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We previously investigated the preclinical state of idiopathic normal pressure hydrocephalus (iNPH): asymptomatic ventriculomegaly with features of iNPH on magnetic resonance imaging (AVIM) found in community inhabitants. The aim of the study was to determine how iNPH develops longitudinally.A previous longitudinal prospective community-based cohort study was initiated in 2000. The 271 70 year-old participants were followed up in 2016 at the age of 86 years. At this time, 104 participants could be reached for clinical examinations and brain magnetic resonance imaging (MRI). iNPH in this study was diagnosed if the participant had more than one symptom in the clinical triad and disproportionately enlarged subarachnoid space hydrocephalus (DESH) on MRI, fulfilling at least an Evans index0.3 (ventricular enlargement, VE) and a narrowing of the subarachnoid space at the high convexity (tight high convexity, THC). Asymptomatic VE (AVE) plus THC were considered AVIM.Longitudinally throughout 16 years, 11 patients with iNPH were found. The hospital consultation rate was only 9%. Five of the eight patients with AVIM (62.5%) and six of 30 with AVE (20.0%) developed iNPH. Cross-sectionally, eight patients had iNPH (8/104, 7.7% prevalence at the age of 86) in 2016. Disease development was classified into THC-preceding and VE-preceding iNPH. One VE-preceding iNPH case was considered a comorbidity of Alzheimer's dementia.Idiopathic normal pressure hydrocephalus had a high prevalence among octogenarians in the evaluated community. iNPH developed not only via AVIM but also via AVE, the latter was also frequent in the elderly.

The cooling capacity of a radiant panel is usually measured in a certified test chamber and the value obtained is provided by manufacturers for engineers to use for in calculations. However, current measurement standards calculate the cooling capacity of a panel based on the heat carried by the circulating water, which includes the heat extraction from the plenum. Thus, sizing the radiant system based on the cooling capacity of the panels may result in an undersized system. The aim of this study was to quantify the effect of plenum temperature on the room- and plenum-side cooling of suspended radiant ceiling panels, and to develop a method to measure and predict the cooling at both sides of the panel. A cooling capacity measurement methodology with controlled room and plenum temperatures was thus proposed. The present study comprises three parts: 1) a cooling capacity measurement in a test chamber with different temperature differences between the room and plenum; 2) development of an empirical model based on the measurement data to predict the room-side cooling ratio of the panels; 3) validation of the model with dataset obtained in the field. Test chamber results revealed that an increase in the plenum temperature resulted in an increase in the measured cooling capacity but a decrease in the proportion of heat extracted from the room side. Within the tested temperature range (plenum temperature of 24–28 °C, room temperature of 26 °C), the heat extracted from the room side was 77–92% when the panels were insulated and decreased to 46–71% when they were not insulated. An empirical approach for estimating the heat extraction at both sides of the panel was then proposed. The developed model was validated through field measurements in a newly constructed office building equipped with the same panel as the ones from the chamber measurements. The predicted room-side heat extraction had an average error of 6% (with a standard deviation of 3%) compared with the measured value. The measurement and modeling procedure in this study may thus be used by manufacturers to more accurately document the cooling performance of their panels, which will enable engineers to avoid under-sizing of the cooling system.

Dysphagia, defined as a dysfunction in any stage or process of eating, is common in patients with acute exacerbation of heart failure (HF). In some diseases, dysphagia worsens in-hospital mortality, length of hospital stay, and discharge disposition. However, it remains unclear whether dysphagia is associated with poor short-term outcomes in HF patients. The objective of the present study was to determine whether dysphagia affects short-term outcomes in patients with acute exacerbation of HF. A total of 327 patients hospitalized with acute exacerbation of HF were eligible for the study. Patients were divided into a dysphagia group (DG) or a non-dysphagia group (NDG) based on results of the functional oral intake scale (FOIS), which evaluates a patient's ability of eating and swallowing. FOIS is a 7-point scale, with a level of ≤ 5 indicating dysphagia. Following the withdrawal of 16 patients, short-term outcomes such as in-hospital mortality, length of hospital stay, and discharge disposition, of 311 patients were analyzed. All indexes of short-term outcomes were significantly worse in the DG than in the NDG. After propensity score matching, which was performed to adjust for baseline characteristics such as age, sex, height, weight, body mass index, medical history, complications, HF severity, ejection fraction, and biochemical data excluding nutritional status, all short-term outcomes remained significantly worse in the DG than in the NDG. Multivariate analysis showed that FOIS was an independent predictor of in-hospital survival, length of hospital stay, and discharge to home. The present study suggested that dysphagia affected short-term outcomes in patients with acute exacerbation of HF. Therefore, early detection and intervention of dysphagia in HF patients are important.

Objective Dementia is a major cause of disruption for a healthy life expectancy in Japan. It has been suggested that the number of teeth is a modifiable risk factor for cognitive impairment and dementia. We therefore examined the possible association between the cognitive function and the number of natural and artificial teeth in community-dwelling Japanese elderly individuals. Methods Among the participants in our prospective, community-based study, 210 elderly individuals (103 men and 107 women; 78.1±4.9 years; mean age±standard deviation) underwent both dental examinations and a Mini-Mental State Examination (MMSE), as well as various medical checkups, in 2016 and 2017. Results The number of natural teeth was significantly associated with an individual's MMSE score. The percentage of cognitively normal subjects (MMSE scores: 27-30) decreased significantly with a decrease in the number of natural teeth. Among the MMSE items, the calculation ability was significantly and independently associated with the number of natural teeth. Regression was calculated as the predicted score of MMSE =21+0.3× (years of schooling) +0.1× (number of natural teeth). Among individuals with 19 or fewer natural teeth, those who had a total of 20 teeth or more, including both natural and artificial teeth, had significantly higher MMSE scores than those who had 19 or fewer natural and artificial teeth combined. Conclusion The number of natural teeth was significantly associated with the cognitive function, especially the calculation ability, and the use of artificial teeth was associated with the preservation of the cognitive function in community-dwelling elderly individuals.

Objective To examine whether cognitive impairment, deep white matter hyperintensity (DWMH) on brain MRI, and shorter telomere length would be predictors of mortality in community-dwelling Japanese elderly. Methods We followed 259 individuals (74% of all the residents at age 70) from age 70 to 83 years. The mean observation period was 133 ± 34 months. The key clinical characteristics examined included DWMH on brain MRI and cognitive function. Telomere length was also measured in 81 subjects. Both univariate and multivariate analyses were performed. Results Of the 259 subjects, 69 subjects (30 men, 39 women; 26.6%) died during the follow-up period. Cognitive impairment, smoking habits, diabetes mellitus, and moderate to severe DWMH were significant predictors of total mortality in univariate analysis. However, only cognitive impairment and moderate to severe DWMH remained as significant independent predictors of death in multivariate analysis. The rate of mortality increased with additional number of risk factors (cognitive impairment and DWMH). The total mortality of subjects with both cognitive impairment and DWMH was 71.4%. The median telomere length was 7.8 kb in the deceased and 8.2 kb in the living subjects. The deceased subjects had significantly shorter telomere length (P = .0025) than the living subjects. Telomere length with moderate to severe DWMH was higher than without moderate to severe DWMH on brain MRI (P = .017). Conclusions The present study revealed that cognitive impairment, DWMH, and shorter telomere length were significant predictors of total mortality in the community-dwelling Japanese elderly. Furthermore, the combination of cognitive impairment and DWMH increased the mortality rate, as compared with a single risk factor. It is also clarified that a significant difference was present in telomere length by severity of DWMH.

Dysphagia, defined as a dysfunction in any stage or process of eating, is common among heart failure (HF) patients. In some diseases state, dysphagia hinders patients from being discharged to home. However, it remains unclear whether dysphagia affects discharge disposition of HF patients. This study aimed to identify the impact of dysphagia on discharge disposition of HF patients. A total of 323 patients, hospitalized with acute exacerbation of HF, were eligible for the study (excluding patients who lived at nursing care facilities before admission). Following the withdrawal of 37 patients, a total of 286 patients were analyzed. Dysphagia was determined using the functional oral intake scale (FOIS), which evaluates a patient's ability to swallow. The FOIS is a 7-point scale, with a level of ≤ 5 indicating dysphagia. Of the 286 patients analyzed, 231 (80.8%) were discharged to home, and 55 were discharged to nursing care facilities or rehabilitation hospitals (non-home). FOIS level was significantly lower, and dysphagia incidence was significantly higher among patients discharged to non-home than among those discharged to home. Multivariate analysis showed that FOIS level was an independent predictor of discharge disposition. Additionally, after propensity score matching, which was performed to adjust for baseline characteristics, FOIS level remained significantly lower in patients discharged to non-home than in those discharged to home. In conclusion, dysphagia hinders patients hospitalized with HF from being discharged to home. We conclude that evaluating dysphagia and its severity on admission is useful for predicting discharge disposition in patients hospitalized with HF.

Introduction Our previous community-based study demonstrated that some individuals with AVIM [asymptomatic ventriculomegaly with features of idiopathic normal pressure hydrocephalus (iNPH) on magnetic resonance imaging (MRI)] progressed to iNPH in several years. In this hospital-based study, we investigated the progression rate from AVIM to iNPH and its possible predictors. Methods We conducted a prospective study of participants with AVIM from several medical institutions/hospitals in Japan. AVIM is defined as “asymptomatic ventriculomegaly with features of iNPH on MRI”; in the present study, asymptomatic was defined as “0 (no symptoms) or 1 (presence of only subjective, but not objective, symptoms) on the iNPH Grading Scale (iNPH-GS).” We also measured possible predicting factors for AVIM-to-iNPH progression, including age, sex, body weight, blood pressure, diabetes mellitus, dyslipidemia, history of mental disease/head injury/sinusitis/smoking/alcohol-intake, Evans index, and the presence of DESH (disproportionately enlarged subarachnoid-space hydrocephalus) findings on brain MRI, and analyzed these potential predictive values. Results In 2012, 93 participants with AVIM were registered and enrolled in the study. Of these, 52 participants were able to be tracked for three years (until 2015). Of the 52 participants, 27 (52%) developed iNPH during the follow-up period (11 definite, 6 probable, and 10 possible iNPH), whereas 25 participants remained asymptomatic in 2015. Among the possible predictive factors examined, the baseline scores of iNPH-GS predicted the AVIM-to-iNPH progression. Conclusions The multicenter prospective study demonstrated that the progression rate from AVIM to iNPH was ~17% per year, and the baseline scores of iNPH-GS predicted the AVIM-to-iNPH progression.

A 58-year-old woman with a 1-month history of right hand clumsiness and speaking difficulty was admitted to our hospital. A neurological examination revealed sensory aphasia and right hemiparesis. Her laboratory tests showed elevated serum levels of IgG and IgG4, pancytopenia, and liver dysfunction. The results of the imaging studies of her abdomen were compatible with sclerosing cholangitis. Brain MRI showed extensive signal abnormalities in the left hemisphere on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images, extending from left internal capsule to the cerebral peduncle with an irregularly enhancing lesion in the left parietal lobe. A brain biopsy revealed lymphocyte and plasma cell infiltration and reactive gliosis. Most of the plasma cells were IgG positive; however, IgG4-positive plasma cells were sparsely observed. After the initiation of betamethasone treatment, her symptoms and the brain MRI abnormalities showed significant improvement. The brain biopsy results did not meet the current criteria of IgG4-related disease. This is the first reported case of a tumefactive lesion of the brain parenchyma with serum IgG4 elevation, which was responsive to steroid treatment. The accumulation of a greater number of reports on the pathological investigation of cases of possible IgG4-related disease may help to elucidate the exact role of IgG4 in IgG4-related disorders.

Background The epidemiology and pathophysiology of iNPH remain unclear. We aimed to investigate the incidence of iNPH in elderly inhabitants of the community, and to identify how ventriculomegaly develops on brain MRIs and how symptoms develop in iNPH patients. Methods In 2000, 350 inhabitants, all 70-year-olds living in the community of Takahata in Japan, were asked to participate in a survey that included a questionnaire, physical examinations, cognitive screenings, and brain MRI studies. Using brain MRI as a screening, we defined having both Evans index of > 0.3 and a narrow subarachnoid space and cortical sulci at high convexity (tight high convexity, THC) as suspicious findings for iNPH. Among the subjects who showed the iNPH feature on brain MRI, those who had gait disturbance and/or dementia were defined as possible iNPH. Twice during the 10 years, we administered the same check-up. Results In the first survey, 271 inhabitants participated. During the 10 years, three new possible iNPH patients were found. The incidence of iNPH above 70 years old was estimated at 1.2/1000 persons per year. The iNPH patients developed their symptoms and brain MRI findings as follows; first, only THC without ventriculomegaly was observed on their brain MRIs, next, asymptomatic ventriculomegaly with features of iNPH on brain MRIs (AVIM) was seen, and then a final expression of symptoms of iNPH was shown. Conclusions The estimated incidence of iNPH in a community was higher than those estimated by previous studies where they collected patients at hospitals. There were subclinical or preclinical states before the development of iNPH.

BACKGROUND Recent epidemiological studies reported a relationship between 24-hour ambulatory blood pressure (ABP) variability and cardiovascular events. However, the impact of ABP variability on small vessel disease (SVD) progression or cognitive decline in the elderly has seldom been investigated in community-based longitudinal studies. METHODS Subjects (n = 210) underwent ABP monitoring, brain magnetic resonance imaging (MRI), and cognitive testing at baseline and 4 years later. ABP variability was quantified by the SD, weighted SD, coefficient of variation (CV), and average real variability (ARV). ABP variability parameters were divided into 2 groups by median values. RESULTS Multivariable logistic regression analyses showed that higher systolic CV, diastolic weighted SD, and diastolic CV were significant predictors of SVD progression (P = 0.02, 0.03, and 0.02, respectively). In subjects with SVD on the first MRI, higher systolic and diastolic ARV also predicted progression (P = 0.04 and 0.03, respectively). Higher quartiles of systolic weighted SD and CV had higher incidences of SVD progression (P trend = 0.03 and 0.03, respectively, Cochran-Armitage test), and higher quartiles of systolic ARV had higher incidences of SVD progression in subjects with SVD on the first MRI (P trend = 0.03). Higher systolic ARV was an independent predictor of cognitive decline (P < 0.01), and higher tertiles of systolic ARV had higher incidences of cognitive decline (P trend = 0.02). CONCLUSIONS This community-based longitudinal study found that increased ABP variability was associated with SVD progression, particularly in individuals with SVD at baseline. Higher systolic ARV predicted SVD progression and cognitive decline.

Objective We previously reported that, on brain MRI, iNPH features were observed in approximately 1% of asymptomatic elderly community dwellers. This phenomenon is designated asymptomatic ventriculomegaly with features of iNPH on MRI (AVIM). The aim of the present study was to clarify whether a subclinical decline in the neuropsychological function is present in patients with AVIM. Methods We examined eight subjects with AVIM, six subjects with possible iNPH and 21 elderly controls. Neuropsychological tests were used, including the mini-mental state examination (MMSE), the Hasegawa dementia scale-revised (HDS-R), the frontal assessment battery (FAB), the trail making test A&B and semantic and letter verbal fluency tests. Results When comparing the individuals with AVIM with the control subjects, significant differences were found in the scores achieved on the semantic verbal fluency tests and Luria's motor series (fist-edge-palm), a subtest of the FAB. Conclusion The present study suggests that individuals with AVIM demonstrate a slight subclinical decline in the cognitive function and motor regulation, which may represent a prodromal stage of iNPH.

Vesicomyid bivalves have a substantial biomass in deep-sea chemosynthetic biological communities in the Pacific. Using a novel multiplex-PCR (mPCR) method to identify the co-occurring vesicomyids in Sagami Bay, we analyzed the distribution of Calyptogena okutanii and Calyptogena soyoae along environmental gradients. All the known distributions of C. okutanii indicated the different preferences in salinity and temperature to those of C. soyoae, and in Sagami Bay, depth seemed to be an important environmental factor, too. Although the concentration of hydrogen sulfide in sediment was not examined, our results showed that the distributions of these two Calyptogena clams were affected by salinity and temperature.

Little is known about genetic risk factors for idiopathic normal pressure hydrocephalus (iNPH). We examined whether a copy number loss in intron 2 of the SFMBT1 gene could be a genetic risk for shunt-responsive, definite iNPH. Quantitative and digital PCR analyses revealed that 26.0% of shunt-responsive definite iNPH patients (n = 50) had such a genetic change, as compared with 4.2% of the healthy elderly (n = 191) (OR = 7.94, 95%CI: 2.82-23.79, p = 1.8 x 10-5) and 6.3% of patients with Parkinson's disease (n = 32) (OR = 5.18, 95%CI: 1.1-50.8, p = 0.038). The present study demonstrates that a copy number loss within intron 2 of the SFMBT1 gene may be a genetic risk factor for shunt-responsive definite iNPH.

Mutations in the SLC25A13 gene lead to neonatal intrahepatic cholestasis caused by citrin deficiency and/or adult-onset type II citrullinemia (CTLN2). A 62-year-old man presented with recurrent episodes of neuropsychiatric manifestations. On admission, he had disorientation and flapping tremor. Laboratory data showed hyperferritinemia in addition to postprandial hyperammonemia and citrullinemia. A liver biopsy specimen revealed moderate hemosiderin deposits and hepatocytes with macrovesicular fat droplets. Genetic analysis of the SLC25A13 gene identified the previously reported p.S225X mutation and a novel p.D493G mutation. Hyperferritinemia might also be a characteristic finding of CTLN2-related fatty changes of the liver.

Objective Age is known to influence the risk of both cerebral ischemic lesions and impaired cognitive function. Diabetes mellitus (DM) can also be associated with cognitive impairment. However, there has been no study of neuropsychological performance in association with glucose metabolism status and cerebral ischemic lesions in same-aged, community-dwelling elderly persons. The present study was performed to clarify which cognitive domains are associated with impaired glucose metabolism/DM and whether the association is independent of cerebral ischemic lesions. Subjects and Methods A total of 172 residents in Takahata, Japan, all of whom were 78 years old, were evaluated in multiple domains through neuropsychological tests and brain MR images, as well as a medical check-up including tests for glucose metabolism status and conventional vascular risk factors. Glucose metabolism status was determined by analysis of HbA1c level. Results In multiple regression analyses, performance on a verbal fluency (VF) test and the Trail Making Test-Part B, both of which represent executive function, was associated with HbA1c level, even after adjustment for sex, education, cerebral ischemic lesions, and conventional vascular risk factors. The subjects with DM also showed lower VF scores than did those without DM. Conclusion The results of the present study demonstrate that impaired glucose metabolism, independent of the conventional vascular risk factors and cerebral ischemic lesions, may be associated with a decline in executive function in community-dwelling elderly.

Objective Idiopathic normal pressure hydrocephalus (iNPH) is clinically important as a treatable gait disturbance or preventable dementia by shunt operation. We have recently reported that approximately 1.5% of the elderly living in a Japanese community showed ventriculomegaly with features of iNPH on MRI (VIM), which may represent a preclinical stage of iNPH. The purpose of the present study was to identify a possible genetic change in VIM subjects. Methods Eight subjects with VIM and 10 healthy individuals were examined for copy number variations (CNV) with a CNV-targeted whole-genome oligonucleotide microarray (Agilent 400 K CNV array). Another panel of 100 healthy Japanese individuals was screened for CNV by whole-genome using the deCODE-Illumina CNV 370 K chip. Immunohistochemical examination of the human brain was performed using an avidin-biotin-peroxidase complex method. Results Among several genetic changes observed, a copy number loss within the SFMBT1 gene was seen in half of the VIM cases (4 of 8 cases), that was rare among the Japanese control subjects (0/10 by Agilent 400 K CNV array or 1/100 by deCODE/Illumina CNV 370 K chip). Immunohistochemical examination of the human brain revealed that the SFMBT1 protein was localized mainly in the arterial walls, the ependymal cells, and the epithelium of the choroid plexus, all of which play a crucial role in the CSF circulation. Conclusion A segmental copy number loss of the SFMBT1 gene may be involved in the pathological process in some individuals with VIM/iNPH.

The patient was a 69-year-old man who had a two-year history of slowly-progressive gait disturbance, paresthesia of the distal legs and bilateral hearing impairment. Nerve conduction study showed symmetric motor-dominant axonal polyneuropathy of the legs. Gadolinium-enhanced brain and spinal cord MRI revealed bilateral vestibular schwannomas, and multiple small schwannomas in the cauda equina, the surface of spinal cord and lumbar muscles. Genetic examination disclosed a point mutation in the exon 2 (T161C: L54P) of the neurofibromatosis 2 (NF2) gene, and the diagnosis of NF2 was made. It has been reported that axonal polyneuropathy is frequently observed in patients with NF2. Therefore, it is possible that axonal polyneuropathy of the present patient may be due to the abnormality of the NF2 gene, but not to the direct compression of the tumors, because the localization of his schwannomas in the cauda equina and the spinal cord could not explain his symmetric polyneuropathy. Although this patient showed no characteristic clinical manifestations such as cutaneous lesions, gadolinium-enhanced brain and spinal cord MRI was useful for the detection of asymptomatic schwannomas. NF2 should be considered as a differential diagnosis in patients with axonal polyneuropathy, even if it is late-onset.

We report on an 80-year-old woman who had shunt-responsive idiopathic normal pressure hydrocephalus (iNPH). Her brain MRI showed an initial change in the subarachnoid space (a disproportional narrowing of the subarachnoid space at the cerebral high convexities) at the age of 70 years, followed by enlargement of the ventricles (Evans index: 0.31) at the age of 78. The observation suggests that changes in the subarachnoid space may precede ventricular enlargement in iNPH.

Objective: The effects of sebum lipid production by sebaceous gland cells were investigated in vitro following inhibition of cell differentiation by the antioxidants (ascorbyl/tocopheryl) phosphoric acid, ascorbic acid, and pyridoxine cyclic phosphate. Methods: Normal hamster sebaceous gland cells were exposed to various concentrations of the antioxidants for 10 days. Lipids were extracted from the cells and quantitated by high-performance thin-layer chromatography. Numbers of lipid-containing differentiated cells were determined by light microscopy. The superoxide anion scavenging ability of each antioxidant was measured by the nitro blue tetrazolium method. Results: All antioxidants suppressed sebocyte cell differentiation and decreased levels of sebum lipid secretion, with (ascorbyl/tocopheryl) phosphoric acid being the most effective. Antioxidant ability, the number of differentiated sebocyte cells, and sebum secretion level were found to highly correlate. Conclusion: These findings indicate that antioxidant compounds inhibit sebaceous lipid production by suppressing differentiation of sebocytes., 5p. Open Access

Recent evidence has shown an effect of ambulatory heart rate (HR) on cardiovascular events and mortality. Our objective was to determine whether ambulatory HR was related to the progression of cerebral small-vessel disease (SVD) or cognitive decline in community-dwelling elderly people. A cohort of 190 community-dwelling elderly people underwent an ambulatory blood pressure monitoring (ABPM), brain magnetic resonance imaging (MRI) and cognitive testing at baseline, with MRI and cognitive tests repeated 4 years later. HR variability in ABPM was quantified by the s.d. (s.d. and the root mean square of successive differences (RMSSD), and the relationship between HR variability and the progression of SVD/cognitive decline was investigated. We also assessed the association of nighttime HR variability and nocturnal HR dipping. The nighttime RMSSD of participants with the progression of SVD was significantly higher than that of those without progression of SVD (P

For forty-three clinical test values presumably associated to common complex human diseases, we carried out a genome-wide association study using 600K SNPs in a general Japanese population of 1,639 individuals (1,252 after quality control procedures) drawn from a regional cohort, followed by a replication study for statistically significant SNPs (p = 1.95 × 10(-9)-8.34 × 10(-39)) using an independent population of 1,671 from another cohort. In this single two-stage study, we newly found strong and robust associations of common variants at the ABO histo-blood glycosyltransferase locus in 9q32 with the plasma levels of pancreatic lipase (P-LIP), in addition to successful confirmation of the known ABO association of angiotensin converting enzyme (ACE) independent of the ACE1 gene in 17q23.2 with the ACE level. Our results are compatible with the previously reported association between the ABO gene and pancreatic cancer, and show that the effect of these common variants at the ABO locus on the P-LIP and ACE levels is largely opposing and pleiotropic.

Background: Citrin, encoded by SLC25A13, is a component of the malate-aspartate shuttle, which is the main NADH-transporting system in the liver. Citrin deficiency causes neonatal intrahepatic cholestasis (NICCD), which usually resolves within the first year of life. However, small numbers of adults with citrin deficiency develop hyperammonemic encephalopathy, adult-onset type II citrullinemia (CTLN2), which leads to death due to cerebral edema. Liver transplantation is the only definitive therapy for patients with CTLN2. We previously reported that a lactose (galactose)-restricted and medium-chain triglyceride (MCT)-supplemented formula is notably effective for patients with NICCD. Citrin deficiency may impair the glycolysis in hepatocytes because of an increase in the cytosolic NADH/NAD+ ratio, leading to an energy shortage. MCT administration can provide energy to hepatocytes and was expected to have a good effect on CTLN2. Methods: An MCT supplementation therapy under a low-carbohydrate formula was administered to five patients with CTLN2. Four of the patients had episodes of hyperammonemic encephalopathy, and one patient had postprandial hyperammonemia with no symptoms. Results: One of the patients displaying hyperammonemic encephalopathy completely recovered with all normal laboratory findings. Others notably improved in terms of clinical and or laboratory findings with no hyperammonemic symptoms; however, the patients displayed persistent mild citrullinemia and occasionally had postprandial mild hyperammonemia most likely due to an irreversible change in the liver. Conclusions: An MCT supplement can provide energy to hepatocytes and promote hepatic lipogenesis, leading to a reduction in the cytosolic NADH/NAD+ ratio. MCT supplementation under a low-carbohydrate formula could be a promising therapy for CTLN2 and should also be used to prevent CTLN2 to avoid irreversible liver damage.

Lymphomatosis cerebri (LC) is a rare form of primary central nervous system lymphoma (PCNSL). Little is known about cases of LC with spinal cord involvement. Among the 11 PCNSL patients treated in our hospital during a four-year period, we identified two cases of LC with spinal cord lesions. One showed a spinal cord lesion followed by leukoencephalopathy. The other showed a spinal cord lesion after LC. In both cases, the histopathology was diffuse large B-cell lymphoma. It is possible that LC may affect the entire central nerve system, and tumor infiltration to the brain and spinal cord in LC may occur more frequently than has been previously considered.

A method to break glass plate was proposed for substrates of display panel by CO2 laser beam heating. Generally, glass plate is broken by growing micro-crack which is generated during scribing from tip of a chisel under optimum load. And then, the generated micro-cracks are grown by mechanical force applied to the scribed trace. For laser breaking, the micro-crack is grown by tensile stress due to thermal expansion which arises from temperature rise by a CO2 laser beam irradiation onto the scribed trace instead of applying mechanical force. This paper deals with experimental results of the optimum laser irradiating condition and discussion of the laser breaking mechanisms. It was possible to break the glass plate finely and precisely without applying mechanical force at the same scribing velocity.

The aluminum surface was modified by CO2 laser beam irradiation onto a surface coated 0.2mm thick with TiO2 powder. Surface and cross sectional views of melted layers formed under different laser irradiating conditions were observed by optical microscope. Cross-sectional hardness was evaluated by micro-Vickers hardness measurement, and the composition was studied by microdiffraction analysis. A hard alloyed layer formed on the surface of the Al substrate at laser power exceeding 2kW. At less than 2kW, a clad layer formed. The alloyed layer consists of eutectic Al+Al3Ti. Hardening in the alloyed layer is caused by crystallization of the Al3Ti intermetallic compound formed by a reaction between substrate Al and Ti separated from TiO2. TiO2 powder is thus useful in laser alloying.

The new functional materials have been studied to apply to micro machines or electronic devices. However in order to develop new materials, it is indispensable to control the film thickness of nano-meter or sub-nanometer and to deposit the fine film of the same roughness as substrate surface. This paper describes the experimental results, the possibility to fabricate metal films of nanometer order thickness and to synthesize new materials of multilayer structure using the Knudsen-cell in the high vacuum MBE chamber. The structure of the films was analyzed by X-ray diffraction.

Chemical oxidative polymerization of dodecylbenzenesulfonic acid o-anisidine salt (DBSAns) with 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) as an electron acceptor in tetrahydrofuran (THF) was studied as a function of polymer yield, conductivity and molecular weight distribution. Polymerization was proceeded to yield a homogeneous transparent and green black solution containing poly(o-anisidine) (PAns) which is soluble in various organic solvents. Molecular weight distribution of PAns was found to be changed from bimodal to unimodal with increasing electron acceptor/monomer (DDQ/DBSAns) molar ratio.

Poly(o-anisidine) (PANs) and PANs-coated silica particles were prepared by oxidative polymerization of o-anisidine using ammonium persulphate in the absence and presence of silica particles, respectively. The entire surface of the silica particles was completely covered with PANs polymerized using low concentration of o-anisidine. The effects on the electrorheological behavior of surface modification of the silica particles coated with PANs were studied under oscillatory shear. Electrorheological properties of PANs and PANs-coated silica particle suspensions were found to exhibit higher performance in nonaqueous solutions than those of silica particle suspensions even at high temperatures.

Some patients with acquired long QT syndrome (LQTS) represent an incomplete form of congenital LQTS in which a mutation or polymorphism in one of the LQTS genes is clinically inapparent until the patient is exposed to a particular drug or other predisposing factor. A 15-year-old man in the

Mutations in the SLC25A13 gene lead to neonatal intrahepatic cholestasis caused by citrin deficiency and/or adult-onset type II citrullinemia (CTLN2). A 62-year-old man presented with recurrent episodes of neuropsychiatric manifestations. On admission, he had disorientation and flapping tremor. Laboratory data showed hyperferritinemia in addition to postprandial hyperammonemia and citrullinemia. A liver biopsy specimen revealed moderate hemosiderin deposits and hepatocytes with macrovesicular fat droplets. Genetic analysis of the SLC25A13 gene identified the previously reported p.S225X mutation and a novel p.D493G mutation. Hyperferritinemia might also be a characteristic finding of CTLN2-related fatty changes of the liver.

In this study, electromigration (EM) reliability of TSV-microbump (μ-bump) joints was investigated. Sn-based μ-bumps with three different schemes of metallization were tested under current stressing at elevated temperatures. EM-stressed μ-bumps, together with thermal anneal-only μ-bumps and as-received controls, were cross-sectioned and characterized using scanning electron microscope (SEM), energy dispersed x-ray (EDX) and focused ion beam (FIB). Intermetallic compound (IMC) growth kinetics under EM for the three types of metallization were obtained, and compared with those subjected to thermal annealing only. Results showed good EM performance of the TSV μ-bump joints, indicating that IMC formation plays an important role in improving the EM reliability of μ-bump joints. However, non-EM related voids were observed in the μ-bumps, and the voiding mechanisms were discussed.

To enable the miniaturization, electrical performance and heterogeneous functionality needs for emerging Analog applications, a stacked Wafer-level Chip Scale Package (WCSP) package platform has been developed using Through-Silicon Via (TSV) technology. This allows stacking of ICs, MEMS, passives and other components in the vertical direction onto active or passive TSV wafers, to create innovative System-in-Package (SiP) product solutions. Since Analog devices are small in size and cost is a key care about, a careful selection of the integration flow is required to achieve a low cost packaging solution. In this work, an integration flow for the stacked WCSP package is presented, along with development details for the Chip-on-Wafer (CoW) bonding and wafer overmolding unit processes. The test vehicle was 3mm × 3mm in size and used 25u diameter Cu TSVs in a 200mm diameter wafer. Interconnect reliability evaluations were done with different micro-bump Under Bump Metallurgy (UBM) and TSV tip surface finish metallization combinations. Wafer ovemolding development included warpage, saw and adhesion evaluations with multiple mold materials. A back-end assembly flow was established with a mass reflow bonding process and an overmold material with low CTE and intermediate T g and modulus. Samples were prepared with mold-on-die and exposed die package structures. Excellent time-zero yields were obtained, with an average TSV micro-bump interconnect resistance of 25 mohms. Results and failures modes from preliminary reliability testing are included.

Bonded soft ferrite using injection molding is expected to have applications, because it conforms with the trend toward miniaturization and complication of the shape of electronic devices, At present, the permeability of bonded soft ferrite is too low for it to have practical applications, because of the mixture of ferrite powder and resin. Increasing its permeability is thus an important problem to be solved. To this end, we used kneading and injection molding to produce bonded soft ferrites mixed with nylon resin and several kinds of NiCuZn ferrite powder with various size distributions, and then measured the soft magnetic properties and electric resistance of bonded NiCuZn ferrites.

We investigated if there are individuals at a preclinical stage of idiopathic normal pressure hydrocephalus (iNPH) in a general population. All the residents aged 61 years and 70-72 years in the two communities of Japan (n=1142) were requested to take brain MRI examination. 790 residents (69.2%) participated in this study. Among them, 51 individuals (6.46%) had the enlarged ventricles (Evans index of >0.3), 12 (1.52%) of which showed the iNPH features on MRI. Of the 12 individuals, 8 were asymptomatic, while 4 had gait disturbance and/or dementia (possible iNPH). During a follow-up period of 4-8 years, two of the 8 asymptomatic subjects developed dementia and/or gait disturbance. The prevalence of possible iNPH was 0.51% (4/790) among Japanese elderly (>61 years of age). Asymptomatic ventriculomegaly with the iNPH features on MRI (AVIM) may represent a preclinical stage of iNPH. To identify a possible genetic change of AVIM and possible iNPH, we performed a genome-wide screening for copy number variations (CNV), and found that a segmental copy number loss of the SFMBT1 gene may be a genetic risk for the disease.

Normal pressure hydrocephalus (NPH) has two clinical forms: secondary NPH and idiopathic NPH (iNPH). Most patients with NPH occur sporadically: until now, only two families have been reported to have sibling cases of NPH. We here report a large family with 4 patients with elderly-onset NPH in three generations. All of them had cognitive impairment, gait disturbance, and urinary problems, along with normal pressure of cerebrospinal fluid. Their brain MRI showed enlargement of the ventricles and a disproportional narrowing of the subarachnoid space and cortical sulci at the high convexity of the cerebrum, which are the features of iNPH on MRI. The family interview also disclosed additional 4 patients who were suspected as having NPH. The disease seems to be inherited in an autosomal-dominant fashion. No known causes of secondary NPH were found in any of the patients. This is the first report to show a large family with NPH patients in three generations, who had clinical and MRI features indistinguishable from iNPH. This seems to represent a novel subgroup of NPH, familial NPH.