DOE Office of Scientific and Technical Information (OSTI.GOV)

Prescott, Ryan; Marger, Bernard L.; Chiu, Ailsa

During the second iteration of the US NDC Modernization Elaboration phase (E2), the SNL US NDC Modernization project team completed follow-on COTS surveys & exploratory prototyping related to the Object Storage & Distribution (OSD) mechanism, and the processing control software infrastructure. This report summarizes the E2 prototyping work.

Medicare Utilization and Expenditures Around Incident Dementia in a Multiethnic Cohort.

PubMed

Zhu, Carolyn W; Cosentino, Stephanie; Ornstein, Katherine; Gu, Yian; Scarmeas, Nikolaos; Andrews, Howard; Stern, Yaakov

2015-11-01

Few studies have examined patterns of health care utilization and costs during the period around incident dementia. Participants were drawn from the Washington Heights-Inwood Columbia Aging Project, a multiethnic, population-based, prospective study of cognitive aging of Medicare beneficiaries in a geographically defined area of northern Manhattan. Medicare utilization and expenditure were examined in individuals with clinically diagnosed dementia from 2 years before until 2 years after the initial diagnosis. A sample of non-demented individuals who were matched on socio-demographic and clinical characteristics at study enrollment was used as controls. Multivariable regression analysis estimated effects on Medicare utilization and expenditures associated with incident dementia. During the 2 years before incident dementia, rates of inpatient admissions and outpatient visits were similar between dementia patients and non-demented controls, but use of home health and skilled nursing care and durable medical equipment were already higher in dementia patients. Results showed a small but significant excess increase associated with incident dementia in inpatient admissions but not in other areas of care. In the 2 years before incident dementia, total Medicare expenditures were already higher in dementia patients than in non-demented controls. But we found no excess increases in Medicare expenditures associated with incident dementia. Demand for medical care already is increasing and costs are higher at the time of incident dementia. There was a small but significant excess risk of inpatient admission associated with incident dementia. Published by Oxford University Press on behalf of the Gerontological Society of America 2015.

Ligand-controlled assembly of Cd(II) coordination polymers based on mixed ligands of naphthalene-dicarboxylate and dipyrido[3,2-d:2‧,3‧-f]quinoxaline: From 0D+1D cocrystal, 2D rectangular network (4,4), to 3D PtS-type architecture

NASA Astrophysics Data System (ADS)

Liu, Guocheng; Chen, Yongqiang; Wang, Xiuli; Chen, Baokuan; Lin, Hongyan

2009-03-01

Three novel Cd(II) coordination polymers, namely, [Cd(Dpq)(1,8-NDC)(H 2O) 2][Cd(Dpq)(1,8-NDC)]·2H 2O ( 1), [Cd(Dpq)(1,4-NDC)(H 2O)] ( 2), and [Cd(Dpq)(2,6-NDC)] ( 3) have been obtained from hydrothermal reactions of cadmium(II) nitrate with the mixed ligands dipyrido [3,2-d:2',3'-f]quinoxaline (Dpq) and three structurally related naphthalene-dicarboxylate ligands [1,8-naphthalene-dicarboxylic acid (1,8-H 2NDC), 1,4-naphthalene-dicarboxylic acid (1,4-H 2NDC), and 2,6-naphthalene-dicarboxylic acid (2,6-H 2NDC)]. Single-crystal X-ray diffraction analysis reveals that the three polymers exhibit novel structures due to different naphthalene-dicarboxylic acid. Compound 1 is a novel cocrystal of left- and right-handed helical chains and binuclear complexes and ultimately packed into a 3D supramolecular structure through hydrogen bonds and π- π stacking interactions. Compound 2 shows a 2D rectangular network (4,4) bridged by 1,4-NDC with two kinds of coordination modes and ultimately packed into a 3D supramolecular structure through inter-layer π- π stacking interactions. Compound 3 is a new 3D coordination polymer with distorted PtS-type network. In addition, the title compounds exhibit blue/green emission in solid state at room temperature.

Frontal white matter hyperintensities, clasmatodendrosis and gliovascular abnormalities in ageing and post-stroke dementia

PubMed Central

Chen, Aiqing; Akinyemi, Rufus O.; Hase, Yoshiki; Firbank, Michael J.; Ndung’u, Michael N.; Foster, Vincent; Craggs, Lucy J. L.; Washida, Kazuo; Okamoto, Yoko; Thomas, Alan J.; Polvikoski, Tuomo M.; Allan, Louise M.; Oakley, Arthur E.; O’Brien, John T.; Horsburgh, Karen; Ihara, Masafumi

2016-01-01

Abstract White matter hyperintensities as seen on brain T 2 -weighted magnetic resonance imaging are associated with varying degrees of cognitive dysfunction in stroke, cerebral small vessel disease and dementia. The pathophysiological mechanisms within the white matter accounting for cognitive dysfunction remain unclear. With the hypothesis that gliovascular interactions are impaired in subjects with high burdens of white matter hyperintensities, we performed clinicopathological studies in post-stroke survivors, who had exhibited greater frontal white matter hyperintensities volumes that predicted shorter time to dementia onset. Histopathological methods were used to identify substrates in the white matter that would distinguish post-stroke demented from post-stroke non-demented subjects. We focused on the reactive cell marker glial fibrillary acidic protein (GFAP) to study the incidence and location of clasmatodendrosis, a morphological attribute of irreversibly injured astrocytes. In contrast to normal appearing GFAP+ astrocytes, clasmatodendrocytes were swollen and had vacuolated cell bodies. Other markers such as aldehyde dehydrogenase 1 family, member L1 (ALDH1L1) showed cytoplasmic disintegration of the astrocytes. Total GFAP+ cells in both the frontal and temporal white matter were not greater in post-stroke demented versus post-stroke non-demented subjects. However, the percentage of clasmatodendrocytes was increased by >2-fold in subjects with post-stroke demented compared to post-stroke non-demented subjects ( P = 0.026) and by 11-fold in older controls versus young controls ( P < 0.023) in the frontal white matter. High ratios of clasmotodendrocytes to total astrocytes in the frontal white matter were consistent with lower Mini-Mental State Examination and the revised Cambridge Cognition Examination scores in post-stroke demented subjects. Double immunofluorescent staining showed aberrant co-localization of aquaporin 4 (AQP4) in retracted GFAP+ astrocytes with disrupted end-feet juxtaposed to microvessels. To explore whether this was associated with the disrupted gliovascular interactions or blood–brain barrier damage, we assessed the co-localization of GFAP and AQP4 immunoreactivities in post-mortem brains from adult baboons with cerebral hypoperfusive injury, induced by occlusion of three major vessels supplying blood to the brain. Analysis of the frontal white matter in perfused brains from the animals surviving 1–28 days after occlusion revealed that the highest intensity of fibrinogen immunoreactivity was at 14 days. At this survival time point, we also noted strikingly similar redistribution of AQP4 and GFAP+ astrocytes transformed into clasmatodendrocytes. Our findings suggest novel associations between irreversible astrocyte injury and disruption of gliovascular interactions at the blood–brain barrier in the frontal white matter and cognitive impairment in elderly post-stroke survivors. We propose that clasmatodendrosis is another pathological substrate, linked to white matter hyperintensities and frontal white matter changes, which may contribute to post-stroke or small vessel disease dementia. PMID:26667280

Military and Security Developments Involving the Democratic People’s Republic of Korea: Annual Report to Congress

DTIC Science & Technology

2013-01-01

underground, cross-border tunnels to attack high-value targets like command and control nodes or air bases. Theater Ballistic Missiles. North Korea has...fomenting unrest and revolution. Command and Control. The DPRK National Defense Commission ( NDC ) is the symbolic nominal authority over the North’s...and control is exercised by its subordinate General Staff Department. The 1992 constitution gives control of the North’s military to the NDC , and

Cerebrovascular Smooth Muscle Actin Is Increased in Non-Demented Subjects with Frequent Senile Plaques at Autopsy: Implications for the Pathogenesis of Alzheimer Disease

PubMed Central

Hulette, Christine M.; Ervin, John F.; Edmonds, Yvette; Antoine, Samantha; Stewart, Nicolas; Szymanski, Mari H.; Hayden, Kathleen M; Pieper, Carl F.; Burke, James R.; Welsh-Bohmer, Kathleen A.

2009-01-01

We previously found that vascular smooth muscle actin (SMA) is reduced in the brains of patients with late stage Alzheimer disease (AD) compared to brains of non-demented, neuropathologically normal subjects. To assess the pathogenetic significance and disease specificity of this finding, we studied 3 additional patient groups: non-demented subjects without significant AD type pathology (“Normal”, n = 20); non-demented subjects with frequent senile plaques at autopsy (“Preclinical AD”, n = 20); and subjects with frontotemporal dementia, (“FTD”, n = 10). The groups were matched for gender and age with those previously reported; SMA immunohistochemistry and image analysis were performed as previously described. Surprisingly, SMA expression in arachnoid, cerebral cortex and white matter arterioles was greater in the Preclinical AD group than in the Normal and FTD groups. The plaques were not associated with amyloid angiopathy or other vascular disease in this group. SMA expression in the brains of the Normal group was intermediate between the Preclinical AD and FTD groups. All 3 groups exhibited much greater SMA expression than in our previous report. The presence of frequent plaques and increased arteriolar SMA expression in the brains of non-demented subjects suggest that increased SMA expression might represent a physiologic response to neurodegeneration that could prevent or delay overt expression dementia in AD. PMID:19287310

In-vivo measurements of regional acetylcholine esterase activity in degenerative dementia: comparison with blood flow and glucose metabolism.

PubMed

Herholz, K; Bauer, B; Wienhard, K; Kracht, L; Mielke, R; Lenz, M O; Strotmann, T; Heiss, W D

2000-01-01

Memory and attention are cognitive functions that depend heavily on the cholinergic system. Local activity of acetylcholine esterase (AChE) is an indicator of its integrity. Using a recently developed tracer for positron emission tomography (PET), C-11-labeled N-methyl-4-piperidyl-acetate (C11-MP4A), we measured regional AChE activity in 4 non-demented subjects, 4 patients with dementia of Alzheimer type (DAT) and 1 patient with senile dementia of Lewy body type (SDLT), and compared the findings with measurements of blood flow (CBF) and glucose metabolism (CMRGlc). Initial tracer extraction was closely related to CBF. AChE activity was reduced significantly in all brain regions in demented subjects, whereas reduction of CMRGlc and CBF was more limited to temporo-parietal association areas. AChE activity in SDLT was in the lower range of values in DAT. Our results indicate that, compared to non-demented controls, there is a global reduction of cortical AChE activity in dementia. Dementia, cholinergic system, acetylcholine esterase, positron emission tomography, cerebral blood flow, cerebral glucose metabolism.

Some aspects of colour perception among patients with Alzheimer's disease.

PubMed

Wijk, H; Sivik, L

1995-01-01

The proportion of elderly people in western societies is on the increase. At the same time, demands are being heard for improvements in the quality of health care, including the design of the physical environment. The aim of this study was to call attention to some aspects of colour and the possibilities of using it as an orientational aid for institutionalized demented patients and thereby enhance the quality of their care. A pilot study was carried out to establish whether patients with Alzheimer's disease are different from non-demented patients regarding certain aspects of colour perception. Twelve hospitalized patients with Alzheimer's disease were compared with a matched control group of non-demented patients regarding colour naming, colour discrimination and colour preference. No significant differences were found between the groups. In an additional experiment to test short-term memory it was found that the patients with Alzheimer's disease gained substantial help from colour cues. It is concluded that colour should be taken into account in the designing of the health care environment, particularly geriatric wards.

Type 2 diabetes and/or its treatment leads to less cognitive impairment in Alzheimer's disease patients.

PubMed

Domínguez, Raúl O; Marschoff, Enrique R; González, Silvia E; Repetto, Marisa G; Serra, Jorge A

2012-10-01

To evaluate the cognitive performance of a homogeneous population of Alzheimer's disease (AD), non-demented Type 2 Diabetes Mellitus (DIAB), demented with concomitant diseases (AD+DIAB) and healthy control subjects. AD is a progressive dementia disorder characterized clinically by impairment of memory, cognition and behavior. Recently, a major research interest in AD has been placed on early evaluation. Diabetes is one of the clinical conditions that represent the greatest risk of developing oxidative stress and dementia. Glucose overload, leading to the development of impaired-induced insulin secretion in DIAB and has been suggested to slow or deter AD pathogenesis. The degree of cognitive impairment was determined on the Alzheimer Disease Assessment Scale-Cognitive (ADAS-Cog) and the Folstein's Mini Mental State Examination (MMSE); the severity of dementia was quantified applying the Clinical Dementia Rating (CDR) test; the Hamilton test was employed to evaluate depressive conditions; the final population studied was 101 subjects. The cognitive deterioration is statistically significantly lower (p<0.05) in AD+DIAB patients as compared with AD patients. In this longitudinal study the superimposed diabetic condition was associated with a lower rate of cognitive decline, while diabetic non-demented patients and controls present normal scores. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

White matter integrity and cognition in Parkinson's disease: a cross-sectional study

PubMed Central

Auning, Eirik; Kjærvik, Veslemøy Krohn; Selnes, Per; Aarsland, Dag; Haram, Astrid; Bjørnerud, Atle; Hessen, Erik; Esnaashari, Abdolreza; Fladby, Tormod

2014-01-01

Objective We used diffusion tensor imaging (DTI) to test the following hypotheses: (1) there is decreased white matter (WM) integrity in non-demented Parkinson’s disease (PD), (2) WM integrity is differentially reduced in PD and early Alzheimer’s disease (AD) and (3) DTI changes in non-demented PD are specifically associated with cognitive performance. Methods This study included 18 non-demented patients with PD, 18 patients with mild cognitive impairment due to incipient AD and 19 healthy elderly normal control (NC) participants in a cross-sectional design. The participants underwent DTI, and tract-based spatial statistics was used to analyse and extract radial diffusivity and fractional anisotropy. Correlations between scores from a battery of neuropsychological tests and DTI were performed in the PD group. Results Patients with PD had significant differences in DTI in WM underlying the temporal, parietal and occipital cortex as compared with NC. There were no significant differences between the PD and AD groups in the primary region of interest analyses, but compared with NC there was a tendency for more anterior changes in AD in contrast to more posterior changes in PD. In a secondary whole-brain analysis there were frontoparietal areas with significant differences between AD and PD. In patients with PD, there were significant correlations between DTI parameters in WM underlying the prefrontal cortex and executive and visuospatial abilities. Conclusions In early, non-demented PD we found reduced WM integrity underlying the temporal, parietal and occipital cortices. In addition, WM integrity changes in prefrontal areas were associated with executive and visuospatial ability. These findings support that DTI may be an important biomarker in early PD, and that WM changes are related to cognitive impairment in PD. PMID:24448846

Ligand-controlled assembly of Cd(II) coordination polymers based on mixed ligands of naphthalene-dicarboxylate and dipyrido[3,2-d:2',3'-f]quinoxaline: From 0D+1D cocrystal, 2D rectangular network (4,4), to 3D PtS-type architecture

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu Guocheng; Chen Yongqiang; Wang Xiuli

Three novel Cd(II) coordination polymers, namely, [Cd(Dpq)(1,8-NDC)(H{sub 2}O){sub 2}][Cd(Dpq)(1,8-NDC)].2H{sub 2}O (1), [Cd(Dpq)(1,4-NDC)(H{sub 2}O)] (2), and [Cd(Dpq)(2,6-NDC)] (3) have been obtained from hydrothermal reactions of cadmium(II) nitrate with the mixed ligands dipyrido [3,2-d:2',3'-f]quinoxaline (Dpq) and three structurally related naphthalene-dicarboxylate ligands [1,8-naphthalene-dicarboxylic acid (1,8-H{sub 2}NDC), 1,4-naphthalene-dicarboxylic acid (1,4-H{sub 2}NDC), and 2,6-naphthalene-dicarboxylic acid (2,6-H{sub 2}NDC)]. Single-crystal X-ray diffraction analysis reveals that the three polymers exhibit novel structures due to different naphthalene-dicarboxylic acid. Compound 1 is a novel cocrystal of left- and right-handed helical chains and binuclear complexes and ultimately packed into a 3D supramolecular structure through hydrogen bonds and {pi}-{pi} stacking interactions. Compoundmore » 2 shows a 2D rectangular network (4,4) bridged by 1,4-NDC with two kinds of coordination modes and ultimately packed into a 3D supramolecular structure through inter-layer {pi}-{pi} stacking interactions. Compound 3 is a new 3D coordination polymer with distorted PtS-type network. In addition, the title compounds exhibit blue/green emission in solid state at room temperature. - Graphical abstract: Three novel Cd(II) compounds have been synthesized under hydrothermal conditions exhibiting a systematic variation of architecture by the employment of three structurally related naphthalene-dicarboxylate ligands.« less

Writing errors as a result of frontal dysfunction in Japanese patients with amyotrophic lateral sclerosis.

PubMed

Tsuji-Akimoto, Sachiko; Hamada, Shinsuke; Yabe, Ichiro; Tamura, Itaru; Otsuki, Mika; Kobashi, Syoji; Sasaki, Hidenao

2010-12-01

Loss of communication is a critical problem for advanced amyotrophic lateral sclerosis (ALS) patients. This loss of communication is mainly caused by severe dysarthria and disability of the dominant hand. However, reports show that about 50% of ALS patients have mild cognitive dysfunction, and there are a considerable number of case reports on Japanese ALS patients with agraphia. To clarify writing disabilities in non-demented ALS patients, eighteen non-demented ALS patients and 16 controls without neurological disorders were examined for frontal cognitive function and writing ability. To assess writing errors statistically, we scored them on their composition ability with the original writing error index (WEI). The ALS and control groups did not differ significantly with regard to age, years of education, or general cognitive level. Two patients could not write a letter because of disability of the dominant hand. The WEI and results of picture arrangement tests indicated significant impairment in the ALS patients. Auditory comprehension (Western Aphasia Battery; WAB IIC) and kanji dictation also showed mild impairment. Patients' writing errors consisted of both syntactic and letter-writing mistakes. Omission, substitution, displacement, and inappropriate placement of the phonic marks of kana were observed; these features have often been reported in Japanese patients with agraphia resulted from a frontal lobe lesion. The most frequent type of error was an omission of kana, the next most common was a missing subject. Writing errors might be a specific deficit for some non-demented ALS patients.

Frontal white matter hyperintensities, clasmatodendrosis and gliovascular abnormalities in ageing and post-stroke dementia.

PubMed

Chen, Aiqing; Akinyemi, Rufus O; Hase, Yoshiki; Firbank, Michael J; Ndung'u, Michael N; Foster, Vincent; Craggs, Lucy J L; Washida, Kazuo; Okamoto, Yoko; Thomas, Alan J; Polvikoski, Tuomo M; Allan, Louise M; Oakley, Arthur E; O'Brien, John T; Horsburgh, Karen; Ihara, Masafumi; Kalaria, Raj N

2016-01-01

White matter hyperintensities as seen on brain T2-weighted magnetic resonance imaging are associated with varying degrees of cognitive dysfunction in stroke, cerebral small vessel disease and dementia. The pathophysiological mechanisms within the white matter accounting for cognitive dysfunction remain unclear. With the hypothesis that gliovascular interactions are impaired in subjects with high burdens of white matter hyperintensities, we performed clinicopathological studies in post-stroke survivors, who had exhibited greater frontal white matter hyperintensities volumes that predicted shorter time to dementia onset. Histopathological methods were used to identify substrates in the white matter that would distinguish post-stroke demented from post-stroke non-demented subjects. We focused on the reactive cell marker glial fibrillary acidic protein (GFAP) to study the incidence and location of clasmatodendrosis, a morphological attribute of irreversibly injured astrocytes. In contrast to normal appearing GFAP+ astrocytes, clasmatodendrocytes were swollen and had vacuolated cell bodies. Other markers such as aldehyde dehydrogenase 1 family, member L1 (ALDH1L1) showed cytoplasmic disintegration of the astrocytes. Total GFAP+ cells in both the frontal and temporal white matter were not greater in post-stroke demented versus post-stroke non-demented subjects. However, the percentage of clasmatodendrocytes was increased by >2-fold in subjects with post-stroke demented compared to post-stroke non-demented subjects (P = 0.026) and by 11-fold in older controls versus young controls (P < 0.023) in the frontal white matter. High ratios of clasmotodendrocytes to total astrocytes in the frontal white matter were consistent with lower Mini-Mental State Examination and the revised Cambridge Cognition Examination scores in post-stroke demented subjects. Double immunofluorescent staining showed aberrant co-localization of aquaporin 4 (AQP4) in retracted GFAP+ astrocytes with disrupted end-feet juxtaposed to microvessels. To explore whether this was associated with the disrupted gliovascular interactions or blood-brain barrier damage, we assessed the co-localization of GFAP and AQP4 immunoreactivities in post-mortem brains from adult baboons with cerebral hypoperfusive injury, induced by occlusion of three major vessels supplying blood to the brain. Analysis of the frontal white matter in perfused brains from the animals surviving 1-28 days after occlusion revealed that the highest intensity of fibrinogen immunoreactivity was at 14 days. At this survival time point, we also noted strikingly similar redistribution of AQP4 and GFAP+ astrocytes transformed into clasmatodendrocytes. Our findings suggest novel associations between irreversible astrocyte injury and disruption of gliovascular interactions at the blood-brain barrier in the frontal white matter and cognitive impairment in elderly post-stroke survivors. We propose that clasmatodendrosis is another pathological substrate, linked to white matter hyperintensities and frontal white matter changes, which may contribute to post-stroke or small vessel disease dementia. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.

Cost-of-illness study in a retrospective cohort of patients with dementia in Lima, Peru

PubMed Central

Custodio, Nilton; Lira, David; Herrera-Perez, Eder; del Prado, Liza Nuñez; Parodi, José; Guevara-Silva, Erik; Castro-Suarez, Sheila; Montesinos, Rosa

2015-01-01

Dementia is a major cause of dependency and disability among older persons, and imposes huge economic burdens. Only a few cost-of-illness studies for dementia have been carried out in middle and low-income countries. Objective The aim of this study was to analyze costs of dementia in demented patients of a private clinic in Lima, Peru. Methods. We performed a retrospective, cohort, 3-month study by extracting information from medical records of demented patients to assess the use of both healthcare and non-healthcare resources. The total costs of the disease were broken down into direct (medical and social care costs) and indirect costs (informal care costs). Results. In 136 outpatients, we observed that while half of non-demented patients had total care costs of less than US$ 23 over three months, demented patients had costs of US$ 1500 or over (and more than US$ 1860 for frontotemporal dementia). In our study, the monthly cost of a demented patient (US$ 570) was 2.5 times higher than the minimum wage (legal minimum monthly wage in Peru for 2011: US$ 222.22). Conclusion. Dementia constitutes a socioeconomic problem even in developing countries, since patients involve high healthcare and non-healthcare costs, with the costs being especially high for the patient's family. PMID:29213939

Cost-of-illness study in a retrospective cohort of patients with dementia in Lima, Peru.

PubMed

Custodio, Nilton; Lira, David; Herrera-Perez, Eder; Del Prado, Liza Nuñez; Parodi, José; Guevara-Silva, Erik; Castro-Suarez, Sheila; Montesinos, Rosa

2015-01-01

Dementia is a major cause of dependency and disability among older persons, and imposes huge economic burdens. Only a few cost-of-illness studies for dementia have been carried out in middle and low-income countries. The aim of this study was to analyze costs of dementia in demented patients of a private clinic in Lima, Peru. We performed a retrospective, cohort, 3-month study by extracting information from medical records of demented patients to assess the use of both healthcare and non-healthcare resources. The total costs of the disease were broken down into direct (medical and social care costs) and indirect costs (informal care costs). In 136 outpatients, we observed that while half of non-demented patients had total care costs of less than US$ 23 over three months, demented patients had costs of US$ 1500 or over (and more than US$ 1860 for frontotemporal dementia). In our study, the monthly cost of a demented patient (US$ 570) was 2.5 times higher than the minimum wage (legal minimum monthly wage in Peru for 2011: US$ 222.22). Dementia constitutes a socioeconomic problem even in developing countries, since patients involve high healthcare and non-healthcare costs, with the costs being especially high for the patient's family.

Specific Impairments in the Recognition of Emotional Facial Expressions in Parkinson’s Disease

PubMed Central

Clark, Uraina S.; Neargarder, Sandy; Cronin-Golomb, Alice

2008-01-01

Studies investigating the ability to recognize emotional facial expressions in non-demented individuals with Parkinson’s disease (PD) have yielded equivocal findings. A possible reason for this variability may lie in the confounding of emotion recognition with cognitive task requirements, a confound arising from the lack of a control condition using non-emotional stimuli. The present study examined emotional facial expression recognition abilities in 20 non-demented patients with PD and 23 control participants relative to their performances on a non-emotional landscape categorization test with comparable task requirements. We found that PD participants were normal on the control task but exhibited selective impairments in the recognition of facial emotion, specifically for anger (driven by those with right hemisphere pathology) and surprise (driven by those with left hemisphere pathology), even when controlling for depression level. Male but not female PD participants further displayed specific deficits in the recognition of fearful expressions. We suggest that the neural substrates that may subserve these impairments include the ventral striatum, amygdala, and prefrontal cortices. Finally, we observed that in PD participants, deficiencies in facial emotion recognition correlated with higher levels of interpersonal distress, which calls attention to the significant psychosocial impact that facial emotion recognition impairments may have on individuals with PD. PMID:18485422

National data centre preparedness exercise 2015 (NPE2015): MY-NDC progress result and experience

NASA Astrophysics Data System (ADS)

Rashid, Faisal Izwan Abdul; Zolkaffly, Muhammed Zulfakar

2017-01-01

Malaysia has established the National Data Centre (MY-NDC) in December 2005. MY-NDC is tasked to perform the Comprehensive Nuclear-Test-Ban-Treaty (CTBT) data management as well as providing relevant information for Treaty related events to the Malaysian Nuclear Agency (Nuclear Malaysia) as the CTBT National Authority. In the late 2015, MY-NDC has participated in the National Data Centre Preparedness Exercise 2015 (NPE 2015) which aims to access the level of readiness at MY-NDC. This paper aims at presenting the progress result of NPE 2015 as well as highlighting MY-NDC experience in NPE 2015 compared to previous participation in NPE 2013. MY-NDC has utilised available resources for NPE 2015. In NPE 2015, MY-NDC has performed five type of analyses compared with only two analyses in NPE 2013. Participation in the NPE 2015 has enabled MY-NDC to assess its capability and identify rooms for improvement.

Evaluation of improved γ-aminobutyric acid production in yogurt using Lactobacillus plantarum NDC75017.

PubMed

Shan, Y; Man, C X; Han, X; Li, L; Guo, Y; Deng, Y; Li, T; Zhang, L W; Jiang, Y J

2015-04-01

Most γ-aminobutyric acid (GABA)-producing microorganisms are lactic acid bacteria (LAB), but the yield of GABA is limited in most of these GABA-producing strains. In this study, the production of GABA was carried out by using Lactobacillus plantarum NDC75017, a strain screened from traditional fermented dairy products in China. Concentrations of substrate (l-monosodium glutamate, L-MSG) and coenzyme (pyridoxal-5-phosphate, PLP) of glutamate decarboxylase (GAD) and culture temperature were investigated to evaluate their effects on GABA yield of Lb. plantarum NDC75017. The results indicated that GABA production was related to GAD activity and biomass of Lb. plantarum NDC75017. Response surface methodology was used to optimize conditions of GABA production. The optimal factors for GABA production were L-MSG at 80 mM, PLP at 18 μM, and a culture temperature of 36 °C. Under these conditions, production of GABA was maximized at 314.56 mg/100 g. Addition of Lb. plantarum NDC75017 to a commercial starter culture led to higher GABA production in fermented yogurt. Flavor and texture of the prepared yogurt and the control yogurt did not differ significantly. Thus, Lb. plantarum NDC75017 has good potential for manufacture of GABA-enriched fermented milk products. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

A[Beta] Deposits in Older Non-Demented Individuals with Cognitive Decline Are Indicative of Preclinical Alzheimer's Disease

ERIC Educational Resources Information Center

Villemagne, V. L.; Pike, K. E.; Darby, D.; Maruff, P.; Savage, G.; Ng, S.; Ackermann, U.; Cowie, T. F.; Currie, J.; Chan, S. G.; Jones, G.; Tochon-Danguy, H.; O'Keefe, G.; Masters, C. L.; Rowe, C. C.

2008-01-01

Approximately 30% of healthy persons aged over 75 years show A[beta] deposition at autopsy. It is postulated that this represents preclinical Alzheimer's disease (AD). We evaluated the relationship between A[beta] burden as assessed by PiB PET and cognitive decline in a well-characterized, non-demented, elderly cohort. PiB PET studies and…

Thalamic volume and related visual recognition are associated with freezing of gait in non-demented patients with Parkinson's disease.

PubMed

Sunwoo, Mun Kyung; Cho, Kyoo H; Hong, Jin Yong; Lee, Ji E; Sohn, Young H; Lee, Phil Hyu

2013-12-01

The pathophysiology of freezing of gait (FOG) in non-demented Parkinson's disease (PD) patients remains poorly understood. Recent studies have suggested that neurochemical alterations in the cholinergic systems play a role in the development of FOG. Here, we evaluated the association between subcortical cholinergic structures and FOG in patients with non-demented PD. We recruited 46 non-demented patients with PD, categorized into PD with (n = 16) and without FOG (n = 30) groups. We performed neuropsychological test, region-of-interest-based volumetric analysis of the substantia innominata (SI) and automatic analysis of subcortical brain structures using a computerized segmentation procedure. The comprehensive neuropsychological assessment showed that PD patients with FOG had lower cognitive performance in the frontal executive and visual-related functions compared with those without freezing of gait. The normalized SI volume did not differ significantly between the two groups (1.65 ± 0.18 vs. 1.68 ± 0.31). The automatic analysis of subcortical structures revealed that the thalamic volumes were significantly reduced in PD patients with FOG compared with those without FOG after adjusting for age, sex, disease duration, the Unified PD Rating Scale scores and total intracranial volume (left: 6.71 vs. 7.16 cm3, p = 0.029, right: 6.47 vs. 6.91 cm3, p = 0.026). Multiple linear regression analysis revealed that thalamic volume showed significant positive correlations with visual recognition memory (left: β = 0.441, p = 0.037, right: β = 0.498, p = 0.04). These data suggest that thalamic volume and related visual recognition, rather than the cortical cholinergic system arising from the SI, may be a major contributor to the development of freezing of gait in non-demented patients with PD. Copyright © 2013. Published by Elsevier Ltd.

Age-dependent effect of Alzheimer’s risk variant of CLU on EEG alpha rhythm in non-demented adults

PubMed Central

Ponomareva, Natalya; Andreeva, Tatiana; Protasova, Maria; Shagam, Lev; Malina, Daria; Goltsov, Andrei; Fokin, Vitaly; Mitrofanov, Andrei; Rogaev, Evgeny

2013-01-01

Polymorphism in the genomic region harboring the CLU gene (rs11136000) has been associated with the risk for Alzheimer’s disease (AD). CLU C allele is assumed to confer risk for AD and the allele T may have a protective effect. We investigated the influence of the AD-associated CLU genotype on a common neurophysiological trait of brain activity (resting-state alpha-rhythm activity) in non-demented adults and elucidated whether this influence is modified over the course of aging. We examined quantitative electroencephalography (EEG) in a cohort of non-demented individuals (age range 20–80) divided into young (age range 20–50) and old (age range 51–80) cohorts and stratified by CLU polymorphism. To rule out the effect of the apolipoprotein E (ApoE) genotype on EEG characteristics, only subjects without the ApoE ε4 allele were included in the study. The homozygous presence of the AD risk variant CLU CC in non-demented subjects was associated with an increase of alpha3 absolute power. Moreover, the influence of CLU genotype on alpha3 was found to be higher in the subjects older than 50 years of age. The study also showed age-dependent alterations of alpha topographic distribution that occur independently of the CLU genotype. The increase of upper alpha power has been associated with hippocampal atrophy in patients with mild cognitive impairment (Moretti etal., 2012a). In our study, the CLU CC-dependent increase in upper alpha rhythm, particularly enhanced in elderly non-demented individuals, may imply that the genotype is related to preclinical dysregulation of hippocampal neurophysiology in aging and that this factor may contribute to the pathogenesis of AD. PMID:24379779

Solvothermal syntheses, structures, and magnetic properties of three cobalt coordination polymers constructed from naphthalene-1,4-dicarboxylic acid and bis(imidazole) linkers

NASA Astrophysics Data System (ADS)

Dong, Jun-Liang; He, Kun-Huan; Wang, Duo-Zhi; Zhang, Ying-Hui; Wang, Dan-Hong

2018-07-01

Three new Co(II) coordination polymers with formulas of {[Co2(L1)(1,4-NDC)2]·3H2O}n (1), [Co3(L2)2(HCOO)2(1,4-NDC)2]n (2) and [Co2(L2)(μ3-OH)(1,4-NDC)1.5]n (3) (1,4-H2NDC = Naphthalene-1,4-dicarboxylic acid, L1 = di(1H-imidazol-1-yl)methane, L2 = 1,4-di(1H-imidazol-1-yl)benzene) were solvothermal synthesized from 1,4-H2NDC with the aid of three different length-controllable auxiliary ligands and fully characterized. Their structures are determined by single-crystal X-ray diffraction, IR spectra, elemental analysis, powder X-ray diffraction and thermogravimetric analysis. Complexes 1 and 3 display 3D framework structures, corresponding to a 6-connected (412·63) net, a 8-connected (424·5·63) net, respectively. However, it is noteworthy that the complex 1 displays a 2-fold interpenetrating framework structure, complex 3 possesses a self-interpenetrating framework structure. Complex 2 displays 2D 4-connected undulating plane net structure. Moreover, magnetic studies indicate antiferromagnetic interactions between the Co(II) ions in the four complexes.

Multivalency of NDC80 in the outer kinetochore is essential to track shortening microtubules and generate forces

PubMed Central

2018-01-01

Presence of multiple copies of the microtubule-binding NDC80 complex is an evolutionary conserved feature of kinetochores, points of attachment of chromosomes to spindle microtubules. This may enable multivalent attachments to microtubules, with implications that remain unexplored. Using recombinant human kinetochore components, we show that while single NDC80 complexes do not track depolymerizing microtubules, reconstituted particles containing the NDC80 receptor CENP-T bound to three or more NDC80 complexes do so effectively, as expected for a kinetochore force coupler. To study multivalency systematically, we engineered modules allowing incremental addition of NDC80 complexes. The modules’ residence time on microtubules increased exponentially with the number of NDC80 complexes. Modules with two or more complexes tracked depolymerizing microtubules with increasing efficiencies, and stalled and rescued microtubule depolymerization in a force-dependent manner when conjugated to cargo. Our observations indicate that NDC80, rather than through biased diffusion, tracks depolymerizing microtubules by harnessing force generated during microtubule disassembly. PMID:29629870

APP with Kunitz type protease inhibitor domain (KPI) correlates with neuritic plaque density but not with cortical synaptophysin immunoreactivity in Alzheimer's disease and non-demented aged subjects: a multifactorial analysis.

PubMed

Zhan, S S; Sandbrink, R; Beyreuther, K; Schmitt, H P

1995-01-01

The formation of beta A4 amyloid protein in neuritic plaques in Alzheimer's disease (AD) and advanced age is a complex process that involves a number of both cellular and molecular mechanisms, the interrelations of which are not yet completely understood. We have examined quantitatively, in AD and aged controls an extended spectrum of amyloid plaque-related cellular and molecular factors and the cortical synaptophysin immunoreactivity (synaptic density) in order to check for interrelations between them by multifactorial analysis. In 3 cases of senile dementia of the Alzheimer type (SDAT) aged 72, 80 and 82 years, and 9 controls aged 43-88 (mean age 65) years, the cortical synaptophysin immunoreactivity was assessed, together with the numbers of neurons, astrocytes and microglial cells, senile plaques, of tangle-bearing neurons, and the amount of beta A4 amyloid precursor protein (APP) with and without the Kunitz type serine protease inhibitor (KPI) domain. The main results were: APP including the KPI domain (KPI-APP) correlated with the number of neuritic plaques, regardless of whether they occurred in SDAT or non-demented controls. There was no significant difference in the amount of KPI-APP between SDAT and controls. Conversely, APP695 (without KPI) was significantly reduced in SDAT. KPI-APP did not correlate with the synaptophysin immunoreactivity (RGVA), while APP695 showed a significant correlation with the latter in all evaluations. It also correlated with the neuron counts, which was not true for KPI-APP. These results support previous findings indicating that KPI-APP is an important local factor for amyloid deposition in the neuritic plaques, both in AD and in non-demented aged people. On the contrary, KPI-APP does not seem to be significantly involved in the mechanisms of synaptic change outside of the plaques.

Effect of Nutrients, Dietary Supplements and Vitamins on Cognition: a Systematic Review and Meta-Analysis of Randomized Controlled Trials

PubMed Central

Forbes, Scott C.; Holroyd-Leduc, Jayna M.; Poulin, Marc J.; Hogan, David B.

2015-01-01

Background Observational studies have suggested that various nutrients, dietary supplements, and vitamins may delay the onset of age-associated cognitive decline and dementia. We systematically reviewed recent randomized controlled trials investigating the effect of nutritional interventions on cognitive performance in older non-demented adults. Methods We searched MEDLINE, CINAHL, Embase, and the Cochrane Library for articles published between 2003 and 2013. We included randomized trials of ≥ 3 months’ duration that examined the cognitive effects of a nutritional intervention in non-demented adults > 40 years of age. Meta-analyses were done when sufficient trials were available. Results Twenty-four trials met inclusion criteria (six omega-3 fatty acids, seven B vitamins, three vitamin E, eight other interventions). In the meta-analyses, omega-3 fatty acids showed no significant effect on Mini-Mental State Examination (MMSE) scores (four trials, mean difference 0.06, 95% CI −0.08 – 0.19) or digit span forward (three trials, mean difference −0.02, 95% CI −0.30 – 0.25), while B vitamins showed no significant effect on MMSE scores (three trials, mean difference 0.02, 95% CI −0.22 – 0.25). None of the vitamin E studies reported significant effects on cognitive outcomes. Among the other nutritional interventions, statistically significant differences between the intervention and control groups on at least one cognitive domain were found in single studies of green tea extract, Concord grape juice, chromium picolinate, beta-carotene, two different combinations of multiple vitamins, and a dietary approach developed for the control of hypertension. Conclusions Omega-3 fatty acids, B vitamins, and vitamin E supplementation did not affect cognition in non-demented middle-aged and older adults. Other nutritional interventions require further evaluation before their use can be advocated for the prevention of age-associated cognitive decline and dementia. PMID:26740832

Apolipoprotein E-epsilon 4 allele and familial risk in Alzheimer's disease.

PubMed

Li, G; Silverman, J M; Altstiel, L D; Haroutunian, V; Perl, D P; Purohit, D; Birstein, S; Lantz, M; Mohs, R C; Davis, K L

1996-01-01

Recent studies have found an association between presence of apolipoprotein E (APOE) epsilon 4 allele and Alzheimer's disease (AD). The present study compared the cumulative risk of primary progressive dementia (PPD) in relatives of AD probands carrying at least one copy of the epsilon 4 allele with the relatives of AD probands not carrying epsilon 4 and with relatives of non-demented controls. Our aim was to determine whether the familial aggregation of PPD in relatives of AD probands is primarily due to those carrying epsilon 4. Seventy-seven neuropathologically diagnosed AD patients were obtained as probands through our Alzheimer's Disease Research Center Brain Bank. AD probands were genotyped for APOE. As a comparison group, 198 non-demented probands were also included. Through family informants, demographic and diagnostic data were collected on 382 first-degree relatives (age > or = 45 years) of AD probands and 848 relatives of the controls. We found that the cumulative risk of PPD in both relatives of AD probands with and without the epsilon 4 allele was significantly higher than that in the relatives of non-demented controls. However, the increased risk in the relatives of AD probands with the epsilon 4 allele was marginally, but not significantly, lower than the risk in the relatives of probands without epsilon 4. A greater likelihood of death by heart diseases over developing PPD in relatives of AD probands with epsilon 4 (3.1-fold increase) was found compared to relatives of probands without epsilon 4 (1.7-fold increase), especially prior to age 70, although the difference was not statistically significant. The increased familial risk for PPD in the relatives of AD probands with the APOE-epsilon 4 allele relative to controls suggests that familial factors in addition to APOE-epsilon 4 are risk factors for AD. Differential censorship from increased mortality of heart diseases may have prevented a higher incidence of PPD among the relatives of probands with epsilon 4.

36 CFR 1260.30 - What is the NDC?

Code of Federal Regulations, 2012 CFR

2012-07-01

... 36 Parks, Forests, and Public Property 3 2012-07-01 2012-07-01 false What is the NDC? 1260.30 Section 1260.30 Parks, Forests, and Public Property NATIONAL ARCHIVES AND RECORDS ADMINISTRATION...) § 1260.30 What is the NDC? The National Declassification Center (NDC) is established within NARA to...

Cluster analysis of cognitive performance in elderly and demented subjects.

PubMed

Giaquinto, S; Nolfe, G; Calvani, M

1985-06-01

48 elderly normals, 14 demented subjects and 76 young controls were tested for basic cognitive functions. All the tests were quantified and could therefore be subjected to statistical analysis. The results show a difference in the speed of information processing and in memory load between the young controls and elderly normals but the age groups differed in quantitative terms only. Cluster analysis showed that the elderly and the demented formed two distinctly separate groups at the qualitative level, the basic cognitive processes being damaged in the demented group. Age thus appears to be only a risk factor for dementia and not its cause. It is concluded that batteries based on precise and measurable tasks are the most appropriate not only for the study of dementia but for rehabilitation purposes too.

Six uranyl-organic frameworks with naphthalene-dicarboxylic acid and bipyridyl-based spacers: syntheses, structures, and properties.

PubMed

Xu, Wei; Ren, Ya-Nan; Xie, Miao; Zhou, Lin-Xia; Zheng, Yue-Qing

2018-03-28

A new series of uranium coordination polymers have been hydrothermally synthesized by using 1,4-naphthalene dicarboxylic acid (H 2 NDC), namely, (H 3 O) 2 [(UO 2 ) 2 (NDC) 3 ]·H 2 O (1), (H 2 -bpp)[(UO 2 ) 2 (NDC) 3 ]·EtOH·5H 2 O (2), (H 2 -bpe) 2/2 [(UO 2 ) 2 (NDC) 3 ]·EtOH (3), (H 2 -bpp)[(UO 2 ) 2 (NDC) 3 ]·5H 2 O (4), (H 2 -bpp)[(UO 2 )(HNDC)(NDC)] 2 ·2H 2 O (5), and (H 2 -bpy)[(UO 2 )(NDC) 2 ] (6) [bpp = 1,3-di(4-pyridyl) propane, bpe = 4,4'-vinylenedipyridine, bpy = 4,4'-bipyridine]. Single-crystal X-ray diffraction demonstrates that complex 1 represents the uranyl-organic polycatenated framework derived from a simple two-dimensional honeycomb grid network structure via a H 2 NDC linker. Complexes 2-4 contain the dinuclear motifs of the two UO 7 pentagonal and one UO 8 hexagonal bipyramids which are linked by NDC 2- anions creating a (UO 2 ) 4 (NDC) 2 unit, and further extend to a 2D layer through NDC 2- anions. Complex 5 displays a 1D zigzag double chain structure, in which the carboxylate groups of the NDC 2- anions adopt a chelate mode and further extends to a 2D framework via hydrogen bonds. The 1D structure of complex 6 is similar to the zigzag chain of complex 5. In addition, powder X-ray diffraction, elemental analysis, IR, thermal stability and luminescence properties of all complexes have also been investigated in this paper. The photocatalytic properties of the six complexes for the degradation of tetracycline hydrochloride (TC) under UV irradiation have been examined. Moreover, density functional theory (DFT) calculations were carried out to explore the electronic structural and bonding properties of the uranyl complexes 1-6.

The Ndc80 complex targets Bod1 to human mitotic kinetochores

PubMed Central

2017-01-01

Regulation of protein phosphatase activity by endogenous protein inhibitors is an important mechanism to control protein phosphorylation in cells. We recently identified Biorientation defective 1 (Bod1) as a small protein inhibitor of protein phosphatase 2A containing the B56 regulatory subunit (PP2A-B56). This phosphatase controls the amount of phosphorylation of several kinetochore proteins and thus the establishment of load-bearing chromosome-spindle attachments in time for accurate separation of sister chromatids in mitosis. Like PP2A-B56, Bod1 directly localizes to mitotic kinetochores and is required for correct segregation of mitotic chromosomes. In this report, we have probed the spatio-temporal regulation of Bod1 during mitotic progression. Kinetochore localization of Bod1 increases from nuclear envelope breakdown until metaphase. Phosphorylation of Bod1 at threonine 95 (T95), which increases Bod1's binding to and inhibition of PP2A-B56, peaks in prometaphase when PP2A-B56 localization to kinetochores is highest. We demonstrate here that kinetochore targeting of Bod1 depends on the outer kinetochore protein Ndc80 and not PP2A-B56. Crucially, Bod1 depletion functionally affects Ndc80 phosphorylation at the N-terminal serine 55 (S55), as well as a number of other phosphorylation sites within the outer kinetochore, including Knl1 at serine 24 and 60 (S24, S60), and threonine T943 and T1155 (T943, T1155). Therefore, Ndc80 recruits a phosphatase inhibitor to kinetochores which directly feeds forward to regulate Ndc80, and Knl1 phosphorylation, including sites that mediate the attachment of microtubules to kinetochores. PMID:29142109

Clinical periodontal variables in patients with and without dementia-a systematic review and meta-analysis.

PubMed

Maldonado, Alejandra; Laugisch, Oliver; Bürgin, Walter; Sculean, Anton; Eick, Sigrun

2018-06-22

Considering the increasing number of elderly people, dementia has gained an important role in today's society. Although the contributing factors for dementia have not been fully understood, chronic periodontitis (CP) seems to have a possible link to dementia. To conduct a systematic review including meta-analysis in order to assess potential differences in clinical periodontal variables between patients with dementia and non-demented individuals. The following focused question was evaluated: is periodontitis associated with dementia? Electronic searches in two databases, MEDLINE and EMBASE, were conducted. Meta-analysis was performed with the collected data in order to find a statistically significant difference in clinical periodontal variables between the group of dementia and the cognitive normal controls. Forty-two articles remained for full text reading. Finally, seven articles met the inclusion criteria and only five studies provided data suitable for meta-analysis. Periodontal probing depth (PPD), bleeding on probing (BOP), gingival bleeding index (GBI), clinical attachment level (CAL), and plaque index (PI) were included as periodontal variables in the meta-analysis. Each variable revealed a statistically significant difference between the groups. In an attempt to reveal an overall difference between the periodontal variables in dementia patients and non-demented individuals, the chosen variables were transformed into units that resulted in a statistically significant overall difference (p < 0.00001). The current findings indicate that compared to systemically healthy individuals, demented patients show significantly worse clinical periodontal variables. However, further epidemiological studies including a high numbers of participants, the use of exact definitions both for dementia and chronic periodontitis and adjusted for cofounders is warranted. These findings appear to support the putative link between CP and dementia. Consequently, the need for periodontal screening and treatment of elderly demented people should be emphasized.

A general approach for the direct fabrication of metal oxide-based electrocatalysts for efficient bifunctional oxygen electrodes

DOE PAGES

Wang, Jie; Wu, Zexing; Han, Lili; ...

2017-03-07

Here, we develop a simple one-pot synthetic strategy for the general preparation of nitrogen doped carbon supported metal/metal oxides (Co@CoO/NDC, Ni@NiO/NDC and MnO/NDC) derived from the complexing function of (ethylenediamine)tetraacetic acid (EDTA). EDTA serves not only as a resource to tune the morphology in terms of the complexation constant for M–EDTA, but also as a nitrogen and oxygen source for nitrogen doping and metal oxide formation, respectively. When the materials are used as electrocatalysts for the oxygen electrode reaction, Co@CoO/NDC-700 and MnO/NDC-700 show superior electrocatalytic activity towards the oxygen reduction reaction (ORR), while Co@CoO/NDC-700 and Ni@NiO/NDC-700 exhibit excellent oxygen evolutionmore » reaction (OER) activities. Taken together, the resultant Co@CoO/NDC-700 exhibits the best catalytic activity with favorable reaction kinetics and durability as a bi-functional catalyst for the ORR and OER, which is much better than the other two catalysts, Pt/C and Ir/C. Moreover, as an air electrode for a homemade zinc–air battery, Co@CoO/NDC-700 shows superior cell performance with a highest power density of 192.1 mW cm -2, the lowest charge–discharge overpotential and high charge–discharge durability over 100 h.« less

Coupling unbiased mutagenesis to high-throughput DNA sequencing uncovers functional domains in the Ndc80 kinetochore protein of Saccharomyces cerevisiae.

PubMed

Tien, Jerry F; Fong, Kimberly K; Umbreit, Neil T; Payen, Celia; Zelter, Alex; Asbury, Charles L; Dunham, Maitreya J; Davis, Trisha N

2013-09-01

During mitosis, kinetochores physically link chromosomes to the dynamic ends of spindle microtubules. This linkage depends on the Ndc80 complex, a conserved and essential microtubule-binding component of the kinetochore. As a member of the complex, the Ndc80 protein forms microtubule attachments through a calponin homology domain. Ndc80 is also required for recruiting other components to the kinetochore and responding to mitotic regulatory signals. While the calponin homology domain has been the focus of biochemical and structural characterization, the function of the remainder of Ndc80 is poorly understood. Here, we utilized a new approach that couples high-throughput sequencing to a saturating linker-scanning mutagenesis screen in Saccharomyces cerevisiae. We identified domains in previously uncharacterized regions of Ndc80 that are essential for its function in vivo. We show that a helical hairpin adjacent to the calponin homology domain influences microtubule binding by the complex. Furthermore, a mutation in this hairpin abolishes the ability of the Dam1 complex to strengthen microtubule attachments made by the Ndc80 complex. Finally, we defined a C-terminal segment of Ndc80 required for tetramerization of the Ndc80 complex in vivo. This unbiased mutagenesis approach can be generally applied to genes in S. cerevisiae to identify functional properties and domains.

36 CFR § 1260.38 - How does the NDC ensure the quality of declassification reviews?

Code of Federal Regulations, 2013 CFR

2013-07-01

... 36 Parks, Forests, and Public Property 3 2013-07-01 2012-07-01 true How does the NDC ensure the quality of declassification reviews? § 1260.38 Section § 1260.38 Parks, Forests, and Public Property... INFORMATION The National Declassification Center (NDC) § 1260.38 How does the NDC ensure the quality of...

Concept for Determining the Life of Ceramic Matrix Composites Using Nondestructive Characterization Techniques

NASA Technical Reports Server (NTRS)

Effinger, M.; Ellingson, B.; Spohnholtz, T.; Koenig, J.

2001-01-01

An idea is put forth for a nondestructive characterization (NDC) generated algorithm-N curve to replace a S-N curve. A scenario for NDC life determination has been proposed. There are many challenges for the NDC life determination and prediction, but it could yield a grand payoff. The justification for NDC life determination and prediction is documented.

Efficacy of motivational interviewing and cognitive behavioral therapy for anxiety and depression symptoms following traumatic brain injury.

PubMed

Ponsford, J; Lee, N K; Wong, D; McKay, A; Haines, K; Alway, Y; Downing, M; Furtado, C; O'Donnell, M L

2016-04-01

Anxiety and depression are common following traumatic brain injury (TBI), often co-occurring. This study evaluated the efficacy of a 9-week cognitive behavioral therapy (CBT) program in reducing anxiety and depression and whether a three-session motivational interviewing (MI) preparatory intervention increased treatment response. A randomized parallel three-group design was employed. Following diagnosis of anxiety and/or depression using the Structured Clinical Interview for DSM-IV, 75 participants with mild-severe TBI (mean age 42.2 years, mean post-traumatic amnesia 22 days) were randomly assigned to an Adapted CBT group: (1) MI + CBT (n = 26), or (2) non-directive counseling (NDC) + CBT (n = 26); or a (3) waitlist control (WC, n = 23) group. Groups did not differ in baseline demographics, injury severity, anxiety or depression. MI and CBT interventions were guided by manuals adapted for individuals with TBI. Three CBT booster sessions were provided at week 21 to intervention groups. Using intention-to-treat analyses, random-effects regressions controlling for baseline scores revealed that Adapted CBT groups (MI + CBT and NDC + CBT) showed significantly greater reduction in anxiety on the Hospital Anxiety and Depression Scale [95% confidence interval (CI) -2.07 to -0.06] and depression on the Depression Anxiety and Stress Scale (95% CI -5.61 to -0.12) (primary outcomes), and greater gains in psychosocial functioning on Sydney Psychosocial Reintegration Scale (95% CI 0.04-3.69) (secondary outcome) over 30 weeks post-baseline relative to WC. The group receiving MI + CBT did not show greater gains than the group receiving NDC + CBT. Findings suggest that modified CBT with booster sessions over extended periods may alleviate anxiety and depression following TBI.

Prosody impairment and associated affective and behavioral disturbances in Alzheimer's disease.

PubMed

Roberts, V J; Ingram, S M; Lamar, M; Green, R C

1996-12-01

We examined the ability to produce, repeat, and comprehend emotional prosody in 20 patients with Alzheimer's disease (AD) and in 11 elderly normal control subjects. In addition, caregivers of AD patients completed affective and behavioral measures with reference to the patient. Relative to control subjects, comprehension of emotional prosody was marginally impaired in mildly demented AD patients, whereas production, comprehension, and repetition of emotional prosody were significantly impaired in moderately demented AD patients. The moderately demented patients performed significantly poorer than the mildly demented patients on the production and repetition tasks. In contrast, there was no significance difference between the two groups on the prosody comprehension task. Additional analyses revealed an inverse relationship between the ability to correctly produce and repeat emotional prosody and the frequency of agitated behaviors and depressive symptomatology in moderately demented patients. This latter findings suggests that the inability to communicate emotional message is associated with disturbances in mood and behavior in AD patients. Implications for the management of disruptive behavior in agitated and aprosodic AD patients include the development of caregiver sensitivity to unexpressed emotion and caregiver assistance with emotional expression.

Purification and characterisation of the fission yeast Ndc80 complex.

PubMed

Matsuo, Yuzy; Maurer, Sebastian P; Surrey, Thomas; Toda, Takashi

2017-07-01

The Ndc80 complex is a conserved outer kinetochore protein complex consisting of Ndc80 (Hec1), Nuf2, Spc24 and Spc25. This complex comprises a major, if not the sole, platform with which the plus ends of the spindle microtubules directly interact. In fission yeast, several studies indicate that multiple microtubule-associated proteins including the Dis1/chTOG microtubule polymerase and the Mal3/EB1 microtubule plus-end tracking protein directly or indirectly bind Ndc80, thereby ensuring stable kinetochore-microtubule attachment. However, the purification of the Ndc80 complex from this yeast has not been achieved, which hampers the in-depth investigation as to how the outer kinetochore attaches to the plus end of the spindle microtubule. Here we report the two-step purification of the fission yeast Ndc80 holo complex from bacteria. First, we purified separately two sub-complexes consisting of Ndc80-Nuf2 and Spc24-Spc25. Then, these two sub-complexes were mixed and applied to size-exclusion chromatography. The reconstituted Ndc80 holo complex is composed of four subunits with equal stoichiometry. The complex possesses microtubule-binding activity, and Total Internal Reflection Fluorescence (TIRF)-microscopy assays show that the complex binds the microtubule lattice. Interestingly, unlike the human complex, the fission yeast complex does not track depolymerising microtubule ends. Further analysis shows that under physiological ionic conditions, the Ndc80 holo complex does not detectably bind Dis1, but instead it interacts with Mal3/EB1, by which the Ndc80 complex tracks the growing microtubule plus end. This result substantiates the notion that the Ndc80 complex plays a crucial role in establishment of the dynamic kinetochore-microtubule interface by cooperating with chTOG and EB1. Copyright © 2017 The Francis Crick Institute. Published by Elsevier Inc. All rights reserved.

Analysis of National Drug Code Identifiers in Ambulatory E-Prescribing.

PubMed

Dhavle, Ajit A; Ward-Charlerie, Stacy; Rupp, Michael T; Amin, Vishal P; Ruiz, Joshua

2015-11-01

Communication of an accurate and interpretable drug identifier between prescriber and pharmacist is critically important for realizing the potential benefits of electronic prescribing (e-prescribing) while minimizing its risk. The National Drug Code (NDC) is the most commonly used codified drug identifier in ambulatory care e-prescribing, but concerns have been raised regarding its use for this purpose.  To (a) assess the frequency of NDC identifier transmission in ambulatory e-prescribing; (b) characterize the type of NDC identifier transmitted (representative, repackaged, obsolete, private label, and unit dose); and (c) assess the level of agreement between drug descriptions corresponding to NDC identifiers in electronic prescriptions (e-prescriptions) and the free-text drug descriptions that were entered by prescribers.  We analyzed a sample of 49,997 e-prescriptions that were transmitted by ambulatory care prescribers to outlets of a national retail drugstore chain during a single day in April 2014. The First Databank MedKnowledge drug database was used as the primary reference data base to assess the frequency and types of NDC numbers in the e-prescription messages. The FDA's Comprehensive NDC Standard Product Labeling Data Elements File and the National Library of Medicine's RxNorm data file were used as secondary and tertiary references, respectively, to identify NDC numbers that could not be located in the primary reference file. Three experienced reviewers compared the free-text drug description that had been entered by the prescriber with the drug description corresponding to the NDC number from 1 of the 3 reference database files to identify discrepancies. Two licensed pharmacists with residency training and ambulatory care experience served as final adjudicators. A total of 42,602 e-prescriptions contained a value in the NDC field, of which 42,335 (84.71%) were found in 1 of the 3 study reference databases and were thus considered to be valid NDC numbers. A total of 28,172 (67.70%) e-prescriptions in the sample were found to contain a representative NDC number, according to the definition used by the National Council for Prescription Drug Programs (NCPDP). The remaining e-prescriptions consisted of 4 subtypes of unrepresentative NDC numbers. In 41,298 (97.55%) e-prescriptions that contained an NDC number, the drug description associated with the number from 1 of the 3 data source files pointed to the identical semantic drug concept as the free-text drug description that had been entered by the prescriber. However, in 87 (0.21%) e-prescriptions, the free-text drug descriptions and the drug description associated with the NDC number pointed to completely different semantic drug concepts. We found the use of NDC identifiers in our sample of e-prescriptions to be relatively high. However, approximately one-third consisted of unrepresentative NDC numbers (obsolete, repackaged, unit dose, or private label) that have the potential to create workflow disruptions at the dispensing pharmacy. Most disturbing was our finding that more than 2 out of every 1,000 e-prescriptions in our sample contained a free-text drug description that pointed to a completely different drug concept than that associated with its NDC value. Our study suggests the need for e-prescribing technology vendors to maintain accurate and up-to-date drug database files within their systems and to conduct regular validation checks to ensure that the drug descriptions associated with the NDC identifier and the free-text drug description that is sent in the e-prescription message point to the same drug concept. The FDA may need to consider a more active role in ensuring the accuracy of NDC assignment by drug manufacturers.

Bulgarian National Digital Seismological Network

NASA Astrophysics Data System (ADS)

Dimitrova, L.; Solakov, D.; Nikolova, S.; Stoyanov, S.; Simeonova, S.; Zimakov, L. G.; Khaikin, L.

2011-12-01

The Bulgarian National Digital Seismological Network (BNDSN) consists of a National Data Center (NDC), 13 stations equipped with RefTek High Resolution Broadband Seismic Recorders - model DAS 130-01/3, 1 station equipped with Quanterra 680 and broadband sensors and accelerometers. Real-time data transfer from seismic stations to NDC is realized via Virtual Private Network of the Bulgarian Telecommunication Company. The communication interruptions don't cause any data loss at the NDC. The data are backed up in the field station recorder's 4Mb RAM memory and are retransmitted to the NDC immediately after the communication link is re-established. The recorders are equipped with 2 compact flash disks able to save more than 1 month long data. The data from the flash disks can be downloaded remotely using FTP. The data acquisition and processing hardware redundancy at the NDC is achieved by two clustered SUN servers and two Blade Workstations. To secure the acquisition, processing and data storage processes a three layer local network is designed at the NDC. Real-time data acquisition is performed using REFTEK's full duplex error-correction protocol RTPD. Data from the Quanterra recorder and foreign stations are fed into RTPD in real-time via SeisComP/SeedLink protocol. Using SeisComP/SeedLink software the NDC transfers real-time data to INGV-Roma, NEIC-USA, ORFEUS Data Center. Regional real-time data exchange with Romania, Macedonia, Serbia and Greece is established at the NDC also. Data processing is performed by the Seismic Network Data Processor (SNDP) software package running on the both Servers. SNDP includes subsystems: Real-time subsystem (RTS_SNDP) - for signal detection; evaluation of the signal parameters; phase identification and association; source estimation; Seismic analysis subsystem (SAS_SNDP) - for interactive data processing; Early warning subsystem (EWS_SNDP) - based on the first arrived P-phases. The signal detection process is performed by traditional STA/LTA detection algorithm. The filter parameters of the detectors are defined on the base of previously evaluated ambient noise at the seismic stations. Some extra modules for network command/control, state-of-health network monitoring and data archiving are running as well in the National Data Center. Three types of archives are produced in the NDC - two continuous - miniSEED format and RefTek PASSCAL format; and one event oriented in CSS3.0 scheme format. Modern digital equipment and broad-band seismometers installed at Bulgarian seismic stations, careful selection of the software packages for automatic and interactive data processing in the data center proved to be suitable choice for the purposes of BNDSN and NDC: ? to ensure reliable automatic localization of the seismic events and rapid notification of the governmental authorities in case of felt earthquakes on the territory of Bulgaria; ? to provide a modern basis for seismological studies in Bulgaria.

Proactive Semantic Interference is Associated with Total and Regional Abnormal Amyloid Load in Non-Demented Community-Dwelling Elders: A Preliminary Study.

PubMed

Loewenstein, David A; Greig, Maria T; Curiel, Rosie; Rodriguez, Rosemarie; Wicklund, Meredith; Barker, Warren W; Hidalgo, Jacqueline; Rosado, Marian; Duara, Ranjan

2015-12-01

To evaluate the relationship between susceptibility to proactive semantic interference (PSI) and retroactive semantic interference (RSI) and brain amyloid load in non-demented elders. 27 participants (11 cognitively normal [CN] with subjective memory complaints, 8 CN without memory complaints, and 8 with mild cognitive impairment [MCI]) underwent complete neurological and neuropsychological evaluations. Participants also received the Semantic Interference Test (SIT) and AV-45 amyloid PET imaging. High levels of association were present between total amyloid load, regional amyloid levels, and the PSI measure (in the entire sample and a subsample excluding MCI subjects). RSI and other memory measures showed much weaker associations or no associations with total and regional amyloid load. No associations between amyloid levels and non-memory performance were observed. In non-demented individuals, vulnerability to PSI was highly associated with total and regional beta-amyloid load and may be an early cognitive marker of brain pathology. Copyright © 2015 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Development of a brain MRI-based hidden Markov model for dementia recognition.

PubMed

Chen, Ying; Pham, Tuan D

2013-01-01

Dementia is an age-related cognitive decline which is indicated by an early degeneration of cortical and sub-cortical structures. Characterizing those morphological changes can help to understand the disease development and contribute to disease early prediction and prevention. But modeling that can best capture brain structural variability and can be valid in both disease classification and interpretation is extremely challenging. The current study aimed to establish a computational approach for modeling the magnetic resonance imaging (MRI)-based structural complexity of the brain using the framework of hidden Markov models (HMMs) for dementia recognition. Regularity dimension and semi-variogram were used to extract structural features of the brains, and vector quantization method was applied to convert extracted feature vectors to prototype vectors. The output VQ indices were then utilized to estimate parameters for HMMs. To validate its accuracy and robustness, experiments were carried out on individuals who were characterized as non-demented and mild Alzheimer's diseased. Four HMMs were constructed based on the cohort of non-demented young, middle-aged, elder and demented elder subjects separately. Classification was carried out using a data set including both non-demented and demented individuals with a wide age range. The proposed HMMs have succeeded in recognition of individual who has mild Alzheimer's disease and achieved a better classification accuracy compared to other related works using different classifiers. Results have shown the ability of the proposed modeling for recognition of early dementia. The findings from this research will allow individual classification to support the early diagnosis and prediction of dementia. By using the brain MRI-based HMMs developed in our proposed research, it will be more efficient, robust and can be easily used by clinicians as a computer-aid tool for validating imaging bio-markers for early prediction of dementia.

Effects of Caring for a Demented Relative on Elders' Life Events and Appraisals.

ERIC Educational Resources Information Center

Reed, Bruce R.; And Others

1990-01-01

Collected weekly ratings of events and appraisals from 19 caregivers of demented patients and 19 control subjects over 4 weeks. Caregivers reported more negative events overall and rated them as more undesirable than did controls, but significant differences were found in events of only 2 of 11 life areas measured. (Author/NB)

Effects of ageing and Alzheimer disease on haemodynamic response function: a challenge for event-related fMRI.

PubMed

Asemani, Davud; Morsheddost, Hassan; Shalchy, Mahsa Alizadeh

2017-06-01

Functional magnetic resonance imaging (fMRI) can generate brain images that show neuronal activity due to sensory, cognitive or motor tasks. Haemodynamic response function (HRF) may be considered as a biomarker to discriminate the Alzheimer disease (AD) from healthy ageing. As blood-oxygenation-level-dependent fMRI signal is much weak and noisy, particularly for the elderly subjects, a robust method is necessary for HRF estimation to efficiently differentiate the AD. After applying minimum description length wavelet as an extra denoising step, deconvolution algorithm is here employed for HRF estimation, substituting the averaging method used in the previous works. The HRF amplitude peaks are compared for three groups HRF of young, non-demented and demented elderly groups for both vision and motor regions. Prior works often reported significant differences in the HRF peak amplitude between the young and the elderly. The authors' experimentations show that the HRF peaks are not significantly different comparing the young adults with the elderly (either demented or non-demented). It is here demonstrated that the contradictory findings of the previous studies on the HRF peaks for the elderly compared with the young are originated from the noise contribution in fMRI data.

Functional Connectivity Density Mapping of Depressive Symptoms and Loneliness in Non-Demented Elderly Male

PubMed Central

Lan, Chen-Chia; Tsai, Shih-Jen; Huang, Chu-Chung; Wang, Ying-Hsiu; Chen, Tong-Ru; Yeh, Heng-Liang; Liu, Mu-En; Lin, Ching-Po; Yang, Albert C.

2016-01-01

Background: Depression and loneliness are prevalent and highly correlated phenomena among the elderly and influence both physical and mental health. Brain functional connectivity changes associated with depressive symptoms and loneliness are not fully understood. Methods: A cross-sectional functional MRI study was conducted among 85 non-demented male elders. Geriatric depression scale-short form (GDS) and loneliness scale were used to evaluate the severity of depressive symptoms and loneliness, respectively. Whole brain voxel-wise resting-state functional connectivity density (FCD) mapping was performed to delineate short-range FCD (SFCD) and long-range FCD (LFCD). Regional correlations between depressive symptoms or loneliness and SFCD or LFCD were examined using general linear model (GLM), with age incorporated as a covariate and depressive symptoms and loneliness as predictors. Results: Positive correlations between depressive symptoms and LFCD were observed in left rectal gyrus, left superior frontal gyrus, right supraorbital gyrus, and left inferior temporal gyrus. Positive correlations between depressive symptoms and SFCD were observed in left middle frontal gyrus, left superior frontal gyrus, bilateral superior medial frontal gyrus, left inferior temporal gyrus, and left middle occipital region. Positive correlations between SFCD and loneliness were centered over bilateral lingual gyrus. Conclusion: Depressive symptoms are associated with FCD changes over frontal and temporal regions, which may involve the cognitive control, affective regulation, and default mode networks. Loneliness is associated with FCD changes in bilateral lingual gyri that are known to be important in social cognition. Depressive symptoms and loneliness may be associated with different brain regions in non-demented elderly male. PMID:26793101

Enhanced cued recall has a high utility as a screening test in the diagnosis of Alzheimer's disease and mild cognitive impairment in Turkish people.

PubMed

Saka, Esen; Mihci, Ebru; Topcuoglu, M Akif; Balkan, Sevin

2006-10-01

Enhanced cued recall (ECR) is highly sensitive and specific in discrimination of demented from non-demented elderly persons. The nature of the test promises that it can be applicable to subjects in different cultures and education level. We studied the utility of the test in a Turkish population. Eighty consecutive cases with dementia or mild cognitive impairment (MCI) and 33 elderly controls were studied. The utility of ECR was high in discriminating dementia from controls (area under curve (AUC)) of the ROC curve: 0.907 (95% confidence interval (CI): 0.830-0.953 for total recall), Alzheimer's disease from controls (AUC: 0.990 (95%CI: 0.934-0.998 for total recall)) and moderate (AUC: 0.625 (95%CI: 0.545-0.812 for third free recall)) in discriminating MCI from controls. Education did not affect the utility of the test. We conclude that ECR is a valuable test in assessment of elderly Turkish patients with a complaint of memory impairment.

Dilational processes accompanying earthquakes in the Long Valley Caldera

USGS Publications Warehouse

Dreger, Douglas S.; Tkalcic, Hrvoje; Johnston, M.

2000-01-01

Regional distance seismic moment tensor determinations and broadband waveforms of moment magnitude 4.6 to 4.9 earthquakes from a November 1997 Long Valley Caldera swarm, during an inflation episode, display evidence of anomalous seismic radiation characterized by non-double couple (NDC) moment tensors with significant volumetric components. Observed coseismic dilation suggests that hydrothermal or magmatic processes are directly triggering some of the seismicity in the region. Similarity in the NDC solutions implies a common source process, and the anomalous events may have been triggered by net fault-normal stress reduction due to high-pressure fluid injection or pressurization of fluid-saturated faults due to magmatic heating.

The effect of non-invasive positive pressure ventilation (NIPPV) on cognitive function in amyotrophic lateral sclerosis (ALS): a prospective study

PubMed Central

Newsom-Davis, I; Lyall, R; Leigh, P; Moxham, J; Goldstein, L

2001-01-01

OBJECTIVES—Neuropsychological investigations have shown a degree of cognitive dysfunction in a proportion of non-demented patients with ALS. Respiratory muscle weakness in ALS can lead to nocturnal hypoventilation, resulting in sleep disturbance and daytime somnolence. Sleep deprivation of this type may cause impairments in cognitive function, but this has not been formally evaluated in ALS.
METHODS—Cognitive functioning was evaluated in nine patients with ALS with sleep disturbance caused by nocturnal hypoventilation (NIPPV group), and in a comparison group of 10 similar patients without ventilation problems (control group). The NIPPV group then started non-invasive positive pressure ventilation (NIPPV) at night. After about 6 weeks, change in cognitive function was evaluated.
RESULTS—Statistically significant improvement in scores on two of the seven cognitive tests was demonstrated in the NIPPV group postventilation, and a trend towards significant improvement was found for two further tests. Scores in the control group did not improve significantly for these four tests, although an improvement was found on one other test.
CONCLUSIONS—Nocturnal hypoventilation and sleep disturbance may cause cognitive dysfunction in ALS. These deficits may be partially improved by NIPPV over a 6 week period. This has important implications for investigations of both cognitive dysfunction in non-demented patients with ALS, and the effect of ventilation on quality of life.

 PMID:11561031

The hairpin region of Ndc80 is important for the kinetochore recruitment of Mph1/MPS1 in fission yeast.

PubMed

Chmielewska, Aldona Ewa; Tang, Ngang Heok; Toda, Takashi

2016-01-01

The establishment of proper kinetochore-microtubule attachments facilitates faithful chromosome segregation. Incorrect attachments activate the spindle assembly checkpoint (SAC), which blocks anaphase onset via recruitment of a cohort of SAC components (Mph1/MPS1, Mad1, Mad2, Mad3/BubR1, Bub1 and Bub3) to kinetochores. KNL1, a component of the outer kinetochore KMN network (KNL1/Mis12 complex/Ndc80 complex), acts as a platform for Bub1 and Bub3 localization upon its phosphorylation by Mph1/MPS1. The Ndc80 protein, a major microtubule-binding site, is critical for MPS1 localization to the kinetochores in mammalian cells. Here we characterized the newly isolated mutant ndc80-AK01 in fission yeast, which contains a single point mutation within the hairpin region. This hairpin connects the preceding calponin-homology domain with the coiled-coil region. ndc80-AK01 was hypersensitive to microtubule depolymerizing reagents with no apparent growth defects without drugs. Subsequent analyses indicated that ndc80-AK01 is defective in SAC signaling, as mutant cells proceeded into lethal cell division in the absence of microtubules. Under mitotic arrest conditions, all SAC components (Ark1/Aurora B, Mph1, Bub1, Bub3, Mad3, Mad2 and Mad1) did not localize to the kinetochore. Further genetic analyses indicated that the Ndc80 hairpin region might act as a platform for the kinetochore recruitment of Mph1, which is one of the most upstream SAC components in the hierarchy. Intriguingly, artificial tethering of Mph1 to the kinetochore fully restored checkpoint signaling in ndc80-AK01 cells, further substantiating the notion that Ndc80 is a kinetochore platform for Mph1. The hairpin region of Ndc80, therefore, plays a critical role in kinetochore recruitment of Mph1.

The hairpin region of Ndc80 is important for the kinetochore recruitment of Mph1/MPS1 in fission yeast

PubMed Central

Chmielewska, Aldona Ewa; Tang, Ngang Heok; Toda, Takashi

2016-01-01

ABSTRACT The establishment of proper kinetochore-microtubule attachments facilitates faithful chromosome segregation. Incorrect attachments activate the spindle assembly checkpoint (SAC), which blocks anaphase onset via recruitment of a cohort of SAC components (Mph1/MPS1, Mad1, Mad2, Mad3/BubR1, Bub1 and Bub3) to kinetochores. KNL1, a component of the outer kinetochore KMN network (KNL1/Mis12 complex/Ndc80 complex), acts as a platform for Bub1 and Bub3 localization upon its phosphorylation by Mph1/MPS1. The Ndc80 protein, a major microtubule-binding site, is critical for MPS1 localization to the kinetochores in mammalian cells. Here we characterized the newly isolated mutant ndc80-AK01 in fission yeast, which contains a single point mutation within the hairpin region. This hairpin connects the preceding calponin-homology domain with the coiled-coil region. ndc80-AK01 was hypersensitive to microtubule depolymerizing reagents with no apparent growth defects without drugs. Subsequent analyses indicated that ndc80-AK01 is defective in SAC signaling, as mutant cells proceeded into lethal cell division in the absence of microtubules. Under mitotic arrest conditions, all SAC components (Ark1/Aurora B, Mph1, Bub1, Bub3, Mad3, Mad2 and Mad1) did not localize to the kinetochore. Further genetic analyses indicated that the Ndc80 hairpin region might act as a platform for the kinetochore recruitment of Mph1, which is one of the most upstream SAC components in the hierarchy. Intriguingly, artificial tethering of Mph1 to the kinetochore fully restored checkpoint signaling in ndc80-AK01 cells, further substantiating the notion that Ndc80 is a kinetochore platform for Mph1. The hairpin region of Ndc80, therefore, plays a critical role in kinetochore recruitment of Mph1. PMID:26900649

Downregulation of protein phosphatase 2A carboxyl methylation and methyltransferase may contribute to Alzheimer disease pathogenesis.

PubMed

Sontag, Estelle; Hladik, Christa; Montgomery, Lisa; Luangpirom, Ampa; Mudrak, Ingrid; Ogris, Egon; White, Charles L

2004-10-01

ABalphaC, a major protein phosphatase 2A (PP2A) heterotrimeric enzyme, binds to and regulates the microtubule cytoskeleton and tau. We have shown that ABalphaC protein expression levels are selectively reduced in Alzheimer disease (AD). Notably, the carboxyl methylation of PP2A catalytic subunit (PP2A(C)) is critically required for ABalphaC holoenzyme assembly, and catalyzed by a specific methyltransferase (PPMT). Here, we provide the first analysis of human PPMT and methylated PP2A(C) in brain regions from AD, non-AD demented, and aged control autopsy cases. Immunoblotting analyses revealed that PPMT protein expression and PP2A(C) methylation levels were quantitatively decreased in AD-affected brain regions. Immunohistochemical studies showed that PPMT was abundant in neurons throughout the cortex in normal control and non-AD demented cases. However, in AD, there was a regional loss of PPMT immunoreactivity that closely paralleled the severity of tau pathology, but not amyloid plaque burden. We propose that the deregulation of PPMT and PP2A methylation/demethylation cycles contributes to AD pathogenesis, by inducing changes in PP2A heteromultimeric composition and substrate specificity. In turn, PP2A dysfunction compromises the mechanisms that control tau, neuronal plasticity, and survival.

Serum amyloid beta peptides in patients with dementia and age-matched non-demented controls as detected by surface-enhanced laser desorption ionisation-time of flight mass spectrometry (SELDI-TOF MS).

PubMed

Frankfort, Suzanne V; van Campen, Jos P C M; Tulner, Linda R; Beijnen, Jos H

2008-09-01

By using surface enhanced laser desorption/ionisation- time of flight mass spectrometry (SELDI-TOF MS) an amyloid beta (Abeta) profile was shown in cerebrospinal fluid (CSF) of patients with dementia. To investigate the Abeta-profile in serum with SELDI-TOF MS, to evaluate if this profile resembles CSF profiles and to investigate the correlation between intensity of Abeta-peptide-peaks in serum and clinical, demographical and genetic variables. Duplicate profiling of Abeta by an SELDI-TOF MS immunocapture assay was performed in 106 patients, suffering from Alzheimer's Disease or Vascular Dementia and age-matched non-demented control patients. Linear regression analyses were performed to investigate the intensities of four selected Abeta peaks as dependent variables in relation to the independent clinical, demographic or genetic variables. Abeta37, Abeta38 and Abeta40 were found among additional unidentified Abeta peptides, with the most pronounced Abeta peak at a molecular mass of 7752. This profile partly resembled the CSF profile. The clinical diagnosis was not a predictive independent variable, however ABCB1 genotypes C1236T, G2677T/A, age and creatinine level showed to be related to Abeta peak intensities in multivariate analyses. We found an Abeta profile in serum that partly resembled the CSF profile in demented patients. Age, creatinine levels, presence of the APOE epsilon4 allele and ABCB1 genotypes (C1236T and G2677T/A) were correlated with the Abeta serum profile. The role of P-gp as an Abeta transporter and the role of ABCB1 genotypes deserves further research. The investigated serum Abeta profile is probably not useful in the diagnosis of dementia.

36 CFR 1260.30 - What is the NDC?

Code of Federal Regulations, 2014 CFR

2014-07-01

... 36 Parks, Forests, and Public Property 3 2014-07-01 2014-07-01 false What is the NDC? 1260.30 Section 1260.30 Parks, Forests, and Public Property NATIONAL ARCHIVES AND RECORDS ADMINISTRATION DECLASSIFICATION DECLASSIFICATION OF NATIONAL SECURITY INFORMATION The National Declassification Center (NDC...

A voltammetric determination of caffeic acid in red wines based on the nitrogen doped carbon modified glassy carbon electrode.

PubMed

Karikalan, Natarajan; Karthik, Raj; Chen, Shen-Ming; Chen, Hsi-An

2017-04-05

We reported an electrochemical determination of caffeic acid (CA) based on the nitrogen doped carbon (NDC). The described sensor material was prepared by the flame synthesis method, which gave an excellent platform for the synthesis of carbon nanomaterials with the hetero atom dopant. The synthesized material was confirmed by various physical characterizations and it was further characterized by different electrochemical experiments. The NDC modified glassy carbon electrode (NDC/GCE) shows the superior electrocatalytic performance towards the determination of CA with the wide linear concentration range from 0.01 to 350 μM. It achieves the lowest detection limit of 0.0024 μM and the limit of quantification of 0.004 μM. The NDC/GCE-CA sensor reveals the good selectivity, stability, sensitivity and reproducibility which endorsed that the NDC is promising electrode for the determination of CA. In addition, NDC modified electrode is applied to the determination of CA in red wines and acquired good results.

Increased serum butyrylcholinesterase activity in type IIb hyperlipidaemic patients.

PubMed

Kálmán, János; Juhász, Anna; Rakonczay, Zoltán; Abrahám, György; Zana, Marianna; Boda, Krisztina; Farkas, Tibor; Penke, Botond; Janka, Zoltán

2004-07-23

The inheritance of the apolipoprotein E4 (APOE4) allele has been shown to increase the plasma cholesterol level, but little information is as concerns the association of the APOE genotype and hyperlipidaemia and the activities of two serum enzymes, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Blood samples from 55 type IIb hyperlipidaemic, non-demented patients and 55 age- and sex-matched controls were therefore examined in this pilot study. A significantly increased BChE activity was found in the serum of type IIb hyperlipidaemic patients, but the AChE activity did not differ significantly as compared with that in the control group. The APOE4 allele was significantly overrepresented among the hyperlipidaemic probands, but neither serum cholinesterase activity was affected by the dosage of the APOE4 gene. Our results point to a possible association between an abnormal lipid metabolism and the BChE activity and might have implications as regards the pathomechanism of both Alzheimer's and vascular dementias and the cholinesterase inhibitor therapy of dementing disorders.

36 CFR § 1260.30 - What is the NDC?

Code of Federal Regulations, 2013 CFR

2013-07-01

... 36 Parks, Forests, and Public Property 3 2013-07-01 2012-07-01 true What is the NDC? § 1260.30 Section § 1260.30 Parks, Forests, and Public Property NATIONAL ARCHIVES AND RECORDS ADMINISTRATION DECLASSIFICATION DECLASSIFICATION OF NATIONAL SECURITY INFORMATION The National Declassification Center (NDC...

Nonlinear current-voltage characteristics and enhanced negative differential conductance in graphene field effect transistors.

PubMed

Wang, Lin; Chen, Xiaoshuang; Hu, Yibin; Yu, Anqi; Lu, Wei

2014-11-07

Recent observations of the negative differential conductance (NDC) phenomenon in graphene field-effect transistors (FET) open up new opportunities for their application in graphene-based fast switches, frequency multipliers and, most importantly, in high frequency oscillators up to the terahertz regime. Unlike conventional two-terminal NDC devices that rely on resonant tunneling and inter-valley transferring, in the present work, it has been shown that the universal NDC phenomenon of graphene-based FETs originates from their intrinsic nonlinear carrier transport under a strong electric field. The operation of graphene-NDC devices depends strongly on the interface between graphene and dielectric materials, the scattering-limited carrier mobility, and on the saturation velocity. To reveal such NDC behavior, the output characteristics of GFET are investigated rigorously, with both an analytical model and self-consistent transport equation, and with a multi-electrical parameter simulation. It is demonstrated that the contact-induced doping effect plays an important role in the operational efficiency of graphene-based NDC devices, rather than the ambipolar behavior associated with the competition between electron and hole conductances. In the absence of a NDC regime or beyond one, ambipolar transport starts at Vds > 2Vgs at the drain end, and as the dielectric layer begins to thin down, the kink-like saturation output characteristic is enhanced by the quantum capacitance contribution. These observations reveal the intrinsic mechanism of the NDC effect and open up new opportunities for the performance improvement of GFETs in future high-frequency applications, beyond the current paradigm based on two-terminal diodes.

A figurative proverb test for dementia: rapid detection of disinhibition, excuse and confabulation, causing discommunication.

PubMed

Yamaguchi, Haruyasu; Maki, Yohko; Yamaguchi, Tomoharu

2011-12-01

Communicative disability is regarded as a prominent symptom of demented patients, and many studies have been devoted to analyze deficits of lexical-semantic operations in demented patients. However, it is often observed that even patients with preserved lexical-semantic skills might fail in interactive social communication. Whereas social interaction requires pragmatic language skills, pragmatic language competencies in demented subjects have not been well understood. We propose here a brief stress-free test to detect pragmatic language deficits, focusing on non-literal understanding of figurative expression. We hypothesized that suppression of the literal interpretation was required for figurative language interpretation.  We examined 69 demented subjects, 13 subjects with mild cognitive impairment and 61 healthy controls aged 65 years or more. The subjects were asked the meaning of a familiar proverb categorized as a figurative expression. The answers were analyzed based on five factors, and scored from 0 to 5. To consider the influence of cognitive inhibition on proverb comprehension, the scores of the Stroop Colour-Word Test were compared concerning correct and incorrect answers for each factor, respectively. Furthermore, the characteristics of answers were considered in the light of excuse and confabulation qualitatively. The proverb comprehension scores gradually decreased significantly as dementia progressed. The literal interpretation of the proverb, which showed difficulties in figurative language comprehension, was related to disinhibition. The qualitative analysis showed that excuse and confabulation increased as the dementia stage progressed. Deficits in cognitive inhibition partly explains the difficulties in interactive social communication in dementia. With qualitative analysis, asking the meaning of a proverb can be a brief test applied in a clinical setting to evaluate the stage of dementia, and to illustrate disinhibition, confabulation and excuse, which might cause discommunication and psychosocial maladjustment in demented patients. © 2011 The Authors. Psychogeriatrics © 2011 Japanese Psychogeriatric Society.

Arterial spin labelling detects posterior cortical hypoperfusion in non-demented patients with Parkinson's disease.

PubMed

Syrimi, Zoe Joanna; Vojtisek, Lubomir; Eliasova, Ilona; Viskova, Jana; Svatkova, Alena; Vanicek, Jiri; Rektorova, Irena

2017-05-01

While previous studies suggested that perfusion abnormalities in Parkinson's disease (PD) are driven by dementia, our study aimed to identify perfusion underpinning of cognitive alteration in non-demented PD patients. Cerebral blood flow was measured using arterial spin labelling (ASL) in 28 PD patients (age 65 years ± 9.9 SD) and 16 age-matched healthy controls (HC) (age 65 years ± 7.8 SD), who also underwent neurological and cognitive testing. The 3D pseudocontinuous ASL and T2-weighted scans from 22 PD patients and 16 HC were analysed in a voxel-wise manner using SPM8 software. Associations between the ASL values in volumes of interest (VOIs) and behavioural and cognitive measures were assessed by Spearman correlation analysis. Posterior cortical hypoperfusion was found in PD patients compared to HC in the left supramarginal gyrus/superior temporal gyrus (VOI1) and left posterior cingulate/precuneus (VOI2). Positive correlation was revealed between perfusion in the VOI2 and Addenbrooke's Cognitive Examination Revised (ACE-R) scores after filtering out the effect of age, levodopa equivalent dose (LED), and total intracranial volume (TIV) (R = 0.51, p = 0.04). Conversely, negative correlation between VOI1 and ACE-R was detected (R = -0.62, p = 0.01) after regressing out the effects of motor impairment, age, LED, and TIV. In non-demented subjects with PD, blood flow abnormalities in precuneus/posterior cingulate were linked to the level of motor impairment and global cognitive performance. Oppositely, perfusion abnormalities in supramarginal gyrus might serve as a compensatory mechanism for brain degeneration and decreased cognitive performance.

The Ndc80 internal loop is required for recruitment of the Ska complex to establish end-on microtubule attachment to kinetochores.

PubMed

Zhang, Gang; Kelstrup, Christian D; Hu, Xiao-Wen; Kaas Hansen, Mathilde J; Singleton, Martin R; Olsen, Jesper V; Nilsson, Jakob

2012-07-01

The Ndc80 complex establishes end-on attachment of kinetochores to microtubules, which is essential for chromosome segregation. The Ndc80 subunit is characterized by an N-terminal region that binds directly to microtubules, and a long coiled-coil region that interacts with Nuf2. A loop region in Ndc80 that generates a kink in the structure disrupts the long coiled-coil region but the exact function of this loop, has until now, not been clear. Here we show that this loop region is essential for end-on attachment of kinetochores to microtubules in human cells. Cells expressing loop mutants of Ndc80 are unable to align the chromosomes, and stable kinetochore fibers are absent. Through quantitative mass spectrometry and immunofluorescence we found that the binding of the spindle and kinetochore associated (Ska) complex depends on the loop region, explaining why end-on attachment is defective. This underscores the importance of the Ndc80 loop region in coordinating chromosome segregation through the recruitment of specific proteins to the kinetochore.

The Ndc80 complex bridges two Dam1 complex rings

PubMed Central

Kim, Jae ook; Zelter, Alex; Umbreit, Neil T; Bollozos, Athena; Riffle, Michael; Johnson, Richard; MacCoss, Michael J; Asbury, Charles L; Davis, Trisha N

2017-01-01

Strong kinetochore-microtubule attachments are essential for faithful segregation of sister chromatids during mitosis. The Dam1 and Ndc80 complexes are the main microtubule binding components of the Saccharomyces cerevisiae kinetochore. Cooperation between these two complexes enhances kinetochore-microtubule coupling and is regulated by Aurora B kinase. We show that the Ndc80 complex can simultaneously bind and bridge across two Dam1 complex rings through a tripartite interaction, each component of which is regulated by Aurora B kinase. Mutations in any one of the Ndc80p interaction regions abrogates the Ndc80 complex’s ability to bind two Dam1 rings in vitro, and results in kinetochore biorientation and microtubule attachment defects in vivo. We also show that an extra-long Ndc80 complex, engineered to space the two Dam1 rings further apart, does not support growth. Taken together, our work suggests that each kinetochore in vivo contains two Dam1 rings and that proper spacing between the rings is vital. DOI: http://dx.doi.org/10.7554/eLife.21069.001 PMID:28191870

Development of a brain MRI-based hidden Markov model for dementia recognition

PubMed Central

2013-01-01

Background Dementia is an age-related cognitive decline which is indicated by an early degeneration of cortical and sub-cortical structures. Characterizing those morphological changes can help to understand the disease development and contribute to disease early prediction and prevention. But modeling that can best capture brain structural variability and can be valid in both disease classification and interpretation is extremely challenging. The current study aimed to establish a computational approach for modeling the magnetic resonance imaging (MRI)-based structural complexity of the brain using the framework of hidden Markov models (HMMs) for dementia recognition. Methods Regularity dimension and semi-variogram were used to extract structural features of the brains, and vector quantization method was applied to convert extracted feature vectors to prototype vectors. The output VQ indices were then utilized to estimate parameters for HMMs. To validate its accuracy and robustness, experiments were carried out on individuals who were characterized as non-demented and mild Alzheimer's diseased. Four HMMs were constructed based on the cohort of non-demented young, middle-aged, elder and demented elder subjects separately. Classification was carried out using a data set including both non-demented and demented individuals with a wide age range. Results The proposed HMMs have succeeded in recognition of individual who has mild Alzheimer's disease and achieved a better classification accuracy compared to other related works using different classifiers. Results have shown the ability of the proposed modeling for recognition of early dementia. Conclusion The findings from this research will allow individual classification to support the early diagnosis and prediction of dementia. By using the brain MRI-based HMMs developed in our proposed research, it will be more efficient, robust and can be easily used by clinicians as a computer-aid tool for validating imaging bio-markers for early prediction of dementia. PMID:24564961

Metacognitive Monitoring and Dementia: How Intrinsic and Extrinsic Cues Influence Judgments of Learning in People with Alzheimer’s disease

PubMed Central

Thomas, Ayanna K.; Lee, Meeyeon; Balota, David A.

2014-01-01

Objective The present research compared metamemorial monitoring processes among younger adults, non-demented older adults, and older adults diagnosed with early stage Dementia of the Alzheimer’s Type (DAT). Method In three experiments we examined the influence of intrinsic and extrinsic cues on Judgment of Learning (JOL) accuracy. Changes in association strength between cue-target word pairs served as our intrinsic manipulation in Experiments 1 and 2. Changes in encoding orientation served as our extrinsic manipulation in Experiment 3. Results Across all experiments we found that young adults, non-demented older adults, and individuals in the early stages of DAT effectively used intrinsic and extrinsic factors to guide JOL predictions. Conclusions We conclude that while certain aspects of metacognition may be impaired in both the normal and demented older populations, these groups remain able to use theory-based processing, or general knowledge about how memory works, to make metamemory monitoring predictions. PMID:23876118

Human Ska complex and Ndc80 complex interact to form a load-bearing assembly that strengthens kinetochore–microtubule attachments

PubMed Central

Zelter, Alex; Riffle, Michael; MacCoss, Michael J.; Asbury, Charles L.; Davis, Trisha N.

2018-01-01

Accurate segregation of chromosomes relies on the force-bearing capabilities of the kinetochore to robustly attach chromosomes to dynamic microtubule tips. The human Ska complex and Ndc80 complex are outer-kinetochore components that bind microtubules and are required to fully stabilize kinetochore–microtubule attachments in vivo. While purified Ska complex tracks with disassembling microtubule tips, it remains unclear whether the Ska complex–microtubule interaction is sufficiently strong to make a significant contribution to kinetochore–microtubule coupling. Alternatively, Ska complex might affect kinetochore coupling indirectly, through recruitment of phosphoregulatory factors. Using optical tweezers, we show that the Ska complex itself bears load on microtubule tips, strengthens Ndc80 complex-based tip attachments, and increases the switching dynamics of the attached microtubule tips. Cross-linking mass spectrometry suggests the Ska complex directly binds Ndc80 complex through interactions between the Ska3 unstructured C-terminal region and the coiled-coil regions of each Ndc80 complex subunit. Deletion of the Ska complex microtubule-binding domain or the Ska3 C terminus prevents Ska complex from strengthening Ndc80 complex-based attachments. Together, our results indicate that the Ska complex can directly strengthen the kinetochore–microtubule interface and regulate microtubule tip dynamics by forming an additional connection between the Ndc80 complex and the microtubule. PMID:29487209

Apolipoprotein E polymorphism and low density lipoprotein (LDL) oxidation in patients with dementia.

PubMed

Wehr, Hanna; Bednarska-Makaruk, Małgorzata; Graban, Ałła; Kunicki, Paweł K; Lojkowska, Wanda; Rodo, Maria; Ryglewicz, Danuta

2003-01-01

In patients with dementia, 29 diagnosed as probably suffering from Alzheimer's disease and 46 subjects with dementia of vascular origin, and in 41 non demented control subjects LDL oxidation in vitro was compared in carriers of various apolipoprotein E alleles. Restriction isotyping was performed by gene amplification and cleavage with Hhal, LDL oxidation was investigated by determination of conjugated dienes and vitamin E (alpha tocopherol) plasma level was measured by HPLC. In subjects with dementia oxidation of LDL was shown to be higher in carriers of epsilon4 allele as compared with non-carriers of this allele. It was especially observed in the propagation phase, which illustrates oxidation intensity after the exhaustion of the antioxidant reserve in LDL. Vitamin E level did not show differences between carriers of different alleles. It is concluded that the differences in oxidation susceptibility of LDL between demented subjects possessing particular apolipoprotein E forms can result partially from differing antioxidant properties of apolipoprotein E isoforms and, in a substantial degree, from the size and quality of LDL.

Multifactorial Analysis of a Biomarker Pool for Alzheimer Disease Risk in a North Indian Population.

PubMed

Talwar, Puneet; Grover, Sandeep; Sinha, Juhi; Chandna, Puneet; Agarwal, Rachna; Kushwaha, Suman; Kukreti, Ritushree

2017-01-01

Alzheimer disease (AD) is a progressive neurodegenerative disease with a complex multifactorial etiology. Here, we aim to identify a biomarker pool comprised of genetic variants and blood biomarkers as predictor of AD risk. We performed a case-control study involving 108 cases and 159 non-demented healthy controls to examine the association of multiple biomarkers with AD risk. The APOE genotyping revealed that ε4 allele frequency was significantly high (p value = 0.0001, OR = 2.66, 95% CI 1.58-4.46) in AD as compared to controls, whereas ε2 (p = 0.0430, OR = 0.29, CI 0.07-1.10) was overrepresented in controls. In biochemical assays, significant differences in levels of total copper, free copper, zinc, copper/zinc ratio, iron, epidermal growth factor receptor (EGFR), leptin, and albumin were also observed. The AD risk score (ADRS) as a linear combination of 6 candidate markers involving age, education status, APOE ε4 allele, levels of iron, Cu/Zn ratio, and EGFR was created using stepwise linear discriminant analysis. The area under the ROC curve of the ADRS panel for predicting AD risk was significantly high (AUC = 0.84, p < 0.0001, 95% CI 0.78-0.89, sensitivity = 70.0%, specificity = 83.8%) compared to individual parameters. These findings support the multifactorial etiology of AD and demonstrate the ability of a panel involving 6 biomarkers to discriminate AD cases from non-demented healthy controls. © 2017 S. Karger AG, Basel.

US NDC Modernization Iteration E1 Prototyping Report: User Interface Framework

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lober, Randall R.

2014-12-01

During the first iteration of the US NDC Modernization Elaboration phase (E1), the SNL US NDC modernization project team completed an initial survey of applicable COTS solutions, and established exploratory prototyping related to the User Interface Framework (UIF) in support of system architecture definition. This report summarizes these activities and discusses planned follow-on work.

US NDC Modernization Iteration E1 Prototyping Report: Common Object Interface

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lewis, Jennifer E.; Hess, Michael M.

2014-12-01

During the first iteration of the US NDC Modernization Elaboration phase (E1), the SNL US NDC modernization project team completed an initial survey of applicable COTS solutions, and established exploratory prototyping related to the Common Object Interface (COI) in support of system architecture definition. This report summarizes these activities and discusses planned follow-on work.

The nuclear pore complex protein ALADIN is anchored via NDC1 but not via POM121 and GP210 in the nuclear envelope

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kind, Barbara, E-mail: barbara.kind@uniklinikum-dresden.de; Koehler, Katrin, E-mail: katrin.koehler@uniklinikum-dresden.de; Lorenz, Mike, E-mail: mlorenz@mpi-cbg.de

2009-12-11

The nuclear pore complex (NPC) consists of {approx}30 different proteins and provides the only sites for macromolecular transport between cytoplasm and nucleus. ALADIN was discovered as a new member of the NPC. Mutations in ALADIN are known to cause triple A syndrome, a rare autosomal recessive disorder characterized by adrenal insufficiency, alacrima, and achalasia. The function and exact location of the nucleoporin ALADIN within the NPC multiprotein complex is still unclear. Using a siRNA-based approach we downregulated the three known membrane integrated nucleoporins NDC1, GP210, and POM121 in stably expressing GFP-ALADIN HeLa cells. We identified NDC1 but not GP210 andmore » POM121 as the main anchor of ALADIN within the NPC. Solely the depletion of NDC1 caused mislocalization of ALADIN. Vice versa, the depletion of ALADIN led also to disappearance of NDC1 at the NPC. However, the downregulation of two further membrane-integral nucleoporins GP210 and POM121 had no effect on ALADIN localization. Furthermore, we could show a direct association of NDC1 and ALADIN in NPCs by fluorescence resonance energy transfer (FRET) measurements. Based on our findings we conclude that ALADIN is anchored in the nuclear envelope via NDC1 and that this interaction gets lost, if ALADIN is mutated. The loss of integration of ALADIN in the NPC is a main pathogenetic aspect for the development of the triple A syndrome and suggests that the interaction between ALADIN and NDC1 may be involved in the pathogenesis of the disease.« less

Oxygen-18 isotope of breath CO2 linking to erythrocytes carbonic anhydrase activity: a biomarker for pre-diabetes and type 2 diabetes

PubMed Central

Ghosh, Chiranjit; Banik, Gourab D.; Maity, Abhijit; Som, Suman; Chakraborty, Arpita; Selvan, Chitra; Ghosh, Shibendu; Chowdhury, Subhankar; Pradhan, Manik

2015-01-01

Carbonic anhydrase (CA), a well-characterized metalloenzyme, is associated with oxygen-18 ( 18O)-isotopic fractionations of CO2. To investigate how CA activity links the 18O of breath CO2 to pre-diabetes (PD) and type 2 diabetes (T2D) during metabolism, we studied pre- and post-dose CA activities in erythrocytes with simultaneous monitoring of 18O/ 16O-isotope ratios of breath CO2 and thereafter elucidated potential metabolic pathways underlying CA alteration in the pathogenesis of T2D. Here we show that the post-dose CA activity in both T2D and PD was markedly enhanced, whereas the non-diabetic controls (NDC) exhibited a considerable reduction in post-dose CA activity when compared with their basal CA activities. However, T2D and PD exhibited isotopic enrichments of 18O in breath CO2, while a marked depletion of 18O in CO2 was manifested in NDC. Thus, the isotopic enrichments and depletions of 18O in breath CO2 were well correlated with the changes in CA activities for controls, PD and T2D. Our findings suggest the changes in CA activities in erythrocytes may contribute to the pathogenesis of T2D and the breath C 18O 16O regulated by the CA activity as a potential biomarker for non-invasive assessment of T2D, and thus may open a new method for treating T2D. PMID:25633556

Bone density and brain atrophy in early Alzheimer's disease.

PubMed

Loskutova, Natalia; Honea, Robyn A; Vidoni, Eric D; Brooks, William M; Burns, Jeffrey M

2009-01-01

Studies suggest a link between bone loss and Alzheimer's disease. To examine bone mineral density (BMD) in early Alzheimer's disease (AD) and its relationship to brain structure and cognition, we evaluated 71 patients with early stage AD (Clinical Dementia Rating (CDR) 0.5 and 1) and 69 non-demented elderly control participants (CDR 0). Measures included whole body BMD by dual energy x-ray absorptiometry (DXA) and normalized whole brain volumes computed from structural MRI scans. Cognition was assessed with a standard neuropsychological test battery. Mean BMD was lower in the early AD group (1.11 +/- 0.13) compared to the non-demented control group (1.16 +/- 0.12, p = 0.02), independent of age, gender, habitual physical activity, smoking, depression, estrogen replacement, and apolipoprotein E4 carrier status. In the early AD group, BMD was related to whole brain volume (b = 0.18, p = 0.03). BMD was also associated with cognitive performance, primarily in tests of memory (logical memory [b = 0.15, p = 0.04], delayed logical memory [b = 0.16, p = 0.02], and the selective reminding task - free recall [b = 0.18, p = 0.009]). BMD is reduced in the earliest clinical stages of AD and associated with brain atrophy and memory decline, suggesting that central mechanisms may contribute to bone loss in early AD.

Highly selective luminescent sensing of picric acid based on a water-stable europium metal-organic framework

NASA Astrophysics Data System (ADS)

Xia, Tifeng; Zhu, Fengliang; Cui, Yuanjing; Yang, Yu; Wang, Zhiyu; Qian, Guodong

2017-01-01

A water-stable metal-organic framework (MOF) EuNDC has been synthesized for selective detection of the well-known contaminant and toxicant picric acid (PA) in aqueous solution. Due to the photo-induced electron transfer and self-absorption mechanism, EuNDC displayed rapid, selective and sensitive detection of PA with a detection limit of 37.6 ppb. Recyclability experiments revealed that EuNDC retains its initial luminescent intensity and same quenching efficiency in each cycle, suggesting high photostability and reusability for long-term sensing applications. The excellent detection performance of EuNDC makes it a promising PA sensing material for practical applications.

Comprehensive measurement of total nondigestible carbohydrates in foods by enzymatic-gravimetric method and liquid chromatography.

PubMed

Nishibata, Toyohide; Tashiro, Kouichi; Kanahori, Sumiko; Hashizume, Chieko; Kitagawa, Machiko; Okuma, Kazuhiro; Gordon, Dennis T

2009-09-09

Total nondigestible carbohydrate (NDC) in foods was determined by combining, not modifications, AOAC Official Methods 991.43, 2001.03, and 2002.02. Total NDC included insoluble dietary fiber (IDF) + high-molecular-weight soluble dietary fiber (HMWSDF), nondigestible oligosaccharides (NDO) not precipitated in ethanol solution, and resistant starch (RS). Eight sources of NDC (cellulose, wheat bran, gum arabic, resistant maltodextrin, polydextrose, fructooligosaccharide, galactooligosaccharides, and RS) were incorporated in different combinations into standard formula bread samples. All of the NDC sources and bread samples were analyzed for their (1) IDF + HMWSDF content with corrections for residual RS amount using AOAC Official Method 991.43, (2) NDO by liquid chromatography (LC) in AOAC Official Method 2001.03, and (3) RS by AOAC Official Method 2002.02. The correlation coefficient (R(2)) comparing calculated amounts versus measured amounts of total NDC in 11 bread samples was 0.92. Analysis of commercial food samples was also well matched with the DF + NDO value on their nutritional label. Consequently, we confirmed a single measurement of LC can determine all NDO in foods, and total NDC in foods can be determined by unifying existing AOAC Official Methods.

Regulation of outer kinetochore Ndc80 complex-based microtubule attachments by the central kinetochore Mis12/MIND complex

PubMed Central

Kudalkar, Emily M.; Scarborough, Emily A.; Umbreit, Neil T.; Zelter, Alex; Gestaut, Daniel R.; Riffle, Michael; Johnson, Richard S.; MacCoss, Michael J.; Asbury, Charles L.; Davis, Trisha N.

2015-01-01

Multiple protein subcomplexes of the kinetochore cooperate as a cohesive molecular unit that forms load-bearing microtubule attachments that drive mitotic chromosome movements. There is intriguing evidence suggesting that central kinetochore components influence kinetochore–microtubule attachment, but the mechanism remains unclear. Here, we find that the conserved Mis12/MIND (Mtw1, Nsl1, Nnf1, Dsn1) and Ndc80 (Ndc80, Nuf2, Spc24, Spc25) complexes are connected by an extensive network of contacts, each essential for viability in cells, and collectively able to withstand substantial tensile load. Using a single-molecule approach, we demonstrate that an individual MIND complex enhances the microtubule-binding affinity of a single Ndc80 complex by fourfold. MIND itself does not bind microtubules. Instead, MIND binds Ndc80 complex far from the microtubule-binding domain and confers increased microtubule interaction of the complex. In addition, MIND activation is redundant with the effects of a mutation in Ndc80 that might alter its ability to adopt a folded conformation. Together, our results suggest a previously unidentified mechanism for regulating microtubule binding of an outer kinetochore component by a central kinetochore complex. PMID:26430240

Association between late-onset depression and incident dementia in Chinese older persons.

PubMed

Tam, C W C; Lam, L C W

2013-12-01

OBJECTIVE. Previous studies have shown that depression is a precursor / prodrome or susceptible state for the development of dementia. This study aimed to examine the relationship between late-onset depression and subsequent cognitive and functional decline in a cohort of non-demented older Chinese persons at their 2-year follow-up and investigate for possible predictors of cognitive decline. METHODS. A total of 81 depressed subjects and 468 non-depressed community controls were recruited. RESULTS. Subjects with late-onset depression showed significantly more incident Clinical Dementia Rating (CDR) scale decline (odds ratio = 3.87, 95% confidence interval = 2.23-6.70) and dementia (odds ratio = 3.44, 95% confidence interval = 1.75-6.77) than those without depression. A higher proportion of depressed CDR 0 subjects had CDR and functional decline than their non-depressed counterparts. Depressed CDR 0.5 subjects had significantly higher rates of functional decline and lower rates of improvement in CDR than their non-depressed counterparts. CONCLUSION. Diagnosis of depression was a robust predictor of incident very mild dementia (i.e. CDR of 0.5) and depression severity was a predictor of progression to dementia from CDR of 0.5. The association between depression and the risk of CDR decline and dementia was observed in non-demented Chinese subjects. Depression was also associated with persistent mild cognitive deficits in CDR 0.5 subjects.

Assessment of Boron Doped Diamond Electrode Quality and Application to In Situ Modification of Local pH by Water Electrolysis.

PubMed

Read, Tania L; Macpherson, Julie V

2016-01-06

Boron doped diamond (BDD) electrodes have shown considerable promise as an electrode material where many of their reported properties such as extended solvent window, low background currents, corrosion resistance, etc., arise from the catalytically inert nature of the surface. However, if during the growth process, non-diamond-carbon (NDC) becomes incorporated into the electrode matrix, the electrochemical properties will change as the surface becomes more catalytically active. As such it is important that the electrochemist is aware of the quality and resulting key electrochemical properties of the BDD electrode prior to use. This paper describes a series of characterization steps, including Raman microscopy, capacitance, solvent window and redox electrochemistry, to ascertain whether the BDD electrode contains negligible NDC i.e. negligible sp(2) carbon. One application is highlighted which takes advantage of the catalytically inert and corrosion resistant nature of an NDC-free surface i.e. stable and quantifiable local proton and hydroxide production due to water electrolysis at a BDD electrode. An approach to measuring the local pH change induced by water electrolysis using iridium oxide coated BDD electrodes is also described in detail.

Assessment of Boron Doped Diamond Electrode Quality and Application to In Situ Modification of Local pH by Water Electrolysis

PubMed Central

Read, Tania L.; Macpherson, Julie V.

2016-01-01

Boron doped diamond (BDD) electrodes have shown considerable promise as an electrode material where many of their reported properties such as extended solvent window, low background currents, corrosion resistance, etc., arise from the catalytically inert nature of the surface. However, if during the growth process, non-diamond-carbon (NDC) becomes incorporated into the electrode matrix, the electrochemical properties will change as the surface becomes more catalytically active. As such it is important that the electrochemist is aware of the quality and resulting key electrochemical properties of the BDD electrode prior to use. This paper describes a series of characterization steps, including Raman microscopy, capacitance, solvent window and redox electrochemistry, to ascertain whether the BDD electrode contains negligible NDC i.e. negligible sp2 carbon. One application is highlighted which takes advantage of the catalytically inert and corrosion resistant nature of an NDC-free surface i.e. stable and quantifiable local proton and hydroxide production due to water electrolysis at a BDD electrode. An approach to measuring the local pH change induced by water electrolysis using iridium oxide coated BDD electrodes is also described in detail. PMID:26779959

Salience and Default Mode Network Coupling Predicts Cognition in Aging and Parkinson's Disease.

PubMed

Putcha, Deepti; Ross, Robert S; Cronin-Golomb, Alice; Janes, Amy C; Stern, Chantal E

2016-02-01

Cognitive impairment is common in Parkinson's disease (PD). Three neurocognitive networks support efficient cognition: the salience network, the default mode network, and the central executive network. The salience network is thought to switch between activating and deactivating the default mode and central executive networks. Anti-correlated interactions between the salience and default mode networks in particular are necessary for efficient cognition. Our previous work demonstrated altered functional coupling between the neurocognitive networks in non-demented individuals with PD compared to age-matched control participants. Here, we aim to identify associations between cognition and functional coupling between these neurocognitive networks in the same group of participants. We investigated the extent to which intrinsic functional coupling among these neurocognitive networks is related to cognitive performance across three neuropsychological domains: executive functioning, psychomotor speed, and verbal memory. Twenty-four non-demented individuals with mild to moderate PD and 20 control participants were scanned at rest and evaluated on three neuropsychological domains. PD participants were impaired on tests from all three domains compared to control participants. Our imaging results demonstrated that successful cognition across healthy aging and Parkinson's disease participants was related to anti-correlated coupling between the salience and default mode networks. Individuals with poorer performance scores across groups demonstrated more positive salience network/default-mode network coupling. Successful cognition relies on healthy coupling between the salience and default mode networks, which may become dysfunctional in PD. These results can help inform non-pharmacological interventions (repetitive transcranial magnetic stimulation) targeting these specific networks before they become vulnerable in early stages of Parkinson's disease.

Architecture and Flexibility of the Yeast Ndc80 Kinetochore Complex

PubMed Central

Wang, Hong-Wei; Long, Sydney; Ciferri, Claudio; Westermann, Stefan; Drubin, David; Barnes, Georjana; Nogales, Eva

2008-01-01

Kinetochores mediate microtubule–chromosome attachment and ensure accurate segregation of sister chromatids. The highly conserved Ndc80 kinetochore complex makes direct contacts with the microtubule and is essential for spindle checkpoint signaling. It contains a long coiled-coil region with globular domains at each end involved in kinetochore localization and microtubule binding, respectively. We have directly visualized the architecture of the yeast Ndc80 complex and found a dramatic kink within the 560-Å coiled-coil rod located about 160 Å from the larger globular head. Comparison of our electron microscopy images to the structure of the human Ndc80 complex allowed us to position the kink proximal to the microtubule-binding end and to define the conformational range of the complex. The position of the kink coincides with a coiled-coil breaking region conserved across eukaryotes. We hypothesize that the kink in Ndc80 is essential for correct kinetochore geometry and could be part of a tension-sensing mechanism at the kinetochore. PMID:18793650

Single molecular orientation switching of an endohedral metallofullerene.

PubMed

Yasutake, Yuhsuke; Shi, Zujin; Okazaki, Toshiya; Shinohara, Hisanori; Majima, Yutaka

2005-06-01

The single molecular orientation switching of the Tb@C82 endohedral metallofullerene has been studied by using low-temperature ultrahigh vacuum (UHV) scanning tunneling microscopy (STM). An octanethiol self-assembled monolayer (SAM) was introduced between Tb@C82 and the Au111 substrate to control the thermal rotational states of Tb@C82. Scanning tunneling spectroscopy (STS) of Tb@C82 on an octanethiol SAM at 13 K demonstrated hysteresis including negative differential conductance (NDC). This observed hysteresis and NDC is interpreted in terms of a switching of the Tb@C82 molecular orientation caused by the interaction between its electric dipole moment and an external electric field.

Observation of negative differential capacitance (NDC) in Ti Schottky diodes on SiGe islands

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rangel-Kuoppa, Victor-Tapio; Jantsch, Wolfgang; Tonkikh, Alexander

2013-12-04

The Negative Differential Capacitance (NDC) effect on Ti Schottky diodes formed on n-type Silicon samples with embedded Germanium Quantum Dots (QDs) is observed and reported. The NDC-effect is detected using capacitance-voltage (CV) method at temperatures below 200 K. It is explained by the capture of electrons in Germanium QDs. Our measurements reveal that each Ge QD captures in average eight electrons.

Spontaneous Language Production in Bilingual Parkinson's Disease Patients: Evidence of Greater Phonological, Morphological and Syntactic Impairments in Native Language

ERIC Educational Resources Information Center

Zanini, Sergio; Tavano, Alessandro; Fabbro, Franco

2010-01-01

Nine early non-demented bilingual (L1--Friulian, L2--Italian) patients with Parkinson's disease and nine normal controls matched for age, sex and years of education were studied on a spontaneous language production task. All subjects had acquired L1 from birth in a home environment and L2 at the age of six at school formally. Patients with PD…

21 CFR 1308.22 - Excluded substances.

Code of Federal Regulations, 2011 CFR

2011-04-01

....C. 811(g) (1)): Excluded Nonnarcotic Products Company Trade name NDC code Form Controlled substance... TB Phenobarbital 8.00 Hawthorne Products Inc Choate's Leg Freeze LQ Chloral hydrate 246.67 Parke...

Temporal Lobe and Frontal-Subcortical Dissociations in Non-Demented Parkinson's Disease with Verbal Memory Impairment.

PubMed

Tanner, Jared J; Mareci, Thomas H; Okun, Michael S; Bowers, Dawn; Libon, David J; Price, Catherine C

2015-01-01

The current investigation examined verbal memory in idiopathic non-dementia Parkinson's disease and the significance of the left entorhinal cortex and left entorhinal-retrosplenial region connections (via temporal cingulum) on memory impairment in Parkinson's disease. Forty non-demented Parkinson's disease patients and forty non-Parkinson's disease controls completed two verbal memory tests--a wordlist measure (Philadelphia repeatable Verbal Memory Test) and a story measure (Logical Memory). All participants received T1-weighted and diffusion magnetic resonance imaging (3T; Siemens) sequences. Left entorhinal volume and left entorhinal-retrosplenial connectivity (temporal cingulum edge weight) were the primary imaging variables of interest with frontal lobe thickness and subcortical structure volumes as dissociating variables. Individuals with Parkinson's disease showed worse verbal memory, smaller entorhinal volumes, but did not differ in entorhinal-retrosplenial connectivity. For Parkinson's disease entorhinal-retrosplenial edge weight had the strongest associations with verbal memory. A subset of Parkinson's disease patients (23%) had deficits (z-scores < -1.5) across both memory measures. Relative to non-impaired Parkinson's peers, this memory-impaired group had smaller entorhinal volumes. Although entorhinal cortex volume was significantly reduced in Parkinson's disease patients relative to non-Parkinson's peers, only white matter connections associated with the entorhinal cortex were significantly associated with verbal memory performance in our sample. There was also no suggestion of contribution from frontal-subcortical gray or frontal white matter regions. These findings argue for additional investigation into medial temporal lobe gray and white matter connectivity for understanding memory in Parkinson's disease.

The metabolic syndrome, diabetes, and Alzheimer's disease.

PubMed

García-Lara, Juan Miguel Antonio; Aguilar-Navarro, Sara; Gutiérrez-Robledo, Luis Miguel; Avila-Funes, José Alberto

2010-01-01

The metabolic syndrome (MS) is a cluster of metabolic abnormalities that has been controversially associated with Alzheimer's disease (AD), so the purpose of this report was to investigate the association between these two chronic diseases a sample of older persons. Case-control study of 90 consecutive outpatients with AD and 180 non-demented controls from a dementia clinic at a tertiary care hospital in Mexico City. Probable or possible AD was diagnosed according to the guidelines of the Consortium to Establish a Registry for Alzheimer's Disease, whereas control participants where those classified as normal by the same instrument. MS was defined according to the World Health Organization criteria. Patients were matched 1:2 by age, sex, and years of education. Conditional regression analysis was used to test the association between MS and AD. Compared to controls, MS was more frequent among AD patients (72.2% vs. 23.3%; P < 0.01). While all components of MS were more frequent among cases than control patients, only diabetes was statistically significant, whereas hypertriglyceridemia and low HDL cholesterol were marginally associated. Conditional regression analysis showed that among AD participants, the probability of having MS was about sevenfold higher than for their non-demented counterparts (OR 6.72, 95% CI 3.72-12.13; P < 0.01). The MS is a clinical entity that encompasses a diverse range of chronic diseases, which could be a better risk indicator than any individual MS component for adverse health outcomes, like AD. Our findings underscore the harmful role of MS in the health status of the elderly.

Widespread Decrease of Nicotinic Acetylcholine Receptors in Parkinson's Disease

PubMed Central

Ichise, Masanori; Zoghbi, Sami S; Liow, Jeih-San; Ghose, Subroto; Vines, Douglass C; Sangare, Janet; Lu, Jian-Qiang; Cropley, Vanessa L; Iida, Hidehiro; Kim, Kyeong Min; Cohen, Robert M; Bara-Jimenez, William; Ravina, Bernard; Innis, Robert B

2005-01-01

Nicotinic acetylcholine receptors (nAChRs) have close interactions with the dopaminergic system and play critical roles in cognitive function. nAChRs were imaged in 10 non-demented Parkinson's disease (PD) patients and 15 age-matched healthy subjects using a single photon emission computed tomography ligand [123I]5-iodo-3-[2(S)-2-azetidinylmethoxy]pyridine. Using an arterial input function, we measured the total distribution volume (V; specific plus non-displaceable) as well as the delivery (K1). PD showed a widespread significant decrease (∼10%) of V in both cortical and subcortical regions without a significant change in K1. These results indicate the importance of extending the study to demented patients. PMID:16374823

Memory, Mood, and Vitamin D in Persons with Parkinson’s Disease

PubMed Central

Peterson, Amie L.; Murchison, Charles; Zabetian, Cyrus; Leverenz, James B.; Watson, G. Stennis; Montine, Thomas; Carney, Natasha; Bowman, Gene L.; Edwards, Karen; Quinn, Joseph F.

2014-01-01

Background Research in recent years has suggested a role of vitamin D in the central nervous system. The final converting enzyme and the vitamin D receptor are found throughout the human brain. From animal studies vitamin D appears important in neurodevelopment, up-regulation of neurotrophic factors, stabilization of mitochondrial function, and antioxidation. Objective To examine the relationship between serum vitamin D and neuropsychiatric function in persons with Parkinson’s disease (PD). Methods This is an add-on study to a longitudinal study following neuropsychiatric function in persons with PD. Baseline neuropsychiatric performance and serum 25-hydroxyvitamin D were examined for 286 participants with PD. Measures of global cognitive function (MMSE, MOCA, Mattis Dementia Scale), verbal memory (Hopkins Verbal Learning Test), fluency (animals, vegetables, and FAS words), visuospatial function (Benton Line Orientation), executive function (Trails Making Test and Digit-Symbol Substitution), PD severity (Hoehn & Yahr and Unified Parkinson’s Disease Rating Scale) and depression (Geriatric Depression Scale (GDS)) were administered. Multivariate linear regression assessed the association between vitamin D concentration and neuropsychiatric function, in the entire cohort as well as the non-demented and demented subsets. Results Using a multivariate model, higher vitamin concentrations were associated with better performance on numerous neuropsychiatric tests in the non-demented subset of the cohort. Significant associations were specifically found between vitamin D concentration and verbal fluency and verbal memory (t = 4.31, p < 0.001 and t = 3.04, p = 0.0083). Vitamin D concentrations also correlated with depression scores (t =−3.08, p = 0.0083) in the non-demented subset. Conclusions Higher plasma vitamin D is associated with better cognition and better mood in this sample of PD patients without dementia. Determination of causation will require a vitamin D intervention study. PMID:24081441

One-year survival of demented stroke patients: data from the Dijon Stroke Registry, France (1985-2008).

PubMed

Béjot, Y; Jacquin, A; Rouaud, O; Durier, J; Aboa-Eboulé, C; Hervieu, M; Osseby, G-V; Giroud, M

2012-05-01

  Dementia is a frequent condition after stroke that may affect the prognosis of patients. Our aim was to determine whether post-stroke dementia was a predictor of 1-year case-fatality and to evaluate factors that could influence survival in demented stroke patients. From 1985 to 2008, all first-ever strokes were recorded in the population-based stroke registry of Dijon, France (150, 000 inhabitants). Dementia was diagnosed during the first month following stroke, according to DSM-III and DSM-IV criteria. Survival was evaluated at 1 year and multivariate analyses were performed using Cox proportional hazards to identify independent predictive factors.   We recorded 3948 first-ever strokes. Among these stroke patients, 3201 (81%) were testable, and of these, 653 (20.4%) had post-stroke dementia (337 women and 316 men). Demented patients had lower 1-year survival than patients without dementia (82.9% vs. 86.9%, P = 0.013). However, in multivariate analysis, dementia did not appear as an independent predictor of 1-year death. In demented stroke patients, age >80 years old, severe handicap at discharge, recurrent stroke within the first year and subarachnoid haemorrhage were associated with a higher risk of 1-year death, and the risk was lower in the study period 2003-2008.   Dementia after stroke is not independently associated with an increased risk of death at 1 year. In recent years, 1-year case-fatality decreased in demented as well as in and non-demented patients suggesting that improvements in the management of stroke also benefited the most fragile patients. © 2011 The Author(s). European Journal of Neurology © 2011 EFNS.

Geothermal induced seismicity: What links source mechanics and event magnitudes to faulting regime and injection rates?

NASA Astrophysics Data System (ADS)

Martinez-Garzon, Patricia; Kwiatek, Grzegorz; Bohnhoff, Marco; Dresen, Georg

2017-04-01

Improving estimates of seismic hazard associated to reservoir stimulation requires advanced understanding of the physical processes governing induced seismicity, which can be better achieved by carefully processing large datasets. To this end, we investigate source-type processes (shear/tensile/compaction) and rupture geometries with respect to the local stress field using seismicity from The Geysers (TG) and Salton Sea geothermal reservoirs, California. Analysis of 869 well-constrained full moment tensors (MW 0.8-3.5) at TG reveals significant non-double-couple (NDC) components (>25%) for 65% of the events and remarkably diversity in the faulting mechanisms. Volumetric deformation is clearly governed by injection rates with larger NDC components observed near injection wells and during high injection periods. The overall volumetric deformation from the moment tensors increases with time, possibly reflecting a reservoir pore pressure increase after several years of fluid injection with no significant production nearby. The obtained source mechanisms and fault orientations are magnitude-dependent and vary significantly between faulting regimes. Normal faulting events (MW < 2) reveal substantial NDC components indicating dilatancy, and they occur on varying fault orientations. In contrast, strike-slip events dominantly reveal a double-couple source, larger magnitudes (MW > 2) and mostly occur on optimally oriented faults with respect to the local stress field. NDC components indicating closure of cracks and pore spaces in the source region are found for reverse faulting events with MW > 2.5. Our findings from TG are generally consistent with preliminary source-type results from a reduced subset of well-recorded seismicity at the Salton Sea geothermal reservoir. Combined results imply that source processes and magnitudes of geothermal-induced seismicity are strongly affected by and systematically related to the hydraulic operations and the local stress state.

Synthesis, X-ray crystal structures, and gas sorption properties of pillared square grid nets based on paddle-wheel motifs: implications for hydrogen storage in porous materials.

PubMed

Chun, Hyungphil; Dybtsev, Danil N; Kim, Hyunuk; Kim, Kimoon

2005-06-06

A systematic modulation of organic ligands connecting dinuclear paddle-wheel motifs leads to a series of isomorphous metal-organic porous materials that have a three-dimensional connectivity and interconnected pores. Aromatic dicarboxylates such as 1,4-benzenedicarboxylate (1,4-bdc), tetramethylterephthalate (tmbdc), 1,4-naphthalenedicarboxylate (1,4-ndc), tetrafluoroterephthalate (tfbdc), or 2,6-naphthalenedicarboxylate (2,6-ndc) are linear linkers that form two-dimensional layers, and diamine ligands, 4-diazabicyclo[2.2.2]octane (dabco) or 4,4'-dipyridyl (bpy), coordinate at both sides of Zn(2) paddle-wheel units to bridge the layers vertically. The resulting open frameworks [Zn(2)(1,4-bdc)(2)(dabco)] (1), [Zn(2)(1,4-bdc)(tmbdc)(dabco)] (2), [Zn(2)(tmbdc)(2)(dabco)] (3), [Zn(2)(1,4-ndc)(2)(dabco)] (4), [Zn(2)(tfbdc)(2)(dabco)] (5), and [Zn(2)(tmbdc)(2)(bpy)] (8) possess varying size of pores and free apertures originating from the side groups of the 1,4-bdc derivatives. [Zn(2)(1,4-bdc)(2)(bpy)] (6) and [Zn(2)(2,6-ndc)(2)(bpy)] (7) have two- and threefold interpenetrating structures, respectively. The non-interpenetrating frameworks (1-5 and 8) possess surface areas in the range of 1450-2090 m(2)g(-1) and hydrogen sorption capacities of 1.7-2.1 wt % at 78 K and 1 atm. A detailed analysis of the sorption data in conjunction with structural similarities and differences concludes that porous materials with straight channels and large openings do not perform better than those with wavy channels and small openings in terms of hydrogen storage through physisorption.

Microstructural White Matter Changes Underlying Cognitive and Behavioural Impairment in ALS – An In Vivo Study Using DTI

PubMed Central

Kasper, Elisabeth; Schuster, Christina; Machts, Judith; Kaufmann, Joern; Bittner, Daniel; Vielhaber, Stefan; Benecke, Reiner; Teipel, Stefan; Prudlo, Johannes

2014-01-01

Background A relevant fraction of patients with amyotrophic lateral sclerosis (ALS) exhibit a fronto-temporal pattern of cognitive and behavioural disturbances with pronounced deficits in executive functioning and cognitive control of behaviour. Structural imaging shows a decline in fronto-temporal brain areas, but most brain imaging studies did not evaluate cognitive status. We investigated microstructural white matter changes underlying cognitive impairment using diffusion tensor imaging (DTI) in a large cohort of ALS patients. Methods We assessed 72 non-demented ALS patients and 65 matched healthy control subjects using a comprehensive neuropsychological test battery and DTI. We compared DTI measures of fiber tract integrity using tract-based spatial statistics among ALS patients with and without cognitive impairment and healthy controls. Neuropsychological performance and behavioural measures were correlated with DTI measures. Results Patients without cognitive impairment demonstrated white matter changes predominantly in motor tracts, including the corticospinal tract and the body of corpus callosum. Those with impairments (ca. 30%) additionally presented significant white matter alterations in extra-motor regions, particularly the frontal lobe. Executive and memory performance and behavioural measures were correlated with fiber tract integrity in large association tracts. Conclusion In non-demented cognitively impaired ALS patients, white matter changes measured by DTI are related to disturbances of executive and memory functions, including prefrontal and temporal regions. In a group comparison, DTI is able to observe differences between cognitively unimpaired and impaired ALS patients. PMID:25501028

Real benefit of a protective factor against dementia: Importance of controlling for death. Example of sport practice.

PubMed

Grasset, Leslie; Joly, Pierre; Jacqmin-Gadda, Hélène; Letenneur, Luc; Wittwer, Jérôme; Amieva, Hélène; Helmer, Catherine; Dartigues, Jean François

2017-01-01

To analyse the impact of a risk factor on several epidemiological indicators of death and dementia; the example of sport practice is presented. A population of 3670 non-demented subjects living at home and aged 65 and older from the PAQUID study were followed for 22 years. Sport practice was documented at baseline. Dementia (according to DSM-III-R criteria) and death were assessed at each visit. Analyses were performed with an Illness-Death model, providing results on the risks of dementia and death, probabilities and life expectancies. A total of 743 subjects (20.2%) participated in regular sport practice. During the follow-up, the proportion of death was lower in the elderly people practicing sport (EPPS), whereas the proportion of incident dementia cases was the same. The adjusted model showed a decreased risk of dementia (HR = 0.84 (0.72-1.00)) and of death for non-demented subjects (HR = 0.61 (0.51-0.71)) for EPPS but a similar risk of death with dementia in both sport groups. The probability of remaining alive without dementia was higher in EPPS, whereas the probability of dying was lower. The mean lifetime without dementia was 3 years higher for the EPPS, but the mean lifetime with dementia was the same. A preventive measure on a protective factor that is more effective for preventing death than dementia could lead to an increased lifetime without dementia; however, the number of demented cases may remain unchanged, even if the risk of developing dementia is reduced. This dynamic is important to forecast the need for health care and social services for the elderly.

Participation of the NDC Austria at the NDC Preparedness Exercise 2012

NASA Astrophysics Data System (ADS)

Mitterbauer, Ulrike; Wotawa, Gerhard; Schraick, Irene

2013-04-01

NDC Preparedness Exercises (NPEs) are conducted annually by the National Data Centers (NDCs) of CTBT States Signatories to train the detection of a (hypothetical) nuclear test. During the NDC Preparedness Exercise 2012, a fictitious radionuclide scenario originating from a real seismic event (mining explosion) was calculated by the German NDC and distributed among all NDCs. For the scenario computation, it was assumed that the selected seismic event was the epicentre of an underground nuclear fission explosion. The scenario included detections of the Iodine isotopes I-131 and I-133 (both particulates), and the Radioxenon Isotopes Xe-133, Xe-133M, Xe-131M and Xe-135 (noble gas). By means of atmospheric transport modelling (ATM), concentrations of all these six isotopes which would result from the hypothetical explosion were calculated and interpolated to the IMS station locations. The participating NDCs received information about the concentration of the isotopes at the station locations without knowing the underlying seismic event. The aim of the exercise was to identify this event based on the detection scenario. The Austrian NDC performed the following analyses: • Atmospheric backtracking and data fusion to identify seismic candidate events, • Seismic analysis of candidate events within the possible source region, • Atmospheric transport modelling (forward mode) from identified candidate events, comparison between "measured" and simulated concentrations based on certain release assumptions. The main goal of the analysis was to identify the event selected by NDC Germany to calculate the radionuclide scenario, and to exclude other events. In the presentation, the analysis methodology as well as the final results and conclusions will be shown and discussed in detail.

Solar tower enhanced natural draft dry cooling tower

NASA Astrophysics Data System (ADS)

Yang, Huiqiang; Xu, Yan; Acosta-Iborra, Alberto; Santana, Domingo

2017-06-01

Concentrating Solar Power (CSP) plants are located in desert areas where the Direct Normal Irradiance (DNI) value is very high. Since water resource is scarcely available, mechanical draft cooing technology is commonly used, with power consumption of mechanical fans being approximately 2% of the total power generated. Today, there is only one solar power plant (Khi Solar One in South Africa) uses a condenser installed in a Natural Draft Cooling (NDC) tower that avoids the windage loss of water occurring in wet cooling towers. Although, Khi Solar One is a cavity receiver power tower, the receivers can be hung onto the NDC tower. This paper looks at a novel integration of a NDC tower into an external molten salt receiver of a solar power plant, which is one of a largest commercial molten salt tower in China, with 100MWe power capacity. In this configuration study, the NDC tower surrounds the concrete tower of the receiver concentrically. In this way, the receiver concrete tower is the central support of the NDC tower, which consists of cable networks that are fixed to the concrete tower and suspended at a certain height over the floor. The cable networks support the shell of the NDC tower. To perform a preliminary analysis of the behavior of this novel configuration, two cases of numerical simulation in three dimensional (3D) models have been solved using the commercial Computational Fluid Dynamics (CFD) code, ANSYS Fluent 6.3. The results show that the integration of the NDC tower into an external central receiver tower is feasible. Additionally, the total heat transfer rate is not reduced but slightly increases when the molten salt receiver is in operation because of the additional natural draft induced by the high temperature of the receiver.

Physical Frailty Is Associated with Longitudinal Decline in Global Cognitive Function in Non-Demented Older Adults: A Prospective Study.

PubMed

Chen, S; Honda, T; Narazaki, K; Chen, T; Kishimoto, H; Haeuchi, Y; Kumagai, S

2018-01-01

To assess the relationship between physical frailty and subsequent decline in global cognitive function in the non-demented elderly. A prospective population-based study in a west Japanese suburban town, with two-year follow-up. Community-dwellers aged 65 and older without placement in long-term care, and not having a history of dementia, Parkinson's disease and depression at baseline, who participated in the cohort of the Sasaguri Genkimon Study and underwent follow-up assessments two years later (N = 1,045). Global cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). Physical frailty was identified according to the following five components: weight loss, low grip strength, exhaustion, slow gait speed and low physical activities. Linear regression models were used to examine associations between baseline frailty status and the MoCA scores at follow-up. Logistic regression models were used to estimate the risk of cognitive decline (defined as at least two points decrease of MoCA score) according to baseline frailty status. Seven hundred and eight non-demented older adults were included in the final analyses (mean age: 72.6 ± 5.5 years, male 40.3%); 5.8% were frail, and 40.8% were prefrail at baseline. One hundred and fifty nine (22.5%) participants experienced cognitive decline over two years. After adjustment for baseline MoCA scores and all confounders, being frail at baseline was significantly associated with a decline of 1.48 points (95% confidence interval [CI], -2.37 to -0.59) in MoCA scores, as compared with non-frailty. Frail persons were over two times more likely to experience cognitive decline (adjusted odds ratio 2.28; 95% CI, 1.02 to 5.08), compared to non-frail persons. Physical frailty is associated with longitudinal decline in global cognitive function in the non-demented older adults over a period of two years. Physically frail older community-dwellers should be closely monitored for cognitive decline that can be sensitively captured by using the MoCA.

Highly selective luminescent sensing of picric acid based on a water-stable europium metal-organic framework

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xia, Tifeng; Zhu, Fengliang; Cui, Yuanjing, E-mail: cuiyj@zju.edu.cn

A water-stable metal-organic framework (MOF) EuNDC has been synthesized for selective detection of the well-known contaminant and toxicant picric acid (PA) in aqueous solution. Due to the photo-induced electron transfer and self-absorption mechanism, EuNDC displayed rapid, selective and sensitive detection of PA with a detection limit of 37.6 ppb. Recyclability experiments revealed that EuNDC retains its initial luminescent intensity and same quenching efficiency in each cycle, suggesting high photostability and reusability for long-term sensing applications. The excellent detection performance of EuNDC makes it a promising PA sensing material for practical applications. - Graphical abstract: A water-stable europium-based metal-organic framework hasmore » been reported for highly selective sensing of picric acid (PA) with a detection limit of 37.6 ppb in aqueous solution. - Highlights: • A water-stable metal-organic framework (MOF) EuNDC was synthesized. • The highly selective detection of picric acid with a detection limit of 37.6 ppb was realized. • The detection mechanism were also presented and discussed.« less

Non-Double-Couple Component Analysis of Induced Microearthquakes in the Val D'Agri Basin (Italy)

NASA Astrophysics Data System (ADS)

Roselli, P.; Improta, L.; Saccorotti, G.

2017-12-01

In recent years it has become accepted that earthquake source can attain significant Non-Double-Couple (NDC) components. Among the driving factors of deviation from normal double-couple (DC) mechanisms there is the opening/closing of fracture networks and the activation of pre-existing faults by pore fluid pressure perturbations. This observation makes the thorough analysis of source mechanism of key importance for the understanding of withdrawal/injection induced seismicity from geothermal and hydrocarbon reservoirs, as well as of water reservoir induced seismicity. In addition to the DC component, seismic moment tensor can be decomposed into isotropic (ISO) and compensated linear vector dipole (CLVD) components. In this study we performed a careful analysis of the seismic moment tensor of induced microseismicity recorded in the Val d'Agri (Southern Apennines, Italy) focusing our attention on the NDC component. The Val d'Agri is a Quaternary extensional basin that hosts the largest onshore European oil field and a water reservoir (Pertusillo Lake impoundment) characterized by severe seasonal level oscillations. Our input data-set includes swarm-type induced micro-seismicity recorded between 2005-2006 by a high-performance network and accurately localized by a reservoir-scale local earthquake tomography. We analyze two different seismicity clusters: (i) a swarm of 69 earthquakes with 0.3 ≤ ML ≤ 1.8 induced by a wastewater disposal well of the oilfield during the initial daily injection tests (10 days); (ii) 526 earthquakes with -0.2 ≤ ML ≤ 2.7 induced by seasonal volume changes of the artificial lake. We perform the seismic moment tensor inversion by using HybridMT code. After a very accurate signal-to-noise selection and hand-made picking of P-pulses, we obtain %DC, %ISO, %CLVD for each event. DC and NDC components are analyzed and compared with the spatio-temporal distribution of seismicity, the local stress field, the injection parameters and the water level in the impoundment. We find significant NDC components and abrupt temporal variations in the %DC and %ISO components that appear linked to the extremely variable parameters of the injection tests into the disposal well.

Cognitive deficits in amyotrophic lateral sclerosis evaluated by event-related potentials.

PubMed

Ogawa, Tomohiro; Tanaka, Hideaki; Hirata, Koichi

2009-04-01

To determine the cognitive profiles in non-demented, relatively less handicapped patients with early-stage sporadic amyotrophic lateral sclerosis (ALS) by using neuropsychological tests, event-related potentials (ERPs) and clinical scale. We recruited 19 patients with sporadic ALS (eight with limb-onset, 11 with bulbar-onset) and 19 controls. In addition to the mini-mental state examination and the Wechsler adult intelligence scale-revised, we assessed the frontal lobe function with Wisconsin card sorting test, Stroop test and trail making test. We used auditory 'oddball' counting paradigm for the ERPs under 20-channel electroencephalogram (EEG) recording. Global field power (GFP) was computed, and its peak amplitudes and latencies of N1/N2/P3 were determined. The results of ERP and neuropsychological tests were correlated with respiratory function and clinical scale. No global cognitive impairment except for subtle frontal dysfunction was detected, although N1/N2/P3 GFP latencies were significantly prolonged in ALS patients than in the controls. Vital capacity correlated with P3 GFP amplitude, and the relative bulbar functional rating scale correlated with P3 GFP latency. Our findings indicated the presence of sub-clinical cognitive deficits in non-demented, sporadic ALS patients. In addition, clinical sub-types and respiratory function dependently influenced cognitive function in patients with sporadic ALS. ERP confirmed cognitive impairment in patients with sporadic ALS.

Modeling of frequency-dependent negative differential capacitance in InGaAs/InP photodiode

NASA Astrophysics Data System (ADS)

Wang, Yidong; Chen, Jun; Xu, Jintong; Li, Xiangyang

2018-03-01

The negative differential capacitance (NDC) of p-i-n InGaAs/InP photodetector has been clearly observed, and the small signal model of frequency-dependent NDC is established, based on the accumulation and emission of electrons at the p-InP/i-InGaAs interface. The NDC phenomenon is contributed by the additional capacitance (CT), which is caused by the charging-discharging process in the p-InP/i-InGaAs interface. It is found that the NDC becomes more obvious with decreasing frequency, which is consistent with the conclusion of the experiment. It is proved that the probability of electron capture/escape in the p-i interface is affected by frequency. Therefore, the smaller frequency applied, the higher additional capacitance is obtained.

39 CFR 121.4 - Package Services.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Center Facility (SCF) turnaround Package Services mail accepted at the origin SCF before the day zero... origin before the day-zero Critical Entry Time is 3 days, for each remaining (non-intra-SCF) 3-digit ZIP... intra-Network Distribution Center (NDC) Package Services mail accepted at origin before the day-zero...

39 CFR 121.4 - Package Services.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Center Facility (SCF) turnaround Package Services mail accepted at the origin SCF before the day zero... origin before the day-zero Critical Entry Time is 3 days, for each remaining (non-intra-SCF) 3-digit ZIP... intra-Network Distribution Center (NDC) Package Services mail accepted at origin before the day-zero...

Engineering negative differential conductance with the Cu(111) surface state.

PubMed

Heinrich, B W; Rastei, M V; Choi, D-J; Frederiksen, T; Limot, L

2011-12-09

Low-temperature scanning tunneling microscopy and spectroscopy are employed to investigate electron tunneling from a C60-terminated tip into a Cu(111) surface. Tunneling between a C60 orbital and the Shockley surface states of copper is shown to produce negative differential conductance (NDC) contrary to conventional expectations. NDC can be tuned through barrier thickness or C60 orientation up to complete extinction. The orientation dependence of NDC is a result of a symmetry matching between the molecular tip and the surface states.

The pedunculopontine nucleus is related to visual hallucinations in Parkinson's disease: preliminary results of a voxel-based morphometry study.

PubMed

Janzen, J; van 't Ent, D; Lemstra, A W; Berendse, H W; Barkhof, F; Foncke, E M J

2012-01-01

Visual hallucinations (VH) are common in Parkinson's disease (PD) and lead to a poor quality of life. For a long time, dopaminergic therapy was considered to be the most important risk factor for the development of VH in PD. Recently, the cholinergic system, including the pedunculopontine nucleus (PPN), has been implicated in the pathophysiology of VH. The aim of the present study was to investigate grey matter density of the PPN region and one of its projection areas, the thalamus. Thirteen non-demented PD patients with VH were compared to 16 non-demented PD patients without VH, 13 demented PD patients (PDD) with VH and 11 patients with dementia with Lewy bodies (DLB). Isotropic 3-D T1-weighted MRI images (3T) were analysed using voxel-based morphometry (VBM) with the PPN region and thalamus as ROIs. PD and PDD patients with VH showed grey matter reductions of the PPN region and the thalamus compared to PD patients without VH. VH in PD(D) patients are associated with atrophy of the PPN region and its thalamic target area, suggesting that a cholinergic deficit may be involved in the development of VH in PD(D).

Sleep quality and duration in relation to memory in the elderly: Initial results from the Hellenic Longitudinal Investigation of Aging and Diet.

PubMed

Tsapanou, A; Gu, Y; O'Shea, D M; Yannakoulia, M; Kosmidis, M; Dardiotis, E; Hadjigeorgiou, G; Sakka, P; Stern, Y; Scarmeas, N

2017-05-01

Sleep is crucial for cognition, particularly for memory, given its complex association with neurodegenerative processes. The aim of the present study was to examine the association between sleep quality as well as sleep duration and memory performance in a Greek elderly population. Cross-sectional design in the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD), a population representative study of Greek elderly (65years or older). Data from 1589 participants free of sleep medication were included. Sleep quality was estimated by using the Sleep Scale from the Medical Outcomes Study. An extensive neuropsychological assessment examining memory was administered to each participant. Linear regression analyses were used to examine whether sleep quality (higher score, poor quality) and/or sleep duration were associated with memory expressed in the form of a z-score. Age, sex, education, and body mass index were included as covariates. The main analyses were conducted first on the total sample, then with the exclusion of demented participants, and finally with the exclusion of both demented and participants with Mild Cognitive Impairment (MCI). We then conducted further analyses on the non-demented, non-MCI group, initially stratified by Apolipoprotein E-ε4 gene. We further examined the role of co-morbidities, as well as the association between sleep duration groups and memory. We also explored any interaction effect between sex and sleep quality/duration on memory. We then examined the associations between components of sleep measures and memory scores. Lastly, we examined the associations between sleep quality/duration and verbal/non-verbal memory separately. In the total sample, we noted significant associations between sleep duration and memory (B=-0.001, p≤0.0001), but not for sleep quality and memory (B=-0.038, p=0.121). After excluding the demented participants, the associations were significant for: sleep quality and memory (B=-0.054, p=0.023), and sleep duration and memory (B=-0.001, p≤0.0001). After excluding both the MCI and the demented subjects, the associations between sleep quality and memory (B=-0.065, p=0.006), and sleep duration and memory (B=-0.001, p=0.003) were still significant. The association between the sleep duration groups and memory function was also significant, such that poor memory performance was associated with the longer sleep duration group. The results remained significant even after controlling for the co-morbidities, as well as after adding in the model anxiety and depression as covariates. Associations between sleep quality and memory, and sleep duration and memory were present in the ApoE-ε4 non-carriers. The individual sleep questions that were probably shown to be driving the associations between sleep and memory were: time to fall asleep, sleep not quiet, getting enough sleep to feel rested upon waking in the morning, and getting the amount of sleep needed. Sleep duration was associated with both verbal and non-verbal memory, while sleep quality was only associated with verbal memory. Poor sleep quality and longer sleep duration were linked to low memory performance, independent of demographic and clinical factors, in a large sample of cognitively healthy older Greek adults. Other parameters than sleep and memory measurements could play an important role on the association. Levels of melatonin, or circadian rhythms dysregulation might play a crucial role in the above associations. Copyright © 2017 Elsevier Inc. All rights reserved.

US NDC Modernization Iteration E2 Prototyping Report: User Interface Framework

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lewis, Jennifer E.; Palmer, Melanie A.; Vickers, James Wallace

2014-12-01

During the second iteration of the US NDC Modernization Elaboration phase (E2), the SNL US NDC Modernization project team completed follow-on Rich Client Platform (RCP) exploratory prototyping related to the User Interface Framework (UIF). The team also developed a survey of browser-based User Interface solutions and completed exploratory prototyping for selected solutions. This report presents the results of the browser-based UI survey, summarizes the E2 browser-based UI and RCP prototyping work, and outlines a path forward for the third iteration of the Elaboration phase (E3).

Tunable Rare Earth fcu-MOF Platform: Access to Adsorption Kinetics Driven Gas/Vapor Separations via Pore Size Contraction.

PubMed

Xue, Dong-Xu; Belmabkhout, Youssef; Shekhah, Osama; Jiang, Hao; Adil, Karim; Cairns, Amy J; Eddaoudi, Mohamed

2015-04-22

Reticular chemistry approach was successfully employed to deliberately construct new rare-earth (RE, i.e., Eu(3+), Tb(3+), and Y(3+)) fcu metal-organic frameworks (MOFs) with restricted window apertures. Controlled and selective access to the resultant contracted fcu-MOF pores permits the achievement of the requisite sorbate cutoff, ideal for selective adsorption kinetics based separation and/or molecular sieving of gases and vapors. Predetermined reaction conditions that permitted the formation in situ of the 12-connected RE hexanuclear molecular building block (MBB) and the establishment of the first RE-fcu-MOF platform, especially in the presence of 2-fluorobenzoic acid (2-FBA) as a modulator and a structure directing agent, were used to synthesize isostructural RE-1,4-NDC-fcu-MOFs based on a relatively bulkier 2-connected bridging ligand, namely 1,4-naphthalenedicarboxylate (1,4-NDC). The subsequent RE-1,4-NDC-fcu-MOF structural features, contracted windows/pores and high concentration of open metal sites combined with exceptional hydrothermal and chemical stabilities, yielded notable gas/solvent separation properties, driven mostly by adsorption kinetics as exemplified in this work for n-butane/methane, butanol/methanol, and butanol/water pair systems.

Narrative Organization Deficit in Lewy Body Disorders Is Related to Alzheimer Pathology

PubMed Central

Grossman, Murray; Irwin, David J.; Jester, Charles; Halpin, Amy; Ash, Sharon; Rascovsky, Katya; Weintraub, Daniel; McMillan, Corey T.

2017-01-01

Background: Day-to-day interactions depend on conversational narrative, and we examine here the neurobiological basis for difficulty organizing narrative discourse in patients with Lewy body disorders (LBD). Method: Narrative organization was examined in 56 non-aphasic LBD patients, including a non-demented cohort (n = 30) with Parkinson's disease (PD) or PD-Mild Cognitive Impairment PD-MCI,) and a cohort with mild dementia (n = 26) including PD-dementia (PDD) and dementia with Lewy bodies (DLB), with similar age and education but differing in MMSE (p < 0.001). We used a previously reported procedure that probes patients' judgments of the organization of brief, familiar narratives (e.g., going fishing, wrapping a present). A subgroup of 24 patients had MRI assessment of regional gray matter (GM) atrophy and cerebrospinal fluid (CSF) levels of biomarkers for Alzheimer's disease (AD) pathology, including beta amyloid (Aβ), total-tau (t-tau), and phosphorylated-tau (p-tau). Results: Mildly demented LBD patients had a significant deficit judging narratives compared to non-demented patients, but this deficit was not correlated with MMSE. Regression analyses instead related narrative organization to regions of frontal GM atrophy, and CSF levels of Aβ and t-tau associated with presumed AD pathology in these frontal regions. Conclusion: These findings are consistent with the hypothesis that CSF markers of AD pathology associated with frontal regions play a role in difficulty organizing narratives in LBD. PMID:28228714

Narrative Organization Deficit in Lewy Body Disorders Is Related to Alzheimer Pathology.

PubMed

Grossman, Murray; Irwin, David J; Jester, Charles; Halpin, Amy; Ash, Sharon; Rascovsky, Katya; Weintraub, Daniel; McMillan, Corey T

2017-01-01

Background: Day-to-day interactions depend on conversational narrative, and we examine here the neurobiological basis for difficulty organizing narrative discourse in patients with Lewy body disorders (LBD). Method: Narrative organization was examined in 56 non-aphasic LBD patients, including a non-demented cohort ( n = 30) with Parkinson's disease (PD) or PD-Mild Cognitive Impairment PD-MCI,) and a cohort with mild dementia ( n = 26) including PD-dementia (PDD) and dementia with Lewy bodies (DLB), with similar age and education but differing in MMSE ( p < 0.001). We used a previously reported procedure that probes patients' judgments of the organization of brief, familiar narratives (e.g., going fishing, wrapping a present). A subgroup of 24 patients had MRI assessment of regional gray matter (GM) atrophy and cerebrospinal fluid (CSF) levels of biomarkers for Alzheimer's disease (AD) pathology, including beta amyloid (Aβ), total-tau ( t -tau), and phosphorylated-tau ( p -tau). Results: Mildly demented LBD patients had a significant deficit judging narratives compared to non-demented patients, but this deficit was not correlated with MMSE. Regression analyses instead related narrative organization to regions of frontal GM atrophy, and CSF levels of Aβ and t -tau associated with presumed AD pathology in these frontal regions. Conclusion: These findings are consistent with the hypothesis that CSF markers of AD pathology associated with frontal regions play a role in difficulty organizing narratives in LBD.

Validation of the Danish Addenbrooke's Cognitive Examination as a screening test in a memory clinic.

PubMed

Stokholm, Jette; Vogel, Asmus; Johannsen, Peter; Waldemar, Gunhild

2009-01-01

Addenbrooke's Cognitive Examination (ACE) is a cognitive screening test developed to detect dementia. It has been validated in several countries. Validation studies have predominantly included patients with various degrees of dementia and healthy controls. The aim of this study was to evaluate the Danish version of ACE as a screening test for early dementia in an outpatient memory clinic. Further, we wanted to investigate the ability of the ACE to discriminate patients with early Alzheimer's disease (AD) from patients with depression. 78 patients with mild AD (MMSE >or=20), 30 non-demented patients diagnosed with depression (originally referred for evaluation of cognitive symptoms), and 63 healthy volunteers, all between 60 and 85 years of age, were included. All patients were given the ACE as a supplement to the standard diagnostic work-up. The cut-off points for optimal trade-off between sensitivity and specificity for ACE were 85/86 (sensitivity 0.99, specificity 0.94). When these cut-off points were applied to the group of depressive patients, the specificity dropped to 0.64, indicating a great overlap in individual test scores for demented and depressed patients. The optimal cut-off points for ACE found in this Danish study were close to what is reported in most other European studies. The great overlap in ACE scores for demented and depressed patients emphasize that test scores must be interpreted with great caution when used in diagnostic work-up.

Negative Differential Conductivity in an Interacting Quantum Gas.

PubMed

Labouvie, Ralf; Santra, Bodhaditya; Heun, Simon; Wimberger, Sandro; Ott, Herwig

2015-07-31

We report on the observation of negative differential conductivity (NDC) in a quantum transport device for neutral atoms employing a multimode tunneling junction. The system is realized with a Bose-Einstein condensate loaded in a one-dimensional optical lattice with high site occupancy. We induce an initial difference in chemical potential at one site by local atom removal. The ensuing transport dynamics are governed by the interplay between the tunneling coupling, the interaction energy, and intrinsic collisions, which turn the coherent coupling into a hopping process. The resulting current-voltage characteristics exhibit NDC, for which we identify atom number-dependent tunneling as a new microscopic mechanism. Our study opens new ways for the future implementation and control of complex neutral atom quantum circuits.

42 CFR 447.520 - FFP: Conditions relating to physician-administered drugs.

Code of Federal Regulations, 2011 CFR

2011-10-01

... using Healthcare Common Procedure Coding System codes or NDC numbers in order to secure rebates. (2) As... Medicaid Program using NDC numbers in order to secure rebates. (b) As of January 1, 2007, a State must...

42 CFR 447.520 - FFP: Conditions relating to physician-administered drugs.

Code of Federal Regulations, 2013 CFR

2013-10-01

... using Healthcare Common Procedure Coding System codes or NDC numbers in order to secure rebates. (2) As... Medicaid Program using NDC numbers in order to secure rebates. (b) As of January 1, 2007, a State must...

42 CFR 447.520 - FFP: Conditions relating to physician-administered drugs.

Code of Federal Regulations, 2012 CFR

2012-10-01

... using Healthcare Common Procedure Coding System codes or NDC numbers in order to secure rebates. (2) As... Medicaid Program using NDC numbers in order to secure rebates. (b) As of January 1, 2007, a State must...

42 CFR 447.520 - FFP: Conditions relating to physician-administered drugs.

Code of Federal Regulations, 2014 CFR

2014-10-01

... using Healthcare Common Procedure Coding System codes or NDC numbers in order to secure rebates. (2) As... Medicaid Program using NDC numbers in order to secure rebates. (b) As of January 1, 2007, a State must...

42 CFR 447.520 - FFP: Conditions relating to physician-administered drugs.

Code of Federal Regulations, 2010 CFR

2010-10-01

... using Healthcare Common Procedure Coding System codes or NDC numbers in order to secure rebates. (2) As... Medicaid Program using NDC numbers in order to secure rebates. (b) As of January 1, 2007, a State must...

Ectopic expression of plasma membrane targeted subunits of the Ndc80-complex as a tool to study kinetochore biochemistry.

PubMed

Holmström, Tim H; Rehnberg, Jonathan; Ahonen, Leena J; Kallio, Marko J

2009-06-01

Genomic stability depends on the normal function of the kinetochore, a multi-protein assemblage, which consists of over 80 molecules including both constitutive and transiently binding components. Information regarding the spatial-temporal assembly of kinetochore subcomplexes is often limited by technical difficulties in their isolation. To study kinetochore subcomplex formation, we targeted separately Hec1 and Spc24, two subunits of the Ndc80 kinetochore compilation, to the plasma membrane by fusing them with the amino-terminal palmitoylation and myristoylation (pm) sequence of the receptor tyrosine kinase Fyn. We found that in early mitotic cells, pm-GFP-Hec1 and pm-GFP-Spc24 fusion proteins localised to the plasma membrane and were able to recruit all subunits of the Ndc80 complex (Ndc80/Hec1, Nuf2, Spc24 and Spc25) to these foci. In interphase cells, only Hec1-Nuf2 and Spc24-Spc25 heterodimers accumulated to the plasma membrane foci. The results propose that the assembly of Ndc80 tetramer can take place outside of the kinetochore but requires co-factors that are only present in mitotic cells. These findings provide the first experimental evidence on the successful employment of the plasma membrane targeting technique in the study of kinetochore biochemistry.

Nitrogen doped activated carbon from pea skin for high performance supercapacitor

NASA Astrophysics Data System (ADS)

Ahmed, Sultan; Ahmed, Ahsan; Rafat, M.

2018-04-01

In this work, nitrogen doped porous carbon (NDC) has been synthesized employing a facile two-step process. Firstly, carbon precursor (pea skin) was heated with melamine (acting as nitrogen source) followed by activation with KOH in different ratios. The dependence of porosity and nitrogen content on impregnation ratio was extensively studied. Other textural properties of prepared NDC sample were studied using standard techniques of material characterization. The electrochemical performance of NDC sample as an electrode was studied in two-electrode symmetric supercapacitor system. 1 M LiTFSI (lithium bis-trifluoromethanesulfonimide) solution in IL EMITFSI (1-Ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide), was used as electrolyte. It was found that the fabricated supercapacitor cell offers high values of specific capacitance (141.1 F g‑1), specific energy (19.6 Wh kg‑1) and specific power (25.4 kW kg‑1) at current density of 1.3 A g‑1. More importantly, the fabricated supercapacitor cell shows capacitance retention of ∼75%, for more than 5000 cycles. The enhanced performance of NDC sample is primarily due to large surface area with favorable surface structure (contributing to double layer capacitance) and presence of nitrogen functionalities (contributing to pseudo-capacitance). Such important features make the synthesized NDC sample, an attractive choice for electrode material in high performance supercapacitor.

Comorbidity of dementia with amyotrophic lateral sclerosis (ALS): insights from a large multicenter Italian cohort.

PubMed

Trojsi, Francesca; Siciliano, Mattia; Femiano, Cinzia; Santangelo, Gabriella; Lunetta, Christian; Calvo, Andrea; Moglia, Cristina; Marinou, Kalliopi; Ticozzi, Nicola; Drago Ferrante, Gianluca; Scialò, Carlo; Sorarù, Gianni; Conte, Amelia; Falzone, Yuri M; Tortelli, Rosanna; Russo, Massimo; Sansone, Valeria Ada; Chiò, Adriano; Mora, Gabriele; Poletti, Barbara; Volanti, Paolo; Caponnetto, Claudia; Querin, Giorgia; Sabatelli, Mario; Riva, Nilo; Logroscino, Giancarlo; Messina, Sonia; Fasano, Antonio; Monsurrò, Maria Rosaria; Tedeschi, Gioacchino; Mandrioli, Jessica

2017-11-01

To assess the association, at diagnosis, between amyotrophic lateral sclerosis (ALS) and dementia in a large cohort of well-characterized Italian patients. We investigated the phenotypic profile of 1638 incident patients with definite, probable or laboratory-supported probable ALS, diagnosed from January 2009 to December 2013 in 13 Italian Referral Centers, located in 10 Italian Regions, and classified in two independent subsamples accounting for presence or not of dementia. The collected ALS features, including survival and other follow-up data, were compared between the two subgroups using a one-way analysis of variance and Chi-square test, as appropriate, logistic regression models and Kaplan-Meier survival analysis. Between-subgroup comparisons showed an older age at clinical observation (p = .006), at onset and at diagnosis (p = .002) in demented versus non demented ALS patients. After adjustment for these variables, diagnosis of dementia was significantly associated with higher odds of family history of ALS (p = .001) and frontotemporal dementia (p = .003) and of bulbar onset (p = .004), and lower odds of flail leg phenotype (p = .019) and spinal onset (p = .008). The median survival time was shorter in demented versus non-demented patients, especially in case of classical, bulbar and flail limb phenotypes and both bulbar and spinal onset. Our multicenter study emphasized the importance of an early diagnosis of comorbid dementia in ALS patients, which may have clinical impact and prognostic relevance. Moreover, our results may give further inputs to validation of ALS-specific tools for the screening of cognitive impairment in clinical practice.

Efficient light harvesting within a C153@Zr-based MOF embedded in a polymeric film: spectral and dynamical characterization.

PubMed

Gutiérrez, M; López-González, M; Sánchez, F; Douhal, A

2017-07-21

Light harvesting is a natural phenomenon that scientists try to mimic in artificial systems. Having this in mind, attention has been focused on using new smart-materials for photonics. Herein, we report on the photobehaviour of a Zr-NDC MOF (NDC = dimethyl 2,6-naphthalenedicarboxylate) and its composite material, Coumarin153@Zr-NDC, embedded within a polymeric membrane of poly[bisphenol A carbonate-co-4,4'-(3,3,5-trimethylcyclohexylidene)diphenol carbonate] (PC). For the mixed matrix membrane (MMM) Zr-NDC/PC, we observed interparticle excimer-like formation, taking place in times shorter than 15 ps and giving rise to a red-shifted broad emission band. The interparticle interactions are supported by the SEM images, as they reflect the contact between the MOF crystals. The C153@Zr-NDC/PC material presents an energy transfer (ET) process from the excited MOF to the trapped C153 molecules in 820 ps, with a 35 nm red-shifted emission band corresponding to C153 in PC. The fluorescence quantum yield, as a result of this ET from the MOF, is high enough (25%) to explore the possibility of using this new composite material in a LED device. To elucidate the observed photobehavior, we compared it with those of C153/PC and (2,6-NDC + C153)/PC films. These results shed light on the spectroscopic and dynamical properties of these new composite materials formed by a highly fluorescent molecule, and easily synthesized MOFs and polymeric matrices, opening the way for more research based on these mixed inorganic and organic compounds for possible applications in the fields of luminescence sensing and emitting devices.

Stability of kinetochore-microtubule attachment and the role of different KMN network components in Drosophila.

PubMed

Feijão, Tália; Afonso, Olga; Maia, André F; Sunkel, Claudio E

2013-10-01

Kinetochores bind spindle microtubules and also act as signaling centers that monitor this interaction. Defects in kinetochore assembly lead to chromosome missegregation and aneuploidy. The interaction between microtubules and chromosomes involves a conserved super-complex of proteins, known as the KNL1Mis12Ndc80 (KMN) network, composed by the KNL1 (Spc105), Mis12, and Ndc80 complexes. Previous studies indicate that all components of the network are required for kinetochore-microtubule attachment and all play relevant functions in chromosome congression, biorientation, and segregation. Here, we report a comparative study addressing the role of the different KMN components using dsRNA and in vivo fluorescence microscopy in Drosophila S2 cells allowing us to suggest that different KMN network components might perform different roles in chromosome segregation and the mitotic checkpoint signaling. Depletion of different components results in mostly lateral kinetochore-microtubule attachments that are relatively stable on depletion of Mis12 or Ndc80 but very unstable after Spc105 depletion. In vivo analysis on depletion of Mis12, Ndc80, and to some extent Spc105, shows that lateral kinetochore-microtubule interactions are still functional allowing poleward kinetochore movement. We also find that different KMN network components affect differently the localization of spindle assembly checkpoint (SAC) proteins at kinetochores. Depletion of Ndc80 and Spc105 abolishes the mitotic checkpoint, whereas depletion of Mis12 causes a delay in mitotic progression. Taken together, our results suggest that Mis12 and Ndc80 complexes help to properly orient microtubule attachment, whereas Spc105 plays a predominant role in the kinetochore-microtubule attachment as well as in the poleward movement of chromosomes, SAC response, and cell viability. Copyright © 2013 Wiley Periodicals, Inc.

The Association between High Neuroticism-Low Extraversion and Dual-Task Performance during Walking While Talking in Non-demented Older Adults

PubMed Central

LeMonda, Brittany C.; Mahoney, Jeannette R.; Verghese, Joe; Holtzer, Roee

2016-01-01

The Walking While Talking (WWT) dual-task paradigm is a mobility stress test that predicts major outcomes, including falls, frailty, disability, and mortality in aging. Certain personality traits, such as neuroticism, extraversion, and their combination, have been linked to both cognitive and motor outcomes. We examined whether individual differences in personality dimensions of neuroticism and extraversion predicted dual-task performance decrements (both motor and cognitive) on a WWT task in non-demented older adults. We hypothesized that the combined effect of high neuroticism-low extraversion would be related to greater dual-task costs in gait velocity and cognitive performance in non-demented older adults. Participants (N = 295; age range, = 65–95 years; female = 164) completed the Big Five Inventory and WWT task involving concurrent gait and a serial 7's subtraction task. Gait velocity was obtained using an instrumented walkway. The high neuroticism-low extraversion group incurred greater dual-task costs (i.e., worse performance) in both gait velocity {95% confidence interval (CI) [−17.68 to −3.07]} and cognitive performance (95% CI [−19.34 to −2.44]) compared to the low neuroticism-high extraversion group, suggesting that high neuroticism-low extraversion interferes with the allocation of attentional resources to competing task demands during the WWT task. Older individuals with high neuroticism-low extraversion may be at higher risk for falls, mobility decline and other adverse outcomes in aging. PMID:26527241

Diabetes, impaired fasting glucose, and cognitive decline in a population of elderly community residents.

PubMed

Rouch, Isabelle; Roche, Frédéric; Dauphinot, Virginie; Laurent, Bernard; Antérion, Catherine Thomas; Celle, Sébastien; Krolak-Salmon, Pierre; Barthélémy, Jean-Claude

2012-08-01

Diabetes and impaired fasting glucose, as well as cognitive impairment, are common in the elderly. Although several cross-sectional studies have demonstrated the influence of diabetes on cognitive impairment, only a few longitudinal studies have assessed the relationship between diabetes, impaired fasting glucose and cognitive decline in non-demented elderly community dwellers, by means of extensive neuropsychological batteries. The present study assesses the relationship between baseline diabetes, impaired fasting glucose (IFG) and 2- year evolution of memory, attention and executive performance in a sample of non-demented elderly subjects. Population-based cohort study [(PROgnostic indicator OF cardiovascular and cerebrovascular events (PROOF)]. One hundred and sixty-three community dwellers aged 65 years without dementia at recruitment. Memory, attention and executive performance. A significant association was observed between baseline diabetes mellitus and a higher 2-year decline in the Trial Making Test B and Stroop test exploring attention and executive function. This effect remained significant after adjusting for age, gender, education, anxiety and depressive symptoms, as well as other cardiovascular risk factors (F=2.41; p=0.007). Instead, no relationship was observed between IFG and cognitive decline. Our study showed that, in a sample of elderly non-demented community dwellers, diabetes mellitus (but not IFG) is associated with a higher decline in selective attention and executive functioning. These results emphasize the importance of detecting and man- aging diabetes and impaired fasting glucose, in order to prevent cognitive impairment and dementia.

Light Regulation of the Arabidopsis Respiratory Chain. Multiple Discrete Photoreceptor Responses Contribute to Induction of Type II NAD(P)H Dehydrogenase Genes1

PubMed Central

Escobar, Matthew A.; Franklin, Keara A.; Svensson, Å. Staffan; Salter, Michael G.; Whitelam, Garry C.; Rasmusson, Allan G.

2004-01-01

Controlled oxidation reactions catalyzed by the large, proton-pumping complexes of the respiratory chain generate an electrochemical gradient across the mitochondrial inner membrane that is harnessed for ATP production. However, several alternative respiratory pathways in plants allow the maintenance of substrate oxidation while minimizing the production of ATP. We have investigated the role of light in the regulation of these energy-dissipating pathways by transcriptional profiling of the alternative oxidase, uncoupling protein, and type II NAD(P)H dehydrogenase gene families in etiolated Arabidopsis seedlings. Expression of the nda1 and ndc1 NAD(P)H dehydrogenase genes was rapidly up-regulated by a broad range of light intensities and qualities. For both genes, light induction appears to be a direct transcriptional effect that is independent of carbon status. Mutant analyses demonstrated the involvement of two separate photoreceptor families in nda1 and ndc1 light regulation: the phytochromes (phyA and phyB) and an undetermined blue light photoreceptor. In the case of the nda1 gene, the different photoreceptor systems generate distinct kinetic induction profiles that are integrated in white light response. Primary transcriptional control of light response was localized to a 99-bp region of the nda1 promoter, which contains an I-box flanked by two GT-1 elements, an arrangement prevalent in the promoters of photosynthesis-associated genes. Light induction was specific to nda1 and ndc1. The only other substantial light effect observed was a decrease in aox2 expression. Overall, these results suggest that light directly influences the respiratory electron transport chain via photoreceptor-mediated transcriptional control, likely for supporting photosynthetic metabolism. PMID:15333756

The (Nutrition Education) Gospel According to NDC.

ERIC Educational Resources Information Center

Kilburn, Eric

1978-01-01

Discusses the flaws in nutrition education as presented by the National Dairy Council (NDC). Those discussed include the presentation of diets that contain high amounts of sugar and cholesterol and the failure to connect diet to heart disease. Suggests ways of monitoring these materials in the schools. (MA)

Do differences in visuospatial ability between senile dementias of the Alzheimer and Lewy body types reflect differences solely in mnemonic function?

PubMed

Sahgal, A; McKeith, I G; Galloway, P H; Tasker, N; Steckler, T

1995-02-01

Visuospatial memory was investigated in two groups of patients suffering from senile dementias of the Alzheimer (SDAT) or Lewy body (SDLT) types; a, third, age-matched, healthy control group was also included. The two patient groups were mildly demented and could not be distinguished from each other by traditional tests of cognitive function. A different pattern of performance emerged in the two groups on a computerised test of spatial working memory, which is a self-ordered pointing task requiring the subject to search for hidden tokens. An analysis of the pattern of errors revealed that the SDLT group made more of both possible types of error ("Within Search" and "Between Search") than the SDAT group. Neither patient groups' performance differed from each other when assessed on a computerised Corsi spatial span task. A measure of planning ability was obtained by examining search strategies. Although an index previously developed to measure the subject's use of a particular strategy in the spatial working memory task failed to detect any differences between the three groups, a novel index was calculated which focuses on performance within a search, and this revealed deficits in both demented groups. Since the two patient groups differed from each other in the spatial working memory, but not the Corsi spatial span, task, it is suggested that the differences between the two demented groups are not due to a specific mnemonic impairment, but reflect dysfunctions in non-mnemonic processes mediated by fronto-subcortical circuits, which are more severely damaged in SDLT.

Gender and nurturance in families of children with neurodevelopmental conditions.

PubMed

Shapiro, Danielle N; Dixon-Thomas, Pamela; Warschausky, Seth

2014-05-01

This study tested the hypothesis that gender differences in parent-reported nurturance of children would be attenuated in families of children with neurodevelopmental conditions (NDCs). In this cross-sectional study, participants included 49 (29 male) children diagnosed with an NDC and 60 (30 male) typically developing (TD) children. Children in the NDC group had a diagnosis of cerebral palsy (CP; n = 41) or spina bifida (SB; n = 8). Parental nurturance was measured using the nurturance subscale of the Parenting Dimensions Inventory (PDI; Power, 1991). Data were analyzed using a 2 × 2 (gender × diagnosis) analysis of covariance (ANCOVA) with child age as the covariate. As a simple main effect, parents reported more nurturing behavior toward TD girls than TD boys. However, girls with an NDC received less nurturance, thereby eliminating the gender difference in parental nurturance in the NDC sample. This pattern was reflected in the larger ANCOVA as a 2-way interaction between diagnosis and gender. Group differences in other PDI subscales were not statistically significant. This pattern of results suggests that the parents of girls with NDCs may be less nurturing toward them, thereby attenuating gender differences observed in families with TD children. Findings highlight the need for more research on the gendered dynamics in families with a child with an NDC to develop systemic models of family functioning and targeted parenting interventions for this group. (c) 2014 APA, all rights reserved.

Conformational diversity of flexible ligand in metal-organic frameworks controlled by size-matching mixed ligands

NASA Astrophysics Data System (ADS)

Hua, Xiu-Ni; Qin, Lan; Yan, Xiao-Zhi; Yu, Lei; Xie, Yi-Xin; Han, Lei

2015-12-01

Hydrothermal reactions of N-auxiliary flexible exo-bidentate ligand 1,3-bis(4-pyridyl)propane (bpp) and carboxylates ligands naphthalene-2,6-dicarboxylic acid (2,6-H2ndc) or 4,4‧-(hydroxymethylene)dibenzoic acid (H2hmdb), in the presence of cadmium(II) salts have given rise to two novel metal-organic frameworks based on flexible ligands (FL-MOFs), namely, [Cd2(2,6-ndc)2(bpp)(DMF)]·2DMF (1) and [Cd3(hmdb)3(bpp)]·2DMF·2EtOH (2) (DMF=N,N-Dimethylformamide). Single-crystal X-ray diffraction analyses revealed that compound 1 exhibits a three-dimensional self-penetrating 6-connected framework based on dinuclear cluster second building unit. Compound 2 displays an infinite three-dimensional 'Lucky Clover' shape (2,10)-connected network based on the trinuclear cluster and V-shaped organic linkers. The flexible bpp ligand displays different conformations in 1 and 2, which are successfully controlled by size-matching mixed ligands during the self-assembly process.

Increased fMRI signal with age in familial Alzheimer’s disease mutation carriers

PubMed Central

Braskie, Meredith N.; Medina, Luis D.; Rodriguez-Agudelo, Yaneth; Geschwind, Daniel H.; Macias-Islas, Miguel Angel; Cummings, Jeffrey L.; Bookheimer, Susan Y.; Ringman, John M.

2010-01-01

Although many Alzheimer’s disease (AD) patients have a family history of the disease, it is rarely inherited in a predictable way. Functional magnetic resonance imaging (fMRI) studies of non-demented adults carrying familial AD mutations provide an opportunity to prospectively identify brain differences associated with early AD-related changes. We compared fMRI activity of 18 non-demented autosomal dominant AD mutation carriers with fMRI activity in 8 of their non-carrier relatives as they performed a novelty encoding task in which they viewed novel and repeated images. Because age of disease onset is relatively consistent within families, we also correlated fMRI activity with subjects’ distance from the median age of diagnosis for their family. Mutation carriers did not show significantly different voxelwise fMRI activity from non-carriers as a group. However, as they approached their family age of disease diagnosis, only mutation carriers showed increased fMRI activity in the fusiform and middle temporal gyri. This suggests that during novelty encoding, increased fMRI activity in the temporal lobe may relate to incipient AD processes. PMID:21129823

21 CFR 607.35 - Notification of registrant; blood product establishment registration number and NDC Labeler Code.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 7 2013-04-01 2013-04-01 false Notification of registrant; blood product... PRODUCT LISTING FOR MANUFACTURERS OF HUMAN BLOOD AND BLOOD PRODUCTS Procedures for Domestic Blood Product Establishments § 607.35 Notification of registrant; blood product establishment registration number and NDC...

21 CFR 607.35 - Notification of registrant; blood product establishment registration number and NDC Labeler Code.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 7 2012-04-01 2012-04-01 false Notification of registrant; blood product... PRODUCT LISTING FOR MANUFACTURERS OF HUMAN BLOOD AND BLOOD PRODUCTS Procedures for Domestic Blood Product Establishments § 607.35 Notification of registrant; blood product establishment registration number and NDC...

21 CFR 607.35 - Notification of registrant; blood product establishment registration number and NDC Labeler Code.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Notification of registrant; blood product... PRODUCT LISTING FOR MANUFACTURERS OF HUMAN BLOOD AND BLOOD PRODUCTS Procedures for Domestic Blood Product Establishments § 607.35 Notification of registrant; blood product establishment registration number and NDC...

36 CFR 1260.38 - How does the NDC ensure the quality of declassification reviews?

Code of Federal Regulations, 2012 CFR

2012-07-01

... 36 Parks, Forests, and Public Property 3 2012-07-01 2012-07-01 false How does the NDC ensure the quality of declassification reviews? 1260.38 Section 1260.38 Parks, Forests, and Public Property NATIONAL ARCHIVES AND RECORDS ADMINISTRATION DECLASSIFICATION DECLASSIFICATION OF NATIONAL SECURITY INFORMATION The...

36 CFR 1260.38 - How does the NDC ensure the quality of declassification reviews?

Code of Federal Regulations, 2014 CFR

2014-07-01

... 36 Parks, Forests, and Public Property 3 2014-07-01 2014-07-01 false How does the NDC ensure the quality of declassification reviews? 1260.38 Section 1260.38 Parks, Forests, and Public Property NATIONAL ARCHIVES AND RECORDS ADMINISTRATION DECLASSIFICATION DECLASSIFICATION OF NATIONAL SECURITY INFORMATION The...

75 FR 9343 - Nomenclature Change Relating to the Network Distribution Center Transition

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-02

... POSTAL SERVICE 39 CFR Parts 111 and 121 Nomenclature Change Relating to the Network Distribution... (BMC) to network distribution centers (NDC), by replacing all text references to ``BMC'' with ``NDC...: Background: The BMC network was established in the 1970s to process Parcel Post[supreg], Bound Printed Matter...

76 FR 16588 - Combined Mailings of Standard Mail and Periodicals Flats

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-24

... may be combined in carrier route, 5-digit (scheme), 3-digit, ADC, and Mixed ADC bundles when prepared...-digit scheme through NDC pallets must contain at least 250 pounds of combined Standard Mail and... scheme through NDC pallets must contain at least 250 pounds of combined Standard Mail and Periodicals...

Nitrogen doped microporous carbon by ZnCl2 activation of protein

NASA Astrophysics Data System (ADS)

Wilson, Praveen; Vijayan, Sujith; Prabhakaran, K.

2017-09-01

ZnCl2 activation of protein containing biomass has been studied for the preparation of N-doped activated carbon (NDC) using powdered dry fish as a source of protein. Nearly 52% increase in the yield of NDC is observed by activation with ZnCl2 due to an increase in the thermal stability of Zn2+-fish protein complex compared to the protein alone. The NDCs obtained are characterized by XRD, IR, XPS, Raman spectroscopy, SEM, TEM, elemental analysis and N2 adsorption-desorption studies. The activation at 550 °C produces NDC with the highest surface area and total pore volume of 1001 m2 g-1 and 0.719 cm3 g-1, respectively, at a ZnCl2 to fish powder weight ratio of 3. A maximum micropore volume of 0.273 cm3 g-1 is obtained at a ZnCl2 to fish powder weight ratio of 1:1. The N-content (12.4-5.2 wt%) decreases with an increase in activation temperature and ZnCl2 to fish powder weight ratio. The NDC obtained by activation at 550 °C at a ZnCl2 to fish powder weight ratio of 1:1 shows the maximum CO2 adsorption capacity of 2.4 and 3.73 mmol g-1 at 25 and 0 °C, respectively, at 1 atmosphere. The CO2 adsorption on the NDC shows excellent cyclic stability and high selectivity over nitrogen gas.

North Korea’s Foreign Policy Towards the United States

DTIC Science & Technology

2006-09-01

NDC ),[8] which has been chaired by Kim Jong Il since 1993. Kim has been using his positions as NDC chairman and KWP General-Secretary[9] to exert...overview of North Korea’s tunnels and underground facilities, see Barbara Demick, “ N. Korea’s Ace in the Hole,” The Los Angeles Times, November 14

76 FR 10757 - Combined Mailings of Standard Mail and Periodicals Flats

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-28

... (scheme), 3-digit, ADC, and Mixed ADC bundles when prepared according to 707.19.0 and these additional... to the standards in 8.0 and in the sequence listed below. Merged 5-digit scheme through NDC pallets... according to the standards in 8.0 and in the sequence listed below. Merged 5-digit scheme through NDC...

21 CFR 607.35 - Notification of registrant; blood product establishment registration number and NDC Labeler Code.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Notification of registrant; blood product establishment registration number and NDC Labeler Code. 607.35 Section 607.35 Food and Drugs FOOD AND DRUG... PRODUCT LISTING FOR MANUFACTURERS OF HUMAN BLOOD AND BLOOD PRODUCTS Procedures for Domestic Blood Product...

21 CFR 607.35 - Notification of registrant; blood product establishment registration number and NDC Labeler Code.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Notification of registrant; blood product establishment registration number and NDC Labeler Code. 607.35 Section 607.35 Food and Drugs FOOD AND DRUG... PRODUCT LISTING FOR MANUFACTURERS OF HUMAN BLOOD AND BLOOD PRODUCTS Procedures for Domestic Blood Product...

Alzheimer's lymphocytes are resistant to ultraviolet B-induced apoptosis.

PubMed

Zana, Marianna; Juhász, Anna; Rimanóczy, Agnes; Bjelik, Annamária; Baltás, Eszter; Ocsovszki, Imre; Boda, Krisztina; Penke, Botond; Dobozy, Attila; Kemény, Lajos; Janka, Zoltán; Kálmán, János

2006-06-01

In the present pilot investigation, the susceptibility of T-lymphocytes from Alzheimer's disease (AD) subjects (n=22) and aged-matched, non-demented controls (CNT) (n=12) was examined with ultraviolet (UV) B light-induced apoptosis in vitro. The basal apoptotic ratios were similar in both groups. However, the AD lymphocytes displayed significantly (p<0.0001) lower apoptotic levels than those of the CNT lymphocytes at all of the applied UVB exposure doses (100, 200 and 300 mJ/cm(2)). These observations indicate that AD lymphocytes are more resistant than CNT lymphocytes to UVB irradiation.

Protective effects of notoginsenoside R1 on cerebral ischemia-reperfusion injury in rats.

PubMed

Zou, Shun; Zhang, Mingxiong; Feng, Limei; Zhou, Yuanfang; Li, Li; Ban, Lili

2017-12-01

The objective of this study was to investigate the protective effect of notoginsenoside R1 (NGR1) on cerebral ischemia-reperfusion injury (CIRI) in rats, and its molecular mechanism, to provide new insights into the diagnosis and treatment of CIRI. Sixty Sprague-Dawley rats were randomly divided into four groups including the sham-operation group (Sham), cerebral ischemia-reperfusion model group (CIR), NGR1 treatment group (NGR1), and nimodipine positive control group (NDC) with 15 rats each. Bilateral common carotid arteries occlusion was used to establish the rat CIRI model. The area of cerebral infarction at the end of reperfusion was calculated by triphenyl tetrazolium chloride staining. Apoptosis of hippocampal neurons in each group was detected by Annexin V/propidium iodide double staining. Hippocampal expression of brain-derived neurotrophic factor (BDNF) mRNA, and Bcl-2 and Bax protein at the end of reperfusion were measured by RT-qPCR and western blot analysis, respectively. Data were analyzed by SPSS software analysis to ensure statistical significance. At the end of reperfusion, the area of cerebral infarction in the NGR1 and NDC groups was significantly smaller than that of the CIR group. Apoptosis analysis showed that compared with the CIR group, the apoptosis rate of hippocampal neurons was significantly decreased in the NGR1 and NDC groups. RT-qPCR and western blot analysis showed that at the end of reperfusion, higher levels of BDNF mRNA and the anti-apoptotic factor, Bcl-2, and lower levels of the pro-apoptotic factor, Bax, in the hippocampus were found in the NGR1 and NDC groups compared with the CIR group. The protective effect of NGR1 on CIRI was significantly stronger than that of nimodipine. In conclusion, NGR1 can reduce the area of cerebral infarction, reduce apoptosis of hippocampal neurons, and protect rats from CIRI. Those effects were achieved by activating the expression of BDNF and Bcl-2, and by inhibiting the expression of Bax.

Sec66-Dependent Regulation of Yeast Spindle-Pole Body Duplication Through Pom152

PubMed Central

Katta, Santharam S.; Chen, Jingjing; Gardner, Jennifer M.; Friederichs, Jennifer M.; Smith, Sarah E.; Gogol, Madelaine; Unruh, Jay R.; Slaughter, Brian D.; Jaspersen, Sue L.

2015-01-01

In closed mitotic systems such as Saccharomyces cerevisiae, the nuclear envelope (NE) does not break down during mitosis, so microtubule-organizing centers such as the spindle-pole body (SPB) must be inserted into the NE to facilitate bipolar spindle formation and chromosome segregation. The mechanism of SPB insertion has been linked to NE insertion of nuclear pore complexes (NPCs) through a series of genetic and physical interactions between NPCs and SPB components. To identify new genes involved in SPB duplication and NE insertion, we carried out genome-wide screens for suppressors of deletion alleles of SPB components, including Mps3 and Mps2. In addition to the nucleoporins POM152 and POM34, we found that elimination of SEC66/SEC71/KAR7 suppressed lethality of cells lacking MPS2 or MPS3. Sec66 is a nonessential subunit of the Sec63 complex that functions together with the Sec61 complex in import of proteins into the endoplasmic reticulum (ER). Cells lacking Sec66 have reduced levels of Pom152 protein but not Pom34 or Ndc1, a shared component of the NPC and SPB. The fact that Sec66 but not other subunits of the ER translocon bypass deletion mutants in SPB genes suggests a specific role for Sec66 in the control of Pom152 levels. Based on the observation that sec66∆ does not affect the distribution of Ndc1 on the NE or Ndc1 binding to the SPB, we propose that Sec66-mediated regulation of Pom152 plays an NPC-independent role in the control of SPB duplication. PMID:26510791

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Lu; Zhang, Sheng; Qu, Xiaoni

Lanthanide MOFs, [Eu(TCA)(NDC)·H{sub 2}O]{sub n} (1) and [Tb(TCA)(NDC)·H{sub 2}O]{sub n} (2), have been prepared with the mixed aromatic carboxylate ligands, namely, 4,4′,4″-tricarboxytriphenylamine (H{sub 3}TCA) and 1,4-naphthalenedicarboxylate (H{sub 2}NDC). Single-crystal X-ray diffraction analysis reveals that isomorphic 1 and 2 present pillar-layered 3D framework that Eu/Tb(III) bond with carboxylate in various coordination fashions. Optical investigation indicates that the as-prepared compounds feature characteristic luminescence emission bands of Eu/Tb ions in the visible regions at room temperature. Moreover, compound 2 shows a relatively longer luminescence lifetime (τ=0.342 ms) and significantly enhanced quantum yield (Φ{sub overall}=11%) comparing with those of 1 (τ=0.335 ms, Φ{sub overall}=0.06%).more » - Graphical abstract: Synoptic: Two Ln-MOFs (Ln=Eu{sup III}, Tb{sup III}) with mixed polycarboxylate ligands present different luminescent properties. - Highlights: • Two Eu/Tb-MOFs with H{sub 3}TCA and H{sub 2}NDC ligands have been obtained. • The ancillary ligand is employed to decrease water molecule coordinate numbers. • 2displays superior quantum yield and lifetime than those of 1.« less

Effect of three bis-pyridyl-bis-amide ligands with various spacers on the structural diversity of new multifunctional cobalt(II) coordination polymers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Hong-Yan; Lu, Huizhe; Le, Mao

2015-03-15

Three new cobalt(II) coordination polymers [Co{sub 2}(1,4-NDC){sub 2}(3-bpye)(H{sub 2}O)] (1), [Co(1,4-NDC)(3-bpfp)(H{sub 2}O)] (2) and [Co(1,4-NDC)(3-bpcb)] (3) [3-bpye=N,N′-bis(3-pyridinecarboxamide)-1,2-ethane, 3-bpfp=bis(3-pyridylformyl)piperazine, 3-bpcb=N,N′-bis(3-pyridinecarboxamide)-1,4-benzene, and 1,4-H{sub 2}NDC=1,4-naphthalenedicarboxylic acid] have been hydrothermally synthesized. The structures of complexes 1–3 have been determined by X-ray single crystal diffraction analyses and further characterized by infrared spectroscopy (IR), powder X-ray diffraction (PXRD) and thermogravimetric analyses (TGA). Complex 1 is a 3D coordination structure with 8-connected (4{sup 20}.6{sup 8}) topology constructed from 3D [Co{sub 2}(1,4-NDC){sub 2}(H{sub 2}O)]{sub n} framework and bidentate 3-bpye ligands. Complex 2 shows 1D “cage+cage”-like chain formed by 1D [Co{sub 2}(1,4-NDC){sub 2}]{sub n} ribbon chains and [Co{sub 2}(3-bpfp){submore » 2}] loops, which are further linked by hydrogen bonding interactions to form a 3D supramolecular network. Complex 3 displays a 3D coordination network with a 6-connected (4{sup 12}.6{sup 3}) topology based on 2D [Co{sub 2}(1,4-NDC){sub 2}]{sub n} layers and bidentate 3-bpcb bridging ligands. The influences of different bis-pyridyl-bis-amide ligands with various spacers on the structures of title complexes are studied. Moreover, the fluorescent properties, electrochemical behaviors and magnetic properties of complexes 1–3 have been investigated. - Graphical abstract: Three multifunctional cobalt(II) complexes constructed from three bis-pyridyl-bis-amide and 1,4-naphthalenedicarboxylic acid have been hydrothermally synthesized and characterized. The fluorescent, electrochemical and magnetic properties of 1–3 have been investigated. - Highlights: • Three multifunctional cobalt(II) complexes based on various bis-pyridyl-bis-amide ligands. • Complex 1 is a 3D coordination structure with 8-connected (4{sup 20}.6{sup 8}) topology. • Complex 2 is a 1D “cage+cage”-like chain. • Complex 3 is a 3D coordination network with a 6-connected (4{sup 12}.6{sup 3}) topology. • The fluorescent, electrochemical and magnetic properties of 1–3 were reported.« less

White Matter Integrity on DTI, Amyloid Load, and Neurodegeneration in Non-demented Elderly

PubMed Central

Kantarci, Kejal; Schwarz, Christopher G.; Reid, Robert; Przybelski, Scott A.; Lesnick, Timothy; Zuk, Samantha M.; Senjem, Matthew L.; Gunter, Jeffrey L.; Lowe, Val; Machulda, Mary M.; Knopman, David S.; Petersen, Ronald C.; Jack, Clifford R.

2016-01-01

Importance Pathophysiologic mechanisms leading to loss of white matter (WM) integrity and the temporal positioning of biomarkers of WM integrity relative to the biomarkers of gray matter (GM) neurodegeneration and amyloid load in the course of AD are poorly understood. Objective To investigate the effects of Alzheimer’s disease (AD)-related GM neurodegeneration and high β-amyloid on white matter (WM) microstructure in non-demented older adults. Design Longitudinal cohort study Setting Population-based Mayo Clinic Study of Aging. Participants Participants (n=701) with MRI/DTI and PET studies diagnosed as cognitively normal (CN; n=570) or mild cognitive impairment (MCI; n=131) were included. CN and MCI subjects were divided into biomarker-negative, amyloid- positive only, neurodegeneration- positive only, and amyloid plus neurodegeneration-positive groups based on their amyloid load on 11C-Pittsburgh compound-B PET, AD hypometabolic pattern on 18F-fluorodeoxyglucose PET and/or hippocampal atrophy on MRI. Main Outcome Measure Fractional anisotrophy (FA) from diffusion tensor imaging (DTI) Results No FA alterations were observed in biomarker-negative MCI, and amyloid-positive only CN and MCI groups. Conversely, neurodegeneration-positive only and amyloid plus neurodegeneration- positive CN and MCI groups consistently had decreased FA in the fornix, which correlated with cognitive performance (Rho=0.38; p<0.001). Patients with MCI had more extensive WM involvement than CN subjects, and greatest FA decreases were observed in the amyloid plus neurodegeneration-positive MCI group. Conclusions and Relevance High amyloid load does not influence DTI-based measures of WM integrity in the absence of co-existent GM neurodegeneration in non-demented older adults. PMID:25347157

Validation of a novel Montreal Cognitive Assessment scoring algorithm in non-demented Parkinson's disease patients.

PubMed

Sulzer, Patricia; Becker, Sara; Maetzler, Walter; Kalbe, Elke; van Nueten, Luc; Timmers, Maarten; Machetanz, Gerrit; Streffer, Johannes; Salvadore, Giacomo; Scholz, Erich; Tkaczynska, Zuzanna; Brockmann, Kathrin; Berg, Daniela; Liepelt-Scarfone, Inga

2018-06-23

The early diagnosis of mild cognitive impairment (PD-MCI) in Parkinson's disease (PD) is essential as it increases the future risk for PD dementia (PDD). Recently, a novel weighting algorithm for the Montreal Cognitive Assessment (MoCA) subtests has been reported, to best discriminate between those with and without cognitive impairment in PD. The aim of our study was to validate this scoring algorithm in a large sample of non-demented PD patients, hypothesizing that the weighted MoCA would have a higher diagnostic accuracy for PD-MCI than the original MoCA. In 202 non-demented PD patients, we evaluated cognitive status, clinical and demographic data, as well as the MoCA with a weighted and unweighted score. Receiver operating characteristic (ROC) curve analysis was used to evaluate discriminative ability of the MoCA. Group comparisons and ROC analysis were performed for PD-MCI classifications with a cut-off ≤ 1, 1.5, and 2 standard deviation (SD) below appropriate norms. PD-MCI patients scored lower on the weighted than the original MoCA version (p < 0.001) compared to PD patients with normal cognitive function. Areas under the curve only differed significantly for the 2 SD cut-off, leading to an increased sensitivity of the weighted MoCA score (72.9% vs. 70.5%) and specificity compared to the original version (79.0% vs. 65.4%). Our results indicate better discriminant power for the weighted MoCA compared to the original for more advanced stages of PD-MCI (2 SD cut-off). Future studies are needed to evaluate the predictive value of the weighted MoCA for PDD.

Regional brain amyloid-β accumulation associates with domain-specific cognitive performance in Parkinson disease without dementia.

PubMed

Akhtar, Rizwan S; Xie, Sharon X; Chen, Yin J; Rick, Jacqueline; Gross, Rachel G; Nasrallah, Ilya M; Van Deerlin, Vivianna M; Trojanowski, John Q; Chen-Plotkin, Alice S; Hurtig, Howard I; Siderowf, Andrew D; Dubroff, Jacob G; Weintraub, Daniel

2017-01-01

Parkinson disease patients develop clinically significant cognitive impairment at variable times over their disease course, which is often preceded by milder deficits in memory, visuo-spatial, and executive domains. The significance of amyloid-β accumulation to these problems is unclear. We hypothesized that amyloid-β PET imaging by 18F-florbetapir, a radiotracer that detects fibrillar amyloid-β plaque deposits, would identify subjects with global cognitive impairment or poor performance in individual cognitive domains in non-demented Parkinson disease patients. We assessed 61 non-demented Parkinson disease patients with detailed cognitive assessments and 18F-florbetapir PET brain imaging. Scans were interpreted qualitatively (positive or negative) by two independent nuclear medicine physicians blinded to clinical data, and quantitatively by a novel volume-weighted method. The presence of mild cognitive impairment was determined through an expert consensus process using Level 1 criteria from the Movement Disorder Society. Nineteen participants (31.2%) were diagnosed with mild cognitive impairment and the remainder had normal cognition. Qualitative 18F-florbetapir PET imaging was positive in 15 participants (24.6%). Increasing age and presence of an APOE ε4 allele were associated with higher composite 18F-florbetapir binding. In multivariable models, an abnormal 18F-florbetapir scan by expert rating was not associated with a diagnosis of mild cognitive impairment. However, 18F-florbetapir retention values in the posterior cingulate gyrus inversely correlated with verbal memory performance. Retention values in the frontal cortex, precuneus, and anterior cingulate gyrus retention values inversely correlated with naming performance. Regional cortical amyloid-β amyloid, as measured by 18F-florbetapir PET, may be a biomarker of specific cognitive deficits in non-demented Parkinson disease patients.

Peripheral Blood Mononuclear Cells HIV DNA Levels Impact Intermittently on Neurocognition

PubMed Central

Cysique, Lucette A.; Hey-Cunningham, William J.; Dermody, Nadene; Chan, Phillip; Brew, Bruce J.; Koelsch, Kersten K.

2015-01-01

Objectives To determine the contribution of peripheral blood mononuclear cells’ (PBMCs) HIV DNA levels to HIV-associated dementia (HAD) and non-demented HIV-associated neurocognitive disorders (HAND) in chronically HIV-infected adults with long-term viral suppression on combined antiretroviral treatment (cART). Methods Eighty adults with chronic HIV infection on cART (>97% with plasma and CSF HIV RNA <50 copies/mL) were enrolled into a prospective observational cohort and underwent assessments of neurocognition and pre-morbid cognitive ability at two visits 18 months apart. HIV DNA in PBMCs was measured by real-time PCR at the same time-points. Results At baseline, 46% had non-demented HAND; 7.5% had HAD. Neurocognitive decline occurred in 14% and was more likely in those with HAD (p<.03). Low pre-morbid cognitive ability was uniquely associated with HAD (p<.05). Log10 HIV DNA copies were stable between study visits (2.26 vs. 2.22 per 106 PBMC). Baseline HIV DNA levels were higher in those with lower pre-morbid cognitive ability (p<.04), and higher in those with no ART treatment during HIV infection 1st year (p = .03). Baseline HIV DNA was not associated with overall neurocognition. However, % ln HIV DNA change was associated with decline in semantic fluency in unadjusted and adjusted analyses (p = .01-.03), and motor-coordination (p = .02-.12) to a lesser extent. Conclusions PBMC HIV DNA plays a role in HAD pathogenesis, and this is moderated by pre-morbid cognitive ability in the context of long-term viral suppression. While the HIV DNA levels in PBMC are not associated with current non-demented HAND, increasing HIV DNA levels were associated with a decline in neurocognitive functions associated with HAND progression. PMID:25853424

Cognitive Slowing and Learning of Target Detection Skills in Pre-Demented Subjects

ERIC Educational Resources Information Center

Amieva, Helene; Rouch-Leroyer, Isabelle; Letenneur, Luc; Dartigues, Jean Francois; Fabrigoule, Collette

2004-01-01

Alzheimer's disease produces a generalized slowing of cognitive processing increasing with the progression of dementia. However little is known about this phenomenon in the pre-demented stages. Our purpose was to investigate cognitive slowing in pre-demented subjects and their ability to develop target detection skills while performing a…

Changes in gait while backward counting in demented older adults with frontal lobe dysfunction.

PubMed

Allali, Gilles; Kressig, Reto W; Assal, Frédéric; Herrmann, François R; Dubost, Véronique; Beauchet, Olivier

2007-10-01

Gait disorders caused by dementia have been associated with frontal lobe dysfunction. Dual-tasking is used to explore the involvement of cortical level in gait control. It has been shown that dual-task induced gait changes that could be related to (1) the efficiency of executive function, (2) the level of difficulty involved in the walking-associated task, or (3) the articulo-motor components comprised in the walking-associated task. A better understanding of dual-task related changes in demented subjects with frontal lobe dysfunction could help us to clarify the role of the frontal lobe in motor gait control. To assess and compare the effects of two mental arithmetic tasks involving similar articulo-motor components but different level of difficulty on the mean values and coefficient of variation (CV) of stride time among demented older adults with impaired executive function. The mean values and coefficients of variation of stride time were measured using a GAITRite-System among 16 demented older adults with impaired executive function while walking with and without forward counting (FC) and backward counting (BC). The mean values and CV of stride time were significantly higher under both dual-task conditions than during a simple walking task (p<0.05). The change in CV of stride time during BC was significantly higher when compared with the change during FC (p=0.015), whereas the change in mean value was not significant (p=0.056). There was no difference between the dual-task and single task condition as far the number of enumerated figures were concerned (p=0.678 for FC and p=0.069 for BC), but significantly fewer figures were enumerated while BC compared with FC (p<0.001). BC provoked more changes in gait parameters than FC with major modification in gait variability related to an inappropriate focusing of attention. These findings suggest that the CV may be a suitable criterion for the assessment of gait control.

Longitudinal decline in speech production in Parkinson's disease spectrum disorders.

PubMed

Ash, Sharon; Jester, Charles; York, Collin; Kofman, Olga L; Langey, Rachel; Halpin, Amy; Firn, Kim; Dominguez Perez, Sophia; Chahine, Lama; Spindler, Meredith; Dahodwala, Nabila; Irwin, David J; McMillan, Corey; Weintraub, Daniel; Grossman, Murray

2017-08-01

We examined narrative speech production longitudinally in non-demented (n=15) and mildly demented (n=8) patients with Parkinson's disease spectrum disorder (PDSD), and we related increasing impairment to structural brain changes in specific language and motor regions. Patients provided semi-structured speech samples, describing a standardized picture at two time points (mean±SD interval=38±24months). The recorded speech samples were analyzed for fluency, grammar, and informativeness. PDSD patients with dementia exhibited significant decline in their speech, unrelated to changes in overall cognitive or motor functioning. Regression analysis in a subset of patients with MRI scans (n=11) revealed that impaired language performance at Time 2 was associated with reduced gray matter (GM) volume at Time 1 in regions of interest important for language functioning but not with reduced GM volume in motor brain areas. These results dissociate language and motor systems and highlight the importance of non-motor brain regions for declining language in PDSD. Copyright © 2017 Elsevier Inc. All rights reserved.

Integrity and Function of the Saccharomyces cerevisiae Spindle Pole Body Depends on Connections Between the Membrane Proteins Ndc1, Rtn1, and Yop1

PubMed Central

Casey, Amanda K.; Dawson, T. Renee; Chen, Jingjing; Friederichs, Jennifer M.; Jaspersen, Sue L.; Wente, Susan R.

2012-01-01

The nuclear envelope in Saccharomyces cerevisiae harbors two essential macromolecular protein assemblies: the nuclear pore complexes (NPCs) that enable nucleocytoplasmic transport, and the spindle pole bodies (SPBs) that mediate chromosome segregation. Previously, based on metazoan and budding yeast studies, we reported that reticulons and Yop1/DP1 play a role in the early steps of de novo NPC assembly. Here, we examined if Rtn1 and Yop1 are required for SPB function in S. cerevisiae. Electron microscopy of rtn1Δ yop1Δ cells revealed lobular abnormalities in SPB structure. Using an assay that monitors lateral expansion of the SPB central layer, we found that rtn1Δ yop1Δ SPBs had decreased connections to the NE compared to wild type, suggesting that SPBs are less stable in the NE. Furthermore, large budded rtn1Δ yop1Δ cells exhibited a high incidence of short mitotic spindles, which were frequently misoriented with respect to the mother–daughter axis. This correlated with cytoplasmic microtubule defects. We found that overexpression of the SPB insertion factors NDC1, MPS2, or BBP1 rescued the SPB defects observed in rtn1Δ yop1Δ cells. However, only overexpression of NDC1, which is also required for NPC biogenesis, rescued both the SPB and NPC associated defects. Rtn1 and Yop1 also physically interacted with Ndc1 and other NPC membrane proteins. We propose that NPC and SPB biogenesis are altered in cells lacking Rtn1 and Yop1 due to competition between these complexes for Ndc1, an essential common component of both NPCs and SPBs. PMID:22798490

Copper and manganese complexes based on 1,4-naphthalene dicarboxylic acid ligand and its derivative: Syntheses, crystal structures, and magnetic properties

NASA Astrophysics Data System (ADS)

Xing, Yubo; Liu, Yuqi; Xue, Xiaofei; Wang, Xinying; Li, Wei

2018-02-01

Three new metal-organic coordination polymers, {[Mn2(1,4-NDC)2 (C2H5OH) (DMF) (H2O)]·CH3OH}n(1), {[Mn(III)(1,4-NDC)(C2H5O)][Mn(II)(1,4-NDC)(DMF)(H2O)]}n(2) and {[Cu2(C13H9O4)4(H2O)2]}n(3) based on1,4-H2NDC and its derivative were hydrothermally synthesized (1,4-H2NDC = 1,4-naphthalene-dicarboxylic acid, C13H10O4 = 4-methyl formate-1-naphthalenecarboxylic acid), and characterized by techniques of single crystal X-ray diffraction, infrared spectra (IR), elemental analysis, powder X-ray diffraction(PXRD) and variable-temperature magnetic susceptibility measurements. X-ray crystal structure analyses reveal that complexes 1 and 2 show a same 3,5-connected fsc 3D topology network with the Schlȁfli symbol of {4·6·8}{4·66·83}. But, the valence of some Mn atom in complex 2 take place transition from the +II oxidation state to the +III oxidation state, which may be the effect of the different solvent ratio. In complex 3, the Cu⋯Cu distance of 2.620(13) Å is significantly shorter than the sum of the van der Waals radii of Cu (1.40 Å), resulting in a strong ferromagnetic interaction between the Cu(II) centers. Furthermore, the temperature-dependent magnetic susceptibility measurements exhibit overall antiferromagnetic interactions between manganese ions for complexes 1 and 2, and a strong ferromagnetic interaction between the Cu(II) centers for complex 3.

The Mps1 kinase modulates the recruitment and activity of Cnn1(CENP-T) at Saccharomyces cerevisiae kinetochores.

PubMed

Thapa, Kriti Shrestha; Oldani, Amanda; Pagliuca, Cinzia; De Wulf, Peter; Hazbun, Tony R

2015-05-01

Kinetochores are conserved protein complexes that bind the replicated chromosomes to the mitotic spindle and then direct their segregation. To better comprehend Saccharomyces cerevisiae kinetochore function, we dissected the phospho-regulated dynamic interaction between conserved kinetochore protein Cnn1(CENP-T), the centromere region, and the Ndc80 complex through the cell cycle. Cnn1 localizes to kinetochores at basal levels from G1 through metaphase but accumulates abruptly at anaphase onset. How Cnn1 is recruited and which activities regulate its dynamic localization are unclear. We show that Cnn1 harbors two kinetochore-localization activities: a C-terminal histone-fold domain (HFD) that associates with the centromere region and a N-terminal Spc24/Spc25 interaction sequence that mediates linkage to the microtubule-binding Ndc80 complex. We demonstrate that the established Ndc80 binding site in the N terminus of Cnn1, Cnn1(60-84), should be extended with flanking residues, Cnn1(25-91), to allow near maximal binding affinity to Ndc80. Cnn1 localization was proposed to depend on Mps1 kinase activity at Cnn1-S74, based on in vitro experiments demonstrating the Cnn1-Ndc80 complex interaction. We demonstrate that from G1 through metaphase, Cnn1 localizes via both its HFD and N-terminal Spc24/Spc25 interaction sequence, and deletion or mutation of either region results in anomalous Cnn1 kinetochore levels. At anaphase onset (when Mps1 activity decreases) Cnn1 becomes enriched mainly via the N-terminal Spc24/Spc25 interaction sequence. In sum, we provide the first in vivo evidence of Cnn1 preanaphase linkages with the kinetochore and enrichment of the linkages during anaphase. Copyright © 2015 by the Genetics Society of America.

Synthesis, structure and magnetic property of a two-dimensional coordination polymer decorated with sine wave-like 1D double chain

NASA Astrophysics Data System (ADS)

Yao, Xiao-Qiang; Li, Dan-Yang; Xiao, Guo-Bin; Ma, Heng-Chang; Lei, Zi-Qiang; Liu, Jia-Cheng

2018-04-01

A new compound, {[Co(BPFI)(NDC)]H2O·0.5DMF}n (1) has been synthesized under hydrothermal condition by the self-assembly of V-shaped N-containing rigid ligand BPFI with Co(II) ions in the presence of H2NDC acid, where BPFI = 2,8-di(1H-imidazole-1-yl)dibenzo[b,d]furan, H2NDC = naphthalene-1,4-dicarboxylic acid. Compound 1 was characterized by elemental analysis, single crystal X-ray diffraction, FT-IR spectroscopy and UV-visible spectra. Structural analysis reveals that compound 1 is a unique dinuclear Co-based 2D (4,4) layer structure decorated with parallel double chains. In addition, magnetic study reveals the existence of antiferromagnetic coupling interactions between the Co(II) ions within the dinuclear unit of 1.

Measurements of temperature characteristics and estimation of terahertz negative differential conductance in resonant-tunneling-diode oscillators

NASA Astrophysics Data System (ADS)

Asada, M.; Suzuki, S.; Fukuma, T.

2017-11-01

The temperature dependences of output power, oscillation frequency, and current-voltage curve are measured for resonant-tunneling-diode terahertz (THz) oscillators. The output power largely changes with temperature owing to the change in Ohmic loss. In contrast to the output power, the oscillation frequency and current-voltage curve are almost insensitive to temperature. The measured temperature dependence of output power is compared with the theoretical calculation including the negative differential conductance (NDC) as a fitting parameter assumed to be independent of temperature. Very good agreement was obtained between the measurement and calculation, and the NDC in the THz frequency region is estimated. The results show that the absolute values of NDC in the THz region significantly decrease relative to that at DC, and increases with increasing frequency in the measured frequency range.

Nata de coco (NDC) hydrogel as nanoreactors for preparation iron nanoparticles (FeNps) from ferrocenium reduction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Andarini, Mellissa; Lazim, Azwan

This study focuses on hydrogel as nano template to produce iron nanoparticles (FeNps). Radical polymerization was used to synthesize the hydrogel from nata de coco (NDC-g-PAA). Ferrocenium (FcCL) with 1 × 10{sup −4} g/ml has successfully incorporated with NDC-g-PAA hydrogel system and reduce using sodium hydroxide (NaOH) at different concentrations. Transmission electron microscopy (TEM) result demonstrates that the size of FeNps produced was about 5 – 20 nm. Morphological analysis of hydrogel is carried out by scanning electron microscopy (SEM), SEM-EDEX is used to determine percentage of iron (Fe) in hydrogel. The results offer a wide range of application inmore » various areas, especially the use of hydrogel system as a responsive template.« less

Is resistant starch protective against colorectal cancer via modulation of the WNT signalling pathway?

PubMed

Malcomson, Fiona C; Willis, Naomi D; Mathers, John C

2015-08-01

Epidemiological and experimental evidence suggests that non-digestible carbohydrates (NDC) including resistant starch are protective against colorectal cancer. These anti-neoplastic effects are presumed to result from the production of the SCFA, butyrate, by colonic fermentation, which binds to the G-protein-coupled receptor GPR43 to regulate inflammation and other cancer-related processes. The WNT pathway is central to the maintenance of homeostasis within the large bowel through regulation of processes such as cell proliferation and migration and is frequently aberrantly hyperactivated in colorectal cancers. Abnormal WNT signalling can lead to irregular crypt cell proliferation that favours a hyperproliferative state. Butyrate has been shown to modulate the WNT pathway positively, affecting functional outcomes such as apoptosis and proliferation. Butyrate's ability to regulate gene expression results from epigenetic mechanisms, including its role as a histone deacetylase inhibitor and through modulating DNA methylation and the expression of microRNA. We conclude that genetic and epigenetic modulation of the WNT signalling pathway may be an important mechanism through which butyrate from fermentation of resistant starch and other NDC exert their chemoprotective effects.

Design of a Behavior of Robot That Attracts the Interest of the Mildly Demented Elderly.

PubMed

Nihei, Misato; Sakuma, Natsuki; Yabe, Hiroyuki; Kamata, Minoru; Inoue, Takenobu

2017-01-01

In this study, using the unexpected intervention overturning the interaction amount of the field and the mental model, an interaction of a robot system that enables sustained nonverbal communication with the mildly demented elderly was proposed and its effectiveness was shown in the group home of the mildly demented elderly.

Effect of carbon supports on RhRe bifunctional catalysts for selective hydrogenolysis of tetrahydropyran-2-methanol

DOE PAGES

Karanjkar, Pranav U.; Burt, Samuel P.; Chen, Xiaoli; ...

2016-09-12

Tetrahydropyran-2-methanol undergoes selective C–O–C hydrogenolysis to produce 1,6-hexanediol using a bifunctional RhRe (reducible metal with an oxophilic promoter) catalyst supported on Vulcan XC-72 carbon (VXC) with >90% selectivity. This RhRe/VXC catalyst is stable over 40 h of reaction in a continuous flow fixed bed reactor. The hydrogenolysis activity of RhRe/VXC is two orders-of-magnitude higher than that of RhRe supported on Norit Darco 12X40 activated carbon (NDC). STEM–EDS analysis reveals that, compared to the RhRe/VXC catalyst, the Re and Rh component metals are segregated on the surface of the low activity RhRe/NDC catalyst, suggesting that Rh and Re in close proximitymore » (“bimetallic” particles) are required for an active hydrogenolysis catalyst. Differences in metal distribution on the carbon surfaces are, in turn, linked to the properties of the carbons: NDC has both a higher surface area and surface oxygen content. Thus, the low areal density of Rh and Re precursors on the high area NDC and/or interactions of the precursors with its O functional groups may interfere with the formation of the bimetallic species required for an active catalyst.« less

Differential associations between types of verbal memory and prefrontal brain structure in healthy aging and late life depression.

PubMed

Lamar, Melissa; Charlton, Rebecca; Zhang, Aifeng; Kumar, Anand

2012-07-01

Verbal memory deficits attributed to late life depression (LLD) may result from executive dysfunction that is more detrimental to list-learning than story-based recall when compared to healthy aging. Despite these behavioral dissociations, little work has been done investigating related neuroanatomical dissociations across types of verbal memory performance in LLD. We compared list-learning to story-based memory performance in 24 non-demented individuals with LLD (age ~ 66.1 ± 7.8) and 41 non-demented/non-depressed healthy controls (HC; age ~ 67.6 ± 5.3). We correlated significant results of between-group analyses across memory performance variables with brain volumes of frontal, temporal and parietal regions known to be involved with verbal learning and memory. When compared to the HC group, the LLD group showed significantly lower verbal memory performance for spontaneous recall after repeated exposure and after a long-delay but only for the list-learning task; groups did not differ on story-based memory performance. Despite equivalent brain volumes across regions, only the LLD group showed brain associations with verbal memory performance and only for the list-learning task. Specifically, frontal volumes important for subjective organization and response monitoring correlated with list-learning performance in the LLD group. This study is the first to demonstrate neuroanatomical dissociations across types of verbal memory performance in individuals with LLD. Results provide structural evidence for the behavioral dissociations between list-learning and story-based recall in LLD when compared to healthy aging. More specifically, it points toward a network of predominantly anterior brain regions that may underlie the executive contribution to list-learning in older adults with depression. Copyright © 2012 Elsevier Ltd. All rights reserved.

Rates of transition between amyloid and neurodegeneration biomarker states and to dementia among non-demented individuals: a population-based cohort study

PubMed Central

Jack, Clifford R.; Therneau, Terry M.; Wiste, Heather J.; Weigand, Stephen D.; Knopman, David S.; Lowe, Val J.; Mielke, Michelle M.; Vemuri, Prashanthi; Roberts, Rosebud O.; Machulda, Mary M.; Senjem, Matthew L.; Gunter, Jeffrey L.; Rocca, Walter A.; Petersen, Ronald C.

2016-01-01

Summary Background We previously observed in a cross-sectional analysis that frequencies of amyloid and neurodegeneration biomarker states varied greatly by age among cognitively non-impaired participants, suggesting dynamic within-person processes. Our objective in this longitudinal study was to estimate rates of transitioning from a less- to a more-abnormal biomarker state by age among non-demented individuals, as well as rates of transitioning to dementia by biomarker state. Methods All participants (n=4049) were non-demented at baseline. A subset of 1541 underwent multi-modality imaging. Amyloid PET was used to classify individuals as amyloid positive (A+) or negative (A−). FDG PET and MRI were used to classify individuals as neurodegeneration positive (N+) or negative (N−). All observations from the 4049 individuals were used in a multi-state model to estimate four different age-specific biomarker state transition rates among non-demented individuals: A−N− to A+N−; A−N− to A−N+ (suspected non-Alzheimer pathology, SNAP); A+N− to A+N+; A−N+ (SNAP) to A+N+. We also estimated two age-specific rates to dementia: A+N+ to dementia; and A−N+ (SNAP) to dementia. Using these state-to-state transition rates, we estimated biomarker state frequencies by age. Findings All transition rates were low at age 50 and (with one exception) were well-characterized by an exponential increase with age. The rates per 100-person years at ages 65 versus 85 were 1.6 versus 17.2 for A−N− to A−N+, 6.1 versus 20.8 for A+N− to A+N+, 2.6 versus 13.2 for A−N+ to A+N+, 0.8 versus 7.0 for A+N+ to dementia, and 0.6 versus 1.7 for A−N+ to dementia. The one exception to an exponential increase with age was the transition rate from A−N− to A+N− which increased from 4.0 transitions per 100 person-years at age 65 to approximately 7 transitions per 100 person-years in the 70s and then plateaued beyond that age. Estimated biomarker frequencies by age from the multistate model were similar to cross-sectional biomarker frequencies. Interpretation Dynamic state-to-state transition rates illustrate important measurable aspects of the changing biology underlying brain aging. The biomarker states we describe relate to both AD and non-AD processes. Our transition rates suggest that brain aging can be conceptualized as a nearly inevitable acceleration toward worse biomarker and clinical states. The one exception was that transition to amyloidosis without neurodegeneration was most dynamic from age 60 to 70 and then plateaued beyond that age. We found that simple transition rates can explain complex, highly interdependent biomarker state frequencies in our sample. PMID:26597325

Crystal conversion between metal-organic frameworks with different crystal topologies for efficient crystal design on two-dimensional substrates

NASA Astrophysics Data System (ADS)

Tsuruoka, Takaaki; Inoue, Kohei; Miyanaga, Ayumi; Tobiishi, Kaho; Ohhashi, Takashi; Hata, Manami; Takashima, Yohei; Akamatsu, Kensuke

2018-04-01

Crystal conversion of metal-organic frameworks (MOFs) between different crystal topologies on a polymer substrate has been successfully achieved by localized dissolution of MOF crystals followed by a rapid self-assembly of framework components. Upon addition of the desired organic linkers to the reaction system containing MOF crystals on the substrate, reversible crystal conversion between the [Cu2(btc)3]n and [Cu2(ndc)2(dabco)]n frameworks (btc = 1,3,5-benzene tricarboxylate, ndc = 1,4-naphthalene dicarboxylate, dabco = 1,4-diazabicyclo[2.2.2]octane) could be routinely achieved in high yields. Most surprisingly, in the case of conversion from the [Cu2(ndc)2(dabco)]n to [Cu2(btc)3]n frameworks, the [Cu2(btc)3]n crystals with unique shapes (cuboctahedron and truncated cube) could be prepared using butanol as a reaction medium.

Conserved tetramer junction in the kinetochore Ndc80 complex

PubMed Central

Valverde, Roberto; Ingram, Jessica; Harrison, Stephen C.

2016-01-01

Summary The heterotetrameric Ndc80 complex establishes connectivity along the principal longitudinal axis of a kinetochore. Its two heterodimeric subcomplexes, each with a globular end and a coiled-coil shaft, connect end-to-end to create a ∼600 Å long rod spanning the gap from centromere-proximal structures to spindle microtubules. Neither subcomplex has a known function on its own, but the heterotetrameric organization and the characteristics of the junction are conserved from yeast to man. We have determined crystal structures of two shortened (“dwarf”) Ndc80 complexes that contain the full tetramer junction and both globular ends. The junction connects two α-helical coiled coils through regions of four-chain and three-chain overlap. The complexity of its structure depends on interactions among conserved amino-acid residues, suggesting a binding site for additional cellular factor(s) not yet identified. PMID:27851957

Mental status testing in the elderly nursing home population.

PubMed

Nadler, J D; Relkin, N R; Cohen, M S; Hodder, R A; Reingold, J; Plum, F

1995-07-01

The clinical utility of selected brief cognitive screening instruments in detecting dementia in an elderly nursing home population was examined. One hundred twenty nursing home residents (mean age 87.9) were administered the Mini-Mental State Exam (MMSE) and the Modified Mini-Mental State Exam (3MS). The majority of the subjects (75%) were also administered the Dementia Rating Scale (DRS). Both clinically diagnosed demented (n = 57) and non-demented (n = 63) subjects participated in the study. Dementia was diagnosed in accordance with DSM-III-R criteria by physicians specializing in geriatric medicine. Using standard cutoffs for impairment, the 3MS, MMSE, and DRS achieved high sensitivity (82% to 100%) but low specificity (33% to 52%) in the detection of dementia among nursing home residents. Positive predictive values ranged from 52% to 61%, and negative predictive values from 77% to 100%. Higher age, lower education, and history of depression were significantly associated with misclassification of non-demented elderly subjects. Receiver Operating Characteristic (ROC) curve analyses revealed optimal classification of dementia with cutoff values of 74 for the 3MS, 22 for the MMSE, and 110 for the DRS. The results suggest that the 3MS, MMSE, and DRS do not differ significantly with respect to classification accuracy of dementia in a nursing home population. Elderly individuals of advanced age (i.e., the oldest-old) with lower education and a history of depression appear at particular risk for dementia misclassification with these instruments. Revised cutoff values for impairment should be employed when these instruments are applied to elderly residents of nursing homes and the oldest-old.

Tuning the gate-opening pressure and particle size distribution of the switchable metal-organic framework DUT-8(Ni) by controlled nucleation in a micromixer.

PubMed

Miura, Hiroki; Bon, Volodymyr; Senkovska, Irena; Ehrling, Sebastian; Watanabe, Satoshi; Ohba, Masaaki; Kaskel, Stefan

2017-10-17

Controlled nucleation in a micromixer and further crystal growth were used to synthesize Ni 2 (2,6-ndc) 2 dabco (2,6-ndc - 2,6-naphthalenedicarboxylate, dabco - 1,4-diazabicyclo[2.2.2]octane), also termed DUT-8(Ni) (DUT = Dresden University of Technology), with narrow particle size distribution in a range of a few nm to several μm. The crystal size was found to significantly affect the switching characteristics, in particular the gate opening pressure in nitrogen adsorption isotherms at 77 K for this highly porous and flexible network. Below a critical size of about 500 nm, a type Ia isotherm typical of rigid MOFs is observed, while above approximately 1000 nm a pronounced gating behaviour is detected, starting at p/p 0 = 0.2. With increasing crystal size this transition gate becomes steeper indicating a more uniform distribution of activation energies within the crystal ensemble. At an intermediate size (500-1000 nm), the DUT-8(Ni) crystals close during activation but cannot be reopened by nitrogen at 77 K possibly indicating monodomain switching.

Decreased NURR1 gene expression in patients with Parkinson’s disease

PubMed Central

Le, Weidong; Pan, Tianhong; Huang, Maosheng; Xu, Pingyi; Xie, Wenjie; Zhu, Wen; Zhang, Xiong; Deng, Hao; Jankovic, Joseph

2008-01-01

NURR1 is a transcription factor essential for the development, survival, and functional maintenance of midbrain dopaminergic (DAergic) neurons and NURR1 is a potential susceptibility gene for Parkinson’s disease (PD). To determine whether NURR1 gene expression is altered in patients with PD we measured its expression in human peripheral blood lymphocytes (PBL) in 278 patients with PD, 166 healthy controls (HC), and 256 neurological disease controls (NDC) by quantitative real-time PCR. NURR1 gene expression was significantly decreased in patients with PD (particularly those with family history of PD) as compared with HC (p < 0.01) and also as compared with NDC (p < 0.05). There was no significant difference in NURR1 gene expression among PD patients with or without anti-PD medications. When adjusted for gender, age, and ethnicity, lower levels of NURR1 gene expression were associated with significantly increased risk for PD in women, in patients 60 years old or older, and in patients of Caucasian origin. The observed reduction in PBL NURR1 gene expression indicates possible systemic involvement in PD, and the finding may help identify individuals with PD and other disorders associated with impaired central DAergic system. PMID:18684475

Subtle imitation behaviour in convenience samples of normal, demented, and currently depressed elderly subjects.

PubMed

von Gunten, Armin; Duc, René

2007-06-01

The clinical significance of imitation behaviour (IB) is unclear. The aim of this study was to investigate the prevalence of subtle naïve and obstinate IB in convenience samples of normal elderly, demented, and depressed subjects. Subtle IB was assessed using a protocol constructed ad hoc in 146 patients, consecutively referred to a memory clinic having received an ICD-10 diagnosis of either dementia or depression, and in 241 healthy subjects. The prevalence of IB in the three groups was determined and the association with possible demographic, cognitive, and non-cognitive variables analysed. Subtle naïve IB was frequent in the elderly with dementia, intermediate in the depressed, and rare in the normal elderly except that the latter frequently stretched out their arms. Obstinate IB never occurred in the normal elderly. IB was predicted by none of the variables used. The groups included were convenience samples with the depressed being a small group precluding further distinction of depressive subtypes. Although naïve IB is a frequent clinical feature in the demented, it also accompanies depressive disorders in the elderly. It can be observed as context-specific IB in the normal elderly. Obstinate IB does not occur in the normal elderly. Copyright 2006 John Wiley & Sons, Ltd.

The Nun Study: risk factors for pathology and clinical-pathologic correlations.

PubMed

Mortimer, James A

2012-07-01

The Nun Study was the first cohort study to enroll and follow a large, well-defined population that included demented and non-demented participants, all of whom agreed to donate their brains for research. The inclusion of systematic neuropathologic analysis in this study has resulted in a greater understanding of the role of Alzheimer and vascular pathology in the expression of memory deficits and dementia and has provided data showing that biomarkers for the pathology may be evident many decades earlier in adult life. Findings related to neuropathology in this study have included the following: (1) Although clinical outcomes were strongly correlated with Alzheimer neuropathology, about one-third of the participants fulfilling criteria for neuropathologic Alzheimer's disease (AD) were not demented at the time of death. (2) Brain infarcts by themselves had little effect on cognitive status, but played an important role in increasing the risk of dementia associated with Alzheimer pathology. (3) Hippocampal volume was strongly correlated with Braak neurofibrillary stage even in participants with normal cognitive function. (4) A linguistic characteristic of essays written in early adult life, idea density, had a strong association with not only clinical outcomes in late life, but the severity of Alzheimer neuropathology as well. (5) The effect of apolipoprotein E-e4 on dementia was mediated through Alzheimer, but not vascular pathology.

Evaluation of the Sensitivity and Signal Response of the DT-702 LiF:Mg,Cu,P TLD

DTIC Science & Technology

2007-06-27

energy stored from the radiation interactions that occurs prior to the TLD being read. Electrons can absorb additional energy from sources other...thermoluminescent dosimetry , annealing is the 24 process used to clear any radiation exposure information from a TLD , preparing it for reuse...702 four-chip TLDs were obtained from the Naval Dosimetry Center (NDC), Bethesda, MD. Each card was tested by Thermo prior to delivery to NDC to

Two three-dimensional coordination polymers of lead(II) with iminodiacetate and naphthalene-dicarboxylate anions: Synthesis, characterization and luminescence behavior

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hazari, Debdoot; Jana, Swapan Kumar; Fleck, Michel

2014-11-15

Two lead(II) compounds [Pb{sub 3}(idiac){sub 3}(phen){sub 2}(H{sub 2}O)]·2(H{sub 2}O) (1) and [Pb(ndc)]{sub n} (2), where H{sub 2}idiac=iminodiacetic acid, phen=1,10-phenanthroline and H{sub 2}ndc=naphthalene-2,6-dicarboxylic acid, have been synthesized and structurally characterized. Single crystal X-ray diffraction analysis showed that compound 1 is a discrete trinuclear complex (of two-fold symmetry) which evolves to a supramolecular 3D network via π–π interactions, while in compound 2 the naphthalene dicarboxylate anion act as a linker to form a three dimensional architecture, where the anion adopts a bis-(bidentate bridging) coordination mode connecting four Pb(II) centers. The photoluminescence property of the two complexes has been studied. - graphical abstract:more » Two new topologically different 1D coordination polymers formed by Pb{sub 4} clusters have been synthesized and characterized by x-ray analysis. The luminescence and thermal properties have been studied. - Highlights: • 1 is a trinuclear complex of Pb(II) growing to 3D network via weak interactions. • In 1, layers of (4,4) rhomboidal topology are identified. • In 2, the ndc anion adopts interesting bis-(bidentate bridging) coordination. • In 2, network is reinforced by C–H…π-ring interactions between the ndc rings.« less

Hot electrons injection in carbon nanotubes under the influence of quasi-static ac-field

NASA Astrophysics Data System (ADS)

Amekpewu, M.; Mensah, S. Y.; Musah, R.; Mensah, N. G.; Abukari, S. S.; Dompreh, K. A.

2016-07-01

The theory of hot electrons injection in carbon nanotubes (CNTs) where both dc electric field (Ez), and a quasi-static ac field exist simultaneously (i.e. when the frequency ω of ac field is much less than the scattering frequency v (ω ⪡ v or ωτ ⪡ 1, v =τ-1) where τ is relaxation time) is studied. The investigation is done theoretically by solving semi-classical Boltzmann transport equation with and without the presence of the hot electrons source to derive the current densities. Plots of the normalized current density versus dc field (Ez) applied along the axis of the CNTs in the presence and absence of hot electrons reveal ohmic conductivity initially and finally negative differential conductivity (NDC) provided ωτ ⪡ 1 (i.e. quasi- static case). With strong enough axial injection of the hot electrons, there is a switch from NDC to positive differential conductivity (PDC) about Ez ≥ 75 kV / cm and Ez ≥ 140 kV / cm for a zigzag CNT and an armchair CNT respectively. Thus, the most important tough problem for NDC region which is the space charge instabilities can be suppressed due to the switch from the NDC behaviour to the PDC behaviour predicting a potential generation of terahertz radiations whose applications are relevance in current-day technology, industry, and research.

A Dedicated Type II NADPH Dehydrogenase Performs the Penultimate Step in the Biosynthesis of Vitamin K1 in Synechocystis and Arabidopsis

PubMed Central

Fatihi, Abdelhak; Latimer, Scott; Schmollinger, Stefan; Block, Anna; Dussault, Patrick H.; Vermaas, Wim F.J.; Merchant, Sabeeha S.; Basset, Gilles J.

2015-01-01

Mutation of Arabidopsis thaliana NAD(P)H DEHYDROGENASE C1 (NDC1; At5g08740) results in the accumulation of demethylphylloquinone, a late biosynthetic intermediate of vitamin K1. Gene coexpression and phylogenomics analyses showed that conserved functional associations occur between vitamin K biosynthesis and NDC1 homologs throughout the prokaryotic and eukaryotic lineages. Deletion of Synechocystis ndbB, which encodes for one such homolog, resulted in the same defects as those observed in the cyanobacterial demethylnaphthoquinone methyltransferase knockout. Chemical modeling and assay of purified demethylnaphthoquinone methyltransferase demonstrated that, by virtue of the strong electrophilic nature of S-adenosyl-l-methionine, the transmethylation of the demethylated precursor of vitamin K is strictly dependent on the reduced form of its naphthoquinone ring. NDC1 was shown to catalyze such a prerequisite reduction by using NADPH and demethylphylloquinone as substrates and flavine adenine dinucleotide as a cofactor. NDC1 displayed Michaelis-Menten kinetics and was markedly inhibited by dicumarol, a competitive inhibitor of naphthoquinone oxidoreductases. These data demonstrate that the reduction of the demethylnaphthoquinone ring represents an authentic step in the biosynthetic pathway of vitamin K, that this reaction is enzymatically driven, and that a selection pressure is operating to retain type II NAD(P)H dehydrogenases in this process. PMID:26023160

Placing a Disrupted Degradation Motif at the C Terminus of Proteasome Substrates Attenuates Degradation without Impairing Ubiquitylation*

PubMed Central

Alfassy, Omri S.; Cohen, Itamar; Reiss, Yuval; Tirosh, Boaz; Ravid, Tommer

2013-01-01

Protein elimination by the ubiquitin-proteasome system requires the presence of a cis-acting degradation signal. Efforts to discern degradation signals of misfolded proteasome substrates thus far revealed a general mechanism whereby the exposure of cryptic hydrophobic motifs provides a degradation determinant. We have previously characterized such a determinant, employing the yeast kinetochore protein Ndc10 as a model substrate. Ndc10 is essentially a stable protein that is rapidly degraded upon exposure of a hydrophobic motif located at the C-terminal region. The degradation motif comprises two distinct and essential elements: DegA, encompassing two amphipathic helices, and DegB, a hydrophobic sequence within the loosely structured C-terminal tail of Ndc10. Here we show that the hydrophobic nature of DegB is irrelevant for the ubiquitylation of substrates containing the Ndc10 degradation motif, but is essential for proteasomal degradation. Mutant DegB, in which the hydrophobic sequence was disrupted, acted as a dominant degradation inhibitory element when expressed at the C-terminal regions of ubiquitin-dependent and -independent substrates of the 26S proteasome. This mutant stabilized substrates in both yeast and mammalian cells, indicative of a modular recognition moiety. The dominant function of the mutant DegB provides a powerful experimental tool for evaluating the physiological implications of stabilization of specific proteasome substrates in intact cells and for studying the associated pathological effects. PMID:23519465

Nitrogen-doped MOF-derived micropores carbon as immobilizer for small sulfur molecules as a cathode for lithium sulfur batteries with excellent electrochemical performance.

PubMed

Li, Zhaoqiang; Yin, Longwei

2015-02-25

Nitrogen-doped carbon (NDC) spheres with abundant 22 nm mesopores and 0.5 nm micropores are obtained by directly carbonization of nitrogen-contained metal organic framework (MOF) nanocrystals. Large S8 and small S2-4 molecules are successfully infiltrated into 22 nm mesopores and 0.5 nm micropores, respectively. We successfully investigate the effect of sulfur immobilization in mesopores and micropores on the electrochemical performance of lithium-sulfur (Li-S) battery based on NDC-sulfur hybrid cathodes. The large S8 molecules in 22 nm mesopores can be removed by a prolonged heat treatment, with only small molecules of S2-4 immobilized in micropores of NDC matrices. The NDC/S2-4 hybrid exhibits excellent cycling performance, high Coulombic efficiency, and good rate capability as cathode for Li-S batteries. The confinement of smaller S2-4 molecules in the micropores of NDS efficiently avoids the loss of active sulfur and formation of soluble high-order Li polysulfides. The porous carbon can buffer the volume expansion and contraction changes, promising a stable structure for cathode. Furthermore, N doping in MOF-derived carbon not only facilitates the fast charge transfer but also is helpful in building a stronger interaction between carbon and sulfur, strengthening immobilization ability of S2-4 in micropores. The NDS-sulfur hybrid cathode exhibits a reversible capacity of 936.5 mAh g(-1) at 100th cycle with a Coulombic efficiency of 100% under a current density of 335 mA g(-1). It displays a superior rate capability performance, delivering a capacity of 632 mAh g(-1) at a high rate of 5 A g(-1). This uniquely porous NDC derived from MOF nanocrystals could be applied in related high-energy storage devices.

Alzheimer Disease Pathology in Cognitively Healthy Elderly:A Genome-wide Study

PubMed Central

Kramer, Patricia L; Xu, Haiyan; Woltjer, Randall L; Westaway, Shawn K; Clark, David; Erten-Lyons, Deniz; Kaye, Jeffrey A; Welsh-Bohmer, Kathleen A; Troncoso, Juan C; Markesbery, William R; Petersen, Ronald C; Turner, R Scott; Kukull, Walter A; Bennett, David A; DouglasGalasko; Morris, John C; Ott, Jurg

2010-01-01

Many elderly individuals remain dementia-free throughout their life. However, some of these individuals exhibit Alzheimer disease neuropathology on autopsy, evidenced by neurofibrillary tangles (NFTs) in AD-specific brain regions. We conducted a genome-wide association study to identify genetic mechanisms that distinguish non-demented elderly with a heavy NFT burden from those with a low NFT burden. The study included 344 non-demented subjects with autopsy (201 subjects with low and 143 with high NFT levels). Both a genotype test, using logistic regression, and an allele test provided genome-wide significant evidence that variants in the RELNgene are associated with neuropathology in the context of cognitive health. Immunohistochemical data for reelin expression in AD-related brain regions added support for these findings. Reelin signaling pathways modulate phosphorylation of tau, the major component of NFTs, either directly or through β-amyloid pathways that influence tau phosphorylation. Our findings suggest that up-regulation of reelin may be a compensatory response to tau-related or beta-amyloid stress associated with AD even prior to the onset of dementia. PMID:20452100

Reduced Empathy Scores in Patients with Parkinson's Disease: A Non-Motor Symptom Associated with Advanced Disease Stages.

PubMed

Schmidt, Nele; Paschen, Laura; Deuschl, Günther; Witt, Karsten

2017-01-01

Empathy describes the ability to infer and share emotional experiences of other people and is a central component of normal social functioning. Impaired empathy might be a non-motor symptom in Parkinson's disease (PD). To examine empathic abilities and their relationship to clinical and cognitive functioning in PD patients. Empathy was measured in 75 non-demented PD patients and 34 age-matched healthy controls using a German version of the Interpersonal Reactivity Index. Moreover, we collected demographic and clinical data and conducted a comprehensive neuropsychological test battery. PD patients had a significant lower global empathy score than healthy controls. Furthermore, we found significant group differences for the cognitive empathy scales but not for the scales which are sensitive for affective empathy components. The empathy decrease was significantly higher in advanced Hoehn & Yahr stages. There were only sporadic significant correlations between empathy scores and cognitive variables. PD patients show a stage dependent empathy score decrease which is driven mainly by cognitive aspects of empathy. However, emotional empathy aspects are not reduced.

Hydrogen bonded supra-molecular framework in inorganic-organic hybrid compounds: Syntheses, structures, and photoluminescent properties

NASA Astrophysics Data System (ADS)

Yan, Li; Liu, Wei; Li, Chuanbi; Wang, Yifei; Ma, Li; Dong, Qinqin

2013-03-01

Two novel compounds constructed from aromatic acid and N-Heterocyclic ligands have been synthesized by hydrothermal reaction: [Cd(mip)(1,8-NDC)(H2O)]2 (1) [mip = 2-(3-methoxyphenyl)-1H-imidazo[4,5-f][1,10]phenanthroline, 1,8-NDC = naphthalene-1,8-dicarboxylic acid] and Cd(mip)2(NTC)2 (2) [NTC = nicotinic acid]. Compounds 1 and 2 are characterized by elemental analysis, IR, single crystal X-ray diffraction and thermogravimetric analysis (TGA). Single-crystal X-ray investigation reveals that compounds 1-2 are 0 dimensional (0D) structures, and the existence of hydrogen bonds and π-π interactions lead the 0D to 2D novel framework. Hydrogen bonds and π-π interactions are powerful non-covalent intermolecular interactions for directing supra-molecular architectures. TG analysis shows clear courses of weight loss, which corresponds to the decomposition of different ligands. At room temperature, compound 1 exhibits emission at 449 nm upon excitation at 325 nm, and compound 2 shows a strong emission at 656 nm upon excitation at 350 nm. Fluorescent spectrum displays that compounds 1 and 2 are potential luminescent materials.

Quantitative neuropathological study of Alzheimer-type pathology in the hippocampus: comparison of senile dementia of Alzheimer type, senile dementia of Lewy body type, Parkinson's disease and non-demented elderly control patients.

PubMed

Ince, P; Irving, D; MacArthur, F; Perry, R H

1991-12-01

A Lewy body dementing syndrome in the elderly has been recently described and designated senile dementia of Lewy body type (SDLT) on the basis of a distinct clinicopathological profile. The pathological changes seen in SDLT include the presence of cortical Lewy bodies (LB) frequently, but not invariably, associated with senile plaque (SP) formation. Whilst neocortical neurofibrillary tangles (NFT) are sparse or absent, a proportion of these cases show involvement of the temporal archicortex by lesions comprising Alzheimer-type pathology (ATP, i.e. NFT, SP and granulovacuolar degeneration [GVD]). Thus the relationship between SDLT and senile dementia of Alzheimer type (SDAT) is complex and controversial. In this study quantitative neuropathology was used to compare the intensity and distribution of ATP in the hippocampus and entorhinal cortex of 53 patients from 3 disease groups (SDLT, SDAT, Parkinson's disease (PD)) and a group of neurologically and mentally normal elderly control patients. For most brain areas examined the extent of ATP between the patient groups followed the trend SDAT greater than SDLT greater than PD greater than control. Statistical comparison of these groups revealed significant differences between the mean densities of NFT, SP and GVD although individual cases showed considerable variability. These results confirm additional pathological differences between SDAT and SDLT regarding the intensity of involvement of the temporal archicortex by ATP. Many patients with Lewy body disorders (LBdis) show a predisposition to develop ATP albeit in a more restricted distribution (e.g. low or absent neocortical NFT) and at lower densities than is found in SDAT. Some cases of SDLT show minimal SP and NFT formation in both neocortex and archicortex supporting previously published data distinguishing this group from Alzheimer's disease.

Establishing biorientation occurs with precocious separation of the sister kinetochores, but not the arms, in the early spindle of budding yeast.

PubMed

Goshima, G; Yanagida, M

2000-03-17

Sister kinetochores are bioriented toward the spindle poles in higher eukaryotic prometaphase before chromosome segregation. We show that, in budding yeast, the sister kinetochores are separated in the very early spindle, while the sister arms remain associated. Biorientation of the separated kinetochores is achieved already after replication. Mtw1p, a homolog of fission yeast Mis12 required for biorientation, locates at the centromeres in an Ndc10p-dependent manner. Mtw1p and the sequences 1.8 and 3.8 kb from CEN3 and CEN15, respectively, behave like the precociously separated kinetochores, whereas the sequences 23 and 35 kb distant from CEN3 and CEN5 previously used as the centromere markers behave like a part of the arm. Mtw1p and Ndc10p are identically located except for additional spindle localization of Ndc10p. A model explaining small centromeres and early spindle formation in budding yeast is proposed.

Sundowning in Dementia: Clinical Relevance, Pathophysiological Determinants, and Therapeutic Approaches.

PubMed

Canevelli, Marco; Valletta, Martina; Trebbastoni, Alessandro; Sarli, Giuseppe; D'Antonio, Fabrizia; Tariciotti, Leonardo; de Lena, Carlo; Bruno, Giuseppe

2016-01-01

Sundowning means the emergence or worsening of neuropsychiatric symptoms (NPS) in the late afternoon or early evening. This syndrome has been recognized since a long time in the field of dementing illnesses and is well known among most of health-care providers involved in the assistance of people with dementia. Indeed, it represents a common manifestation among persons with dementia and is associated with several adverse outcomes (such as institutionalization, faster cognitive worsening, and greater caregiver burden). Its occurrence and phenotypic characteristics may be influenced by diverse neurobiological, psychosocial, and environmental determinants. Moreover, it may pose diagnostic challenges in relation to other common causes of behavioral disruptions. Beside these considerations, this phenomenon has so far drawn limited clinical and scientific interest compared to other specific NPS occurring in dementias, as indicated by the lack of commonly agreed definitions, specific screening/assessment tools, and robust estimates on its prevalence. Accordingly, no randomized controlled trial specifically investigating the effectiveness of pharmacological and non-pharmacological strategies in managing this condition among demented patients has been yet conducted. In the present narrative review, we present and discuss available evidence concerning sundowning occurring in people with dementia. A special focus is given to its definitions, pathophysiological determinants, and clinical relevance, as well as to the clinical and therapeutic approaches required for its management in the daily practice.

Sundowning in Dementia: Clinical Relevance, Pathophysiological Determinants, and Therapeutic Approaches

PubMed Central

Canevelli, Marco; Valletta, Martina; Trebbastoni, Alessandro; Sarli, Giuseppe; D’Antonio, Fabrizia; Tariciotti, Leonardo; de Lena, Carlo; Bruno, Giuseppe

2016-01-01

Sundowning means the emergence or worsening of neuropsychiatric symptoms (NPS) in the late afternoon or early evening. This syndrome has been recognized since a long time in the field of dementing illnesses and is well known among most of health-care providers involved in the assistance of people with dementia. Indeed, it represents a common manifestation among persons with dementia and is associated with several adverse outcomes (such as institutionalization, faster cognitive worsening, and greater caregiver burden). Its occurrence and phenotypic characteristics may be influenced by diverse neurobiological, psychosocial, and environmental determinants. Moreover, it may pose diagnostic challenges in relation to other common causes of behavioral disruptions. Beside these considerations, this phenomenon has so far drawn limited clinical and scientific interest compared to other specific NPS occurring in dementias, as indicated by the lack of commonly agreed definitions, specific screening/assessment tools, and robust estimates on its prevalence. Accordingly, no randomized controlled trial specifically investigating the effectiveness of pharmacological and non-pharmacological strategies in managing this condition among demented patients has been yet conducted. In the present narrative review, we present and discuss available evidence concerning sundowning occurring in people with dementia. A special focus is given to its definitions, pathophysiological determinants, and clinical relevance, as well as to the clinical and therapeutic approaches required for its management in the daily practice. PMID:28083535

Autobiographical Memory and Depression in the Later Age: The Bump Is a Turning Point

ERIC Educational Resources Information Center

Gidron, Yori; Alon, Shirly

2007-01-01

This preliminary study integrated previous findings of the distribution of autobiographical memories in the later age according to their age of occurrence, with the overgeneral memory bias predictive of depression. Twenty-five non-demented, Israeli participants between 65-89 years of age provided autobiographical memories to 4 groups of word cues…

Sentence Processing in Lewy Body Spectrum Disorder: The Role of Working Memory

ERIC Educational Resources Information Center

Gross, Rachel G.; McMillan, Corey T.; Chandrasekaran, Keerthi; Dreyfuss, Michael; Ash, Sharon; Avants, Brian; Cook, Philip; Moore, Peachie; Libon, David J.; Siderowf, Andrew; Grossman, Murray

2012-01-01

Prior work has related sentence processing to executive deficits in non-demented patients with Parkinson's disease (PD). We extended this investigation to patients with dementia with Lewy bodies (DLB) and PD dementia (PDD) by examining grammatical and working memory components of sentence processing in the full range of patients with Lewy body…

[Effect of filial imprinting procedure on cell proliferation in the chick brain].

PubMed

Komissarova, N V; Anokhin, K V

2007-01-01

In the present study we tested the hypothesis that memory formation during visual imprinting might be related to generation of new cells in the brain of newborn domestic chicks. Cell proliferation was examined in the intermediate medial mesopallium (IMM), arcopallium intermedium (AI), medial part of nidopallium and mesopallium (MNM), nidopallium dorso-caudalis (Ndc), hippocampus (Hp) and area parahippocampalis (APH), as well as in corresponding ventricular zones. Number of new cells was measured by BrdU incorporation 24 h or 7 days after training, BrdU was injected before training. 24 h after imprinting the number of BrdU-positive cells increased significantly in IMM. 7 days after training no changes were observed in IMM, while the number of new cells decreased in MNM and Ndc in comparison to the control group. These data suggest that newly generated cells in the brain of young chicks are influenced by imprinting procedure, which has opposite short-term and long-term effects. A possible reason for such double action of imprinting in contrast to conventional learning can be its additional stimulation of development of predisposition for features of natural parents.

Syntheses, structures, photoluminescence of four dicarboxylate-controlled Zn(II) coordination complexes incorporating flexible 1-(4-pyridylmethyl)-benzimidazole ligand

NASA Astrophysics Data System (ADS)

Hao, Hong-Jun; Du, Ming-Yue; Wang, Dan-Feng; Sun, Cheng-Jie; Wang, Zhan-Hui; Huang, Rong-Bin; Zheng, Lan-Sun

2013-09-01

Four Zn(II) coordination complexes, namely {[Zn(pmbm)2(tpa)]·H2O}n (1), {[Zn(pmbm)(phda)]·2(H2O)}n (2), [Zn(pmbm)(aze)]n (3), {[Zn(pmbm)(1,4-ndc)]·2(CH3OH)}n (4) [pmbm = 1-(4-pyridylmethyl)-benzimidazole, H2tpa = terephthalic acid, H2phda = phenylenediacetic acid, H2aze = azelaic acid, 1,4-ndcH2 = 1,4-naphthalenedicarboxylic acid] have been synthesized by solution phase ultrasonic reactions of Zn(AC)2·2H2O with pmbm and various dicarboxylates ligands under the ammoniacal condition. All the complexes have been characterized by elemental analyses, IR spectra and X-ray diffraction. Complexes 1 and 2 exhibit one-dimensional chains structure and complex 3 and 4 are two-dimensional sheets structure with (4,4) topology. Complexes 1-4 spanning from one-dimensional chains to two-dimensional sheets suggest that dicarboxylates play significant roles in the formation of such coordination architectures. The photoluminescences of the complexes were also investigated in the solid state at room temperature.

Nitro Lignin-Derived Nitrogen-Doped Carbon as an Efficient and Sustainable Electrocatalyst for Oxygen Reduction.

PubMed

Graglia, Micaela; Pampel, Jonas; Hantke, Tina; Fellinger, Tim-Patrick; Esposito, Davide

2016-04-26

The use of lignin as a precursor for the synthesis of materials is nowadays considered very interesting from a sustainability standpoint. Here we illustrate the synthesis of a micro-, meso-, and macroporous nitrogen-doped carbon (NDC) using lignin extracted from beech wood via alkaline hydrothermal treatment and successively functionalized via aromatic nitration. The so obtained material is thus carbonized in the eutectic salt melt KCl/ZnCl2. The final NDC shows an excellent activity as electrocatalyst for the oxygen reduction reaction.

Exercise Improves Cognition in Parkinson’s Disease: the PRET-PD Randomized Clinical Trial

PubMed Central

David, Fabian J.; Robichaud, Julie A.; Leurgans, Sue E.; Poon, Cynthia; Kohrt, Wendy M.; Goldman, Jennifer G.; Comella, Cynthia L.; Vaillancourt, David E.; Corcos, Daniel M.

2015-01-01

Background This paper reports on the findings of the effect of two structured exercise interventions on secondary cognitive outcomes which were gathered as part of the Progressive Resistance Exercise Training in Parkinson’s disease randomized controlled trial. Methods This study was a prospective, parallel-group, single-center trial. Fifty-one non-demented patients with mild-to-moderate Parkinson’s disease were randomly assigned either to modified Fitness Counts or to Progressive Resistance Exercise, and were followed for 24 months. Cognitive outcomes were the Digit Span, Stroop, and Brief Test of Attention. Results Eighteen patients in modified Fitness Counts and 20 patients in Progressive Resistance Exercise completed the trial. At 12 and at 24 months no differences between groups were observed. At 12 months, relative to baseline, modified Fitness Counts improved on the Digit Span (estimated change, 0.3; Inter-Quartile Range, 0, 0.7; p=0.04) and Stroop (0.3; 0, 0.6; p=0.04), and Progressive Resistance Exercise improved only on the Digit Span (0.7; 0.3, 1; p<0.01). At 24 months, relative to baseline, modified Fitness Counts improved on the Digit Span (0.7; 0.3, 1.7; p<0.01) and Stroop (0.3; 0.1, 0.5; p=0.03), while Progressive Resistance Exercise improved on the Digit Span (0.5; 0.2, 0.8; p<0.01), Stroop (0.2; −0.1, 0.6; p=0.048), and Brief Test of Attention (0.3; 0, 0.8; p=0.048). No neurologic or cognitive adverse events were seen. Conclusions This study provides Class IV level of evidence that 24 months of Progressive Resistance Exercise or modified Fitness Counts may improve attention and working memory in non-demented patients with mild-to-moderate Parkinson’s disease. PMID:26148003

Geochronologic Constraints on the Location of the Sino-Korean/Yangtze Suture and Evolution of the Northern Dabie Shan

NASA Astrophysics Data System (ADS)

Bryant, D. L.; Ayers, J. C.; Gao, S.; Miller, C. F.; Zhang, H.

2002-05-01

The Northern Dabie Complex (NDC) has been proposed to be either a Paleozoic magmatic arc, an exhumed piece of subducted continental crust, or young crust produced almost entirely by Cretaceous extensional magmatism. Ion microprobe zircon 238U-206Pb ages of separates from NDC gneisses center around 689Ma (+/- 31(95%CL)), consistent with the characteristic zircon dates of the Yangtze Craton [1]. Field observations also show that these gneisses, ranging from granitic to dioritic composition, make up a sizeable area ( ~30%) of the NDC. Zircon separates from the Baimajian granitoid, the largest of the widespread Cretaceous intrusions in the NDC, have yielded ages clustered around 677Ma (+/- 79), and 120Ma (+/- 3.4), the latter of which agrees with ion probe Th-Pb monazite ages. The ~700Ma age indicates that this intrusion may be linked with partial melting of underlying Yangtze crust, while the 120Ma age is the age of its crystallization. Granitic intrusions from Sanzushi and Yerenshai in the Dabie ultrahigh-pressure (UHP) region also show clusters of ages at 714Ma (+/- 55) from zircon cores, as well as rims around 250Ma (+/- 38), which is interpreted as the time of collision of the two continental blocks. These age data support the hypothesis set forth by Zhang et al. [2] using Sm-Nd and Pb isotopic data, that the Yangtze block lies beneath the exhumed UHP belt and outcrops as the NDC, which lies between the UHP belt and the Sino-Korean/Yangtze suture. The Baimajian granitoid, however, also shows a range of older zircon core ages from 1.4-2.0Ga, which may represent the early stages of formation of the Yangtze craton. Zhang et al. [2] suggested craton formation at 1.6-2.4Ga but few such ages have been reported for rocks of the Yangtze or Sino-Korean cratons. 1. Hacker, et al. (2000) Journal of Geophysical Research. Vol. 105. p. 13,339. 2. Zhang, et al. (In press) Chemical Geology.

The Emissions Scenarios Portal: Visualizing Low-Carbon Pathways for the 21st Century

NASA Astrophysics Data System (ADS)

Hennig, R. J.; Friedrich, J.; Ge, M.; Mountford, H.; Fransen, T.; Altamirano, J. C.; Thanawala, Z.; Arcipowska, A.

2017-12-01

The Emissions Scenarios Portal (ESP) is a newly developed exploration tool for 21st century low-carbon pathways and investigation of the Nationally Determined Contributions (NDC's) that countries have put forward under the Paris Agreement. It is open to the public and aims to help achieve the goal of limiting global temperature increase to well below 2 degrees Celsius above pre-industrial levels by enhancing access to high-quality, up-to-date scenario information. It can guide users to set ambitious, realistic emission mitigation goals and understand what these goals imply for different sectors of the economy. Data will be integrated from a wide variety of economic and energy-system models with results from both national models as well as globally integrated assessment models (IAM's) and countries biennial update reports (BUR's). This information can support policy and investment decision making that will lead to a low carbon future. It is designed to help find answers to questions such as "Are the NDC's enough to put the world on a 2DC track?", "What do NDC's imply for different sectors of the economy under different assumptions?" or "What are good ways to increase ambition beyond NDC's?". The portal strives to achieve both inter-comparability across a wide range of different models and nationally reported scenarios, as well as flexibility to allow modelers to bring out the strengths and purpose of their model on the platform. Furthermore, it aims to enhance standardized and transparent reporting of emissions scenarios and relevant metadata, assumptions and results to improve understanding, accessibility and impact of the scenarios. On the data side, these rivaling objectives present interesting challenges for both the collection and communication of the data and in this presentation we will present some of our ideas for tackling these. This project will be part of Climate Watch, a new data platform developed jointly by the World Resources Institute and the NDC Partnership in collaboration with GIZ, UNFCCC, World Bank, and Climate Analytics. See also Abstract ID# 231913 for more information on Climate Watch.

Bright Light Delights: Effects of Daily Light Exposure on Emotions, Restactivity Cycles, Sleep and Melatonin Secretion in Severely Demented Patients.

PubMed

Münch, Mirjam; Schmieder, Michael; Bieler, Katharina; Goldbach, Rolf; Fuhrmann, Timo; Zumstein, Naomi; Vonmoos, Petra; Scartezzini, Jean-Louis; Wirz-Justice, Anna; Cajochen, Christian

2017-01-01

We tested whether the effects of a dynamic lighting system are superior to conventional lighting on emotions, agitation behaviour, quality of life, melatonin secretion and circadian restactivity cycles in severely demented patients. As a comparison, an age matched control patient group was exposed to conventional lighting. For none of the output measures were significant differences between the two lighting conditions found during the 8 study weeks in fall/winter. Thus, we divided the patient cohort (n = 89) into two groups, solely based on the median of their daily individual light exposure. Patients with higher average daily light exposure (>417 lx) showed significantly longer emotional expressions of pleasure and alertness per daily observations than patients with lower daily light exposure. Moreover, they had a higher quality of life, spent less time in bed, went to bed later and initiated their sleep episodes later, even though the two groups did not differ with respect to age, severity of cognitive impairment and mobility. In general, men were more agitated, had shorter sleep with more wake episodes, had a lower circadian amplitude of relative rest-wake activity and interdaily circadian stability than women. In particular, lower daily light exposures significantly predicted lower circadian amplitudes of rest-activity cycles in men but not in women. This may indicate sex specific susceptibility to daily light exposures for rest-activity regulation in older demented patients. Our results provide evidence that a higher daily light exposure has beneficial effects on emotions and thus improved quality of life in a severely demented patient group. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Molecular Analysis of Core Kinetochore Composition and Assembly in Drosophila melanogaster

PubMed Central

Przewloka, Marcin R.; Archambault, Vincent; D'Avino, Pier Paolo; Lilley, Kathryn S.; Laue, Ernest D.; McAinsh, Andrew D.; Glover, David M.

2007-01-01

Background Kinetochores are large multiprotein complexes indispensable for proper chromosome segregation. Although Drosophila is a classical model organism for studies of chromosome segregation, little is known about the organization of its kinetochores. Methodology/Principal Findings We employed bioinformatics, proteomics and cell biology methods to identify and analyze the interaction network of Drosophila kinetochore proteins. We have shown that three Drosophila proteins highly diverged from human and yeast Ndc80, Nuf2 and Mis12 are indeed their orthologues. Affinity purification of these proteins from cultured Drosophila cells identified a further five interacting proteins with weak similarity to subunits of the SPC105/KNL-1, MIND/MIS12 and NDC80 kinetochore complexes together with known kinetochore associated proteins such as dynein/dynactin, spindle assembly checkpoint components and heterochromatin proteins. All eight kinetochore complex proteins were present at the kinetochore during mitosis and MIND/MIS12 complex proteins were also centromeric during interphase. Their down-regulation led to dramatic defects in chromosome congression/segregation frequently accompanied by mitotic spindle elongation. The systematic depletion of each individual protein allowed us to establish dependency relationships for their recruitment onto the kinetochore. This revealed the sequential recruitment of individual members of first, the MIND/MIS12 and then, NDC80 complex. Conclusions/Significance The Drosophila MIND/MIS12 and NDC80 complexes and the Spc105 protein, like their counterparts from other eukaryotic species, are essential for chromosome congression and segregation, but are highly diverged in sequence. Hierarchical dependence relationships of individual proteins regulate the assembly of Drosophila kinetochore complexes in a manner similar, but not identical, to other organisms. PMID:17534428

Sleep dysfunctions influence decision making in undemented Parkinson's disease patients: a study in a virtual supermarket.

PubMed

Albani, Giovanni; Raspelli, Simona; Carelli, Laura; Priano, Lorenzo; Pignatti, Riccardo; Morganti, Francesca; Gaggioli, Andrea; Weiss, Patrice L; Kizony, Rachel; Katz, Noomi; Mauro, Alessandro; Riva, Giuseppe

2011-01-01

In the early-middle stages of Parkinson's disease (PD), polysomnographic studies show early alterations of the structure of the sleep, which may explain frequent symptoms reported by patients, such as daytime drowsiness, loss of attention and concentration, feeling of tiredness. The aim of this study was to verify if there is a correlation between the sleep dysfunction and decision making ability. We used a Virtual Reality version of the Multiple Errand Test (VMET), developed using the NeuroVR free software (http://www.neurovr2.org), to evaluate decision-making ability in 12 PD not-demented patients and 14 controls. Five of our not-demented 12 PD patients showed abnormalities in the polysomnographic recordings associated to significant differences in the VMET performance.

Does Implicit Learning in Non-Demented Parkinson's Disease depend on the Level of Cognitive Functioning?

ERIC Educational Resources Information Center

Vandenbossche, Jochen; Deroost, Natacha; Soetens, Eric; Kerckhofs, Eric

2009-01-01

We investigated the influence of the level of cognitive functioning on sequence-specific learning in Parkinson's disease (PD). This was done by examining the relationship between the scales for outcomes in Parkinson's disease-cognition [SCOPA-COG, Marinus, J., Visser, M., Verwey, N. A., Verhey, F. R. J., Middelkoop, H. A. M.,Stiggelbout, A., et…

A Validity Study of the Working Group's Orientation Test for Individuals with Moderate to Severe Intellectual Disability

ERIC Educational Resources Information Center

Pyo, G.; Curtis, K.; Curtis, R.; Markwell, S.

2009-01-01

Background: Decline in orientation skill has been reported as an early indicator of Dementia of Alzheimer's Type (DAT). Orientation subtest of the Working Group's Test Battery was examined whether this test is useful to identify DAT patients among adults with moderate to severe ID. Methods: Sixteen DAT patients and 35 non-demented normal controls…

Relation of plasma lipids to all-cause mortality in Caucasian, African-American and Hispanic elders

PubMed Central

Akerblom, Jennifer L.; Costa, Rosann; Luchsinger, Jose A.; Manly, Jennifer J.; Tang, Ming-Xin; Lee, Joseph H; Mayeux, Richard; Schupf, Nicole

2009-01-01

Objectives to investigate the relation of plasma lipids to all-cause mortality in a multi-ethnic cohort of non-demented elderly. Setting community-based sample of Medicare recipients, 65 years and older, residing in Northern Manhattan. Participants about two thousand five hundred and fifty-six non-demented elderly, 65–103 years. Among participants, 66.1% were women, 27.6% were White/non-Hispanic, 31.2% were African-American and 41.2% were Hispanic. Methods a standardised assessment, including functional ability, medical history, physical and neurological examination and a neuropsychological battery was conducted. Vital status was ascertained through the National Death Index (NDI). We used survival analyses stratified by race and ethnicity to examine the relation of plasma lipids to subsequent all-cause mortality. Results hispanics had the best overall survival, followed by African-Americans and Whites. Whites and African-Americans in the lowest quartiles of total cholesterol, non-HDL cholesterol and low-density lipoprotein cholesterol (LDL cholesterol) were approximately twice as likely to die as those in the highest quartile (White HR: 2.2, for lowest total cholesterol quartile; HR: 2.3, for lowest non-HDL cholesterol quartile; and HR: 1.8, for lowest LDL cholesterol quartile. African-American HR: 1.9, for lowest total cholesterol, HR: 2.0, for lowest non-HDL cholesterol and HR: 1.9, for lowest LDL cholesterol). In contrast, plasma lipid levels were not related to mortality risk among Hispanics. Conclusions hispanic ethnicity modifies the associations between lipid levels and all-cause mortality in the elderly. PMID:18349015

3D lanthanide metal-organic frameworks constructed from 2,6-naphthalenedicarboxylate ligand: synthesis, structure, luminescence and dye adsorption

NASA Astrophysics Data System (ADS)

Zhu, Yajing; Wang, Li; Chen, Xiaodong; Wang, Pengcheng; Fan, Yong; Zhang, Ping

2017-07-01

A series of novel isostructural 3D lanthanide metal-organic frameworks {[Ln2(NDC)3(H2O)4]·(DMF)4}n (Ln=Eu(1), Gd(2), Tb(3), Er(4), Yb(5), Dy(6), Y(7), Lu(8), H2NDC =2,6-Naphthalenedicarboxylic acid, DMF=N,N-dimethylformamide) with a rhombic channel along the b axis and high thermal stabilities, have been successfully synthesized under solvothermal conditions. The network can be described as 2, 4, 5-connected net with Schäfli symbol of (42.62.82)2(42.63.85)2(6). Luminescent studies illustrate that 1, 2, 7 and 8 exhibit strong luminescent emitting of the corresponding Ln(III) centers in the visible range, while 5 shows near-infrared range (NIR) luminescence. Further studies of 1 and 2A (activated product of 2) show that 1 displays good stability in different solvents and excellent fluorescence sensing for organic solvent small molecules and 2A ([Gd2(NDC)3(H2O)4]n) exhibits good adsorption capacity for organic dyes in water, especially for crystal violet.

Structural and Electrical-Optical Characterizations of Semiconductor-Atomic Superlattice

DTIC Science & Technology

2007-05-01

and Avalanche diodes certainly fall into this category. Resonant tunneling diodes like Esaki Tunnel diodes are NDC devices belong to a class where...Heterostructures, Eds. M. Dutta and M. Stroscio, (World Sci. 2003, Singapore), p221 177 Cooling by Inverse Nottingham Effect with Resonant Tunneling ...controlled emitter, V. Semet, V.T. Binh, J.Zhang, J.Yang, M.A. Khan, and R. Tsu, APL. 84,1937 (2004) 186 Stability Issues in Tunneling via Quantum

Portuguese version of Wechsler Memory Scale-3rd edition's utility with demented elderly adults.

PubMed

Gonçalves, Cátia; Pinho, Maria S; Cruz, Vítor; Gens, Helena; Oliveira, Fátima; Pais, Joana; Rente, José; Santana, Isabel; Santos, José M

2017-01-01

The purpose of this study is to analyze the utility of the Portuguese version of the Wechsler Memory Scale-3rd edition (WMS-III) with demented elderly people, namely its capacity to detect and discriminate between subcortical vascular dementia (SVD) and Alzheimer's disease (AD). We assessed early demented patients (SVD = 16; AD = 36) aged 65 or older who were compared to a control group (n = 40). Both clinical groups were adequately matched in terms of disease severity, overall cognitive functioning, depressive symptomatology, and pre-morbid intelligence. Between-group's differences were evaluated using the Quade's rank analysis of covariance. We also computed indexes and subtests optimal cut-off scores, and the corresponding sensitivity, specificity, and positive and negative predictive values, which were able to successfully discriminate between patients and healthy subjects. The SVD patients had a better overall memory performance than AD patients on the majority of the indexes and the delayed condition subtests of the WMS-III. The AD patients only showed a better performance on digit span subtest. Several measures discriminated patients from healthy subjects. This study suggests some recommendations for the diagnostic accuracy of the Portuguese version of WMS-III in dementia and about differential diagnosis between SVD and AD.

Surface-initiated ring-opening metathesis polymerization (SI-ROMP) to attach a tethered organic corona onto CdSe/ZnS core/shell quantum dots

PubMed Central

Vatansever, Fatma; Hamblin, Michael R.

2016-01-01

Core–shell CdSe/ZnS quantum dots (QDs) are useful as tunable photostable fluorophores for multiple applications in industry, biology, and medicine. However, to achieve the optimum optical properties, the surface of the QDs must be passivated to remove charged sites that might bind extraneous substances and allow aggregation. Here we describe a method of growing an organic polymer corona onto the QD surface using the bottom-up approach of surface-initiated ring-opening metathesis polymerization (SI-ROMP) with Grubbs catalyst. CdSe/ZnS QDs were first coated with mercaptopropionic acid by displacing the original trioctylphosphine oxide layer, and then reacted with 7-octenyl dimethyl chlorosilane. The resulting octenyl double bonds allowed the attachment of ruthenium alkylidene groups as a catalyst. A subsequent metathesis reaction with strained bicyclic monomers (norbornene-dicarbonyl chloride (NDC), and a mixture of NDC and norbornenylethylisobutyl-polyhedral oligomeric silsesquioxane (norbornoPOSS)) allowed the construction of tethered organic homo-polymer or co-polymer layers onto the QD. Compounds were characterized by FT-IR, 1H-NMR, X-ray photoelectron spectroscopy, differential scanning calorimetry, and transmission electron microscopy. Atomic force microscopy showed that the coated QDs were separate and non-aggregated with a range of diameter of 48–53 nm. PMID:28360819

Dynamin 2 gene is a novel susceptibility gene for late-onset Alzheimer disease in non-APOE-epsilon4 carriers.

PubMed

Aidaralieva, Nuripa Jenishbekovna; Kamino, Kouzin; Kimura, Ryo; Yamamoto, Mitsuko; Morihara, Takeshi; Kazui, Hiroaki; Hashimoto, Ryota; Tanaka, Toshihisa; Kudo, Takashi; Kida, Tomoyuki; Okuda, Jun-Ichiro; Uema, Takeshi; Yamagata, Hidehisa; Miki, Tetsuro; Akatsu, Hiroyasu; Kosaka, Kenji; Takeda, Masatoshi

2008-01-01

Alzheimer disease (AD) is characterized by progressive cognitive decline caused by synaptic dysfunction and neurodegeneration in the brain, and late-onset AD (LOAD), genetically classified as a polygenetic disease, is the major form of dementia in the elderly. It has been shown that beta amyloid, deposited in the AD brain, interacts with dynamin 1 and that the dynamin 2 (DNM2) gene homologous to the dynamin 1 gene is encoded at chromosome 19p13.2 where a susceptibility locus has been detected by linkage analysis. To test the genetic association of LOAD with the DNM2 gene, we performed a case-control study of 429 patients with LOAD and 438 sex- and age-matched control subjects in a Japanese population. We found a significant association of LOAD with single nucleotide polymorphism markers of the DNM2 gene, especially in non-carriers of the apolipoprotein E-epsilon4 allele. Even though subjects with the genotype homozygous for the risk allele at rs892086 showed no mutation in exons of the DNM2 gene, expression of DNM2 mRNA in the hippocampus was decreased in the patients compared to non-demented controls. We propose that the DNM2 gene is a novel susceptibility gene for LOAD.

The influence of Coulomb correlations on nonequilibrium quantum transport in quadruple quantum-dot structure

NASA Astrophysics Data System (ADS)

Kagan, M. Yu.; Aksenov, S. V.

2018-04-01

The description of quantum transport in a quadruple quantum-dot structure (QQD) is proposed taking into account the Coulomb correlations and nonzero bias voltages. To achieve this goal the combination of nonequilibrium Green's functions and equation-of-motion technique is used. It is shown that the anisotropy of kinetic processes in the QQD leads to negative differential conductance (NDC). The reason of the effect is an interplay of the Fano resonances which are induced by the interdot Coulomb correlations. Different ways to increase the peak-to-valley ratio related to the observed NDC are discussed.

Spouse caregivers' perceptions of influence of dementia on marriage.

PubMed

Eloniemi-Sulkava, Ulla; Notkola, Irma-Leena; Hämäläinen, Kaija; Rahkonen, Terhi; Viramo, Petteri; Hentinen, Maija; Kivelä, Sirkka-Liisa; Sulkava, Raimo

2002-03-01

To investigate what kind of changes spouse caregivers of demented patients experience after the onset of dementia (a) in the general atmosphere, happiness, and relations of marriage and (b) in the sexual side of marriage. Semistructured telephone interviews of spouse caregivers of demented patients. Community-living demented patients and their spouse caregivers in eastern Finland. The spouse caregivers of 42 demented patients recruited from a previous intervention study. The questionnaire covered different areas of marriage from the time before and after the onset of dementia. A statistically significant decline had occurred in extent of happiness (p = .012), in equal relations (p = .001), and in patients' expressions of sexual needs (p < .001) when compared the time before and after dementia. Twenty-five (60%) of the caregivers reported that the demented patient had shown at least one negative sexual behavioral change during the course of dementia. Seven male patients (24%) had shown the behavioral symptom of constantly expressing need for making love. One in 10 caregivers had experienced positive sexual behavioral changes. In one third of the patients, the expressions of tenderness towards the caregiver had increased. Dementia did not affect significantly the general atmosphere of the marriage. Out of those still in home care, at 3 years from the onset of dementia, 19 couples (46%) continued to practice intercourse, at 5 years the number was 15 couples (41%), and at 7 years it had declined to 7 couples (28%). Dementing illness has a major negative impact on many dimensions of marriage. However, there are also positive changes and preserved aspects of marriage. Dementia seems to have a surprisingly little impact on whether the couple continues to have intercourse when compared with the general aging population.

A magnesium-carboxylate framework showing luminescent sensing for CS{sub 2} and nitroaromatic compounds

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Zhao-Feng; Tan, Bin; University of Chinese Academy of Sciences, Beijing 100049

2015-03-15

A magnesium metal-organic framework compound, namely [NH{sub 2}(CH{sub 3}){sub 2}][Mg{sub 3}(NDC){sub 2.5}(HCO{sub 2}){sub 2}(DMF){sub 0.75}(H{sub 2}O){sub 0.25}]·1.25DMF·0.75H{sub 2}O (1) (H{sub 2}NDC=1,4-naphthalene dicarboxylic acid, DMF=N,N′-dimethylformamide), has been synthesized in solvothermal conditions and structurally characterized. It features a three-dimensionally anionic framework with aligned channels parallel to the b-axis. Luminescent studies indicated that it showed significant luminescence quenching for carbon disulfide (CS{sub 2}) and nitrobenzene after being activated, at a content of only 3.0 and 0.1 vol% in DMF, respectively. In addition, the activated sample showed sensitive luminescence quenching for 1,3,5-trinitrophenol with a low concentration of 5×10{sup −5} mol/L. - Graphical abstract: Presentedmore » is a microporous 3D Mg-MOF, namely, [NH{sub 2}(CH{sub 3}){sub 2}][Mg{sub 3}(NDC){sub 2.5}(HCO{sub 2}){sub 2}(DMF){sub 0.75}(H{sub 2}O){sub 0.25}]·1.25DMF·0.75H{sub 2}O (1) (H{sub 2}NDC=1,4-naphthalene dicarboxylic acid) showing significant luminescence quenching for carbon disulfide and nitrobenzene. - Highlights: • A microporous 3D metal-organic framework based on Mg. • The compound shows significant luminescence quenching for CS{sub 2} and nitrobenzene after activated. • The compound shows sensitive luminescence quenching for 1,3,5-trinitrophenol with a low concentration of 5×10{sup −5} mol/L.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hua, Xiu-Ni; Qin, Lan; Yan, Xiao-Zhi

Hydrothermal reactions of N-auxiliary flexible exo-bidentate ligand 1,3-bis(4-pyridyl)propane (bpp) and carboxylates ligands naphthalene-2,6-dicarboxylic acid (2,6-H{sub 2}ndc) or 4,4′-(hydroxymethylene)dibenzoic acid (H{sub 2}hmdb), in the presence of cadmium(II) salts have given rise to two novel metal-organic frameworks based on flexible ligands (FL-MOFs), namely, [Cd{sub 2}(2,6-ndc){sub 2}(bpp)(DMF)]·2DMF (1) and [Cd{sub 3}(hmdb){sub 3}(bpp)]·2DMF·2EtOH (2) (DMF=N,N-Dimethylformamide). Single-crystal X-ray diffraction analyses revealed that compound 1 exhibits a three-dimensional self-penetrating 6-connected framework based on dinuclear cluster second building unit. Compound 2 displays an infinite three-dimensional ‘Lucky Clover’ shape (2,10)-connected network based on the trinuclear cluster and V-shaped organic linkers. The flexible bpp ligand displays different conformations inmore » 1 and 2, which are successfully controlled by size-matching mixed ligands during the self-assembly process. - Graphical abstract: Compound 1 exhibits a 3D self-penetrating 6-connected framework based on dinuclear cluster, and 2 displays an infinite 3D ‘Lucky Clover’ shape (2,10)-connected network based on the trinuclear cluster. The flexible 1,3-bis(4-pyridyl)propane ligand displays different conformations in 1 and 2, which successfully controlled by size-matching mixed ligands during the self-assembly process.« less

The development of a multidisciplinary fall risk evaluation tool for demented nursing home patients in the Netherlands.

PubMed

Neyens, Jacques C L; Dijcks, Béatrice P J; van Haastregt, Jolanda C M; de Witte, Luc P; van den Heuvel, Wim J A; Crebolder, Harry F J M; Schols, Jos M G A

2006-03-21

Demented nursing home patients are at high risk for falls. Falls and associated injuries can have a considerable influence on the autonomy and quality of life of patients. The prevention of falls among demented patients is therefore an important issue. In order to intervene in an efficient way in this group of patients, it is important to systematically evaluate the fall risk profile of each individual patient so that for each patient tailor-made preventive measures can be taken. Therefore, the objective of the present study is to develop a feasible and evidence based multidisciplinary fall risk evaluation tool to be used for tailoring preventive interventions to the needs of individual demented patients. To develop this multidisciplinary fall risk evaluation tool we have chosen to combine scientific evidence on the one hand and experts' opinions on the other hand. Firstly, relevant risk factors for falling in elderly persons were gathered from the literature. Secondly, a group of Dutch experts in the field of falls and fall prevention in the elderly were consulted to judge the suitability of these risk factors for use in a multidisciplinary fall risk evaluation tool for demented nursing home patients. Thirdly, in order to generate a compact list of the most relevant risk factors for falling in demented elderly, all risk factors had to fulfill a set of criteria indicating their relevance for this specific target population. Lastly the final list of risk factors resulting from the above mentioned procedure was presented to the expert group. The members were also asked to give their opinion about the practical use of the tool. The multidisciplinary fall risk evaluation tool we developed includes the following items: previous falls, use of medication, locomotor functions, and (correct) choice and use of assistive and protective devices. The tool is developed for the multidisciplinary teams of the nursing homes. This evidence and practice based multidisciplinary fall risk evaluation tool targets the preventive interventions aimed to prevent falls and their negative consequences in demented nursing home patients.

Cognitive-Behavioral Interventions for Treatment of Depression in Alzheimer's Patients.

ERIC Educational Resources Information Center

Teri, Linda; Gallagher-Thompson, Dolores

1991-01-01

Presents two strategies for treating depression in Alzheimer's patients: cognitive therapy for mildly demented adults which challenges patient's negative cognitions to reduce distortions and enable patient to generate more adaptive ways of viewing specific events; and behavioral intervention for moderately or severely demented adults which…

Striatal and Hippocampal Atrophy in Idiopathic Parkinson's Disease Patients without Dementia: A Morphometric Analysis.

PubMed

Tanner, Jared J; McFarland, Nikolaus R; Price, Catherine C

2017-01-01

Analyses of subcortical gray structure volumes in non-demented idiopathic Parkinson's disease (PD) often, but not always, show volume loss of the putamen, caudate nucleus, nucleus accumbens, and hippocampus. There is building evidence that structure morphometry might be more sensitive to disease-related processes than volume. To assess morphometric differences of subcortical structures (putamen, caudate nucleus, thalamus, globus pallidus, nucleus accumbens, and amygdala) as well as the hippocampus in non-demented individuals with PD relative to age and education matched non-PD peers. Prospective recruitment of idiopathic no-dementia PD and non-PD peers as part of a federally funded investigation. T1-weighted isovoxel metrics acquired via 3-T Siemens Verio for all individuals [PD n  = 72 (left side onset n  = 27, right side onset n  = 45); non-PD n  = 48]. FIRST (FMRIB Software Library) applications provided volumetric and vertex analyses on group differences for structure size and morphometry. Group volume differences were observed only for putamen and hippocampi (PD < non-PD) with hippocampal volume significantly associating with disease duration. Group shape differences were observed for bilateral putamen, caudate nucleus, and hippocampus with greater striatal atrophy contralateral to side of motor symptom onset. Hippocampal shape differences disappeared when removing the effects of volume. The putamen was the primary structure to show both volume and shape differences in PD, indicating that the putamen is the predominant site of basal ganglia atrophy in early- to mid-stage PD. Side of PD symptom onset associates with contralateral striatal atrophy. Left-onset PD might experience more extensive striatal atrophy than right-onset PD. Hippocampus morphometric results suggest possible primary atrophy of CA3/4 and dentate gyrus.

Interference effects on vibration-mediated tunneling through interacting degenerate molecular states.

PubMed

Zhong, X; Cao, J C

2009-07-22

We study the combined effects of quantum electronic interference and Coulomb interaction on electron transport through near-degenerate molecular states with strong electron-vibration interaction. It is found that quantum electronic interference strongly affects the current and its noise properties. In particular, destructive interference induces pronounced negative differential conductances (NDCs) accompanying the vibrational excited states, and such NDC characters are not related to asymmetric tunnel coupling and are robust to the damping of a thermal bath. In a certain transport regime, the non-equilibrium vibration distribution even shows a peculiar sub-Poissonian behavior, which is enhanced by quantum electronic interference.

Treating Families of Demented Patients: Two Group Models.

ERIC Educational Resources Information Center

Kramer, Joel

The prevalence of dementias in the elderly is steadily increasing. While caring for a dementing patient at home, families are subject to tremendous physical stresses and emotional reactions such as guilt, anger, grief, role confusion, depression, resentment, and loneliness. Two group treatment models addressing the mental health needs of…

A Training Program in Breast Cancer Research Using NMR Techniques

DTIC Science & Technology

2005-07-01

to explore the application NMR molecular imaging techniques developed in this program in detection of amyloid plaques in the Alzheimer diseased mouse...one is to utilize the molecular imaging technique to exploit new application in imaging of amyloid plaques in Alzheimer disease. A abridge of each...matched, non-demented elderly suggests that volumetric studies of ante-mortem neuroimages may provide an early marker of AD in aging populations. In

Posterior limb of the internal capsule predicts poor quality of life in patients with Parkinson's disease: connectometry approach.

PubMed

Ghazi Sherbaf, Farzaneh; Mojtahed Zadeh, Mahtab; Haghshomar, Maryam; Aarabi, Mohammad Hadi

2018-03-14

Psychiatric symptoms and motor impairment are major contributions to the poor quality of life in patients with Parkinson's disease (PD). Here, we applied a novel diffusion-weighted imaging approach, diffusion MRI connectometry, to investigate the correlation of quality of life, evaluated by Parkinson's Disease Questionnaire (PDQ39) with the white matter structural connectivity in 27 non-demented PD patients (disease duration of 5.3 ± 2.9 years, H and Y stage = 1.5 ± 0.6, UPDRS-III = 13.7 ± 6.5, indicating unilateral and mild motor involvement). The connectometry analysis demonstrated bilateral posterior limbs of the internal capsule (PLIC) with increased connectivity related to the higher quality of life (FDR = 0.027) in a multiple regression model. The present study suggests for the first time a neural basis of the quality of life in PD in the light of major determinants of poor quality of life in these patients: anxiety, depression, apathy and motor impairment. Results in our sample of non-demented PD patients with relatively mild motor impairment and no apparent sign of depression/anxiety also identify a unique and inexplicable association of the PLIC to the quality of life in PD patients.

Applications of Known Quantitative Techniques for Developing Airborne ASW Crew Performance Criteria,

DTIC Science & Technology

1967-07-01

environmental foot tunnel enable’s accurate tests to be conducted under specifications, controlled conditions, MA Ch I N E ( ‘OMI ’l ’F t T ION SERVICES C...ph~- 51 olo gical nioni tur ing equ ip— cc i dt’ a r t e ’t~ cci C ~~ii ’ ri iue ’nt s can hi’ ~‘onc1ui-ted u ndc r V a t t e s t s nie ’ni ; I

Efficacy and acceptance of professional dental cleaning among nursing home residents.

PubMed

Barbe, Anna Greta; Kottmann, Hannah Elisa; Hamacher, Stefanie; Derman, Sonja Henny Maria; Noack, Michael Johannes

2018-05-13

To determine the impact of general and oral health status of nursing home residents in Germany on efficacy and acceptance of professional dental cleaning performed by a dental nurse. Participants (N = 41; mean age 83 ± 8 years) living in a nursing home were included. Personal and general health, oral health, oral hygiene habits, and needs were investigated. Individual acceptance regarding professional dental cleaning via different devices (scaler, interdental brushes, ultrasonic cleaning) was assessed, as was the efficacy of this method using after-cleaning indices. Oral health among nursing home residents was impaired and independent from dementia status. Most residents (33/41) performed oral hygiene procedures independently and showed better index values than those in need of external help. Residents requiring help with oral hygiene showed increased risk profiles (higher age, more often immobile, demented, more xerostomia). The dental cleaning procedure required a mean time of 37 ± 11 min, was widely accepted (36/41), and achieved clean results (plaque index 0.1 ± 0.5, oral hygiene index 0.2 ± 1.6, Volpe-Manhold index 0.4 ± 1.6); food residues were reduced to 0 independent from cognitive status. Regarding the cleaning methods, scalers were accepted best without difference between demented and non-demented residents. Professional dental cleaning in nursing homes is an accepted and efficacious oral hygiene procedure among nursing home residents. Professional dental cleaning is an efficacious and accepted method as a first step in line with strategies to improve oral health and should be considered in nursing home residents.

Intuition: Two Caregivers' Descriptions of How They Provide Severely Demented Patients with Loving Care.

ERIC Educational Resources Information Center

Hellner, Britt Mari; Norberg, Astrid

1994-01-01

Interviewed two expert caregivers about their experiences of caring for severely demented patients. Ethical reasoning, exemplified by tender descriptions of relatedness to patients, indicated that expert caregivers used sound knowledge combined with imagination, empathy, and intuition to grasp situation, where patient is regarded as person with…

Contrasting Olfaction, Vision, and Audition as Predictors of Cognitive Change and Impairment in Non-Demented Older Adults

PubMed Central

MacDonald, Stuart W.S.; Keller, Connor J.C.; Brewster, Paul W.H.; Dixon, Roger A.

2017-01-01

Objective This study examines the relative utility of a particular class of non-invasive functional biomarkers -- sensory functions -- for detecting those at risk of cognitive decline and impairment. Three central research objectives were examined including whether: (1) olfactory function, vision, and audition exhibited significant longitudinal declines in non-demented older adults, (2) multi-wave change for these sensory function indicators predicted risk of mild cognitive impairment, and (3) change within persons for each sensory measure shared dynamic time-varying associations with within-person change in cognitive functioning. Method A longitudinal sample (n=408) from the Victoria Longitudinal Study was assembled. Three cognitive status subgroups were identified: not impaired cognitively (NIC), single assessment mild cognitive impairment (SA-MCI), and multiple assessment mild cognitive impairment (MA-MCI). Results We tested independent predictive associations, contrasting change in sensory function as predictors of cognitive decline and impairment, utilizing both linear mixed models and logistic regression analysis. Olfaction and, to a lesser extent, vision were identified as the most robust predictors of cognitive status and decline; audition showed little predictive influence. Conclusions These findings underscore the potential utility of deficits in olfactory function, in particular, as an early marker of age- and pathology-related cognitive decline. Functional biomarkers may represent potential candidates for use in the early stages of a multi-step screening approach for detecting those at risk of cognitive impairment, as well as for targeted intervention. PMID:29809033

Evaluation of the Costs of Caring for the Senile Demented Elderly: A Pilot Study.

ERIC Educational Resources Information Center

Hu, Teh-wei; And Others

1986-01-01

Evaluated economic costs for nursing home patients and elderly living in their own homes. Using time records compiled by nurses or family members, the costs incurred annually in caring for a senile demented elderly person at home were estimated to average $11,735, and in a nursing home, $22,458. (Author/BL)

Neuropsychiatric Symptoms in Latino Elders with Dementia or Cognitive Impairment without Dementia and Factors that Modify Their Association with Caregiver Depression

ERIC Educational Resources Information Center

Hinton, Ladson; Haan, Mary; Geller, Sue; Mungas, Dan

2003-01-01

Purpose: The purpose of this study was to determine neuropsychiatric symptom frequency and intensity in demented and cognitively impaired but not demented Latino elderly persons, evaluate whether overall neuropsychiatric symptom intensity is associated with higher levels of caregiver depression, and identify factors that modify the relationship…

[Sensory stimulation: new apparatus for demented men].

PubMed

de Groot, M D; Molenbroek, J F

2001-10-01

In order to study the feasibility of new sensorily stimulating material for elderly demented men, their behaviour was observed while the material was handed over to them. The newly developed materials consisted of five different constructions, i.e. a mirrorbox, a simple hand-operated stroboscope, a spring-operated ball for ringing a bell, two rotating wooden cogwheels, and a box having a sandpaper bottom of different grains causing a tactile contrast. In their verbal and nonverbal responses the demented men showed clear signs of interest in the constructions and the materials. The seven participating men showed much interest in materials made of wood and metal, and in the working of the constructions. The different constructions and materials could be combined into one complete 'snoezelproduct'.

Dynamic localization of Mps1 kinase to kinetochores is essential for accurate spindle microtubule attachment

PubMed Central

Dou, Zhen; Liu, Xing; Wang, Wenwen; Zhu, Tongge; Wang, Xinghui; Xu, Leilei; Abrieu, Ariane; Fu, Chuanhai; Hill, Donald L.; Yao, Xuebiao

2015-01-01

The spindle assembly checkpoint (SAC) is a conserved signaling pathway that monitors faithful chromosome segregation during mitosis. As a core component of SAC, the evolutionarily conserved kinase monopolar spindle 1 (Mps1) has been implicated in regulating chromosome alignment, but the underlying molecular mechanism remains unclear. Our molecular delineation of Mps1 activity in SAC led to discovery of a previously unidentified structural determinant underlying Mps1 function at the kinetochores. Here, we show that Mps1 contains an internal region for kinetochore localization (IRK) adjacent to the tetratricopeptide repeat domain. Importantly, the IRK region determines the kinetochore localization of inactive Mps1, and an accumulation of inactive Mps1 perturbs accurate chromosome alignment and mitotic progression. Mechanistically, the IRK region binds to the nuclear division cycle 80 complex (Ndc80C), and accumulation of inactive Mps1 at the kinetochores prevents a dynamic interaction between Ndc80C and spindle microtubules (MTs), resulting in an aberrant kinetochore attachment. Thus, our results present a previously undefined mechanism by which Mps1 functions in chromosome alignment by orchestrating Ndc80C–MT interactions and highlight the importance of the precise spatiotemporal regulation of Mps1 kinase activity and kinetochore localization in accurate mitotic progression. PMID:26240331

Dynamic localization of Mps1 kinase to kinetochores is essential for accurate spindle microtubule attachment.

PubMed

Dou, Zhen; Liu, Xing; Wang, Wenwen; Zhu, Tongge; Wang, Xinghui; Xu, Leilei; Abrieu, Ariane; Fu, Chuanhai; Hill, Donald L; Yao, Xuebiao

2015-08-18

The spindle assembly checkpoint (SAC) is a conserved signaling pathway that monitors faithful chromosome segregation during mitosis. As a core component of SAC, the evolutionarily conserved kinase monopolar spindle 1 (Mps1) has been implicated in regulating chromosome alignment, but the underlying molecular mechanism remains unclear. Our molecular delineation of Mps1 activity in SAC led to discovery of a previously unidentified structural determinant underlying Mps1 function at the kinetochores. Here, we show that Mps1 contains an internal region for kinetochore localization (IRK) adjacent to the tetratricopeptide repeat domain. Importantly, the IRK region determines the kinetochore localization of inactive Mps1, and an accumulation of inactive Mps1 perturbs accurate chromosome alignment and mitotic progression. Mechanistically, the IRK region binds to the nuclear division cycle 80 complex (Ndc80C), and accumulation of inactive Mps1 at the kinetochores prevents a dynamic interaction between Ndc80C and spindle microtubules (MTs), resulting in an aberrant kinetochore attachment. Thus, our results present a previously undefined mechanism by which Mps1 functions in chromosome alignment by orchestrating Ndc80C-MT interactions and highlight the importance of the precise spatiotemporal regulation of Mps1 kinase activity and kinetochore localization in accurate mitotic progression.

Day-to-Day Variability of Postural Sway and Its Association With Cognitive Function in Older Adults: A Pilot Study

PubMed Central

Leach, Julia M.; Mancini, Martina; Kaye, Jeffrey A.; Hayes, Tamara L.; Horak, Fay B.

2018-01-01

Introduction: Increased variability in motor function has been observed during the initial stages of cognitive decline. However, the natural variability of postural control, as well as its association with cognitive status and decline, remains unknown. The objective of this pilot study was to characterize the day-to-day variability in postural sway in non-demented older adults. We hypothesized that older adults with a lower cognitive status would have higher day-to-day variability in postural sway. Materials and Methods: A Nintendo Wii balance board (WBB) was used to quantify postural sway in the home twice daily for 30 days in 20 non-demented, community-dwelling older adults: once under a single-task condition and once under a dual-task condition (using a daily word search task administered via a Nook tablet). Mean sway distance, velocity, area, centroidal frequency and frequency dispersion were derived from the center of pressure data acquired from the WBB. Results: Linear relationships were observed between the day-to-day variability in postural sway and cognitive status (indexed by cognitive global z-scores). More variability in time-domain postural sway (sway distance and area) and less variability in frequency-domain postural sway (centroidal sway frequency) were associated with a lower cognitive status under both the single- and dual-task conditions. Additionally, lower cognitive performance rates on the daily word search task were related to a lower cognitive status. Discussion: This small pilot study conducted on a short time scale motivates large-scale implementations over more extended time periods. Tracking longitudinal changes in postural sway may further our understanding of early-stage postural decline and its association with cognitive decline and, in turn, may aid in the early detection of dementia during preclinical stages when the utility of disease-modifying therapies would be greatest. PMID:29780319

Modifiable Risk Factors and Brain PET Measures of Amyloid and Tau in Non-Demented Adults with Memory Complaints

PubMed Central

Merrill, David A.; Siddarth, Prabha; Raji, Cyrus A.; Emerson, Natacha D.; Rueda, Florangel; Ercoli, Linda M.; Miller, Karen J.; Lavretsky, Helen; Harris, Laurel M.; Burggren, Alison C.; Bookheimer, Susan Y.; Barrio, Jorge R.; Small, Gary W.

2016-01-01

Objective Exercise and diet impact body composition, but their age-related brain effects are unclear at the molecular imaging level. To address these issues, we determined whether body mass index (BMI), physical activity, and diet relate to brain positron emission tomography (PET) of amyloid plaques and tau tangles using 2-(1-(6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl)ethylidene)malononitrile (FDDNP). Methods Volunteers (n = 44, mean age = 62.6 ± 10.7 years) with subjective memory impairment (n = 24) or mild cognitive impairment (MCI; n = 20) were recruited by soliciting for memory complaints. Levels of physical activity and extent of following a Mediterranean-type diet were self-reported. FDDNP-PET scans assessed plaque/tangle binding in Alzheimer’s disease (AD)-associated regions (frontal, parietal, medial and lateral temporal, posterior cingulate). Mixed models controlling for known covariates examined BMI, physical activity, and diet in relation to FDDNP-PET. Results MCI subjects with above normal BMI (>25) had higher FDDNP-PET binding compared to those with normal BMI (1.11(.03) vs 1.08(.03), ES=1.04, t(35)=3.3, p=.002). Greater physical activity was associated with lower FDDNP-PET binding in MCI subjects (1.07(.03) vs 1.11(.03), ES=1.13, t(35) =−3.1, p=.004) but not in subjects with subjective memory impairment (1.07 (.03) vs 1.07(.03), ES=.02, t(35)=−0.1, p=.9). Healthier diet related to lower FDDNP-PET binding, regardless of cognitive status (1.07(.03) vs 1.09(.02), ES=0.72, t(35)=−2.1, p = .04). Conclusion and Relevance These preliminary findings are consistent with a relationship between risk modifiers and brain plaque/tangle deposition in non-demented individuals and supports maintenance of normal body weight, regular physical activity, and healthy diet adherence to protect the brain during aging. PMID:27421618

A randomized clinical trial to evaluate the effects of rasagiline on depressive symptoms in non-demented Parkinson's disease patients.

PubMed

Barone, P; Santangelo, G; Morgante, L; Onofrj, M; Meco, G; Abbruzzese, G; Bonuccelli, U; Cossu, G; Pezzoli, G; Stanzione, P; Lopiano, L; Antonini, A; Tinazzi, M

2015-08-01

Depressed mood is a common psychiatric problem associated with Parkinson's disease (PD), and studies have suggested a benefit of rasagiline treatment. ACCORDO (see the ) was a 12-week, double-blind, placebo-controlled trial to evaluate the effects of rasagiline 1 mg/day on depressive symptoms and cognition in non-demented PD patients with depressive symptoms. The primary efficacy variable was the change from baseline to week 12 in depressive symptoms measured by the Beck Depression Inventory (BDI-IA) total score. Secondary outcomes included change from baseline to week 12 in cognitive function as assessed by a comprehensive neuropsychological battery; Parkinson's disease quality of life questionnaire (PDQ-39) scores; Apathy Scale scores; and Unified Parkinson's Disease Rating Scale (UPDRS) subscores. One hundred and twenty-three patients were randomized. At week 12 there was no significant difference between groups for the reduction in total BDI-IA score (primary efficacy variable). However, analysis at week 4 did show a significant difference in favour of rasagiline (marginal means difference ± SE: rasagiline -5.46 ± 0.73 vs. placebo -3.22 ± 0.67; P = 0.026). There were no significant differences between groups on any cognitive test. Rasagiline significantly improved UPDRS Parts I (P = 0.03) and II (P = 0.003) scores versus placebo at week 12. Post hoc analyses showed the statistical superiority of rasagiline versus placebo in the UPDRS Part I depression item (P = 0.04) and PDQ-39 mobility (P = 0.007) and cognition domains (P = 0.026). Treatment with rasagiline did not have significant effects versus placebo on depressive symptoms or cognition in PD patients with moderate depressive symptoms. Although limited by lack of correction for multiple comparisons, post hoc analyses signalled some improvement in patient-rated cognitive and depression outcomes. © 2015 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.

A randomized clinical trial to evaluate the effects of rasagiline on depressive symptoms in non-demented Parkinson’s disease patients

PubMed Central

Barone, P; Santangelo, G; Morgante, L; Onofrj, M; Meco, G; Abbruzzese, G; Bonuccelli, U; Cossu, G; Pezzoli, G; Stanzione, P; Lopiano, L; Antonini, A; Tinazzi, M

2015-01-01

Background and purpose Depressed mood is a common psychiatric problem associated with Parkinson’s disease (PD), and studies have suggested a benefit of rasagiline treatment. Methods ACCORDO (see the 1) was a 12-week, double-blind, placebo-controlled trial to evaluate the effects of rasagiline 1 mg/day on depressive symptoms and cognition in non-demented PD patients with depressive symptoms. The primary efficacy variable was the change from baseline to week 12 in depressive symptoms measured by the Beck Depression Inventory (BDI-IA) total score. Secondary outcomes included change from baseline to week 12 in cognitive function as assessed by a comprehensive neuropsychological battery; Parkinson’s disease quality of life questionnaire (PDQ-39) scores; Apathy Scale scores; and Unified Parkinson’s Disease Rating Scale (UPDRS) subscores. Results One hundred and twenty-three patients were randomized. At week 12 there was no significant difference between groups for the reduction in total BDI-IA score (primary efficacy variable). However, analysis at week 4 did show a significant difference in favour of rasagiline (marginal means difference ± SE: rasagiline −5.46 ± 0.73 vs. placebo −3.22 ± 0.67; P = 0.026). There were no significant differences between groups on any cognitive test. Rasagiline significantly improved UPDRS Parts I (P = 0.03) and II (P = 0.003) scores versus placebo at week 12. Post hoc analyses showed the statistical superiority of rasagiline versus placebo in the UPDRS Part I depression item (P = 0.04) and PDQ-39 mobility (P = 0.007) and cognition domains (P = 0.026). Conclusions Treatment with rasagiline did not have significant effects versus placebo on depressive symptoms or cognition in PD patients with moderate depressive symptoms. Although limited by lack of correction for multiple comparisons, post hoc analyses signalled some improvement in patient-rated cognitive and depression outcomes. PMID:25962410

Day-to-Day Variability of Postural Sway and Its Association With Cognitive Function in Older Adults: A Pilot Study.

PubMed

Leach, Julia M; Mancini, Martina; Kaye, Jeffrey A; Hayes, Tamara L; Horak, Fay B

2018-01-01

Introduction : Increased variability in motor function has been observed during the initial stages of cognitive decline. However, the natural variability of postural control, as well as its association with cognitive status and decline, remains unknown. The objective of this pilot study was to characterize the day-to-day variability in postural sway in non-demented older adults. We hypothesized that older adults with a lower cognitive status would have higher day-to-day variability in postural sway. Materials and Methods : A Nintendo Wii balance board (WBB) was used to quantify postural sway in the home twice daily for 30 days in 20 non-demented, community-dwelling older adults: once under a single-task condition and once under a dual-task condition (using a daily word search task administered via a Nook tablet). Mean sway distance, velocity, area, centroidal frequency and frequency dispersion were derived from the center of pressure data acquired from the WBB. Results : Linear relationships were observed between the day-to-day variability in postural sway and cognitive status (indexed by cognitive global z-scores). More variability in time-domain postural sway (sway distance and area) and less variability in frequency-domain postural sway (centroidal sway frequency) were associated with a lower cognitive status under both the single- and dual-task conditions. Additionally, lower cognitive performance rates on the daily word search task were related to a lower cognitive status. Discussion : This small pilot study conducted on a short time scale motivates large-scale implementations over more extended time periods. Tracking longitudinal changes in postural sway may further our understanding of early-stage postural decline and its association with cognitive decline and, in turn, may aid in the early detection of dementia during preclinical stages when the utility of disease-modifying therapies would be greatest.

The effect of encoding condition on free recall in Parkinson's disease: incidental and intentional memory are equally affected.

PubMed

Ellfolk, Ulla; Huurinainen, Salla; Joutsa, Juho; Karrasch, Mira

2012-01-01

Free recall memory deficits are common at early stages of Parkinson's disease (PD). As most studies have used intentional memory tasks, there is little information on how non-intentional, incidental encoding conditions affect memory performance in PD. We studied possible differences between PD patients and controls on free recall using incidental and intentional visual memory tasks. Free recall was examined in relation to attentive/executive functioning and subjective memory complaints. A total of 29 non-demented, medicated PD patients (age 60, disease duration 19 months) and 29 healthy controls (age 61) participated in the study. Incidental free recall was studied using a memory-modification of the Boston naming test (Memo-BNT) and intentional free recall with the 20 Objects test. There was a significant main effect for group due to worse free recall performances in the PD group. No statistically significant interaction between group and encoding condition was observed. The free recall deficit in the PD group was related to cognitive/psychomotor slowing, but not to attentive/executive task demands, or to subjective memory complaints. The results indicate that PD patients are impaired on free recall irrespective of encoding condition.

Signs of impaired selective attention in patients with amyotrophic lateral sclerosis.

PubMed

Pinkhardt, Elmar H; Jürgens, Reinhart; Becker, Wolfgang; Mölle, Matthias; Born, Jan; Ludolph, Albert C; Schreiber, Herbert

2008-04-01

The evidence for involvement of extramotor cortical areas in non-demented patients with amyotrophic lateral sclerosis (ALS) has been provided by recent neuropsychological and functional brain imaging studies. The aim of this study was to investigate possible alterations in selective attention, as an important constituent part of frontal brain function in ALS patients. A classical dichotic listening task paradigm was employed to assess event-related EEG potential (ERPs) indicators of selective attention as well as preattentive processing of mismatch, without interference by motor impairment.A total of 20 patients with sporadic ALS according to the revised El Escorial criteria and 20 healthy controls were studied. Additionally a neuropsychological test battery of frontotemporal functions was applied. Compared with the controls, the ALS patients showed a distinct decrease of the fronto-precentral negative difference wave (Nd), i.e., the main ERP indicator of selective attention. Analysis of the P3 component of the ERPs indicated an increased processing of non-relevant stimuli in ALS patients confirming a reduced focus of attention. We conclude impaired selective attention reflects a subtle variant of frontotemporal dementia frequently observed in ALS patients at a relatively early stage of the disease.

Unraveling the multi-functional behavior in a series of Metal Organic Frameworks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sanda, Suresh; Biswas, Soumava; Parshamoni, Srinivasulu

2015-09-15

Three new 2D/3D Metal-Organic Frameworks (MOFs), ([Zn(2,6-ndc)(aldrithiol)]·3(H{sub 2}O)){sub n} (1), ([Co(2,6-ndc)(aldrithiol)(H{sub 2}O){sub 2}]·2(H{sub 2}O)){sub n} (2), ([Cd{sub 2}(2,6-ndc){sub 2}(aldrithiol){sub 2}(H{sub 2}O){sub 2}]·(aldrithiol)·(EtOH)·3(H{sub 2}O)){sub n} (3), (2,6-ndc = 2,6-naphthalene dicarboxylic acid; aldrithiol = 4,4'-dipyridyl disulphide) have been synthesized and structurally characterized. Compounds 1 and 2 have 2D layered architectures with similar framework topology whereas 3 is a 2-fold interwoven three dimensional framework. Sorption studies reveal that compounds 1-3 selectively adsorbs CO{sub 2} over other gases and H{sub 2}O over other solvents. Proton conductivity study of compounds 1 and 2 show highest values of 6.73 x 10{sup -7} S.cm{sup -1}, 1.96 xmore » 10{sup -5} S.cm{sup -1} at 318 K and 95% RH and these values are humidity dependent. Photoluminescent properties of compounds 1 and 3 show metal perturbed (π*–π and π*-n) intra ligand charge transfer transitions. Additionally, Compound 3 also displays reversible adsorption of molecular iodine. - Graphical abstarct: Three new 2D/3D interpenetrated MOFs are synthesized and their multifunctional material properties such as adsorption, proton conduction, iodine adsorption as well as luminscence have been explored. - Highlights: • We report multifunctional material properties in a series MOFs (Compounds 1-3) • All the compounds show selective adsorption of CO{sub 2} over other gases and H{sub 2}O over other solvents. • The proton conduction property studies of all the compounds reveal the humidity dependent conductivity. • Compound 2 shows reversible adsorption of molecular iodine in the framework. • Photoluminescent properties of compounds 1 and 2 show metal perturbed intra ligand charge transfer transitions.« less

Gait analysis in demented subjects: Interests and perspectives

PubMed Central

Beauchet, Olivier; Allali, Gilles; Berrut, Gilles; Hommet, Caroline; Dubost, Véronique; Assal, Frédéric

2008-01-01

Gait disorders are more prevalent in dementia than in normal aging and are related to the severity of cognitive decline. Dementia-related gait changes (DRGC) mainly include decrease in walking speed provoked by a decrease in stride length and an increase in support phase. More recently, dual-task related changes in gait were found in Alzheimer’s disease (AD) and non-Alzheimer dementia, even at an early stage. An increase in stride-to-stride variability while usual walking and dual-tasking has been shown to be more specific and sensitive than any change in mean value in subjects with dementia. Those data show that DRGC are not only associated to motor disorders but also to problem with central processing of information and highlight that dysfunction of temporal and frontal lobe may in part explain gait impairment among demented subjects. Gait assessment, and more particularly dual-task analysis, is therefore crucial in early diagnosis of dementia and/or related syndromes in the elderly. Moreover, dual-task disturbances could be a specific marker of falling at a pre-dementia stage. PMID:18728766

Reactive sulfur species: kinetics and mechanism of the oxidation of cystine by hypochlorous acid to give N,N'-dichlorocystine.

PubMed

Nagy, Péter; Ashby, Michael T

2005-06-01

Cystine and HOCl (a neutrophil-derived oxidant) react to form an intermediate that has a half-life of ca. 5 min at pH 7.5. The intermediate subsequently decomposes to eventually yield a mixture of cystine, higher oxides of Cys, and other uncharacterized species. Spectral titrations, transitory (1)H NMR and UV-vis spectra, and the reaction properties of the intermediate are consistent with a formulation of N,N'-dichlorocystine {NDC = [-SCH(2)CH(NHCl)(CO(2)H)](2)}. The reaction of equimolar amounts of HOCl with cystine at pH 11.3 does not yield N-chlorocystine [NCC = (-O2C)(H3N+)CHCH(2)SSCH(2)CH(NHCl)(CO(2)H)] but rather a 1:1 mixture of NDC and cystine. This result could be explained by two mechanisms: rapid disproportionation of NCC to produce NDC and cystine or a faster reaction of the second equivalent of HOCl with NCC than the first equivalent of HOCl reacts with cystine. The latter mechanism is favored because of our observation by NMR spectroscopy that NDC decomposes via a species that we have assigned as NCC. Thus, disproportionation of NCC is apparently a relatively slow process. The rates of reaction of cystine(0) = [-SCH(2)CH(NH(3)(+))(CO(2)(-))](2) degrees , cystine(1-) = [((-)O(2)C)(H(2)N)CHCH(2)SSCH(2)CH(NH(3)(+))(CO(2)(-))](-), and cystine(2-) = [-SCH(2)CH(NH2)(CO2)(-))]2(2-) have been investigated, and it is clear that cystine(0) is unreactive, whereas cystine(2-) is about four times more reactive than cystine(1-). Accordingly, the following mechanism is proposed (constants for 5 degrees C): HOCl = H+ + OCl-, pK1 = 7.47; cystine(0) = cystine(1-) + H+, pK2 = 8.15; cystine(1-) = cystine(2-) + H+, pK3 = 9.00; cystine(1-) + HOCl --> NCC(1-) + H2O, k4 = 4.3(2) x 10(6) M(-1) s(-1); cystine(2-) + HOCl --> NCC(2)(-) + H2O, k5 = 1.6(2) x 10(7) M(-1) s(-1); NCC(1-) --> NCC(2-) + H+, k6 = fast; NCC(2-) + HOCl --> NDC(2-) + H2O, k7 = fast. At physiologic pH, the k4 pathway dominates. The generation of long-lived chloramine derivatives of cystine may have physiological consequences, since such compounds are known to react with nucleophiles via mechanisms that are also characteristic of HOCl, electrophilic transfer C+.

US NDC Modernization: Service Oriented Architecture Proof of Concept

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hamlet, Benjamin R.; Encarnacao, Andre Villanova; Jackson, Keilan R.

2014-12-01

This report is a progress update on the US NDC Modernization Service Oriented Architecture (SOA) study describing results from a proof of concept project completed from May through September 2013. Goals for this proof of concept are 1) gain experience configuring, using, and running an Enterprise Service Bus (ESB), 2) understand the implications of wrapping existing software in standardized interfaces for use as web services, and 3) gather performance metrics for a notional seismic event monitoring pipeline implemented using services with various data access and communication patterns. The proof of concept is a follow on to a previous SOA performancemore » study. Work was performed by four undergraduate summer student interns under the guidance of Sandia staff.« less

Effects of Annular Electromagnetic Stirring Coupled with Intercooling on Grain Refinement and Homogeneity During Direct Chill Casting of Large-Sized 7005 Alloy Billet

NASA Astrophysics Data System (ADS)

Luo, Yajun; Zhang, Zhifeng; Li, Bao; Gao, Mingwei; Qiu, Yang; He, Min

2017-12-01

To obtain a large-sized, high-quality aluminum alloy billet, an advanced uniform direct chill (UDC) casting method was developed by combining annular electromagnetic stirring (A-EMS) with intercooling in the sump. The 7005 alloy was chosen to investigate the effect of UDC on grain refinement and homogeneity during normal direct chill (NDC) casting. It was concluded that the microstructure consisting of both primary α-Al phase and secondary phases becomes finer and more homogeneous for the billets prepared with UDC casting compared to those prepared with NDC casting, and the forced cooling from both the inner and outer melt under A-EMS has a measurable effect on grain refinement and homogeneity.

Stable Size Distribution of Amyloid Plaques Over the Course of Alzheimer Disease

PubMed Central

Serrano-Pozo, Alberto; Mielke, Matthew L.; Muzitansky, Alona; Gómez-Isla, Teresa; Growdon, John H.; Bacskai, Brian J.; Betensky, Rebecca A.; Frosch, Matthew P.; Hyman, Bradley T.

2012-01-01

Amyloid-β plaques are a key pathological feature of Alzheimer disease (AD), but whether plaque sizes increase or stabilize over the course of AD is unknown. We measured the size distribution of total immunoreactive (10D5-positive) and dense-core (Thioflavine-S-positive) plaques in the temporal neocortex of a large group of AD and plaque-bearing age-matched non-demented subjects to test the hypothesis that amyloid plaques continue to grow along with the progression of the disease. The size of amyloid-β (10D5)-positive plaques did not differ between groups whereas dense-core plaques from the AD group were slightly larger than those in the non-demented group (~25%–30%, p = 0.01). Within the AD group, dense-core plaque size did not independently correlate with duration of clinical disease (from 4 to 21 years, p = 0.68), whereas 10D5-positive plaque size correlated negatively with disease duration (p = 0.01). By contrast, an earlier age of symptom onset strongly predicted a larger postmortem plaque size; this effect was independent of disease duration and the presence of the APOEε4 allele (p = 0.0001). We conclude that plaques vary in size among patients, with larger size distributions correlating with an earlier age of onset, but plaques do not substantially increase in size over the clinical course of the disease. PMID:22805771

Age-Related Changes of Adaptive and Neuropsychological Features in Persons with Down Syndrome

PubMed Central

Ghezzo, Alessandro; Salvioli, Stefano; Solimando, Maria Caterina; Palmieri, Alice; Chiostergi, Chiara; Scurti, Maria; Lomartire, Laura; Bedetti, Federica; Cocchi, Guido; Follo, Daniela; Pipitone, Emanuela; Rovatti, Paolo; Zamberletti, Jessica; Gomiero, Tiziano; Castellani, Gastone; Franceschi, Claudio

2014-01-01

Down Syndrome (DS) is characterised by premature aging and an accelerated decline of cognitive functions in the vast majority of cases. As the life expectancy of DS persons is rapidly increasing, this decline is becoming a dramatic health problem. The aim of this study was to thoroughly evaluate a group of 67 non-demented persons with DS of different ages (11 to 66 years), from a neuropsychological, neuropsychiatric and psychomotor point of view in order to evaluate in a cross-sectional study the age-related adaptive and neuropsychological features, and to possibly identify early signs predictive of cognitive decline. The main finding of this study is that both neuropsychological functions and adaptive skills are lower in adult DS persons over 40 years old, compared to younger ones. In particular, language and short memory skills, frontal lobe functions, visuo-spatial abilities and adaptive behaviour appear to be the more affected domains. A growing deficit in verbal comprehension, along with social isolation, loss of interest and greater fatigue in daily tasks, are the main features found in older, non demented DS persons evaluated in our study. It is proposed that these signs can be alarm bells for incipient dementia, and that neuro-cognitive rehabilitation and psycho-pharmacological interventions must start as soon as the fourth decade (or even earlier) in DS persons, i.e. at an age where interventions can have the greatest efficacy. PMID:25419980

Multiple SNPs Within and Surrounding the Apolipoprotein E Gene Influence Cerebrospinal Fluid Apolipoprotein E Protein Levels

PubMed Central

Bekris, Lynn M.; Millard, Steven P.; Galloway, Nichole M.; Vuletic, Simona; Albers, John J.; Li, Ge; Galasko, Douglas R.; DeCarli, Charles; Farlow, Martin R.; Clark, Chris M.; Quinn, Joseph F.; Kaye, Jeffrey A.; Schellenberg, Gerard D.; Tsuang, Debby; Peskind, Elaine R.; Yu, Chang-En

2010-01-01

The ε4 allele of the apolipoprotein E gene (APOE) is associated with increased risk and earlier age at onset in late onset Alzheimer’s disease (AD). Other factors, such as expression level of apolipoprotein E protein (apoE), have been postulated to modify the APOE related risk of developing AD. Multiple loci in and outside of APOE are associated with a high risk of AD. The aim of this exploratory hypothesis generating investigation was to determine if some of these loci predict cerebrospinal fluid (CSF) apoE levels in healthy non-demented subjects. CSF apoE levels were measured from healthy non-demented subjects 21–87 years of age (n = 134). Backward regression models were used to evaluate the influence of 21 SNPs, within and surrounding APOE, on CSF apoE levels while taking into account age, gender, APOE ε4 and correlation between SNPs (linkage disequilibrium). APOE ε4 genotype does not predict CSF apoE levels. Three SNPs within the TOMM40 gene, one APOE promoter SNP and two SNPs within distal APOE enhancer elements (ME1 and BCR) predict CSF apoE levels. Further investigation of the genetic influence of these loci on apoE expression levels in the central nervous system is likely to provide new insight into apoE regulation as well as AD pathogenesis. PMID:18430993

A Cold Temperature Evaluation of the Bonding Adhesives Used for the MUST Inflatable Shelters

DTIC Science & Technology

1975-04-01

been known as the US Army Natick Laboratories (NLABS), and the US Army Natick Development Center ( NDC ). AMIN 1W 5Th Whit# WIN~ zD DI• ~kti u...section throughout the test period. The arctic climatic chamber is a closed ci;•uit wind tunnel in which the temperature can be lowered, controlled...and maintained at any level down to -54WC (-65°F). The shelter section was too large to fit in the test section of the tunnel . The shelter had to be

36 CFR 1260.32 - How is the NDC administered?

Code of Federal Regulations, 2012 CFR

2012-07-01

..., Defense, Energy, and Homeland Security, the Attorney General, and the Director of National Intelligence... ADMINISTRATION DECLASSIFICATION DECLASSIFICATION OF NATIONAL SECURITY INFORMATION The National Declassification...

36 CFR 1260.32 - How is the NDC administered?

Code of Federal Regulations, 2014 CFR

2014-07-01

..., Defense, Energy, and Homeland Security, the Attorney General, and the Director of National Intelligence... ADMINISTRATION DECLASSIFICATION DECLASSIFICATION OF NATIONAL SECURITY INFORMATION The National Declassification...

Visuoperceptive region atrophy independent of cognitive status in patients with Parkinson's disease with hallucinations.

PubMed

Goldman, Jennifer G; Stebbins, Glenn T; Dinh, Vy; Bernard, Bryan; Merkitch, Doug; deToledo-Morrell, Leyla; Goetz, Christopher G

2014-03-01

Visual hallucinations are frequent, disabling complications of advanced Parkinson's disease, but their neuroanatomical basis is incompletely understood. Previous structural brain magnetic resonance imaging studies suggest volume loss in the mesial temporal lobe and limbic regions in subjects with Parkinson's disease with visual hallucinations, relative to those without visual hallucinations. However, these studies have not always controlled for the presence of cognitive impairment or dementia, which are common co-morbidities of hallucinations in Parkinson's disease and whose neuroanatomical substrates may involve mesial temporal lobe and limbic regions. Therefore, we used structural magnetic resonance imaging to examine grey matter atrophy patterns associated with visual hallucinations, comparing Parkinson's disease hallucinators to Parkinson's disease non-hallucinators of comparable cognitive function. We studied 50 subjects with Parkinson's disease: 25 classified as current and chronic visual hallucinators and 25 as non-hallucinators, who were matched for cognitive status (demented or non-demented) and age (± 3 years). Subjects underwent (i) clinical evaluations; and (ii) brain MRI scans analysed using whole-brain voxel-based morphometry techniques. Clinically, the Parkinson's disease hallucinators did not differ in their cognitive classification or performance in any of the five assessed cognitive domains, compared with the non-hallucinators. The Parkinson's disease groups also did not differ significantly in age, motor severity, medication use or duration of disease. On imaging analyses, the hallucinators, all of whom experienced visual hallucinations, exhibited grey matter atrophy with significant voxel-wise differences in the cuneus, lingual and fusiform gyri, middle occipital lobe, inferior parietal lobule, and also cingulate, paracentral, and precentral gyri, compared with the non-hallucinators. Grey matter atrophy in the hallucinators occurred predominantly in brain regions responsible for processing visuoperceptual information including the ventral 'what' and dorsal 'where' pathways, which are important in object and facial recognition and identification of spatial locations of objects, respectively. Furthermore, the structural brain changes seen on magnetic resonance imaging occurred independently of cognitive function and age. Our findings suggest that when hallucinators and non-hallucinators are similar in their cognitive performance, the neural networks involving visuoperceptual pathways, rather than the mesial temporal lobe regions, distinctively contribute to the pathophysiology of visual hallucinations and may explain their predominantly visual nature in Parkinson's disease. Identification of distinct structural MRI differences associated with hallucinations in Parkinson's disease may permit earlier detection of at-risk patients and ultimately, development of therapies specifically targeting hallucinations and visuoperceptive functions.

Visuoperceptive region atrophy independent of cognitive status in patients with Parkinson’s disease with hallucinations

PubMed Central

Stebbins, Glenn T.; Dinh, Vy; Bernard, Bryan; Merkitch, Doug; deToledo-Morrell, Leyla; Goetz, Christopher G.

2014-01-01

Visual hallucinations are frequent, disabling complications of advanced Parkinson’s disease, but their neuroanatomical basis is incompletely understood. Previous structural brain magnetic resonance imaging studies suggest volume loss in the mesial temporal lobe and limbic regions in subjects with Parkinson’s disease with visual hallucinations, relative to those without visual hallucinations. However, these studies have not always controlled for the presence of cognitive impairment or dementia, which are common co-morbidities of hallucinations in Parkinson’s disease and whose neuroanatomical substrates may involve mesial temporal lobe and limbic regions. Therefore, we used structural magnetic resonance imaging to examine grey matter atrophy patterns associated with visual hallucinations, comparing Parkinson’s disease hallucinators to Parkinson’s disease non-hallucinators of comparable cognitive function. We studied 50 subjects with Parkinson’s disease: 25 classified as current and chronic visual hallucinators and 25 as non-hallucinators, who were matched for cognitive status (demented or non-demented) and age (±3 years). Subjects underwent (i) clinical evaluations; and (ii) brain MRI scans analysed using whole-brain voxel-based morphometry techniques. Clinically, the Parkinson’s disease hallucinators did not differ in their cognitive classification or performance in any of the five assessed cognitive domains, compared with the non-hallucinators. The Parkinson’s disease groups also did not differ significantly in age, motor severity, medication use or duration of disease. On imaging analyses, the hallucinators, all of whom experienced visual hallucinations, exhibited grey matter atrophy with significant voxel-wise differences in the cuneus, lingual and fusiform gyri, middle occipital lobe, inferior parietal lobule, and also cingulate, paracentral, and precentral gyri, compared with the non-hallucinators. Grey matter atrophy in the hallucinators occurred predominantly in brain regions responsible for processing visuoperceptual information including the ventral ‘what’ and dorsal ‘where’ pathways, which are important in object and facial recognition and identification of spatial locations of objects, respectively. Furthermore, the structural brain changes seen on magnetic resonance imaging occurred independently of cognitive function and age. Our findings suggest that when hallucinators and non-hallucinators are similar in their cognitive performance, the neural networks involving visuoperceptual pathways, rather than the mesial temporal lobe regions, distinctively contribute to the pathophysiology of visual hallucinations and may explain their predominantly visual nature in Parkinson’s disease. Identification of distinct structural MRI differences associated with hallucinations in Parkinson’s disease may permit earlier detection of at-risk patients and ultimately, development of therapies specifically targeting hallucinations and visuoperceptive functions. PMID:24480486

Cognitively-Impaired-Not-Demented Status Moderates the Time-Varying Association between Finger Tapping Inconsistency and Executive Performance.

PubMed

Halliday, Drew W R; Stawski, Robert S; MacDonald, Stuart W S

2017-02-01

Response time inconsistency (RTI) in cognitive performance predicts deleterious health outcomes in late-life; however, RTI estimates are often confounded by additional influences (e.g., individual differences in learning). Finger tapping is a basic sensorimotor measure largely independent of higher-order cognition that may circumvent such confounds of RTI estimates. We examined the within-person coupling of finger-tapping mean and RTI on working memory, and the moderation of these associations by cognitive status. A total of 262 older adults were recruited and classified as controls, cognitively-impaired-not-demented (CIND) unstable or CIND stable. Participants completed finger-tapping and working-memory tasks during multiple weekly assessments, repeated annually for 4 years. Within-person coupling estimates from multilevel models indicated that on occasions when RTI was greater, working-memory response latency was slower for the CIND-stable, but not for the CIND-unstable or control individuals. The finger-tapping task shows potential for minimizing confounds on RTI estimates, and for yielding RTI estimates sensitive to central nervous system function and cognitive status. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The cost of dementia in Denmark: the Odense Study.

PubMed

Kronborg Andersen, C; Søgaard, J; Hansen, E; Kragh-Sørensen, A; Hastrup, L; Andersen, J; Andersen, K; Lolk, A; Nielsen, H; Kragh-Sørensen, P

1999-01-01

In a population-based study of dementia, the cost of care for 245 demented elderly and 490 controls matched by age and gender was estimated. Dementia of Alzheimer's type was diagnosed according to the NINCDS-ADRDA criteria, and vascular dementia and other types of dementia were diagnosed according to the DSM-IIIR criteria. Severity of dementia was determined by the Clinical Dementia Rating scale. The annual cost of medical care, domestic care, home help, nursing home and special equipment for nondemented patients was DKK 22,000 per person while the cost for very mildly, mildly, moderately and severely demented patients was DKK 49,000, DKK 93,000, DKK 138,000 and DKK 206,000, respectively. Except for very mild dementia the cost did not differ between elderly who suffer from Alzheimer's disease and those with other types of dementia. The net cost of dementia is the difference in cost between those with dementia and the matched controls and amounts on average to DKK 77,000 per person per year. However, priority setting cannot be based on the cost of dementia per se, but only on the cost of a specific dementia intervention compared to its health benefit.

Gain in Brain Immunity in the Oldest-Old Differentiates Cognitively Normal from Demented Individuals

PubMed Central

Katsel, Pavel; Tan, Weilun; Haroutunian, Vahram

2009-01-01

Background Recent findings suggest that Alzheimer's disease (AD) neuropathological features (neuritic plaques and NFTs) are not strongly associated with dementia in extreme old (over 90 years of age) and compel a search for neurobiological indices of dementia in this rapidly growing segment of the elderly population. We sought to characterize transcriptional and protein profiles of dementia in the oldest-old. Methods and Findings Gene and protein expression changes relative to non-demented age-matched controls were assessed by two microarray platforms, qPCR and Western blot in different regions of the brains of oldest-old and younger old persons who died at mild or severe stages of dementia. Our results indicate that: i) consistent with recent neuropathological findings, gene expression changes associated with cognitive impairment in oldest-old persons are distinct from those in cognitively impaired youngest-old persons; ii) transcripts affected in young-old subjects with dementia participate in biological pathways related to synaptic function and neurotransmission while transcripts affected in oldest-old subjects with dementia are associated with immune/inflammatory function; iii) upregulation of immune response genes in cognitively intact oldest-old subjects and their subsequent downregulation in dementia suggests a potential protective role of the brain immune-associated system against dementia in the oldest-old; iv) consistent with gene expression profiles, protein expression of several selected genes associated with the inflammatory/immune system in inferior temporal cortex is significantly increased in cognitively intact oldest-old persons relative to cognitively intact young-old persons, but impaired in cognitively compromised oldest-old persons relative to cognitively intact oldest-old controls. Conclusions These results suggest that disruption of the robust immune homeostasis that is characteristic of oldest-old individuals who avoided dementia may be directly associated with dementia in the oldest-old and contrast with the synaptic and neurotransmitter system failures that typify dementia in younger old persons. PMID:19865478

36 CFR § 1260.32 - How is the NDC administered?

Code of Federal Regulations, 2013 CFR

2013-07-01

..., Defense, Energy, and Homeland Security, the Attorney General, and the Director of National Intelligence... ADMINISTRATION DECLASSIFICATION DECLASSIFICATION OF NATIONAL SECURITY INFORMATION The National Declassification...

Effects of multicomponent training of cognitive control on cognitive function and brain activation in older adults.

PubMed

Kim, Hoyoung; Chey, Jeanyung; Lee, Sanghun

2017-11-01

The aim of this study was to investigate the changes in cognitive functions and brain activation after multicomponent training of cognitive control in non-demented older adults, utilizing neuropsychological tests and fMRI. We developed and implemented a computerized Multicomponent Training of Cognitive Control (MTCC), characterized by task variability and adaptive procedures, in order to maximize training effects in cognitive control and transfer to other cognitive domains. Twenty-seven community-dwelling adults, aged 64-77 years, without any history of neurological or psychiatric problems, participated in this study (14 in the training group and 13 in the control group). The MTCC was administered to the participants assigned to the training group for 8 weeks, while those in the control group received no training. Neuropsychological tests and fMRI were administered prior to and after the training. Trained participants showed improvements in cognitive control, recognition memory and general cognitive functioning. Furthermore, the MTCC led to an increased brain activation of the regions adjacent to the baseline cognitive control-related areas in the frontoparietal network. Future studies are necessary to confirm our hypothesis that MTCC improves cognitive functioning of healthy elderly individuals by expanding their frontoparietal network that is involved in cognitive control. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

MOFs for the Sensitive Detection of Ammonia: Deployment of fcu-MOF Thin Films as Effective Chemical Capacitive Sensors.

PubMed

Assen, Ayalew H; Yassine, Omar; Shekhah, Osama; Eddaoudi, Mohamed; Salama, Khaled N

2017-09-22

This work reports on the fabrication and deployment of a select metal-organic framework (MOF) thin film as an advanced chemical capacitive sensor for the sensing/detection of ammonia (NH 3 ) at room temperature. Namely, the MOF thin film sensing layer consists of a rare-earth (RE) MOF (RE-fcu-MOF) deposited on a capacitive interdigitated electrode (IDE). Purposely, the chemically stable naphthalene-based RE-fcu-MOF (NDC-Y-fcu-MOF) was elected and prepared/arranged as a thin film on a prefunctionalized capacitive IDE via the solvothermal growth method. Unlike earlier realizations, the fabricated MOF-based sensor showed a notable detection sensitivity for NH 3 at concentrations down to 1 ppm, with a detection limit appraised to be around 100 ppb (at room temperature) even in the presence of humidity and/or CO 2 . Distinctly, the NDC-Y-fcu-MOF based sensor exhibited the required stability to NH 3 , in contrast to other reported MOFs, and a remarkable detection selectivity toward NH 3 vs CH 4 , NO 2 , H 2 , and C 7 H 8 . The NDC-Y-fcu-MOF based sensor exhibited excellent performance for sensing ammonia for simulated breathing system in the presence of the mixture of carbon dioxide and/or humidity (water vapor), with no major alteration in the detection signal.

[The screen for caregiver burden of demented patients].

PubMed

Lubart, Emily; Segal, Refael; Pankin, Marianna; Madjar, Jack; Leibovitz, Arthur

2009-08-01

Most elderly individuals with dementia live in the community with the assistance of their caregivers, usually their family members. Their strength is essential for continuing home care and avoiding or postponing institutionalization. The screen for caregiver burden (SCB) is a 25 item scale, in use for the evaluation of caregivers of demented persons in the USA. A recent study in the USA showed that answers to 7 of those 25 questions, rapid screen for caregiver burden (RSCB), are sufficiently indicative and may replace and simplify the application of this questionnaire. In this study, the authors translated the SCB into Hebrew and tested it on 94 caregivers of demented elderly patients. The study results suggest that the shortened cluster of 7 items could also be used in Israel and is adequately indicative for the evaluation of the caregiver's burden.

Suicide in Older Adults: The Role of Emotions and Cognition

PubMed Central

Szanto, Katalin; Alexopoulos, George S.

2014-01-01

Suicide in older adults is a significant clinical concern. In this review of recent findings, we concentrate on the role of emotions and cognition in suicide risk and behavior in older adults. We discuss the epidemiology of suicide in older adults, integrate recent findings on non-psychotic major depression, schizophrenia and suicidal ideation, explore the relationship of emotion regulation with suicide, present recent advances on suicide in demented patients, and describe the latest developments on cognition and decision processes in suicide. PMID:25226883

36 CFR 1260.34 - What are the responsibilities of the NDC?

Code of Federal Regulations, 2012 CFR

2012-07-01

... ADMINISTRATION DECLASSIFICATION DECLASSIFICATION OF NATIONAL SECURITY INFORMATION The National Declassification... databases; and (f) Storage, and related services, on a reimbursable basis, for Federal records containing...

36 CFR 1260.34 - What are the responsibilities of the NDC?

Code of Federal Regulations, 2014 CFR

2014-07-01

... ADMINISTRATION DECLASSIFICATION DECLASSIFICATION OF NATIONAL SECURITY INFORMATION The National Declassification... databases; and (f) Storage, and related services, on a reimbursable basis, for Federal records containing...

FERRET-SAND II physics-dosimetry analysis for N Reactor Pressure Tubes 2954, 3053 and 1165 using a WIMS calculated input spectrum

DOE Office of Scientific and Technical Information (OSTI.GOV)

McElroy, W.N.; Kellogg, L.S.; Matsumoto, W.Y.

1988-05-01

This report is in response to a request from Westinghouse Hanford Company (WHC) that the PNL National Dosimetry Center (NDC) perform physics-dosimetry analyses (E > MeV) for N Reactor Pressure Tubes 2954 and 3053. As a result of these analyses, and recommendations for additional studies, two physics-dosimetry re-evaluations for Pressure Tube 1165 were also accomplished. The primary objective of Pacific Northwest Laboratories' (PNL) National Dosimetry Center (NDC) physics-dosimetry work for N Reactor was to provide FERRET-SAND II physics-dosimetry results to assist in the assessment of neutron radiation-induced changes in the physical and mechanical properties of N Reactor pressure tubes. 15more » refs., 6 figs., 5 tabs.« less

Rating counselor-client behavior in online counseling: development and preliminary psychometric properties of the Counseling Progress and Depth Rating Instrument.

PubMed

Bagraith, Karl; Chardon, Lydia; King, Robert John

2010-11-01

Although there are widely accepted and utilized models and frameworks for nondirective counseling (NDC), there is little in the way of tools or instruments designed to assist in determining whether or not a specific episode of counseling is consistent with the stated model or framework. The Counseling Progress and Depth Rating Instrument (CPDRI) was developed to evaluate counselor integrity in the use of Egan's skilled helper model in online counseling. The instrument was found to have sound internal consistency, good interrater reliability, and good face and convergent validity. The CPDRI is, therefore, proposed as a useful tool to facilitate investigation of the degree to which counselors adhere to and apply a widely used approach to NDC.

Visible Virchow-Robin spaces on magnetic resonance imaging of Alzheimer's disease patients and normal elderly from the Sunnybrook Dementia Study.

PubMed

Ramirez, Joel; Berezuk, Courtney; McNeely, Alicia A; Scott, Christopher J M; Gao, Fuqiang; Black, Sandra E

2015-01-01

Visible Virchow-Robin spaces (VRS) are commonly used markers for small vessel disease in aging and dementia. However, as previous reports were based on subjective visual ratings, the goal of this project was to validate and apply an MRI-based quantitative measure of VRS as a potential neuroimaging biomarker. A modified version of Lesion Explorer was applied to MRIs from Alzheimer's disease patients (AD: n = 203) and normal elderly controls (NC: n = 94). Inter-rater reliability, technique validity, group/gender differences, and correlations with other small vessel disease markers were examined (lacunes and white matter hyperintensities, WMH). Inter-rater reliability and spatial congruence was excellent (ICC = 0.99, SI = 0.96), and VRS volumes were highly correlated with established rating scales (CS: ρ = 0.84, p < 0.001; BG: ρ = 0.75, p < 0.001). Compared to NC, AD had significantly greater volumes of WMH (p < 0.01), lacunes (p < 0.001), and VRS in the white matter (p < 0.01), but not in the basal ganglia (n.s.). Compared to women, demented and non-demented men had greater VRS in the white matter (p < 0.001), but not in the basal ganglia (n.s.). Additionally, VRS were correlated with lacunes and WMH, but only in AD (r = 0.3, p < 0.01). Compared to women, men may be more susceptible to greater volumes of VRS, particularly in the white matter. RESULTS support the hypothesis that VRS in the white matter may be more related to AD-related vascular pathology compared to VRS found in the basal ganglia. Future work using this novel VRS segmentation tool will examine its potential utility as an imaging biomarker of vascular rather than parenchymal amyloid.

Early Detection of Alzheimer's Disease Based on the Patient's Creative Drawing Process: First Results with a Novel Neuropsychological Testing Method.

PubMed

Heymann, Petra; Gienger, Regine; Hett, Andreas; Müller, Stephan; Laske, Christoph; Robens, Sibylle; Ostermann, Thomas; Elbing, Ulrich

2018-01-01

Based on the knowledge of art therapy, we developed a new neuropsychological drawing test in order to identify individuals with mild cognitive impairment (MCI) as well as dementia patients and healthy controls (HC). By observing a variety of drawing characteristics of 92 participants with a mean age of 67.7, art therapy and dementia experts discriminate HC from MCI, early dementia of the Alzheimer-type (eDAT), and moderate dementia of the Alzheimer-type (mDAT) by the process analysis of tree drawings on a digitizing tablet. The art therapist's average categorical rating of healthy and MCI or demented individuals matched the clinical diagnosis by 88%. In a first small study, we analyzed interrater reliability, sensitivity, specificity, negative and positive predicted values of our tree drawing test (TDT) in comparison with the clock drawing test (CDT). Similar values of moderate interrater reliability were found for the TDT (0.56) as well as for the CDT (0.54). A significant high sensitivity of 0.9 within this binary impairment scale (HC versus impaired or demented) can be demonstrated. Substantial values for the specificity (0.67) could be obtained that however remain under a perfect value of the CDT (1.0). Considering 31 individuals that received the clinical diagnosis "impaired or demented" the TDT shows a higher recognition rate for the MCI group than the CDT. Furthermore in 8 of 12 borderline cases of clinical diagnosis, the outcome of the TDT diagnosis was consistent with the final clinical result.

36 CFR § 1260.34 - What are the responsibilities of the NDC?

Code of Federal Regulations, 2013 CFR

2013-07-01

... RECORDS ADMINISTRATION DECLASSIFICATION DECLASSIFICATION OF NATIONAL SECURITY INFORMATION The National... databases; and (f) Storage, and related services, on a reimbursable basis, for Federal records containing...

Nicergoline in the treatment of dizziness in elderly patients. A review.

PubMed

Felisati, G; Pignataro, O; Di Girolamo, A; Bruno, E; Alessandrini, M; Guidetti, G; Monzani, D; Beldi, A M; Mira, E; Benazzo, M; Pallestrini, E; Caligo, G; Casani, A; Battaglia, A

2004-01-01

In elderly patients, dizziness occurs very frequently with significant effects on the patient's life. Its frequency increases with age, and may arise from a variety of causes. Chronic dysequilibrium in elderly patients is most probably related to disturbances within the central nervous system, due either to altered neuronal functions or to an underlying vascular disease. Nicergoline, a drug used in the treatment of cognitive disturbances in geriatric patients, improves dizziness in elderly demented and non-demented patients. In a double blind,placebo controlled trial the drug improved (i) the severity of symptoms, measured by the dizziness assessment rating scale (DARS), (ii) the overall clinical conditions revealed by global impression scale, and (iii) the perceived quality of life estimated by the dizziness handicap inventory (DHI). These results indicate a possible positive effect also on posturographic measures. Moreover, the improvement occurred at no expense of the established strategy of postural control suggesting that the effect is mediated by a substitute compensatory mechanism allowing the patient to preserve consolidated postural strategies. The results of previous open clinical studies in about 3000 patients are in agreement with those findings. Overall, severity of symptoms decreased by 68 % (57 % in the control study). Globally, the results indicate a beneficial effect of nicergoline on symptoms related to balance disorders of central origin. Animal studies show that the drug displays a broad spectrum of actions on cellular and molecular mechanisms. Moreover, animal research specifically aimed at vestibular pathophysiology has revealed that nicergoline improves vestibular compensation in models of vestibular lesion. Chronic treatment with nicergoline improved the time-course of behavioral recovery in old rats after hemi-labyrinthectomy and counteracted the regulation of cholinergic receptors observed after lesion in old rats. Nicergoline interacts at several levels by various mechanisms, from the molecular level to cognitive function, probably enhancing spontaneous plasticity phenomena underlying the central vestibular compensation. This effect is not dependent from the interaction with a single-transmitter-identified neural pathway, but from anatomical, functional and neurochemical synergistic adjustments in several brain areas.

Disremembering the holocaust.

PubMed

Kannai, Ruth

2012-11-01

The essay describes an elderly Holocaust survivor, who re-experiences the horrors of the Holocaust through his senile hallucinations. Although he is demented, telling and re-telling the story to a therapist helps him regain a sense of control and feel less frightened. He is finally able to revise the nightmarish story into a narrative that enables him to find strength and meaning. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Cognitive and Neural Bases of Skilled Performance.

DTIC Science & Technology

1987-10-04

advantage is that this method is not computationally demanding, and model -specific analyses such as high -precision source localization with realistic...and a two- < " high -threshold model satisfy theoretical and pragmatic independence. Discrimination and bias measures from these two models comparing...recognition memory of patients with dementing diseases, amnesics, and normal controls. We found the two- high -threshold model to be more sensitive Lloyd

'Yes' ifs, ands or buts: examining performance and correlates of the repetition task in the mini-mental state examination.

PubMed

Werner, P; Heinik, J; Lin, R; Bleich, A

1999-09-01

The aim of this study was to examine whether the type of sentence used in the repetition task included in the Mini-Mental State Examination (MMSE) affected performance in a group of 79 demented and 19 non-demented Hebrew-speaking elderly persons. The cognitive functioning of the participants was assessed using the MMSE and CAMCOG examinations. The performance of the repetition task was evaluated by using three sentences: the literal translation of the English language expression used in the original MMSE; a well-known Hebrew proverb consisting of monosyllabic words and rhythmic effects; and another well-known Hebrew proverb without such attributes. Only a third of the participants successfully repeated the literally translated expression. It showed low predictive value and was highly affected by education. The well-known Hebrew monosyllabic proverb showed moderate predictive value but no discriminatory ability. The other well-known Hebrew proverb performed the best. The translation of the repetition task in the MMSE to other languages is problematic. Strict adherence to the original language proved to be the least desirable choice. Copyright 1999 John Wiley & Sons, Ltd.

Apathy, Novelty Processing, and the P3 Potential in Parkinson’s Disease

PubMed Central

Kaufman, David A. S.; Bowers, Dawn; Okun, Michael S.; Van Patten, Ryan; Perlstein, William M.

2016-01-01

Parkinson’s disease (PD) is characterized by deficits in goal-directed behavior as well as mood and motivational symptoms, including apathy, depression, and anxiety. The present study investigated novelty processing in PD, using event-related potentials (ERPs) to characterize electrophysiological reflections of visual novelty processing. Since apathy has been associated with decreased novelty processing (P3 potentials) in highly apathetic PD patients, we were particularly interested to see if this relationship exists in a sample of PD patients with heterogeneous levels of apathy. Non-demented patients with PD receiving dopaminergic treatment (n = 14) and healthy control participants (n = 12) completed a three-stimulus oddball task while EEG was recorded. Relative to controls, the PD patients exhibited reductions in centrofrontally distributed P3 potentials when viewing novel distracters during this task. Distracter-related P3 amplitudes evoked by novel distracters were strongly associated with apathy symptoms, even after controlling for the effects of depression, anxiety, and executive function. Executive dysfunction was also predictive of novelty-related P3 processing, yet this relationship was independent from that of apathy. These findings suggest that the brain’s electrophysiological response to novelty is closely related to both motivational and cognitive symptoms in PD, even for patients whose apathy symptoms are not excessive. These results have significant implications for our understanding of non-motor symptoms in this clinical population. PMID:27445962

The mini-cog: a cognitive 'vital signs' measure for dementia screening in multi-lingual elderly.

PubMed

Borson, S; Scanlan, J; Brush, M; Vitaliano, P; Dokmak, A

2000-11-01

The Mini-Cog, a composite of three-item recall and clock drawing, was developed as a brief test for discriminating demented from non-demented persons in a community sample of culturally, linguistically, and educationally heterogeneous older adults. All 129 who met criteria for probable dementia based on informant interviews and 120 with no history of cognitive decline were included; 124 were non-English speakers. Sensitivity, specificity, and diagnostic value of the Mini-Cog were compared with those of the Mini-Mental State Exam (MMSE) and Cognitive Abilities Screening Instrument (CASI). The Mini-Cog had the highest sensitivity (99%) and correctly classified the greatest percentage (96%) of subjects. Moreover, its diagnostic value was not influenced by education or language, while that of the CASI was adversely influenced by low education, and both education and language compromised the diagnostic value of the MMSE. Administration time for the Mini-Cog was 3 minutes vs 7 minutes for the MMSE. The Mini-Cog required minimal language interpretation and training to administer, and no test forms of scoring modifications were needed to compensate for the extensive linguistic and educational heterogeneity of the sample. Validation in clinical and population-based samples is warranted, as its brevity and ease of administration suggest that the Mini-Cog might be readily incorporated into general practice and senior care settings as a routine 'cognitive vital signs' measure. Copyright 2000 John Wiley & Sons, Ltd.

Symptom Dimensions of Depression and Apathy and Their Relationship With Cognition in Parkinson's Disease.

PubMed

Szymkowicz, Sarah M; Dotson, Vonetta M; Jones, Jacob D; Okun, Michael S; Bowers, Dawn

2018-03-01

Both depression and apathy, alone and in combination, have been shown to negatively affect cognition in patients with Parkinson's disease (PD). However, the influence of specific symptom dimensions of depression and apathy on cognition is not well understood. The current study investigated the relationship between symptom dimensions of depression and apathy, based on factors identified in Kirsch-Darrow et al. (2011), and memory and executive function in PD. A sample of 138 non-demented individuals with PD (mean age=64.51±7.43 years) underwent neuropsychological testing and completed the Beck Depression Inventory, 2nd Edition, and Apathy Scale. Separate hierarchical regression models examined the relationship between symptom dimensions of depression and apathy ("pure" depressive symptoms, "pure" apathy, loss of interest/pleasure [anhedonia], and somatic symptoms) and three cognitive domain composites: immediate verbal memory, delayed verbal memory, and executive function. After adjusting for general cognitive status and the influence of the other symptom dimensions, "pure" depressive symptoms were negatively associated with the delayed verbal memory composite (p<.034) and somatic symptoms were positively associated with the executive function composite (p<.026). No symptom dimensions were significantly related to the immediate verbal memory composite. Findings suggest that specific mood symptoms are associated with delayed verbal memory and executive function performance in non-demented patients with PD. Further research is needed to better understand possible mechanisms through which specific symptom dimensions of depression and apathy are associated with cognition in PD. (JINS, 2018, 24, 269-282).

A longitudinal study of brain atrophy over two years in community-dwelling older individuals.

PubMed

Jiang, Jiyang; Sachdev, Perminder; Lipnicki, Darren M; Zhang, Haobo; Liu, Tao; Zhu, Wanlin; Suo, Chao; Zhuang, Lin; Crawford, John; Reppermund, Simone; Trollor, Julian; Brodaty, Henry; Wen, Wei

2014-02-01

Most previous neuroimaging studies of age-related brain structural changes in older individuals have been cross-sectional and/or restricted to clinical samples. The present study of 345 community-dwelling non-demented individuals aged 70-90years aimed to examine age-related brain volumetric changes over two years. T1-weighted magnetic resonance imaging scans were obtained at baseline and at 2-year follow-up and analyzed using the FMRIB Software Library and FreeSurfer to investigate cortical thickness and shape and volumetric changes of subcortical structures. The results showed significant atrophy across much of the cerebral cortex with bilateral transverse temporal regions shrinking the fastest. Atrophy was also found in a number of subcortical structures, including the CA1 and subiculum subfields of the hippocampus. In some regions, such as left and right entorhinal cortices, right hippocampus and right precentral area, the rate of atrophy increased with age. Our analysis also showed that rostral middle frontal regions were thicker bilaterally in older participants, which may indicate its ability to compensate for medial temporal lobe atrophy. Compared to men, women had thicker cortical regions but greater rates of cortical atrophy. Women also had smaller subcortical structures. A longer period of education was associated with greater thickness in a number of cortical regions. Our results suggest a pattern of brain atrophy with non-demented people that resembles a less extreme form of the changes associated with Alzheimer's disease (AD). © 2013 Elsevier Inc. All rights reserved.

Decline in cerebral glucose utilisation and cognitive function with aging in Down's syndrome.

PubMed Central

Schapiro, M B; Haxby, J V; Grady, C L; Duara, R; Schlageter, N L; White, B; Moore, A; Sundaram, M; Larson, S M; Rapoport, S I

1987-01-01

The cerebral metabolic rate for glucose (CMRglc) was measured with positron emission tomography and [18F]2-fluoro-2-deoxy-D-glucose in 14 healthy subjects with Down's syndrome, 19 to 33 years old, and in six healthy Down's syndrome subjects over 35 years, two of whom were demented. Dementia was diagnosed from a history of mental deterioration, disorientation and hallucinations. All Down's syndrome subjects were trisomy 21 karyotype. CMRglc also was examined in 15 healthy men aged 20-35 years and in 20 healthy men aged 45-64 years. All subjects were at rest with eyes covered and ears plugged. Mean hemispheric CMRglc in the older Down's syndrome subjects was significantly less, by 23%, than in the young Down's syndrome group; statistically significant decreases in regional metabolism (rCMRglc) also were present in all lobar regions. Comparison of the younger control group with the older control group showed no difference in CMRglc or any rCMRglc (p greater than 0.05). Assessment of language, visuospatial ability, attention and memory showed significant reductions in test scores of the old as compared with the young Down's syndrome subjects. These results show that significant age differences in CMRglc and rCMRglc occur in Down's syndrome but not in healthy controls, and that, although only some older Down's syndrome subjects are demented, significant age reductions in neuropsychologic variables occur in all of them. PMID:2956363

Perceptual, Cognitive, and Personality Rigidity in Parkinson’s Disease

PubMed Central

Díaz-Santos, Mirella; Cao, Bo; Yazdanbakhsh, Arash; Norton, Daniel J.; Neargarder, Sandy; Cronin-Golomb, Alice

2015-01-01

Parkinson’s disease (PD) is associated with motor and non-motor rigidity symptoms (e.g., cognitive and personality). The question is raised as to whether rigidity in PD also extends to perception, and if so, whether perceptual, cognitive, and personality rigidities are correlated. Bistable stimuli were presented to 28 non-demented individuals with PD and 26 normal control adults (NC). Necker cube perception and binocular rivalry were examined during passive viewing, and the Necker cube was additionally used for two volitional-control conditions: Hold one percept in front, and Switch between the two percepts. Relative to passive viewing, PD were significantly less able than NC to reduce dominance durations in the Switch condition, indicating perceptual rigidity. Tests of cognitive flexibility and a personality questionnaire were administered to explore the association with perceptual rigidity. Cognitive flexibility was not correlated with perceptual rigidity for either group. Personality (novelty seeking) correlated with dominance durations on Necker passive viewing for PD but not NC. The results indicate the presence in mild-moderate PD of perceptual rigidity and suggest shared neural substrates with novelty seeking, but functional divergence from those supporting cognitive flexibility. The possibility is raised that perceptual rigidity may be a harbinger of cognitive inflexibility later in the disease course. PMID:25640973

32 CFR 2001.32 - Declassification guides.

Code of Federal Regulations, 2010 CFR

2010-07-01

... agency head or the designated senior agency official; (2) Provide the date of issuance or last review; (3... guides or detailed declassification guidance shall be submitted to the Director of the NDC in accordance...

A Family of Uranyl Coordination Polymers Containing O-Donor Dicarboxylates and Trispyridyltriazine Guests

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thangavelu, Sonia G.; Cahill, Christopher L.

Four uranyl coordination polymers [UO2(C6H8O4)(H2O)2](C18H12N6)2 (1), [UO2(C8H4O4)(H2O)2](C18H12N6)2 (2), Na[(UO2)(C12H6O4)2](C18H13N6)·H2O (3), and Na[(UO2)(C16H8O4)(C6H3NO2)](C18H12N6)·H2O (4) containing aliphatic (adipic acid) or aromatic linkers (1,4-benzene dicarboxylic acid (BDC), 1,4-napthalene dicarboxylic acid (NDC), anthracene 9,10-dicarboxylic acid (ADC)) were synthesized and characterized using single crystal X-ray diffraction, powder X-ray diffraction, and luminescence spectroscopy. The π-stacking distances or the number of π–π interactions present between trispyridyltriazine (TPTZ) guests or the host framework in 1–4 may be affected by the size of the O-donor linker (adipic acid < BDC < NDC < ADC). Luminescence studies show that substitution between adipic acid and BDC influences the emission of 1more » and 2, in which the emission of 1 shows a red shift relative to that of 2. Uranyl emission was not observed in 3 and 4, and may be attributed to the position of the NDC and ADC triplet state relative to the emissive uranyl species.« less

A Family of Uranyl Coordination Polymers Containing O-Donor Dicarboxylates and Trispyridyltriazine Guests

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thangavelu, Sonia G.; Cahill, Christopher L.

2016-01-06

Four uranyl coordination polymers [UO2(C6H8O4)(H2O)2](C18H12N6)2 (1), [UO2(C8H4O4)(H2O)2](C18H12N6)2 (2), Na[(UO2)(C12H6O4)2](C18H13N6)·H2O (3), and Na[(UO2)(C16H8O4)(C6H3NO2)](C18H12N6)·H2O (4) containing aliphatic (adipic acid) or aromatic linkers (1,4-benzene dicarboxylic acid (BDC), 1,4-napthalene dicarboxylic acid (NDC), anthracene 9,10-dicarboxylic acid (ADC)) were synthesized and characterized using single crystal X-ray diffraction, powder X-ray diffraction, and luminescence spectroscopy. The π-stacking distances or the number of π–π interactions present between trispyridyltriazine (TPTZ) guests or the host framework in 1–4 may be affected by the size of the O-donor linker (adipic acid < BDC < NDC < ADC). Luminescence studies show that substitution between adipic acid and BDC influences the emission of 1more » and 2, in which the emission of 1 shows a red shift relative to that of 2. Uranyl emission was not observed in 3 and 4, and may be attributed to the position of the NDC and ADC triplet state relative to the emissive uranyl species.« less

Changes in Brain Volume and Cognition in a Randomized Trial of Exercise and Social Interaction in a Community-Based Sample of Non-Demented Chinese Elders

PubMed Central

Mortimer, James A.; Ding, Ding; Borenstein, Amy R.; DeCarli, Charles; Guo, Qihao; Wu, Yougui; Zhao, Qianhua; Chu, Shugang

2013-01-01

Physical exercise has been shown to increase brain volume and improve cognition in randomized trials of non-demented elderly. Although greater social engagement was found to reduce dementia risk in observational studies, randomized trials of social interventions have not been reported. A representative sample of 120 elderly from Shanghai, China was randomized to four groups (Tai Chi, Walking, Social Interaction, No Intervention) for 40 weeks. Two MRIs were obtained, one before the intervention period, the other after. A neuropsychological battery was administered at baseline, 20 weeks, and 40 weeks. Comparison of changes in brain volumes in intervention groups with the No Intervention group were assessed by t-tests. Time-intervention group interactions for neuropsychological measures were evaluated with repeated-measures mixed models. Compared to the No Intervention group, significant increases in brain volume were seen in the Tai Chi and Social Intervention groups (p < 0.05). Improvements also were observed in several neuropsychological measures in the Tai Chi group, including the Mattis Dementia Rating Scale score (p = 0.004), the Trailmaking Test A (p = 0.002) and B (p = 0.0002), the Auditory Verbal Learning Test (p = 0.009), and verbal fluency for animals (p = 0.01). The Social Interaction group showed improvement on some, but fewer neuropsychological indices. No differences were observed between the Walking and No Intervention groups. The findings differ from previous clinical trials in showing increases in brain volume and improvements in cognition with a largely non-aerobic exercise (Tai Chi). In addition, intellectual stimulation through social interaction was associated with increases in brain volume as well as with some cognitive improvements. PMID:22451320

Changes in brain volume and cognition in a randomized trial of exercise and social interaction in a community-based sample of non-demented Chinese elders.

PubMed

Mortimer, James A; Ding, Ding; Borenstein, Amy R; DeCarli, Charles; Guo, Qihao; Wu, Yougui; Zhao, Qianhua; Chu, Shugang

2012-01-01

Physical exercise has been shown to increase brain volume and improve cognition in randomized trials of non-demented elderly. Although greater social engagement was found to reduce dementia risk in observational studies, randomized trials of social interventions have not been reported. A representative sample of 120 elderly from Shanghai, China was randomized to four groups (Tai Chi, Walking, Social Interaction, No Intervention) for 40 weeks. Two MRIs were obtained, one before the intervention period, the other after. A neuropsychological battery was administered at baseline, 20 weeks, and 40 weeks. Comparison of changes in brain volumes in intervention groups with the No Intervention group were assessed by t-tests. Time-intervention group interactions for neuropsychological measures were evaluated with repeated-measures mixed models. Compared to the No Intervention group, significant increases in brain volume were seen in the Tai Chi and Social Intervention groups (p < 0.05). Improvements also were observed in several neuropsychological measures in the Tai Chi group, including the Mattis Dementia Rating Scale score (p = 0.004), the Trailmaking Test A (p = 0.002) and B (p = 0.0002), the Auditory Verbal Learning Test (p = 0.009), and verbal fluency for animals (p = 0.01). The Social Interaction group showed improvement on some, but fewer neuropsychological indices. No differences were observed between the Walking and No Intervention groups. The findings differ from previous clinical trials in showing increases in brain volume and improvements in cognition with a largely non-aerobic exercise (Tai Chi). In addition, intellectual stimulation through social interaction was associated with increases in brain volume as well as with some cognitive improvements.

42 CFR 423.2315 - Medicare Coverage Gap Discount Program Agreement.

Code of Federal Regulations, 2013 CFR

2013-10-01

...) Maintain up-to-date NDC listings with the electronic database vendors for which the manufacturer provides... under this subpart must comply with the requirements imposed by CMS or the third party administrator (as...

42 CFR 423.2315 - Medicare Coverage Gap Discount Program Agreement.

Code of Federal Regulations, 2012 CFR

2012-10-01

...) Maintain up-to-date NDC listings with the electronic database vendors for which the manufacturer provides... under this subpart must comply with the requirements imposed by CMS or the third party administrator (as...

42 CFR 423.2315 - Medicare Coverage Gap Discount Program Agreement.

Code of Federal Regulations, 2014 CFR

2014-10-01

...) Maintain up-to-date NDC listings with the electronic database vendors for which the manufacturer provides... under this subpart must comply with the requirements imposed by CMS or the third party administrator (as...

Nondestructive Characterization Techniques Used for Ceramic Matrix Composite Life Determination

NASA Technical Reports Server (NTRS)

Effinger, Michael; Koenig, John; Ellingson, Bill; Spohnholtz, Todd

2000-01-01

Recent results indicate that the specific damping capacity and resonant frequency measurements taken periodically during a component's lifetime is able to quantify the mechanical fatigue of CMCS. This gives hope for the potential of determining the actual and residual life of CMC materials using a combination of nondestructive techniques. If successful, then this new paradigm for life prediction of CMCs could revolutionize the approach for designing and servicing CMC components, thereby significantly reducing costs for design, development, health monitoring, and maintenance of CMC components and systems. The Nondestructive Characterization (NDC) life prediction approach would complement life prediction using micromechanics and continuum finite element models. This paper reports on the initial concept of NDC life prediction, a review of the C/SiC blisk damping data, and how changes in the specific damping capacity & ultrasonic elastic modulus data have established the concept as a possibility.

Concept for Determining the Life of Ceramic Matrix Composites Using Nondestructive Characterization Techniques

NASA Technical Reports Server (NTRS)

Effinger, Michael; Ellingson, Bill; Spohnholtz, Todd; Koenig, John

2000-01-01

Damping measurements have been taken on ceramic matrix composite (CMC) turbopump blisks in the as fabricated, post proof testing, and post turbopump testing conditions. These results indicate that damping is able to quantify fatigue of the CMC blisk. This gives hope for the potential of determining the actual and residual life of CMC materials using a combination of nondestructive techniques. If successful, then this new paradigm for life prediction of CMCs could revolutionize the approach for designing and servicing CMC components, thereby significantly reducing costs for design, development, health monitoring, and maintenance of CMC components and systems. The Nondestructive Characterization (NDC) life prediction approach would complement life prediction using micromechanics and continuum finite element models. This paper reports on the initial concept of NDC life prediction and how changes in damping and ultrasonic elastic modulus data have established the concept as a possibility.

Validity of the Cambridge Cognitive Examination-Revised new Executive Function Scores in the diagnosis of dementia: some early findings.

PubMed

Heinik, Jeremia; Solomesh, Isaac

2007-03-01

The Cambridge Cognitive Examination-Revised introduces 2 new executive items (Ideational Fluency and Visual Reasoning), which separately or combined with 2 executive items in the former version (word list generation and similarities) might constitute an Executive Function Score (EFS). The authors studied the validity of these new EFSs in 51 demented (dementia of the Alzheimer's type, vascular dementia) and nondemented individuals (depressives and normals). The new EFSs were found valid to accurately differentiate between demented and nondemented subjects; however, they were considerably less so when specific diagnoses were considered. Correlations between the variously combined executive scores and the cognitive scales and subscales studied were prevalently low to moderate, and ranged from high and significant to low and nonsignificant when the 4 executive items were correlated to each other. The ability of the executive scores to discriminate demented from nondemented individuals was lower compared with the Cambridge Cognitive Examination-Revised scores. EFS was found internally consistent.

GENETIC INFLUENCE OF APOE4 GENOTYPE ON HIPPOCAMPAL MORPHOMETRY - AN N=725 SURFACE-BASED ADNI STUDY

PubMed Central

Shi, Jie; Leporé, Natasha; Gutman, Boris A.; Thompson, Paul M.; Baxter, Leslie C.; Caselli, Richard L.; Wang, Yalin

2014-01-01

The apolipoprotein E (APOE) e4 allele is the most prevalent genetic risk factor for Alzheimer’s disease (AD). Hippocampal volumes are generally smaller in AD patients carrying the e4 allele compared to e4 non-carriers. Here we examined the effect of APOE e4 on hippocampal morphometry in a large imaging database – the Alzheimer’s Disease Neuroimaging Initiative (ADNI). We automatically segmented and constructed hippocampal surfaces from the baseline MR images of 725 subjects with known APOE genotype information including 167 with AD, 354 with mild cognitive impairment (MCI), and 204 normal controls. High-order correspondences between hippocampal surfaces were enforced across subjects with a novel inverse consistent surface fluid registration method. Multivariate statistics consisting of multivariate tensor-based morphometry (mTBM) and radial distance were computed for surface deformation analysis. Using Hotelling’s T2 test, we found significant morphological deformation in APOE e4 carriers relative to non-carriers in the entire cohort as well as in the non-demented (pooled MCI and control) subjects, affecting the left hippocampus more than the right, and this effect was more pronounced in e4 homozygotes than heterozygotes. Our findings are consistent with previous studies that showed e4 carriers exhibit accelerated hippocampal atrophy; we extend these findings to a novel measure of hippocampal morphometry. Hippocampal morphometry has significant potential as an imaging biomarker of early stage AD. PMID:24453132

Use of Archived Information by the United States National Data Center

NASA Astrophysics Data System (ADS)

Junek, W. N.; Pope, B. M.; Roman-Nieves, J. I.; VanDeMark, T. F.; Ichinose, G. A.; Poffenberger, A.; Woods, M. T.

2012-12-01

The United States National Data Center (US NDC) is responsible for monitoring international compliance to nuclear test ban treaties, acquiring data and data products from the International Data Center (IDC), and distributing data according to established policy. The archive of automated and reviewed event solutions residing at the US NDC is a valuable resource for assessing and improving the performance of signal detection, event formation, location, and discrimination algorithms. Numerous research initiatives are currently underway that are focused on optimizing these processes using historic waveform data and alphanumeric information. Identification of optimum station processing parameters is routinely performed through the analysis of archived waveform data. Station specific detector tuning studies produce and compare receiver operating characteristics for multiple detector configurations (e.g., detector type, filter passband) to identify an optimum set of processing parameters with an acceptable false alarm rate. Large aftershock sequences can inundate automated phase association algorithms with numerous detections that are closely spaced in time, which increases the number of false and/or mixed associations in automated event solutions and increases analyst burden. Archived waveform data and alphanumeric information are being exploited to develop an aftershock processor that will construct association templates to assist the Global Association (GA) application, reduce the number of false and merged phase associations, and lessen analyst burden. Statistical models are being developed and evaluated for potential use by the GA application for identifying and rejecting unlikely preliminary event solutions. Other uses of archived data at the US NDC include: improved event locations using empirical travel time corrections and discrimination via a statistical framework known as the event classification matrix (ECM).

Degradation analysis of anode-supported intermediate temperature-solid oxide fuel cells under various failure modes

NASA Astrophysics Data System (ADS)

Lee, Tae-Hee; Park, Ka-Young; Kim, Ji-Tae; Seo, Yongho; Kim, Ki Buem; Song, Sun-Ju; Park, Byoungnam; Park, Jun-Young

2015-02-01

This study focuses on mechanisms and symptoms of several simulated failure modes, which may have significant influences on the long-term durability and operational stability of intermediate temperature-solid oxide fuel cells (IT-SOFCs), including fuel/oxidation starvation by breakdown of fuel/air supply components and wet and dry cycling atmospheres. Anode-supported IT-SOFCs consisting of a Ba0.5Sr0.5Co0.8Fe0.2O3-δ (BSCF)-Nd0.1Ce0.9O2-δ (NDC) composite cathode with an NDC electrolyte on a Ni-NDC anode substrate are fabricated via dry-pressings followed by the co-firing method. Comprehensive and systematic research based on the failure mode and effect analysis (FMEA) of anode-supported IT-SOFCs is conducted using various electrochemical and physiochemical analysis techniques to extend our understanding of the major mechanisms of performance deterioration under SOFC operating conditions. The fuel-starvation condition in the fuel-pump failure mode causes irreversible mechanical degradation of the electrolyte and cathode interface by the dimensional expansion of the anode support due to the oxidation of Ni metal to NiO. In contrast, the BSCF cathode shows poor stability under wet and dry cycling modes of cathode air due to the strong electroactivity of SrO with H2O. On the other hand, the air-depletion phenomena under air-pump failure mode results in the recovery of cell performance during the long-term operation without the visible microstructural transformation through the reduction of anode overvoltage.

Blockade of N-methyl-d-aspartate receptor activation suppresses learning-induced synaptic elimination

PubMed Central

Bock, Jörg; Braun, Katharina

1999-01-01

Auditory filial imprinting in the domestic chicken is accompanied by a dramatic loss of spine synapses in two higher associative forebrain areas, the mediorostral neostriatum/hyperstriatum ventrale (MNH) and the dorsocaudal neostriatum (Ndc). The cellular mechanisms that underlie this learning-induced synaptic reorganization are unclear. We found that local pharmacological blockade of N-methyl-d-aspartate (NMDA) receptors in the MNH, a manipulation that has been shown previously to impair auditory imprinting, suppresses the learning-induced spine reduction in this region. Chicks treated with the NMDA receptor antagonist 2-amino-5-phosphonovaleric acid (APV) during the behavioral training for imprinting (postnatal day 0–2) displayed similar spine frequencies at postnatal day 7 as naive control animals, which, in both groups, were significantly higher than in imprinted animals. Because the average dendritic length did not differ between the experimental groups, the reduced spine frequency can be interpreted as a reduction of the total number of spine synapses per neuron. In the Ndc, which is reciprocally connected with the MNH and not directly influenced by the injected drug, learning-induced spine elimination was partly suppressed. Spine frequencies of the APV-treated, behaviorally trained but nonimprinted animals were higher than in the imprinted animals but lower than in the naive animals. These results provide evidence that NMDA receptor activation is required for the learning-induced selective reduction of spine synapses, which may serve as a mechanism of information storage specific for juvenile emotional learning events. PMID:10051669

On the impact of RN network coverage on event selection and data fusion during the 2009 National Data Centres Preparedness Exercise

NASA Astrophysics Data System (ADS)

Becker, Andreas; Krysta, Monika; Auer, Matthias; Brachet, Nicolas; Ceranna, Lars; Gestermann, Nicolai; Nikkinen, Mika; Zähringer, Matthias

2010-05-01

The so-called National Data Centres (NDCs) to the Provisional Technical Secretariat of the Preparatory Commission for the Comprehensive Nuclear-Test-Ban Treaty (CTBT) Organization are in charge to provide for the final judgement on the CTBT relevance of explosion events encountered in the PTS International Monitoring System (IMS). The latter is a 321 stations network set-up by the PTS (to date completion level: 80%) in order to globally monitor for occurrence of CTBT relevant seismo-acoustic and radionuclide signals. In doing so, NDCs learn about any seismo-acoustic or radionuclide event by active retrieval or subscription to corresponding event lists and products provided by the International Data Centre (IDC) to the PTS. To prepare for their instrumental role in case of a CTBT relevant event, the NDCs jointly conduct annually so-called NDC Preparedness Exercises. In 2009, NDC Germany was in charge to lead the exercise and to choose a seismo-acoustic event out of the list of events provided by the PTS (Gestermann et al., EGU2010-13067). The novelty in this procedure was that also the infrasound readings and the monitoring coverage of existing (certified) radionuclide stations into the area of consideration were taken into account during the event selection process (Coyne et al., EGU2010-12660). Hence, the event finally chosen and examined took place near Kara-Zhyra mine in Eastern Kazakhstan on 28 November 2009 around 07:20:31 UTC (Event-ID 5727516). NDC Austria performed forward atmospheric transport modelling in order to predict RN measurements that should have occurred in the radionuclide IMS. In doing so the fictitious case that there would have been a release of radionuclides taking place at the same location (Wotawa and Schraik, 2010; EGU2010-4907) in a strength being typical for a non-contained nuclear explosion is examined. The stations indicated should then be analysed for their actual radionuclide readings in order to confirm the non nuclear character of the event (negative testing scenario). Obviously only stations already set up and ‘certified' of being capable of full operations, could be recruited for this. In doing so an issue was encountered with regard to the availability of RN data at certified RN stations. Despite the support to the event selection, PTS also supplied so-called data fusion bulletins that apply a method to collocate the RN and seismo-acoustic source location results (Krysta and Becker, EGU2010-10218). In this paper we demonstrate the impact of gaps in network coverage that appear due to the aforementioned reduced RN data availability for source location capacities. Network coverage assessments for the set of certified stations and the reduced set of stations actually sending data shall therefore be discussed. Furthermore, the capabilities and constraints of the data fusion method to make up for the RN source location accuracy losses related to reduced RN data availability at certified stations shall be presented.

Impulse control disorder and rapid eye movement sleep behavior disorder in Parkinson's disease.

PubMed

Bayard, Sophie; Dauvilliers, Yves; Yu, Huan; Croisier-Langenier, Muriel; Rossignol, Alexia; Charif, Mahmoud; Geny, Christian; Carlander, Bertrand; Cochen De Cock, Valérie

2014-12-01

The relationship between ICD and RBD is still not yet understood and the results from the current literature are contradictory in PD. We aimed to explore the association between rapid eye movement (REM) sleep behavior disorder (RBD) and impulse control disorder in Parkinson's disease. Ninety-eight non-demented patients with Parkinson's disease underwent one night of video-polysomnography recording. The diagnosis of RBD was established according to clinical and polysomnographic criteria. Impulse control disorders were determined by a gold standard, semi-structured diagnostic interview. Half of the patients (n = 49) reported clinical history of RBD while polysomnographic diagnosis of RBD was confirmed in 31.6% of the patients (n = 31). At least one impulse control disorder was identified in 21.4% of patients, 22.6% with RBD and 20.9% without. Logistic regression controlling for potential confounders indicated that both clinical RBD (OR = 0.34, 95% CI = 0.07-1.48, P = 0.15) and polysomnographic confirmed RBD diagnoses (OR = 0.1.28, 95% CI = 0.31-5.33, P = 0.34) were not associated with impulse control disorder. In Parkinson's disease, REM Sleep Behavior Disorder is not associated with impulse control disorder. The results of our study do not support the notion that PSG-confirmed RBD and ICD share a common pathophysiology. Copyright © 2014 Elsevier Ltd. All rights reserved.

[REHABILITATION OF MOBILITY AND MOTOR FUNCTION IN NURSING HOME RESIDENTS WITH DEMENTIA].

PubMed

Aizen, Efraim; Lubosky, Enna; Sobeh, Saleh; Ibrahim, Rasha; Pressburger, Dina; Oliven, Roni

2018-04-01

Few clinical trials have evaluated exercise programs developed specifically for patients with dementia in nursing home settings. To determine if a training program tailored for demented patients, can be implemented in a nursing home setting in order to improve motor performances in patients with dementia who suffered functional decline. The present intervention was conducted in wards of patients suffering from dementia in three nursing homes. Patients suffering from dementia and hospitalized in a rehabilitation hospital were the control arm. Eligible patients in the wards assigned to the intervention group (NH; n = 24) received exercise training specifically designed for patients with dementia. Patients in the rehabilitation hospital were observed as a control group (RH; n = 50) and received usual care treatment. Primary endpoints were changes in Functional Independence Measure (FIM), 5X Sit-to-Stand Test, Timed up and go test and ADL. Basic parameters were examined as predictors of positive training response. Both the nursing home residents and rehabilitation hospital patients improved significantly in both primary endpoints (change: in Functional Independence Measure, NH: +119.2 ± 30.8 % versus RH: +83.3 ± 41.9%, p < 0.001; ADL, NH: +143.5 ± 102.6% versus RH: +59.0 ± 90.2%, p < 0.001). Age was found to be a predictor of positive training response. This functional training program tailored for demented patients can be implemented in a nursing home setting to improve motor performances in patients with dementia. Such interventions should be further evaluated in larger randomized controlled trials.

Wheeled and standard walkers in Parkinson's disease patients with gait freezing.

PubMed

Cubo, Esther; Moore, Charity G; Leurgans, Sue; Goetz, Christopher G

2003-10-01

Compare the efficacy of two walking assistance devices (wheeled walker and standard walker) to unassisted walking for patients with PD and gait freezing. Although numerous walking devices are used clinically, their relative effects on freezing and walking speed have never been systematically tested. Nineteen PD patients (14 non-demented) walked under three conditions in randomized order: unassisted walking, standard walker, and wheeled walker. Patients walked up to three times in each condition through a standard course that included rising from a chair, walking through a doorway, straightway walking, pivoting, and return. Total walking time, freezing time and number of freezes were compared for the three conditions using mixed models (walking time) and Friedman's test (freezing). The wheeled walker was further studied by comparing the effect of an attached laser that projected a bar of light on the floor as a visual walking cue. Use of either type of device significantly slowed walking compared to unassisted walking. Neither walker reduced any index of freezing, nor the laser attachment offered any advantage to the wheeled walker. The standard walker increased freezing, and the wheeled walker had no effect on freezing. Among the non-demented subjects (n=14), the same patterns occurred, although the walking speed was less impaired by the wheeled walker than the standard walker in this group. Though walkers may stabilize patients and increase confidence, PD patients walk more slowly when using them, without reducing freezing. Because the wheeled walker was intermediate for walking time and does not aggravate freezing, if walkers are used for these subjects, this type of walker should be favored.

Online assessment of risk factors for dementia and cognitive function in healthy adults.

PubMed

Huntley, J; Corbett, A; Wesnes, K; Brooker, H; Stenton, R; Hampshire, A; Ballard, C

2018-02-01

Several potentially modifiable risk factors for cognitive decline and dementia have been identified, including low educational attainment, smoking, diabetes, physical inactivity, hypertension, midlife obesity, depression, and perceived social isolation. Managing these risk factors in late midlife and older age may help reduce the risk of dementia; however, it is unclear whether these factors also relate to cognitive performance in older individuals without dementia. Data from 14 201 non-demented individuals aged >50 years who enrolled in the online PROTECT study were used to examine the relationship between cognitive function and known modifiable risk factors for dementia. Multivariate regression analyses were conducted on 4 cognitive outcomes assessing verbal and spatial working memory, visual episodic memory, and verbal reasoning. Increasing age was associated with reduced performance across all tasks. Higher educational achievement, the presence of a close confiding relationship, and moderate alcohol intake were associated with benefits across all 4 cognitive tasks, and exercise was associated with better performance on verbal reasoning and verbal working memory tasks. A diagnosis of depression was negatively associated with performance on visual episodic memory and working memory tasks, whereas being underweight negatively affected performance on all tasks apart from verbal working memory. A history of stroke was negatively associated with verbal reasoning and working memory performance. Known modifiable risk factors for dementia are associated with cognitive performance in non-demented individuals in late midlife and older age. This provides further support for public health interventions that seek to manage these risk factors across the lifespan. Copyright © 2017 John Wiley & Sons, Ltd.

The association between pulse wave velocity and cognitive function: the Sydney Memory and Ageing Study.

PubMed

Singer, Joel; Trollor, Julian N; Crawford, John; O'Rourke, Michael F; Baune, Bernhard T; Brodaty, Henry; Samaras, Katherine; Kochan, Nicole A; Campbell, Lesley; Sachdev, Perminder S; Smith, Evelyn

2013-01-01

Pulse wave velocity (PWV) is a measure of arterial stiffness and its increase with ageing has been associated with damage to cerebral microvessels and cognitive impairment. This study examined the relationship between carotid-femoral PWV and specific domains of cognitive function in a non-demented elderly sample. Data were drawn from the Sydney Memory and Ageing Study, a cohort study of non-demented community-dwelling individuals aged 70-90 years, assessed in successive waves two years apart. In Wave 2, PWV and cognitive function were measured in 319 participants. Linear regression was used to analyse the cross-sectional relationship between arterial stiffness and cognitive function in the whole sample, and separately for men and women. Analysis of covariance was used to assess potential differences in cognition between subjects with PWV measurements in the top and bottom tertiles of the cohort. Covariates were age, education, body mass index, pulse rate, systolic blood pressure, cholesterol, depression, alcohol, smoking, hormone replacement therapy, apolipoprotein E ε4 genotype, use of anti-hypertensive medications, history of stroke, transient ischemic attack, myocardial infarction, angina, diabetes, and also sex for the whole sample analyses. There was no association between PWV and cognition after Bonferroni correction for multiple testing. When examining this association for males and females separately, an association was found in males, with higher PWV being associated with lower global cognition and memory, however, a significant difference between PWV and cognition between males and females was not found. A higher level of PWV was not associated with lower cognitive function in the whole sample.

High Risk of Dementia in Ventricular Enlargement with Normal Pressure Hydrocephalus Related Symptoms1.

PubMed

Koivisto, Anne M; Kurki, Mitja I; Alafuzoff, Irina; Sutela, Anna; Rummukainen, Jaana; Savolainen, Sakari; Vanninen, Ritva; Jääskeläinen, Juha E; Soininen, Hilkka; Leinonen, Ville

2016-03-22

Differential diagnosis of ventricular enlargement with normal pressure hydrocephalus (NPH) related symptoms is challenging. Patients with enlarged ventricles often manifest cognitive deterioration but their long-term outcome is not well known. We aim to evaluate long-term cognitive outcome in patients with enlarged ventricles and clinically suspected NPH. A neurologist and a neurosurgeon clinically evaluated 468 patients with enlarged ventricles and suspected NPH using radiological methods, intraventricular pressure monitoring, and frontal cortical brain biopsy. The neurologist confirmed final diagnoses after a median follow-up interval of 4.8 years. Altogether, 232 patients (50%) with enlarged ventricles did not fulfill the criteria for shunt surgery. The incidence of dementia among patients with enlarged ventricles, and at least one NPH-related symptom with adequate follow-up data (n = 446) was high, varying from 77 (iNPH, shunt responders) to 141/1000 person-years (non-shunted patients with enlarged ventricles). At the end of the follow-up, 59% of all these patients were demented. The demented population comprised 73% of non-shunted patients with enlarged ventricles, 63% of shunted iNPH patients that did not respond to treatment, and 46% of iNPH patients that were initially responsive to shunting. The most common cause of dementia was Alzheimer's disease (n = 94, 36%), followed by vascular dementia (n = 68, 26%). One-half of patients with enlarged ventricles and clinically suspected NPH were not shunted after intraventricular pressure monitoring. Dementia caused by various neurodegenerative diseases was frequently seen in patients with ventricular enlargement. Thus, careful diagnostic evaluation in collaboration with neurologists and neurosurgeons is emphasized.

Diagnosis, assessment and management of delusional jealousy in Parkinson's disease with and without dementia.

PubMed

Perugi, Giulio; Poletti, Michele; Logi, Chiara; Berti, Caterina; Romano, Anna; Del Dotto, Paolo; Lucetti, Claudio; Ceravolo, Roberto; Dell'Osso, Liliana; Bonuccelli, Ubaldo

2013-09-01

Patients with Parkinson's disease (PD) may present delusional jealousy (DJ). In a previous cross-sectional prevalence study we identified 15 cognitively preserved and five demented PD patients with DJ. The current study aimed at evaluating their clinical (motor and non-motor) characteristics and the pharmacological treatments associated with DJ, and its subsequent pharmacological management. Patients were assessed by neurologists and psychiatrists using the Hoehn and Yahr scale, the Unified Parkinson's Disease Rating Scale, the Brief Psychiatric Rating Scale, the Beck Depression Inventory, the Hamilton Anxiety Scale and the Neuropsychiatric Inventory. Efficacy of DJ management was evaluated in follow-up visits. All patients were in therapy with dopamine agonists. A subgroup of five cognitively preserved patients developed DJ after a short period of treatment of therapy with dopamine agonists, while other patients developed DJ after a longer period of dopaminergic treatment. Psychiatric comorbidities were common in cognitively preserved and in demented patients. The pharmacological management included the interruption of dopamine agonists in two patients and the reduction of dopamine agonist dose plus the use of antipsychotics in other patients. These clinical data suggest that the management of medicated PD patients should include investigation for the presence of DJ and the evaluation of clinical characteristics potentially relevant to the prevention or the early recognition of delusions.

Integrated feature extraction and selection for neuroimage classification

NASA Astrophysics Data System (ADS)

Fan, Yong; Shen, Dinggang

2009-02-01

Feature extraction and selection are of great importance in neuroimage classification for identifying informative features and reducing feature dimensionality, which are generally implemented as two separate steps. This paper presents an integrated feature extraction and selection algorithm with two iterative steps: constrained subspace learning based feature extraction and support vector machine (SVM) based feature selection. The subspace learning based feature extraction focuses on the brain regions with higher possibility of being affected by the disease under study, while the possibility of brain regions being affected by disease is estimated by the SVM based feature selection, in conjunction with SVM classification. This algorithm can not only take into account the inter-correlation among different brain regions, but also overcome the limitation of traditional subspace learning based feature extraction methods. To achieve robust performance and optimal selection of parameters involved in feature extraction, selection, and classification, a bootstrapping strategy is used to generate multiple versions of training and testing sets for parameter optimization, according to the classification performance measured by the area under the ROC (receiver operating characteristic) curve. The integrated feature extraction and selection method is applied to a structural MR image based Alzheimer's disease (AD) study with 98 non-demented and 100 demented subjects. Cross-validation results indicate that the proposed algorithm can improve performance of the traditional subspace learning based classification.

Shorter telomeres may indicate dementia status in older individuals with Down Syndrome

PubMed Central

Jenkins, Edmund C.; Ye, Lingling; Gu, Hong; Ni, Samantha A.; Velinov, Milen; Pang, Deborah; Krinsky-McHale, Sharon J.; Zigman, Warren B.; Schupf, Nicole; Silverman, Wayne P.

2009-01-01

We have recently reported reduced telomere length in T lymphocytes of individuals with Down syndrome (DS) and dementia due to Alzheimer’s disease (AD). We have now replicated and extended that study by finding that people with DS and mild cognitive impairment (MCI-DS) also have shorter telomeres than people with DS without MCI-DS. Additional new findings demonstrated that light intensity measurements from chromosome 21 alone, or in concert with chromosomes 1, 2, and 16, exhibited shorter telomeres in adults with DS and with either dementia or MCI-DS compared to aging per se. Chromosome 21 measurements appeared to be especially promising for use as a biomarker because there was no overlap in the distribution of light intensity measurement scores between demented or MCI-DS and non-demented participants. Given that early clinical symptoms of AD can be very difficult to recognize in this population of adults due to their pre-existing cognitive impairments, a valid biomarker would be of great value. Early detection is especially important because it would allow treatments to begin before significant damage to the central nervous system has occurred. Our findings suggest that it may be feasible to use telomere shortening as a biomarker for accurately inferring dementia status. PMID:18635289

Multimodal and Multiscale Deep Neural Networks for the Early Diagnosis of Alzheimer's Disease using structural MR and FDG-PET images.

PubMed

Lu, Donghuan; Popuri, Karteek; Ding, Gavin Weiguang; Balachandar, Rakesh; Beg, Mirza Faisal

2018-04-09

Alzheimer's Disease (AD) is a progressive neurodegenerative disease where biomarkers for disease based on pathophysiology may be able to provide objective measures for disease diagnosis and staging. Neuroimaging scans acquired from MRI and metabolism images obtained by FDG-PET provide in-vivo measurements of structure and function (glucose metabolism) in a living brain. It is hypothesized that combining multiple different image modalities providing complementary information could help improve early diagnosis of AD. In this paper, we propose a novel deep-learning-based framework to discriminate individuals with AD utilizing a multimodal and multiscale deep neural network. Our method delivers 82.4% accuracy in identifying the individuals with mild cognitive impairment (MCI) who will convert to AD at 3 years prior to conversion (86.4% combined accuracy for conversion within 1-3 years), a 94.23% sensitivity in classifying individuals with clinical diagnosis of probable AD, and a 86.3% specificity in classifying non-demented controls improving upon results in published literature.

Visual processing speed in old age.

PubMed

Habekost, Thomas; Vogel, Asmus; Rostrup, Egill; Bundesen, Claus; Kyllingsbaek, Søren; Garde, Ellen; Ryberg, Charlotte; Waldemar, Gunhild

2013-04-01

Mental speed is a common concept in theories of cognitive aging, but it is difficult to get measures of the speed of a particular psychological process that are not confounded by the speed of other processes. We used Bundesen's (1990) Theory of Visual Attention (TVA) to obtain specific estimates of processing speed in the visual system controlled for the influence of response latency and individual variations of the perception threshold. A total of 33 non-demented old people (69-87 years) were tested for the ability to recognize briefly presented letters. Performance was analyzed by the TVA model. Visual processing speed decreased approximately linearly with age and was on average halved from 70 to 85 years. Less dramatic aging effects were found for the perception threshold and the visual apprehension span. In the visual domain, cognitive aging seems to be most clearly related to reductions in processing speed. © 2012 The Authors. Scandinavian Journal of Psychology © 2012 The Scandinavian Psychological Associations.

Widespread temporo-occipital lobe dysfunction in amyotrophic lateral sclerosis

NASA Astrophysics Data System (ADS)

Loewe, Kristian; Machts, Judith; Kaufmann, Jörn; Petri, Susanne; Heinze, Hans-Jochen; Borgelt, Christian; Harris, Joseph Allen; Vielhaber, Stefan; Schoenfeld, Mircea Ariel

2017-01-01

Recent studies suggest that amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) lie on a single clinical continuum. However, previous neuroimaging studies have found only limited involvement of temporal lobe regions in ALS. To better delineate possible temporal lobe involvement in ALS, the present study aimed to examine changes in functional connectivity across the whole brain, particularly with regard to extra-motor regions, in a group of 64 non-demented ALS patients and 38 healthy controls. To assess between-group differences in connectivity, we computed edge-level statistics across subject-specific graphs derived from resting-state functional MRI data. In addition to expected ALS-related decreases in functional connectivity in motor-related areas, we observed extensive changes in connectivity across the temporo-occipital cortex. Although ALS patients with comorbid FTD were deliberately excluded from this study, the pattern of connectivity alterations closely resembles patterns of cerebral degeneration typically seen in FTD. This evidence for subclinical temporal dysfunction supports the idea of a common pathology in ALS and FTD.

The Cross-Cultural Dementia Screening (CCD): A new neuropsychological screening instrument for dementia in elderly immigrants.

PubMed

Goudsmit, Miriam; Uysal-Bozkir, Özgül; Parlevliet, Juliette L; van Campen, Jos P C M; de Rooij, Sophia E; Schmand, Ben

2017-03-01

Currently, approximately 3.9% of the European population are non-EU citizens, and a large part of these people are from "non-Western" societies, such as Turkey and Morocco. For various reasons, the incidence of dementia in this group is expected to increase. However, cognitive testing is challenging due to language barriers and low education and/or illiteracy. The newly developed Cross-Cultural Dementia Screening (CCD) can be administered without an interpreter. It contains three subtests that assess memory, mental speed, and executive function. We hypothesized the CCD to be a culture-fair test that could discriminate between demented patients and cognitively healthy controls. To test this hypothesis, 54 patients who had probable dementia were recruited via memory clinics. Controls (N = 1625) were recruited via their general practitioners. All patients and controls were aged 55 years and older and of six different self-defined ethnicities (Dutch, Turkish, Moroccan-Arabic, Moroccan-Berber, Surinamese-Creole, and Surinamese-Hindustani). Exclusion criteria included current or previous conditions that affect cognitive functioning. There were performance differences between the ethnic groups, but these disappeared after correcting for age and education differences between the groups, which supports our central hypothesis that the CCD is a culture-fair test. Receiver-operating characteristic (ROC) and logistic regression analyses showed that the CCD has high predictive validity for dementia (sensitivity: 85%; specificity: 89%). The CCD is a sensitive and culture-fair neuropsychological instrument for dementia screening in low-educated immigrant populations.

IDC Reengineering Iteration I2 Architectural Prototype Reports

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hamlet, Benjamin R.

To fulfill the inception phase deliverable “Demonstration of architectural prototype“ the SNL IDC Reengineering project team is providing seven reports describing system prototyping work completed between October 2012 and October 2014as part of the SNL US NDC Modernization project.

75 FR 32229 - National Declassification Center (NDC)

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-07

...) of Executive Order 13526, Classified National Security Information, announcement is made for the... attend must be submitted to the National Declassification Center. Information may be submitted via e-mail..., Washington, DC 20408. FOR FURTHER INFORMATION CONTACT: Don McIlwain, Supervisory Archivist, National...

Evaluating the implementation of RxNorm in ambulatory electronic prescriptions

PubMed Central

Ward-Charlerie, Stacy; Rupp, Michael T; Kilbourne, John; Amin, Vishal P; Ruiz, Joshua

2016-01-01

Objective RxNorm is a standardized drug nomenclature maintained by the National Library of Medicine that has been recommended as an alternative to the National Drug Code (NDC) terminology for use in electronic prescribing. The objective of this study was to evaluate the implementation of RxNorm in ambulatory care electronic prescriptions (e-prescriptions). Methods We analyzed a random sample of 49 997 e-prescriptions that were received by 7391 locations of a national retail pharmacy chain during a single day in April 2014. The e-prescriptions in the sample were generated by 37 801 ambulatory care prescribers using 519 different e-prescribing software applications. Results We found that 97.9% of e-prescriptions in the study sample could be accurately represented by an RxNorm identifier. However, RxNorm identifiers were actually used as drug identifiers in only 16 433 (33.0%) e-prescriptions. Another 431 (2.5%) e-prescriptions that used RxNorm identifiers had a discrepancy in the corresponding Drug Database Code qualifier field or did not have a qualifier (Term Type) at all. In 10 e-prescriptions (0.06%), the free-text drug description and the RxNorm concept unique identifier pointed to completely different drug concepts, and in 7 e-prescriptions (0.04%), the NDC and RxNorm drug identifiers pointed to completely different drug concepts. Discussion The National Library of Medicine continues to enhance the RxNorm terminology and expand its scope. This study illustrates the need for technology vendors to improve their implementation of RxNorm; doing so will accelerate the adoption of RxNorm as the preferred alternative to using the NDC terminology in e-prescribing. PMID:26510879

Werner complex deficiency in cells disrupts the Nuclear Pore Complex and the distribution of lamin B1.

PubMed

Li, Zhi; Zhu, Yizhou; Zhai, Yujia; R Castroagudin, Michelle; Bao, Yifei; White, Tommy E; Glavy, Joseph S

2013-12-01

From the surrounding shell to the inner machinery, nuclear proteins provide the functional plasticity of the nucleus. This study highlights the nuclear association of Pore membrane (POM) protein NDC1 and Werner protein (WRN), a RecQ helicase responsible for the DNA instability progeria disorder, Werner Syndrome. In our previous publication, we connected the DNA damage sensor Werner's Helicase Interacting Protein (WHIP), a binding partner of WRN, to the NPC. Here, we confirm the association of the WRN/WHIP complex and NDC1. In established WRN/WHIP knockout cell lines, we further demonstrate the interdependence of WRN/WHIP and Nucleoporins (Nups). These changes do not completely abrogate the barrier of the Nuclear Envelope (NE) but do affect the distribution of FG Nups and the RAN gradient, which are necessary for nuclear transport. Evidence from WRN/WHIP knockout cell lines demonstrates changes in the processing and nucleolar localization of lamin B1. The appearance of "RAN holes" void of RAN corresponds to regions within the nucleolus filled with condensed pools of lamin B1. From WRN/WHIP knockout cell line extracts, we found three forms of lamin B1 that correspond to mature holoprotein and two potential post-translationally modified forms of the protein. Upon treatment with topoisomerase inhibitors lamin B1 cleavage occurs only in WRN/WHIP knockout cells. Our data suggest the link of the NDC1 and WRN as one facet of the network between the nuclear periphery and genome stability. Loss of WRN complex leads to multiple alterations at the NPC and the nucleolus. © 2013. Published by Elsevier B.V. All rights reserved.

Co-expression of mitosis-regulating genes contributes to malignant progression and prognosis in oligodendrogliomas

PubMed Central

Liu, Yanwei; Hu, Huimin; Zhang, Chuanbao; Wang, Haoyuan; Zhang, Wenlong; Wang, Zheng; Li, Mingyang; Zhang, Wei; Zhou, Dabiao; Jiang, Tao

2015-01-01

The clinical prognosis of patients with glioma is determined by tumor grades, but tumors of different subtypes with equal malignancy grade usually have different prognosis that is largely determined by genetic abnormalities. Oligodendrogliomas (ODs) are the second most common type of gliomas. In this study, integrative analyses found that distribution of TCGA transcriptomic subtypes was associated with grade progression in ODs. To identify critical gene(s) associated with tumor grades and TCGA subtypes, we analyzed 34 normal brain tissue (NBT), 146 WHO grade II and 130 grade III ODs by microarray and RNA sequencing, and identified a co-expression network of six genes (AURKA, NDC80,CENPK, KIAA0101, TIMELESS and MELK) that was associated with tumor grades and TCGA subtypes as well as Ki-67 expression. Validation of the six genes was performed by qPCR in additional 28 ODs. Importantly, these genes also were validated in four high-grade recurrent gliomas and the initial lower-grade gliomas resected from the same patients. Finally, the RNA data on two genes with the highest discrimination potential (AURKA and NDC80) and Ki-67 were validated on an independent cohort (5 NBTs and 86 ODs) by immunohistochemistry. Knockdown of AURKA and NDC80 by siRNAs suppressed Ki-67 expression and proliferation of gliomas cells. Survival analysis showed that high expression of the six genes corporately indicated a poor survival outcome. Correlation and protein interaction analysis provided further evidence for this co-expression network. These data suggest that the co-expression of the six mitosis-regulating genes was associated with malignant progression and prognosis in ODs. PMID:26468983

Subthreshold depression and subjective cognitive complaints in Parkinson's disease.

PubMed

Santangelo, G; Vitale, C; Trojano, L; Angrisano, M G; Picillo, M; Errico, D; Agosti, V; Grossi, D; Barone, P

2014-03-01

Subthreshold depression (SubD) is characterized by clinically relevant depressive symptoms not meeting criteria for major depression. The possible association of SubD with subjective cognitive complaints and/or objective cognitive impairments was investigated in a sample of consecutive, non-demented Parkinson's disease (PD) outpatients. Amongst 115 patients, SubD was identified in 30 patients, major depression in 33; 36 patients were classified as non-depressed. Enrolled patients were administered tests and questionnaires validated in PD for assessing objective and subjective cognitive dysfunctions. On objective cognitive measures SubD patients did not differ from non-depressed patients, whereas depressed patients achieved significantly lower scores than the other two groups. SubD and depressed patients reported more cognitive complaints than non-depressed patients. SubD is a non-motor aspect of PD that is not related to objective cognitive deficits but is associated with subjective cognitive complaints, thus impacting on patients' well-being. © 2013 The Author(s) European Journal of Neurology © 2013 EFNS.

Is language impairment more common than executive dysfunction in amyotrophic lateral sclerosis?

PubMed

Taylor, Lorna J; Brown, Richard G; Tsermentseli, Stella; Al-Chalabi, Ammar; Shaw, Christopher E; Ellis, Catherine M; Leigh, P Nigel; Goldstein, Laura H

2013-05-01

Systematic explorations of language abilities in patients with amyotrophic lateral sclerosis (ALS) are lacking in the context of wider cognitive change. Neuropsychological assessment data were obtained from 51 patients with ALS and 35 healthy controls matched for age, gender and IQ. Composite scores were derived for the domains of language and executive functioning. Domain impairment was defined as a composite score ≤5th centile relative to the control mean. Cognitive impairment was also classified using recently published consensus criteria. The patients with ALS were impaired on language and executive composite scores. Language domain impairment was found in 43% of patients with ALS, and executive domain impairment in 31%. Standardised language and executive composite scores correlated in the ALS group (r=0.68, p<0.001). Multiple regression analyses indicated that scores on the executive composite accounted for 44% of the variance in language composite scores. Language impairments are at least as prevalent as executive dysfunction in ALS. While the two domains are strongly associated, executive dysfunction does not fully account for the profile of language impairments observed, further highlighting the heterogeneity of cognitive impairment in non-demented patients with ALS.

Mismatch Negativity in essential tremor: role of age at onset in pre-attentive auditory discrimination.

PubMed

Pauletti, C; Mannarelli, D; Locuratolo, N; Vanacore, N; De Lucia, M C; Fattapposta, F

2014-04-01

To investigate whether pre-attentive auditory discrimination is impaired in patients with essential tremor (ET) and to evaluate the role of age at onset in this function. Seventeen non-demented patients with ET and seventeen age- and sex-matched healthy controls underwent an EEG recording during a classical auditory MMN paradigm. MMN latency was significantly prolonged in patients with elderly-onset ET (>65 years) (p=0.046), while no differences emerged in either latency or amplitude between young-onset ET patients and controls. This study represents a tentative indication of a dysfunction of auditory automatic change detection in elderly-onset ET patients, pointing to a selective attentive deficit in this subgroup of ET patients. The delay in pre-attentive auditory discrimination, which affects elderly-onset ET patients alone, further supports the hypothesis that ET represents a heterogeneous family of diseases united by tremor; these diseases are characterized by cognitive differences that may range from a disturbance in a selective cognitive function, such as the automatic part of the orienting response, to more widespread and complex cognitive dysfunctions. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Age-related defects in erythrocyte 2,3-diphosphoglycerate metabolism in dementia.

PubMed

Kaminsky, Yury G; Reddy, V Prakash; Ashraf, Ghulam Md; Ahmad, Ausaf; Benberin, Valery V; Kosenko, Elena A; Aliev, Gjumrakch

2013-01-01

Alzheimer disease (AD) is the most common dementing illness. Metabolic defects in the brain with aging contribute to the pathogenesis of AD. These changes can be found systematically and thus can be used as potential biomarkers. Erythrocytes (RBCs) are passive "reporter cells" that are not well studied in AD. In the present study, we analyzed an array of glycolytic and related enzymes and intermediates in RBCs from patients with AD and non-Alzheimer dementia (NA), age-matched controls (AC) and young adult controls (YC). AD is characterized by higher activities of hexokinase, phosphofructokinase, and bisphosphoglycerate mutase and bisphosphoglycerate phosphatase in RBCs. In our study, we observed that glycolytic and related enzymes displayed significantly lower activities in AC. However, similar or significantly higher activities were observed in AD and NA groups as compared to YC group. 2,3-diphosphoglycerate (2,3-DPG) levels were significantly decreased in AD and NA patients. The pattern of changes between groups in the above indices strongly correlates with each other. Collectively, our data suggested that AD and NA patients are associated with chronic disturbance of 2,3-DPG metabolism in RBCs. These defects may play a pivotal role in physiological processes, which predispose elderly subjects to AD and NA.

How Clinicians Feel about Working with Spouses of the Chronically Ill.

PubMed

Ingram, Douglas H

2015-09-01

Clinicians who provide psychotherapy to spouses or partners of the chronically ill were solicited through listserves of psychodynamic and other organizations. The current report excluded those therapists working with spouses of dementia patients. Interviews were conducted with clinicians who responded. The interviews highlight the challenges commonly encountered by psychotherapeutic work with this cohort of therapy patients. A comparison is drawn that shows both overlap and distinctions between the experiences of those therapists engaging with spouses of chronically ill patients without a dementing process and those working with spouses of chronically ill patients who do suffer from a dementing process.

Mental object rotation in Parkinson's disease.

PubMed

Crucian, Gregory P; Barrett, Anna M; Burks, David W; Riestra, Alonso R; Roth, Heidi L; Schwartz, Ronald L; Triggs, William J; Bowers, Dawn; Friedman, William; Greer, Melvin; Heilman, Kenneth M

2003-11-01

Deficits in visual-spatial ability can be associated with Parkinson's disease (PD), and there are several possible reasons for these deficits. Dysfunction in frontal-striatal and/or frontal-parietal systems, associated with dopamine deficiency, might disrupt cognitive processes either supporting (e.g., working memory) or subserving visual-spatial computations. The goal of this study was to assess visual-spatial orientation ability in individuals with PD using the Mental Rotations Test (MRT), along with other measures of cognitive function. Non-demented men with PD were significantly less accurate on this test than matched control men. In contrast, women with PD performed similarly to matched control women, but both groups of women did not perform much better than chance. Further, mental rotation accuracy in men correlated with their executive skills involving mental processing and psychomotor speed. In women with PD, however, mental rotation accuracy correlated negatively with verbal memory, indicating that higher mental rotation performance was associated with lower ability in verbal memory. These results indicate that PD is associated with visual-spatial orientation deficits in men. Women with PD and control women both performed poorly on the MRT, possibly reflecting a floor effect. Although men and women with PD appear to engage different cognitive processes in this task, the reason for the sex difference remains to be elucidated.

Evaluation of extracranial blood flow in Parkinson disease.

PubMed

Haktanir, Alpay; Yaman, Mehmet; Acar, Murat; Gecici, Omer; Demirel, Reha; Albayrak, Ramazan; Demirkirkan, Kemal

2006-01-02

Decreased cerebral flow velocities in Parkinsonian patients were reported previously. Because of the limited data on vascular changes in Parkinson disease (PD), which may have a vascular etiology, we aimed to disclose any possible cerebral hemodynamic alteration in Parkinsonian patients. We prospectively evaluated 28 non-demented, idiopathic parkinsonian patients and 19 age and sex matched controls with Doppler sonography. Flow volumes, peak systolic flow velocities, and cross-sectional areas of vertebral and internal carotid arteries (ICA) were measured and compared between patients and controls. Correlation of patient age and disease duration with Doppler parameters was observed; and each Doppler parameter of patients within each Hoehn-Yahr scale was compared. There was no significant difference of measured parameters between groups. No correlation was found between disease duration and age with flow volume, cross-sectional area or peak systolic velocity. Hoehn-Yahr scale was not found having significant relation with Doppler parameters. Values of vertebral, internal carotid and cerebral blood flow volumes (CBF), peak systolic velocities, and cross-sectional areas were not significantly different between Parkinsonian patients and age and sex matched controls. Although regional blood flow decreases may be seen as reported previously, Parkinson disease is not associated with a flow volume or velocity alteration of extracranial cerebral arteries.

Asymmetric supercapacitors utilizing highly porous metal-organic framework derived Co3O4 nanosheets grown on Ni foam and polyaniline hydrogel derived N-doped nanocarbon electrode materials

NASA Astrophysics Data System (ADS)

Fan, Xin; Chen, Weiliang; Pang, Shuhua; Lu, Wei; Zhao, Yu; Liu, Zheng; Fang, Dong

2017-12-01

In the present work, asymmetric supercapacitors (ASCs) are assembled using a highly conductive N-doped nanocarbon (NDC) material derived from a polyaniline hydrogel as a cathode, and Ni foam covered with flower-like Co3O4 nanosheets (Co3O4-Ni) prepared from a zeolitic imidazolate metal-organic framework as a single precursor serves as a high gravimetric capacitance anode. At a current of 0.2 A g-1, the Co3O4-Ni electrode provides a gravimetric capacitance of 637.7 F g-1, and the NDC electrode provides a gravimetric capacitance of 359.6 F g-1. The ASC assembled with an optimal active material loading operates within a wide potential window of 0-1.1 V, and provides a high areal capacitance of 25.7 mF cm-2. The proposed ASC represents a promising strategy for designing high-performance supercapacitors.

An electrochemical sensor based on nitrogen doped carbon material prepared from nitrogen-containing precursors

NASA Astrophysics Data System (ADS)

Cui, G. Y.; Wang, C. Y.; Xiang, G. Q.; Zhou, B.

2018-01-01

In this work, a nitrogen doped carbon material (NDC) was prepared by using a copper adenine complex as precursor and applied to electrochemical sensing of Vitamin B2 (VB2). The experimental results show that the nitrogen doped carbon material is obtained after calcination at 650 °C under argon atmosphere, afterwards, which were characterized by X-ray diffraction (XRD), transmission electron microscope (TEM), fourier transform infrared (FT-IR), and electrochemical method. According to the XRD data, the product was a carbon material, and infrared data demonstrates that there are two kinds of carbonyl nitrogen combination, respectively, C-N and C = N combination of ways. Importantly, we used NDC to construct electrochemical biosensor to detect VB2 by differential pulse voltammetry (DPV). The linear range was 6 × 10-6 - 3.5 × 10-4 M (R=0.9962), the minimum detection limit was 5.4 × 10-6 M, and the sensitivity is better. Consequently, it has better sensing performance.

The tunnel magnetoresistance in chains of quantum dots weakly coupled to external leads.

PubMed

Weymann, Ireneusz

2010-01-13

We analyze numerically the spin-dependent transport through coherent chains of three coupled quantum dots weakly connected to external magnetic leads. In particular, using the diagrammatic technique on the Keldysh contour, we calculate the conductance, shot noise and tunnel magnetoresistance (TMR) in the sequential and cotunneling regimes. We show that transport characteristics greatly depend on the strength of the interdot Coulomb correlations, which determines the spatial distribution of the electron wavefunction in the chain. When the correlations are relatively strong, depending on the transport regime, we find both negative TMR as well as TMR enhanced above the Julliere value, accompanied with negative differential conductance (NDC) and super-Poissonian shot noise. This nontrivial behavior of tunnel magnetoresistance is associated with selection rules that govern tunneling processes and various high-spin states of the chain that are relevant for transport. For weak interdot correlations, on the other hand, the TMR is always positive and not larger than the Julliere TMR, although super-Poissonian shot noise and NDC can still be observed.

Diagnostic Accuracy of Cerebrospinal Fluid Amyloid-β Isoforms for Early and Differential Dementia Diagnosis.

PubMed

Struyfs, Hanne; Van Broeck, Bianca; Timmers, Maarten; Fransen, Erik; Sleegers, Kristel; Van Broeckhoven, Christine; De Deyn, Peter P; Streffer, Johannes R; Mercken, Marc; Engelborghs, Sebastiaan

2015-01-01

Overlapping cerebrospinal fluid biomarkers (CSF) levels between Alzheimer's disease (AD) and non-AD patients decrease differential diagnostic accuracy of the AD core CSF biomarkers. Amyloid-β (Aβ) isoforms might improve the AD versus non-AD differential diagnosis. To determine the added diagnostic value of Aβ isoforms, Aβ(1-37), Aβ(1-38), and Aβ(1-40), as compared to the AD CSF biomarkers Aβ(1-42), T-tau, and P-tau(181P). CSF from patients with dementia due to AD (n = 50), non-AD dementias (n = 50), mild cognitive impairment due to AD (n = 50) and non-demented controls (n = 50) was analyzed with a prototype multiplex assay using MSD detection technology. The non-AD group consisted of frontotemporal dementia (FTD; n = 17), dementia with Lewy bodies (DLB; n = 17), and vascular dementia (n = 16). Aβ(1-37) and Aβ(1-38) increased accuracy to differentiate AD from FTD or DLB. Aβ(1-37), Aβ(1-38), and Aβ(1-40) levels correlated with Mini-Mental State Examination scores and disease duration in dementia due to AD. The Aβ(1-42)/Aβ(1-40) ratio improved diagnostic performance of Aβ(1-42) in most differential diagnostic situations. Aβ(1-42) levels were lower in APOE ε4 carriers compared to non-carriers. Aβ isoforms help to differentiate AD from FTD and DLB. Aβ isoforms increase diagnostic performance of Aβ(1-42). In contrast to Aβ1-42, Aβ isoforms seem to be correlated with disease severity in AD. Adding the Aβ isoforms to the current biomarker panel could enhance diagnostic accuracy.

Investigating the neuroanatomical substrate of pathological laughing and crying in amyotrophic lateral sclerosis with multimodal neuroimaging techniques.

PubMed

Christidi, Foteini; Karavasilis, Efstratios; Ferentinos, Panagiotis; Xirou, Sophia; Velonakis, Georgios; Rentzos, Michalis; Zouvelou, Vasiliki; Zalonis, Ioannis; Efstathopoulos, Efstathios; Kelekis, Nikolaos; Evdokimidis, Ioannis

2018-02-01

Pathological laughing and crying (PLC) is common in several neurological and psychiatric diseases and is associated with a distributed network involving the frontal cortex, the brainstem and cortico-pontine-cerebellar circuits. By applying multimodal neuroimaging approach, we examined the neuroanatomical substrate of PLC in a sample of patients with amyotrophic lateral sclerosis (ALS). We studied 56 non-demented ALS patients and 25 healthy controls (HC). PLC was measured in ALS using the Center of Neurologic Study Lability Scale (CNS-LS; cutoff score: 13). All participants underwent 3D-T1-weighted and 30-directional diffusion-weighted imaging at 3T. Voxel-based morphometry and tract-based spatial-statistics analysis was used to examine gray matter (GM) and white matter (WM) differences between ALS patients with and without PLC (ALS-PLC and ALS-nonPLC, respectively). Comparisons were restricted to regions with detected differences between ALS and HC, controlling for age, gender, total intracranial volume and depressive symptoms. In regions with significant differences between ALS and HC, ALS-PLC patients showed decreased GM volume in left orbitofrontal cortex, frontal operculum, and putamen and bilateral frontal poles, compared to ALS-nonPLC. They also had decreased fractional anisotropy in left cingulum bundle and posterior corona radiata. WM abnormalities were additionally detected in WM associative and ponto-cerebellar tracts (using a more liberal threshold). PLC in ALS is driven by both GM and WM abnormalities which highlight the role of circuits rather than isolated centers in the emergence of this condition. ALS is suggested as a useful natural experimental model to study PLC.

Short-term and practice effects of metronome pacing in Parkinson's disease patients with gait freezing while in the 'on' state: randomized single blind evaluation.

PubMed

Cubo, Esther; Leurgans, Sue; Goetz, Christopher G

2004-12-01

In a randomized single blind parallel study, we tested the efficacy of an auditory metronome on walking speed and freezing in Parkinson's disease (PD) patients with freezing gait impairment during their 'on' function. No pharmacological treatment is effective in managing 'on' freezing in PD. Like visual cues that can help overcome freezing, rhythmic auditory pacing may provide cues that help normalize walking pace and overcome freezing. Non-demented PD patients with freezing during their 'on' state walked under two conditions, in randomized order: unassisted walking and walking with the use of an audiocassette with a metronome recording. The walking trials were randomized and gait variables were rated from videotapes by a blinded evaluator. Outcome measures were total walking time (total trial time-total freezing time), which was considered the time over a course of specified length, freezing time, average freeze duration and number of freezes. All outcomes were averaged across trials for each person and then compared across conditions using Signed Rank tests. Twelve non-demented PD patients with a mean age of 65.8 +/- 11.2 years, and mean PD duration of 12.4 +/- 7.3 years were included. The use of the metronome slowed ambulation and increased the total walking time (P < 0.0005) only during the first visit, without affecting any freezing variable. In the nine patients who took the metronome recording home and used it daily for 1 week while walking, freezing remained unimproved. Though advocated in prior publications as a walking aid for PD patients, auditory metronome pacing slows walking and is not a beneficial intervention for freezing during their 'on' periods.

Executive dysfunction assessed by Clock-Drawing Test in older non-demented subjects with metabolic syndrome is not mediated by white matter lesions.

PubMed

Viscogliosi, Giovanni; Chiriac, Iulia Maria; Andreozzi, Paola; Ettorre, Evaristo

2015-10-01

Metabolic syndrome (MetS) has been associated with greater occurrence of white matter hyperintensities (WMH). It remains uncertain whether MetS as a construct is associated with poorer cognitive performances. This study explores whether MetS is associated with poorer performances in global and domain-specific cognitive tests in older non-demented subjects independently of its individual components, WMH severity and other variables. MetS was diagnosed according to the National Cholesterol Education Program Adult Treatment Panel III definition. Brain magnetic resonance studies (1.5T) were performed. Deep and periventricular WMH were graded using the Fazekas scale. Subjects underwent the Mini-Mental State Examination, the Babcock Short Story Recall test and the Clock-Drawing Test (CDT). Eighty community-dwellers aged 67-91 years were studied. Subjects with MetS (n = 35) had more severe WMH, and poorer performances on the CDT (P = 0.003) and the Babcock Short Story Recall test (P = 0.027). After multiple adjustment, MetS was inversely associated with CDT scores (B = -1.285; 95% confidence interval = -1.996--0.575; P = 0.001) but not with episodic memory. Results were not affected by WMH severity. Interestingly, none of the individual components of MetS predicted poorer cognitive performances. Impairment in executive functions assessed by CDT may represent an early and specific sign of cognitive decline in older individuals with MetS. Future longitudinal studies are needed to better establish the predictive role of MetS on dementia and to demonstrate the possibility of dementia prevention by targeting MetS. © 2015 The Authors. Psychiatry and Clinical Neurosciences © 2015 Japanese Society of Psychiatry and Neurology.

Improved design of prodromal Alzheimer's disease trials through cohort enrichment and surrogate endpoints.

PubMed

Macklin, Eric A; Blacker, Deborah; Hyman, Bradley T; Betensky, Rebecca A

2013-01-01

Alzheimer's disease (AD) trials initiated during or before the prodrome are costly and lengthy because patients are enrolled long before clinical symptoms are apparent, when disease progression is slow. We hypothesized that design of such trials could be improved by: 1) selecting individuals at moderate near-term risk of progression to AD dementia (the current clinical standard) and 2) by using short-term surrogate endpoints that predict progression to AD dementia. We used a longitudinal cohort of older, initially non-demented, community-dwelling participants (n = 358) to derive selection criteria and surrogate endpoints and tested them in an independent national data set (n = 6,243). To identify a "mid-risk" subgroup, we applied conditional tree-based survival models to Clinical Dementia Rating (CDR) scale scores and common neuropsychological tests. In the validation cohort, a time-to-AD dementia trial applying these mid-risk selection criteria to a pool of all non-demented individuals could achieve equivalent power with 47% fewer participants than enrolling at random from that pool. We evaluated surrogate endpoints measureable over two years of follow-up based on cross-validated concordance between predictions from Cox models and observed time to AD dementia. The best performing surrogate, rate of change in CDR sum-of-boxes, did not reduce the trial duration required for equivalent power using estimates from the validation cohort, but alternative surrogates with better ability to predict time to AD dementia should be able to do so. The approach tested here might improve efficiency of prodromal AD trials using other potential measures and could be generalized to other diseases with long prodromal phases.

Improved design of prodromal Alzheimer’s disease trials through cohort enrichment and surrogate endpoints

PubMed Central

Macklin, Eric A.; Blacker, Deborah; Hyman, Bradley T.; Betensky, Rebecca A.

2013-01-01

Summary Alzheimer’s disease (AD) trials initiated during or before the prodrome are costly and lengthy because patients are enrolled long before clinical symptoms are apparent, when disease progression is slow. We hypothesized that design of such trials could be improved by: (1) selecting individuals at moderate near-term risk of progression to AD dementia (the current clinical standard) and (2) by using short-term surrogate endpoints that predict progression to AD dementia. We used a longitudinal cohort of older, initially non-demented, community-dwelling participants (n=358) to derive selection criteria and surrogate endpoints and tested them in an independent national data set (n=6,243). To identify a “mid-risk” subgroup, we applied conditional tree-based survival models to Clinical Dementia Rating (CDR) scale scores and common neuropsychological tests. In the validation cohort, a time-to-AD dementia trial applying these mid-risk selection criteria to a pool of all non-demented individuals could achieve equivalent power with 47% fewer participants than enrolling at random from that pool. We evaluated surrogate endpoints measureable over two years of follow-up based on cross-validated concordance between predictions from Cox models and observed time to AD dementia. The best performing surrogate, rate of change in CDR sum-of-boxes, did not reduce the trial duration required for equivalent power using estimates from the validation cohort, but alternative surrogates with better ability to predict time to AD dementia should be able to do so. The approach tested here might improve efficiency of prodromal AD trials using other potential measures and could be generalized to other diseases with long prodromal phases. PMID:23629586

A systematic review on the association between inflammatory genes and cognitive decline in non-demented elderly individuals.

PubMed

Stacey, David; Ciobanu, Liliana G; Baune, Bernhard T

2017-06-01

Cognitive impairment, or decline, is not only a feature of Alzheimer׳s disease and other forms of dementia but also normal ageing. Abundant evidence from epidemiological studies points towards perturbed inflammatory mechanisms in aged individuals, though the cause-effect nature of this apparent relationship is difficult to establish. Genetic association studies focusing on polymorphism in and around inflammatory genes represent a viable approach to establish whether inflammatory mechanisms might play a causal role in cognitive decline, whilst also enabling the identification of specific genes potentially influencing specific cognitive facets. Thus, here we provide a review of published genetic association studies investigating inflammatory genes in the context of cognitive decline in elderly, non-demented, samples. Numerous candidate gene association studies have been performed to date, focusing almost exclusively on genes encoding major cytokines. Some of these studies report significant cognitive domain-specific associations implicating Interleukin 1β (IL1β) (rs16944), Tumour Necrosis Factor α (TNFα) (rs1800629) and C-reactive protein (CRP) in various domains of cognitive function. However, the majority of these studies are lacking in statistical power and have other methodological limitations, suggesting some of them may have yielded false positive results. Genome-wide association studies have implicated less direct and less obvious regulators of inflammatory processes (i.e., PDE7A, HS3ST4, SPOCK3), indicating that a shift away from the major cytokine-encoding genes in future studies will be important. Furthermore, better cohesion across studies with regards to the cognitive test batteries administered to participants along with the continued application of longitudinal designs will be vital. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Brain bank of the Brazilian aging brain study group - a milestone reached and more than 1,600 collected brains.

PubMed

Grinberg, Lea Tenenholz; Ferretti, Renata Eloah de Lucena; Farfel, José Marcelo; Leite, Renata; Pasqualucci, Carlos Augusto; Rosemberg, Sérgio; Nitrini, Ricardo; Saldiva, Paulo Hilário Nascimento; Filho, Wilson Jacob

2007-01-01

Brain banking remains a necessity for the study of aging brain processes and related neurodegenerative diseases. In the present paper, we report the methods applied at and the first results of the Brain Bank of the Brazilian Aging Brain Study Group (BBBABSG) which has two main aims: (1) To collect a large number of brains of elderly comprising non-demented subjects and a large spectrum of pathologies related to aging brain processes, (2) To provide quality material to a multidisciplinar research network unraveling multiple aspects of aging brain processes and related neurodegenerative diseases. The subjects are selected from the Sao Paulo Autopsy Service. Brain parts are frozen and fixated. CSF, carotids, kidney, heart and blood are also collected and DNA is extracted. The neuropathological examinations are carried out based on accepted criteria, using immunohistochemistry. Functional status are assessed through a collateral source based on a clinical protocol. Protocols are approved by the local ethics committee and a written informed consent form is obtained. During the first 21 months, 1,602 samples were collected and were classified by Clinical Dementia Rating as CDR0: 65.7%; CDR0.5:12.6%, CDR1:8.2%, CDR2:5.4%, and CDR3:8.1%. On average, the cost for the processing each case stood at 400 US dollars. To date, 14 laboratories have been benefited by the BBBABSG. The high percentage of non- demented subjects and the ethnic diversity of this series may be significantly contributive toward aging brain processes and related neurodegenerative diseases understanding since BBBABSG outcomes may provide investigators the answers to some additional questions.

Differential association of left and right hippocampal volumes with verbal episodic and spatial memory in older adults.

PubMed

Ezzati, Ali; Katz, Mindy J; Zammit, Andrea R; Lipton, Michael L; Zimmerman, Molly E; Sliwinski, Martin J; Lipton, Richard B

2016-12-01

The hippocampus plays a critical role in verbal and spatial memory, thus any pathological damage to this formation may lead to cognitive impairment. It is suggested that right and left hippocampi are affected differentially in healthy or pathologic aging. The purpose of this study was to test the hypothesis that verbal episodic memory performance is associated with left hippocampal volume (HV) while spatial memory is associated with right HV. 115 non-demented adults over age 70 were drawn from the Einstein Aging Study. Verbal memory was measured using the free recall score from the Free and Cued Selective Reminding Test - immediate recall (FCSRT-IR), logical memory immediate and delayed subtests (LM-I and LM-II) from the Wechsler Memory Scale-Revised (WMS-R). Spatial Memory was measured using a computerized dot memory paradigm that has been validated for use in older adults. All participants underwent 3T MRI with subsequent automatized measurement of the volume of each hippocampus. The sample had a mean age of 78.7 years (SD=5.0); 57% were women, and 52% were white. Participants had a mean of 14.3 years (SD=3.5) of education. In regression models, two tests of verbal memory (FCSRT-IR free recall and LM-II) were positively associated with left HV, but not with right HV. Performance on the spatial memory task was associated with right HV, but not left HV. Our findings support the hypothesis that the left hippocampus plays a critical role in episodic verbal memory, while right hippocampus might be more important for spatial memory processing among non-demented older adults. Copyright © 2016 Elsevier Ltd. All rights reserved.

Is Non-Convulsive Status Epilepticus (NCSE) undertreated in patients affected by dementia?

PubMed

Lauretani, Fulvio; Maggio, Marcello; Nardelli, Anna; Saccavini, Marsilio; Ceda, Gian Paolo

2009-01-01

A 80-year-old woman with a history of severe degenerative dementia, with behavioral and psychological symptoms of dementia (BPSD), COPD and hypertension, was admitted to our hospital (Geriatric Unit, University Hospital of Parma) for an acute change in her cognitive status, with stupor status. The clinical question was: "What is the cause of this rapid worsening of cognitive and mental condition in a demented patient?" A diagnosis of Non-Convulsive Status Epilecticus (NCSE), defined by behavioral or cognitive changes from a patient's baseline state of functioning, with seizure activity on EEG, should be considered when patients with severe dementia are admitted to hospital. It is sufficient for the diagnosis of NCSE to be suspected and not strictly confirmed to start preliminary treatment with an antiepileptic drug.

Bias towards dementia: are hip fracture trials excluding too many patients? A systematic review.

PubMed

Hebert-Davies, Jonah; Laflamme, G-Yves; Rouleau, Dominique

2012-12-01

Patients with hip fractures are older and often present many co-morbidities, including dementia. These patients cannot answer quality of life questionnaires and are generally excluded from trials. We hypothesized that a significant number of patients are being excluded from these studies and this may impact outcomes. This was a two part study; the first analyzing databases of two ongoing large-scale multi-centred hip fracture trials and the second being a systematic review. The FAITH and HEALTH studies were analyzed for exclusion incidence directly related to dementia. The second part consisted of a systematic search of all relevant studies within the last 20 years. In the FAITH study, a total of 1690 subjects were excluded, 375 (22.2%) of which were due to dementia or cognitive impairment. In the HEALTH study, 575 were excluded with dementia/cognitive impairment representing 207 patients (36%). Following the systematic review, 251 articles were identified 17 of which were retained. The overall prevalence of dementia was 27.9% (range 2-51%). Only two studies compared demented and non-demented groups. In these studies significant increases in both mortality and complications were found. In summary, when investigating hip fractures, choosing appropriate objective endpoints is essential to ensure results are also applicable to patients with dementia. Copyright © 2012 Elsevier Ltd. All rights reserved.

Scenario design and basic analysis of the National Data Centre Preparedness Exercise 2013

NASA Astrophysics Data System (ADS)

Ross, Ole; Ceranna, Lars; Hartmann, Gernot; Gestermann, Nicolai; Bönneman, Christian

2014-05-01

The Comprehensive Nuclear-Test-Ban Treaty (CTBT) prohibits all kinds of nuclear explosions. For the detection of treaty violations the International Monitoring System (IMS) operates stations observing seismic, hydroacoustic, and infrasound signals as well as radioisotopes in the atmosphere. While the IMS data is collected, processed and technically analyzed in the International Data Center (IDC) of the CTBT-Organization, National Data Centers (NDC) provide interpretation and advice to their government concerning suspicious detections occurring in IMS data. NDC Preparedness Exercises (NPE) are regularly performed dealing with fictitious treaty violations to practice the combined analysis of CTBT verification technologies and for the mutual exchange of information between NDC and also with the IDC. The NPE2010 and NPE2012 trigger scenarios were based on selected seismic events from the Reviewed Event Bulletin (REB) serving as starting point for fictitious Radionuclide dispersion. The main task was the identification of the original REB event and the discrimination between earthquakes and explosions as source. The scenario design of NPE2013 differs from those of previous NPEs. The waveform event selection is not constrained to events in the REB. The exercise trigger is a combination of a tempo-spatial indication pointing to a certain waveform event and simulated radionuclide concentrations generated by forward Atmospheric Transport Modelling based on a fictitious release. For the waveform event the date (4 Sept. 2013) is given and the region is communicated in a map showing the fictitious state of "Frisia" at the Coast of the North Sea in Central Europe. The synthetic radionuclide detections start in Vienna (8 Sept, I-131) and Schauinsland (11 Sept, Xe-133) with rather low activity concentrations and are most prominent in Stockholm and Spitsbergen mid of September 2013. Smaller concentrations in Asia follow later on. The potential connection between the waveform and radionuclide evidence remains unclear. The verification task is to identify the waveform event and to investigate potential sources of the radionuclide findings. Finally the potential conjunction between the sources and the CTBT-relevance of the whole picture has to be evaluated. The overall question is whether requesting an On-Site-Inspection in "Frisia" would be justified. The poster presents the NPE2013 scenario and gives a basic analysis of the initial situation concerning both waveform detections and atmospheric dispersion conditions in Central Europe in early September 2013. The full NPE2013 scenario will be presented at the NDC Workshop mid of May 2014.

Multiple cytokines are involved in the early events leading to the Alzheimer’s disease pathology

PubMed Central

Wilberding, Akiko; Morimoto, Kaori; Satoh, Haruhisa; Harano, Keiko; Harano, Teruo; Arita, Seizaburo; Tooyama, Ikuo; Konishi, Yoshihiro

2009-01-01

It is likely that neuroinflammation begins well before detectable cognitive impairment in Alzheimer’s disease (AD) occurs. Clarifying the alterations occurring prior to the clinical manifestation of overt AD dementia may provide valuable insight into the early diagnosis and management of AD. Herein, to address the issue that neuroinflammation precedes development of AD pathology, we analyzed cytokine expression profiles of the brain, with focus on non-demented control patients with increasing AD pathology, referred to as high pathology control (HPC) cases, who provide an intermediate subset between AD and normal control cases referred to as low pathology control (LPC) cases. With a semi-quantitative analysis of cytokine mRNA, among 15 cytokines and their related molecules tested, we found the involvement of eight: interleukin-1(IL-1) receptor antagonist (IL-1ra), IL-1 converting enzyme (ICE), IL-2, IL-6, IL-8, tumor necrosis factor (TNF) α, macrophage-colony stimulating factor (M-CSF) and transforming growth factor (TGF) β1 during the development from LPC to HPC, while decreases in IL-1ra, IL-8, MCP-1 and TNFα, and an increase in TACE were implicated in the later development from HPC to AD. These findings indicate that neuroinflammation precedes the clinical manifestation of overt dementia, rather than being involved at the later stages of AD. PMID:22586434

Neuropathological findings processed by artificial neural networks (ANNs) can perfectly distinguish Alzheimer's patients from controls in the Nun Study

PubMed Central

Grossi, Enzo; Buscema, Massimo P; Snowdon, David; Antuono, Piero

2007-01-01

Background Many reports have described that there are fewer differences in AD brain neuropathologic lesions between AD patients and control subjects aged 80 years and older, as compared with the considerable differences between younger persons with AD and controls. In fact some investigators have suggested that since neurofibrillary tangles (NFT) can be identified in the brains of non-demented elderly subjects they should be considered as a consequence of the aging process. At present, there are no universally accepted neuropathological criteria which can mathematically differentiate AD from healthy brain in the oldest old. The aim of this study is to discover the hidden and non-linear associations among AD pathognomonic brain lesions and the clinical diagnosis of AD in participants in the Nun Study through Artificial Neural Networks (ANNs) analysis Methods The analyses were based on 26 clinically- and pathologically-confirmed AD cases and 36 controls who had normal cognitive function. The inputs used for the analyses were just NFT and neuritic plaques counts in neocortex and hippocampus, for which, despite substantial differences in mean lesions counts between AD cases and controls, there was a substantial overlap in the range of lesion counts. Results By taking into account the above four neuropathological features, the overall predictive capability of ANNs in sorting out AD cases from normal controls reached 100%. The corresponding accuracy obtained with Linear Discriminant Analysis was 92.30%. These results were consistently obtained in ten independent experiments. The same experiments were carried out with ANNs on a subgroup of 13 non severe AD patients and on the same 36 controls. The results obtained in terms of prediction accuracy with ANNs were exactly the same. Input relevance analysis confirmed the relative dominance of NFT in neocortex in discriminating between AD patients and controls and indicated the lesser importance played by NP in the hippocampus. Conclusion The results of this study suggest that: a) cortical NFT represent the key variable in AD neuropathology; b) the neuropathologic profile of AD subjects is complex, however, c) ANNs can analyze neuropathologic features and differentiate AD cases from controls. PMID:17584929

Neuropathological findings processed by artificial neural networks (ANNs) can perfectly distinguish Alzheimer's patients from controls in the Nun Study.

PubMed

Grossi, Enzo; Buscema, Massimo P; Snowdon, David; Antuono, Piero

2007-06-21

Many reports have described that there are fewer differences in AD brain neuropathologic lesions between AD patients and control subjects aged 80 years and older, as compared with the considerable differences between younger persons with AD and controls. In fact some investigators have suggested that since neurofibrillary tangles (NFT) can be identified in the brains of non-demented elderly subjects they should be considered as a consequence of the aging process. At present, there are no universally accepted neuropathological criteria which can mathematically differentiate AD from healthy brain in the oldest old. The aim of this study is to discover the hidden and non-linear associations among AD pathognomonic brain lesions and the clinical diagnosis of AD in participants in the Nun Study through Artificial Neural Networks (ANNs) analysis The analyses were based on 26 clinically- and pathologically-confirmed AD cases and 36 controls who had normal cognitive function. The inputs used for the analyses were just NFT and neuritic plaques counts in neocortex and hippocampus, for which, despite substantial differences in mean lesions counts between AD cases and controls, there was a substantial overlap in the range of lesion counts. By taking into account the above four neuropathological features, the overall predictive capability of ANNs in sorting out AD cases from normal controls reached 100%. The corresponding accuracy obtained with Linear Discriminant Analysis was 92.30%. These results were consistently obtained in ten independent experiments. The same experiments were carried out with ANNs on a subgroup of 13 non severe AD patients and on the same 36 controls. The results obtained in terms of prediction accuracy with ANNs were exactly the same. Input relevance analysis confirmed the relative dominance of NFT in neocortex in discriminating between AD patients and controls and indicated the lesser importance played by NP in the hippocampus. The results of this study suggest that: a) cortical NFT represent the key variable in AD neuropathology; b) the neuropathologic profile of AD subjects is complex, however, c) ANNs can analyze neuropathologic features and differentiate AD cases from controls.

Performances on the CogState and Standard Neuropsychological Batteries Among HIV Patients Without Dementia

PubMed Central

Overton, Edgar Turner; Kauwe, John S.K.; Paul, Rob; Tashima, Karen; Tate, David F.; Patel, Pragna; Carpenter, Chuck; Patty, David; Brooks, John T.; Clifford, David B

2013-01-01

HIV-associated neurocognitive disorders (HAND) remain prevalent but challenging to diagnose particularly among non-demented individuals. To determine whether a brief computerized battery correlates with formal neurocognitive testing, we identified 46 HIV-infected persons who had undergone both formal neurocognitive testing and a brief computerized battery. Simple detection tests correlated best with formal neuropsychological testing. By multivariable regression model, 53% of the variance in the composite Global Deficit Score was accounted for by elements from the brief computerized tool (p<0.01). These data confirm previous correlation data with the computerized battery, yet illustrate remaining challenges for neurocognitive screening. PMID:21877204

Sustained Attention Training Reduces Spatial Bias in Parkinson's Disease: A Pilot Case Series

PubMed Central

DeGutis, Joseph; Grosso, Mallory; VanVleet, Thomas; Esterman, Michael; Pistorino, Laura; Cronin-Golomb, Alice

2016-01-01

Individuals with Parkinson’s disease (PD) commonly demonstrate lateralized spatial biases, which affect daily functioning. Those with PD with initial motor symptoms on the left body side (LPD) have reduced leftward attention whereas PD with initial motor symptoms on the right side (RPD) may display reduced rightward attention. We investigated whether a sustained attention training program could help reduce these spatial biases. Four non-demented individuals with PD (2 LPD/2 RPD) performed a visual search task before and after one month of computer training. Before training, all participants showed a significant spatial bias and after training, all participants’ spatial bias was eliminated. PMID:26360648

Sustained attention training reduces spatial bias in Parkinson's disease: a pilot case series.

PubMed

DeGutis, Joseph; Grosso, Mallory; VanVleet, Thomas; Esterman, Michael; Pistorino, Laura; Cronin-Golomb, Alice

2016-01-01

Individuals with Parkinson's disease (PD) commonly demonstrate lateralized spatial biases, which affect daily functioning. Those with PD with initial motor symptoms on the left body side (LPD) have reduced leftward attention, whereas PD with initial motor symptoms on the right side (RPD) may display reduced rightward attention. We investigated whether a sustained attention training program could help reduce these spatial biases. Four non-demented individuals with PD (2 LPD, 2 RPD) performed a visual search task before and after 1 month of computer training. Before training, all participants showed a significant spatial bias and after training, all participants' spatial bias was eliminated.

76 FR 65640 - New Standards for Domestic Mailing Services

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-24

...). * * * * * [Revise item 2.2c as follows:] c. Each metered piece must bear full postage at the lowest First- Class... shape, weight, construction, and size to be considered. If the request describes a mailpiece that falls... preparation level (e.g., destination NDC pallets). c. Upon acknowledgement from the manager, Operations...

39 CFR 121.4 - Package Services.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Center Facility (SCF) turnaround Package Services mail accepted at the origin SCF before the day-zero...) Package Services mail accepted at origin before the day-zero Critical Entry Time is 3 days, for each... Center (NDC) Package Services mail accepted at origin before the day-zero Critical Entry Time is 4 days...

Verification Fit Test of Three Size Infantry Helmet

DTIC Science & Technology

1975-01-01

consideration to the helmet designer. This result is consistent with other studies (for example, NDC Technical Report 72-52-CE, " Anthropometry of US Army...FRBQUENCY 18 * 17 * 16 * 15 * 14 * * 13 * * 12 * * * xl . * * 10 * * *S9 * * * * * ° •:i8 * * * * * S7 * * * * * * S6 * * * * * * * S5 4 * * * * * * * *I3

Sexuality in patients with Parkinson's disease, Alzheimer's disease, and other dementias.

PubMed

Bronner, Gila; Aharon-Peretz, Judith; Hassin-Baer, Sharon

2015-01-01

Sexual dysfunction (SD) is common among patients with Parkinson's disease (PD), Alzheimer's disease (AD), and other dementias. Sexual functioning and well-being of patients with PD and their partners are affected by many factors, including motor disabilities, non-motor symptoms (e.g., autonomic dysfunction, sleep disturbances, mood disorders, cognitive abnormalities, pain, and sensory disorders), medication effects, and relationship issues. The common sexual problems are decreased desire, erectile dysfunction, difficulties in reaching orgasm, and sexual dissatisfaction. Hypersexuality is one of a broad range of impulse control disorders reported in PD, attributed to antiparkinsonian therapy, mainly dopamine agonists. Involvement of a multidisciplinary team may enable a significant management of hypersexuality. Data on SD in demented patients are scarce, mainly reporting reduced frequency of sex and erectile dysfunction. Treatment of SD is advised at an early stage. Behavioral problems, including inappropriate sexual behavior (ISB), are distressing for patients and their caregivers and may reflect the prevailing behavior accompanying dementia (disinhibition or apathy associated with hyposexuality). The neurobiologic basis of ISB is still only vaguely understood but assessment and intervention are recommended as soon as ISB is suspected. Management of ISB in dementia demands a thorough evaluation and understanding of the behavior, and can be treated by non-pharmacologic and pharmacologic interventions. © 2015 Elsevier B.V. All rights reserved.

Altered moral decision-making in patients with idiopathic Parkinson's disease.

PubMed

Rosen, Jan B; Rott, Elisa; Ebersbach, Georg; Kalbe, Elke

2015-10-01

Moral decision-making essentially contributes to social conduct. Although patients with Parkinson's disease (PD) show deficits in (non-moral) decision making and related neuropsychological functions, i.e. executive functions, theory of mind (ToM), and empathy, moral decision-making has rarely been examined in PD patients. We examined possible alterations of moral decision-making and associated functions in PD. Twenty non-demented PD patients and 23 age- and education-matched healthy control participants were examined with tests that assess reasoning, executive functions (set-shifting and planning), ToM and empathy, decision-making under risk, and moral intuitions. Moral decision-making was assessed with a close-to-everyday moral dilemma paradigm that opposes socially oriented "altruistic" choices to self-beneficial "egoistic" choices in 20 moral dilemma short stories (10 high and 10 low emotional). Concurrently, electrodermal activity was recorded. PD patients made more egoistic moral decisions than healthy controls. Remarkably, while reasoning, planning and empathy correlated with moral decision-making in the control group, in the PD group neuropsychological functions and dopaminergic medication did not correlate with moral decisions. No evidence for reduced skin conductance responses in PD patients and no relationships between skin conductance responses and moral decisions were observed. This study provides evidence for moral decision-making dysfunctions in PD patients who made more egoistic moral decisions. As a possible underlying mechanism, reduced exercise of attentional control due to a dysfunctional interplay between the prefrontal cortex and the basal ganglia is discussed. Future research will have to determine the impact of PD patients' moral decision-making dysfunctions on everyday life and further determine correlates of the deficits. Copyright © 2015 Elsevier Ltd. All rights reserved.

Frontotemporal white matter changes in amyotrophic lateral sclerosis.

PubMed

Abrahams, Sharon; Goldstein, Laura H; Suckling, John; Ng, Virginia; Simmons, Andy; Chitnis, Xavier; Atkins, Louise; Williams, Steve C R; Leigh, P N

2005-03-01

Cognitive dysfunction can occur in some patients with amyotrophic lateral sclerosis (ALS) who are not suffering from dementia. The most striking and consistent cognitive deficit has been found using tests of verbal fluency. ALS patients with verbal fluency deficits have shown functional imaging abnormalities predominantly in frontotemporal regions using positron emission tomography (PET). This study used automated volumetric voxel-based analysis of grey and white matter densities of structural magnetic resonance imaging (MRI) scans to explore the underlying pattern of structural cerebral change in nondemented ALS patients with verbal fluency deficits. Two groups of ALS patients, defined by the presence or absence of cognitive impairment on the basis of the Written Verbal Fluency Test (ALSi, cognitively impaired, n=11; ALSu, cognitively unimpaired n=12) were compared with healthy age matched controls (n=12). A comparison of the ALSi group with controls revealed significantly (p<0.002) reduced white matter volume in extensive motor and non-motor regions, including regions corresponding to frontotemporal association fibres. These patients demonstrated a corresponding cognitive profile of executive and memory dysfunction. Less extensive white matter reductions were revealed in the comparison of the ALSu and control groups in regions corresponding to frontal association fibres. White matter volumes were also found to correlate with performance on memory tests. There were no significant reductions in grey matter volume in the comparison of either patient group with controls. The structural white matter abnormalities in frontal and temporal regions revealed here may underlie the cognitive and functional imaging abnormalities previously reported in non-demented ALS patients. The results also suggest that extra-motor structural abnormalities may be present in ALS patients with no evidence of cognitive change. The findings support the hypothesis of a continuum of extra-motor cerebral and cognitive change in this disorder.

Antibodies against oxidized LDL and apolipoprotein E polymorphism in demented patients.

PubMed

Bednarska-Makaruk, Małgorzata; Rodo, Maria; Graban, Ałła; Lojkowska, Wanda; Bochyńska, Anna; Ryglewicz, Danuta; Wehr, Hanna

2009-08-15

In serum of 114 patients with dementia and of 102 controls the level of IG class immunoglobulins directed against oxidized LDL and lipids were determined. In isolated DNA apolipoprotein E gene (APOE) polymorphism was identified. In some individuals very high levels of the antibodies were observed. exceeding the 90 percentile in the investigated group. The prevalence of very high anti-ox LDL antibodies level was significantly more frequent in the carriers of epsilon2 allele and less frequent in the carriers of epsilon4 allele.

36 CFR 1260.46 - How does the Department of Defense process referrals?

Code of Federal Regulations, 2014 CFR

2014-07-01

... National Declassification Center (NDC) § 1260.46 How does the Department of Defense process referrals? (a) The Department of Defense (DOD) established the Joint Referral Center (JRC) to review DOD agencies... 36 Parks, Forests, and Public Property 3 2014-07-01 2014-07-01 false How does the Department of...

36 CFR 1260.46 - How does the Department of Defense process referrals?

Code of Federal Regulations, 2012 CFR

2012-07-01

... National Declassification Center (NDC) § 1260.46 How does the Department of Defense process referrals? (a) The Department of Defense (DOD) established the Joint Referral Center (JRC) to review DOD agencies... 36 Parks, Forests, and Public Property 3 2012-07-01 2012-07-01 false How does the Department of...

42 CFR 447.514 - Upper limits for multiple source drugs.

Code of Federal Regulations, 2010 CFR

2010-10-01

... State agency plus an amount established by CMS that is equal to 250 percent of the AMP (as computed... will consider the following additional criteria: (1) The AMP of a terminated NDC will not be used to... section, the AMP of the lowest priced therapeutically and pharmaceutically equivalent drug that is not...

North Korea: Back on the Terrorism List

DTIC Science & Technology

2010-05-24

fabrication.” Pyongyang Korean Central Broadcasting Station, “DPRK NDC Spokesman’s Statement on ROK’s Sunken Ship Investigation Results,” May 20...underground military facilities, including tunnels and bunkers. Takashi Arimoto, Washington correspondent for the Japanese newspaper, Sankei Shimbun, has...underground tunnel with numerous assembly points that Hezbollah 71 Daniel Michaels and

Theoretical Investigation of Device Aspects of Semiconductor Superlattices.

DTIC Science & Technology

1983-09-01

n-i-p-i devices include bulk field effect transistors, ultrasensitive or ultrafast IR photodetectors , tunable light-emitting devices, and ultrafast...transistor4 ultrasensitive or ultrafast IR photodetectors , tunable light-emitt tg devices, and ultrafast optical modulators. Particularlylppealing...differential conductivity ( NDC ) ......................... 19 3.2.2. Spontaneous and stimulated FIR emission from interlayer transitions

North Korean Civil-Military Trends: Military-First Politics to a Point

DTIC Science & Technology

2006-09-01

to the Great Leader. Yi Yong Mu. The NDC’s impact on the formal leadership lineup was made clear by 2001, when Yi Yong Mu, vice chairman of the NDC...to be restricted, as are career bonds that could come about between officers through sequential appointments to same commands. • First time

21 CFR 801.57 - Discontinuation of legacy FDA identification numbers assigned to devices.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Discontinuation of legacy FDA identification... Device Identification § 801.57 Discontinuation of legacy FDA identification numbers assigned to devices... been assigned an FDA labeler code to facilitate use of NHRIC or NDC numbers may continue to use that...

39 CFR 121.3 - Standard Mail.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Facility (SCF) turnaround Standard Mail® pieces accepted at origin before the day zero Critical Entry Time... origin before the day zero Critical Entry Time is 4 days when the OPD&C/F and the ADC are the same... intra-Network Distribution Center (NDC) Standard Mail pieces accepted at origin before the day-zero...

39 CFR 121.3 - Standard Mail.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Facility (SCF) turnaround Standard Mail® pieces accepted at origin before the day zero Critical Entry Time... origin before the day zero Critical Entry Time is 4 days when the OPD&C/F and the ADC are the same... intra-Network Distribution Center (NDC) Standard Mail pieces accepted at origin before the day-zero...

Full counting statistics in a serially coupled double quantum dot system with spin-orbit coupling

NASA Astrophysics Data System (ADS)

Wang, Qiang; Xue, Hai-Bin; Xie, Hai-Qing

2018-04-01

We study the full counting statistics of electron transport through a serially coupled double quantum dot (QD) system with spin-orbit coupling (SOC) weakly coupled to two electrodes. We demonstrate that the spin polarizations of the source and drain electrodes determine whether the shot noise maintains super-Poissonian distribution, and whether the sign transitions of the skewness from positive to negative values and of the kurtosis from negative to positive values take place. In particular, the interplay between the spin polarizations of the source and drain electrodes and the magnitude of the external magnetic field, can give rise to a gate-voltage-tunable strong negative differential conductance (NDC) and the shot noise in this NDC region is significantly enhanced. Importantly, for a given SOC parameter, the obvious variation of the high-order current cumulants as a function of the energy-level detuning in a certain range, especially the dip position of the Fano factor of the skewness can be used to qualitatively extract the information about the magnitude of the SOC.

Diets enriched with cranberry beans alter the microbiota and mitigate colitis severity and associated inflammation.

PubMed

Monk, Jennifer M; Lepp, Dion; Zhang, Claire P; Wu, Wenqing; Zarepoor, Leila; Lu, Jenifer T; Pauls, K Peter; Tsao, Rong; Wood, Geoffrey A; Robinson, Lindsay E; Power, Krista A

2016-02-01

Common beans are rich in phenolic compounds and nondigestible fermentable components, which may help alleviate intestinal diseases. We assessed the gut health priming effect of a 20% cranberry bean flour diet from two bean varieties with differing profiles of phenolic compounds [darkening (DC) and nondarkening (NDC) cranberry beans vs. basal diet control (BD)] on critical aspects of gut health in unchallenged mice, and during dextran sodium sulfate (DSS)-induced colitis (2% DSS wt/vol, 7 days). In unchallenged mice, NDC and DC increased (i) cecal short-chain fatty acids, (ii) colon crypt height, (iii) crypt goblet cell number and mucus content and (iv) Muc1, Klf4, Relmβ and Reg3γ gene expression vs. BD, indicative of enhanced microbial activity and gut barrier function. Fecal 16S rRNA sequencing determined that beans reduced abundance of the Lactobacillaceae (Ruminococcus gnavus), Clostridiaceae (Clostridium perfringens), Peptococcaceae, Peptostreptococcaceae, Rikenellaceae and Pophyromonadaceae families, and increased abundance of S24-7 and Prevotellaceae. During colitis, beans reduced (i) disease severity and colonic histological damage, (ii) increased gene expression of barrier function promoting genes (Muc1-3, Relmβ, and Reg3γ) and (iii) reduced colonic and circulating inflammatory cytokines (IL-1β, IL-6, IFNγ and TNFα). Therefore, prior to disease induction, bean supplementation enhanced multiple concurrent gut health promoting parameters that translated into reduced colitis severity. Moreover, both bean diets exerted similar effects, indicating that differing phenolic content did not influence the endpoints assessed. These data demonstrate a proof-of-concept regarding the gut-priming potential of beans in colitis, which could be extended to mitigate the severity of other gut barrier-associated pathologies. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

Ketoacidosis due to a Low-carbohydrate Diet in an Elderly Woman with Dementia and Abnormal Eating Behavior

PubMed Central

Iwata, Hitoshi; Tsuzuki, Seiichiro; Iwata, Mitsunaga; Terasawa, Teruhiko

2017-01-01

Strict restriction of carbohydrates can induce symptomatic ketoacidosis. We herein report a 76-year-old demented woman who developed ketoacidosis after 1 month of abnormal eating behavior involving selectively eating hamburger steak (estimated carbohydrate =12.7 g/day). Laboratory tests showed high-anion-gap metabolic acidosis with elevated blood ketone levels. She was successfully treated with intravenous fluids followed by oral intake of a regular diet. She remained relapse-free after correcting her eating habits. Healthcare providers should know that abnormal eating behavior in demented people can lead to an extremely-low-carbohydrate diet and cause atypical ketoacidosis unexplained by diabetes, heavy alcohol intake, or starvation conditions. PMID:28883241

Ketoacidosis due to a Low-carbohydrate Diet in an Elderly Woman with Dementia and Abnormal Eating Behavior.

PubMed

Iwata, Hitoshi; Tsuzuki, Seiichiro; Iwata, Mitsunaga; Terasawa, Teruhiko

2017-10-01

Strict restriction of carbohydrates can induce symptomatic ketoacidosis. We herein report a 76-year-old demented woman who developed ketoacidosis after 1 month of abnormal eating behavior involving selectively eating hamburger steak (estimated carbohydrate =12.7 g/day). Laboratory tests showed high-anion-gap metabolic acidosis with elevated blood ketone levels. She was successfully treated with intravenous fluids followed by oral intake of a regular diet. She remained relapse-free after correcting her eating habits. Healthcare providers should know that abnormal eating behavior in demented people can lead to an extremely-low-carbohydrate diet and cause atypical ketoacidosis unexplained by diabetes, heavy alcohol intake, or starvation conditions.

Being prepared to verify the CTBT-Atmospheric Transport modeling and radionuclide analysis at the Austrian National Data Centre during the NDC Preparedness Exercise 2009

NASA Astrophysics Data System (ADS)

Wotawa, Gerhard; Schraick, Irene

2010-05-01

An explosion in the Kara-Zhyra mine in Eastern Kazakhstan on 28 November 2009 around 07:20 UTC was recorded by both the CTBTO seismic and infrasound networks. This event triggered a world-wide preparedness exercise among the CTBTO National Data Centres. Within an hour after the event was selected by the German NDC, a computer program developed by NDC Austria based on weather forecasts from the European Centre for Medium-Range Weather Forecasts (ECMWF) and from the U.S. National Centers for Environmental Prediction (NCEP) was started to analyse what Radionuclide Stations of the CTBTO International Monitoring System (IMS) would be potentially affected by the release from a nuclear explosion at this place in the course of the following 3-10 days. These calculations were daily updated to consider the observed state of the atmosphere instead of the predicted one. Based on these calculations, automated and reviewed radionuclide reports from the potentially affected stations as produced by the CTBTO International Data Centre (IDC) were looked at. An additional analysis of interesting spectra was provided by the Seibersdorf Laboratories. Based on all the results coming in, no evidence whatsoever was found that the explosion in Kazakhstan was nuclear. This is in accordance with ground truth information saying that the event was caused by the detonation of more than 53 Tons of explosives as part of mining operations. A number of conclusions can be drawn from this exercise. First, the international, bilateral as well as national mechanisms and procedures in place for such an event worked smoothly. Second, the products and services from the CTBTO IDC proved to be very useful to assist the member states in their verification efforts. Last but not least, issues with the availability of data from IMS radionuclide stations do remain.

Gas adsorption properties of highly porous metal-organic frameworks containing functionalized naphthalene dicarboxylate linkers.

PubMed

Sim, Jaeung; Yim, Haneul; Ko, Nakeun; Choi, Sang Beom; Oh, Youjin; Park, Hye Jeong; Park, SangYoun; Kim, Jaheon

2014-12-28

Three functionalized metal-organic frameworks (MOFs), MOF-205-NH2, MOF-205-NO2, and MOF-205-OBn, formulated as Zn4O(BTB)4/3(L), where BTB is benzene-1,3,5-tribenzoate and L is 1-aminonaphthalene-3,7-dicarboxylate (NDC-NH2), 1-nitronaphthalene-3,7-dicarboxylate (NDC-NO2) or 1,5-dibenzyloxy-2,6-naphthalenedicarboxylate (NDC-(OBn)2), were synthesized and their gas (H2, CO2, or CH4) adsorption properties were compared to those of the un-functionalized, parent MOF-205. Ordered structural models for MOF-205 and its derivatives were built based on the crystal structures and were subsequently used for predicting porosity properties. Although the Brunauer-Emmett-Teller (BET) surface areas of the three MOF-205 derivatives were reduced (MOF-205, 4460; MOF-205-NH2, 4330; MOF-205-NO2, 3980; MOF-205-OBn, 3470 m(2) g(-1)), all three derivatives were shown to have enhanced H2 adsorption capacities at 77 K and CO2 uptakes at 253, 273, and 298 K respectively at 1 bar in comparison with MOF-205. The results indicate the following trend in H2 adsorption: MOF-205 < MOF-205-NO2 < MOF-205-NH2 < MOF-205-OBn. MOF-205-OBn showed good ideal adsorbed solution theory (IAST) selectivity values of 6.5 for CO2/N2 (15/85 in v/v) and 2.7 for CO2/CH4 (50/50 in v/v) at 298 K. Despite the large reduction (-22%) in the surface area, MOF-205-OBn displayed comparable total volumetric CO2 (at 48 bar) and CH4 (at 35 bar) storage capacities with those of MOF-205 at 298 K: MOF-205-OBn, 305 (CO2) and 112 (CH4) cm(3) cm(-3), and for MOF-205, 307 (CO2) and 120 (CH4) cm(3) cm(-3), respectively.

Hallucinations, dreaming and frequent dozing in Parkinson’s disease: Impact of right-hemisphere neural networks

PubMed Central

Stavitsky, Karina; McNamara, Patrick; Durso, Raymon; Harris, Erica; Auerbach, Sanford; Cronin-Golomb, Alice

2008-01-01

Objective To relate sleep disturbances in Parkinson’s disease (PD) to hemispheric asymmetry of initial presentation. Background Sleep disturbances are common in PD arising from the neurodegenerative process underlying the disease, which is usually lateralized at onset. Patients with left-side onset (LPD: right hemisphere dysfunction) exhibit reduced vigilance relative to those with right-side onset (RPD: left hemisphere dysfunction), leading us to hypothesize that sleep-related disturbances, particularly excessive daytime sleepiness, would be more severe for LPD than for RPD. Methods Thirty-one non-demented participants with PD (17 RPD and 14 LPD) and 17 age-matched control participants with chronic health conditions (CO) were administered the Parkinson’s Disease Sleep Scale and polysomnography was performed on a subset of the PD participants. Results Both PD subgroups exhibited more nighttime motor symptoms than the CO group, but only LPD endorsed more nocturnal hallucinations and daytime dozing. Controlling for mood additionally revealed more vivid dreaming in LPD than RPD. There were no significant differences between LPD and RPD on measures of sleep architecture. Conclusions Increased dreaming, hallucinations, and daytime somnolescence in LPD may be related to changes in right-hemisphere neural networks implicated in the generation and control of visual images, arousal and vigilance. Our results underscore the need to consider side of onset in regard to sleep disturbances in PD. PMID:18797256

Changes in functional organization and white matter integrity in the connectome in Parkinson's disease.

PubMed

Tinaz, Sule; Lauro, Peter M; Ghosh, Pritha; Lungu, Codrin; Horovitz, Silvina G

2017-01-01

Parkinson's disease (PD) leads to dysfunction in multiple cortico-striatal circuits. The neurodegeneration has also been associated with impaired white matter integrity. This structural and functional "disconnection" in PD needs further characterization. We investigated the structural and functional organization of the PD whole brain connectome consisting of 200 nodes using diffusion tensor imaging and resting-state functional MRI, respectively. Data from 20 non-demented PD patients on dopaminergic medication and 20 matched controls were analyzed using graph theory-based methods. We focused on node strength, clustering coefficient, and local efficiency as measures of local network properties; and network modularity as a measure of information flow. PD patients showed reduced white matter connectivity in frontoparietal-striatal nodes compared to controls, but no change in modular organization of the white matter tracts. PD group also showed reduction in functional local network metrics in many nodes distributed across the connectome. There was also decreased functional modularity in the core cognitive networks including the default mode and dorsal attention networks, and sensorimotor network, as well as a lack of modular distinction in the orbitofrontal and basal ganglia nodes in the PD group compared to controls. Our results suggest that despite subtle white matter connectivity changes, the overall structural organization of the PD connectome remains robust at relatively early disease stages. However, there is a breakdown in the functional modular organization of the PD connectome.

A Paleolithic Diet with and without Combined Aerobic and Resistance Exercise Increases Functional Brain Responses and Hippocampal Volume in Subjects with Type 2 Diabetes

PubMed Central

Stomby, Andreas; Otten, Julia; Ryberg, Mats; Nyberg, Lars; Olsson, Tommy; Boraxbekk, Carl-Johan

2017-01-01

Type 2 diabetes is associated with impaired episodic memory functions and increased risk of different dementing disorders. Diet and exercise may potentially reverse these impairments. In this study, sedentary individuals with type 2 diabetes treated by lifestyle ± metformin were randomized to a Paleolithic diet (PD, n = 12) with and without high intensity exercise (PDEX, n = 12) for 12 weeks. Episodic memory function, associated functional brain responses and hippocampal gray matter volume was measured by magnetic resonance imaging. A matched, but not randomized, non-interventional group was included as a reference (n = 6). The PD included a high intake of unsaturated fatty acids and protein, and excluded the intake of dairy products, grains, refined sugar and salt. The exercise intervention consisted of 180 min of supervised aerobic and resistance exercise per week. Both interventions induced a significant weight loss, improved insulin sensitivity and increased peak oxygen uptake without any significant group differences. Furthermore, both interventions were associated with increased functional brain responses within the right anterior hippocampus, right inferior occipital gyrus and increased volume of the right posterior hippocampus. There were no changes in memory performance. We conclude that life-style modification may improve neuronal plasticity in brain areas linked to cognitive function in type 2 diabetes. Putative long-term effects on cognitive functions including decreased risk of dementing disorders await further studies. Clinical trials registration number: Clinicaltrials. gov NCT01513798. PMID:29255413

A Paleolithic Diet with and without Combined Aerobic and Resistance Exercise Increases Functional Brain Responses and Hippocampal Volume in Subjects with Type 2 Diabetes.

PubMed

Stomby, Andreas; Otten, Julia; Ryberg, Mats; Nyberg, Lars; Olsson, Tommy; Boraxbekk, Carl-Johan

2017-01-01

Type 2 diabetes is associated with impaired episodic memory functions and increased risk of different dementing disorders. Diet and exercise may potentially reverse these impairments. In this study, sedentary individuals with type 2 diabetes treated by lifestyle ± metformin were randomized to a Paleolithic diet (PD, n = 12) with and without high intensity exercise (PDEX, n = 12) for 12 weeks. Episodic memory function, associated functional brain responses and hippocampal gray matter volume was measured by magnetic resonance imaging. A matched, but not randomized, non-interventional group was included as a reference ( n = 6). The PD included a high intake of unsaturated fatty acids and protein, and excluded the intake of dairy products, grains, refined sugar and salt. The exercise intervention consisted of 180 min of supervised aerobic and resistance exercise per week. Both interventions induced a significant weight loss, improved insulin sensitivity and increased peak oxygen uptake without any significant group differences. Furthermore, both interventions were associated with increased functional brain responses within the right anterior hippocampus, right inferior occipital gyrus and increased volume of the right posterior hippocampus. There were no changes in memory performance. We conclude that life-style modification may improve neuronal plasticity in brain areas linked to cognitive function in type 2 diabetes. Putative long-term effects on cognitive functions including decreased risk of dementing disorders await further studies. Clinical trials registration number: Clinicaltrials. gov NCT01513798.

A novel presenilin 1 mutation (Ala275Val) as cause of early-onset familial Alzheimer disease.

PubMed

Luedecke, Daniel; Becktepe, Jos S; Lehmbeck, Jan T; Finckh, Ulrich; Yamamoto, Raina; Jahn, Holger; Boelmans, Kai

2014-04-30

Mutations in the presenilin 1 (PS1) gene (PSEN1) are associated with familial Alzheimer disease (FAD). Here, we report on a 50-year-old patient presenting with progressive deterioration of his short-term memory and a family history of early-onset dementia. Diagnostic workup included a neuropsychological examination, structural magnetic resonance (MR) imaging, cerebrospinal fluid (CSF) biomarkers including total tau, phosphorylated tau, and Aβ42 levels, as well as sequencing relevant fragments of the genes PSEN1, PSEN2, and APP. Additionally, we were able to obtain archival paraffin-embedded cerebellar tissue from the patient's father for cosegregation analysis. Clinical, neuropsychological and MR imaging data were indicative of early-onset Alzheimer disease. Furthermore, CSF biomarkers showed a typical pattern for Alzheimer disease. DNA sequencing revealed a heterozygous nucleotide transition (c.824C>T) in exon 8 of PSEN1, leading to an amino acid change from alanine to valine at codon 275 (Ala275Val). The same mutation was found in an archival brain specimen of the patient's demented father, but not in a blood sample of the non-demented mother. This mutation alters a conserved residue in the large hydrophilic loop of PS1, suggesting pathogenic relevance. Cosegregegation analysis and the structural as well as the presumed functional role of the mutated and highly conserved residue suggest FAD causing characteristics of the novel PSEN1 mutation Ala275Val. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Blood folate is associated with asymptomatic or partially symptomatic Alzheimer's disease in the Nun study.

PubMed

Wang, Huifen; Odegaard, Andrew; Thyagarajan, Bharat; Hayes, Jennifer; Cruz, Karen Santa; Derosiers, Mark F; Tyas, Suzanne L; Gross, Myron D

2012-01-01

Asymptomatic and partially symptomatic Alzheimer's disease (APSYMAD) are a series of cognitive states wherein subjects have substantial Alzheimer's disease (AD) pathology (classification B or C by the Consortium to Establish a Registry for AD criteria), but have normal or only partially impaired cognitive function; all of these subjects are non-demented. These cognitive states may arise from the prevention or delay of clinical symptom expression by exposure to certain nutritional factors. This study examined blood levels of folate and antioxidants (i.e., carotenoids) in relation to APSYMAD, nested in the Nun study, a longitudinal study of aging and AD. Sixty elderly female subjects, who had AD on the basis of neuropathology exams, were included. Following adjustment for APOE4 status, education level, and age at blood draw, subjects with the highest blood folate levels had a higher likelihood of being in the APSYMAD group as compared to the demented (AD) group (odds ratio = 1.09, 95% CI = 1.00-1.18. p < 0.06). This association was not significantly influenced by additional adjustment for blood concentrations of carotenoids. Restriction of the population to subjects with near normal cognition on the cognitive state score (score = 1-3) indicated an elevated association with blood folate (odds ratio = 1.12, 95% CI = 1.01-1.25, p < 0.04). Blood carotenoids were not associated with APSYMAD. Thus, folate status may influence the expression of clinical symptoms of AD disease and aid in the delay or prevention of dementia.

Age-Related Defects in Erythrocyte 2,3-Diphosphoglycerate Metabolism in Dementia

PubMed Central

Kaminsky, Yury G.; Reddy, V. Prakash; Ashraf, Ghulam Md; Ahmad, Ausaf; Benberin, Valery V.; Kosenko, Elena A.; Aliev, Gjumrakch

2013-01-01

Alzheimer disease (AD) is the most common dementing illness. Metabolic defects in the brain with aging contribute to the pathogenesis of AD. These changes can be found systematically and thus can be used as potential biomarkers. Erythrocytes (RBCs) are passive “reporter cells” that are not well studied in AD. In the present study, we analyzed an array of glycolytic and related enzymes and intermediates in RBCs from patients with AD and non-Alzheimer dementia (NA), age-matched controls (AC) and young adult controls (YC). AD is characterized by higher activities of hexokinase, phosphofructokinase, and bisphosphoglycerate mutase and bisphosphoglycerate phosphatase in RBCs. In our study, we observed that glycolytic and related enzymes displayed significantly lower activities in AC. However, similar or significantly higher activities were observed in AD and NA groups as compared to YC group. 2,3-diphosphoglycerate (2,3-DPG) levels were significantly decreased in AD and NA patients. The pattern of changes between groups in the above indices strongly correlates with each other. Collectively, our data suggested that AD and NA patients are associated with chronic disturbance of 2,3-DPG metabolism in RBCs. These defects may play a pivotal role in physiological processes, which predispose elderly subjects to AD and NA. PMID:24124630

Hormonal treatment, mild cognitive impairment and Alzheimer's disease

PubMed Central

Ryan, Joanne; Scali, Jaqueline; Carriere, Isabelle; Ritchie, Karen; Ancelin, Marie-Laure

2008-01-01

A plethora of in vitro and in vivo studies have supported the neuroprotective role of estrogens and their impact on the neurotransmitter systems implicated in cognition. Recent hormonal replacement therapy trials in non-demented post-menopausal women suggest a temporary positive effect (notably on verbal memory), and four meta-analyses converge to suggest a possible protective effect in relation to Alzheimer’s disease (reducing risk by 29 to 44%). However, data from the only large randomized controlled trial published to date, the Women’s Health Initiative Memory Study, did not confirm these observations and have even suggested an increase in dementia risk for women using hormonal replacement therapy compared to controls. Apart from methodological differences, one key short-coming of this trial has probably been the focus on late-onset (postmenopausal) hormonal changes, i.e. at a time when the neurodegenerative process has already begun and without taking into account individual lifetime exposure to hormone variability. Multifactorial models based on an exhaustive view of all hormonal events throughout the reproductive life (rather than on a specific exposure to a given steroid) together with other risk factors (notably genetic risk factors related to estrogen receptor polymorphisms) should be explored to clarify the role of hormonal risk factors, or protective factors for cognitive dysfunction and dementia. PMID:18072983

Olfactory Deficit Detected by fMRI in Early Alzheimer’s Disease

PubMed Central

Wang, Jianli; Eslinger, Paul J.; Doty, Richard L.; Zimmerman, Erin K.; Grunfeld, Robert; Sun, Xiaoyu; Connor, James R.; Price, Joseph L.; Smith, Michael B.; Yang, Qing X.

2012-01-01

Alzheimer’s disease (AD) is accompanied by smell dysfunction, as measured by psychophysical tests. Currently it is unknown whether AD-related alterations in central olfactory system neural activity, as measured by functional magnetic resonance imaging (fMRI), are detectable beyond those observed in healthy elderly. Moreover, it is not known whether such changes are correlated with indices of odor perception and dementia. To investigate these issues, twelve early stage AD patients and thirteen non-demented controls underwent fMRI while being exposed to each of three concentrations of lavender oil odorant. All participants were administered the University of Pennsylvania Smell Identification Test (UPSIT), the Mini-Mental State Examination (MMSE), the Mattis Dementia Rating Scale-2 (DRS-2), and the Clinical Dementia Rating Scale (CDR). The Blood oxygen level-dependent (BOLD) signal at primary olfactory cortex (POC) was weaker in AD than in HC subjects. At the lowest odorant concentration, the BOLD signals within POC, hippocampus, and insula were significantly correlated with UPSIT, MMSE, DRS-2, and CDR scores. The BOLD signal intensity and activation volume within the POC increased significantly as a function of odorant concentration in the AD group, but not in the control group. These findings demonstrate that olfactory fMRI is sensitive to the AD-related olfactory and functional cognitive decline. PMID:20709038

Attention in essential tremor: evidence from event-related potentials.

PubMed

Pauletti, C; Mannarelli, D; Locuratolo, N; Vanacore, N; De Lucia, M C; Mina, C; Fattapposta, F

2013-07-01

Clinically subtle executive dysfunctions have recently been described in essential tremor (ET), though the presence of attentional deficits is still unclear. We investigated the psychophysiological aspects of attention in ET, using event-related potentials (ERPs). Twenty-one non-demented patients with ET and 21 age- and sex-matched healthy controls underwent a psychophysiological evaluation. P300 components and the Contingent Negative Variation (CNV) were recorded. The latencies and amplitudes of the P3a and P3b subcomponents and CNV areas were evaluated. Possible correlations between clinical parameters and ERP data were investigated. P3a latency was significantly longer in the ET group (p < 0.05), while no differences emerged between patients and controls in P3b latency. No differences were observed between the two groups in the CNV parameters. ET patients display a difficulty in the response to novelty and in the recruitment of prefrontal attentive circuits, while the memory context-updating process appears to be spared. This selective cognitive dysfunction does not appear to interfere with the attentional set linked to the expectancy evaluated during a complex choice-reaction time task, which is preserved in ET. This multitask psychophysiological approach reveals the presence of a peculiar attentional deficit in patients with ET, thus expanding the clinical features of this disease.

Selective attentional deficit in essential tremor: Evidence from the attention network test.

PubMed

Pauletti, Caterina; Mannarelli, Daniela; De Lucia, Maria Caterina; Locuratolo, Nicoletta; Currà, Antonio; Missori, Paolo; Marinelli, Lucio; Fattapposta, Francesco

2015-11-01

The traditional view of essential tremor (ET) as a monosymptomatic and benign disorder has been reconsidered after patients with ET have been shown to experience cognitive deficits that are also related to attention. The Attention Network Test (ANT) is a rapid, widely used test to measure the efficiency of three attentional networks, i.e. alerting, orienting and executive, by evaluating reaction times (RTs) in response to visual stimuli. The aim of this study was to investigate attentional functioning in ET patients by means of the ANT. 21 non-demented patients with ET and 21 age- and sex-matched healthy controls performed the ANT. RT was significantly longer in ET patients than in controls (p < 0.001). Moreover, a significant difference in alerting and executive efficiency (p = 0.003 and p = 0.01 respectively) was found between groups, while the difference in the orienting efficiency only bordered on significance. Our results point to a difficulty in the alerting and executive domains of attention in ET patients, probably owing to a dysfunction in the cerebello-thalamo-cortical loop. These selective attentional deficits are not related to clinical motor symptoms, contributing to shed further light on the clinical picture of ET. Copyright © 2015 Elsevier Ltd. All rights reserved.

Alzheimer Disease Pathology in Subjects Without Dementia in Two Studies of Aging: The Nun Study and the Adult Changes in Thought Study

PubMed Central

SantaCruz, Karen S.; Sonnen, Joshua A.; Pezhouh, Maryam Kherad; Desrosiers, Mark F.; Nelson, Peter T.; Tyas, Suzanne L.

2012-01-01

Individuals with antemortem preservation of cognition who show autopsy evidence of at least moderate Alzheimer disease (AD) pathology suggest the possibility of brain reserve, that is, functional resistance to structural brain damage. This reserve would, however, only be relevant if the pathologic markers correlate well with dementia. Using data from the Nun Study (n = 498) and the Adult Changes in Thought (ACT) Study (n = 323), we show that Braak staging correlates strongly with dementia status. Moreover, participants with severe (Braak stage V–VI) AD pathology who remained not demented represent only 12% (Nun Study) and 8% (ACT study) of nondemented subjects. Comparison of these subjects to those who were demented revealed that the former group was often significantly memory impaired despite not being classified as demented. Most of these nondemented participants showed only stage V neurofibrillary pathology and frontal tangle counts that were slightly lower than a comparable (Braak stage V) dementia group. In summary, these data indicate that, in individuals with AD-type pathology who do not meet criteria for dementia, neocortical neurofibrillary tangles are somewhat reduced and incipient cognitive decline is present. Our data provide a foundation for helping to define additional factors that may impair, or be protective of, cognition in older adults. PMID:21937909

Alzheimer disease pathology in subjects without dementia in 2 studies of aging: the Nun Study and the Adult Changes in Thought Study.

PubMed

SantaCruz, Karen S; Sonnen, Joshua A; Pezhouh, Maryam Kherad; Desrosiers, Mark F; Nelson, Peter T; Tyas, Suzanne L

2011-10-01

Individuals with antemortem preservation of cognition who show autopsy evidence of at least moderate Alzheimer disease (AD) pathology suggest the possibility of brain reserve, that is, functional resistance to structural brain damage. This reserve would, however, only be relevant if the pathologic markers correlate well with dementia. Using data from the Nun Study (n = 498) and the Adult Changes in Thought (ACT) Study (n = 323), we show that Braak staging correlates strongly with dementia status. Moreover, participants with severe(Braak stage V-VI) AD pathology who remained not demented represent only 12% (Nun Study) and 8% (ACT study) of nondemented subjects. Comparison of these subjects to those who were demented revealed that the former group was often significantly memory-impaired despite not being classified as demented. Most of these nondemented participants showed only stage V neurofibrillary pathology and frontal tangle counts that were slightly lower than a comparable (Braak stage V) dementia group. In summary, these data indicate that, in individuals with AD-type pathology who do not meet criteria for dementia, neocortical neurofibrillary tangles are somewhat reduced and incipient cognitive decline is present. Our data provide a foundation for helping to define additional factors that may impair, or be protective of, cognition in older adults.

Influence of APOE Genotype on Hippocampal Atrophy over Time - An N=1925 Surface-Based ADNI Study

PubMed Central

Li, Bolun; Shi, Jie; Gutman, Boris A.; Baxter, Leslie C.; Thompson, Paul M.; Caselli, Richard J.; Wang, Yalin

2016-01-01

The apolipoprotein E (APOE) e4 genotype is a powerful risk factor for late-onset Alzheimer’s disease (AD). In the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort, we previously reported significant baseline structural differences in APOE e4 carriers relative to non-carriers, involving the left hippocampus more than the right—a difference more pronounced in e4 homozygotes than heterozygotes. We now examine the longitudinal effects of APOE genotype on hippocampal morphometry at 6-, 12- and 24-months, in the ADNI cohort. We employed a new automated surface registration system based on conformal geometry and tensor-based morphometry. Among different hippocampal surfaces, we computed high-order correspondences, using a novel inverse-consistent surface-based fluid registration method and multivariate statistics consisting of multivariate tensor-based morphometry (mTBM) and radial distance. At each time point, using Hotelling’s T2 test, we found significant morphological deformation in APOE e4 carriers relative to non-carriers in the full cohort as well as in the non-demented (pooled MCI and control) subjects at each follow-up interval. In the complete ADNI cohort, we found greater atrophy of the left hippocampus than the right, and this asymmetry was more pronounced in e4 homozygotes than heterozygotes. These findings, combined with our earlier investigations, demonstrate an e4 dose effect on accelerated hippocampal atrophy, and support the enrichment of prevention trial cohorts with e4 carriers. PMID:27065111

Evaluating the capabilities model of dementia care: a non-randomized controlled trial exploring resident quality of life and care staff attitudes and experiences.

PubMed

Moyle, Wendy; Venturato, Lorraine; Cooke, Marie; Murfield, Jenny; Griffiths, Susan; Hughes, Julian; Wolf, Nathan

2016-07-01

This 12 month, Australian study sought to compare the Capabilities Model of Dementia Care (CMDC) with usual long-term care (LTC), in terms of (1) the effectiveness of the CMDC in assisting care staff to improve Quality Of Life (QOL) for older people with dementia; and (2) whether implementation of the CMDC improved staff attitudes towards, and experiences of working and caring for the person with dementia. A single blind, non-randomized controlled trial design, involving CMDC intervention group (three facilities) and a comparison usual LTC practice control group (one facility), was conducted from August 2010 to September 2011. Eighty-one staff members and 48 family members of a person with dementia were recruited from these four LTC facilities. At baseline, 6 and 12 months, staff completed a modified Staff Experiences of Working with Demented Residents questionnaire (SEWDR), and families completed the Quality of Life - Alzheimer's Disease questionnaire (QOL-AD). LTC staff in the usual care group reported significantly lower SEWDR scores (i.e. less work satisfaction) than those in the CMDC intervention group at 12 months (p = 0.005). Similarly, family members in the comparison group reported significantly lower levels of perceived QOL for their relative with dementia (QOL-AD scores) than their counterparts in the CMDC intervention group at 12 months (p = 0.012). Although the study has a number of limitations the CMDC appears to be an effective model of dementia care - more so than usual LTC practice. The CMDC requires further evaluation with participants from a diverse range of LTC facilities and stages of cognitive impairment.

36 CFR § 1260.46 - How does the Department of Defense process referrals?

Code of Federal Regulations, 2013 CFR

2013-07-01

... National Declassification Center (NDC) § 1260.46 How does the Department of Defense process referrals? (a) The Department of Defense (DOD) established the Joint Referral Center (JRC) to review DOD agencies... 36 Parks, Forests, and Public Property 3 2013-07-01 2012-07-01 true How does the Department of...

AQCESS (Automated Quality of Care Evaluation Support System) Ad Hoc Report Generator Quick Reference Guide.

DTIC Science & Technology

1986-06-01

GUIDE JJ TRIMIS Program Office 5401 Westbard Avenue Bethesda, Maryland 20816 W" V NDC Federal Systems. lnc.._" 1300 Piccard Drive .. -Rockville, Marylcn...Project/Teay iUnft1. DOD A A fri-Service Medical Information Systems Program office 11. Contract(C) orGaw a 5401 Westbard Avenue (C) Bethesda, MD 20816

Haste makes waste: Decision making in patients with restless legs syndrome with and without augmentation.

PubMed

Heim, Beatrice; Pertl, Marie-Theres; Stefani, Ambra; Delazer, Margarete; Heidbreder, Anna; Zamarian, Laura; Brandauer, Elisabeth; Seppi, Klaus; Högl, Birgit; Poewe, Werner; Djamshidian, Atbin

2017-01-01

To investigate decision making in patients with primary restless legs syndrome (RLS) with and without augmentation treated with dopaminergic medication. A total of 64 non-demented RLS patients treated with dopaminergic medication with and without augmentation were included in this study. We used an information sampling task to assess how much evidence participants gather before making a decision. Performance was compared to the results of 21 healthy controls. All patients with and without augmentation gathered less information than healthy controls before making a decision (p<0.001), but there was no difference between the two patient groups (p = 1.0). Furthermore, both patient groups made more irrational decisions (e.g. decisions against the evidence they had at the time) than healthy controls (p≤0.002). In addition, RLS patients with augmentation made significantly more irrational decisions than RLS patients without augmentation (p = 0.037) and controls (p<0.001). Our results show that RLS patients treated with dopaminergic drugs, regardless of having augmentation or not, jumped to conclusions and decided significantly more often against the evidence they had at the time of their decision. However, those with augmentation performed worse than all other groups and made more often irrational decisions, a phenomenon which is also common in patients with substance abuse or behavioural addictions. Thus, jumping to conclusions and deciding with a higher degree of uncertainty as well as irrational decision making is more common in RLS patients treated with dopaminergic medication particularly in those with augmentation.

[Euthanasia in advanced dementia: directive is useful].

PubMed

Wijsbek, Henri

2013-01-01

The Dutch Euthanasia Act states that an advance directive can replace an actual request for euthanasia in cases in which a patient has become unable to make autonomous decisions. In Euthanasia and the Severely Demented, I agree with Keizer that the severely demented can suffer unbearably, but contrary to Keizer I do not believe that it is impossible to state in advance the conditions under which one would not wish to go on living any longer. Consequently, euthanasia can be permissible even in patients with late-stage dementia, provided that the other due-care criteria are met. Permissibility by itself, however, will not settle disputes about borderline cases. Due to the erratic course of the disease, the right moment for euthanasia may very well be impossible to determine.

Repeated nightmares

MedlinePlus

Nightmares - repeated; Dream anxiety disorder ... Arnulf I, Nightmares and dream disturbances. In: Kryger M, Roth T, Dement WC, eds. Principles and Practice of Sleep Medicine . 6th ed. Philadelphia, PA: Elsevier; ...

Obstructive sleep apnea - adults

MedlinePlus

... SM. Obstructive sleep apnea: clinical features, evaluation, and principles of management. In: Kryger M, Roth T, Dement WC, eds. Principles and Practice of Sleep Medicine . 6th ed. Philadelphia, ...

Independent contribution of temporal beta-amyloid deposition to memory decline in the pre-dementia phase of Alzheimer's disease.

PubMed

Chételat, Gaël; Villemagne, Victor L; Pike, Kerryn E; Ellis, Kathryn A; Bourgeat, Pierrick; Jones, Gareth; O'Keefe, Graeme J; Salvado, Olivier; Szoeke, Cassandra; Martins, Ralph N; Ames, David; Masters, Colin L; Rowe, Christopher C

2011-03-01

The relationship between β-amyloid deposition and memory deficits in early Alzheimer's disease is unresolved, as past studies show conflicting findings. The present study aims to determine the relative contribution of regional β-amyloid deposition, hippocampal atrophy and white matter integrity to episodic memory deficits in non-demented older individuals harbouring one of the characteristic hallmarks of Alzheimer's disease, i.e. with β-amyloid pathology. Understanding these relationships is critical for effective therapeutic development. Brain magnetic resonance imaging and [(11)C]Pittsburgh Compound B-positron emission tomography scans were obtained in 136 non-demented individuals aged over 60 years, including 93 healthy elderly and 43 patients with mild cognitive impairment. Voxel-based correlations were computed between a memory composite score and grey matter volume, white matter volume and β-amyloid deposition imaging datasets. Hierarchical linear regression analyses were then performed using values extracted in regions of most significant correlations to determine the relative contribution of each modality to memory deficits. All analyses were conducted pooling all groups together as well as within separate subgroups of cognitively normal elderly, patients with mild cognitive impairment and individuals with high versus low neocortical β-amyloid. Brain areas of highest correlation with episodic memory deficits were the hippocampi for grey matter volume, the perforant path for white matter volume and the temporal neocortex for β-amyloid deposition. When considering these three variables together, only hippocampal volume and temporal β-amyloid deposition provided independent contributions to memory deficits. In contrast to global β-amyloid deposition, temporal β-amyloid deposition was still related to memory independently from hippocampal atrophy within subgroups of cognitively normal elderly, patients with mild cognitive impairment or cases with high neocortical β-amyloid. In the pre-dementia stage of Alzheimer's disease, subtle episodic memory impairment is related to β-amyloid deposition, especially in the temporal neocortex, and independently from hippocampal atrophy, suggesting that both factors should be independently targeted in therapeutic trials aimed at reducing cognitive decline.

Mental health and wellbeing in spouses of persons with dementia: the Nord-Trøndelag Health Study.

PubMed

Ask, Helga; Langballe, Ellen Melbye; Holmen, Jostein; Selbæk, Geir; Saltvedt, Ingvild; Tambs, Kristian

2014-05-01

Caring for a spouse diagnosed with dementia can be a stressful situation and can put the caregiving partner at risk of loss of mental health and wellbeing. The main aim of this study was to investigate the relationship between dementia and spousal mental health in a population-based sample of married couples older than 55 years of age. The association was investigated for individuals living together with their demented partner, as well as for individuals whose demented partner was living in an institution. Data on dementia were collected from hospitals and nursing homes in the county of Nord-Trøndelag, Norway. These data were combined with data on spousal mental health, which were collected in a population-based health screening: the Nord-Trøndelag Health Study (HUNT). Of 6,951 participating couples (>55 years), 131 included one partner that had been diagnosed with dementia. Our results indicate that after adjustment for covariates, having a partner with dementia is associated with lower levels of life satisfaction and more symptoms of anxiety and depression than reported by spouses of elderly individuals without dementia. Spouses living together with a partner diagnosed with dementia experienced moderately lower levels of life satisfaction (0.35 standard deviation [SD]) and more symptoms of depression (0.38 SD) and anxiety (0.23 SD) than did their non-caregiving counterparts. Having a partner with dementia that resided in a nursing home was associated with clearly lower life satisfaction. Compared with non-caregivers, these spouses reported lower levels of life satisfaction (1.16 SD), and also more symptoms of depression (0.38 SD), and more symptoms of anxiety (0.42 SD). Having a partner with dementia is associated with loss of mental health and reduced life satisfaction. The risk of adverse mental health outcomes is greatest after the partner's nursing home admission.

Disease-specific expression of the serotonin-receptor 5-HT(2C) in natural killer cells in Alzheimer's dementia.

PubMed

Martins, Luiza Conceição Amorim; Rocha, Natália Pessoa; Torres, Karen Cecília Lima; Dos Santos, Rodrigo Ribeiro; França, Giselle Sabrina; de Moraes, Edgar Nunes; Mukhamedyarov, Marat Alexandrovich; Zefirov, Andrey Lvovich; Rizvanov, Albert Anatolyevich; Kiyasov, Andrey Pavlovich; Vieira, Luciene Bruno; Guimarães, Melissa Monteiro; Yalvaç, Mehmet Emir; Teixeira, Antônio Lúcio; Bicalho, Maria Aparecida Camargo; Janka, Zoltán; Romano-Silva, Marco Aurélio; Palotás, András; Reis, Helton José

2012-10-15

Alzheimer's dementia (AD) is a degenerative brain disorder characterized mainly by cholinergic failure, but other neuro-transmitters are also deficient especially at late stages of the disease. Misfolded β-amyloid peptide has been identified as a causative agent, however inflammatory changes also play a pivotal role. Even though the most prominent pathology is seen in the cognitive functions, specific abnormalities of the central nervous system (CNS) are also reflected in the periphery, particularly in the immune responses of the body. The aim of this study was to characterize the dopaminergic and serotonergic systems in AD, which are also markedly disrupted along with the hallmark acetyl-choline dysfunction. Peripheral blood mono-nuclear cells (PBMCs) from demented patients were judged against comparison groups including individuals with late-onset depression (LOD), as well as non-demented and non-depressed subjects. Cellular sub-populations were evaluated by mono-clonal antibodies against various cell surface receptors: CD4/CD8 (T-lymphocytes), CD19 (B-lymphocytes), CD14 (monocytes), and CD56 (natural-killer (NK)-cells). The expressions of dopamine D(3) and D(4), as well as serotonin 5-HT(1A), 5-HT(2A), 5-HT(2B) and 5-HT(2C) were also assessed. There were no significant differences among the study groups with respect to the frequency of the cellular sub-types, however a unique profound increase in 5-HT(2C) receptor exclusively in NK-cells was observed in AD. The disease-specific expression of 5-HT(2C), as well as the NK-cell cyto-toxicity, has been linked with cognitive derangement in dementia. These changes not only corroborate the existence of bi-directional communication between the immune system and the CNS, but also elucidate the role of inflammatory activity in AD pathology, and may serve as potential biomarkers for less invasive and early diagnostic purposes as well. Copyright © 2012 Elsevier B.V. All rights reserved.

Rhythmic abilities and musical training in Parkinson's disease: do they help?

PubMed

Cochen De Cock, V; Dotov, D G; Ihalainen, P; Bégel, V; Galtier, F; Lebrun, C; Picot, M C; Driss, V; Landragin, N; Geny, C; Bardy, B; Dalla Bella, S

2018-01-01

Rhythmic auditory cues can immediately improve gait in Parkinson's disease. However, this effect varies considerably across patients. The factors associated with this individual variability are not known to date. Patients' rhythmic abilities and musicality (e.g., perceptual and singing abilities, emotional response to music, and musical training) may foster a positive response to rhythmic cues. To examine this hypothesis, we measured gait at baseline and with rhythmic cues in 39 non-demented patients with Parkinson's disease and 39 matched healthy controls. Cognition, rhythmic abilities and general musicality were assessed. A response to cueing was qualified as positive when the stimulation led to a clinically meaningful increase in gait speed. We observed that patients with positive response to cueing ( n  = 17) were more musically trained, aligned more often their steps to the rhythmic cues while walking, and showed better music perception as well as poorer cognitive flexibility than patients with non-positive response ( n  = 22). Gait performance with rhythmic cues worsened in six patients. We concluded that rhythmic and musical skills, which can be modulated by musical training, may increase beneficial effects of rhythmic auditory cueing in Parkinson's disease. Screening patients in terms of musical/rhythmic abilities and musical training may allow teasing apart patients who are likely to benefit from cueing from those who may worsen their performance due to the stimulation.

Nightmares

MedlinePlus

A nightmare is a bad dream that brings out strong feelings of fear, terror, distress, or anxiety . ... Publishing; 2013. Arnulf I, Carr M. Nightmares and dream disturbances. In: Kryger MH, Roth T, Dement WC, ...

21 CFR 207.35 - Notification of registrant; drug establishment registration number and drug listing number.

Code of Federal Regulations, 2011 CFR

2011-04-01

... shall appear and the leading zeros in any segment of the NDC number shall be shown, except that leading... listing. (4)(i) If any change occurs in those product characteristics that clearly distinguish one drug... submit that information to FDA. Such a change includes, but is not limited to, a change in active...

North Korea: Back on the Terrorism List?

DTIC Science & Technology

2010-06-29

Sweden. North Korea has called the investigation’s conclusion a “fabrication.” Pyongyang Korean Central Broadcasting Station, “DPRK NDC Spokesman’s...trainers to southern Lebanon where they instructed Hezbollah cadre in the development of extensive underground military facilities, including tunnels ...Guard” that one such North Korean-assisted facility in southern Lebanon was a sophisticated, 25-kilometer, underground tunnel with numerous assembly

21 CFR 207.35 - Notification of registrant; drug establishment registration number and drug listing number.

Code of Federal Regulations, 2010 CFR

2010-04-01

... shall appear and the leading zeros in any segment of the NDC number shall be shown, except that leading... listing. (4)(i) If any change occurs in those product characteristics that clearly distinguish one drug... submit that information to FDA. Such a change includes, but is not limited to, a change in active...

Trypanosome outer kinetochore proteins suggest conservation of chromosome segregation machinery across eukaryotes

PubMed Central

D’Archivio, Simon

2017-01-01

Kinetochores are multiprotein complexes that couple eukaryotic chromosomes to the mitotic spindle to ensure proper segregation. The model for kinetochore assembly is conserved between humans and yeast, and homologues of several components are widely distributed in eukaryotes, but key components are absent in some lineages. The recent discovery in a lineage of protozoa called kinetoplastids of unconventional kinetochores with no apparent homology to model organisms suggests that more than one system for eukaryotic chromosome segregation may exist. In this study, we report a new family of proteins distantly related to outer kinetochore proteins Ndc80 and Nuf2. The family member in kinetoplastids, KKT-interacting protein 1 (KKIP1), associates with the kinetochore, and its depletion causes severe defects in karyokinesis, loss of individual chromosomes, and gross defects in spindle assembly or stability. Immunopurification of KKIP1 from stabilized kinetochores identifies six further components, which form part of a trypanosome outer kinetochore complex. These findings suggest that kinetochores in organisms such as kinetoplastids are built from a divergent, but not ancestrally distinct, set of components and that Ndc80/Nuf2-like proteins are universal in eukaryotic division. PMID:28034897

Life-span perspective of personality in dementia.

PubMed

Kolanowski, A M; Whall, A L

1996-01-01

To propose an alternative view of personality change in dementia by presenting existing evidence for the continuity of personality. As the population continues to age, dementing illnesses will account for a greater proportion of morbidity and mortality; the care of these people will have a significant effect on the health care system. Life-span perspective of personality continuity. SCOPE METHOD: Review of current literature on personality in dementia using Medline, 1980-1994; CINAHL, 1990-1994; and Psych Lit., 1980-1994. Although there are systematic shifts in personality with dementia, individuals tend to maintain their unique pattern of premorbid personality traits. The personalities of dementia patients seem to reflect adaptive patterns that served them in the past. Use of a life-span perspective can enhance individualized care for demented patients and advance theory development.

Staff attitudes and job satisfaction in the care of demented elderly people: group living compared with long-term care institutions.

PubMed

Alfredson, B B; Annerstedt, L

1994-11-01

The present study is one part of a study evaluating group living (GL) care for demented elderly people in comparison with traditional institutional (TI) care. The present report concentrates on personal and work-related effects on staff. A staff training programme has been implemented, including relevant gerontological knowledge, principles of the new care concept, support and supervision. Effects are evaluated by staff interviews, observation and staff turnover rates. Results show increased knowledge and new emotional and social attitudes, resulting in higher competence and professional conduct towards patients as well as increased motivation, job satisfaction and quality of work for GL staff but not for TI staff. Group living is now a rapidly developing form of care in Sweden.

Cognitive syndromes after the first stroke.

PubMed

Salihović, Denisa; Smajlović, Dževdet; Mijajlović, Milija; Zoletić, Emina; Ibrahimagić, Omer Ć

2018-05-19

The aim of this study is to determine impairments of certain cognitive functions in certain vascular cognitive syndromes and to identify predictors of dementia. One-year prospective study included 275 patients, who were hospitalized at the Department of Neurology Tuzla and therefore fulfilled certain criteria. Patients were divided into following subgroups of vascular cognitive impairment (VCI): dementia of strategic infarct (DSI), cortical dementia (CD), sub cortical dementia (SCD), hemorrhagic dementia (HD), and patients without dementia. Each of the patients underwent the clinical examination and scoring with appropriate measurement scales. Some of the types of VCI were verified in 190 (69%) patients, and the most common was SCD (58%). There was statistically significant connection between the level of intelligence and occurrence of VCI in patients after stroke (p < 0.001). We found significant connection between occurrence of dementia and impairment in narrative memory, numerical memory, visual perceptive, and visual constructive functions in patients with dementia compared with non-demented (p = 0.0001). The executive functions were statistically impaired in patients with CD (p = 0.004) and SCD (p < 0.001). Patients without dementia have significantly better quality of life than the demented ones (p < 0.0001). The algorithm "tree of decision" can help us in the prediction of dementia based on the impairment of certain cognitive functions. Vascular cognitive syndromes are common after stroke. Some of the cognitive functions are significantly impaired in patients with dementia. Impairment of the certain cognitive functions can help in predicting the onset of dementia. Patients without dementia have better quality of life.

Poor dental hygiene and periodontal health in nursing home residents with dementia: an observational study.

PubMed

Zenthöfer, Andreas; Baumgart, Dominik; Cabrera, Tomas; Rammelsberg, Peter; Schröder, Johannes; Corcodel, Nicoleta; Hassel, Alexander Jochen

2017-04-01

Poor oral health conditions are well documented in the institutionalized elderly, but the literature is lacking research on relationships between dementia and periodontal health in nursing home residents. The purpose of this cohort study, therefore, was to assess whether dementia is associated with poor oral health/denture hygiene and an increased risk of periodontal disease in the institutionalized elderly. A total of 219 participants were assessed using the Mini Mental State Examination (MMSE) to determine cognitive state. According to the MMSE outcome, participants scoring ≤20 were assigned to dementia group (D) and those scoring >20 to the non-dementia group (ND), respectively. For each of the groups D and ND, Gingival Bleeding Index (GBI) and Denture Hygiene Index (DHI) linear regression models were used with the confounders age, gender, dementia, number of comorbidities and number of permanent medications. To assess the risk factors for severe periodontitis as measured by the Community Index of Periodontal Treatment Needs, a logistic regression analysis was performed. Statistical analysis revealed no significant differences of GBI as well of DHI for demented and healthy subjects (p > 0.05). Severe periodontitis was detected in 66 % of participants with dementia. The logistic regression showed a 2.9 times increased risk among demented participants (p = 0.006). Oral hygiene, denture hygiene and periodontal health are poor in nursing home residents. The severity of oral problems, primarily periodontitis, seems to be enhanced in subjects suffering from dementia. Longitudinal observations are needed to clarify the cause-reaction relationship.

Capillary cerebral amyloid angiopathy in Alzheimer's disease: association with allocortical/hippocampal microinfarcts and cognitive decline.

PubMed

Hecht, Moritz; Krämer, Lara Maria; von Arnim, Christine A F; Otto, Markus; Thal, Dietmar Rudolf

2018-05-01

Cerebral amyloid angiopathy (CAA) is caused by the deposition of the amyloid β-protein (Aβ) in the wall of cerebral and leptomeningeal blood vessels and is related to Alzheimer's disease (AD). Capillary Aβ deposition is observed in a subset of CAA cases and represents a distinct type of CAA named capillary CAA or CAA type 1. This type of CAA is strongly associated with the presence of the apolipoprotein E ε4 allele. CAA type 1-associated AD cases often exhibit a more severe Aβ plaque pathology but less widespread neurofibrillary tangle (NFT) pathology. The objective of this study was to analyze whether capillary CAA and its effects on cerebral blood flow have an impact on dementia. To address this objective, we performed neuropathological evaluation of 284 autopsy cases of demented and non-demented individuals. We assessed the presence of CAA and its subtypes as well as for that of hemorrhages and infarcts. Capillary CAA and CAA severity were associated with allocortical microinfarcts, comprising the CA1 region of the hippocampus. Allocortical microinfarcts, capillary CAA and CAA severity were, thereby, associated with cognitive decline. In conclusion, allocortical microinfarcts, CAA severity, and the capillary type of CAA were associated with one another and with the development of cognitive decline. Thus, AD cases with CAA type 1 (capillary CAA) appear to develop dementia symptoms not only due to AD-related Aβ plaque and NFT pathology but also due to hippocampal microinfarcts that are associated with CAA type 1 and CAA severity, and that damage a brain region important for memory function.

The physical environment influences neuropsychiatric symptoms and other outcomes in assisted living residents

PubMed Central

Bicket, Mark C.; Samus, Quincy M.; McNabney, Mathew; Onyike, Chiadi U.; Mayer, Lawrence S.; Brandt, Jason; Rabins, Peter; Lyketsos, Constantine; Rosenblatt, Adam

2011-01-01

Objective Although the number of elderly residents living in assisted living (AL) facilities is rising, few studies have examined the AL physical environment and its impact on resident well-being. We sought to quantify the relationship of AL physical environment with resident outcomes including neuropsychiatric symptoms (NPS), quality of life (QOL), and fall risk, and to compare the effects for demented and non-demented residents. Methods Prospective cohort study of a stratified random sample of 326 AL residents living in 21 AL facilities. Measures included the Therapeutic Environmental Screening Scale for Nursing Homes and Residential Care (TESS-NH/RC) to rate facilities and in-person assessment of residents for diagnosis (and assessment of treatment) of dementia, ratings on standardized clinical, cognitive, and QOL measures. Regression models compared environmental measures with outcomes. TESS-NH/RC is modified into a scale for rating the AL physical environment AL-EQS. Results The AL Environmental Quality Score (AL-EQS) was strongly negatively associated with Neuropsychiatric Inventory (NPI) total score (p <0.001), positively associated with Alzheimer Disease Related Quality of Life (ADRQL) score (p = 0.010), and negatively correlated with fall risk (p = 0.042). Factor analysis revealed an excellent two-factor solution, Dignity and Sensory. Both were strongly associated with NPI and associated with ADRQL. Conclusion The physical environment of AL facilities likely affects NPS and QOL in AL residents, and the effect may be stronger for residents without dementia than for residents with dementia. Environmental manipulations that increase resident privacy, as well as implementing call buttons and telephones, may improve resident well-being. PMID:20077498

Cognitive functioning and everyday problem solving in older adults.

PubMed

Burton, Catherine L; Strauss, Esther; Hultsch, David F; Hunter, Michael A

2006-09-01

The relationship between cognitive functioning and a performance-based measure of everyday problem-solving, the Everyday Problems Test (EPT), thought to index instrumental activities of daily living (IADL), was examined in 291 community-dwelling non-demented older adults. Performance on the EPT was found to vary according to age, cognitive status, and education. Hierarchical regression analyses revealed that, after adjusting for demographic and health variables, measures of cognitive functioning accounted for 23.6% of the variance in EPT performance. In particular, measures of global cognitive status, cognitive decline, speed of processing, executive functioning, episodic memory, and verbal ability were significant predictors of EPT performance. These findings suggest that cognitive functioning along with demographic variables are important determinants of everyday problem-solving.

VGKC positive autoimmune encephalopathy mimicking dementia.

PubMed

Molloy, Anna; Cassidy, Eugene; Ryan, Aisling; O' Toole, Orna

2011-12-01

Voltage gated potassium channel antibodies (VGKC Abs) are known to cause three rare neurological syndromes- neuromyotonia, Morvan's syndrome and limbic encephalitis although an increasing array of other associated neurological symptoms are becoming recognised. The authors describe the case of a 60-year-old female who presented to the neurology clinic with an apparent early onset dementing process. She was noted to have both extrapyramidal and frontal release signs on examination and was admitted for further evaluation. Her dementia investigation including a neoplastic screen was negative except for VGKC antibody positivity. Her symptoms dramatically improved with commencement of immunosuppression. A non-paraneoplastic VGKC antibody associated dementia-like syndrome has rarely been described. The authors add to the few existing reports of what represents an important reversible cause of cognitive impairment.

[The expressions of anxiety in the elderly. Their diagnosis and therapy].

PubMed

Scapicchio, P L

1995-10-01

Among the most common manifestations of anxiety in the elderly are those associated with neurological disorders. The etiology is often unclear, as anxiety and agitation may be a consequence of insight into the cognitive impairment rather than the direct expression of the neurological deficit. Benzodiazepines are the treatment of choice, particularly the 3-OH compounds that are non oxidised and without active metabolites. Concern about the use of benzodiazepines in the elderly may have been overstated. If used judiciously this class of drugs can prove extremely helpful in reducing day-time anxiety and night-time insomnia. Other medications that are commonly used to treat agitation and disruptive behaviour in demented elderly patients include antipsychotics, beta-blockers, trazodone, buspirone, anticonvulsants.

Electroencephalographic prodromal markers of dementia across conscious states in Parkinson’s disease

PubMed Central

Latreille, Véronique; Gaudet-Fex, Benjamin; Rodrigues-Brazète, Jessica; Panisset, Michel; Chouinard, Sylvain; Postuma, Ronald B.

2016-01-01

Abstract In Parkinson’s disease, electroencephalographic abnormalities during wakefulness and non-rapid eye movement sleep (spindles) were found to be predictive biomarkers of dementia. Because rapid eye movement sleep is regulated by the cholinergic system, which shows early degeneration in Parkinson’s disease with cognitive impairment, anomalies during this sleep stage might mirror dementia development. In this prospective study, we examined baseline electroencephalographic absolute spectral power across three states of consciousness (non-rapid eye movement sleep, rapid eye movement sleep, and wakefulness) in 68 non-demented patients with Parkinson’s disease and 44 healthy controls. All participants underwent baseline polysomnographic recordings and a comprehensive neuropsychological assessment. Power spectral analyses were performed on standard frequency bands. Dominant occipital frequency during wakefulness and ratios of slow-to-fast frequencies during rapid eye movement sleep and wakefulness were also computed. At follow-up (an average 4.5 years after baseline), 18 patients with Parkinson’s disease had developed dementia and 50 patients remained dementia-free. In rapid eye movement sleep, patients with Parkinson’s disease who later developed dementia showed, at baseline, higher absolute power in delta and theta bands and a higher slowing ratio, especially in temporal, parietal, and occipital regions, compared to patients who remained dementia-free and controls. In non-rapid eye movement sleep, lower baseline sigma power in parietal cortical regions also predicted development of dementia. During wakefulness, patients with Parkinson’s disease who later developed dementia showed lower dominant occipital frequency as well as higher delta and slowing ratio compared to patients who remained dementia-free and controls. At baseline, higher slowing ratios in temporo-occipital regions during rapid eye movement sleep were associated with poor performance on visuospatial tests in patients with Parkinson’s disease. Using receiver operating characteristic curves, we found that best predictors of dementia in Parkinson’s disease were rapid eye movement sleep slowing ratios in posterior regions, wakefulness slowing ratios in temporal areas, and lower dominant occipital frequency. These results suggest that electroencephalographic slowing during sleep is a new promising predictive biomarker for Parkinson’s disease dementia, perhaps as a marker of cholinergic denervation. PMID:26912643

Snoring -- adults

MedlinePlus

... In: Kryger M, Roth T, Dement WC, eds. Principles and Practice of Sleep Medicine . 6th ed. Philadelphia, ... member of Hi-Ethics and subscribes to the principles of the Health on the Net Foundation (www. ...

Reliability of Three Benton Judgment of Line Orientation Short Forms in Idiopathic Parkinson’s Disease

PubMed Central

Gullett, Joseph M.; Price, Catherine C.; Nguyen, Peter; Okun, Michael S.; Bauer, Russell M.; Bowers, Dawn

2013-01-01

Individuals with Parkinson’s disease (PD) often exhibit deficits in visuospatial functioning throughout the course of their disease. These deficits should be carefully assessed as they may have implications for patient safety and disease severity. One of the most commonly administered tests of visuospatial ability, the Benton Judgment of Line Orientation (JLO), consists of 30 pairs of lines requiring the patient to match the orientation of two lines to an array of 11 lines on a separate page. Reliable short forms have been constructed out of the full JLO form, but the reliability of these forms in PD has yet to be examined. Recent functional MRI studies examining the JLO demonstrate right parietal and occipital activation, as well as bilateral frontal activation and PD is known to adversely affect these pathways. We compared the reliability of the original full form to three unique short forms in a sample of 141 non-demented, idiopathic PD patients and 56 age and education matched controls. Results indicated that a two-thirds length short form can be used with high reliability and classification accuracy in patients with idiopathic PD. The other short forms performed in a similar, though slightly less reliable manner. PMID:23957375

Sample entropy and regularity dimension in complexity analysis of cortical surface structure in early Alzheimer's disease and aging.

PubMed

Chen, Ying; Pham, Tuan D

2013-05-15

We apply for the first time the sample entropy (SampEn) and regularity dimension model for measuring signal complexity to quantify the structural complexity of the brain on MRI. The concept of the regularity dimension is based on the theory of chaos for studying nonlinear dynamical systems, where power laws and entropy measure are adopted to develop the regularity dimension for modeling a mathematical relationship between the frequencies with which information about signal regularity changes in various scales. The sample entropy and regularity dimension of MRI-based brain structural complexity are computed for early Alzheimer's disease (AD) elder adults and age and gender-matched non-demented controls, as well as for a wide range of ages from young people to elder adults. A significantly higher global cortical structure complexity is detected in AD individuals (p<0.001). The increase of SampEn and the regularity dimension are also found to be accompanied with aging which might indicate an age-related exacerbation of cortical structural irregularity. The provided model can be potentially used as an imaging bio-marker for early prediction of AD and age-related cognitive decline. Copyright © 2013 Elsevier B.V. All rights reserved.

Cognitive side-effects of electroconvulsive therapy in elderly depressed patients.

PubMed

Dybedal, Gro Strømnes; Tanum, Lars; Sundet, Kjetil; Gaarden, Torfinn Lødøen; Bjølseth, Tor Magne

2014-01-01

Knowledge about cognitive side-effects induced by electroconvulsive therapy (ECT) in depressed elderly patients is sparse. In this study we investigated changes in the cognitive functioning of non-demented elderly depressed patients receiving ECT (n = 62) compared with healthy elderly people (n = 17). Neuropsychological tests were administered at the start of treatment and again within 1 week after treatment. We computed reliable change indices (RCIs) using simple regression methods. RCIs are statistical methods for analyzing change in individuals that have not yet been used in studies of the acute cognitive side-effects of ECT. At the group level, only letter fluency performance was found to be significantly reduced in the ECT group compared with the controls, whereas both groups demonstrated stable or improved performance on all other measures. At the individual level, however, 11% of patients showed retrograde amnesia for public facts post-ECT and 40% of the patients showed a significant decline in neuropsychological functioning. Decline on a measure of delayed verbal anterograde memory was most common. Our findings indicate that there are mild neurocognitive impairments in the acute phase for a substantial minority of elderly patients receiving ECT. Analysis of reliable change facilitated the illumination of cognitive side-effects in our sample.

Balance Confidence and Falls in Non-Demented Essential Tremor Patients: The Role of Cognition

PubMed Central

Rao, Ashwini K.; Gilman, Arthur; Louis, Elan D.

2014-01-01

Objective To examine 1) the effect of cognitive ability on balance confidence and falls, 2) the relationship of balance confidence and falls with quantitative measures of gait, and 3) measures that predict falls, in people with Essential Tremor (ET). Design Cross-sectional study. Setting: General community. Participants One-hundred-eighty participants (132 people with ET and 48 controls). People with ET were divided into two groups based on the median score on the modified Mini Mental State Exam: ET-LCS vs. ET-HCS. Interventions Not applicable. Main Outcome Measures Activities of Balance Confidence-6 (ABC) scale and falls in the previous year. Results ET-LCS had lower ABC-6 scores and a greater number of falls than ET-HCS (p<0.05 for all measures) or controls (p<0.01 for all measures). Quantitative gait measures were significantly correlated with ABC-6 score and falls. Gait speed (p<0.007) and ABC-6 score (p<0.02) were significant predictors of falls. Receiver Operating Characteristic curve analysis revealed that gait speed < 0.9 m/s and ABC-6 score < 51% were associated with moderate sensitivity and specificity in identifying fallers. Conclusions People with ET with low cognitive scores have impaired gait, and report lower balance confidence, and higher number of falls than their counterparts with higher cognitive scores, and controls. We have identified assessments that are easily administered (gait speed and ABC-6 scale), and are associated with falls in ET. PMID:24769121

A PET study of word generation in Huntington's disease: effects of lexical competition and verb/noun category.

PubMed

Lepron, Evelyne; Péran, Patrice; Cardebat, Dominique; Démonet, Jean-François

2009-08-01

Huntington's disease (HD) patients show language production deficits that have been conceptualized as a consequence of executive disorders, e.g. selection deficit between candidate words or switching between word categories. More recently, a deficit of word generation specific to verbs has been reported, which might relate to impaired action representations in HD. We studied the brain correlates of language impairment in HD using H(2)O(15) positron emission tomography (PET). The activation task consisted of generation of semantically appropriate nouns and verbs in dominant (low lexical selection) and selective conditions (high lexical selection). Reaction times were longer and number of errors was higher in 12 non-demented HD than in 17 age-matched controls in all conditions. In both groups, the selective condition yielded longer reaction time and a greater number of errors than the dominant one. PET data revealed that, in control subjects, the left inferior temporal gyrus was involved in the selective condition whereas it was not in HD. Moreover, activity in the anterior cingulate and the inferior frontal gyri was correlated with behavioral performance in control subjects only. In HD, the lack of implication of these regions, already shown to be crucial in lexical selection, might have been partly compensated by the activation in the left supramarginal gyrus (phonological loop activity) and the right inferior frontal gyrus (effortful retrieval processes), which might support accessory language strategies allowing patients to achieve word generation.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moorhouse, Saul J.; Wu, Yue; O’Hare, Dermot, E-mail: dermot.ohare@chem.ox.ac.uk

A newly developed in situ monochromatic high-energy X-ray diffraction setup was used to investigate the synthesis of MOFs using cation-impregnated polymer resin beads as a ion source. The Co–NDC–DMF (NDC=2,6-naphthalenedicarboxylate; DMF=dimethylformamide) system was investigated, a system which is known to produce at least three distinct frameworks. It was found that the resin-assisted synthesis results in the preferential formation of a topology previously impossible to synthesise in bulk, while the comparable nitrate-salt synthesis appeared to form an alternative phases. It was also found that the resin-assisted synthesis is highly diffusion-controlled. - Graphical abstract: In situ monochromatic high-energy X-ray diffraction study ofmore » a MOF synthesis. - Highlights: • Resin-assisted solvothermal MOF synthesis was studied using in situ diffraction. • Full kinetics of reaction can be obtained from in situ data. • Kinetics show that this resin-assisted synthesis is diffusion controlled. • Resin-assisted synthesis enables the production of an alternative bulk phase.« less

Optically controlled low-power on-off mode resonant tunneling oscillator with a heterojunction phototransistor switch.

PubMed

Lee, Kiwon; Park, Jaehong; Lee, Jooseok; Yang, Kyounghoon

2015-03-15

We report an optically controlled low-power on-off mode oscillator based on a resonant tunneling diode (RTD) that is monolithically integrated with a heterojunction phototransistor (HPT) optical switch. In order to achieve a low-power operation at a wavelength of 1.55 μm an InP-based quantum-effect tunneling diode is used for microwave signal generation based on a unique negative differential conductance (NDC) characteristic of the RTD at a low applied voltage. In addition, the high-gain HPT is used for converting incident optical data to an electrical data signal. The fabricated on-off mode oscillator shows a low-power consumption of 5 mW and a high-data-rate of 1  Gb/s at an oscillation frequency of 4.7 GHz. A good energy efficiency of 5  pJ/bit has been obtained due to the low DC power consumption along with high-data-rate performance of the RTD-based optoelectronic integration scheme.

Instrumental nuclear activation techniques and applications to biomedical problems

NASA Astrophysics Data System (ADS)

Akanle, Olufunso Akinbode

The principles and practice of instrumental neutron activation analysis (INAA) which serves as the basis of this work is described. The various irradiation and counting conditions used are also described. As sampling and sample preparation has a large effect on the accuracy of analytical techniques for trace element work, some of the problems faced by the analyst during these processes are identified and ways of minimising these problems are described. A method of obtaining the representative mass for various elements in standard material, Bowen's Kale is described and values for a number of elements in this material have been determined. The application of INAA in the determination of the concentrations of a range of elements in hair and blood samples, whole blood, erythrocytes and plasma obtained from two groups of women, senile demented and depressives and their respective controls is described. The results suggest that the senile dements have significantly higher concentrations of Na, Al, Cl, I and Hg in blood and hair relative to that of the controls whereas, V, Fe, Zn, Cu, Se and Rb were found at higher concentrations in the controls. In the depressives, Na, Al, S, Cl, K, V, Mn, Br, Sc, Ag, I and Hg were found to be significantly elevated in their blood and hair relative to that of controls while Mg, Ca, Zn, Cu, Se, Sb and Au were found at higher concentrations in the controls. The statistical methods used in the interpretation of these results are also described. The effect of Se supplementation on the concentration of Se in whole blood and blood components, collected from three groups of healthy adults given as a supplement to their usual diet, is described. The results indicate that the level of selenium in whole blood and its components increases with dose and time and the concentration of the element is maintained for at least 45 days following cessation of supplementation. The influence of the supplement on some electrolytes was also investigated. The usefulness of the K[0] factor in multielemental analysis is demonstrated by application to a standard material. The method employed for the determination of the parameters needed for accurate determination of the K[0] factor is described.

Inclusive Political Settlements: New Insights from Yemen’s National Dialogue

DTIC Science & Technology

2016-03-01

1990s, negotiated settlements have become important vehicles to renegotiate the social contract of countries. More recently, negotiation processes...inclusive negotiation format, involving large segments of civil society, politicians, and experts, and are usually convened in order to negotiate major...practice of inclusive negotiations . We then describe briefly the context and process of the Yemeni National Dialogue Conference (NDC), including the

Multiple-Barrier Resonant Tunneling Structures for Application in a Microwave Generator Stabilized by Microstrip Resonator

DTIC Science & Technology

2000-06-23

conductivity ( NDC ) effects in double barrier resonant tunneling structures (DBRTS) prove the extremely fast frequency response of charge transport (less...UNCLASSIFIED Defense Technical Information Center Compilation Part Notice ADP013131 TITLE: Multiple-Barrier Resonant Tunneling Structures for...Institute Multiple-barrier resonant tunneling structures for application in a microwave generator stabilized by microstrip resonator S. V. Evstigneev, A. L

Technical Modification Within the Healthcare Industry: Improving Both the Efficacy of the National Drug Code Carrier and the Accessibility of Electronic Health Records to Reduce Adverse Drug Events

DTIC Science & Technology

2013-06-01

with an EHR .................................................. 97 C. SWOT ANALYSIS OF USING QR CODES WITH THE NDC AND WITH EHRS...96 Figure 41. SWOT analysis ................................................................................... 99 xiii LIST OF...Coordinator for Health Information Technology OTC Over-the-Counter PHI Personal Health Information QR Quick Response SWOT Strengths, Weaknesses

Common dysregulation network in the human prefrontal cortex underlies two neurodegenerative diseases.

PubMed

Narayanan, Manikandan; Huynh, Jimmy L; Wang, Kai; Yang, Xia; Yoo, Seungyeul; McElwee, Joshua; Zhang, Bin; Zhang, Chunsheng; Lamb, John R; Xie, Tao; Suver, Christine; Molony, Cliona; Melquist, Stacey; Johnson, Andrew D; Fan, Guoping; Stone, David J; Schadt, Eric E; Casaccia, Patrizia; Emilsson, Valur; Zhu, Jun

2014-07-30

Using expression profiles from postmortem prefrontal cortex samples of 624 dementia patients and non-demented controls, we investigated global disruptions in the co-regulation of genes in two neurodegenerative diseases, late-onset Alzheimer's disease (AD) and Huntington's disease (HD). We identified networks of differentially co-expressed (DC) gene pairs that either gained or lost correlation in disease cases relative to the control group, with the former dominant for both AD and HD and both patterns replicating in independent human cohorts of AD and aging. When aligning networks of DC patterns and physical interactions, we identified a 242-gene subnetwork enriched for independent AD/HD signatures. This subnetwork revealed a surprising dichotomy of gained/lost correlations among two inter-connected processes, chromatin organization and neural differentiation, and included DNA methyltransferases, DNMT1 and DNMT3A, of which we predicted the former but not latter as a key regulator. To validate the inter-connection of these two processes and our key regulator prediction, we generated two brain-specific knockout (KO) mice and show that Dnmt1 KO signature significantly overlaps with the subnetwork (P = 3.1 × 10(-12)), while Dnmt3a KO signature does not (P = 0.017). Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

Verbal memory in drug-naive, newly diagnosed Parkinson's disease. The retrieval deficit hypothesis revisited.

PubMed

Brønnick, Kolbjørn; Alves, Guido; Aarsland, Dag; Tysnes, Ole-Bjørn; Larsen, Jan Petter

2011-01-01

The retrieval deficit hypothesis on memory impairment in patients with Parkinson's disease (PD) implies a selective impairment in recall of learned material with normal encoding, retention, and recognition. This hypothesis has been challenged by new data. We have therefore investigated verbal memory and learning in a large sample of newly diagnosed, drug naïve, non-demented patients with PD. From a sample of patients with PD from the Norwegian ParkWest study, 133 PD patients and 133 controls matched on sex, age, and education were included. The California Verbal Learning Test-2 (CVLT-2) was used to assess verbal memory. Patients performed significantly worse than controls on free and cued recall as well as on recognition memory. Patients used the semantic clustering learning strategy significantly less extensively than the controls and the learning slope of the PD patients was significantly less steep. There was no difference in retention when controlling for encoding. Patients did not perform better on the recognition measure or on cued recall (d-prime), as compared to free recall. Executive functions explained a substantial part of the memory deficits. This study suggests that memory impairment in drug naïve early PD to a large degree is a deficit of learning/ encoding and not of retention or retrieval. An implication is that the retrieval deficit hypothesis should be moderated in its general form. Executive deficits and less extensive use of the efficient semantic clustering learning strategy had a strong impact on learning and memory. (c) 2010 APA, all rights reserved.

Can't sleep? Try these tips

MedlinePlus

... 23320870 . Berry RB, Wagner MH. Behavioral treatment of insomnia. In: Berry RB, Wagner MH, eds. Sleep Medicine ... Davidson JR, Beaulieu-Bonneau S. Cognitive behavior therapies for insomnia. In: Kryger M, Roth T, Dement WC, eds. ...

Work step indication with grid-pattern projection for demented senior people.

PubMed

Uranishi, Yuki; Yamamoto, Goshiro; Asghar, Zeeshan; Pulli, Petri; Kato, Hirokazu; Oshiro, Osamu

2013-01-01

This paper proposes a work step indication method for supporting daily work with a grid-pattern projection. To support an independent life of demented senior people, it is desirable that an instruction is easy to understand visually and not complicated. The proposed method in this paper uses a range image sensor and a camera in addition to a projector. A 3D geometry of a target scene is measured by the range image sensor, and the grid-pattern is projected onto the scene directly. Direct projection of the work step is easier to be associated with the target objects around the assisted person, and the grid-pattern is a solution to indicate the spatial instruction. A prototype has been implemented and has demonstrated that the proposed grid-pattern projection is easy to show the work step.

Neuropsychiatric symptom clusters and functional disability in cognitively-impaired-not-demented individuals.

PubMed

Peters, Kevin R; Rockwood, Kenneth; Black, Sandra E; Hogan, David B; Gauthier, Serge G; Loy-English, Inge; Hsiung, Ging-Yuek R; Jacova, Claudia; Kertesz, Andrew; Feldman, Howard H

2008-02-01

Previous research has shown that cognitively-impaired-not-demented (CIND) individuals with at least one neuropsychiatric symptom (NPS) have more functional disability than individuals without any NPSs. The objectives of the present study were to determine whether there are consistent clusters of NPS in CIND individuals and whether certain NPS clusters are more strongly associated with measures of functional disability than other NPS clusters in this population. This was a cross-sectional baseline study of NPS using the Neuropsychiatric Inventory (NPI) in a national clinic-based observational cohort study (the Canadian Cohort Study of Cognitive Impairment and Related Dementias study). The present investigation focuses on a subset of CIND subjects (73%) whose informant endorsed the presence of at least one NPI item. A hierarchical cluster analysis identified two NPS clusters. One consisted of mood factors (i.e., depression, anxiety, apathy, irritability, and problems with sleep) and the other cluster captured frontal symptoms (i.e., aberrant motor behavior, disinhibition, agitation, and problems with appetite). NPSs grouped within the mood cluster were more common than the frontal cluster (95% of subjects had at least one NPS within the mood cluster versus 53% in the frontal cluster). However, the frontal cluster was more strongly associated with functional disability measures even after controlling for cognitive status (i.e., the Mini-Mental State Exam) and the mood cluster score. The frontal cluster of NPSs was more strongly associated with functional disability than the mood cluster.

[Aspects of senile dementia in ancient Rome: literary fiction and factual reality].

PubMed

Moog, Ferdinand Peter; Schäfer, Daniel

2007-01-01

Old people and their pecularities have been the object of writers since the beginning of Western literature. The aim of this study is to verify the social and juridical significance of senile dementia in ancient Rome. Among the few relevant sources the 10th satire of Juvenal attracts attention. It describes a demented patient who revises his succession in favour of a lady with bad reputation. Logically, we wonder whether such dispositions were possible and after all legally binding. Or did Juvenal exaggerate? A look at the Roman legislation shows: Since the Twelve Tablet Law there were instruments to control or to help demented people. This meant care in the sense of the today's curatorship or guardianship. These measures were supposed to prevent extravagancy or doing business and legal acts like marriages or last wills in the state of diminished responsibility. Nevertheless, it must be assumed that there was a considerable discrepancy between juridical theory and daily practice, because the position of the "pater familias" was virtually untouchable, the individual freedom of the full citizen was firmly underlined and the Roman civil law allowed only little executive interferences. Juvenal's bizarre example should not only be taken as good literary fiction. It might reflect the sad, but nevertheless probable reality of the people directly concerned. Apart from that it has to be said that senile dementia played only a minor role in Roman legislation. Mainly because there were considerably less very old people--and in particular people with senile dementia--than today.

Inequalities in Oral Health for Children with Disabilities: A French National Survey in Special Schools

PubMed Central

Hennequin, Martine; Moysan, Véronique; Jourdan, Didier; Dorin, Martine; Nicolas, Emmanuel

2008-01-01

Background Despite wide recognition that children with disability often have poor oral health, few high quality, controlled results are available. Method Twenty-four objective and subjective criteria covering feeding, autonomy, access to dental care, oral hygiene, oral disease, general health and behavior were evaluated in a observational cross-sectional study of 2,487 children with disability (DC group), 4,772 adolescents with disability (DA group) and 1,641 children without disability (NDC group). Five algorithms ranked the subjects according to clinical criteria in three original oral health indices: the Clinical Oral Health Index (COHI), indicating the level of oral health problems, the Clinical Oral Care Needs Index (COCNI) giving dental care need levels, and the Clinical Oral Prevention Index (COPI) determining possible needs in terms of dental education initiatives. Results DC-group children presented poorer oral health and had greater needs in both treatment and preventive oral health actions than NDC-group children (OR = 3.97, 95% CI = 3.25–4.86 for COHI; OR = 2.01, 95% CI = 1.77–2.28 for COCNI; OR = 5.25, 95% CI = 4.55–6.02 for COPI). These conditions were worse again in the DA group comparing to the DC group (OR = 3.52, 95% CI = 2.7–4.6 for COHI; OR = 1.52, 95% CI = 1.38–1.69 for COCNI; OR = 1.53, 95% CI = 1.39–1.69 for COPI). Conclusion Clinical indices generated by algorithmic association of various clinical indicators allow sensitive clinical measurement, and in this study demonstrated inequalities in oral health for children with disabilities schooling in institutions. Questions need now to be addressed as to the measures that could be taken to compensate for this situation. PMID:18575600

Benefits of game-based leisure activities in normal aging and dementia.

PubMed

Narme, Pauline

2016-12-01

Given the increasing prevalence of dementia and the limited efficacy of pharmacological treatments, it is crucial to improve the knowledge of the factors that might delay the onset of dementia for developing non-pharmacological interventions. Recent studies have provided evidence that game-based interventions, especially the practice of video games, could improve the cognitive functioning (e.g. executive functions) in older adults and in demented patients. The positive effects of these games have also been demonstrated on physical health (e.g. improvement of balance and gait). Video gamed-based interventions may also alleviate mood or behavioral disorders, and increase interactions with friends, family, caregivers or other patients. The positive impact of games on these domains (cognitive and physical decline, social isolation) suggests that game-based interventions might contribute to delay the onset of dementia. Thus, playing games might be considered as a protective factor in dementia and even more as a potential non-pharmacological strategy in dementia rather than leisure activity.

US NDC Modernization: Service Oriented Architecture Study Status

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hamlet, Benjamin R.; Encarnacao, Andre Villanova; Harris, James M.

2014-12-01

This report is a progress update on the USNDC Modernization Service Oriented Architecture (SOA) study describing results from Inception Iteration 1, which occurred between October 2012 and March 2013. The goals during this phase are 1) discovering components of the system that have potential service implementations, 2) identifying applicable SOA patterns for data access, service interfaces, and service orchestration/choreography, and 3) understanding performance tradeoffs for various SOA patterns

Southeast Asia Report, No. 1357

DTIC Science & Technology

1983-10-21

observations as a working journalist. The rah-rah boys in one corner were in high spirit. The inquisition got to a point where a former woman...Business Club held that so-called dialogue, working newspapermen themselves have been discussing their predicament and have come up with some...Interbank is still being worked out. The foreign bank, Ongpin said, wants to get into Interbank even before its’ takeover by NDC. Ongpin

Summaries of Research - Fiscal Year 1991.

DTIC Science & Technology

1992-05-01

determine the cost effectiveness of Navy dental technicians applying occlusal sealants to teeth with incipient caries has been completed at NDC, San Diego... Water and Sodium Ion Concentration on the rate of Crack Propagation and Transverse Strength in Dental Porcelains" has been submitted for publication. An...MARYLAND A long term study to evaluate release kinetics of fluoride from various composite materials was begun. To date, ten different materials have

Building a Capabilities Network to Improve Disaster Preparation Efforts in the Southern Command (SOUTHCOM) Area of Responsibility (AOR)

DTIC Science & Technology

2013-11-14

Rica, Ecuador , El Salvador, Guatemala, Guyana, Haiti, Honduras, Jamaica, Nicaragua, Panama, Paraguay, Peru, Saint Lucia (American Red Cross, n.d.c) 3...contribute to society. (Children International, n.d.a) Currently or previously involved in SOUTHCOM: Honduras, Ecuador , Guatemala, Chile, Honduras...Republic, El Salvador, Guatemala, Guyana, Haiti, Honduras, Jamaica, Nicaragua, Columbia, Ecuador , Bolivia, Brazil, Peru, Paraguay, Chile, and Argentina

MRI or not to MRI! Should brain MRI be a routine investigation in children with autistic spectrum disorders?

PubMed

Zeglam, Adel M; Al-Ogab, Marwa F; Al-Shaftery, Thouraya

2015-09-01

To evaluate the routine usage of Magnetic Resonance Imaging (MRI) of brain and estimate the prevalence of brain abnormalities in children presenting to the Neurodevelopment Clinic of Al-Khadra Hospital (NDC-KH), Tripoli, Libya with autistic spectrum disorders (ASD). The records of all children with ASD presented to NDC-KH over 4-year period (from January 2009 to December 2012) were reviewed. All MRIs were acquired with a 1.5-T Philips (3-D T1, T2, FLAIR coronal and axial sequences). MRIs were reported to be normal, abnormal or no significant abnormalities by a consultant neuroradiologist. One thousand and seventy-five children were included in the study. Seven hundred and eighty-two children (72.7 %) had an MRI brain of whom 555 (71 %) were boys. 26 children (24 males and 2 females) (3.3 %) demonstrated MRI abnormalities (8 leukodystrophic changes, 4 periventricular leukomalacia, 3 brain atrophy, 2 tuberous sclerosis, 2 vascular changes, 1 pineoblastoma, 1 cerebellar angioma, 1 cerebellar hypoplasia, 3 agenesis of corpus callosum, 1 neuro-epithelial cyst). An unexpectedly high rate of MRI abnormalities was found in the first large series of clinical MRI investigations in children with autism. These results could contribute to further research into the pathogenesis of autistic spectrum disorder.

Understanding the origin of Paris Agreement emission uncertainties

NASA Astrophysics Data System (ADS)

Rogelj, Joeri; Fricko, Oliver; Meinshausen, Malte; Krey, Volker; Zilliacus, Johanna J. J.; Riahi, Keywan

2017-06-01

The UN Paris Agreement puts in place a legally binding mechanism to increase mitigation action over time. Countries put forward pledges called nationally determined contributions (NDC) whose impact is assessed in global stocktaking exercises. Subsequently, actions can then be strengthened in light of the Paris climate objective: limiting global mean temperature increase to well below 2 °C and pursuing efforts to limit it further to 1.5 °C. However, pledged actions are currently described ambiguously and this complicates the global stocktaking exercise. Here, we systematically explore possible interpretations of NDC assumptions, and show that this results in estimated emissions for 2030 ranging from 47 to 63 GtCO2e yr-1. We show that this uncertainty has critical implications for the feasibility and cost to limit warming well below 2 °C and further to 1.5 °C. Countries are currently working towards clarifying the modalities of future NDCs. We identify salient avenues to reduce the overall uncertainty by about 10 percentage points through simple, technical clarifications regarding energy accounting rules. Remaining uncertainties depend to a large extent on politically valid choices about how NDCs are expressed, and therefore raise the importance of a thorough and robust process that keeps track of where emissions are heading over time.

Nuclear pore complex integrity requires Lnp1, a regulator of cortical endoplasmic reticulum

PubMed Central

Casey, Amanda K.; Chen, Shuliang; Novick, Peter; Ferro-Novick, Susan; Wente, Susan R.

2015-01-01

The nuclear envelope (NE) and endoplasmic reticulum (ER) are components of the same contiguous membrane system and yet have distinct cellular functions. Mounting evidence suggests roles for some ER proteins in the NE for proper nuclear pore complex (NPC) structure and function. In this study, we identify a NE role in Saccharomyces cerevisiae for Lnp1 and Sey1, proteins required for proper cortical ER formation. Both lnp1Δ and sey1Δ mutants exhibit synthetic genetic interactions with mutants in genes encoding key NPC structural components. Both Lnp1 and Sey1 physically associate with other ER components that have established NPC roles, including Rtn1, Yop1, Pom33, and Per33. Of interest, lnp1Δ rtn1Δ mutants but not rtn1Δ sey1Δ mutants exhibit defects in NPC distribution. Furthermore, the essential NPC assembly factor Ndc1 has altered interactions in the absence of Sey1. Lnp1 dimerizes in vitro via its C-terminal zinc finger motif, a property that is required for proper ER structure but not NPC integrity. These findings suggest that Lnp1's role in NPC integrity is separable from functions in the ER and is linked to Ndc1 and Rtn1 interactions. PMID:26041935

Aurora A kinase contributes to a pole-based error correction pathway

PubMed Central

Ye, Anna A.; Deretic, Jovana; Hoel, Christopher M.; Hinman, Albert W.; Cimini, Daniela; Welburn, Julie P.; Maresca, Thomas J.

2015-01-01

Summary Chromosome biorientation, where sister kinetochores attach to microtubules (MTs) from opposing spindle poles, is the configuration that best ensures equal partitioning of the genome during cell division. Erroneous kinetochore-microtubule (kt-MT) attachments are commonplace but often corrected prior to anaphase [1, 2]. Error correction, thought to be mediated primarily by the centromere-enriched Aurora B kinase (ABK) [3-5], typically occurs near spindle poles [6]; albeit, the relevance of this locale is unclear. Furthermore, polar ejection forces (PEFs), highest near poles [7], can stabilize improper attachments by pushing mal-oriented chromosome arms away from spindle poles [8, 9]. Hence, a conundrum: erroneous kt-MT attachments are weakened where PEFs are most likely to strengthen them. Here, we report that Aurora A kinase (AAK) opposes the stabilizing effect of PEFs. AAK activity contributes to phosphorylation of kinetochore substrates near poles and its inhibition results in chromosome mis-alignment and an increased incidence of erroneous kt-MT attachments. Furthermore, AAK directly phosphorylates a site in the N-terminal tail of Ndc80/Hec1 that has been implicated in reducing the affinity of the Ndc80 complex for MTs when phosphorylated [10-12]. We propose that an AAK activity gradient contributes to correcting mal-oriented kt-MT attachments in the vicinity of spindle poles. PMID:26166783

IDC Reengineering Phase 2 & 3 Rough Order of Magnitude (ROM) Cost Estimate Summary (Leveraged NDC Case).

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harris, James M.; Prescott, Ryan; Dawson, Jericah M.

2014-11-01

Sandia National Laboratories has prepared a ROM cost estimate for budgetary planning for the IDC Reengineering Phase 2 & 3 effort, based on leveraging a fully funded, Sandia executed NDC Modernization project. This report provides the ROM cost estimate and describes the methodology, assumptions, and cost model details used to create the ROM cost estimate. ROM Cost Estimate Disclaimer Contained herein is a Rough Order of Magnitude (ROM) cost estimate that has been provided to enable initial planning for this proposed project. This ROM cost estimate is submitted to facilitate informal discussions in relation to this project and is NOTmore » intended to commit Sandia National Laboratories (Sandia) or its resources. Furthermore, as a Federally Funded Research and Development Center (FFRDC), Sandia must be compliant with the Anti-Deficiency Act and operate on a full-cost recovery basis. Therefore, while Sandia, in conjunction with the Sponsor, will use best judgment to execute work and to address the highest risks and most important issues in order to effectively manage within cost constraints, this ROM estimate and any subsequent approved cost estimates are on a 'full-cost recovery' basis. Thus, work can neither commence nor continue unless adequate funding has been accepted and certified by DOE.« less

A program to generate simulated radioxenon beta–gamma data for concentration verification and validation and training exercises

DOE Office of Scientific and Technical Information (OSTI.GOV)

McIntyre, Justin I.; Schrom, Brian T.; Cooper, Matthew W.

2016-03-08

Abstract Several hundred simulated radioxenon beta-gamma data files were developed to assist in evaluating the performance and results from radioxenon concentration calculation analysis at the International Data Center (IDC) and other National Data Centers (NDC). PNNL developed a Beta-Gamma Simulator (BGSim) that incorporated GEANT-modeled data sets from radioxenon decay chains, as well as functionality to use nuclear detector-acquired data sets to create new beta-gamma spectra with varying amounts of background, 133Xe, 131mXe, 133mXe, 135Xe, and 222Rn and its decay products. The program has been implemented on a web-based applications platform and allows the user to create very specific data setsmore » that incorporate most of the operational parameters for the current beta-gamma systems deployed in the International Monitoring System (IMS) and the On-site Inspection (OSI) equipment. After an initial beta-gamma simulations program was developed, additional uses began to be identified for the program output: training sets of two-dimensional spectra for data analysts at the IDC and other NDC, spectra for exercises such as the Integrated Field Exercise 2014 (IFE14) held in Jordan at the Dead Sea, and testing new analysis methods and algorithms« less

Understanding the origin of Paris Agreement emission uncertainties

PubMed Central

Rogelj, Joeri; Fricko, Oliver; Meinshausen, Malte; Krey, Volker; Zilliacus, Johanna J. J.; Riahi, Keywan

2017-01-01

The UN Paris Agreement puts in place a legally binding mechanism to increase mitigation action over time. Countries put forward pledges called nationally determined contributions (NDC) whose impact is assessed in global stocktaking exercises. Subsequently, actions can then be strengthened in light of the Paris climate objective: limiting global mean temperature increase to well below 2 °C and pursuing efforts to limit it further to 1.5 °C. However, pledged actions are currently described ambiguously and this complicates the global stocktaking exercise. Here, we systematically explore possible interpretations of NDC assumptions, and show that this results in estimated emissions for 2030 ranging from 47 to 63 GtCO2e yr−1. We show that this uncertainty has critical implications for the feasibility and cost to limit warming well below 2 °C and further to 1.5 °C. Countries are currently working towards clarifying the modalities of future NDCs. We identify salient avenues to reduce the overall uncertainty by about 10 percentage points through simple, technical clarifications regarding energy accounting rules. Remaining uncertainties depend to a large extent on politically valid choices about how NDCs are expressed, and therefore raise the importance of a thorough and robust process that keeps track of where emissions are heading over time. PMID:28585924

Understanding the origin of Paris Agreement emission uncertainties.

PubMed

Rogelj, Joeri; Fricko, Oliver; Meinshausen, Malte; Krey, Volker; Zilliacus, Johanna J J; Riahi, Keywan

2017-06-06

The UN Paris Agreement puts in place a legally binding mechanism to increase mitigation action over time. Countries put forward pledges called nationally determined contributions (NDC) whose impact is assessed in global stocktaking exercises. Subsequently, actions can then be strengthened in light of the Paris climate objective: limiting global mean temperature increase to well below 2 °C and pursuing efforts to limit it further to 1.5 °C. However, pledged actions are currently described ambiguously and this complicates the global stocktaking exercise. Here, we systematically explore possible interpretations of NDC assumptions, and show that this results in estimated emissions for 2030 ranging from 47 to 63 GtCO 2 e yr -1 . We show that this uncertainty has critical implications for the feasibility and cost to limit warming well below 2 °C and further to 1.5 °C. Countries are currently working towards clarifying the modalities of future NDCs. We identify salient avenues to reduce the overall uncertainty by about 10 percentage points through simple, technical clarifications regarding energy accounting rules. Remaining uncertainties depend to a large extent on politically valid choices about how NDCs are expressed, and therefore raise the importance of a thorough and robust process that keeps track of where emissions are heading over time.

VGKC positive autoimmune encephalopathy mimicking dementia

PubMed Central

Molloy, Anna; Cassidy, Eugene; Ryan, Aisling; O’ Toole, Orna

2011-01-01

Voltage gated potassium channel antibodies (VGKC Abs) are known to cause three rare neurological syndromes- neuromyotonia, Morvan’s syndrome and limbic encephalitis although an increasing array of other associated neurological symptoms are becoming recognised. The authors describe the case of a 60-year-old female who presented to the neurology clinic with an apparent early onset dementing process. She was noted to have both extrapyramidal and frontal release signs on examination and was admitted for further evaluation. Her dementia investigation including a neoplastic screen was negative except for VGKC antibody positivity. Her symptoms dramatically improved with commencement of immunosuppression. A non-paraneoplastic VGKC antibody associated dementia-like syndrome has rarely been described. The authors add to the few existing reports of what represents an important reversible cause of cognitive impairment. PMID:22674939

Senile dementia of Lewy body type and Alzheimer type are biochemically distinct in terms of paired helical filaments and hyperphosphorylated tau protein.

PubMed

Harrington, C R; Perry, R H; Perry, E K; Hurt, J; McKeith, I G; Roth, M; Wischik, C M

1994-01-01

We have used biochemical assays to examine cingulate and occipital cortices from age-matched cases of Alzheimer's disease (AD; n = 12), senile dementia of the Lewy body type (SDLT; n = 13), Parkinson's disease (PD; 5 non-demented cases and 7 cognitively impaired cases) and controls (n = 11) for paired helical filaments (PHFs), phosphorylated and normal tau protein and beta/A4-protein. Whereas cingulate cortex is characterised by relatively high densities of cortical Lewy bodies in the SDLT cases and lower numbers in PD, these inclusion bodies were absent in the cingulate cortex from AD and control cases. Protease-resistant PHFs and hyperphosphorylated tau protein were found in AD and, at low levels, in a minority of SDLT cases. Qualitatively, both of these preparations were indistinguishable in SDLT from those found in AD but levels of both parameters in SDLT were less than 5% of those in AD. SDLT, PD and control groups did not differ from each other in terms of the quantity of protease-resistant PHFs or the level of hyperphosphorylated tau. Furthermore, PHF accumulation did not distinguish between PD cases with or without dementia. The levels of normal tau protein did not differ between the four groups. beta/A4 protein levels did not distinguish between PD and control groups, between AD and SDLT groups, or between SDLT and control groups for either cingulate or occipital cortices. Thus extensive accumulation of PHFs in either neurofibrillary tangles or dystrophic neurites is not a feature of either SDLT or PD. Our findings provide molecular support for the neuropathological and clinical separation of SDLT as a form of dementia that is distinct from AD.

Electron-Phonon and Electron-Electron Interactions in Individual Suspended Carbon Nanotubes

NASA Astrophysics Data System (ADS)

Cronin, Stephen

2010-03-01

The fabrication of pristine, nearly defect-free, suspended carbon nanotubes (CNTs) enables the observation of several phenomena not seen before in carbon nanotubes, including breakdown of the Born-Oppenheimer approximation^1, mode selective electron-phonon coupling^2, and a Mott insulator transition^3. Raman spectroscopy of these nanotubes under applied gate and bias potentials reveals exceptionally strong electron-phonon coupling, arising from Kohn anomalies, which result in mode selective electron-phonon coupling, negative differential conductance (NDC), and non-equilibrium phonon populations^2,4. Due to the extremely long electron lifetimes, we observe a breakdown of the Born-Oppenheimer approximation, as deduced from the gate voltage-induced changes in the vibrational energies of suspended carbon nanotubes^1. We also report strikingly large variations in the Raman intensity of pristine metallic CNTs in response to gate voltages, which are attributed to a Mott insulating state of the strongly correlated electrons^3. As will be shown, preparing clean, defect-free devices is an essential prerequisite for studying the rich low-dimensional physics of CNTs. (1.) Bushmaker, A.W., Deshpande, V.V., Hsieh, S., Bockrath, M.W., and Cronin, S.B., ``Direct Observation of Born-Oppenheimer Approximation Breakdown in Carbon Nanotubes.'' Nano Letters, 9, 607 (2009). (2.) Bushmaker, A.W., Deshpande, V.V., Bockrath, M.W., and Cronin, S.B., ``Direct Observation of Mode Selective Electron-Phonon Coupling in Suspended Carbon Nanotubes.'' Nano Letters, 7, 3618 (2007) (3.) Bushmaker, A.W., Deshpande, V.V., Hsieh, S., Bockrath, M.W., and Cronin, S.B., ``Large Modulations in the Intensity of Raman-Scattered Light from Pristine Carbon Nanotubes.'' Physical Review Letters, 103, 067401 (2009). (4.) Bushmaker, A.W., Deshpande, V.V., Hsieh, S., Bockrath, M.W., and Cronin, S.B., ``Gate Voltage Controlled Non-Equilibrium and Non-Ohmic Behavior in Suspended Carbon Nanotubes.'' Nano Letters, 9, 2862 (2009)

The Effects of Information Displays in Decisions about Tamoxifen Use for Breast Cancer Chemoprevention

DTIC Science & Technology

2007-09-01

Comparing a  reminder letter, tailored stepped‐care and self‐choice for repeat mammography. Am J Prev  Med.. 25, 308‐314, 2003.  Dement J,  Pompeii  L, Lipkus... Pompeii  L, Ransohoff DF. Accuracy of  Self‐reports of Fecal Occult Blood Tests and Test Results among Individuals in the  Carpentry Trade. Prev Med...Psych Health, 20: 373‐387, 2005.  Lipkus IM, Skinner CE, Dement J,  Pompeii  L, Moser B, Samsa G, Ransohoff D. Increasing  colorectal cancer screening

Effect of education and gender adjustment on the sensitivity and specificity of a cognitive screening battery for dementia: results from the MoVIES Project. Monongahela Valley Independent Elders Survey.

PubMed

Belle, S H; Seaberg, E C; Ganguli, M; Ratcliff, G; DeKosky, S; Kuller, L H

1996-01-01

The Monongahela Valley Independent Elders Survey (MoVIES) used a multiphase process to identify demented persons among 1,366 randomly selected noninstitutionalized individuals 65 years and older. Raw test scores from a cognitive screening battery were used to identify cognitively impaired individuals who were referred for a clinical evaluation. Subsequently, test scores were adjusted for education and gender within age strata. Adjusting test scores affected sensitivity for dementia only among the most educated, increasing sensitivity among younger subjects and decreasing among the older subjects. Specificity increased among the least educated and the oldest subjects. Overall, the adjusted criteria did not perform as well as the unadjusted criteria in this sample. Adjustment for education will not necessarily improve the ability of a screening battery for cognitive function to identify demented persons, particularly if unadjusted scores perform well.

Effects of exercise and horticultural intervention on the brain and mental health in older adults with depressive symptoms and memory problems: study protocol for a randomized controlled trial [UMIN000018547].

PubMed

Makizako, Hyuma; Tsutsumimoto, Kota; Doi, Takehiko; Hotta, Ryo; Nakakubo, Sho; Liu-Ambrose, Teresa; Shimada, Hiroyuki

2015-11-04

Depressive symptoms and memory problems are significant risk factors for dementia. Exercise can reduce depressive symptoms and improve cognitive function in older people. In addition, the benefits of horticultural activity on physical and mental well-being have been demonstrated in people with dementia. Although evidence of such non-pharmacological interventions is mounting, no studies have examined whether physical exercise and horticultural activity exert a positive impact on brain and mental health (e.g., depressive symptoms) in non-demented older adults at high risk of cognitive impairment and depression. Therefore, we propose a randomized controlled trial to assess the efficacy and efficiency of physical exercise and horticultural activity in improving brain and mental health in community-dwelling older adults with memory problems and depressive symptoms. The 20-week randomized controlled trial will include 90 community-dwelling adults aged 65 years or older with memory problems and depressive symptoms. Participants will be randomized to one of three experiments: exercise, horticultural activity, or educational control group, using a 1:1:1 allocation ratio. The combined exercise program and horticultural activity program will consist of 20 weekly 90-minute sessions. Participants in the exercise group will practice aerobic exercise, muscle strength training, postural balance retraining, and dual-task training. The horticultural activity program will include crop-related activities, such as field cultivation, growing, and harvesting. Participants in the educational control group will attend two 90-minute educational classes during the 6-month trial period. Depressive symptoms and memory performance will be measured by the Geriatric Depression Scale-15, and the Logical Memory subtests of the Wechsler Memory Scale-Revised will be used to measure depressive symptoms and memory performance as primary outcomes, at baseline (prior to randomization), immediately following intervention (6 months from baseline), and 6 months after intervention. Hippocampal volume will be measured at baseline and immediately after intervention, using magnetic resonance imaging. Secondary outcomes will comprise cognitive function, including language, attention/executive performance, and processing speed; brain-derived neurotrophic-factor serum levels; and health-related quality of life. This intervention study will determine the clinical importance and efficacy of physical exercise and horticultural activity as non-pharmacological interventions in community-dwelling older adults at high risk of poor brain and mental health. UMIN000018547 ; registered 7 August 2015.

North Korea after Kim Chong-il: Leadership Dynamics and Potential Crisis Scenarios

DTIC Science & Technology

2011-11-01

legal responsibility, and with specified procedures , the actual process is different.3 To date, regime dynamics in the Kim Chong-il era have been... procedures and regulations provide the outlines of formal rule, the 3 For a detailed examination of how...was also made an alternate member. It is also worth noting that 10 of the 12 members of the NDC were represented in the new Politburo lineup , thus

On-Chip Timing of Solid State QUBITS

DTIC Science & Technology

2002-11-13

NDC is well pronounced – with the increase of some 100 mT the gap is considerably quenched and single electron tunneling re-emerges. Apparently we...quantum dots contain roughly 10 - 100 electrons and are attached to metallic leads by tunneling barriers. The main advantage of heterostructures is the...blockade of transport at the peak marked B. The resonances left and right indicate single electron tunneling (A) and a quantum dot state with a

Use of the Dexamethasone Suppression Test with Mentally Retarded Persons: Review and Recommendations.

ERIC Educational Resources Information Center

Wolkowitz, Owen M.

1990-01-01

Studies on the use of the Dexamethasone Suppression Test to detect depression are described, with special emphasis on use of the test with children, demented elderly persons, and mentally retarded persons. (Author/JDD)

Predictors of length of stay in a ward for demented elderly: gender differences.

PubMed

Ono, Toshiyuki; Tamai, Akira; Takeuchi, Daisuke; Tamai, Yuzuru; Iseki, Hidenori; Fukushima, Hiromi; Kasahara, Sumie

2010-09-01

In our previous studies, we found both gender differences among care recipients and predictors that influenced outcomes after discharge from a ward for demented elderly. Here, we investigate predictors that influence the length of stay for each sex. We studied the data of 390 patients with dementia who were hospitalized in a ward for demented elderly between 1 April 2000 and 31 March 2008, and treated until 31 March 2009. The patients were divided into groups classified by gender. We analyzed the gender differences of characteristics and evaluated the predictors that influenced the length of stay in the ward for demented elderly using Cox's proportional hazards model. A model using the initial scores of the Revised Hasegawa Dementia Scale (HDS-R), Assessment Scale for Symptoms of Dementia (ASSD) and Nishimura's activity of daily living scale (N-ADL), which were examined on admission, was named Model 1. In Model 1, we checked the effect of each patient's characteristics, except for complications and destinations, on their length of stay. Model 2 used the final scores of HDS-R, ASSD and N-ADL including complications and destinations. There was a clear gender difference in the length of stay. The length of stay of women was longer than that of men. It was difficult to predict the length of stay in Model 1. Age was the only predictor in women and no predictor was identified in men. In Model 2, complications and the final HDS-R and N-ADL scores were predictors of the length of stay in men. Age, complications and destinations were predictors of the length of stay in women. It was observed that there were gender differences among predictors of the length of stay. However, it was difficult to predict the length of stay on admission. Retrospectively, the length of stay was determined by physical and psychological conditions, not by the social variables in men. In women, it was supposed that the caregiver's wish to give care at home reduced the length of stay. Besides, complication was a common predictor of the extension of stay in each sex. We have to decrease the number of complications as much as possible to reduce the length of stay. © 2010 The Authors. Psychogeriatrics © 2010 Japanese Psychogeriatric Society.

Executive dysfunction affects word list recall performance: Evidence from amyotrophic lateral sclerosis and other neurodegenerative diseases.

PubMed

Consonni, Monica; Rossi, Stefania; Cerami, Chiara; Marcone, Alessandra; Iannaccone, Sandro; Francesco Cappa, Stefano; Perani, Daniela

2017-03-01

The Rey Auditory Verbal Learning Test (RAVLT) is widely used in clinical practice to evaluate verbal episodic memory. While there is evidence that RAVLT performance can be influenced by executive dysfunction, the way executive disorders affect the serial position curve (SPC) has not been yet explored. To this aim, we analysed immediate and delayed recall performances of 13 non-demented amyotrophic lateral sclerosis (ALS) patients with a specific mild executive dysfunction (ALSci) and compared their performances to those of 48 healthy controls (HC) and 13 cognitively normal patients with ALS. Moreover, to control for the impact of a severe dysexecutive syndrome and a genuine episodic memory deficit on the SPC, we enrolled 15 patients with a diagnosis of behavioural variant of frontotemporal dementia (bvFTD) and 18 patients with probable Alzheimer's disease (AD). Results documented that, compared to cognitively normal subjects, ALSci patients had a selective mid-list impairment for immediate recall scores. The bvFTD group obtained low performances with a selectively increased forgetting rate for terminal items, whereas the AD group showed a disproportionately large memory loss on the primary and middle part of the SPC for immediate recall scores and were severely impaired in the delayed recall trial. These results suggested that subtle executive dysfunctions might influence the recall of mid-list items, possibly reflecting deficiency in control strategies at retrieval of word lists, whereas severer dysexecutive syndrome might also affect the recall of terminal items possibly due to attention deficit or retroactive interference. © 2015 The British Psychological Society.

Analysis of the Cerebrospinal Fluid Proteome in Alzheimer's Disease

PubMed Central

Khoonsari, Payam Emami; Häggmark, Anna; Lönnberg, Maria; Mikus, Maria; Kilander, Lena; Lannfelt, Lars; Bergquist, Jonas; Ingelsson, Martin; Nilsson, Peter

2016-01-01

Alzheimer’s disease is a neurodegenerative disorder accounting for more than 50% of cases of dementia. Diagnosis of Alzheimer’s disease relies on cognitive tests and analysis of amyloid beta, protein tau, and hyperphosphorylated tau in cerebrospinal fluid. Although these markers provide relatively high sensitivity and specificity for early disease detection, they are not suitable for monitor of disease progression. In the present study, we used label-free shotgun mass spectrometry to analyse the cerebrospinal fluid proteome of Alzheimer’s disease patients and non-demented controls to identify potential biomarkers for Alzheimer’s disease. We processed the data using five programs (DecyderMS, Maxquant, OpenMS, PEAKS, and Sieve) and compared their results by means of reproducibility and peptide identification, including three different normalization methods. After depletion of high abundant proteins we found that Alzheimer’s disease patients had lower fraction of low-abundance proteins in cerebrospinal fluid compared to healthy controls (p<0.05). Consequently, global normalization was found to be less accurate compared to using spiked-in chicken ovalbumin for normalization. In addition, we determined that Sieve and OpenMS resulted in the highest reproducibility and PEAKS was the programs with the highest identification performance. Finally, we successfully verified significantly lower levels (p<0.05) of eight proteins (A2GL, APOM, C1QB, C1QC, C1S, FBLN3, PTPRZ, and SEZ6) in Alzheimer’s disease compared to controls using an antibody-based detection method. These proteins are involved in different biological roles spanning from cell adhesion and migration, to regulation of the synapse and the immune system. PMID:26950848

SPECT neuroimaging and neuropsychological functions in different stages of Parkinson's disease.

PubMed

Paschali, Anna; Messinis, Lambros; Kargiotis, Odysseas; Lakiotis, Velissarios; Kefalopoulou, Zinovia; Constantoyannis, Costantinos; Papathanasopoulos, Panagiotis; Vassilakos, Pavlos

2010-06-01

The present study investigated differences and associations between cortical perfusion, nigrostriatal dopamine pathway and neuropsychological functions in different stages of Parkinson's disease (PD). We recruited 53 non-demented PD patients divided into four groups according to the Hoehn and Yahr (HY) staging system and 20 healthy controls who were used in the comparison of the neuropsychological findings. Each patient underwent two separate brain single photon emission computed tomography (SPECT) studies (perfusion and dopamine transporter binding) as well as neuropsychological evaluation. Perfusion images of each patient were quantified and compared with a normative database provided by the NeuroGam software manufacturers. Mean values obtained from the cortical areas and neuropsychological measures in the different groups were also compared by analysis of covariance (ANCOVA) controlling for disease duration and educational level. We found cognitive deficits especially in the late PD stages (HY 3, 4 and 5) compared to the early stages (HY 1 and 2) and associations between cognitive decrements and cortical perfusion deterioration mainly in the frontal and posterior cortical areas. Compared with controls, PD patients showed impairments of cognition and cerebral perfusion that increased with clinical severity. Furthermore, we found a significant correlation between the performance on the phonemic fluency task and regional cerebral blood flow (rCBF) in the left frontal lobe. Dopamine transporter binding in the left caudate nucleus significantly correlated with blood flow in the left dorsolateral prefrontal cortex (DLPFC), but not with measures of executive functions. There are significant cognitive and perfusion deficits associated with PD progression, implying a multifactorial neurodegeneration process apart from dopamine depletion in the substantia nigra pars compacta (SNc).

Microstructural Correlates of Emotional Attribution Impairment in Non-Demented Patients with Amyotrophic Lateral Sclerosis.

PubMed

Crespi, Chiara; Cerami, Chiara; Dodich, Alessandra; Canessa, Nicola; Iannaccone, Sandro; Corbo, Massimo; Lunetta, Christian; Falini, Andrea; Cappa, Stefano F

2016-01-01

Impairments in the ability to recognize and attribute emotional states to others have been described in amyotrophic lateral sclerosis patients and linked to the dysfunction of key nodes of the emotional empathy network. Microstructural correlates of such disorders are still unexplored. We investigated the white-matter substrates of emotional attribution deficits in a sample of amyotrophic lateral sclerosis patients without cognitive decline. Thirteen individuals with either probable or definite amyotrophic lateral sclerosis and 14 healthy controls were enrolled in a Diffusion Tensor Imaging study and administered the Story-based Empathy Task, assessing the ability to attribute mental states to others (i.e., Intention and Emotion attribution conditions). As already reported, a significant global reduction of empathic skills, mainly driven by a failure in Emotion Attribution condition, was found in amyotrophic lateral sclerosis patients compared to healthy subjects. The severity of this deficit was significantly correlated with fractional anisotropy along the forceps minor, genu of corpus callosum, right uncinate and inferior fronto-occipital fasciculi. The involvement of frontal commissural fiber tracts and right ventral associative fronto-limbic pathways is the microstructural hallmark of the impairment of high-order processing of socio-emotional stimuli in amyotrophic lateral sclerosis. These results support the notion of the neurofunctional and neuroanatomical continuum between amyotrophic lateral sclerosis and frontotemporal dementia.

Microstructural Correlates of Emotional Attribution Impairment in Non-Demented Patients with Amyotrophic Lateral Sclerosis

PubMed Central

Cerami, Chiara; Dodich, Alessandra; Canessa, Nicola; Iannaccone, Sandro; Corbo, Massimo; Lunetta, Christian; Falini, Andrea; Cappa, Stefano F.

2016-01-01

Impairments in the ability to recognize and attribute emotional states to others have been described in amyotrophic lateral sclerosis patients and linked to the dysfunction of key nodes of the emotional empathy network. Microstructural correlates of such disorders are still unexplored. We investigated the white-matter substrates of emotional attribution deficits in a sample of amyotrophic lateral sclerosis patients without cognitive decline. Thirteen individuals with either probable or definite amyotrophic lateral sclerosis and 14 healthy controls were enrolled in a Diffusion Tensor Imaging study and administered the Story-based Empathy Task, assessing the ability to attribute mental states to others (i.e., Intention and Emotion attribution conditions). As already reported, a significant global reduction of empathic skills, mainly driven by a failure in Emotion Attribution condition, was found in amyotrophic lateral sclerosis patients compared to healthy subjects. The severity of this deficit was significantly correlated with fractional anisotropy along the forceps minor, genu of corpus callosum, right uncinate and inferior fronto-occipital fasciculi. The involvement of frontal commissural fiber tracts and right ventral associative fronto-limbic pathways is the microstructural hallmark of the impairment of high-order processing of socio-emotional stimuli in amyotrophic lateral sclerosis. These results support the notion of the neurofunctional and neuroanatomical continuum between amyotrophic lateral sclerosis and frontotemporal dementia. PMID:27513746

Mapping of Synaptic-Neuronal Impairment on the Brain Surface through Fluctuation Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Musha, Toshimitsu; Kurachi, Takayoshi; Suzuki, Naohoro

2005-08-25

Increase of demented population year by year is becoming a serious social problem to be solved urgently. The most effective way to block this increase is in its early detection by means of an inexpensive, non-invasive, sensitive, reliable and easy-to-operate diagnosis method. We have developed a method satisfying these requirements by using scalp potential fluctuations. We have collected 21ch EEG and SPECT data of 25 very mild Alzheimer's disease (AD) (MMSE=26{+-}1.8), moderately severe AD (MMSE=15.3{+-}6.4) and age-matched normal controls. As AD progresses, local synaptic-neuronal activity becomes abnormal, either more unstable or more inactive than in normal state. Such abnormality ismore » detected in terms of normalized power variance (NPV) of a scalp potential recorded with a scalp electrode. The z-score is defined by z = ((NPV of a subject) - (mean NPV of normal subjects))/(standard deviation of NPV of normal subjects). Correlation of a measured z-score map with the mean z-score map for AD patients characterizes likelihood to AD, in terms of which AD is discriminated from normal with 75% of true positive and 25% false negative probability. By introducing two thresholds, we have 90% of true positive and 10% of false negative discrimination.« less

Relationship between impulsive sensation seeking traits, smoking, alcohol and caffeine intake, and Parkinson's disease.

PubMed

Evans, A H; Lawrence, A D; Potts, J; MacGregor, L; Katzenschlager, R; Shaw, K; Zijlmans, J; Lees, A J

2006-03-01

An inverse relation exists between smoking and coffee intake and Parkinson's disease (PD). The present study explored whether this is explained by low sensation seeking, a personality trait believed to characterise PD. A total of 106 non-demented patients with PD and 106 age and sex matched healthy controls completed a short version of Zuckerman's Sensation Seeking Scale (SSS), the Geriatric Depression Scale, and the Trait Anxiety Inventory. Data were collected on past and current cigarette smoking, and participants also completed food frequency questionnaires to estimate current caffeine and alcohol intake. Patients with PD had lower sensation seeking and higher depression and anxiety scores. They were also less likely to have ever smoked, and had lower caffeine and alcohol intakes. Analysis of the data using conditional logistic regression suggested that the inverse association of PD risk with sensation seeking was independent of smoking, and caffeine and alcohol intake. Moreover, low sensation seeking explained some of the apparent effect of caffeine and alcohol intake on PD. However, the effect of smoking was weakened only slightly when SSS was included in the regression model. This study raises the possibility that there is a neurobiological link between low sensation seeking traits--which might underlie the parkinsonian personality--and the hypothetical protective effect of cigarette smoking and caffeine consumption on PD.

Protein levels of ADAM10, BACE1, and PSEN1 in platelets and leukocytes of Alzheimer's disease patients.

PubMed

Bram, Jessyka Maria de França; Talib, Leda Leme; Joaquim, Helena Passarelli Giroud; Sarno, Tamires Alves; Gattaz, Wagner Farid; Forlenza, Orestes Vicente

2018-05-29

The clinical diagnosis of Alzheimer's disease (AD) is a probabilistic formulation that may lack accuracy particularly at early stages of the dementing process. Abnormalities in amyloid-beta precursor protein (APP) metabolism and in the level of APP secretases have been demonstrated in platelets, and to a lesser extent in leukocytes, of AD patients, with conflicting results. The aim of the present study was to compare the protein level of the APP secretases A-disintegrin and metalloprotease 10 (ADAM10), Beta-site APP-cleaving enzyme 1 (BACE1), and presenilin-1 (PSEN1) in platelets and leukocytes from 20 non-medicated older adults with AD and 20 healthy elders, and to determine the potential use of these biomarkers to discriminate cases of AD from controls. The protein levels of all APP secretases were significantly higher in platelets compared to leukocytes. We found statistically a significant decrease in ADAM10 (52.5%, p < 0.0001) and PSEN1 (32%, p = 0.02) in platelets from AD patients compared to controls, but not in leukocytes. Combining all three secretases to generate receiver-operating characteristic (ROC) curves, we found a good discriminatory effect (AD vs. controls) when using platelets (the area under the curve-AUC-0.90, sensitivity 88.9%, specificity 66.7%, p = 0.003), but not in leukocytes (AUC 0.65, sensitivity 77.8%, specificity 50.0%, p = 0.2). Our findings indicate that platelets represent a better biological matrix than leukocytes to address the peripheral level of APP secretases. In addition, combining the protein level of ADAM10, BACE1, and PSEN1 in platelets, yielded a good accuracy to discriminate AD from controls.

Impaired Perception of Biological Motion in Parkinson’s Disease

PubMed Central

Jaywant, Abhishek; Shiffrar, Maggie; Roy, Serge; Cronin-Golomb, Alice

2016-01-01

Objective We examined biological motion perception in Parkinson’s disease (PD). Biological motion perception is related to one’s own motor function and depends on the integrity of brain areas affected in PD, including posterior superior temporal sulcus. If deficits in biological motion perception exist, they may be specific to perceiving natural/fast walking patterns that individuals with PD can no longer perform, and may correlate with disease-related motor dysfunction. Method 26 non-demented individuals with PD and 24 control participants viewed videos of point-light walkers and scrambled versions that served as foils, and indicated whether each video depicted a human walking. Point-light walkers varied by gait type (natural, parkinsonian) and speed (0.5, 1.0, 1.5 m/s). Participants also completed control tasks (object motion, coherent motion perception), a contrast sensitivity assessment, and a walking assessment. Results The PD group demonstrated significantly less sensitivity to biological motion than the control group (p<.001, Cohen’s d=1.22), regardless of stimulus gait type or speed, with a less substantial deficit in object motion perception (p=.02, Cohen’s d=.68). There was no group difference in coherent motion perception. Although individuals with PD had slower walking speed and shorter stride length than control participants, gait parameters did not correlate with biological motion perception. Contrast sensitivity and coherent motion perception also did not correlate with biological motion perception. Conclusion PD leads to a deficit in perceiving biological motion, which is independent of gait dysfunction and low-level vision changes, and may therefore arise from difficulty perceptually integrating form and motion cues in posterior superior temporal sulcus. PMID:26949927

Frontotemporal dementia: evidence for impairment of ascending serotoninergic but not noradrenergic innervation. Immunocytochemical and quantitative study using a graph method.

PubMed

Yang, Y; Schmitt, H P

2001-03-01

A graph method was employed to analyze the spatial neuronal patterns of nuclear grays of the pontine tegmentum with ascending aminergic projections to the forebrain in 12 cases of frontotemporal dementia (FTD). The nuclear grays examined were the nucleus centralis superior (NCS), a part of the nucleus raphae dorsalis (NRD), and the locus coeruleus (LC). The results were compared with 30 cases of Alzheimer's disease (AD) and 35 non-demented controls. In addition to the graph evaluations, neuronal cytoplasmic inclusion bodies were stained by silver impregnation and ubiquitin (Ub) and tau immunohistochemistry. The FTD cases showed a significant, 40%, decline in number of neurons in the NCS and NRD, while the LC was spared. The magnitude of neuronal loss matched that of AD where, by contrast, the LC was also severely changed. Amyloid deposition and Alzheimer neurofibrillary tangles occurred in the aminergic nuclei almost exclusively in AD and, to a minor extent, in some aged controls. No cytoplasmic inclusion bodies were found in the aminergic nuclei of the FTD cases. However, 6 cases had Ub-positive but tau-negative neuronal inclusions in the hippocampal dentate fascia and in layer 2 of the prefrontal isocortex, and 3 showed clinical and histological signs of motor neuron disease. Our results suggest that the serotoninergic raphe nuclei with ascending projections to the forebrain, but not the LC, become directly or indirectly involved in frontotemporal dementia both with and without motor neuron disease.

Selective attention and the three-process memory model for the interpretation of verbal free recall in amyotrophic lateral sclerosis.

PubMed

Christidi, Foteini; Zalonis, Ioannis; Smyrnis, Nikolaos; Evdokimidis, Ioannis

2012-09-01

The present study investigates selective attention and verbal free recall in amyotrophic lateral sclerosis (ALS) and examines the contribution of selective attention, encoding, consolidation, and retrieval memory processes to patients' verbal free recall. We examined 22 non-demented patients with sporadic ALS and 22 demographically related controls using Stroop Neuropsychological Screening Test (SNST; selective attention) and Rey Auditory Verbal Learning Test (RAVLT; immediate & delayed verbal free recall). The item-specific deficit approach (ISDA) was applied to RAVLT to evaluate encoding, consolidation, and retrieval difficulties. ALS patients performed worse than controls on SNST (p < .001) and RAVLT immediate and delayed recall (p < .001) and showed deficient encoding (p = .001) and consolidation (p = .002) but not retrieval (p = .405). Hierarchical regression analysis revealed that SNST and ISDA indices accounted for: (a) 91.1% of the variance in RAVLT immediate recall, with encoding (p = .016), consolidation (p < .001), and retrieval (p = .032) significantly contributing to the overall model and the SNST alone accounting for 41.6%; and (b) 85.2% of the variance in RAVLT delayed recall, with consolidation (p < .001) and retrieval (p = .008) significantly contributing to the overall model and the SNST alone accounting for 39.8%. Thus, selective attention, encoding, and consolidation, and to a lesser extent of retrieval, influenced both immediate and delayed verbal free recall. Concluding, selective attention and the memory processes of encoding, consolidation, and retrieval should be considered while interpreting patients' impaired free recall. (JINS, 2012, 18, 1-10).

High cognitive reserve is associated with a reduced age-related deficit in spatial conflict resolution

PubMed Central

Puccioni, Olga; Vallesi, Antonino

2012-01-01

Several studies support the existence of a specific age-related difficulty in suppressing potentially distracting information. The aim of the present study is to investigate whether spatial conflict resolution is selectively affected by aging. The way aging affects individuals could be modulated by many factors determined by the socieconomic status: we investigated whether factors such as cognitive reserve (CR) and years of education may play a compensatory role against age-related deficits in the spatial domain. A spatial Stroop task with no feature repetitions was administered to a sample of 17 non-demented older adults (69–79 years-old) and 18 younger controls (18–34 years-old) matched for gender and years of education. The two age groups were also administered with measures of intelligence and CR. The overall spatial Stroop effect did not differ according to age, neither for speed nor for accuracy. The two age groups equally showed sequential effects for congruent trials: reduced response times (RTs) if another congruent trial preceded them, and accuracy at ceiling. For incongruent trials, older adults, but not younger controls, were influenced by congruency of trialn−1, since RTs increased with preceding congruent trials. Interestingly, such an age-related modulation negatively correlated with CR. These findings suggest that spatial conflict resolution in aging is predominantly affected by general slowing, rather than by a more specific deficit. However, a high level of CR seems to play a compensatory role for both factors. PMID:23248595

Cortical atrophy patterns in early Parkinson's disease patients using hierarchical cluster analysis.

PubMed

Uribe, Carme; Segura, Barbara; Baggio, Hugo Cesar; Abos, Alexandra; Garcia-Diaz, Anna Isabel; Campabadal, Anna; Marti, Maria Jose; Valldeoriola, Francesc; Compta, Yaroslau; Tolosa, Eduard; Junque, Carme

2018-05-01

Cortical brain atrophy detectable with MRI in non-demented advanced Parkinson's disease (PD) is well characterized, but its presence in early disease stages is still under debate. We aimed to investigate cortical atrophy patterns in a large sample of early untreated PD patients using a hypothesis-free data-driven approach. Seventy-seven de novo PD patients and 50 controls from the Parkinson's Progression Marker Initiative database with T1-weighted images in a 3-tesla Siemens scanner were included in this study. Mean cortical thickness was extracted from 360 cortical areas defined by the Human Connectome Project Multi-Modal Parcellation version 1.0, and a hierarchical cluster analysis was performed using Ward's linkage method. A general linear model with cortical thickness data was then used to compare clustering groups using FreeSurfer software. We identified two patterns of cortical atrophy. Compared with controls, patients grouped in pattern 1 (n = 33) were characterized by cortical thinning in bilateral orbitofrontal, anterior cingulate, and lateral and medial anterior temporal gyri. Patients in pattern 2 (n = 44) showed cortical thinning in bilateral occipital gyrus, cuneus, superior parietal gyrus, and left postcentral gyrus, and they showed neuropsychological impairment in memory and other cognitive domains. Even in the early stages of PD, there is evidence of cortical brain atrophy. Neuroimaging clustering analysis is able to detect two subgroups of cortical thinning, one with mainly anterior atrophy, and the other with posterior predominance and worse cognitive performance. Copyright © 2018 Elsevier Ltd. All rights reserved.

Neurocognition in individuals with incidentally-identified meningioma.

PubMed

Butts, Alissa M; Weigand, Stephen; Brown, Paul D; Petersen, Ronald C; Jack, Clifford R; Machulda, Mary M; Cerhan, Jane H

2017-08-01

Meningiomas are primary intracranial tumors that are often asymptomatic. To our knowledge, no study has attempted to describe neurocognitive function in patients with incidentally-discovered meningioma. We utilized the Mayo Clinic Study of Aging (MCSA), which is a population-based sample of Olmsted County, Minnesota residents that includes neuropsychological testing and brain MRI approximately every 15 months. Using a text search of radiologists' notes of 2402 MCSA individuals (mean age 77 years, scanned between 2004 and 2014) we identified 48 eligible subjects (2%) who had at least one meningioma. Most meningiomas were small (90% <3 cm). We matched each of the 48 subjects to 5 non-demented MCSA controls (n = 240) on age, sex, and education. Cognitive domains assessed included memory, attention-executive function, language, and visuospatial. More women (67%) had a meningioma than men (33%). Groups did not differ on prevalence of Mild Cognitive Impairment (Meningioma = 19%, Controls = 13%). Across cognitive domains, we observed similar performance for the two groups (p's ≥ 0.21). Subtle differences emerged in memory and language domains (p = 0.05 and p = 0.11) when we divided the Meningioma group by tumor location, wherein the small group with an infratentorial tumor performed more poorly than controls globally as well as on select memory and language measures. Our findings suggest that small meningiomas are generally cognitively benign, but that may change as the tumor evolves, and might be impacted by other factors such as meningioma location.

The similar effects of verbal and non-verbal intervening tasks on word recall in an elderly population.

PubMed

Williams, B R; Sullivan, S K; Morra, L F; Williams, J R; Donovick, P J

2014-01-01

Vulnerability to retroactive interference has been shown to increase with cognitive aging. Consistent with the findings of memory and aging literature, the authors of the California Verbal Learning Test-II (CVLT-II) suggest that a non-verbal task be administered during the test's delay interval to minimize the effects of retroactive interference on delayed recall. The goal of the present study was to determine the extent to which retroactive interference caused by non-verbal and verbal intervening tasks affects recall of verbal information in non-demented, older adults. The effects of retroactive interference on recall of words during Long-Delay recall on the California Verbal Learning Test-II (CVLT-II) were evaluated. Participants included 85 adults age 60 and older. During a 20-minute delay interval on the CVLT-II, participants received either a verbal (WAIS-III Vocabulary or Peabody Picture Vocabulary Test-IIIB) or non-verbal (Raven's Standard Progressive Matrices or WAIS-III Block Design) intervening task. Similarly to previous research with young adults (Williams & Donovick, 2008), older adults recalled the same number of words across all groups, regardless of the type of intervening task. These findings suggest that the administration of verbal intervening tasks during the CVLT-II do not elicit more retroactive interference than non-verbal intervening tasks, and thus verbal tasks need not be avoided during the delay interval of the CVLT-II.

The contribution of sectoral climate change mitigation options to national targets: a quantitative assessment of dairy production in Kenya

NASA Astrophysics Data System (ADS)

Brandt, Patric; Herold, Martin; Rufino, Mariana C.

2018-03-01

Reducing greenhouse gas (GHG) emissions from agriculture has become a critical target in national climate change policies. More than 80% of the countries in Sub-Saharan Africa (SSA) refer to the reduction of agricultural emissions, including livestock, in their nationally determined contribution (NDC) to mitigate climate change. The livestock sector in Kenya contributes largely to the gross domestic product and to GHG emissions from the land use sector. The government has recently pledged in its NDC to curb total GHG emissions by 30% by 2030. Quantifying and linking the mitigation potential of farm practices to national targets is required to support realistically the implementation of NDCs. Improvements in feed and manure management represent promising mitigation options for dairy production. This study aimed (i) to assess mitigation and food production benefits of feed and manure management scenarios, including land use changes covering Kenya’s entire dairy production region and (ii) to analyse the contribution of these practices to national targets on milk production and mitigation, and their biophysical feasibility given the availability of arable land. The results indicate that improving forage quality by increasing the use of Napier grass and supplementing dairy concentrates supports Kenya’s NDC target, reduces emission intensities by 26%-31%, partially achieves the national milk productivity target for 2030 by 38%-41%, and shows high feasibility given the availability of arable land. Covering manure heaps may reduce emissions from manure management by 68%. In contrast, including maize silage in cattle diets would not reduce emission intensities due to the risk of ten-fold higher emissions from the conversion of land required to grow additional maize. The shortage of arable land may render the implementation of these improved feed practices largely infeasible. This assessment provides the first quantitative estimates of the potential of feed intensification and manure management to mitigate GHG emissions and to increase milk yields at sectoral-level and at a high spatial resolution for an SSA country. The scientific evidence is tailored to support actual policy and decision-making processes at the national level, such as ‘Nationally Appropriate Mitigation Actions’. Linking feed intensification and manure management strategies with spatially-explicit estimates of mitigation and food production to national targets may help the sector to access climate financing while contributing to food security.

Brain Morphology and Cerebrovascular Risk in Mild Cognitive Impairment and Dementia: SCOBHI-P study

PubMed Central

He, Jing; Iosif, Ana-Maria; Lee, Dong Young; Martinez, Oliver; Ding, Ding; Carmichael, Owen; Mortimer, James A.; Zhao, Qianhua; Chu, Shugang; Guo, Qihao; Galasko, Douglas; Salmon, David; Dai, Qi; Wu, Yougui; Petersen, Ron; Hong, Zhen; Borenstein, Amy R.; DeCarli, Charles

2010-01-01

Objective To investigate associations between MRI brain morphology, cerebrovascular risk (VR), clinical diagnosis and cognition among elders living in urban Shanghai. Design Cross-sectional study. Setting Memory Disorders Clinic and community normal control (NC) subject recruitment. Participants Ninety-six older subjects, 32 with normal cognition, 30 with amnestic MCI (aMCI) and 34 with dementia. Main outcome measures Each subject received medical history, neurological/physical exams, neuropsychological evaluations, brain MRI and apolipoprotein E-ε4 (APOE -ε4) genotype test. MRI volumes were assessed using a semi-automatic method. Results Brain volume (BV) was significantly smaller in the demented compared with NC (p < 0.001) or aMCI (p = 0.043). Hippocampal volume (HV) was lower, and white matter hyperintensity volume (WMH) was higher, in aMCI (HV: p = 0.028; WMH: p = 0.041) and dementia (HV: p < 0.001; WMH: p = 0.002) compared with NC. APOE -ε4 presence was significantly associated with reduced HV (p = 0.02). Systolic blood pressure was positively associated with VR score (p = 0.037); diastolic blood pressure (p = 0.021) and VR score (p = 0.036) were both positively associated with WMH. WMH (p = 0.029) and VR (p = 0.031) were both higher among the demented than NC. Conclusion MRI brain morphology changes were significantly associated clinical diagnosis, in addition, blood pressure was highly associated with VR score and WMH. These results suggest that MRI is a valuable measure of brain injury in a Chinese cohort and can serve to assess the effects of various degenerative and cerebrovascular pathologies. PMID:20937951

Screening for DSM-IV-TR Cognitive Disorder NOS in Parkinson’s disease using the Mattis Dementia Rating Scale

PubMed Central

Pontone, Gregory M.; Palanci, Justin; Williams, James R.; Bassett, Susan Spear

2012-01-01

Objective This study explores the utility of the Mattis Dementia Rating Scale (MDRS) as a screening tool for the Diagnostic and Statistical Manual for Mental Disorders 4th edition (DSM-IV-TR) diagnosis Cognitive Disorder Not Otherwise Specified in Parkinson’s disease(PD). Methods 125 individuals with PD were diagnosed using DSM-IV-TR criteria for Cognitive Disorder NOS and dementia. Receiver operating characteristics tested the discriminant validity of the MDRS, with the clinician’s diagnosis serving as the gold standard. Results The MDRS ROC curve to discriminate subjects with Cognitive Disorder NOS from non-demented subjects had an AUC of 0.59 (std. err.= 0.08, 95% CI: 0.43–0.74). Conclusions The MDRS is not effective for identifying PD patients with Cognitive Disorder NOS without dementia. PMID:22628158

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gallant,M.; Rak, M.; Szeghalmi, A.

The creatine/phosphocreatine system, regulated by creatine kinase, plays an important role in maintaining energy balance in the brain. Energy metabolism and the function of creatine kinase are known to be affected in Alzheimer diseased brain and in cells exposed to the {beta}-amyloid peptide. We used infrared microspectroscopy to examine hippocampal, cortical, and caudal tissue from 21-89-week-old transgenic mice expressing doubly mutant (K670N/M671L and V717F) amyloid precursor protein and displaying robust pathology from an early age. Microcrystalline deposits of creatine, suggestive of perturbed energetic status, were detected by infrared microspectroscopy in all animals with advanced plaque pathology. Relatively large creatine depositsmore » were also found in hippocampal sections from post-mortem Alzheimer diseased human brain, compared with hippocampus from non-demented brain. We therefore speculate that this molecule is a marker of the disease process.« less

WESCOM. A Fortran Code for Evaluation of Nuclear Weapon Effects on Satellite Communications. Volume 2. Code Structure

DTIC Science & Technology

1981-01-31

quantities for h i ;.;h-:t It i 1 ndc hurst s 1BMI.I Determines t ime-independent fireball quantities for low-altitude bursts 10 Table 1...of reference Oval of Cassini (km) LAFBP - vortex longitudinal radius (km) LAFBP - vortex transverse radius (km) Power law exponent Inner scale...Maximum slant range of ionization from transmitter (km) Power law exponent Frequency (Hz) Striation velocity flag Propagation path index Radius

Environmental Aspects of Dredging: What About Air Quality?

DTIC Science & Technology

2009-01-01

District, IL, 61204, PH (309) 794-5735 ext.6108, FAX: (309) 794-5 5712, email: mark.j.anderson@usace.army.mil 6 2Civil & Environmental Engineering Dept...Michigan Tech University , Houghton, MI 7 49931, PH: (906) 487-1981, FAX: (906) 487-2943, email: barkdoll@mtu.edu 8 9 ABSTRACT 10 Dredging has...the U. S. Army Corps of Engineers (USACE) dredged a total of 26 204.2 million cubic yards (CY) of sediment (NDC 2007). Navigation maintenance 27

Kif4 Is Essential for Mouse Oocyte Meiosis.

PubMed

Camlin, Nicole J; McLaughlin, Eileen A; Holt, Janet E

2017-01-01

Progression through the meiotic cell cycle must be strictly regulated in oocytes to generate viable embryos and offspring. During mitosis, the kinesin motor protein Kif4 is indispensable for chromosome condensation and separation, midzone formation and cytokinesis. Additionally, the bioactivity of Kif4 is dependent on phosphorylation via Aurora Kinase B and Cdk1, which regulate Kif4 function throughout mitosis. Here, we examine the role of Kif4 in mammalian oocyte meiosis. Kif4 localized in the cytoplasm throughout meiosis I and II, but was also observed to have a dynamic subcellular distribution, associating with both microtubules and kinetochores at different stages of development. Co-localization and proximity ligation assays revealed that the kinetochore proteins, CENP-C and Ndc80, are potential Kif4 interacting proteins. Functional analysis of Kif4 in oocytes via antisense knock-down demonstrated that this protein was not essential for meiosis I completion. However, Kif4 depleted oocytes displayed enlarged polar bodies and abnormal metaphase II spindles, indicating an essential role for this protein for correct asymmetric cell division in meiosis I. Further investigation of the phosphoregulation of meiotic Kif4 revealed that Aurora Kinase and Cdk activity is critical for Kif4 kinetochore localization and interaction with Ndc80 and CENP-C. Finally, Kif4 protein but not gene expression was found to be upregulated with age, suggesting a role for this protein in the decline of oocyte quality with age.

Mild cognitive impairment: applicability of research criteria in a memory clinic and characterization of cognitive profile.

PubMed

Alladi, Suvarna; Arnold, Robert; Mitchell, Joanna; Nestor, Peter J; Hodges, John R

2006-04-01

We explored the applicability of recently proposed research criteria for mild cognitive impairment (MCI) in a memory clinic and changes in case definition related to which memory tests are used and the status of general cognitive function in MCI. A total of 166 consecutive GP referrals to the Cambridge Memory Clinic underwent comprehensive neuropsychological and psychiatric evaluation. Of 166 cases, 42 were excluded (significant depression 8, established dementia 29 and other disorders 5). Of 124 non-demented, non-depressed patients, 72 fulfilled Petersen's criteria for amnestic MCI based upon verbal memory performance [the Rey Auditory Verbal Learning Test (RAVLT)] and 90 met criteria if performance on verbal and/or non-verbal memory tests [the Rey figure recall or the Paired Associates Learning test (PAL)] was considered. Of the 90 broadly defined MCI cases, only 25 had pure amnesia: other subtle semantic and/or attention deficits were typically present. A further 12 were classed as non-amnestic MCI and 22 as 'worried well'. Definition of MCI varies considerably dependent upon the tests used for case definition. The majority have other cognitive deficits despite normal performance on the Mini-mental State Examination (MMSE) and intact activities of daily living (ADL) and fit within multi-domain MCI. Pure amnesic MCI is rare.

["Accepting Demented Minds". Opinion Group, Information and Support on Stigma of Mental Illness on Facebook].

PubMed

Mancera, Katherine Cárdenas; De Santacruz, Cecilia; Salamanca, Mayra Alejandra

2014-01-01

Mental illness is one of the diseases that generates more disability worldwide, and it is estimated that one in four people has or has had this kind of illness during their lives. Since the beginning, mental illness has been frequently linked to stigma and prejudice, which has important implications for the exercise of their human rights, including the right to health, as these preconceptions can delay their early detection and timely treatment. Eliminating stigma requires multiple interventions, in which the participation of people with these illnesses can be very helpful. Social networks portray an alternative for them and for people interested in this topic, helping them interact, clarify some concerns and doubts, and perhaps even modify their exclusion status. Describing the experience of the opinion and support group on Facebook called "Aceptando mentes dementes" ("Accepting Demented Minds"), created for people with mental illnesses, their families and any person interested in this matter, which seeks to make the impact and consequences that result from stigma more noticable. Analysis of qualitative and quantitative data collected over two and a half years of operation of the group, formed by 764 members from different countries. The aims of the group, as regards the spreading of information, interaction through shared experiences, and obtaining support were reached. Social networks allow the creation of communities that share specific needs, such as understanding and support, and all this at low cost. Knowing and being conscious about the stigma linked to mental illness helps raise awareness and generate options for change. To maintain and link it to other resources, the group will be included in the web site www.mentalpuntoapoyo.com. Copyright © 2013 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

The effect of integrated emotion-oriented care versus usual care on elderly persons with dementia in the nursing home and on nursing assistants: a randomized clinical trial.

PubMed

Finnema, Evelyn; Dröes, Rose-Marie; Ettema, Teake; Ooms, Marcel; Adèr, Herman; Ribbe, Miel; van Tilburg, Willem

2005-04-01

To examine the effect of integrated emotion-oriented care on nursing home residents with dementia and nursing assistants. A multi-site randomized clinical trial with matched groups, and measurements at baseline and after seven months. Sixteen psychogeriatric wards in fourteen nursing homes in the Netherlands. One hundred and forty-six elderly residents with the diagnosis dementia of the Alzheimer (DAT) type, mixed DAT and vascular dementia, and dementia syndrome (NAO) and 99 nursing assistants. Integrated emotion-oriented care and usual care. MESUREMENTS: Demented elderly: Behaviour and mood related to adaptation to the illness and the institutionalization. Nursing assistants: General health as measured by feelings of stress, stress reactions, feeling of competence and illness. Positive effects in favour of the integrated emotion-oriented care were found in mild to moderately demented residents on two adaptive tasks: maintaining an emotional balance (less anxiety) and preserving a positive self-image (less dissatisfaction). In the trained group of nursing assistants fewer stress reactions were found only in those who perceived improvement in their emotion-oriented care skills after training. Emotion-oriented care is more effective with regard to the emotional adaptation in nursing homes of persons with a mild to moderate dementia. For the severely demented elderly we did not find this surplus value. This outcome is of clinical importance for elderly persons with dementia who are cared for in nursing homes. With respect to the nursing assistants it is concluded that emotion-oriented care has a positive influence on stress reactions in some of them. Copyright 2005 John Wiley & Sons, Ltd.

Long-term cognitive decline in older subjects was not attributable to non-cardiac surgery or major illness

PubMed Central

Avidan, Michael S; FCASA; Searleman, Adam C; Storandt, Martha; Barnett, Kara; Vannucci, Andrea; Saager, Leif; Xiong, Chengjie; Grant, Elizabeth A; Kaiser, Dagmar; Morris, John C; Evers, Alex S

2009-01-01

Background Persistent postoperative cognitive decline is thought to be a public health problem, but its severity may have been overestimated because of limitations in statistical methodology. This study assessed whether long-term cognitive decline occurred after surgery or illness by using an innovative approach and including participants with early Alzheimer's disease to overcome some limitations. Methods In this retrospective cohort study, three groups were identified from participants tested annually at Washington University's Alzheimer Disease Research Center in St. Louis: those with non-cardiac surgery, illness, or neither. This enabled long-term tracking of cognitive function before and after surgery and illness. The effect of surgery and illness on longitudinal cognitive course was analyzed using a general linear mixed effects model. For participants without initial dementia, time to dementia onset was analyzed using sequential Cox proportional hazards regression. Results Of the 575 participants, 214 were nondemented and 361 had very mild or mild dementia at enrollment. Cognitive trajectories did not differ among the three groups (surgery, illness, control), although demented participants declined more markedly than nondemented. Of the initially nondemented participants, 23% progressed to a clinical dementia rating greater than zero, but this was not more common following surgery or illness. Conclusions The study did not detect long-term cognitive decline independently attributable to surgery or illness nor were these events associated with accelerated progression to dementia. The decision to proceed with surgery in elderly people, including those with early Alzheimer's disease, may presently be made without factoring in the specter of persistent cognitive deterioration. PMID:19786858

Give Deterrence a Chance: A Strategy Against Al Qaeda

DTIC Science & Technology

2007-03-28

Al Qaeda Terrorists have been described as sociopaths , narcissists, fanatics, extremists, zealots, true-believers, jihadists or demented criminals...If terrorists are sociopaths or other deviants (and it is probable that some are), then it is unlikely that deterrence with its reliance on rational

An Evaluation of North Korea’s Nuclear Test by Belbasi Nuclear Tests Monitoring Center-KOERI

NASA Astrophysics Data System (ADS)

Necmioglu, O.; Meral Ozel, N.; Semin, K.

2009-12-01

Bogazici University and Kandilli Observatory and Earthquake Research Institute (KOERI) is acting as the Turkish National Data Center (NDC) and responsible for the operation of the International Monitoring System (IMS) Primary Seismic Station (PS-43) under Belbasi Nuclear Tests Monitoring Center for the verification of compliance with the Comprehensive Nuclear-Test-Ban Treaty (CTBT) since February 2000. The NDC is responsible for operating two arrays which are part of the IMS, as well as for transmitting data from these stations to the International Data Centre (IDC) in Vienna. The Belbasi array was established in 1951, as a four-element (Benioff 1051) seismic array as part of the United States Atomic Energy Detection System (USAEDS). Turkish General Staff (TGS) and U.S. Air Force Technical Application Center (AFTAC) under the Defense and Economic Cooperation Agreement (DECA) jointly operated this short period array. The station was upgraded and several seismometers were added to array during 1951 and 1994 and the station code was changed from BSRS (Belbasi Seismic Research Station) to BRTR-PS43 later on. PS-43 is composed of two sub-arrays (Ankara and Keskin): the medium-period array with a ~40 km radius located in Ankara and the short-period array with a ~3 km radius located in Keskin. Each array has a broadband element located at the middle of the circular geometry. Short period instruments are installed at depth 30 meters from the surface while medium and broadband instruments are installed at depth 60 meters from surface. On 25 May 2009, The Democratic People’s Republic of Korea (DPRK) claimed that it had conducted a nuclear test. Corresponding seismic event was recorded by IMS and IDC released first automatic estimation of time (00:54:43 GMT), location (41.2896°N and 129.0480°E) and the magnitude (4.52 mb) of the event in less than two hours time (USGS: 00:54:43 GMT; 41.306°N, 129.029°E; 4.7 mb) During our preliminary analysis of the 25th May 2009 DPRK event, we saw a very clear P arrival at 01:05:47 (GMT) at BRTR SP array. The result of the f-k analysis performed in Geotool software, installed at NDC facilities in 2008 and is in full use currently, was also indicating that the arrival belongs to the DPRK event. When comparing our f-k results (calculated at 1-2 Hz) with IDC-REB, however, we have noticed that our calculation and therefore corresponding residuals (calculated with reference to REB residuals) are much better in comparison to REB. The reasons of this ambiguity have been explored and for the first time a comprehensive seismological analysis of a Nuclear Test has been conducted in Turkey. CTBT has an important role for the implementation of the non-proliferation of nuclear weapons and it is a key element for the pursuit of nuclear disarmament. In this study, we would like to reflect the technical and scientific aspects of the 25 May 2009 DPRK event analysis, together with our involvement in CTBT(O) affairs, which we believe it brings new dimensions to Turkey especially in the area of Geophysics.

Kant on euthanasia and the duty to die: clearing the air.

PubMed

Cholbi, Michael

2015-08-01

Thanks to recent scholarship, Kant is no longer seen as the dogmatic opponent of suicide that he appears to be at first glance. However, some interpreters have recently argued for a Kantian view of the morality of suicide with surprising, even radical, implications. More specifically, they have argued that Kantianism (1) requires that those with dementia or other rationality-eroding conditions end their lives before their condition results in their loss of identity as moral agents and (2) requires subjecting the fully demented or those confronting future dementia to non-voluntary euthanasia. Properly understood, Kant's ethics have neither of these implications (1) wrongly assumes that rational agents' duty of self-preservation entails a duty of self-destruction when they become non-rational, (2) further neglects Kant's distinction between duties to self and duties to others and wrongly assumes that duties can be owed to rational agents only during the time of their existence. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

[Cognitive plasticity in Alzheimer's disease patients receiving cognitive stimulation programs].

PubMed

Zamarrón Cassinello, Ma Dolores; Tárraga Mestre, Luis; Fernández-Ballesteros, Rocío

2008-08-01

The main purpose of this article is to examine whether cognitive plasticity increases after cognitive training in Alzheimer's disease patients. Twenty six patients participated in this study, all of them diagnosed with mild Alzheimer's disease, 17 of them received a cognitive training program during 6 months, and the other 9 were assigned to the control group. Participants were assigned to experimental or control conditions for clinical reasons. In order to assess cognitive plasticity, all patients were assessed before and after treatment with three subtests from the "Bateria de Evaluación de Potencial de Aprendizaje en Demencias" [Assessment Battery of Learning Potential in Dementia] (BEPAD). After treatment, Alzheimer's disease patients improved their performance in all the tasks assessing cognitive plasticity: viso-spatial memory, audio-verbal memory and verbal fluency. However, the cognitive plasticity scores of the patients in the control group decreased. In conclusion, this study showed that cognitive stimulation programs can improve cognitive functioning in mildly demented patients, and patients who do not receive any cognitive interventions may reduce their cognitive functioning.

U.S. Navy Capstone Strategies and Concepts (1991-2000): Strategy, Policy, Concept, and Vision Documents

DTIC Science & Technology

2012-03-01

PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) CNA Corporation,4825 Mark Center Drive... industry & USMC OMFTS experience  Project Team created BPR “activity model” (Oct-Dec 1995) OPNAV N513, N812; HQMC Plans, PP&O; MCCDC; NDC; SRA...Alexandria,VA,22311 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING/MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR’S ACRONYM(S) 11

Particle Sizing in a Fuel-Rich Ramjet Combustor.

DTIC Science & Technology

1983-08-01

Scattering wind tunnel , and for his assistance during the opera- Technique for Particle Sizing Based on Laser tions in the test cell and on other...000 40 0 0 -L .. 00 zzz C00 < 0 0 0 0 *Y -0 000 CL QU 00- V00 c 0 N 0 2 0000 4 008 -- I ~-_______ 00 0z m0 c00 00j i40 06.1 4~ < NDc . o4 i P-0 0 0 4

Force Method Optimization II. Volume II. User’s Manual.

DTIC Science & Technology

1982-11-01

column labels ICC Iteration counter ICHECK Vector for intermediate output, identifying the convergence status of unknowns, 0 = has not converged, 1...NDC,NW,SIG,ND,IDYN,UP,LOW,IAREA,IMU, ALAMBDW,WARAY,NSN.,NDCNL,NXNL,NWNL,NDNNL, NSENLIRST, ICHECK ,WDYN,PR1,MAXIT,WS,ARAY) 8. Input Tapes: None 9. Output...IMUSL,IMUDL,IAREA, IMU, P,NDN,UP,LOW,IX,IDYN,NW,IMUXL,IMUWL,ICC,ALAMBD, AMIN,WT,KL,NODE,ND,COND, IDEL .NSNL,NDCNL, NXNL, NWNL, ICHECK ,WDYN,PRI,WS,MAXT

NATO Nuclear Reductions and the Assurance of Central and Eastern European Allies

DTIC Science & Technology

2013-10-01

entirely. 35 Endnotes 1 Ronald D. Asmus and Alexandr Vondra, “The Origins of Atlanticism in Central and Eastern Europe,” Cambridge...pp. 3-6, available at http://www.ndc.nato.int/download/downloads.php?icode=195. 61 Asmus and Vondra, “The Origins of Atlanticism in Central and... Origins of Atlanticism in Central and Eastern Europe,” op. cit., p. 211. 132 Credible Deterrence for NATO in the XXI Century, op. cit, pp. 12-13

Validation of the Dementia Care Assessment Packet-Instrumental Activities of Daily Living

PubMed Central

Lee, Seok Bum; Park, Jeong Ran; Yoo, Jeong-Hwa; Park, Joon Hyuk; Lee, Jung Jae; Yoon, Jong Chul; Jhoo, Jin Hyeong; Lee, Dong Young; Woo, Jong Inn; Han, Ji Won; Huh, Yoonseok; Kim, Tae Hui

2013-01-01

Objective We aimed to evaluate the psychometric properties of the IADL measure included in the Dementia Care Assessment Packet (DCAP-IADL) in dementia patients. Methods The study involved 112 dementia patients and 546 controls. The DCAP-IADL was scored in two ways: observed score (OS) and predicted score (PS). The reliability of the DCAP-IADL was evaluated by testing its internal consistency, inter-rater reliability and test-retest reliability. Discriminant validity was evaluated by comparing the mean OS and PS between dementia patients and controls by ANCOVA. Pearson or Spearman correlation analysis was performed with other instruments to assess concurrent validity. Receiver operating characteristics curve analysis was performed to examine diagnostic accuracy. Results Chronbach's α coefficients of the DCAP-IADL were above 0.7. The values in dementia patients were much higher (OS=0.917, PS=0.927), indicating excellent degrees of internal consistency. Inter-rater reliabilities and test-retest reliabilities were statistically significant (p<0.05). PS exhibited higher reliabilities than OS. The mean OS and PS of dementia patients were significantly higher than those of the non-demented group after controlling for age, sex and education level. The DCAP-IADL was significantly correlated with other IADL instruments and MMSE-KC (p<0.001). Areas under the curves of the DCAP-IADL were above 0.9. Conclusion The DCAP-IADL is a reliable and valid instrument for evaluating instrumental ability of daily living for the elderly, and may also be useful for screening dementia. Moreover, administering PS may enable the DCAP-IADL to overcome the differences in gender, culture and life style that hinders accurate evaluation of the elderly in previous IADL instruments. PMID:24302946

Ptau-Aβ42 ratio as a continuous trait for biomarker discovery for early stage Alzheimer’s disease in multiplex immunoassay panels of Cerebrospinal fluid

PubMed Central

Harari, Oscar; Cruchaga, Carlos; Kauwe, John S.K.; Ainscough, Benjamin J.; Bales, Kelly; Pickering, Eve H.; Bertelsen, Sarah; Fagan, Anne M.; Holtzman, David M.; Morris, John C.; Goate, Alison M.

2014-01-01

Background Identification of the physiological changes that occur during the early stages of Alzheimer’s disease (AD) may provide critical insights for the diagnosis, prognosis and treatment of disease. Cerebrospinal fluid (CSF) biomarkers are a rich source of information that reflect the brain proteome. Methods We applied a novel approach to screen a panel of ~190 CSF analytes quantified by multiplex immunoassay and detected common associations in the Knight- Alzheimer’s Disease Research Center (ADRC;N=311) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI;N=293) cohorts. CSF ptau181-Aβ42 ratio was used as a continuous trait, rather than case control status in these analyses. Results We demonstrate the ptau181-Aβ42 ratio has more statistical power than traditional modeling approaches and that the levels of CSF Fatty Acid Binding Protein (H-FABP) and 12 other correlated analytes increase as the disease progresses. These results were validated using the traditional case control status model. Stratification of our dataset demonstrated that increases in these analytes occur very early in the disease course and were apparent even in non-demented individuals with AD pathology (low ptau181, low Aβ42) compared to pathology-negative elderly control subjects (low ptau181, high Aβ42). FABP-Aβ42 ratio demonstrates a similar hazard ratio for disease conversion to ptau181-Aβ42 even though the overlap in classification is incomplete suggesting that FABP contributes independent information as a predictor Conclusions Our results clearly indicate that the approach presented here can be employed to correctly identify novel biomarkers for AD, and that CSF H-FABP levels start to increase at very early stages of the disease. PMID:24548642

The prognosis and incidence of social phobia in an elderly population. A 5-year follow-up.

PubMed

Karlsson, B; Sigström, R; Waern, M; Ostling, S; Gustafson, D; Skoog, I

2010-07-01

To examine the prognosis and incidence of social fears and phobia in an elderly population sample followed for 5 years. A general population sample (N = 612) of non-demented men (baseline age 70) and women (baseline age 70 and 78-86) was investigated in 2000-2001 and in 2005-2006 with semi-structured psychiatric examinations including the Comprehensive Psychopathological Rating Scale, and the Mini International Neuropsychiatric Interview. Social phobia was diagnosed according to the DSM-IV criteria. Among nine individuals with DSM-IV social phobia in 2000, 5 (55.6%) had no social fears in 2005, and 1 (11.1%) still met the criteria for DSM-IV social phobia. Among individuals without DSM-IV social phobia in 2000 (N = 603), 12 (2.0%) had DSM-IV social phobia in 2005. These findings challenge the notion that social phobia is a chronic disorder with rare occurrence in old age.

Performances on the CogState and standard neuropsychological batteries among HIV patients without dementia.

PubMed

Overton, Edgar Turner; Kauwe, John S K; Paul, Robert; Tashima, Karen; Tate, David F; Patel, Pragna; Carpenter, Charles C J; Patty, David; Brooks, John T; Clifford, David B

2011-11-01

HIV-associated neurocognitive disorders remain prevalent but challenging to diagnose particularly among non-demented individuals. To determine whether a brief computerized battery correlates with formal neurocognitive testing, we identified 46 HIV-infected persons who had undergone both formal neurocognitive testing and a brief computerized battery. Simple detection tests correlated best with formal neuropsychological testing. By multivariable regression model, 53% of the variance in the composite Global Deficit Score was accounted for by elements from the brief computerized tool (P < 0.01). These data confirm previous correlation data with the computerized battery. Using the five significant parameters from the regression model in a Receiver Operating Characteristic curve, 90% of persons were accurately classified as being cognitively impaired or not. The test battery requires additional evaluation, specifically for identifying persons with mild impairment, a state upon which interventions may be effective.

The relationship between everyday problem solving and inconsistency in reaction time in older adults.

PubMed

Burton, Catherine L; Strauss, Esther; Hultsch, David F; Hunter, Michael A

2009-09-01

The purpose of the present study was to investigate whether inconsistency in reaction time (RT) is predictive of older adults' ability to solve everyday problems. A sample of 304 community dwelling non-demented older adults, ranging in age from 62 to 92, completed a measure of everyday problem solving, the Everyday Problems Test (EPT). Inconsistency in latencies across trials was assessed on four RT tasks. Performance on the EPT was found to vary according to age and cognitive status. Both mean latencies and inconsistency were significantly associated with EPT performance, such that slower and more inconsistent RTs were associated with poorer everyday problem solving abilities. Even after accounting for age, education, and mean level of performance, inconsistency in reaction time continued to account for a significant proportion of the variance in EPT scores. These findings suggest that indicators of inconsistency in RT may be of functional relevance.

Ultrastructural localization of acetylcholinesterase in neurofibrillary tangles, neuropil threads and senile plaques in aged and Alzheimer's brain.

PubMed

Gomez-Ramos, P; Mufson, E J; Moran, M A

1992-01-13

Acetylcholinesterase (AChE) histochemistry was used to evaluate the accumulation of this enzyme in senile plaques, neurofibrillary tangles and neuropil threads using light and electron microscopy in Alzheimer's disease as well as non-demented aged brains. Under the electron microscope, a crystalline-like AChE precipitate was localized over paired helical filaments and straight filaments in both neurofibrillary tangles and neuropil threads. AChE reaction product also decorated the amyloid fibrils in diffuse plaques as well as the halo and the heavy accumulation of amyloid which forms the core of classical plaques. In both diffuse plaques and the halo of classical plaques, we found AChE-positive structures resembling cell processes, which in some cases appeared to contain amyloid fibrils. The possible origin and significance of AChE localized over paired helical filaments, straight filaments and amyloid is discussed.

Do subjective memory complaints predict senile Alzheimer dementia?

PubMed

Jungwirth, Susanne; Zehetmayer, Sonja; Weissgram, Silvia; Weber, Germain; Tragl, Karl Heinz; Fischer, Peter

2008-01-01

Many elderly complain about their memory and undergo dementia screening by the Mini-Mental State Examination (MMSE). While objective memory impairment always precedes Alzheimer dementia (AD) it is unclear whether subjective memory complaints are predicting AD. We tried to answer this question in a prospective cohort study. The 75-years old non-demented inhabitants of Vienna-Transdanube were investigated for conversion to AD after 30 months. The predictive value of subjective memory complaints was analysed in two groups: subjects with high MMSE-score (28-30) and subjects with low MMSE-score (23-27). Only in subjects with high MMSE univariate analyses showed an association between subjective memory complaints and incident AD. In both groups the verbal memory test was the main predictor of AD in multivariate analyses. We suggest to perform memory testing in subjects complaining about memory irrespective of their performance in a screening procedure like the MMSE.

Visual and cognitive predictors of driving safety in Parkinson's disease patients

PubMed Central

Amick, M.M.; Grace, J.; Ott, B.R.

2012-01-01

This study assessed the clinical utility of contrast sensitivity (CS) relative to attention, executive function, and visuospatial abilities for predicting driving safety in participants with Parkinson's disease (PD). Twenty-five, non-demented PD patients completed measures of contrast sensitivity, visuospatial skills, executive functions, and attention. All PD participants also underwent a formal on-road driving evaluation. Of the 25 participants, 11 received a marginal or unsafe rating on the road test. Poorer driving performance was associated with worse performance on measures of CS, visuospatial constructions, set shifting, and attention. While impaired driving was associated with a range of cognitive and visual abilities, only a composite measure of executive functioning and visuospatial abilities, and not CS or attentional skills, predicted driving performance. These findings suggest that neuropsychological tests, which are multifactorial in nature and require visual perception and visual spatial judgments are the most useful screening measures for hazardous driving in PD patients. PMID:17851032

Visual and cognitive predictors of driving safety in Parkinson's disease patients.

PubMed

Amick, M M; Grace, J; Ott, B R

2007-11-01

This study assessed the clinical utility of contrast sensitivity (CS) relative to attention, executive function, and visuospatial abilities for predicting driving safety in participants with Parkinson's disease (PD). Twenty-five, non-demented PD patients completed measures of contrast sensitivity, visuospatial skills, executive functions, and attention. All PD participants also underwent a formal on-road driving evaluation. Of the 25 participants, 11 received a marginal or unsafe rating on the road test. Poorer driving performance was associated with worse performance on measures of CS, visuospatial constructions, set shifting, and attention. While impaired driving was associated with a range of cognitive and visual abilities, only a composite measure of executive functioning and visuospatial abilities, and not CS or attentional skills, predicted driving performance. These findings suggest that neuropsychological tests, which are multifactorial in nature and require visual perception and visual spatial judgments are the most useful screening measures for hazardous driving in PD patients.

Semantic memory assessment in 15 patients with amyotrophic lateral sclerosis.

PubMed

Hervieu-Bègue, M; Rouaud, O; Graule Petot, A; Catteau, A; Giroud, M

2016-01-01

A total of 30 to 50% of amyotrophic lateral sclerosis patients suffer from cognitive disorders. The aim of the study is to characterize these disorders and to assess semantic memory in non-demented ALS patients. The secondary aim is to look for a link between disease type and neuropsychological characteristics. Patients were followed in an ALS center in Dijon. The following neuropsychological tests were used in this study: Folstein test, BREF test, verbal fluency, Isaac test, GRESEM test and TOP 30 test. Fifteen ALS patients were included. Nine of them (60%) were suffering from a semantic memory disorder. There was no correlation between ALS characteristics and the semantic memory disorder. This is the first study to reveal a semantic memory disorder in ALS. This result accentuates the hypothesis that ALS and semantic dementia are two phenotypes of the same degenerative process linked to TDP 43 proteinopathy. Copyright © 2016. Published by Elsevier Masson SAS.

The Uses of Rudeness.

ERIC Educational Resources Information Center

Machiavelli, Nick

1992-01-01

Exploding in anger has its charm, though putting sand in the social oil is not simple. Rudeness, like celebrity deaths, comes in threes: daily, demented, and inspired. Administrators should be forewarned: rudeness is effective only when coming from power. Powerless rude people are called nuts; powerful rude people are deemed eccentric. (MLH)

Low Cognitive Functioning in Nondemented 80+-Year-Old Twins Is Not Heritable.

ERIC Educational Resources Information Center

Petrill, Stephen A.; Johansson, Boo; Pedersen, Nancy L.; Berg, Stig; Plomin, Robert; Ahern, Frank; McClearn, Gerald E.

2001-01-01

Studied the genetic influence of low cognitive functioning in 200 pairs of twins aged at least 80 years and identified as not demented. Results suggest that the heritability of low cognitive functioning in this group was nonsignificant, but above-average cognitive functioning shows substantial group heritability. (SLD)

"A Demented Form of the Familiar": Postmodernism and Educational Research

ERIC Educational Resources Information Center

Maclure, Maggie

2006-01-01

What can postmodernism do for, or to, educational research? The article discusses its potential for resisting closure and simplification. Developing a "preposterous", anachronistic postmodern method that is caught up with surrealism and the baroque, the article plays with "trompel'oeil" paintings and outmoded popular entertainments such as magic…