was 0.941, indicating high internal consistency. Moreover, the coefficients for each domain were as follows: function/activity, 0.864; pain, 0.783; self-image/appearance, 0.858; mental health, 0.916; and satisfaction, 0.763. The total SRS-30 score was significantly correlated with the total SRS-22r score (r = 0.966, P < 0.001) and ODI (r = -0.752, P < 0.001). The SRS-30 domains showed strong correlations with the corresponding SRS-22r domains, with the r values ranging from 0.878 to 1.000 (all P < 0.001 except mental health)., Conclusions: The Japanese SRS-30 demonstrated good internal and external validity. The Japanese SRS-30 can be used to assess health-related quality of life in patients with ASD., Competing Interests: Declaration of competing interest HA, YY, YS, HO, JT, KW, RS, KT, YA, TA, SD, TD, AM, SS, ST, TT, HU, and NH have nothing to disclose., (Copyright © 2024 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Introduction: Staphylococcus aureus bacteremia (SAB), especially when caused by methicillin-resistant S. aureus (MRSA), is of considerable clinical importance. In recent years, the proportion of MRSA among S. aureus has decreased, and a relative increase in the proportion of methicillin-susceptible S. aureus (MSSA) has been observed. It is therefore necessary to consider both MRSA and MSSA when assessing the microbiological and clinical significance of SAB., Materials and Methods: We included SAB cases from the Nara Medical University Hospital between January 2015 and February 2017. We performed drug susceptibility testing, toxicity gene analysis, multilocus sequence typing (MLST), and polymerase chain reaction-based open reading frame typing (POT) of stored strains to integrate clinical and bacteriological characteristics., Results: There were 90 cases during the experimental period (42 MRSA and 48 MSSA), with 30-day mortality rates of 19 % for MRSA and 10.4 % for MSSA. Deaths were more frequently complicated by septic shock and disseminated intravascular coagulation. MLST studies showed that ST8, ST764, ST1, and ST15 were prevalent in the MRSA group, whereas ST5, ST188, and ST12 were prevalent in MSSA. Infective endocarditis cases had a long time from onset to the initiation of effective antimicrobials and were all MSSA. MLST and POT results correlated well, and POT appeared to have better discriminatory power., Conclusions: The severity and mortality of SAB, along with the microbiological characteristics of causative isolates, vary by location and time. Continued studies integrating clinical and microbiological investigations are thus needed., Competing Interests: Declarations of interest None., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: The prevalence of pleural injury during surgery for adolescent idiopathic scoliosis using an extrapleural approach and the association of pleural injury with postoperative pulmonary function remain unclear. We sought to determine the prevalence of pleural injury associated with an extrapleural approach to adolescent idiopathic scoliosis, and to determine any difference in respiratory function between patients with or without pleural injury., Methods: Data from consecutive patients with scoliosis of the thoracolumbar/lumbar spine who underwent anterior spinal fusion using an extrapleural approach were assessed in this retrospective study. We had diagnosed and treated pleural injury according to our algorithm. Pre- and postoperative values of pulmonary function tests and postoperative change rates were compared between patients with and without pleural injury. FVC, %FVC, FEV1.0, and FEV1.0% were evaluated from pulmonary function tests., Results: We included data from 51 patients with adolescent idiopathic scoliosis (45 female and 6 male) with a mean age of 17.2 ± 3.5 years in this retrospective study. The group with pleural injury comprised 31 patients and the group without 20. Therefore, the prevalence of pleural injury during an extrapleural approach was 61%. We found no significant differences in preoperative FVC, %FVC, FEV1.0, and FEV1.0% between the groups. We found no significant differences in FVC, %FVC, FEV1.0, and FEV1.0% between the groups at 3 months or 1 year postoperatively. Furthermore, we found no significant differences in the postoperative change ratio of FVC, %FVC, FEV1.0, and FEV1.0% between the groups., Conclusion: The prevalence of pleural injury associated with an extrapleural approach to scoliosis was 61%. Pleural injury was not associated with a decrease in postoperative pulmonary function in patients with scoliosis treated using an extrapleural approach., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2022 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Objective: Resting state functional magnetic resonance imaging (rs-fMRI) is a technique for the analyzing functional connectivity (FC) between anatomically distant brain regions at rest. The purpose of this study was to analyze postoperative FC changes in patients with compression cervical myelopathy, to evaluate their relationship with clinical scores, and to examine the changes in spinal cord function associated with brain networks., Methods: This prospective study comprised 15 patients with cervical myelopathy who underwent planned surgery. Rs-fMRI was performed preoperatively and 6 months postoperatively with the similar protocol. Clinical function was assessed by the Japanese Orthopedic Association (JOA) score, the Japanese Orthopedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ), and the numerical rating scale (NRS). We performed a seed-based analysis, and identified the networks that changed significantly following surgery. Furthermore, we performed a correlation analysis to compare the postoperative changes in FC with clinical scores., Results: Five FCs were significantly increased postoperatively; 4 were between the sensorimotor network (SMN) and other regions. We observed a significant correlation between the FC of the right SMN and the left precentral gyrus with the JOA score, the left SMN with the JOACMEQ for upper extremity function, and the left postcentral gyrus with the NRS., Conclusions: The reorganization of the sensorimotor cortex occurred postoperatively in patients with compression cervical myelopathy. In addition, each change in FC was significantly correlated with the clinical scores, thus indicating an association between the recovery of spinal cord function and plastic changes in the sensorimotor cortex., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Alzheimer's disease (AD) has a long preclinical phase during which beta-amyloid accumulates in the brain without cognitive impairment. However, the pattern of brain network alterations in this early stage of the disease remains to be clarified. In this study we examined the relationships between regional brain network indices and beta-amyloid deposits. Twenty-four elderly subjects with the APOE4 allele underwent both a 1.5-Tesla magnetic resonance imaging (MRI) scan and a positron emission tomography (PET) scan using [ 18 F]Florbetapir. We computed network metrics such as the degree, betweenness centrality, and clustering coefficient, and examined the relationships between the beta-amyloid accumulation and these regional brain network connectivity metrics. We found a significant positive correlation between the global standardized uptake value ratio (SUVR) of [ 18 F]Florbetapir and the betweenness centrality in the left parietal region. However, there were no significant correlations between the SUVR score and other network indices or the regional gray matter volume. Our data suggest a relationship between the beta-amyloid accumulation and the regional brain network connectivity in subjects at risk of AD. The brain connectome may provide an adjunct biomarker for the early detection of AD., (Copyright © 2021. Published by Elsevier B.V.)

Background: Stress from brace treatment in patients with adolescent idiopathic scoliosis (AIS) can deteriorate their quality of life. A Japanese version of the Bad Sobernheim Stress Questionnaire-Brace (JBSSQ-brace) was developed to assess the stress from brace treatment for Japanese patients with AIS. However, the specific factors causing stress under brace treatment have remained unknown., Method: We enrolled 69 consecutive Japanese patients with AIS. Stress from brace treatment was assessed by JBSSQ-brace and Scoliosis Research Society-22 (SRS-22) instruments. The correlations of JBSSQ-brace with SRS-22 score, patient demographics and Cobb angle were analyzed by Spearman's rank correlation. Exploratory factor analysis was used to determine the psychological factor causing stress from brace treatment., Results: JBSSQ-brace score was correlated with total score of SRS-22, self-image and mental health domain, but not age, degree of curvature, or other domains of the SRS-22. Factor analysis detected one underlying factor, which was more related to Questions 4 or 5 with the factor loadings of 0.8 than Questions 1 or 6 with loadings of 0.65., Conclusion: Stress from brace treatment was not associated with age, spinal curve severity, pain, or satisfaction of treatment. Exploratory factor analysis suggested "anxious feeling about how we are perceived by others" induces the stress from brace treatment in Japanese patients with AIS., (Copyright © 2020 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: The penetrating end plate screw (PES) technique improved the fixation strength of the pedicle screw by penetrating the end plate in posterior fusion. The "double" PES, which is a trajectory that penetrates both the upper end plate of the corresponding vertebra and the lower end plate of the upper adjacent vertebral body, provides a stronger tricortical fixation but requires a stricter trajectory. The purpose of this study was to measure the cephalad angles from T7-L5 that would allow a safe trajectory for "double" PES., Methods: We analyzed 1078 pedicles of 539 vertebral bodies of 50 consecutive cases (27 males and 23 females, mean age, 63.3 years) who underwent computed tomography (CT) myelography for evaluation of spinal disorders. The mean cephalad angle to obtain the double PES trajectory of each vertebra was examined, except for cases in which the appropriate trajectory would perforate the pedicles., Results: The cephalad angle for the appropriate trajectory of "double" PES ranged from 23.4 to 37.6 degrees in the thoracic spine and 34.8 to 40.8 degrees in the lumbar spine. The ratio of pedicle perforation was significantly higher at T7 (16%), L4 (26%), and L5 (52%)., Conclusions: It is important to measure the optimal cephalad angle by preoperative computed tomography imaging according to the vertebral level. In L4 and L5, "double" PES should be avoided because it is often unsafe., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Escherichia coli is one of the most popularly used hosts to produce recombinant proteins. Most recombinant proteins are produced in the cytoplasm and periplasm, requiring multiple steps to extract and purify recombinant proteins. The Serratia marcescens Lip system (LipB-LipC-LipD) is a type 1 secretion system that selectively secretes LipA from the intracellular to extracellular space in a single step. This study aimed to establish a secretory production system for nanobodies, camelid-derived small molecule antibody fragments, using the S. marcescens Lip system. Surprisingly, E. coli harboring only LipC, a membrane fusion protein of the Lip system, could secrete an anti-green fluorescent protein (GFP)-Nb, a nanobody against GFP, without the addition of a long amino acid sequence. The LipC-based secretion system recognized the Val-Thr-Val sequence at the C-terminus of the nanobody. Finally, Strep-tagged anti-GFP-Nb was purified from culture supernatants of E. coli harboring LipC by Strep-affinity chromatography at a final yield of >5 mg per liter of culture supernatant. These results potently supported that the S. marcescens LipC-based secretion system has the potential to establish an efficient secretory production system for nanobodies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Although scoliosis surgery early in life may affect the career choice of the patient in favor of a healthcare field, no study has analyzed this relationship. We investigated the career paths of patients after scoliosis surgery., Methods: A total of 212 patients with scoliosis who underwent corrective surgery at 12-17 years of age were mailed a questionnaire, of whom 98 (mean age at survey: 21.0 ± 1.7, years) responded. Choice of study major was determined by the same questions used in the Japanese national census., Results: Of the 98 patients, 35% chose a career in healthcare compared with 11% of the general population of the same age, based on the national census. Healthcare was the most popular career choice of patients, whereas it ranked fourth according to the national census. Furthermore, 87% of patients reported that their decision to pursue a healthcare-related career was affected by their own medical experiences. Among the healthcare-related occupations, nursing ranked first, accounting for 35% of all healthcare professions chosen by the patients. Compared with patients who chose a non-healthcare career, those choosing a healthcare career decided on their study major at a significantly lower age., Conclusions: One-third of patients with scoliosis who underwent spine surgery chose a career in a healthcare field. Furthermore, an earlier age at the time of making a career decision was a significant factor associated with choosing a healthcare career. These findings suggest that the patients' experiences in the hospital positively affected their future career paths., (Copyright © 2019 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: Patients with adolescent idiopathic scoliosis (AIS) under brace treatment perceive stress, not only from scoliosis, but from wearing the brace itself. The Bad Sobernheim Stress Questionnaire-Brace (BSSQbrace) was developed to assess the level of psychological stress induced by brace treatment for AIS. However, a Japanese version of BSSQbrace had not yet been developed., Methods: We developed a Japanese adaptation of the Bad Sobernheim Stress Questionnaire-Brace (JBSSQ-brace) through a guideline-based process to adapt assessment of the psychological effect of brace treatment for AIS in Japanese patients. We administered the JBSSQ-brace to 71 patients with AIS under brace treatment in our clinic. Internal consistency and reproducibility were analyzed using Cronbach's alpha and a test-retest method., Results: We included 44 patients that responded adequately. JBSSQ-brace achieved excellent internal consistency (Cronbach's alpha = 0.84 for the first questionnaire, and 0.87 for the second) and substantial reproducibility (interclass correlation coefficient = 0.75). The average score for JBSSQ-brace was 16.5 and 16.8, and almost 40% of AIS patients felt a moderate-to-high stress from brace treatment., Conclusions: JBSSQ-brace is an effective instrument with which to evaluate the stress level from brace treatment in Japanese patients with AIS., (Copyright © 2019 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Objective: To examine whether coenzyme Q10, a potent antioxidant, is associated with risk of dementia, which has not yet been elucidated., Approach and Results: We performed a case-control study nested in a community-based cohort of approximately 6000 Japanese aged 40-69 years at baseline (1984-1994). Serum coenzyme Q10 was measured in 65 incident cases of disabling dementia with dementia-related behavioral disturbance or cognitive impairment incident between 1999 and 2004, and in 130 age-, sex- and baseline year-matched controls. Serum coenzyme Q10 was inversely associated with dementia: the multivariate odds ratios (95% confidence intervals) were 0.68 (0.26-1.78), 0.92 (0.33-2.56), and 0.23 (0.06-0.86) for individuals with the second, third, and highest quartiles of coenzyme Q10, respectively, as compared with the lowest quartile (P for trend = 0.05). A similar association was found for the coenzyme Q10/total cholesterol ratio: the respective ORs were 0.67 (0.25-1.78), 0.73 (0.28-1.92), and 0.21 (0.05-0.90) (P for trend = 0.04)., Conclusions: Serum coenzyme Q10 levels were inversely associated with risk of disabling dementia., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objective: Studies have shown that elevated high-sensitivity C-reactive protein (hs-CRP) predicts stroke, which is a risk factor for dementia. It remains, however, unclear whether hs-CRP increases risk of dementia., Methods: A prospective nested case-control study of Japanese 40-69 years of age was conducted using frozen serum samples collected from approximately 7531men and women who participated in cardiovascular risk surveys from 1984 to 1994 in one community and 1989-1995 in another community under the Circulatory Risk in Communities Study (CIRCS). Two control subjects per case were matched by sex, age, community, and year of serum storage. The hs-CRP was measured using a latex particle-enhanced immunonephelometric assay., Results: Between 1999 and 2013, we identified 275 disabling dementia cases (96 cases with history of stroke and 179 without it). There was a positive association between hs-CRP levels and risk of dementia with history of stroke. No significant association was observed between hs-CRP levels and risk of dementia without history of stroke. After adjustment for hypertension, diabetes and other confounding variables, the positive association remained statistically significant. The multivariable odds ratios associated with 1-SD increment of log hs-CRP were 1.02 (0.87-1.20) for total dementia, 1.35 (1.02-1.79) for dementia with history of stroke, and 0.89 (0.72-1.10) for dementia without history of stroke., Conclusion: Elevated hs-CRP levels were associated with increased risk of disabling dementia in individuals with history of stroke but not in those without it., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Non-fatal suicide attempt is the most important risk factor for later suicide. Emergency department visits for attempted suicide are increasingly recognised as opportunities for intervention. However, no strong evidence exists that any intervention is effective at preventing repeated suicide attempts. We aimed to investigate whether assertive case management can reduce repetition of suicide attempts in people with mental health problems who had attempted suicide and were admitted to emergency departments., Methods: In this multicentre, randomised controlled trial in 17 hospital emergency departments in Japan, we randomly assigned people aged 20 years and older with mental health problems who had attempted suicide to receive either assertive case management (based on psychiatric diagnoses, social risks, and needs of the patients) or enhanced usual care (control), using an internet-based randomisation system. Interventions were provided until the end of the follow-up period (ie, at least 18 months and up to 5 years). Outcome assessors were masked to group allocation, but patients and case managers who provided the interventions were not. The primary outcome was the incidence of first recurrent suicidal behaviour (attempted suicide or completed suicide); secondary outcomes included completed suicide and all-cause mortality. This study is registered at ClinicalTrials.gov (NCT00736918) and UMIN-CTR (C000000444)., Findings: Between July 1, 2006, and Dec 31, 2009, 914 eligible participants were randomly assigned, 460 to the assertive case management group and 456 to the enhanced usual care group. We noted no significant difference in incidence of first recurrent suicidal behaviour between the assertive case management group and the enhanced usual care group over the full study period (log-rank p=0·258). Because the proportional hazards assumption did not hold, we did ad-hoc analyses for cumulative incidence of the primary outcome at months 1, 3, 6, 12, and 18 after randomisation, adjusting for multiplicity with the Bonferroni method. Assertive case management significantly reduced the incidence of first recurrent suicidal behaviour up to the 6-month timepoint (6-month risk ratio 0·50, 95% CI 0·32-0·80; p=0·003), but not at the later timepoints. Prespecified subgroup analyses showed that the intervention had a greater effect in women (up to 18 months), and in participants younger than 40 years and those with a history of previous suicide attempts (up to 6 months). We did not identify any differences between the intervention and control groups for completed suicide (27 [6%] of 460 vs 30 [7%] of 454, log-rank p=0·660) or all-cause mortality (46 [10%] of 460 vs 42 [9%] of 454, log-rank p=0·698)., Interpretation: Our results suggest that assertive case management is feasible in real-world clinical settings. Although it was not effective at reducing the incidence of repetition of suicide attempts in the long term, the results of our ad-hoc analyses suggested that it was effective for up to 6 months. This finding should be investigated in future research., Funding: The Ministry of Health, Labour, and Welfare of Japan., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Isolation techniques for anthocyanidin 3,5-diglucosides and their derivatives from three types of supramolecular pigments were newly developed using two SPE (Discovery DPA-6S and DSC-SCX) cartridges. Initially, malonylawobanin from commelinin supramolecular complex yielded 79.5% with 85.7% purity using DPA-6S, while DSC-SCX gave a rather lower yield (62.5%) of malonylawobanin with high purity (90.8%). Delphinidin 3,5-diglucoside and awobanin from acidic hydrolysis of commelinin were easily separated using DPA-6S. Secondary, artificial Perilla supramolecules (reconstructed from Perilla crude pigment, flavocommelin and Mg(2+)) result in a high purity of a malonylshisonin and shisonin mixture (96.1%) with DSC-SCX. Finally, succinylcyanin, which is a component of protocyanin, yielded 64.3% with 86.1% purity using DPA-6S and 51.8% with 74.1% purity using DSC-SCX. Moreover, cyanidin 3,5-diglucoside yielded 43.4% with 97.0% purity using DPA-6S after partial acidic hydrolysis of protocyanin., (Copyright © 2014 Elsevier B.V. All rights reserved.)

We examined the combined effect of plasma lipids/hypertension and apolipoprotein E (APOE) genotype on cognitive function in elderly individuals. Plasma concentrations of high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglyceride (TG), total cholesterol (TC), APOE, and history of hypertension were evaluated in 622 community-dwelling individuals aged 65 years and older. We investigated the associations between plasma lipids/hypertension and cognitive function in apolipoprotein E4 allele (APOE4) carrier (E4+) and APOE4 noncarrier (E4-) groups using 3-year longitudinal data. At baseline and 3 years later, cognitive scores were correlated with plasma APOE levels in both E4- and E4+, and HDL level in E4-. The combination of hypertension and E4+, but not E4-, was associated with a significant deterioration in cognitive function during the 3-year follow-up. Our findings suggest that an interaction between APOE and HDL is facilitated by APOE4, and is possibly linked with a protective effect on cognitive decline in later life. The findings also indicate a synergistic effect of an APOE4 allele and hypertension on the acceleration of cognitive decline., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: Although the relationship between cognitive function and plasma lipids has attracted attention, previous studies have shown conflicting results. One possible confounding factor is due to the influence of gene-related modulator. We investigated the relationship between cognitive function and lipid plasma levels of old age after controlling for apolipoprotein E (APOE) genotype., Methods: One thousand three hundred ninety-five subjects without dementia age 65 and older participated in this study. They were divided into two groups, with and without APOE4 [E4 (+) and E4 (-)]. Plasma concentrations of high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglyceride (TG), total cholesterol (TC) and apolipoprotein E (apoE) were measured. Associations between plasma concentrations of lipids and cognitive function were investigated for each group., Results: We found a positive association between cognitive scores and plasma apoE level in both E4 (-) and E4 (+) groups. A positive relationship was also observed between cognitive score and HDL level in the E4 (-) group, but not in the E4 (+) group. No substantial association between cognitive score and LDL, TG, and TC levels was found in either of the groups., Conclusions: Our findings suggest that plasma apoE have a positive influence on cognitive function in both E4 (-) and E4 (+) groups, whereas the positive influence of plasma HDL was shown only in E4 (-) group. The identification of the influences of (APOE) genotype and the intracellular linkage among apoE and HDL metabolism is hoped for new preventive and therapeutic strategies for cognitive change of elderly.

Context: Although an evidence-based clinical guideline for parenteral hydration therapy was established in Japan, the efficacy of the guideline has not been assessed., Objectives: Our purpose was to explore the effect of parenteral hydration therapy based on this clinical guideline on quality of life (QoL), discomfort, symptoms, and fluid retention signs in patients with advanced cancer., Methods: This multicenter, prospective, observational study included 161 patients with advanced abdominal cancer who received guideline-based hydration therapy. We evaluated the longitudinal changes of the global QoL (Item 30 of European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire-C30); the Discomfort Scale; the intensity of seven physical symptoms; and the severity of fluid retention signs. We also evaluated patient satisfaction and the feeling of benefit from hydration one week after the study commenced, and bronchial secretions, hyperactive delirium, communication capacity, and agitation 48 hours before a patient's death., Results: The global QoL, the Discomfort Scale, and the intensities of all physical symptoms, except for vomiting and drowsiness, were stable throughout the study period. More than 80% of patients maintained all fluid retention signs. Patient global satisfaction was 76.4 (0-100) and feeling of benefit was 5.43 (range 0-7)., Conclusion: Guideline-based parenteral hydration therapy contributed to maintaining global QoL and provided satisfaction and a feeling of benefit without increasing discomfort and worsening symptoms and fluid retention signs in patients with advanced cancer., (Copyright © 2012 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.)

Background: Peripheral benzodiazepine receptor (PBR) in the brain of Alzheimer's disease (AD) patients has been discussed in relation to the role of gliosis in AD. The PBR was shown to have the ability to reflect activated glial cells, including microglia. The role of activated microglia in AD is an important topic in the pathophysiology of AD. The aim of this study was to quantify PBR in AD brain with a new high-sensitive PBR ligand, [(11)C]DAA1106., Methods: Positron emission tomography (PET) scans with [(11)C]DAA1106, a potent and selective ligand for PBR, were performed on 10 patients with AD and 10 age-matched control subjects. All patients had mild to moderate dementia. Duration of illness was 1-3 years at the time of the scans. The PBR binding in the regions of interest was quantified by binding potential (BP) obtained from compartmental model analysis with plasma input function., Results: Mean BP was increased in the brain of AD patients compared with control subjects in all measured regions. Statistical significance reached across many of the regions examined, including dorsal and medial prefrontal cortex, lateral temporal cortex, parietal cortex, occipital cortex, anterior cingulate cortex, striatum, and cerebellum., Conclusions: The broad increase of PBR binding measured with [(11)C]DAA1106 in the brain of AD patients suggests a widespread existence of cellular reactions with PBR in relatively early-stage AD.

A mechanism by which exercise improves brain function may be attributed to increase in cerebral blood volume (CBV) with physical activity. However, the exact exercise intensity that influences CBV is still uncertain. To clarify this issue, 10 healthy young male participants were asked to perform a graded cycling exercise to the point of exhaustion while their prefrontal cortex CBVs are being monitored using near-infrared spectroscopy. Overall responsive cerebral oxygenation showed a non-linear pattern with three distinct phases. The CBV-threshold (CBVT), an event where rapid oxygenation takes place, occurred at approximately 42% of the V O2max. The CBVT preceded the lactate threshold (LT), which was at approximately 55% of the V O2max. The V O2max was not predictive of the CBVT in among the subjects. Our results indicate that oxygenation of the prefrontal cortex increases during graded cycling even at exercise intensities below the LT, suggesting the potential role of mild exercise in enhancing CBV.

A simple one-step extraction and cleanup using a pressurized liquid extraction method was developed for the gas chromatographic-mass spectrometric determination of pesticides in vegetables. The pressurized liquid extraction conditions were optimized and cleanup agents were evaluated. The investigated pesticides included six insecticides, chlorpyrifos methyl, pirimiphos-methyl, malathion, chlorpyrifos, O-ethyl O-4-nitrophenylphenyl phosphonothioate (EPN) and permethrins, a fungicide, isoprothiolane, and a herbicides, thiobencarb. The cleanup agent and a mixture of the vegetable and anhydrous sodium sulfate were separately packed in an extraction vessel. A transparent and colorless extract was obtained using graphitized carbon as the cleanup agent. The overall recoveries were 71-103% and the relative standard deviations ranged from 5.6 to 24%. The limit of detection values were 3-8 microg kg(-1). This method was successfully applied to green leafy vegetables.

The incidence of dementia and risk factors has not been fully investigated in Japan. Following a prevalence study in 1998, we investigated the incidence and associated factors in the same population in 2003 and 2005. Randomly selected 771 residents in Tajiri were targeted. The final participants included 204 (65.2%) healthy older adults (Clinical Dementia Rating, CDR 0) and 335 (73.1%) people with questionable dementia (CDR 0.5). We analyzed the incidence of dementia and dementing diseases, and possible risk factors. The risk factors included demographics, lifestyle-related factors, vascular risk factors, cognitive functions, and MRI findings. Overall, 3.9% of the CDR 0 and 37.0% of the CDR 0.5 participants developed dementia during the 5-year period, whereas 40.2% of the CDR 0.5 participants developed dementia during the 7-year period. Older adults had a higher incidence. Higher CDR Box scores had a higher incidence. Of the dementing diseases, 60.8% of participants developed Alzheimer' disease (AD), followed by vascular dementia (VaD), 17.9%. Logistic regression analyses showed that age, MMSE, cognitive functions such as recent memory, and generalized atrophy were significant predictors of progression to AD. Similarly, predictive factors for progression to VaD were age, MMSE, cognitive functions such as frontal function, and white matter lesions and cerebrovascular diseases. A comprehensive system including CDR, cognitive tests, and MRI, is recommended in community-based health policy planning.

The CLOCK gene has attracted attention due to its influence on the circadian rhythm, as well as its impacts on the dopaminergic system. We conducted a preliminary study to examine whether the T3111C single nucleotide polymorphism of the CLOCK gene is associated with the development of schizophrenia by examining samples from schizophrenics (n=145) and normal controls (n=128). Both genotype and allele frequencies were significantly different between schizophrenics and controls (p=0.022, p=0.015, respectively). Schizophrenics had a significantly higher frequency of the C allele compared to controls (odds ratio 1.76, 95% CI 1.12-2.75). In particular, disorganized and residual type schizophrenics had significantly higher C allele frequencies than controls (p=0.004 and p=0.037, respectively). Our results suggest that the T3111C polymorphism of the CLOCK gene is associated with schizophrenia. It is important to explore the association between CLOCK and dopamine function, and to examine the impact of CLOCK on phenotypes such as symptoms and drug response in patients with schizophrenia.

Loss of dopamine synthesis in the striatum with normal human aging has been observed in the postmortem brain. To investigate whether there is age-associated change in dopamine synthesis in the extrastriatal brain regions similar to that in the striatum, positron emission tomography studies with (11)C-labelled l-DOPA were performed on 21 normal healthy male subjects (age range 20-67 years). Decline in the tissue fraction of gray matter per region of interest was also investigated. The overall uptake rate constant for each region of interest was quantified by the Patlak plot method using the occipital cortex as reference region. Regions of interest were set on the dorsolateral prefrontal cortex, lateral temporal cortex, medial temporal cortex, occipital cortex, parietal cortex, anterior cingulate, thalamus, midbrain, caudate nucleus, and putamen. Test-retest analysis indicated good reproducibility of the overall uptake rate constant. Significant age-related declines of dopamine synthesis were observed in the striatum and extrastriatal regions except midbrain. The decline in the overall uptake rate constant was more prominent than in the tissue fraction of gray matter. These results indicate that the previously demonstrated age-related decline in striatal dopamine synthesis extends to several extrastriatal regions in normal human brain.

A gas chromatographic-mass spectrometric method was developed for the determination of pesticides in compost. The investigated pesticides included two fungicides, two herbicides and 10 insecticides. The pesticides were extracted from the compost by pressurized liquid extraction. The extract was cleaned up by a partition between hexane and acetonitrile followed by a dispersive solid-phase extraction using a porous carbon made from Moso bamboo (Phyllostachys pubescens). The overall recoveries were 81-104% and the relative standard deviations (RSDs) ranged from 2.4 to 12%. The minimum detectable concentrations were 0.02-0.04 microg g(-1). This method was successfully applied to a compost sample from food waste as well as commercial compost.

Objective: Development of an EEG preprocessing technique for improvement of detection of Alzheimer's disease (AD). The technique is based on filtering of EEG data using blind source separation (BSS) and projection of components which are possibly sensitive to cortical neuronal impairment found in early stages of AD., Methods: Artifact-free 20s intervals of raw resting EEG recordings from 22 patients with Mild Cognitive Impairment (MCI) who later proceeded to AD and 38 age-matched normal controls were decomposed into spatio-temporally decorrelated components using BSS algorithm 'AMUSE'. Filtered EEG was obtained by back projection of components with the highest linear predictability. Relative power of filtered data in delta, theta, alpha 1, alpha 2, beta 1, and beta 2 bands were processed with Linear Discriminant Analysis (LDA)., Results: Preprocessing improved the percentage of correctly classified patients and controls computed with jack-knifing cross-validation from 59 to 73% and from 76 to 84%, correspondingly., Conclusions: The proposed approach can significantly improve the sensitivity and specificity of EEG based diagnosis., Significance: Filtering based on BSS can improve the performance of the existing EEG approaches to early diagnosis of Alzheimer's disease. It may also have potential for improvement of EEG classification in other clinical areas or fundamental research. The developed method is quite general and flexible, allowing for various extensions and improvements.

In order to examine the post-transcriptional regulations in Alzheimer's disease, we employed immunohistochemical techniques and examined the expression of heterogeneous nuclear ribonucleoprotein (hnRNP) B1 in the inferior temporal cortex of subjects with Alzheimer's disease. In the mild cases, intense B1 immunoreactivity was observed in neurons of layer V, and less intense immunoreactivity was observed in layers II and III. The overall distributions and intensities of B1 immunoreactivity were undistinguishable among mild, moderate, and severe cases. Double-immunolabeling with MC1 and B1 demonstrated that B1 immunoreactivity was preserved in the majority of neurofibrillary tangle (NFT)-bearing neurons. Our study suggests that hnRNP B1-associated post-transcriptional regulations are preserved in the inferior temporal cortex of Alzheimer's disease.

Background: Wnt signaling plays important roles in neurodevelopmental processes. Frizzled is a receptor of Wnt protein, and the Frizzled 3 (FZD3) gene was recently reported to be associated with schizophrenia. Our study attempted to confirm associations between FZD3 and schizophrenia in Japanese family and case-control samples., Methods: Genetic associations were evaluated using family-based transmission tests (212 families, 643 subjects) and case--control analysis (540 schizophrenia patients, 540 control sample). Six single nucleotide polymorphisms (SNPs) on the FZD3 locus were genotyped, and levels of FZD3 mRNA expression in postmortem brains were examined., Results: Neither family- nor population-based studies supported associations between FZD3 and schizophrenia. FZD3 expression was unaltered in schizophrenic brains., Conclusions: Although two prior studies have reported associations using limited numbers of SNPs on FZD3, our intensive study failed to support any major contribution of FZD3 to schizophrenia susceptibility.

A number of investigations have provided a growing body of evidence of the involvement of the gamma-aminobutyric acid (GABA) transmitter system in the pathophysiology of schizophrenia and bipolar disorder. In this study, immunohistochemical and immunoblot techniques were employed in order to examine alterations of the GABA(A) receptor alpha1 and beta2/3 subunits in the prefrontal cortex from postmortem subjects with schizophrenia and bipolar disorder. alpha1 immunoreactivity was observed in the neuropil of the prefrontal cortex and in the neuronal soma in specimens from both groups, as well as from normal controls. alpha1 immunolabeling in the neuronal soma from the schizophrenic group was more intense than that of the other two groups. The distribution of beta2/3 immunoreactivity was similar to that of alpha1. beta2/3 immunolabeling in the neuronal soma from the schizophrenia and bipolar disorder groups was more intense than that of the normal controls. The densitometry measurements, as well as the immunoblot analysis for alpha1 and beta2/3 were highly consistent with the alpha1 and beta2/3 immunohistochemistry results. The present study suggests that the expression of these two GABA(A) receptor subunits was altered in subjects with schizophrenia and bipolar disorder, but that the patterns of change differed between those with these two disorders.

We studied the neural substrates of clock drawing using functional magnetic resonance imaging in 18 right-handed volunteers. In the test condition, subjects were required to draw the hands of a clock corresponded to the time presented acoustically. In the control task, they drew horizontal and vertical lines after reciting silently the numerals of three figures presented acoustically. In group analyses, comparison between the test and control condition revealed brain areas related to clock drawing; bilateral posterior parietal cortices with a right side dominance, bilateral dorsal premotor areas, the left pre-supplementary motor area, the left ventral prefrontal cortex, the left precentral gyrus, and bilateral cerebellum. In particular, the posterior parietal cortex and the dorsal premotor area, which were strongly activated in all 18 subjects examined in individual analyses, appear to be the main constituent of the parieto-frontal cortical networks for clock drawing., (Copyright 2002 Elsevier Science Ireland Ltd and the Japan Neuroscience Society)

Objectives: To test the hypothesis that elecetroencephalographic (EEG) analysis is sensitive to cortical neuronal impairment in early stage Alzheimer's disease (AD), and that this analysis correlates with corresponding changes in cerebral blood flow., Methods: We examined an EEG measure of neuronal impairment in the cerebral cortex in terms of its ability to detect very mild AD. This measure, the mean value of the resting state EEG alpha dipolarity (D(alpha)), approaches unity without cortical sulcal lesions, whereas brains with randomly distributed cortical sulcal lesions lower D(alpha) values well below unity. D(alpha) was evaluated in 25 patients with very mild AD, 33 patients with moderately severe AD, and 56 normal age-matched subjects. These subjects also received SPECT, and strong correlation between D(alpha) and regional cerebral blood flow (rCBF) was observed., Results: D(alpha) values greater than 0.977 correctly classified normal subjects, but also included 10% of very mild AD. D(alpha) values less than 0.952 correctly classified very mild AD as well as moderately severe AD, but also included 10% of normal subjects. D(alpha) values also correlated positively with bilateral temporal-parietal rCBF (a characteristic finding in AD patients); both declined with increasing dementia severity., Conclusions: Analysis of D(alpha) in this sample supports the hypothesis that early stages of AD can be discriminated from normal aging using measures of cortical neuronal impairment. Furthermore, dementia severity, as reflected by the degree of impairment, is reflected in declining D(alpha) values and increasing variance (greater spread of the D(alpha) values).

Although hydrogen sulfide (H2S) is generally thought of in terms of a poisonous gas, it is endogenously produced in the brain from cysteine by cystathionine beta-synthase (CBS). H2S functions as a neuromodulator as well as a smooth muscle relaxant. Here we show that the levels of H2S are severely decreased in the brains of Alzheimer's disease (AD) patients compared with the brains of the age matched normal individuals. In addition to H2S production CBS also catalyzes another metabolic pathway in which cystathionine is produced from the substrate homocysteine. Previous findings, which showed that S-adenosyl-l-methionine (SAM), a CBS activator, is much reduced in AD brain and that homocysteine accumulates in the serum of AD patients, were confirmed. These observations suggest that CBS activity is reduced in AD brains and the decrease in H2S may be involved in some aspects of the cognitive decline in AD.

A new method to skeletonize and harvest the internal thoracic artery using an ultrasonic scalpel is presented. The technique is simple, safe, and minimally invasive. It is possible to obtain sufficient vessel length for anastomosis to most coronary arteries for bypass grafting.

Background: Time limits for neuroprotection by retrograde cerebral perfusion (RCP) and selective cerebral perfusion (SCP) in aortic arch aneurysm repair or dissection are undergoing definition., Methods: Using near-infrared optical spectroscopy, changes in regional cerebrovascular oxygen saturation (rSO2) were compared between the two perfusion methods., Results: Immediately before cardiopulmonary bypass, baseline rSO2 was 63.9%+/-6.9% for the RCP and 66.1%+/-5.3% for the SCP group (no significant difference). As patients were core-cooled to 20 degrees C, rSO2 increased to 73.1%+/-8.8% and 74.1%+/-7.9% in the RCP and SCP groups, respectively. With circulatory arrest, rSO2 suddenly decreased. After starting cerebral perfusion, rSO2 returned to prearrest values in the SCP group but continued decreasing steadily in the RCP group, to levels below baseline after about 25 minutes. At the end of perfusion, rSO2 was 57.4%+/-12.2% for the RCP group and 71.7%+/-6.9% for the SCP group, and the ratio of rSO2 to baseline value was 0.89 for RCP and 1.08 for SCP despite a shorter brain perfusion time for RCP (38.8+/-18.0 versus 103.3+/-43.3 minutes). Three of 5 patients whose ratios of rSO2 to baseline at the end of brain protection were 0.7 or less had neurologic deficits., Conclusions: Although SCP showed no clinically important time limitation, rSO2 continued to decrease with time during RCP. An rSO2 ratio less than 0.7 could represent a critical lower limit.

More than 40 missense mutations and a splice-site mutation in the presenilin 1 (PS-1) gene, two missense mutations of presenilin 2 (PS-2), and more than three missense mutations of amyloid precursor protein (APP) cosegregate with early onset familial Alzheimer's disease (FAD). In order to determine the incidence of mutations of these genes in Japanese patients, we screened 25 early onset FAD families, one late-onset FAD case, 33 early onset AD cases and five late-onset AD cases for mutations in the coding regions of the genes using SSCP analysis. Four different missense mutations of the PS-1 gene, including a novel mutation, Glu273Ala, were identified in five early onset FAD families and one missense mutation of PS-1 in one isolated AD patient. While no missense mutations of PS-2 were detected, four silent nucleotide substitutions were observed. Our data indicate that PS-1 mutations account for 20.0% of early onset FAD cases in Japan. Since mutations in PS-2 and APP genes were not found in the remaining cases, which could be explained only partially by apolipoprotein E epsilon4, important FAD genes or risk-factor genes remain to be identified.

We studied the polymorphism of alpha1-antichymotrypsin (ACT), very low density lipoprotein receptor (VLDLR) and apolipoprotein E (ApoE) genes in 200 control subjects and 65 patients with Alzheimer's disease (AD) in Japanese. The subjects consisted of 30 patients with early onset familial Alzheimer's disease (FAD), a patient with late onset FAD, 29 patients with an early onset isolated form of AD, and 5 patients with late onset AD. ApoE genotypes were significantly different between controls and FAD (p < 0.0005) or AD (p < 0.05), and patients carrying at least one ApoE epsilon4 allele were found in 44% of FAD and 34.3% of AD; both were significantly different (p < 0.001) from the controls (12.5%). ACT genotypes and allele frequencies were not different among these groups except for genotypes between ApoE epsilon4 FAD and ApoE epsilon4 controls (p = 0.019). There was a slight but significant increase of the 5 repeat allele of VLDLR in AD (p = 0.014), but the difference was rather diminished in the presence of an ApoE epsilon4 allele. None of combinations of ACT and VLDLR genotypes in the presence or absence of an ApoE epsilon4 allele gave significant difference. Thus, we conclude that among the reported genetic risk factors, ApoE epsilon4 is the only definite risk factor for both FAD and AD, and the VLDLR polymorphism might be associated with AD cases in Japanese.

In order to investigate glucose transport at the blood-brain barrier (BBB), glucose transport properties were studied pharmacologically with a novel model system of inverted bovine brain cortical arteries. These vessels displayed glucose transport characteristics of facilitative glucose transporters (GLUT1-5) and of sodium- and energy-dependent glucose transporters (SGLT1-2). So far, glucose transport in the central nervous system (CNS) has only been shown to be achieved by facilitative transporters, in particular by GLUT1 at the blood-brain barrier and in glial cells and by GLUT3 in a subset of neurons. We report here that a SGLT-like transporter might partake in glucose transport at the bovine BBB, as indicated by immunocytochemical analysis and by Western immunoblot analysis of cultured bovine brain endothelial cells. A RNA protection assay revealed the presence of a SGLT-like gene fragment in rabbit cortex.

We report a very rare case of hugh aortic arch aneurysm associated with aortic restenosis, which caused severe hypoxia due to ventilation-perfusion mismatch by compression of the left main bronchus and the right pulmonary artery. Aortic arch replacement was performed under circulatory arrest and deep hypothermia in addition to aortic valve replacement as a redo operation, and consequently such hypoxia was relieved.

It has been postulated that an accumulation of a sulfhydryl-containing amino acid, homocysteine in plasma may induce arteriosclerosis. In order to explore a possible contribution of homocysteine to the development of cerebral infarction in middle-aged and elderly patients, plasma sulfhydryl-containing amino acid profiles of 45 patients with cerebral infarction (CI) were compared with those of 45 normotensive and 45 hypertensive controls, and 20 patients with cerebral bleeding (CB), of similar ages and sex. The concentrations of both free and total homocysteine in plasma were highest in patients with CI among the 4 groups, while plasma free and total cysteinylglycine levels were similar. Although both free and total cysteine levels were also higher in patients with CI than in normotensive controls, the total homocysteine/total cysteine ratio was highest in patients with CI among the four groups. The hypertensive controls had higher plasma free and total concentrations than normotensive controls, but the levels did not differ between the 21 normotensive and 24 hypertensive CI patients. Our results suggest that high levels of plasma homocysteine in conjunction with hypertension could be one of the risk factors for arteriosclerotic CI.