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Sample records for differentiates cognitively normal

  1. Development of Planning Abilities in Normal Aging: Differential Effects of Specific Cognitive Demands

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    Köstering, Lena; Stahl, Christoph; Leonhart, Rainer; Weiller, Cornelius; Kaller, Christoph P.

    2014-01-01

    In line with the frontal hypothesis of aging, the ability to plan ahead undergoes substantial change during normal aging. Although impairments on the Tower of London planning task were reported earlier, associations between age-related declines and specific cognitive demands on planning have not been studied. Here we investigated the impact of…

  2. Cortical Thinning in Network-Associated Regions in Cognitively Normal and Below-Normal Range Schizophrenia

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    R. Walter Heinrichs

    2017-01-01

    Full Text Available This study assessed whether cortical thickness across the brain and regionally in terms of the default mode, salience, and central executive networks differentiates schizophrenia patients and healthy controls with normal range or below-normal range cognitive performance. Cognitive normality was defined using the MATRICS Consensus Cognitive Battery (MCCB composite score (T=50 ± 10 and structural magnetic resonance imaging was used to generate cortical thickness data. Whole brain analysis revealed that cognitively normal range controls (n=39 had greater cortical thickness than both cognitively normal (n=17 and below-normal range (n=49 patients. Cognitively normal controls also demonstrated greater thickness than patients in regions associated with the default mode and salience, but not central executive networks. No differences on any thickness measure were found between cognitively normal range and below-normal range controls (n=24 or between cognitively normal and below-normal range patients. In addition, structural covariance between network regions was high and similar across subgroups. Positive and negative symptom severity did not correlate with thickness values. Cortical thinning across the brain and regionally in relation to the default and salience networks may index shared aspects of the psychotic psychopathology that defines schizophrenia with no relation to cognitive impairment.

  3. Differential diagnosis for cognitive decline in elderly

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    Om Prakash

    2016-01-01

    Full Text Available Cognitive decline has a spectrum of presentations, which manifest from normality as part of senility to the established form of various neurodegenerative illnesses causing dementia. Understanding these various differential diagnoses is of great clinical significance as they have different management and interventional strategies. The neuropsychological deficits which are identified should follow known neuropathological disease patterns that helps in distinguishing different types of cognitive impairment to established dementia. It is important to look at different cognitive impairment in elderly with core diagnostic sense to define severity, type of cognitive impairments, identifying patients need for accommodation or adaptation, associated risks, effectiveness of therapies and predict mortality. This would help clinicians to identify and plan management based on individual needs in cases with variable cognitive impairment.

  4. Relevance of the serial position effect in the differential diagnosis of mild cognitive impairment, Alzheimer-type dementia, and normal ageing.

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    Martín, M E; Sasson, Y; Crivelli, L; Roldán Gerschovich, E; Campos, J A; Calcagno, M L; Leiguarda, R; Sabe, L; Allegri, R F

    2013-05-01

    Serial position effects are observed when a person memorises a series of words exceeding his or her attention span. Cognitively normal individuals recall words at the beginning and end of the list more frequently than those in the middle, which reflects the way that short- and long-term episodic memory works. To study the serial position effect in patients with mild cognitive impairment (MCI) compared to subjects with Alzheimer-type dementia (AD) or normal ageing (NA). 30 AD, 25 MCI and 20 NA subjects underwent neurological and neuropsychological assessment. The Rey Auditory Verbal Learning Test (RAVLT) was used to study primacy, middle, and recency effects and delayed recall for each group. The general memory pattern of MCI subjects was very similar to that of AD subjects, and was characterised by reduced learning capacity, rapid forgetfulness and clear recency effect in learning. With regard to delayed recall, however, there were differences in performance; MCI subjects' ability to recall words at the beginning and middle of the list was similar to that of normal subjects, while their memory of words at the end of the list was poor, as in AD subjects. RAVLT is a tool permitting us to distinguish between MCI and NA subjects. The recency index for the delayed recall task is a valid indicator for distinguishing between MCI patients and patients with normal ageing. Copyright © 2011 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  5. Which part of the Quick mild cognitive impairment screen (Qmci) discriminates between normal cognition, mild cognitive impairment and dementia?

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    O'Caoimh, Rónán

    2013-05-01

    the Qmci is a sensitive and specific test to differentiate between normal cognition (NC), mild cognitive impairment (MCI) and dementia. We compared the sensitivity and specificity of the subtests of the Qmci to determine which best discriminated NC, MCI and dementia.

  6. Brain Signal Variability Differentially Affects Cognitive Flexibility and Cognitive Stability.

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    Armbruster-Genç, Diana J N; Ueltzhöffer, Kai; Fiebach, Christian J

    2016-04-06

    Recent research yielded the intriguing conclusion that, in healthy adults, higher levels of variability in neuronal processes are beneficial for cognitive functioning. Beneficial effects of variability in neuronal processing can also be inferred from neurocomputational theories of working memory, albeit this holds only for tasks requiring cognitive flexibility. However, cognitive stability, i.e., the ability to maintain a task goal in the face of irrelevant distractors, should suffer under high levels of brain signal variability. To directly test this prediction, we studied both behavioral and brain signal variability during cognitive flexibility (i.e., task switching) and cognitive stability (i.e., distractor inhibition) in a sample of healthy human subjects and developed an efficient and easy-to-implement analysis approach to assess BOLD-signal variability in event-related fMRI task paradigms. Results show a general positive effect of neural variability on task performance as assessed by accuracy measures. However, higher levels of BOLD-signal variability in the left inferior frontal junction area result in reduced error rate costs during task switching and thus facilitate cognitive flexibility. In contrast, variability in the same area has a detrimental effect on cognitive stability, as shown in a negative effect of variability on response time costs during distractor inhibition. This pattern was mirrored at the behavioral level, with higher behavioral variability predicting better task switching but worse distractor inhibition performance. Our data extend previous results on brain signal variability by showing a differential effect of brain signal variability that depends on task context, in line with predictions from computational theories. Recent neuroscientific research showed that the human brain signal is intrinsically variable and suggested that this variability improves performance. Computational models of prefrontal neural networks predict differential

  7. Distributive justice and cognitive enhancement in lower, normal intelligence.

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    Dunlop, Mikael; Savulescu, Julian

    2014-01-01

    There exists a significant disparity within society between individuals in terms of intelligence. While intelligence varies naturally throughout society, the extent to which this impacts on the life opportunities it affords to each individual is greatly undervalued. Intelligence appears to have a prominent effect over a broad range of social and economic life outcomes. Many key determinants of well-being correlate highly with the results of IQ tests, and other measures of intelligence, and an IQ of 75 is generally accepted as the most important threshold in modern life. The ability to enhance our cognitive capacities offers an exciting opportunity to correct disabling natural variation and inequality in intelligence. Pharmaceutical cognitive enhancers, such as modafinil and methylphenidate, have been shown to have the capacity to enhance cognition in normal, healthy individuals. Perhaps of most relevance is the presence of an 'inverted U effect' for most pharmaceutical cognitive enhancers, whereby the degree of enhancement increases as intelligence levels deviate further below the mean. Although enhancement, including cognitive enhancement, has been much debated recently, we argue that there are egalitarian reasons to enhance individuals with low but normal intelligence. Under egalitarianism, cognitive enhancement has the potential to reduce opportunity inequality and contribute to relative income and welfare equality in the lower, normal intelligence subgroup. Cognitive enhancement use is justifiable under prioritarianism through various means of distribution; selective access to the lower, normal intelligence subgroup, universal access, or paradoxically through access primarily to the average and above average intelligence subgroups. Similarly, an aggregate increase in social well-being is achieved through similar means of distribution under utilitarianism. In addition, the use of cognitive enhancement within the lower, normal intelligence subgroup negates, or at

  8. Cognitive Change in Elderly Populations: "Normal" Aging, Senile Dementia and Depression.

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    Bach, Paul J.

    Cognitive change in the elderly can be due to several etiological factors which are empirically difficult to separate and clinically problematic to differentiate. Normal aging is accompanied by behavioral slowing. The slowing down of psycho-motor processes results in a lowered intelligence quotient, but cannot be taken as unequivocal evidence for…

  9. Agent-Centered Decision Making in Normal and Abnormal Cognition

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    Goldberg, Elkhonon

    2012-08-01

    Full Text Available Much of human cognition is “agent-centered,” subjective, and in that sense relative, directed at deciding, “What is best for me”. This is very different from “veridical” cognition, directed at finding an objectively correct solution inherent in the task and independent of the agent. The frontal lobes in particular are central to agent-centered decision making. Yet very little is available in the arsenal of cognitive paradigms used in the cognitive neuroscience research and in clinical neuropsychology test design to examine “agent-centered” decision making. Current paradigms and tests used to measure decision making clinically and experimentally are veridical in nature and as such miss the essence of “agent-centered” cognition. The dearth of “agent-centered” cognitive paradigms severely limits our ability to understand fully the function and dysfunction of the frontal lobes. The Cognitive Bias Task (CBT is an agent-centered paradigm designed to fill this gap. CBT has been used as a cognitive activation task in fMRI, SPECT, and EEG, as well as in studies of normal development, addiction, dementia, focal lesions, and schizophrenia. This resulted in a range of findings that eluded more traditional “veridical” paradigms and are reviewed here.

  10. Behavioral symptoms in community-dwelling elderly Nigerians with dementia, mild cognitive impairment, and normal cognition.

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    Baiyewu, Olusegun; Unverzagt, Fred W; Ogunniyi, Adesola; Smith-Gamble, Valerie; Gureje, Oye; Lane, Kathleen A; Gao, Sujuan; Hall, Kathleen S; Hendrie, Hugh C

    2012-09-01

    Few studies have examined the neuropsychiatric status of patients with dementia and cognitive impairment in the developing world despite the fact that current demographic trends suggest an urgent need for such studies. To assess the level of neuropsychiatric symptoms in community-dwelling individuals with dementia, cognitive impairment no dementia and normal cognition. Subjects were from the Ibadan site of Indianapolis-Ibadan Dementia Project with stable diagnoses of normal cognition, cognitive impairment, no dementia/mild cognitive impairment (CIND/MCI), and dementia. Informants of subjects made ratings on the neuropsychiatric inventory and blessed dementia scale; subjects were tested with the mini mental state examination. One hundred and eight subjects were included in the analytic sample, 21 were cognitively normal, 34 were demented, and 53 were CIND/MCI. The diagnostic groups did not differ in age, per cent female, or per cent with any formal education. The most frequent symptoms among subjects with CIND/MCI were depression (45.3%), apathy (37.7%), night time behavior (28.3%), appetite change (24.5%), irritability (22.6%), delusions (22.6%), anxiety (18.9%), and agitation (17.0%). Depression was significantly more frequent among the CIND/MCI and dementia (44.1%) groups compared with the normal cognition group (9.5%). Distress scores were highest for the dementia group, lowest for the normal cognition group, and intermediate for the CIND/MCI group. Significant neuropsychiatric symptomatology and distress are present among cognitively impaired persons in this community-based study of older adults in this sub-Saharan African country. Programs to assist family members of cognitively impaired and demented persons should be created or adapted for use in developing countries. Copyright © 2012 John Wiley & Sons, Ltd.

  11. Nevanlinna theory, normal families, and algebraic differential equations

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    Steinmetz, Norbert

    2017-01-01

    This book offers a modern introduction to Nevanlinna theory and its intricate relation to the theory of normal families, algebraic functions, asymptotic series, and algebraic differential equations. Following a comprehensive treatment of Nevanlinna’s theory of value distribution, the author presents advances made since Hayman’s work on the value distribution of differential polynomials and illustrates how value- and pair-sharing problems are linked to algebraic curves and Briot–Bouquet differential equations. In addition to discussing classical applications of Nevanlinna theory, the book outlines state-of-the-art research, such as the effect of the Yosida and Zalcman–Pang method of re-scaling to algebraic differential equations, and presents the Painlevé–Yosida theorem, which relates Painlevé transcendents and solutions to selected 2D Hamiltonian systems to certain Yosida classes of meromorphic functions. Aimed at graduate students interested in recent developments in the field and researchers wor...

  12. Safety of disclosing amyloid status in cognitively normal older adults.

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    Burns, Jeffrey M; Johnson, David K; Liebmann, Edward P; Bothwell, Rebecca J; Morris, Jill K; Vidoni, Eric D

    2017-09-01

    Disclosing amyloid status to cognitively normal individuals remains controversial given our lack of understanding the test's clinical significance and unknown psychological risk. We assessed the effect of amyloid status disclosure on anxiety and depression before disclosure, at disclosure, and 6 weeks and 6 months postdisclosure and test-related distress after disclosure. Clinicians disclosed amyloid status to 97 cognitively normal older adults (27 had elevated cerebral amyloid). There was no difference in depressive symptoms across groups over time. There was a significant group by time interaction in anxiety, although post hoc analyses revealed no group differences at any time point, suggesting a minimal nonsustained increase in anxiety symptoms immediately postdisclosure in the elevated group. Slight but measureable increases in test-related distress were present after disclosure and were related to greater baseline levels of anxiety and depression. Disclosing amyloid imaging results to cognitively normal adults in the clinical research setting with pre- and postdisclosure counseling has a low risk of psychological harm. Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  13. Aberrant Intrinsic Activity and Connectivity in Cognitively Normal Parkinson's Disease.

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    Harrington, Deborah L; Shen, Qian; Castillo, Gabriel N; Filoteo, J Vincent; Litvan, Irene; Takahashi, Colleen; French, Chelsea

    2017-01-01

    Disturbances in intrinsic activity during resting-state functional MRI (rsfMRI) are common in Parkinson's disease (PD), but have largely been studied in a priori defined subnetworks. The cognitive significance of abnormal intrinsic activity is also poorly understood, as are abnormalities that precede the onset of mild cognitive impairment. To address these limitations, we leveraged three different analytic approaches to identify disturbances in rsfMRI metrics in 31 cognitively normal PD patients (PD-CN) and 30 healthy adults. Subjects were screened for mild cognitive impairment using the Movement Disorders Society Task Force Level II criteria. Whole-brain data-driven analytic approaches first analyzed the amplitude of low-frequency intrinsic fluctuations (ALFF) and regional homogeneity (ReHo), a measure of local connectivity amongst functionally similar regions. We then examined if regional disturbances in these metrics altered functional connectivity with other brain regions. We also investigated if abnormal rsfMRI metrics in PD-CN were related to brain atrophy and executive, visual organization, and episodic memory functioning. The results revealed abnormally increased and decreased ALFF and ReHo in PD-CN patients within the default mode network (posterior cingulate, inferior parietal cortex, parahippocampus, entorhinal cortex), sensorimotor cortex (primary motor, pre/post-central gyrus), basal ganglia (putamen, caudate), and posterior cerebellar lobule VII, which mediates cognition. For default mode network regions, we also observed a compound profile of altered ALFF and ReHo. Most regional disturbances in ALFF and ReHo were associated with strengthened long-range interactions in PD-CN, notably with regions in different networks. Stronger long-range functional connectivity in PD-CN was also partly expanded to connections that were outside the networks of the control group. Abnormally increased activity and functional connectivity appeared to have a pathological

  14. Differential Intracochlear Sound Pressure Measurements in Normal Human Temporal Bones

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    Nakajima, Hideko Heidi; Dong, Wei; Olson, Elizabeth S.; Merchant, Saumil N.; Ravicz, Michael E.; Rosowski, John J.

    2009-02-01

    We present the first simultaneous sound pressure measurements in scala vestibuli and scala tympani of the cochlea in human cadaveric temporal bones. Micro-scale fiberoptic pressure sensors enabled the study of differential sound pressure at the cochlear base. This differential pressure is the input to the cochlear partition, driving cochlear waves and auditory transduction. Results showed that: pressure of scala vestibuli was much greater than scala tympani except at low and high frequencies where scala tympani pressure affects the input to the cochlea; the differential pressure proved to be an excellent measure of normal ossicular transduction of sound (shown to decrease 30-50 dB with ossicular disarticulation, whereas the individual scala pressures were significantly affected by non-ossicular conduction of sound at high frequencies); the middle-ear gain and differential pressure were generally bandpass in frequency dependence; and the middle-ear delay in the human was over twice that of the gerbil. Concurrent stapes velocity measurements allowed determination of the differential impedance across the partition and round-window impedance. The differential impedance was generally resistive, while the round-window impedance was consistent with a compliance in conjunction with distributed inertia and damping. Our techniques can be used to study inner-ear conductive pathologies (e.g., semicircular dehiscence), as well as non-ossicular cochlear stimulation (e.g., round-window stimulation) - situations that cannot be completely quantified by measurements of stapes velocity or scala-vestibuli pressure by themselves.

  15. Normal people working in normal organizations with normal equipment: system safety and cognition in a mid-air collision.

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    de Carvalho, Paulo Victor Rodrigues; Gomes, José Orlando; Huber, Gilbert Jacob; Vidal, Mario Cesar

    2009-05-01

    A fundamental challenge in improving the safety of complex systems is to understand how accidents emerge in normal working situations, with equipment functioning normally in normally structured organizations. We present a field study of the en route mid-air collision between a commercial carrier and an executive jet, in the clear afternoon Amazon sky in which 154 people lost their lives, that illustrates one response to this challenge. Our focus was on how and why the several safety barriers of a well structured air traffic system melted down enabling the occurrence of this tragedy, without any catastrophic component failure, and in a situation where everything was functioning normally. We identify strong consistencies and feedbacks regarding factors of system day-to-day functioning that made monitoring and awareness difficult, and the cognitive strategies that operators have developed to deal with overall system behavior. These findings emphasize the active problem-solving behavior needed in air traffic control work, and highlight how the day-to-day functioning of the system can jeopardize such behavior. An immediate consequence is that safety managers and engineers should review their traditional safety approach and accident models based on equipment failure probability, linear combinations of failures, rules and procedures, and human errors, to deal with complex patterns of coincidence possibilities, unexpected links, resonance among system functions and activities, and system cognition.

  16. Normalization and microbial differential abundance strategies depend upon data characteristics.

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    Weiss, Sophie; Xu, Zhenjiang Zech; Peddada, Shyamal; Amir, Amnon; Bittinger, Kyle; Gonzalez, Antonio; Lozupone, Catherine; Zaneveld, Jesse R; Vázquez-Baeza, Yoshiki; Birmingham, Amanda; Hyde, Embriette R; Knight, Rob

    2017-03-03

    Data from 16S ribosomal RNA (rRNA) amplicon sequencing present challenges to ecological and statistical interpretation. In particular, library sizes often vary over several ranges of magnitude, and the data contains many zeros. Although we are typically interested in comparing relative abundance of taxa in the ecosystem of two or more groups, we can only measure the taxon relative abundance in specimens obtained from the ecosystems. Because the comparison of taxon relative abundance in the specimen is not equivalent to the comparison of taxon relative abundance in the ecosystems, this presents a special challenge. Second, because the relative abundance of taxa in the specimen (as well as in the ecosystem) sum to 1, these are compositional data. Because the compositional data are constrained by the simplex (sum to 1) and are not unconstrained in the Euclidean space, many standard methods of analysis are not applicable. Here, we evaluate how these challenges impact the performance of existing normalization methods and differential abundance analyses. Effects on normalization: Most normalization methods enable successful clustering of samples according to biological origin when the groups differ substantially in their overall microbial composition. Rarefying more clearly clusters samples according to biological origin than other normalization techniques do for ordination metrics based on presence or absence. Alternate normalization measures are potentially vulnerable to artifacts due to library size. Effects on differential abundance testing: We build on a previous work to evaluate seven proposed statistical methods using rarefied as well as raw data. Our simulation studies suggest that the false discovery rates of many differential abundance-testing methods are not increased by rarefying itself, although of course rarefying results in a loss of sensitivity due to elimination of a portion of available data. For groups with large (~10×) differences in the average

  17. Brain signal variability differentially affects cognitive flexibility and cognitive stability

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    Armbruster-Genç, D.J.N.; Ültzhöffer, K.; Fiebach, C.J.

    2016-01-01

    Recent research yielded the intriguing conclusion that, in healthy adults, higher levels of variability in neuronal processes are beneficial for cognitive functioning. Beneficial effects of variability in neuronal processing can also be inferred from neurocomputational theories of working memory,

  18. Destination memory and cognitive theory of mind in normal ageing.

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    El Haj, Mohamad; Raffard, Stéphane; Gély-Nargeot, Marie-Christine

    2016-01-01

    Destination memory is the ability to remember the destination to which a piece of information has been addressed (e.g., "Did I tell you about the promotion?"). This ability is found to be impaired in normal ageing. Our work aimed to link this deterioration to the decline in theory of mind. Forty younger adults (M age = 23.13 years, SD = 4.00) and 36 older adults (M age = 69.53 years, SD = 8.93) performed a destination memory task. They also performed the False-belief test addressing cognitive theory of mind and the Reading the mind in the eyes test addressing affective theory of mind. Results showed significant deterioration in destination memory, cognitive theory of mind and affective theory of mind in the older adults. The older adults' performance on destination memory was significantly correlated with and predicted by their performance on cognitive theory of mind. Difficulties in the ability to interpret and predict others' mental states are related to destination memory decline in older adults.

  19. Age Effects on Cortical Thickness in Cognitively Normal Elderly Individuals

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    Sona Hurtz

    2014-07-01

    Full Text Available Background/Aims: Atrophy in both grey and white matter is found in normal aging. The prefrontal cortex and the frontal lobe white matter are thought to be the most affected regions. Our aim was to examine the effects of normal aging on cortical grey matter using a 3D quantitative cortical mapping method. Methods: We analyzed 1.5-tesla brain magnetic resonance imaging data from 44 cognitively normal elderly subjects using cortical pattern matching and cortical thickness analyses. Linear regression analysis was used to study the effect of age on cortical thickness. 3D map-wide correction for multiple comparisons was conducted with permutation analyses using a threshold of p Results: We found a significant negative association between age and cortical thickness in the right hemisphere (pcorrected = 0.009 and a trend level association in the left hemisphere (pcorrected = 0.081. Age-related changes were greatest in the sensorimotor, bilateral dorsal anterior cingulate and supplementary motor cortices, and the right posterior middle and inferior frontal gyri. Age effects greater in the medial than lateral visual association cortices were also seen bilaterally. Conclusion: Our novel method further validates that normal aging results in diffuse cortical thinning that is most pronounced in the frontal and visual association cortices.

  20. Magnetization transfer ratio relates to cognitive impairment in normal elderly

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    Stephan eSeiler

    2014-09-01

    Full Text Available Magnetization transfer imaging (MTI can detect microstructural brain tissue changes and may be helpful in determining age-related cerebral damage. We investigated the association between the magnetization transfer ratio (MTR in gray and white matter and cognitive functioning in 355 participants of the Austrian Stroke Prevention Family Study (ASPS-Fam aged 38 to 86 years. MTR maps were generated for the neocortex, deep gray matter structures, white matter hyperintensities, and normal appearing white matter. Adjusted mixed models determined whole brain and lobar cortical MTR to be directly and significantly related to performance on tests of memory, executive function and motor skills. There existed an almost linear dose-effect relationship. MTR of deep gray matter structures and normal appearing white matter correlated to executive functioning. All associations were independent of demographics, vascular risk factors, focal brain lesions and cortex volume.Further research is needed to understand the basis of this association at the tissue level, and to determine the role of MTR in predicting cognitive decline and dementia.

  1. Moderating Effects of Cortisol on Neural-Cognitive Association in Cognitively Normal Elderly Subjects

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    Way K. W. Lau

    2017-05-01

    Full Text Available Cortisol homeostasis is important for healthy brain and cognitive aging. The aim of the current study is to investigate the role of serum cortisol levels in the relationship between regional brain volumes and cognitive processing speed in a group of cognitively normal elderly subjects. Forty-one healthy elderly participants were from a parallel longitudinal study. The reported data in this study reflects baseline measurements. Whole-brain anatomical scanning was performed using a 3.0 Tesla Philips Medical Systems Achieva scanner. Cognitive processing speed was assessed by the digit-symbol and symbol search tests, from the Chinese version of the Wechsler Adult Intelligence Scale—third edition (WAIS-III. Serum cortisol levels (sampled in the late morning were measured by ELISA kits. Whole-brain regression analysis revealed that serum cortisol levels positively predicted the white matter volumes (WMV of the right thalamus, the gray matter volumes (GMV of the left thalamus and right cerebellar tonsil, and negatively predicted the WMV and GMV of the left middle temporal gyrus (MTG in 41 healthy elderly participants. Furthermore, serum cortisol significantly moderated the relationship between the GMV of the left MTG and processing speed, as well as the GMV of the left thalamus and processing speed. This study provided the first piece of evidence supporting serum cortisol levels in moderating the relationship between regional brain volumes and processing speed in healthy elderly subjects. This observation enriches our understanding of the role of cortisol in brain morphology and cognitive functioning.

  2. Moderating Effects of Cortisol on Neural-Cognitive Association in Cognitively Normal Elderly Subjects

    Science.gov (United States)

    Lau, Way K. W.; Leung, Mei Kei; Law, Andrew C. K.; Lee, Tatia M. C.

    2017-01-01

    Cortisol homeostasis is important for healthy brain and cognitive aging. The aim of the current study is to investigate the role of serum cortisol levels in the relationship between regional brain volumes and cognitive processing speed in a group of cognitively normal elderly subjects. Forty-one healthy elderly participants were from a parallel longitudinal study. The reported data in this study reflects baseline measurements. Whole-brain anatomical scanning was performed using a 3.0 Tesla Philips Medical Systems Achieva scanner. Cognitive processing speed was assessed by the digit-symbol and symbol search tests, from the Chinese version of the Wechsler Adult Intelligence Scale—third edition (WAIS-III). Serum cortisol levels (sampled in the late morning) were measured by ELISA kits. Whole-brain regression analysis revealed that serum cortisol levels positively predicted the white matter volumes (WMV) of the right thalamus, the gray matter volumes (GMV) of the left thalamus and right cerebellar tonsil, and negatively predicted the WMV and GMV of the left middle temporal gyrus (MTG) in 41 healthy elderly participants. Furthermore, serum cortisol significantly moderated the relationship between the GMV of the left MTG and processing speed, as well as the GMV of the left thalamus and processing speed. This study provided the first piece of evidence supporting serum cortisol levels in moderating the relationship between regional brain volumes and processing speed in healthy elderly subjects. This observation enriches our understanding of the role of cortisol in brain morphology and cognitive functioning. PMID:28596732

  3. Early Alzheimer-type lesions in cognitively normal subjects.

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    Tsartsalis, Stergios; Xekardaki, Aikaterini; Hof, Patrick R; Kövari, Enikö; Bouras, Constantin

    2018-02-01

    Amyloid deposits and tau-immunoreactive neurofibrillary tangles, together with neuronal and synaptic loss, are the neuropathological hallmarks of Alzheimer's disease (AD). Both proteins are present in the normal brain during aging. However, the temporal sequence of their involvement in the onset of AD pathology remains controversial. To define whether amyloid β protein deposits or tau protein lesions appear first during normal brain aging, we performed an immunohistological study on serial sections from 105 autopsy brains (age range: 40-104 years) from patients free of clinical signs of cognitive decline, using anti-tau (AT8) and anti-amyloid (4G8) antibodies in the hippocampus, entorhinal cortex, inferior temporal cortex (Brodmann area 20), prefrontal cortex (Brodmann area 9), occipital cortex (Brodmann areas 17 and 18), and in the brainstem. All cases older than 48 years displayed at least a few neurofibrillary tangles, which appeared more frequently in the entorhinal than in the transentorhinal cortex. Tau pathology in these areas preceded tau inclusions in the brainstem. Furthermore, the first site of the apparition of tau pathology is inconsistent, being the entorhinal cortex in most cases, and in fewer cases, the transentorhinal region. There was no case presenting with amyloid deposition in the absence of neurofibrillary tangles, lending evidence to the fact that neurofibrillary tangles appear earlier than amyloid plaques during normal brain aging. However, the role of amyloid in promoting tau deposition cannot be excluded in some cases but may not represent the sole mechanism of disease induction and progression. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Prefrontal activation may predict working-memory training gain in normal aging and mild cognitive impairment

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    Vermeij, A.; Kessels, R.P.C.; Heskamp, L.; Simons, E.M.F.; Dautzenberg, P.LJ.; Claassen, J.A.H.R.

    2017-01-01

    Cognitive training has been shown to result in improved behavioral performance in normal aging and mild cognitive impairment (MCI), yet little is known about the neural correlates of cognitive plasticity, or about individual differences in responsiveness to cognitive training. In this study, 21

  5. Differential Gene Expression of Fibroblasts: Keloid versus Normal

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    Michael F. Angel

    2002-11-01

    Full Text Available Abstract: This study investigated gene regulation and unique gene products in both keloid (KDF and normal (NDF dermal fibroblasts in established cell lines. For gene regulation, NDF versus KDF were compared using Clontech's Atlas™ Human cDNA Expression Array while unique gene products were studied using RNA Fingerprinting Kit. RNA from each sample was converted to cDNA using oligo-dT primers. Down-regulated genes using Atlas Array in KDF were 1 60 S ribosomal protein, 2 Thioredoxin dependent peroxidase, 3 Nuclease sensitive element DNA binding protein, 4 c-myc purine-binding transcription factor, 5 c-AMP dependent protein kinase, and, 6 Heat Shock Protein 90 kDa. Genes that are up regulated in KDF were 1 Tubulin and 2 Heat Shock Protein 27 kDa. With the differential display, we found 17 bands unique to both KDF and NDF. The specific gene and the manner in which they were differentially regulated have direct implications to understanding keloid fibroblast proliferation.

  6. An experimental-differential investigation of cognitive complexity

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    2009-12-01

    Full Text Available Cognitive complexity as defined by differential and experimental traditions was explored to investigate the theoretical advantage and utility of relational complexity (RC theory as a common framework for studying fluid cognitive functions. RC theory provides a domain general account of processing demand as a function of task complexity. In total, 142 participants completed two tasks in which RC was manipulated, and two tasks entailing manipulations of complexity derived from the differential psychology literature. A series of analyses indicated that, as expected, task manipulations influenced item difficulty. However, comparable changes in a psychometric index of complexity were not consistently observed. Active maintenance of information across multiple steps of the problem solving process, which entails strategic coordination of storage and processing that cannot be modelled under the RC framework was found to be an important component of cognitive complexity.

  7. Cerebral Blood Flow and Amyloid-β Interact to Affect Memory Performance in Cognitively Normal Older Adults

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    Katherine J. Bangen

    2017-06-01

    Full Text Available Cerebral blood flow (CBF alterations and amyloid-β (Aβ accumulation have been independently linked to cognitive deficits in older adults at risk for dementia. Less is known about how CBF and Aβ may interact to affect cognition in cognitively normal older adults. Therefore, we examined potential statistical interactions between CBF and Aβ status in regions typically affected in Alzheimer’s disease (AD within a sample of older adults from the Alzheimer’s Disease Neuroimaging Initiative (ADNI study. Sixty-two cognitively normal participants (mean age = 72 years underwent neuroimaging and memory testing. Arterial spin labeling magnetic resonance imaging was used to quantify CBF and florbetapir PET amyloid imaging was used to measure Aβ deposition. Aβ status (i.e., positivity versus negativity was determined based on established cutoffs (Landau et al., 2013. The Rey Auditory Verbal Learning Test was used to assess memory. Linear regression models adjusted for age, education, and sex, demonstrated significant interactions between CBF and Aβ status on memory performance. Among Aβ positive older adults, there were significant negative associations between higher CBF in hippocampus, posterior cingulate, and precuneus and poorer memory performance. In contrast, among Aβ negative older adults, there were no significant associations between CBF and cognition. Our findings extend previous CBF studies of dementia risk by reporting interactions between Aβ status and CBF on memory performance in a sample of well-characterized, cognitively normal older adults. Results suggest that differential CBF-cognition associations can be identified in healthy, asymptomatic Aβ positive older adults relative to Aβ negative individuals. Associations between higherCBF and poorer memory among Aβ positive older adults may reflect a cellular and/or vascular compensatory response to pathologic processes whereby higher CBF is needed to maintain normal memory

  8. Ultradian rhythmicity of plasma cortisol is necessary for normal emotional and cognitive responses in man.

    Science.gov (United States)

    Kalafatakis, K; Russell, G M; Harmer, C J; Munafo, M R; Marchant, N; Wilson, A; Brooks, J C; Durant, C; Thakrar, J; Murphy, P; Thai, N J; Lightman, S L

    2018-04-24

    Glucocorticoids (GCs) are secreted in an ultradian, pulsatile pattern that emerges from delays in the feedforward-feedback interaction between the anterior pituitary and adrenal glands. Dynamic oscillations of GCs are critical for normal cognitive and metabolic function in the rat and have been shown to modulate the pattern of GC-sensitive gene expression, modify synaptic activity, and maintain stress responsiveness. In man, current cortisol replacement therapy does not reproduce physiological hormone pulses and is associated with psychopathological symptoms, especially apathy and attenuated motivation in engaging with daily activities. In this work, we tested the hypothesis that the pattern of GC dynamics in the brain is of crucial importance for regulating cognitive and behavioral processes. We provide evidence that exactly the same dose of cortisol administered in different patterns alters the neural processing underlying the response to emotional stimulation, the accuracy in recognition and attentional bias toward/away from emotional faces, the quality of sleep, and the working memory performance of healthy male volunteers. These data indicate that the pattern of the GC rhythm differentially impacts human cognition and behavior under physiological, nonstressful conditions and has major implications for the improvement of cortisol replacement therapy.

  9. Heterogeneity of cognitive aging in Brazilian normal elderls

    Directory of Open Access Journals (Sweden)

    Maria Paula Foss

    Full Text Available Abstract With aging, several cognitive skills inevitably decline. However, cognitive losses do not occur homogenously in all elderly people, differing in number and severity of affected cognitive functions. These differences could be exacerbated by socioeconomic differences in a developing country like Brazil. Objectives: to characterize the cognitive functioning of healthy elderly subjects whose socioeconomic conditions differ to those of other studies. Methods: 60 elderly subjects with a mean age of 68 years, 43 women and 17 men, and mean schooling of 7.1 years, were studied. The cognitive function of this group was assessed using the following neuropsychological tests: Mattis Dementia Rating Scale (MDRS, Stroop Test, Verbal Fluency, Wisconsin Card Sorting Test (WCST, Rey Complex Figure, Vocabulary - Wais - III, Logical Memory (WMS-R, Visual Reproduction (WMS-R, and Rey Auditory-Verbal Learning Test (RAVLT. The neuropsychological data were submitted to Multivariate cluster analysis using SAS - Proc Cluster software and the complete binding hierarchical method. Results: Variability was found allowing classification of the studied group into 4 clusters of individuals who had above-average (C1, average (C3 and C4 and below average (C2 performance. Schooling determined the results obtained, with less educated subjects showing poorer performance than higher-educated subjects. Conclusions: Significant differences in the process of cognitive aging were detected on neuropsychological tests in this group of healthy elderly from the developing country of Brazil, where socioeconomic differences may exacerbate cognitive differences among older adults.

  10. Neural underpinnings of background acoustic noise in normal aging and mild cognitive impairment.

    Science.gov (United States)

    Sinanaj, Indrit; Montandon, Marie-Louise; Rodriguez, Cristelle; Herrmann, François; Santini, Francesco; Haller, Sven; Giannakopoulos, Panteleimon

    2015-12-03

    Previous contributions in younger cohorts have revealed that reallocation of cerebral resources, a crucial mechanism for working memory (WM), may be disrupted by parallel demands of background acoustic noise suppression. To date, no study has explored the impact of such disruption on brain activation in elderly individuals with or without subtle cognitive deficits. We performed a functional Magnetic Resonance Imaging (fMRI) study in 23 cases (mean age=75.7 y.o., 16 men) with mild cognitive impairment (MCI) and 16 elderly healthy controls (HC, mean age=70.1 y.o., three men) using a 2-back WM task, under two distinct MRI background acoustic noise conditions (louder vs. lower noise echo-planar imaging). General linear models were used to assess brain activation as a function of group and noise. In both groups, lower background noise is associated with increased activation of the working memory network (WMN). A decrease of the normally observed deactivation of the default mode network (DMN) is found under louder noise in both groups. Unlike HC, MCI cases also show decreased deactivation of the DMN under both louder and lower background noise. Under louder noise, this decrease is observed in anterior parts of the DMN in HC, and in the posterior cingulate cortex in MCI cases. Our results suggest that background acoustic noise has a differential impact on WMN activation in normal aging as a function of the cognitive status. Only louder noise has a disruptive effect on the usually observed DMN deactivation during WM task performance in HC. In contrast, MCI cases show altered DMN reactivity even in the presence of lower noise. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  11. Cognitive behavior therapy for eating disorders versus normalization of eating behavior.

    Science.gov (United States)

    Södersten, P; Bergh, C; Leon, M; Brodin, U; Zandian, M

    2017-05-15

    We examine the science and evidence supporting cognitive behavior therapy (CBT) for the treatment of bulimia nervosa and other eating disorders. Recent trials focusing on the abnormal cognitive and emotional aspects of bulimia have reported a remission rate of about 45%, and a relapse rate of about 30% within one year. However, an early CBT trial that emphasized the normalization of eating behavior had a better outcome than treatment that focused on cognitive intervention. In support of this finding, another treatment, that restores a normal eating behavior using mealtime feedback, has an estimated remission rate of about 75% and a relapse rate of about 10% over five years. Moreover, when eating behavior was normalized, cognitive and emotional abnormalities were resolved at remission without cognitive therapy. The critical aspect of the CBT treatment of bulimia nervosa therefore may actually have been the normalization of eating behavior. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Comparison of the quick mild cognitive impairment (Qmci) screen and the SMMSE in screening for mild cognitive impairment.

    LENUS (Irish Health Repository)

    O'Caoimh, Rónán

    2012-09-01

    differentiating mild cognitive impairment (MCI) from normal cognition (NC) is difficult. The AB Cognitive Screen (ABCS) 135, sensitive in differentiating MCI from dementia, was modified to improve sensitivity and specificity, producing the quick mild cognitive impairment (Qmci) screen.

  13. Are Prescription Stimulants "Smart Pills"? The Epidemiology and Cognitive Neuroscience of Prescription Stimulant Use by Normal Healthy Individuals

    Science.gov (United States)

    Smith, M. Elizabeth; Farah, Martha J.

    2011-01-01

    Use of prescription stimulants by normal healthy individuals to enhance cognition is said to be on the rise. Who is using these medications for cognitive enhancement, and how prevalent is this practice? Do prescription stimulants in fact enhance cognition for normal healthy people? We review the epidemiological and cognitive neuroscience…

  14. Cognition of normal pattern of myocardial polar map

    International Nuclear Information System (INIS)

    Fujisawa, Yasuo; Sasaki, Jiro; Kashima, Kenji; Matsumura, Yasushi; Yamamoto, Kazuhiro; Kodama, Kazuhisa

    1989-01-01

    When we diagnose the presence of ischemic heart disease by the diagrams of computer-generated polar map of exercised thallium images, the estimation of the presence of the deficit is not sufficient, because many normal subjects are considered as abnormal. The mean+2SD of defect severity index (DSI) of 118 normal subjects was 120, and we defined the patients with DSI≤120 as normal. But in 139 patients with their DSI≤120, 28 patients had significant coronary stenosis (>75%) and this means that false negative was 20%. We estimated the pattern of the deficit and found that in 109 of 111 subjects with normal coronary arteries, and 16 of 28 patients with ischemic heart disease, the patterns of the diagrams of polar map were patchy. This means that the diagram of the polar map show patchy pattern more frequently in normal subjects. In 125 patients whose diagrams of polar map were patchy, 16 patients with ischemic heart disease were included (false negative was 13%). We conclude that the estimation of DSI and the pattern of the diagram of polar map should be simultaneously considered and this makes the more accurate diagnosis possible. (author)

  15. Perceptual differentiation and category effects in normal object recognition

    DEFF Research Database (Denmark)

    Gerlach, Christian; Law, I; Gade, A

    1999-01-01

    The purpose of the present PET study was (i) to investigate the neural correlates of object recognition, i.e. the matching of visual forms to memory, and (ii) to test the hypothesis that this process is more difficult for natural objects than for artefacts. This was done by using object decision...... tasks where subjects decided whether pictures represented real objects or non-objects. The object decision tasks differed in their difficulty (the degree of perceptual differentiation needed to perform them) and in the category of the real objects used (natural objects versus artefacts). A clear effect...... be the neural correlate of matching visual forms to memory, and the amount of activation in these regions may correspond to the degree of perceptual differentiation required for recognition to occur. With respect to behaviour, it took significantly longer to make object decisions on natural objects than...

  16. Cognitive capacity limitations and Need for Cognition differentially predict reward-induced cognitive effort expenditure.

    Science.gov (United States)

    Sandra, Dasha A; Otto, A Ross

    2018-03-01

    While psychological, economic, and neuroscientific accounts of behavior broadly maintain that people minimize expenditure of cognitive effort, empirical work reveals how reward incentives can mobilize increased cognitive effort expenditure. Recent theories posit that the decision to expend effort is governed, in part, by a cost-benefit tradeoff whereby the potential benefits of mental effort can offset the perceived costs of effort exertion. Taking an individual differences approach, the present study examined whether one's executive function capacity, as measured by Stroop interference, predicts the extent to which reward incentives reduce switch costs in a task-switching paradigm, which indexes additional expenditure of cognitive effort. In accordance with the predictions of a cost-benefit account of effort, we found that a low executive function capacity-and, relatedly, a low intrinsic motivation to expend effort (measured by Need for Cognition)-predicted larger increase in cognitive effort expenditure in response to monetary reward incentives, while individuals with greater executive function capacity-and greater intrinsic motivation to expend effort-were less responsive to reward incentives. These findings suggest that an individual's cost-benefit tradeoff is constrained by the perceived costs of exerting cognitive effort. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Differentiating cancerous from normal breast tissue by redox imaging

    Science.gov (United States)

    Xu, He N.; Tchou, Julia; Feng, Min; Zhao, Huaqing; Li, Lin Z.

    2015-02-01

    Abnormal metabolism can be a hallmark of cancer occurring early before detectable histological changes and may serve as an early detection biomarker. The current gold standard to establish breast cancer (BC) diagnosis is histological examination of biopsy. Previously we have found that pre-cancer and cancer tissues in animal models displayed abnormal mitochondrial redox state. Our technique of quantitatively measuring the mitochondrial redox state has the potential to be implemented as an early detection tool for cancer and may provide prognostic value. We therefore in this present study, investigated the feasibility of quantifying the redox state of tumor samples from 16 BC patients. Tumor tissue aliquots were collected from both normal and cancerous tissue from the affected cancer-bearing breasts of 16 female patients (5 TNBC, 9 ER+, 2 ER+/Her2+) shortly after surgical resection. All specimens were snap-frozen with liquid nitrogen on site and scanned later with the Chance redox scanner, i.e., the 3D cryogenic NADH/oxidized flavoprotein (Fp) fluorescence imager. Our preliminary results showed that both NADH and Fp (including FAD, i.e., flavin adenine dinucleotide) signals in the cancerous tissues roughly tripled to quadrupled those in the normal tissues (pcancerous tissues than in the normal ones (pcancer and non-cancer breast tissues in human patients and this novel redox scanning procedure may assist in tissue diagnosis in freshly procured biopsy samples prior to tissue fixation. We are in the process of evaluating the prognostic value of the redox imaging indices for BC.

  18. Differential effects of white noise in cognitive and perceptual tasks

    Directory of Open Access Journals (Sweden)

    Nora Alicia Herweg

    2015-11-01

    Full Text Available Beneficial effects of noise on higher cognition have recently attracted attention. Hypothesizing an involvement of the mesolimbic dopamine system and its functional interactions with cortical areas, the current study aimed to demonstrate a facilitation of dopamine-dependent attentional and mnemonic functions by externally applying white noise in five behavioral experiments including a total sample of 167 healthy human subjects. During working memory, acoustic white noise impaired accuracy when presented during the maintenance period (experiment 1-3. In a reward based long-term memory task, white noise accelerated perceptual judgments for scene images during encoding but left subsequent recognition memory unaffected (experiment 4. In a modified Posner task (experiment 5, the benefit due to white noise in attentional orienting correlated weakly with reward dependence, a personality trait that has been associated with the dopaminergic system. These results suggest that white noise has no general effect on cognitive functions. Instead, they indicate differential effects on perception and cognition depending on a variety of factors such as task demands and timing of white noise presentation.

  19. Differential effects of white noise in cognitive and perceptual tasks.

    Science.gov (United States)

    Herweg, Nora A; Bunzeck, Nico

    2015-01-01

    Beneficial effects of noise on higher cognition have recently attracted attention. Hypothesizing an involvement of the mesolimbic dopamine system and its functional interactions with cortical areas, the current study aimed to demonstrate a facilitation of dopamine-dependent attentional and mnemonic functions by externally applying white noise in five behavioral experiments including a total sample of 167 healthy human subjects. During working memory, acoustic white noise impaired accuracy when presented during the maintenance period (Experiments 1-3). In a reward based long-term memory task, white noise accelerated perceptual judgments for scene images during encoding but left subsequent recognition memory unaffected (Experiment 4). In a modified Posner task (Experiment 5), the benefit due to white noise in attentional orienting correlated weakly with reward dependence, a personality trait that has been associated with the dopaminergic system. These results suggest that white noise has no general effect on cognitive functions. Instead, they indicate differential effects on perception and cognition depending on a variety of factors such as task demands and timing of white noise presentation.

  20. Social cognition in the differential diagnosis of autism spectrum disorders and personality disorders

    NARCIS (Netherlands)

    Duijkers, J.C.L.M.; Vissers, C.Th.W.M.; Verbeeck, W.; Arntz, A.; Egger, J.I.M.

    2014-01-01

    Average intelligent patients with autism spectrum disorders (ASD) and patients with personality disorders (PD) are expected to show different problems in social cognition. Consequently, measuring social cognition may contribute to a better understanding and differentiation of ASD and PD. Therefore,

  1. Lower extremity function in normal cognitive aging, mild cognitive impairment, and Alzheimer’s disease

    NARCIS (Netherlands)

    Eggermont, L.H.P.; Gavett, B.E.; Volkers, K.M.; Blankevoort, C.G.; Scherder, E.J.A.; Jefferson, A.L.; Steinberg, E.; Nair, A.; Green, R.C.; Stern, R.A.

    2010-01-01

    Eggermont LH, Gavett BE, Volkers KM, Blankevoort CG, Scherder EJ, Jefferson AL, Steinberg E, Nair A, Green RC, Stern RA. Lower-extremity function in cognitively healthy aging, mild cognitive impairment, and Alzheimer's disease. Objective: To examine differences in lower-extremity function in

  2. DIFFERENTIAL HISTOMORPHOMETRIC CHANGES IN NORMAL AND INFLAMED GINGIVAL EPITHELIUM

    Directory of Open Access Journals (Sweden)

    Tanaskovic Stankovic Sanja

    2016-12-01

    Full Text Available Introduction and aim: In recent decades, many factors such as smoking, unhealthy diet as well as high alcohol intake were marked as risk factors that can lead to increased incidence of malignant alterations, gingivitis, periodontal disease and other oral epithelium pathological changes. Having in mind that in the group of non-malignant and non-dental oral pathology gingivitis and periodontal disease are the most common oral mucosa alterations aim of our research was to investigate histomorphometric characteristics of healthy and altered oral and gingival epithelium. Material and methods: Tissue samples of 24 oral and gingival mucosa specimens were collected. Samples were fixed in 10% buffered paraformaldehyde, routinely processed and embedded in paraffin blocks. From each block sections 5 micrometer thin were made and standard H/E staining as well as immunocytochemical detection of Ki-67 proliferation marker and CD79a lymphocyte marker were performed. Measurements and image analysis was performed with Image Pro Plus software (Media Cybernetics, USA and Axiovision (Ziess, USA. Results: We showed that inflamed gingival epithelium is increasing its thickness in proportion to the severity of adjacent inflammation. Furthermore, mitotic index is rising (up to 132% in the same manner as well as basal lamina length (up to 70% when normal and inflamed gingiva is compared. Architecture of epithelial ridges is changed from straightforward to mesh-like. Conclusion: Assessment of the free gingival epithelium thickness is directly related to the severity of the inflammation process i

  3. Overweight and obese infants present lower cognitive and motor development scores than normal-weight peers.

    Science.gov (United States)

    Camargos, Ana Cristina Resende; Mendonça, Vanessa Amaral; Andrade, Camila Alves de; Oliveira, Katherine Simone Caires; Lacerda, Ana Cristina Rodrigues

    2016-12-01

    Compare the cognitive and motor development in overweight/obese infants versus normal-weight peers and investigate the correlation of body weight, body length and body mass index with cognitive and motor development. We conducted a cross-sectional study with 28 overweight/obese infants and 28 normal-weight peers between 6 and 24 months of age. Both groups were evaluated with cognitive and motor scales of the Bayley-III infant development test. The t-test for independent samples was performed to compare the groups, and the Spearman correlation was used to verify the association between variables. Overweight/obese infants showed lower cognitive and motor composite scores than their normal-weight peers. A significant negative association was found of body weight and body length with cognitive development and of body mass index with motor development. This is the first study that found an effect on both cognitive and motor development in overweight/obese infants when compared with normal-weight peers between 6 and 24 months of age. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Tau, APP, NCT and BACE1 in lymphocytes through cognitively normal ageing and neuropathology

    Directory of Open Access Journals (Sweden)

    MARISOL HERRERA-RIVERO

    2013-01-01

    Full Text Available Although Alzheimer's disease is a brain disorder, a number of peripheral alterations have been found in these patients; however, little is known about how the key genes involved in the pathophysiology express in peripheral cells such as lymphocytes during normal compared to neuropathological ageing. We analysed the expression of tau, of the amyloid precursor protein, of nicastrin and of the β-site APP cleaving enzyme genes by RT-PCR in lymphocytes from a small group of late-onset Alzheimer's disease patients, from aged patients suffering from neuropsychological conditions different from Alzheimer's and from cognitively healthy subjects divided in four groups by age. We also investigated correlations between gene expression and levels of blood pressure, glucose, total cholesterol and triglycerides as risk factors for Alzheimer's. Results show no tau expression in lymphocytes, a lack of detection of nicastrin expression in Alzheimer's patients and correlations between the medical conditions studied and gene expression in lymphocytes. We believe nicastrin gene expression in lymphocytes should be considered of interest for further analyses in a wider population to investigate whether it might represent a potential biomarker to differentiate Alzheimer's from other neuropsychological disorders.

  5. Performances on a cognitive theory of mind task: specific decline or general cognitive deficits? Evidence from normal aging.

    Science.gov (United States)

    Fliss, Rafika; Lemerre, Marion; Mollard, Audrey

    2016-06-01

    Compromised theory of mind (ToM) can be explained either by a failure to implement specific representational capacities (mental state representations) or by more general executive selection demands. In older adult populations, evidence supporting affected executive functioning and cognitive ToM in normal aging are reported. However, links between these two functions remain unclear. In the present paper, we address these shortcomings by using a specific task of ToM and classical executive tasks. We studied, using an original cognitive ToM task, the effect of age on ToM performances, in link with the progressive executive decline. 96 elderly participants were recruited. They were asked to perform a cognitive ToM task, and 5 executive tests (Stroop test and Hayling Sentence Completion Test to appreciate inhibitory process, Trail Making Test and Verbal Fluency for shifting assessment and backward span dedicated to estimate working memory capacity). The results show changes in cognitive ToM performance according to executive demands. Correlational studies indicate a significant relationship between ToM performance and the selected executive measures. Regression analyzes demonstrates that level of vocabulary and age as the best predictors of ToM performance. The results are consistent with the hypothesis that ToM deficits are related to age-related domain-general decline rather than as to a breakdown in specialized representational system. The implications of these findings for the nature of social cognition tests in normal aging are also discussed.

  6. Cognitive functioning and its influence on sexual behavior in normal aging and dementia.

    Science.gov (United States)

    Hartmans, Carien; Comijs, Hannie; Jonker, Cees

    2014-05-01

    Motivational aspects, emotional factors, and cognition, all of which require intact cognitive functioning may be essential in sexual functioning. However, little is known about the association between cognitive functioning and sexual behavior. The aim of this article is to review the current evidence for the influence of cognitive functioning on sexual behavior in normal aging and dementia. A systematic literature search was conducted in PubMed, Ovid, Cochrane, and PsycINFO databases. The databases were searched for English language papers focusing on human studies published relating cognitive functioning to sexual behavior in the aging population. Keywords included sexual behavior, sexuality, cognitive functioning, healthy elderly, elderly, aging and dementia. Eight studies fulfilled our inclusion criteria. Of these studies, five included dementia patients and/or their partners, whereas only three studies included healthy older persons. Although not consistently, results indicated a trend that older people who are not demented and continue to engage in sexual activity have better overall cognitive functioning. Cognitive decline and dementia seem to be associated with diminished sexual behavior in older persons. The association between cognitive functioning and sexual behavior in the aging population is understudied. The results found are inconclusive. Copyright © 2013 John Wiley & Sons, Ltd.

  7. Serial position effects in Alzheimer's disease, mild cognitive impairment, and normal aging: predictive value for conversion to dementia.

    Science.gov (United States)

    Cunha, Catarina; Guerreiro, Manuela; de Mendonça, Alexandre; Oliveira, Paulo Eduardo; Santana, Isabel

    2012-01-01

    Serial position effects in word list learning have been used to differentiate normal aging and dementia. Prominent recency and diminished primacy have consistently been observed in Alzheimer's disease (AD). We examined serial position effects in patients with mild cognitive impairment (MCI), in patients with AD, and in normal healthy controls. Additionally, we classified MCI patients into those who progressed to AD (MCI-p) and those who did not (MCI-np). We compared two serial position measures: regional and standard scores. Regional scores, mainly the primacy effect, improved discrimination between MCI and controls and between MCI-np and MCI-p, proving to be more sensitive and specific than the recency effect.

  8. Association of Plasma Neurofilament Light Chain with Neocortical Amyloid-β Load and Cognitive Performance in Cognitively Normal Elderly Participants.

    Science.gov (United States)

    Chatterjee, Pratishtha; Goozee, Kathryn; Sohrabi, Hamid R; Shen, Kaikai; Shah, Tejal; Asih, Prita R; Dave, Preeti; ManYan, Candice; Taddei, Kevin; Chung, Roger; Zetterberg, Henrik; Blennow, Kaj; Martins, Ralph N

    2018-01-01

    The disruption of neurofilament, an axonal cytoskeletal protein, in neurodegenerative conditions may result in neuronal damage and its release into the cerebrospinal fluid and blood. In Alzheimer's disease (AD), neurofilament light chain (NFL), a neurofilament subunit, is elevated in the cerebrospinal fluid and blood. Investigate the association of plasma NFL with preclinical-AD features, such as high neocortical amyloid-β load (NAL) and subjective memory complaints, and cognitive performance in cognitively normal older adults. Plasma NFL concentrations were measured employing the single molecule array platform in participants from the Kerr Anglican Retirement Village Initiative in Ageing Health cohort, aged 65- 90 years. Participants underwent a battery of neuropsychological testing to evaluate cognitive performance and were categorized as low NAL (NAL-, n = 65) and high NAL (NAL+, n = 35) assessed via PET, and further stratified into subjective memory complainers (SMC; nNAL- = 51, nNAL+ = 25) and non-SMC (nNAL- = 14, nNAL+ = 10) based on the Memory Assessment Clinic- Questionnaire. Plasma NFL inversely correlated with cognitive performance. No significant difference in NFL was observed between NAL+ and NAL- participants; however, within APOEɛ4 non-carriers, higher NAL was observed in individuals with NFL concentrations within quartiles 3 and 4 (versus quartile 1). Additionally, within the NAL+ participants, SMC had a trend of higher NFL compared to non-SMC. Plasma NFL is inversely associated with cognitive performance in elderly individuals. While plasma NFL may not reflect NAL in individuals with normal global cognition, the current observations indicate that onset of axonal injury, reflected by increased plasma NFL, within the preclinical phase of AD may contribute to the pathogenesis of AD.

  9. Integrating the Differentiated: A Review of the Personal Construct Approach to Cognitive Complexity

    OpenAIRE

    Kovářová, M. (Marie); Filip, M. (Miroslav)

    2015-01-01

    This article reviews personal construct psychology (PCP) research on cognitive complexity. It examines conceptual foundations, measures of cognitive complexity, and a large body of empirical findings. It identifies several ambiguities in the conceptualization of the two components of cognitive complexity: differentiation and integration. These ambiguities lead to inconsistent interpretations of indexes proposed for their measurement and consequently to an inconsistent interpretation of em...

  10. Association between memory complaints and incident Alzheimer's disease in elderly people with normal baseline cognition.

    NARCIS (Netherlands)

    Geerlings, M.I.; Jonker, C.; Bouter, L.M.; Adèr, H.J.; Schmand, B.

    1999-01-01

    In the community-based Amsterdam Study of the Elderly, a sample of 3,778 nondemented persons, 65-84 yrs old, was divided into 2 cognitive categories: normal, and borderline and impaired. At baseline, the presence or absence of memory complaints was assessed with a single question. At follow-up,

  11. Amyloid and metabolic positron emission tomography imaging of cognitively normal adults with Alzheimer's parents

    DEFF Research Database (Denmark)

    Mosconi, Lisa; Rinne, Juha O; Tsui, Wai H

    2013-01-01

    This study examines the relationship between fibrillar beta-amyloid (Aβ) deposition and reduced glucose metabolism, a proxy for neuronal dysfunction, in cognitively normal (NL) individuals with a parent affected by late-onset Alzheimer's disease (AD). Forty-seven 40-80-year-old NL received positr...

  12. Morphometric connectivity analysis to distinguish normal, mild cognitive impaired, and Alzheimer subjects based on brain MRI

    DEFF Research Database (Denmark)

    Erleben, Lene Lillemark; Sørensen, Lauge; Mysling, Peter

    2013-01-01

    This work investigates a novel way of looking at the regions in the brain and their relationship as possible markers to classify normal control (NC), mild cognitive impaired (MCI), and Alzheimer Disease (AD) subjects. MRI scans from a subset of 101 subjects from the ADNI study at baseline was used...

  13. Quantifying cognition and behavior in normal aging, mild cognitive impairment, and Alzheimer's disease

    Science.gov (United States)

    Giraldo, Diana L.; Sijbers, Jan; Romero, Eduardo

    2017-11-01

    The diagnosis of Alzheimer's disease (AD) and mild cognitive impairment (MCI) is based on neuropsychological evaluation of the patient. Different cognitive and memory functions are assessed by a battery of tests that are composed of items devised to specifically evaluate such upper functions. This work aims to identify and quantify the factors that determine the performance in neuropsychological evaluation by conducting an Exploratory Factor Analysis (EFA). For this purpose, using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), EFA was applied to 67 item scores taken from the baseline neuropsychological battery of the three phases of ADNI study. The found factors are directly related to specific brain functions such as memory, behavior, orientation, or verbal fluency. The identification of factors is followed by the calculation of factor scores given by weighted linear combinations of the items scores.

  14. A Network Flow-based Analysis of Cognitive Reserve in Normal Ageing and Alzheimer's Disease.

    Science.gov (United States)

    Wook Yoo, Sang; Han, Cheol E; Shin, Joseph S; Won Seo, Sang; Na, Duk L; Kaiser, Marcus; Jeong, Yong; Seong, Joon-Kyung

    2015-05-20

    Cognitive reserve is the ability to sustain cognitive function even with a certain amount of brain damages. Here we investigate the neural compensation mechanism of cognitive reserve from the perspective of structural brain connectivity. Our goal was to show that normal people with high education levels (i.e., cognitive reserve) maintain abundant pathways connecting any two brain regions, providing better compensation or resilience after brain damage. Accordingly, patients with high education levels show more deterioration in structural brain connectivity than those with low education levels before symptoms of Alzheimer's disease (AD) become apparent. To test this hypothesis, we use network flow measuring the number of alternative paths between two brain regions in the brain network. The experimental results show that for normal aging, education strengthens network reliability, as measured through flow values, in a subnetwork centered at the supramarginal gyrus. For AD, a subnetwork centered at the left middle frontal gyrus shows a negative correlation between flow and education, which implies more collapse in structural brain connectivity for highly educated patients. We conclude that cognitive reserve may come from the ability of network reorganization to secure the information flow within the brain network, therefore making it more resistant to disease progress.

  15. Differentiating Animality from Agency. Towards a Foundation for Cognition

    NARCIS (Netherlands)

    Keijzer, F.A.

    2006-01-01

    The notion of cognition has been difficult to pin down. Embodied and situated approaches to cognition now suggests that agency, construed in terms of perceptionaction coupling, might provide a clear foundation for cognition. Yet, this attempt has problems of its own. First, a demarcation problem:

  16. Normal weight children have higher cognitive performance - Independent of physical activity, sleep, and diet.

    Science.gov (United States)

    Hjorth, Mads F; Sørensen, Louise B; Andersen, Rikke; Dyssegaard, Camilla B; Ritz, Christian; Tetens, Inge; Michaelsen, Kim F; Astrup, Arne; Egelund, Niels; Sjödin, Anders

    2016-10-15

    Aside from the health consequences, observational studies indicate that being overweight may also negatively affect cognitive function. However, existing evidence has to a large extent not controlled for the possible confounding effect of having different lifestyles. Therefore, the objective was to examine the independent associations between weight status and lifestyle indicators with cognitive performance in 8-11year old Danish children. The analyses included 828 children (measured in 2011-2012) each having one to three measurement occasions separated by approximately 100days. Dietary intake, physical activity, sedentary time, and sleep duration were measured using dietary records and accelerometers. The Children's Sleep Habits Questionnaire was used to access sleep problems and the Andersen test was carried out to estimate cardio-respiratory fitness (CRF). Weight status (underweight, normal weight, and overweight/obese) was defined according to body mass index and cognitive performance was assessed using the d2-test of attention, a reading test, and a math test. A linear mixed model including a number of fixed and random effects was used to test associations between lifestyle indicators as well as BMI category and cognitive performance. After adjustment for demographics, socioeconomics, and multiple lifestyle indicators, normal weight children had higher cognitive test scores than overweight/obese and underweight children of up to 89% and 48% of expected learning within one school year (Pbreakfast consumption, fewer sleep problems, higher CRF, less total physical activity, more sedentary time, and less light physical activity were associated with higher cognitive performance independently of each other in at least one of the three cognitive tests (Pperformance compared to overweight/obese as well as underweight children, independent of multiple lifestyle indicators. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Normal uniform mixture differential gene expression detection for cDNA microarrays

    Directory of Open Access Journals (Sweden)

    Raftery Adrian E

    2005-07-01

    Full Text Available Abstract Background One of the primary tasks in analysing gene expression data is finding genes that are differentially expressed in different samples. Multiple testing issues due to the thousands of tests run make some of the more popular methods for doing this problematic. Results We propose a simple method, Normal Uniform Differential Gene Expression (NUDGE detection for finding differentially expressed genes in cDNA microarrays. The method uses a simple univariate normal-uniform mixture model, in combination with new normalization methods for spread as well as mean that extend the lowess normalization of Dudoit, Yang, Callow and Speed (2002 1. It takes account of multiple testing, and gives probabilities of differential expression as part of its output. It can be applied to either single-slide or replicated experiments, and it is very fast. Three datasets are analyzed using NUDGE, and the results are compared to those given by other popular methods: unadjusted and Bonferroni-adjusted t tests, Significance Analysis of Microarrays (SAM, and Empirical Bayes for microarrays (EBarrays with both Gamma-Gamma and Lognormal-Normal models. Conclusion The method gives a high probability of differential expression to genes known/suspected a priori to be differentially expressed and a low probability to the others. In terms of known false positives and false negatives, the method outperforms all multiple-replicate methods except for the Gamma-Gamma EBarrays method to which it offers comparable results with the added advantages of greater simplicity, speed, fewer assumptions and applicability to the single replicate case. An R package called nudge to implement the methods in this paper will be made available soon at http://www.bioconductor.org.

  18. Improved Patient Outcomes by Normalizing Sympathovagal Balance: Differentiating Syncope—Precise Subtype Differentiation Leads to Improved Outcomes

    Directory of Open Access Journals (Sweden)

    Nicholas L. DePace

    2018-01-01

    Full Text Available Syncope is difficult to definitively diagnose, even with tilt-table testing and beat-to-beat blood pressure measurements, the gold-standard. Both are qualitative, subjective assessments. There are subtypes of syncope associated with autonomic conditions for which tilt-table testing is not useful. Heart rate variability analyses also include too much ambiguity. Three subtypes of syncope are differentiated: vasovagal syncope (VVS due to parasympathetic excess (VVS-PE, VVS with abnormal heart rate response (VVS-HR, and VVS without PE (VVS-PN. P&S monitoring (ANSAR, Inc., Philadelphia, PA differentiates subtypes in 2727 cardiology patients (50.5% female; average age: 57 years; age range: 12–100 years, serially tested over four years (3.3 tests per patient, average. P&S monitoring noninvasively, independently, and simultaneously measures parasympathetic and sympathetic (P&S activity, including the normal P-decrease followed by an S-increase with head-up postural change (standing. Syncope, as an S-excess (SE with stand, is differentiated from orthostatic dysfunction (e.g., POTS as S-withdrawal with stand. Upon standing, VVS-PE is further differentiated as SE with PE, VVS-HR as SE with abnormal HR, and VVS-PN as SE with normal P- and HR-responses. Improved understanding of the underlying pathophysiology by more accurate subtyping leads to more precise therapy and improved outcomes.

  19. Use of the Internet as a prevention tool against cognitive decline in normal aging

    Directory of Open Access Journals (Sweden)

    Klimova B

    2016-09-01

    Full Text Available Blanka Klimova Department of Applied Linguistics, Faculty of Informatics and Management, University of Hradec Kralove, Hradec Kralove, Czech Republic Abstract: Recent demographic trends indicate that older people appear to be one of the fastest growing population groups worldwide. In the year 2000, people older than 65 years represented 12.4% of the population. This number is expected to rise to 19% by 2030, particularly in developed countries. Therefore, there is sustained effort at both national and international levels to prolong the active life of these people as long as possible. Since the present older generation at the age of 55 years is already digitally literate, the use of technologies is one of the solutions. The purpose of this study is to discuss the role of the Internet in the prevention of cognitive decline in normal aging. The author examines clinical studies that exploit the use of the Internet, including online training programs, in the prevention of cognitive decline in healthy older individuals. The findings of the clinical studies indicate that the use of the Internet, especially online cognitive training programs, may have a positive effect on the improvement of cognitive functions in healthy older adults. Nevertheless, larger sample longitudinal randomized controlled clinical trials aimed at the prevention of cognitive decline among healthy older adults are needed. Keywords: healthy older individuals, Internet, prevention, cognitive functions, training

  20. Timed Up and Go test, atrophy of medial temporal areas and cognitive functions in community-dwelling older adults with normal cognition and mild cognitive impairment.

    Science.gov (United States)

    Kose, Yujiro; Ikenaga, Masahiro; Yamada, Yosuke; Morimura, Kazuhiro; Takeda, Noriko; Ouma, Shinji; Tsuboi, Yoshio; Yamada, Tatsuo; Kimura, Misaka; Kiyonaga, Akira; Higaki, Yasuki; Tanaka, Hiroaki

    2016-12-01

    This study aimed to ascertain if performance on the Timed Up and Go (TUG) test is associated with indicators of brain volume and cognitive functions among community-dwelling older adults with normal cognition or mild cognitive impairment. Participants were 80 community-dwelling older adults aged 65-89years (44 men, 36 women), including 20 with mild cognitive impairment. Participants completed the TUG and a battery of cognitive assessments, including the Mini-Mental State Examination (MMSE), the Logical Memory I and II (LM-I, LM-II) subtests of the Wechsler Memory Scale-Revised; and the Trail Making Test A and B (TMT-A, TMT-B). Bilateral, right- and left-side medial temporal area atrophy as well as whole gray and white matter indices were determined with the Voxel-based Specific Regional Analysis System for Alzheimer's Disease. We divided participants into three groups based on TUG performance: "better" (≤6.9s); "normal" (7-10s); and "poor" (≥10.1s). Worse TMT-A and TMT-B performance showed significant independent associations with worse TUG performance (Pareas were significantly independently associated with worse TUG performance (Parea atrophy in community-dwelling older adults. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Neuropsychological profile in Chinese patients with Parkinson's disease and normal global cognition according to Mini-Mental State Examination Score.

    Science.gov (United States)

    Qiao, Jin; Zheng, Xiyuan; Wang, Xiaoyan; Lu, Wenhui; Cao, Hongmei; Qin, Xing

    2015-01-01

    Cognitive impairments have been reported to be more common in non-demented patients with Parkinson's disease (PD) and education levels play an important role in intelligence. The studies on cognitive impairments in Chinese PD patients with higher education levels and normal global cognition according to Mini-Mental State Examination Score (MMSE) have not been reported. We enrolled 69 consecutive PD patients with over 6 years education levels and a MMSE score above 24 (of 30) and performed a battery of neuropsychological scales. There are extensive cognitive domain impairments in PD patients with "normal" global cognitive according to MMSE. Montreal Cognitive Assessment (MoCA) is a highly sensitive scale to screen cognitive impairments in PD. The cutoff score of 28 on the MMSE screening for cognitive impairment in Chinese PD patients with high education levels may be more appropriate.

  2. Clinical utility of spatially normalized PET and SPECT to evaluate patients with memory and cognitive impairments

    International Nuclear Information System (INIS)

    Okumura, Ayumi; Nakayama, Noriyuki; Soeda, Akio; Miwa, Kazuhiro; Shinoda, Jun; Iwama, Toru

    2004-01-01

    We assessed cerebral metabolism and blood flow in patients with memory and other cognitive impairment using the easy Z score imaging system (eZIS) and statistical parametric mapping (SPM) of FDG-PET and SPECT scans. Twenty patients with dementia (12 Alzheimer's disease (AD), 3 diffuse Lewy body disease (DLB), and 2 frontotemporal dementia (FTD)) and twenty with diffuse axonal injury (DAI) and cognitive impairments were studied with FDG-PET and ECD-SPECT. All images were analyzed using eZIS with the same processing procedures, including smoothing, normalization, and z-transformation, and compared to a database of normals. Z score maps were super-imposed on 3D MRI brain images. Group analyses were performed using SPM. Age-related declines in cerebral metabolism and blood flow were observed in the anterior cingulate association area. In contrast, reductions in these cerebral functions correlated best with severity of AD in the posterior cingulate association areas. In DLB and FTD, eZIS analysis of PET and SPECT revealed reductions of cerebral functions in specific areas. DAI showed low metabolism and blood flow in mesiofrontal cortex including the anterior cingulate association area. Dysfunction of the anterior cingulate association area in DAI, which resembled age-related cognitive decline, may be responsible for cognitive impairments. Overall, PET and SPECT scans showed significant correlations according to the type of dementia. Spatially normalized maps contributed to PET and SPECT image interpretation for patients with memory and cognitive impairments because better 3D visualization allowed more objective and systematic investigations. (author)

  3. Normal Forms for Retarded Functional Differential Equations and Applications to Bogdanov-Takens Singularity

    Science.gov (United States)

    Faria, T.; Magalhaes, L. T.

    The paper addresses, for retarded functional differential equations (FDEs), the computation of normal forms associated with the flow on a finite-dimensional invariant manifold tangent to invariant spaces for the infinitesimal generator of the linearized equation at a singularity. A phase space appropriate to the computation of these normal forms is introduced, and adequate nonresonance conditions for the computation of the normal forms are derived. As an application, the general situation of Bogdanov-Takens singularity and its versal unfolding for scalar retarded FDEs with nondegeneracy at second order is considered, both in the general case and in the case of differential-delay equations of the form ẋ( t) = ƒ( x( t), x( t-1)).

  4. A high-glycemic diet is associated with cerebral amyloid burden in cognitively normal older adults.

    Science.gov (United States)

    Taylor, Matthew K; Sullivan, Debra K; Swerdlow, Russell H; Vidoni, Eric D; Morris, Jill K; Mahnken, Jonathan D; Burns, Jeffrey M

    2017-12-01

    Background: Little is known about the relation between dietary intake and cerebral amyloid accumulation in aging. Objective: We assessed the association of dietary glycemic measures with cerebral amyloid burden and cognitive performance in cognitively normal older adults. Design: We performed cross-sectional analyses relating dietary glycemic measures [adherence to a high-glycemic-load diet (HGLDiet) pattern, intakes of sugar and carbohydrates, and glycemic load] with cerebral amyloid burden (measured by florbetapir F-18 positron emission tomography) and cognitive performance in 128 cognitively normal older adults who provided eligibility screening data for the University of Kansas's Alzheimer's Prevention through Exercise (APEX) Study. The study began in November 2013 and is currently ongoing. Results: Amyloid was elevated in 26% ( n = 33) of participants. HGLDiet pattern adherence ( P = 0.01), sugar intake ( P = 0.03), and carbohydrate intake ( P = 0.05) were significantly higher in participants with elevated amyloid burden. The HGLDiet pattern was positively associated with amyloid burden both globally and in all regions of interest independently of age, sex, and education (all P ≤ 0.001). Individual dietary glycemic measures (sugar intake, carbohydrate intake, and glycemic load) were also positively associated with global amyloid load and nearly all regions of interest independently of age, sex, and educational level ( P ≤ 0.05). Cognitive performance was associated only with daily sugar intake, with higher sugar consumption associated with poorer global cognitive performance (global composite measure and Mini-Mental State Examination) and performance on subtests of Digit Symbol, Trail Making Test B, and Block Design, controlling for age, sex, and education. Conclusion: A high-glycemic diet was associated with greater cerebral amyloid burden, which suggests diet as a potential modifiable behavior for cerebral amyloid accumulation and subsequent Alzheimer

  5. Cognitive functions in methamphetamine induced psychosis compared to schizophrenia and normal subjects.

    Directory of Open Access Journals (Sweden)

    Zahra Ezzatpanah

    2014-09-01

    Full Text Available The purpose of this research was to study the cognitive functions in patients with methamphetamine-induced psychosis (MIP in comparison with schizophrenia patients and normal subjects.This was a cross-sectional study, 30 patients with MIP, 30 patients with schizophrenia and 30 normal individuals were selected via convenient sampling and were matched on age, sex and education. Wisconsin Cards Sorting, Stroop, Visual Search and Attention and Wechsler Memory Tests were used to assess the subjects.The study showed that patients with MIP and schizophrenia have more deficits in executive functions, selective attention, sustained attention and memory than normal subjects. There were no significant differences in cognitive functions between patients with MIP and schizophrenia except for visual search and attention that showed more impairment in patients with schizophrenia.Although, cognitive dysfunctions of patients with MIP are mostly similar to patients with schizophrenia, some differences seem to exist, especially in those functions that are not primarily dependent on frontal lobe.

  6. Prefrontal activation may predict working-memory training gain in normal aging and mild cognitive impairment.

    Science.gov (United States)

    Vermeij, Anouk; Kessels, Roy P C; Heskamp, Linda; Simons, Esther M F; Dautzenberg, Paul L J; Claassen, Jurgen A H R

    2017-02-01

    Cognitive training has been shown to result in improved behavioral performance in normal aging and mild cognitive impairment (MCI), yet little is known about the neural correlates of cognitive plasticity, or about individual differences in responsiveness to cognitive training. In this study, 21 healthy older adults and 14 patients with MCI received five weeks of adaptive computerized working-memory (WM) training. Before and after training, functional Near-Infrared Spectroscopy (fNIRS) was used to assess the hemodynamic response in left and right prefrontal cortex during performance of a verbal n-back task with varying levels of WM load. After training, healthy older adults demonstrated decreased prefrontal activation at high WM load, which may indicate increased processing efficiency. Although MCI patients showed improved behavioral performance at low WM load after training, no evidence was found for training-related changes in prefrontal activation. Whole-group analyses showed that a relatively strong hemodynamic response at low WM load was related to worse behavioral performance, while a relatively strong hemodynamic response at high WM load was related to higher training gain. Therefore, a 'youth-like' prefrontal activation pattern at older age may be associated with better behavioral outcome and cognitive plasticity.

  7. Use of the Internet as a prevention tool against cognitive decline in normal aging.

    Science.gov (United States)

    Klimova, Blanka

    Recent demographic trends indicate that older people appear to be one of the fastest growing population groups worldwide. In the year 2000, people older than 65 years represented 12.4% of the population. This number is expected to rise to 19% by 2030, particularly in developed countries. Therefore, there is sustained effort at both national and international levels to prolong the active life of these people as long as possible. Since the present older generation at the age of 55 years is already digitally literate, the use of technologies is one of the solutions. The purpose of this study is to discuss the role of the Internet in the prevention of cognitive decline in normal aging. The author examines clinical studies that exploit the use of the Internet, including online training programs, in the prevention of cognitive decline in healthy older individuals. The findings of the clinical studies indicate that the use of the Internet, especially online cognitive training programs, may have a positive effect on the improvement of cognitive functions in healthy older adults. Nevertheless, larger sample longitudinal randomized controlled clinical trials aimed at the prevention of cognitive decline among healthy older adults are needed.

  8. R2* mapping for brain iron: associations with cognition in normal aging.

    Science.gov (United States)

    Ghadery, Christine; Pirpamer, Lukas; Hofer, Edith; Langkammer, Christian; Petrovic, Katja; Loitfelder, Marisa; Schwingenschuh, Petra; Seiler, Stephan; Duering, Marco; Jouvent, Eric; Schmidt, Helena; Fazekas, Franz; Mangin, Jean-Francois; Chabriat, Hugues; Dichgans, Martin; Ropele, Stefan; Schmidt, Reinhold

    2015-02-01

    Brain iron accumulates during aging and has been associated with neurodegenerative disorders including Alzheimer's disease. Magnetic resonance (MR)-based R2* mapping enables the in vivo detection of iron content in brain tissue. We investigated if during normal brain aging iron load relates to cognitive impairment in region-specific patterns in a community-dwelling cohort of 336 healthy, middle aged, and older adults from the Austrian Stroke Prevention Family Study. MR imaging and R2* mapping in the basal ganglia and neocortex were done at 3T. Comprehensive neuropsychological testing assessed memory, executive function, and psychomotor speed. We found the highest iron concentration in the globus pallidus, and pallidal and putaminal iron was significantly and inversely associated with cognitive performance in all cognitive domains, except memory. These associations were iron load dependent. Vascular brain lesions and brain volume did not mediate the relationship between iron and cognitive performance. We conclude that higher R2*-determined iron in the basal ganglia correlates with cognitive impairment during brain aging independent of concomitant brain abnormalities. The prognostic significance of this finding needs to be determined. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Glutamate-glutamine and GABA in brain of normal aged and patients with cognitive impairment.

    Science.gov (United States)

    Huang, Dandan; Liu, Dan; Yin, Jianzhong; Qian, Tianyi; Shrestha, Susan; Ni, Hongyan

    2017-07-01

    To explore the changes of glutamate-glutamine (Glx) and gamma-aminobutyric acid (GABA) in the brain in normal old age and cognitive impairment using magnetic resonance spectroscopy (MRS). Seventeen normal young controls (NYC), 15 normal elderly controls (NEC), 21 patients with mild cognitive impairment (MCI) and 17 with Alzheimer disease (AD) patients were included in this study. Glx and GABA+ levels in the anterior cingulate cortex (ACC) and right hippocampus (rHP) were measured by using a MEGA-PRESS sequence. Glx/Cr and GABA+/Cr ratios were compared between NYC and NEC and between the three elderly groups using analysis of covariance (ANCOVA); the tissue fractions of voxels were used as covariates. The relationships between metabolite ratios and cognitive performance were analysed using Spearman correlation coefficients. For NEC and NYC groups, Glx/Cr and GABA+/Cr ratios were lower in NEC in ACC and rHP. For the three elderly groups, Glx/Cr ratio was lower in AD in ACC compared to NEC and MCI; Glx/Cr ratio was lower in AD in rHP compared to NEC. There was no significant decrease for GABA+/Cr ratio. Glx and GABA levels may decrease simultaneously in normal aged, and Glx level decreased predominantly in AD, and it is helpful in the early diagnosis of AD. • Glx and GABA levels may decrease simultaneously in normal aged. • Glx level may decrease predominantly in Alzheimer disease. • The balance in excitatory-inhibitory systems may be broken in AD. • Decreased Glx level may be helpful in early diagnosis of AD.

  10. Testosterone and Dihydrotestosterone Differentially Improve Cognition in Aged Female Mice

    Science.gov (United States)

    Benice, Ted S.; Raber, Jacob

    2009-01-01

    Compared with age-matched male mice, female mice experience a more severe age-related cognitive decline (ACD). Since androgens are less abundant in aged female mice compared with aged male mice, androgen supplementation may enhance cognition in aged female mice. To test this, we assessed behavioral performance on a variety of tasks in 22- to…

  11. Aberrant Intrinsic Activity and Connectivity in Cognitively Normal Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Deborah L. Harrington

    2017-06-01

    Full Text Available Disturbances in intrinsic activity during resting-state functional MRI (rsfMRI are common in Parkinson’s disease (PD, but have largely been studied in a priori defined subnetworks. The cognitive significance of abnormal intrinsic activity is also poorly understood, as are abnormalities that precede the onset of mild cognitive impairment. To address these limitations, we leveraged three different analytic approaches to identify disturbances in rsfMRI metrics in 31 cognitively normal PD patients (PD-CN and 30 healthy adults. Subjects were screened for mild cognitive impairment using the Movement Disorders Society Task Force Level II criteria. Whole-brain data-driven analytic approaches first analyzed the amplitude of low-frequency intrinsic fluctuations (ALFF and regional homogeneity (ReHo, a measure of local connectivity amongst functionally similar regions. We then examined if regional disturbances in these metrics altered functional connectivity with other brain regions. We also investigated if abnormal rsfMRI metrics in PD-CN were related to brain atrophy and executive, visual organization, and episodic memory functioning. The results revealed abnormally increased and decreased ALFF and ReHo in PD-CN patients within the default mode network (posterior cingulate, inferior parietal cortex, parahippocampus, entorhinal cortex, sensorimotor cortex (primary motor, pre/post-central gyrus, basal ganglia (putamen, caudate, and posterior cerebellar lobule VII, which mediates cognition. For default mode network regions, we also observed a compound profile of altered ALFF and ReHo. Most regional disturbances in ALFF and ReHo were associated with strengthened long-range interactions in PD-CN, notably with regions in different networks. Stronger long-range functional connectivity in PD-CN was also partly expanded to connections that were outside the networks of the control group. Abnormally increased activity and functional connectivity appeared to have a

  12. Cognition in anxious children with attention deficit hyperactivity disorder: a comparison with clinical and normal children

    Directory of Open Access Journals (Sweden)

    Young Arlene

    2007-01-01

    Full Text Available Abstract Background Cognition in children with anxiety disorders (ANX and comorbid Attention Deficit Disorder (ADHD has received little attention, potentially impacting clinical and academic interventions in this highly disabled group. This study examined several cognitive features relative to children with either pure condition and to normal controls. Methods One hundred and eight children ages 8–12 and parents were diagnosed by semi-structured parent interview and teacher report as having: ANX (any anxiety disorder except OCD or PTSD; n = 52, ADHD (n = 21, or ANX + ADHD (n = 35. All completed measures of academic ability, emotional perception, and working memory. Clinical subjects were compared to 35 normal controls from local schools. Results Groups did not differ significantly on age, gender, or estimated IQ. On analyses of variance, groups differed on academic functioning (Wide Range Achievement Test, p Conclusion Though requiring replication, findings suggest that ANX + ADHD relates to greater cognitive and academic vulnerability than ANX, but may relate to reduced perception of anger.

  13. Cognitive levels of performance account for hemispheric lateralisation effects in dyslexic and normally reading children.

    Science.gov (United States)

    Heim, Stefan; Grande, Marion; Meffert, Elisabeth; Eickhoff, Simon B; Schreiber, Helen; Kukolja, Juraj; Shah, Nadim Jon; Huber, Walter; Amunts, Katrin

    2010-12-01

    Recent theories of developmental dyslexia explain reading deficits in terms of deficient phonological awareness, attention, visual and auditory processing, or automaticity. Since dyslexia has a neurobiological basis, the question arises how the reader's proficiency in these cognitive variables affects the brain regions involved in visual word recognition. This question was addressed in two fMRI experiments with 19 normally reading children (Experiment 1) and 19 children with dyslexia (Experiment 2). First, reading-specific brain activation was assessed by contrasting the BOLD signal for reading aloud words vs. overtly naming pictures of real objects. Next, ANCOVAs with brain activation during reading the individuals' scores for all five cognitive variables assessed outside the scanner as covariates were performed. Whereas the normal readers' brain activation during reading showed co-variation effects predominantly in the right hemisphere, the reverse pattern was observed for the dyslexics. In particular, middle frontal gyrus, inferior parietal cortex, and precuneus showed contralateral effects for controls as compared to dyslexics. In line with earlier findings in the literature, these data hint at a global change in hemispheric asymmetry during cognitive processing in dyslexic readers, which, in turn, might affect reading proficiency. Copyright © 2010 Elsevier Inc. All rights reserved.

  14. Differential effects of cognitive inhibition and intelligence on creativity

    OpenAIRE

    Benedek, Mathias; Franz, Fabiola; Heene, Moritz; Neubauer, Aljoscha C.

    2012-01-01

    There are different conceptions about how cognitive inhibition is related to creativity. Creativity has either been associated with effective inhibition, or with disinhibition, or with an adaptive engagement of inhibition. In this study, we examined the relationship of cognitive inhibition, assessed by means of the random motor generation task, with different measures of creativity. We also analyzed whether this relation is mediated by intelligence. We generally found a positive correlation o...

  15. Differential effects of MDMA and methylphenidate on social cognition.

    Science.gov (United States)

    Schmid, Yasmin; Hysek, Cédric M; Simmler, Linda D; Crockett, Molly J; Quednow, Boris B; Liechti, Matthias E

    2014-09-01

    Social cognition is important in everyday-life social interactions. The social cognitive effects of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') and methylphenidate (both used for neuroenhancement and as party drugs) are largely unknown. We investigated the acute effects of MDMA (75 mg), methylphenidate (40 mg) and placebo using the Facial Emotion Recognition Task, Multifaceted Empathy Test, Movie for the Assessment of Social Cognition, Social Value Orientation Test and the Moral Judgment Task in a cross-over study in 30 healthy subjects. Additionally, subjective, autonomic, pharmacokinetic, endocrine and adverse drug effects were measured. MDMA enhanced emotional empathy for positive emotionally charged situations in the MET and tended to reduce the recognition of sad faces in the Facial Emotion Recognition Task. MDMA had no effects on cognitive empathy in the Multifaceted Empathy Test or social cognitive inferences in the Movie for the Assessment of Social Cognition. MDMA produced subjective 'empathogenic' effects, such as drug liking, closeness to others, openness and trust. In contrast, methylphenidate lacked such subjective effects and did not alter emotional processing, empathy or mental perspective-taking. MDMA but not methylphenidate increased the plasma levels of oxytocin and prolactin. None of the drugs influenced moral judgment. Effects on emotion recognition and emotional empathy were evident at a low dose of MDMA and likely contribute to the popularity of the drug. © The Author(s) 2014.

  16. Oral methylphenidate normalizes cingulate activity in cocaine addiction during a salient cognitive task

    International Nuclear Information System (INIS)

    Goldstein, R.Z.; Woicik, P.A.; Maloney, T.; Tomasi, D.; Alia-Klein, N.; Shan, J.; Honorario, J.; Samaras, D.; Wang, R.; Telang, F.; Wang, G.-J.; Volkow, N.D.

    2010-01-01

    Anterior cingulate cortex (ACC) hypoactivations during cognitive demand are a hallmark deficit in drug addiction. Methylphenidate (MPH) normalizes cortical function, enhancing task salience and improving associated cognitive abilities, in other frontal lobe pathologies; however, in clinical trials, MPH did not improve treatment outcome in cocaine addiction. We hypothesized that oral MPH will attenuate ACC hypoactivations and improve associated performance during a salient cognitive task in individuals with cocaine-use disorders (CUD). In the current functional MRI study, we used a rewarded drug cue-reactivity task previously shown to be associated with hypoactivations in both major ACC subdivisions (implicated in default brain function) in CUD compared with healthy controls. The task was performed by 13 CUD and 14 matched healthy controls on 2 d: after ingesting a single dose of oral MPH (20 mg) or placebo (lactose) in a counterbalanced fashion. Results show that oral MPH increased responses to this salient cognitive task in both major ACC subdivisions (including the caudal-dorsal ACC and rostroventromedial ACC extending to the medial orbitofrontal cortex) in the CUD. These functional MRI results were associated with reduced errors of commission (a common impulsivity measure) and improved task accuracy, especially during the drug (vs. neutral) cue-reactivity condition in all subjects. The clinical application of such MPH-induced brain-behavior enhancements remains to be tested.

  17. Cognitive decline in normal aging and its prevention: a review on non-pharmacological lifestyle strategies

    Directory of Open Access Journals (Sweden)

    Klimova B

    2017-05-01

    Full Text Available Blanka Klimova,1,2 Martin Valis,2 Kamil Kuca3,4 1Department of Applied Linguistics, Faculty of Informatics and Management, University of Hradec Kralove, 2Department of Neurology, 3Biomedical Research Centre, University Hospital Hradec Kralove, 4Department of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove, Czech Republic Abstract: The purpose of this study is to examine the effects of the selected non-pharmacological lifestyle activities on the delay of cognitive decline in normal aging. This was done by conducting a literature review in the four acknowledged databases Web of Science, Scopus, MEDLINE, and Springer, and consequently by evaluating the findings of the relevant studies. The findings show that physical activities, such as walking and aerobic exercises, music therapy, adherence to Mediterranean diet, or solving crosswords, seem to be very promising lifestyle intervention tools. The results indicate that non-pharmacological lifestyle intervention activities should be intense and possibly done simultaneously in order to be effective in the prevention of cognitive decline. In addition, more longitudinal randomized controlled trials are needed in order to discover the most effective types and the duration of these intervention activities in the prevention of cognitive decline, typical of aging population groups. Keywords: cognitive impairment, healthy older individuals, intervention, benefits

  18. Depressive Symptom Clusters and Neuropsychological Performance in Mild Alzheimer's and Cognitively Normal Elderly

    Directory of Open Access Journals (Sweden)

    James R. Hall

    2011-01-01

    Full Text Available Objectives. Determine the relationship between depressive symptom clusters and neuropsychological test performance in an elderly cohort of cognitively normal controls and mild Alzheimer's disease (AD. Design. Cross-sectional analysis. Setting. Four health science centers in Texas. Participants. 628 elderly individuals (272 diagnosed with mild AD and 356 controls from ongoing longitudinal study of Alzheimer's disease. Measurements. Standard battery of neuropsychological tests and the 30-item Geriatric Depression Scale with regressions model generated on GDS-30 subscale scores (dysphoria, apathy, meaninglessness and cognitive impairment as predictors and neuropsychological tests as outcome variables. Follow-up analyses by gender were conducted. Results. For AD, all symptom clusters were related to specific neurocognitive domains; among controls apathy and cognitive impairment were significantly related to neuropsychological functioning. The relationship between performance and symptom clusters was significantly different for males and females in each group. Conclusion. Findings suggest the need to examine disease status and gender when considering the impact of depressive symptoms on cognition.

  19. Exploring the Factor Structure of Financial Capacity in Cognitively Normal and Impaired Older Adults.

    Science.gov (United States)

    Gerstenecker, Adam; Triebel, Kristen; Eakin, Amanda; Martin, Roy; Marson, Daniel

    2018-01-01

    To investigate the factor structure of financial capacity using a direct-performance measure of financial skills (The Financial Capacity Instrument [FCI]) as a proxy for the financial capacity construct. The study sample was composed of 440 older adults who represented the cognitive spectrum from normal cognitive aging to mild cognitive impairment (MCI) to mild dementia: 179 healthy older adults, 149 participants with MCI, and 112 participants with mild Alzheimer's dementia (AD). Both Velicer's Minimum Average Partial test and Horn's parallel analysis supported a four-factor solution which accounted for 46% of variance. The four extracted factors were interpreted as: (1) Basic Monetary Knowledge and Calculation Skills, (2) Financial Judgment, (3) Financial Conceptual Knowledge, and (4) Financial Procedural Knowledge. The study findings represent an important first step in empirically articulating the financial capacity construct in aging. The four identified factors can guide both clinical practice and future instrument utilization and development. Cognitively impaired older adults with MCI and mild AD dementia are likely to show financial changes in one or more of the four identified financial factors. Clinicians working with older adults should routinely examine for potential changes in these four areas of financial function.

  20. Oral methylphenidate normalizes cingulate activity in cocaine addiction during a salient cognitive task

    Energy Technology Data Exchange (ETDEWEB)

    Goldstein, R.Z.; Goldstein, R.Z.; Woicik, P.A.; Maloney, T.; Tomasi, D.; Alia-Klein, N.; Shan, J.; Honorario, J.; Samaras, d.; Wang, R.; Telang, F.; Wang, G.-J.; Volkow, N.D.

    2010-09-21

    Anterior cingulate cortex (ACC) hypoactivations during cognitive demand are a hallmark deficit in drug addiction. Methylphenidate (MPH) normalizes cortical function, enhancing task salience and improving associated cognitive abilities, in other frontal lobe pathologies; however, in clinical trials, MPH did not improve treatment outcome in cocaine addiction. We hypothesized that oral MPH will attenuate ACC hypoactivations and improve associated performance during a salient cognitive task in individuals with cocaine-use disorders (CUD). In the current functional MRI study, we used a rewarded drug cue-reactivity task previously shown to be associated with hypoactivations in both major ACC subdivisions (implicated in default brain function) in CUD compared with healthy controls. The task was performed by 13 CUD and 14 matched healthy controls on 2 d: after ingesting a single dose of oral MPH (20 mg) or placebo (lactose) in a counterbalanced fashion. Results show that oral MPH increased responses to this salient cognitive task in both major ACC subdivisions (including the caudal-dorsal ACC and rostroventromedial ACC extending to the medial orbitofrontal cortex) in the CUD. These functional MRI results were associated with reduced errors of commission (a common impulsivity measure) and improved task accuracy, especially during the drug (vs. neutral) cue-reactivity condition in all subjects. The clinical application of such MPH-induced brain-behavior enhancements remains to be tested.

  1. Size evolution of ultrafine particles: Differential signatures of normal and episodic events

    International Nuclear Information System (INIS)

    Joshi, Manish; Khan, Arshad; Anand, S.; Sapra, B.K.

    2016-01-01

    The effect of fireworks on the aerosol number characteristics of atmosphere was studied for an urban mega city. Measurements were made at 50 m height to assess the local changes around the festival days. Apart from the increase in total number concentration and characteristic accumulation mode, short-term increase of ultrafine particle concentration was noted. Total number concentration varies an order of magnitude during the measurement period in which peak occurs at a frequency of approximately one per day. On integral scale, it seems not possible to distinguish an episodic (e.g. firework bursting induced aerosol emission) and a normal (ambient atmospheric changes) event. However these events could be differentiated on the basis of size evolution analysis around number concentration peaks. The results are discussed relative to past studies and inferences are drawn towards aerosol signatures of firework bursting. The short-term burst in ultrafine particle concentration can pose an inhalation hazard. - Highlights: • Effect of firework emissions on atmospheric aerosol characteristics was studied. • Significant increase in ultrafine particle concentration was observed during firework bursting. • Size distribution evolution analysis of number concentration peaks has been performed. • Differential signatures of normal and episodic event were noted. - Notable increase in ultrafine particle concentration during firework bursting was seen. Normal and episodic event could be differentiated on the basis of size evolution analysis.

  2. Effects of Human Mesenchymal Stem Cells Coculture on Calcium-Induced Differentiation of Normal Human Keratinocytes.

    Science.gov (United States)

    Sah, Shyam Kishor; Kim, Hae Young; Lee, Ji Hae; Lee, Seong-Wook; Kim, Hyung-Sik; Kim, Yeon-Soo; Kang, Kyung-Sun; Kim, Tae-Yoon

    2017-06-01

    The influence of mesenchymal stem cells (MSCs) on keratinocytes in altered microenvironments is poorly understood. Here, we cocultured umbilical cord blood-derived MSCs with normal human epidermal keratinocytes to evaluate their paracrine effect in the presence of high extracellular calcium (Ca 2+ ) concentration. High Ca 2+ environment to keratinocytes can disrupt normal skin barrier function due to abnormal/premature differentiation of keratinocytes. Surprisingly, we found that MSCs suppress both proliferation and differentiation of keratinocytes under a high Ca 2+ environment in transforming growth factors β1 (TGFβ1)-dependent manner. Furthermore, we determined that MSCs can regulate the mitogen-activated protein kinases, phosphatidylinositol 3-kinase/protein kinase B, and protein kinase C pathways in Ca 2+ -induced differentiated keratinocytes. Knockdown of TGFβ1 from MSCs results in decreased suppression of differentiation with significantly increased proliferation of keratinocytes compared with control MSCs. MSCs-derived TGFβ1 further induced growth inhibition of keratinocyte in high extracellular Ca 2+ environment as analyzed by a decrease in DNA synthesis, accumulation of phosphorylated retinoblastoma protein, cdc2, and increased mRNA level of p21, and independent of TGFβ1/SMAD pathway. Taken together, we found that MSCs-derived TGFβ1 is a critical regulator of keratinocyte function, and involves multiple proximal signaling cascades. Stem Cells 2017;35:1592-1602. © 2017 AlphaMed Press.

  3. High and Low LET Radiation Differentially Induce Normal Tissue Damage Signals

    International Nuclear Information System (INIS)

    Niemantsverdriet, Maarten; Goethem, Marc-Jan van; Bron, Reinier; Hogewerf, Wytse; Brandenburg, Sytze; Langendijk, Johannes A.; Luijk, Peter van; Coppes, Robert P.

    2012-01-01

    Purpose: Radiotherapy using high linear energy transfer (LET) radiation is aimed at efficiently killing tumor cells while minimizing dose (biological effective) to normal tissues to prevent toxicity. It is well established that high LET radiation results in lower cell survival per absorbed dose than low LET radiation. However, whether various mechanisms involved in the development of normal tissue damage may be regulated differentially is not known. Therefore the aim of this study was to investigate whether two actions related to normal tissue toxicity, p53-induced apoptosis and expression of the profibrotic gene PAI-1 (plasminogen activator inhibitor 1), are differentially induced by high and low LET radiation. Methods and Materials: Cells were irradiated with high LET carbon ions or low LET photons. Cell survival assays were performed, profibrotic PAI-1 expression was monitored by quantitative polymerase chain reaction, and apoptosis was assayed by annexin V staining. Activation of p53 by phosphorylation at serine 315 and serine 37 was monitored by Western blotting. Transfections of plasmids expressing p53 mutated at serines 315 and 37 were used to test the requirement of these residues for apoptosis and expression of PAI-1. Results: As expected, cell survival was lower and induction of apoptosis was higher in high -LET irradiated cells. Interestingly, induction of the profibrotic PAI-1 gene was similar with high and low LET radiation. In agreement with this finding, phosphorylation of p53 at serine 315 involved in PAI-1 expression was similar with high and low LET radiation, whereas phosphorylation of p53 at serine 37, involved in apoptosis induction, was much higher after high LET irradiation. Conclusions: Our results indicate that diverse mechanisms involved in the development of normal tissue damage may be differentially affected by high and low LET radiation. This may have consequences for the development and manifestation of normal tissue damage.

  4. Differentially expressed proteins among normal cervix, cervical intraepithelial neoplasia and cervical squamous cell carcinoma.

    Science.gov (United States)

    Zhao, Q; He, Y; Wang, X-L; Zhang, Y-X; Wu, Y-M

    2015-08-01

    To explore the differentially expressed proteins in normal cervix, cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma (CSCC) tissues by differential proteomics technique. Cervical tissues (including normal cervix, CIN and CSCC) were collected in Department of Gynecologic Oncology of Beijing Obstetrics and Gynecology Hospital. Two-dimensional fluorescence difference in gel electrophoresis (2-D DIGE) and DeCyder software were used to detect the differentially expressed proteins. Matrix-assisted laser desorption/ionization-time-of-flight tandem mass spectrometry (MALDI-TOF/TOF MS) was used to identify the differentially expressed proteins. Western blot (WB) and immunohistochemistry (IHC) were performed to validate the expressions of selected proteins among normal cervix, CIN and CSCC. 2-D DIGE images with high resolution and good repeatability were obtained. Forty-six differentially expressed proteins (27 up-regulated and 19 down-regulated) were differentially expressed among the normal cervix, CIN and CSCC. 26 proteins were successfully identified by MALDI-TOF/TOF MS. S100A9 (S100 calcium-binding protein A9) was the most significantly up-regulated protein. Eukaryotic elongation factor 1-alpha-1 (eEF1A1) was the most significantly down-regulated protein. Pyruvate kinase isozymes M2 (PKM2) was both up-regulated and down-regulated. The results of WB showed that with the increase in the severity of cervical lesions, the expression of S100A9 protein was significantly increased among the three groups (P = 0.010). The expression of eEF1A1 was reduced but without significant difference (P = 0.861). The expression of PKM2 was significantly reduced (P = 0.000). IHC showed that protein S100A9 was mainly expressed in the cytoplasm, and its positive expression rate was 20.0 % in normal cervix, 70.0 % in CIN and 100.0 % in CSCC, with a significant difference among them (P = 0.006). eEF1A1 was mainly expressed in the cell plasma, and its

  5. Severe hyposmia and aberrant functional connectivity in cognitively normal Parkinson's disease.

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    Noritaka Yoneyama

    Full Text Available Severe hyposmia is a risk factor of dementia in Parkinson's disease (PD, while the underlying functional connectivity (FC and brain volume alterations in PD patients with severe hyposmia (PD-SH are unclear.We examined voxel-based morphometric and resting state functional magnetic resonance imaging findings in 15 cognitively normal PD-SH, 15 cognitively normal patients with PD with no/mild hyposmia (PD-N/MH, and 15 healthy controls (HCs.Decreased gray matter volume (GMV was observed in the bilateral cuneus, right associative visual area, precuneus, and some areas in anterior temporal lobes in PD-SH group compared to HCs. Both the PD-SH and PD-N/MH groups showed increased GMV in the bilateral posterior insula and its surrounding regions. A widespread significant decrease in amygdala FC beyond the decreased GMV areas and olfactory cortices were found in the PD-SH group compared with the HCs. Above all, decreased amygdala FC with the inferior parietal lobule, lingual gyrus, and fusiform gyrus was significantly correlated with both reduction of Addenbrooke's Cognitive Examination-Revised scores and severity of hyposmia in all participants. Canonical resting state networks exhibited decreased FC in the precuneus and left executive control networks but increased FC in the primary and high visual networks of patients with PD compared with HCs. Canonical network FC to other brain regions was enhanced in the executive control, salience, primary visual, and visuospatial networks of the PD-SH.PD-SH showed extensive decreased amygdala FC. Particularly, decreased FC between the amygdala and inferior parietal lobule, lingual gyrus, and fusiform gyrus were associated with the severity of hyposmia and cognitive performance. In contrast, relatively preserved canonical networks in combination with increased FC to brain regions outside of canonical networks may be related to compensatory mechanisms, and preservation of brain function.

  6. Neuroimaging Characteristics of Small-Vessel Disease in Older Adults with Normal Cognition, Mild Cognitive Impairment, and Alzheimer Disease

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    Alberto Mimenza-Alvarado

    2018-05-01

    Full Text Available Introduction: Cerebral small-vessel disease (SVD represents the most frequent type of vascular brain lesions, often coexisting with Alzheimer disease (AD. By quantifying white matter hyperintensities (WMH and hippocampal and parietal atrophy, we aimed to describe the prevalence and severity of SVD among older adults with normal cognition (NC, mild cognitive impairment (MCI, and probable AD and to describe associated risk factors. Methods: This study included 105 older adults evaluated with magnetic resonance imaging and clinical and neuropsychological tests. We used the Fazekas scale (FS for quantification of WMH, the Scheltens scale (SS for hippocampal atrophy, and the Koedam scale (KS for parietal atrophy. Logistic regression models were performed to determine the association between FS, SS, and KS scores and the presence of NC, MCI, or probable AD. Results: Compared to NC subjects, SVD was more prevalent in MCI and probable AD subjects. After adjusting for confounding factors, logistic regression showed a positive association between higher scores on the FS and probable AD (OR = 7.6, 95% CI 2.7–20, p < 0.001. With the use of the SS and KS (OR = 4.5, 95% CI 3.5–58, p = 0.003 and OR = 8.9, 95% CI 1–72, p = 0.04, respectively, the risk also remained significant for probable AD. Conclusions: These results suggest an association between severity of vascular brain lesions and neurodegeneration.

  7. Fluorescence Spectrum and Decay Measurement for Hsil VS Normal Cytology Differentiation in Liquid Pap Smear Supernatant

    Science.gov (United States)

    Vaitkuviene, A.; Gegzna, V.; Juodkazis, S.; Jursenas, S.; Miasojedovas, S.; Kurtinaitiene, R.; Rimiene, J.; Vaitkus, J.

    2009-06-01

    Cervical smear material contains endo and exocervical cells, mucus and inflammative, immune cells in cases of pathology. Just not destroyed keratinocytes lay on the glass for microscopy. Liquid cytology supernatant apart other diagnostics could be used for photodiagnostic. The spectroscopic parameters suitable for Normal and HSIL cytology groups supernatant differentiation are demonstrated. The dried liquid PAP supernatant fractions—sediment and liquid were investigated. Excitation and emission matrices (EEM), supernatant fluorescence decay measured under 280 nm diode short pulse excitation and fluorescence spectroscopy by excitation with 355 nm laser light were analyzed. The differences between Normal and HSIL groups were statistically proven in the certain spectral regions. Fluorescence decay peculiarities show spectral regions consisting of few fluorophores. Obtained results on fluorescence differences in Normal and HSIL groups' supernatant shows the potency of photodiagnosis application in cervical screening.

  8. An analysis of lymphographic signs for differentiating cancerous, lymphomatous, and normal lymph nodes

    International Nuclear Information System (INIS)

    Tatsuzaki, Hideo; Nakajima, Teiichi; Okumura, Toshiyuki; Akisada, Masayoshi

    1987-01-01

    Twenty-four lymphographic signs, obtained from a total of 204 cancerous (C), lymphomatous (L), and normal (N) lymph nodes, were analyzed based on the final diagnosis. Univariate analyses with correlation coefficient and multivariate regression analyses were employed to differentiate C, L, or N lymph nodes. Based on univariate analyses, lymphographic sings for C nodes were - enlarged node, irregular or deficient capsules or marginal sinuses, block of lymph vessels, extravasation, and defect in lymph-vascular and nodal phase (combination defect). The signs for L node were - enlarged node, elliptic shape from 2 projections, irregular or deficient capsules or marginal sinuses, and extravasation. Using multivariate analyses, the following signs were necessary for differentiating individual lymph nodes: (a) combination defect, specific pattern, granularity, nodal shape and stasis or preservation of lymph vessels for differentiating C from N nodes; (b) deficiencies of capsules, nodal shape, specific pattern, dislocation of lymph vessels, and nodal contrast for differentiating L from N nodes; and (c) character of defect, specific pattern, deformity, soft tissue shadow and nodal shape for differentiating C from L nodes. Should lymphography be used in the visualization of inside structure and lymphatic canal, it would even more increase the ability to diagnose cancer and malignant lymphomas. (Namekawa, K.)

  9. Super-delta: a new differential gene expression analysis procedure with robust data normalization.

    Science.gov (United States)

    Liu, Yuhang; Zhang, Jinfeng; Qiu, Xing

    2017-12-21

    Normalization is an important data preparation step in gene expression analyses, designed to remove various systematic noise. Sample variance is greatly reduced after normalization, hence the power of subsequent statistical analyses is likely to increase. On the other hand, variance reduction is made possible by borrowing information across all genes, including differentially expressed genes (DEGs) and outliers, which will inevitably introduce some bias. This bias typically inflates type I error; and can reduce statistical power in certain situations. In this study we propose a new differential expression analysis pipeline, dubbed as super-delta, that consists of a multivariate extension of the global normalization and a modified t-test. A robust procedure is designed to minimize the bias introduced by DEGs in the normalization step. The modified t-test is derived based on asymptotic theory for hypothesis testing that suitably pairs with the proposed robust normalization. We first compared super-delta with four commonly used normalization methods: global, median-IQR, quantile, and cyclic loess normalization in simulation studies. Super-delta was shown to have better statistical power with tighter control of type I error rate than its competitors. In many cases, the performance of super-delta is close to that of an oracle test in which datasets without technical noise were used. We then applied all methods to a collection of gene expression datasets on breast cancer patients who received neoadjuvant chemotherapy. While there is a substantial overlap of the DEGs identified by all of them, super-delta were able to identify comparatively more DEGs than its competitors. Downstream gene set enrichment analysis confirmed that all these methods selected largely consistent pathways. Detailed investigations on the relatively small differences showed that pathways identified by super-delta have better connections to breast cancer than other methods. As a new pipeline, super

  10. Energetic heavy ions accelerate differentiation in the descendants of irradiated normal human diploid fibroblasts

    International Nuclear Information System (INIS)

    Hamada, Nobuyuki; Hara, Takamitsu; Funayama, Tomoo; Sakashita, Tetsuya; Kobayashi, Yasuhiko

    2008-01-01

    Ionizing radiation-induced genomic instability has been demonstrated in a variety of endpoints such as delayed reproductive death, chromosome instability and mutations, which occurs in the progeny of survivors many generations after the initial insult. Dependence of these effects on the linear energy transfer (LET) of the radiation is incompletely characterized; however, our previous work has shown that delayed reductions in clonogenicity can be most pronounced at LET of 108 keV/μm. To gain insight into potential cellular mechanisms involved in LET-dependent delayed loss of clonogenicity, we investigated morphological changes in colonies arising from normal human diploid fibroblasts exposed to γ-rays or energetic carbon ions (108 keV/μm). Exposure of confluent cultures to carbon ions was 4-fold more effective at inactivating cellular clonogenic potential and produced more abortive colonies containing reduced number of cells per colony than γ-rays. Second, colonies were assessed for clonal morphotypic heterogeneity. The yield of differentiated cells was elevated in a dose- and LET-dependent fashion in clonogenic colonies, whereas differentiated cells predominated to a comparable extent irrespective of radiation type or dose in abortive colonies. The incidence of giant or multinucleated cells was also increased but much less frequent than that of differentiated cells. Collectively, our results indicate that carbon ions facilitate differentiation more effectively than γ-rays as a major response in the progeny of irradiated fibroblasts. Accelerated differentiation may account, at least in part, for dose- and LET-dependent delayed loss of clonogenicity in normal human diploid cells, and could be a defensive mechanism that minimizes further expansion of aberrant cells

  11. An efficient approach for differentiating Alzheimer's disease from normal elderly based on multicenter MRI using gray-level invariant features.

    Directory of Open Access Journals (Sweden)

    Muwei Li

    Full Text Available Machine learning techniques, along with imaging markers extracted from structural magnetic resonance images, have been shown to increase the accuracy to differentiate patients with Alzheimer's disease (AD from normal elderly controls. Several forms of anatomical features, such as cortical volume, shape, and thickness, have demonstrated discriminative capability. These approaches rely on accurate non-linear image transformation, which could invite several nuisance factors, such as dependency on transformation parameters and the degree of anatomical abnormality, and an unpredictable influence of residual registration errors. In this study, we tested a simple method to extract disease-related anatomical features, which is suitable for initial stratification of the heterogeneous patient populations often encountered in clinical data. The method employed gray-level invariant features, which were extracted from linearly transformed images, to characterize AD-specific anatomical features. The intensity information from a disease-specific spatial masking, which was linearly registered to each patient, was used to capture the anatomical features. We implemented a two-step feature selection for anatomic recognition. First, a statistic-based feature selection was implemented to extract AD-related anatomical features while excluding non-significant features. Then, seven knowledge-based ROIs were used to capture the local discriminative powers of selected voxels within areas that were sensitive to AD or mild cognitive impairment (MCI. The discriminative capability of the proposed feature was measured by its performance in differentiating AD or MCI from normal elderly controls (NC using a support vector machine. The statistic-based feature selection, together with the knowledge-based masks, provided a promising solution for capturing anatomical features of the brain efficiently. For the analysis of clinical populations, which are inherently heterogeneous

  12. Relating Memory To Functional Performance In Normal Aging to Dementia Using Hierarchical Bayesian Cognitive Processing Models

    Science.gov (United States)

    Shankle, William R.; Pooley, James P.; Steyvers, Mark; Hara, Junko; Mangrola, Tushar; Reisberg, Barry; Lee, Michael D.

    2012-01-01

    Determining how cognition affects functional abilities is important in Alzheimer’s disease and related disorders (ADRD). 280 patients (normal or ADRD) received a total of 1,514 assessments using the Functional Assessment Staging Test (FAST) procedure and the MCI Screen (MCIS). A hierarchical Bayesian cognitive processing (HBCP) model was created by embedding a signal detection theory (SDT) model of the MCIS delayed recognition memory task into a hierarchical Bayesian framework. The SDT model used latent parameters of discriminability (memory process) and response bias (executive function) to predict, simultaneously, recognition memory performance for each patient and each FAST severity group. The observed recognition memory data did not distinguish the six FAST severity stages, but the latent parameters completely separated them. The latent parameters were also used successfully to transform the ordinal FAST measure into a continuous measure reflecting the underlying continuum of functional severity. HBCP models applied to recognition memory data from clinical practice settings accurately translated a latent measure of cognition to a continuous measure of functional severity for both individuals and FAST groups. Such a translation links two levels of brain information processing, and may enable more accurate correlations with other levels, such as those characterized by biomarkers. PMID:22407225

  13. Specific algorithm method of scoring the Clock Drawing Test applied in cognitively normal elderly

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    Liana Chaves Mendes-Santos

    Full Text Available The Clock Drawing Test (CDT is an inexpensive, fast and easily administered measure of cognitive function, especially in the elderly. This instrument is a popular clinical tool widely used in screening for cognitive disorders and dementia. The CDT can be applied in different ways and scoring procedures also vary. OBJECTIVE: The aims of this study were to analyze the performance of elderly on the CDT and evaluate inter-rater reliability of the CDT scored by using a specific algorithm method adapted from Sunderland et al. (1989. METHODS: We analyzed the CDT of 100 cognitively normal elderly aged 60 years or older. The CDT ("free-drawn" and Mini-Mental State Examination (MMSE were administered to all participants. Six independent examiners scored the CDT of 30 participants to evaluate inter-rater reliability. RESULTS AND CONCLUSION: A score of 5 on the proposed algorithm ("Numbers in reverse order or concentrated", equivalent to 5 points on the original Sunderland scale, was the most frequent (53.5%. The CDT specific algorithm method used had high inter-rater reliability (p<0.01, and mean score ranged from 5.06 to 5.96. The high frequency of an overall score of 5 points may suggest the need to create more nuanced evaluation criteria, which are sensitive to differences in levels of impairment in visuoconstructive and executive abilities during aging.

  14. Three families with mild PMM2-CDG and normal cognitive development.

    Science.gov (United States)

    Vals, Mari-Anne; Morava, Eva; Teeäär, Kai; Zordania, Riina; Pajusalu, Sander; Lefeber, Dirk J; Õunap, Katrin

    2017-06-01

    Congenital disorders of glycosylation (CDG) are caused by defective glycosylation of proteins and lipids. PMM2-CDG is the most common subtype among the CDG. The severity of PMM2-CDG is variable. Patients often have a recognizable phenotype with neurological and multisystem symptoms that might cause early death. We report six patients from three families who are diagnosed with a clinically mild PMM2-CDG and have normal cognitive development. All these patients had delayed gross motor skills with mild-to-moderate neurological findings. Cerebellar hypoplasia was detected in all siblings for whom brain MRI was performed. In 5/6 children the Wechsler Intelligence Scale for Children (WISC) showed normal cognitive development with full scale IQ scores ranging from borderline to average. Four patients were diagnosed with PMM2-CDG at the age of 8 years or later as their neurological symptoms were quite mild and they had been able to participate in regular school programs. We report patients with p.Val231Met/p.Arg239Trp and p.Ile120Thr/p.Gly228Cys genotypes which may cause milder variants of PMM2-CDG. © 2017 Wiley Periodicals, Inc.

  15. Association of Higher Cortical Amyloid Burden With Loneliness in Cognitively Normal Older Adults.

    Science.gov (United States)

    Donovan, Nancy J; Okereke, Olivia I; Vannini, Patrizia; Amariglio, Rebecca E; Rentz, Dorene M; Marshall, Gad A; Johnson, Keith A; Sperling, Reisa A

    2016-12-01

    Emotional and behavioral symptoms in cognitively normal older people may be direct manifestations of Alzheimer disease (AD) pathophysiology at the preclinical stage, prior to the onset of mild cognitive impairment. Loneliness is a perceived state of social and emotional isolation that has been associated with cognitive and functional decline and an increased risk of incident AD dementia. We hypothesized that loneliness might occur in association with elevated cortical amyloid burden, an in vivo research biomarker of AD. To determine whether cortical amyloid burden is associated with greater loneliness in cognitively normal older adults. Cross-sectional analyses using data from the Harvard Aging Brain Study of 79 cognitively normal, community-dwelling participants. A continuous, aggregate measure of cortical amyloid burden, determined by Pittsburgh Compound B-positron emission tomography (PiB-PET), was examined in association with loneliness in linear regression models adjusting for age, sex, apolipoprotein E ε4 (APOEε4), socioeconomic status, depression, anxiety, and social network (without and with the interaction of amyloid and APOEε4). We also quantified the association of high amyloid burden (amyloid-positive group) to loneliness (lonely group) using logistic regression, controlling for the same covariates, with the amyloid-positive group and the lonely group, each composing 32% of the sample (n = 25). Loneliness, as determined by the 3-item UCLA Loneliness Scale (possible range, 3-12, with higher score indicating greater loneliness). The 79 participants included 43 women and 36 men with a mean (SD) age of 76.4 (6.2) years. Mean (SD) cortical amyloid burden via PiB-PET was 1.230 (0.209), and the mean (SD) UCLA-3 loneliness score was 5.3 (1.8). Twenty-two (28%) had positive APOEε4 carrier status, and 25 (32%) were in the amyloid-positive group with cortical PiB distribution volume ratio greater than 1.2. Controlling for age, sex, APOEε4, socioeconomic

  16. Perineal Ultrasound Findings of Stress Urinary Incontinence : Differentiation from Normal Findings

    International Nuclear Information System (INIS)

    Baek, Seung Yon; Chung, Eun Chul; Rhee, Chung Sik; Suh, Jeong Soo

    1995-01-01

    Perineal ultrasonography is a noninvasive method that is easier than chain cystoure-thrography in the diagnosis of stress urinary incontinence(SUI). We report the findings of stress urinary incontinence at peritoneal ultrasound and its differential points form normal control. Twenty-two patients with SUI and l6 normal controls were included in our study. Aloka SSD 650 with 3.5MHz convex transducer was used, and sagittal image through the bladder, bladder base, urethrovesical junction and pubis was obtained from the vulva area, We measured thepdsterior urethrovesical angle(PUVA) at rest and stress, and calculated the difference between the two angles. We also measured the distance of bladder neck descent during stress and the diameter of proximal urethra at rest. The data were analyzed with student t-test. At rest, PUVA was 135.3 .deg. in patients with SUI group and 134.5 .deg. in normal control group(P=0.8376). During streets, PUVA was 149.5 .deg. in SUI group and 142.1 .deg. in normal group(P=0.0135). The difference PUVAs at rest and during stress was 14.2 .deg. in SUI group and 7.6 .deg. in normal group(P=0.0173). The distance of bladder neck descent during stress was 14.5mm in SUI group and 9.8mm in normal group(P=0.0029). The diameter of proxiaml urethra at rest was 4.4mm in SUI group and 3.6mm in normal group(P=0.0385). In conclusion, ultrasound parameters that include the PUVA during stress, the difference between PUVAs at rest and during stress, the distance of bladder neck descent during stress and the diameter of proximal ureyhra at rest are useful in diagnosis of the stress urinary incontinence

  17. Perineal Ultrasound Findings of Stress Urinary Incontinence : Differentiation from Normal Findings

    Energy Technology Data Exchange (ETDEWEB)

    Baek, Seung Yon; Chung, Eun Chul; Rhee, Chung Sik; Suh, Jeong Soo [Ewha Womans University Hospital, Seoul (Korea, Republic of)

    1995-06-15

    Perineal ultrasonography is a noninvasive method that is easier than chain cystoure-thrography in the diagnosis of stress urinary incontinence(SUI). We report the findings of stress urinary incontinence at peritoneal ultrasound and its differential points form normal control. Twenty-two patients with SUI and l6 normal controls were included in our study. Aloka SSD 650 with 3.5MHz convex transducer was used, and sagittal image through the bladder, bladder base, urethrovesical junction and pubis was obtained from the vulva area, We measured thepdsterior urethrovesical angle(PUVA) at rest and stress, and calculated the difference between the two angles. We also measured the distance of bladder neck descent during stress and the diameter of proximal urethra at rest. The data were analyzed with student t-test. At rest, PUVA was 135.3 .deg. in patients with SUI group and 134.5 .deg. in normal control group(P=0.8376). During streets, PUVA was 149.5 .deg. in SUI group and 142.1 .deg. in normal group(P=0.0135). The difference PUVAs at rest and during stress was 14.2 .deg. in SUI group and 7.6 .deg. in normal group(P=0.0173). The distance of bladder neck descent during stress was 14.5mm in SUI group and 9.8mm in normal group(P=0.0029). The diameter of proxiaml urethra at rest was 4.4mm in SUI group and 3.6mm in normal group(P=0.0385). In conclusion, ultrasound parameters that include the PUVA during stress, the difference between PUVAs at rest and during stress, the distance of bladder neck descent during stress and the diameter of proximal ureyhra at rest are useful in diagnosis of the stress urinary incontinence

  18. Thinking versus feeling: differentiating between cognitive and affective components of perceived cancer risk.

    Science.gov (United States)

    Janssen, Eva; van Osch, Liesbeth; Lechner, Lilian; Candel, Math; de Vries, Hein

    2012-01-01

    Despite the increased recognition of affect in guiding probability estimates, perceived risk has been mainly operationalised in a cognitive way and the differentiation between rational and intuitive judgements is largely unexplored. This study investigated the validity of a measurement instrument differentiating cognitive and affective probability beliefs and examined whether behavioural decision making is mainly guided by cognition or affect. Data were obtained from four surveys focusing on smoking (N=268), fruit consumption (N=989), sunbed use (N=251) and sun protection (N=858). Correlational analyses showed that affective likelihood was more strongly correlated with worry compared to cognitive likelihood and confirmatory factor analysis provided support for a two-factor model of perceived likelihood instead of a one-factor model (i.e. cognition and affect combined). Furthermore, affective likelihood was significantly associated with the various outcome variables, whereas the association for cognitive likelihood was absent in three studies. The findings provide support for the construct validity of the measures used to assess cognitive and affective likelihood. Since affective likelihood might be a better predictor of health behaviour than the commonly used cognitive operationalisation, both dimensions should be considered in future research.

  19. Effectiveness of diffusion tensor imaging in differentiating early-stage subcortical ischemic vascular disease, Alzheimer's disease and normal ageing.

    Directory of Open Access Journals (Sweden)

    Min-Chien Tu

    Full Text Available To describe and compare diffusion tensor imaging (DTI parameters between patients with subcortical ischemic vascular disease (SIVD and Alzheimer's disease (AD diagnosed using structuralized neuropsychiatric assessments, and investigate potential neuronal substrates related to cognitive performance.Thirty-five patients with SIVD, 40 patients with AD, and 33 cognitively normal control (NC subjects matched by age and education level were consecutively recruited and underwent cognitive function assessments and DTI examinations. Comparisons among these three subgroups with regards to cognitive performance and DTI parameters including fractional anisotropy (FA and mean diffusivity (MD values were performed. Partial correlation analysis after controlling for age and education was used to evaluate associations between cognitive performance and DTI parameters.With regards to cognitive performance, the patients with SIVD had lower total scores in frontal assessment battery (FAB compared to those with AD (p < 0.05 in the context of comparable Mini-Mental Status Examination and Cognitive Abilities Screening Instrument scores. With regards to DTI parameters, there were more regions of significant differences in FA among these three subgroups compared with MD. Compared with NC group, the patients with SIVD had significant global reductions in FA (p < 0.001 ~ 0.05, while significant reductions in FA among the patients with AD were regionally confined within the left superior longitudinal fasciculus, genu and splenium of the corpus callosum, and bilateral forceps major, and the anterior thalamic radiation, uncinate fasciculus, and cingulum of the left side (p < 0.01 ~ 0.05. Analysis of FA values within the left forceps major, left anterior thalamic radiation, and genu of the corpus callosum revealed a 71.8% overall correct classification (p < 0.001 with sensitivity of 69.4%, specificity of 73.8%, positive predictive value of 69.4%, and negative predictive value

  20. Differential effects of white noise in cognitive and perceptual tasks

    OpenAIRE

    Herweg, Nora A.; Bunzeck, Nico

    2015-01-01

    Beneficial effects of noise on higher cognition have recently attracted attention. Hypothesizing an involvement of the mesolimbic dopamine system and its functional interactions with cortical areas, the current study aimed to demonstrate a facilitation of dopamine-dependent attentional and mnemonic functions by externally applying white noise in five behavioral experiments including a total sample of 167 healthy human subjects. During working memory, acoustic white noise impaired accuracy whe...

  1. DTI studies in patients with Alzheimer's disease, mild cognitive impairment, or normal cognition with evaluation of the intrinsic background gradients

    International Nuclear Information System (INIS)

    Jahng, Geon-Ho; Xu, Songfan; Weiner, Micheal W.; Meyerhoff, Dieter J.; Schuff, Norbert; Park, Seungjoon

    2011-01-01

    The objective of the study was to explore the impact of the background gradients on diffusion tensor (DT) magnetic resonance imaging (DT-MRI) in patients with Alzheimer's disease (AD), mild cognitive impairment (MCI), or cognitively normal (CN) aging. Two DT-MRI sets with positive and negative polarities of the diffusion-sensitizing gradients were obtained in 15 AD patients, 18 MCI patients, and 16 CN control subjects. The maps of mean diffusivity (MD) and fractional anisotropy (FA) were computed separately for positive (p: pMD and pFA) and negative (n: nMD and nFA) polarities, and we computed the geometric mean (gm) of the DT-MRI to obtain the gmFA and gmMD with reducing the background gradient effects. Regional variations were assessed across the groups using one-way analysis of variance. Increased regional gmMD values in the AD subjects, as compared to the regional gmMD values in the MCI and CN subjects, were found primarily in the frontal, limbic, and temporal lobe regions. We also found increased nMD and pMD values in the AD subjects compared to those values in the MCI and CN subjects, including in the temporal lobe and the left limbic parahippocampal gyrus white matter. Results of comparisons among the three methods showed that the left limbic parahippocampal gyrus and right temporal gyrus were the increased MD in the AD patients for all three methods. Background gradients affect the DT-MRI measurements in AD patients. Geometric average diffusion measures can be useful to minimize the intrinsic local magnetic susceptibility variations in brain tissue. (orig.)

  2. Differential Effects of Tea Extracts on Growth and Cytokine Production by Normal and Leukemic Human Leukocytes

    Directory of Open Access Journals (Sweden)

    Diana Bayer

    2012-04-01

    Full Text Available Background: Tea is one of the world’s most highly consumed beverages, second only to water. It is affordable and abundant and thus has great potential for improving health of those in both developed and developing areas. Green, oolong, and black teas differ in the extent of fermentation and types of bioactive polyphenols produced. Green tea and its major polyphenol decrease growth of some cancer cells and effect production of immune system cytokines. This study compares the effects of different types of tea extracts on viability and cytokine production by normal and leukemic human T lymphocytes. Generation of the toxic reactive oxygen species H2O2 by extracts was also examined.Methods: The Jurkat T lymphoblastic leukemia cells and mitogen-stimulated normal human peripheral blood mononuclear cells were used in this study. Cell viability was determined by (3-4,5-dimethylthiamizol-2-yl-diphenyltetrazolium bromide assay and production of interleukin-2 by Enzyme-Linked ImmunoSorbent Assay. Levels of H2O2 generated by tea extracts were determined using the xylenol-orange method.Results: We found that green, oolong, and black tea extracts differentially effect the growth and viability of T lymphoblastic leukemia cells and normal peripheral blood mononuclear cells, substantially decreasing both growth and viability of leukemic T lymphocytes and having much lesser effects on their normal counterparts. Tea extracts also had differential effects on the production of the T lymphocyte growth factor interleukin-2, significantly decreasing production by leukemic cells while having only minor effects on normal cells. All three extracts induced H2O2 generation, with green and oolong tea extracts having the greatest effect. Leukemic cells were much more susceptible to growth inhibition and killing by H2O2 than normal lymphocytes.Functional Foods in Health and Disease 2012, 2(4:72-85 Conclusions: The three tea extracts studied altered leukemic T lymphocyte

  3. Incorporation of tritiated thymidine and uridine in normal and endopolyploid nuclei of differentiated tissue

    International Nuclear Information System (INIS)

    Bansal, Y.K.; Sen, Sumitra

    1987-01-01

    Rate of replication and transcription between normal and giant endopolyploid nuclei of differentiated tissue of Hordeum vulgare L. (2n=14) roots and Phlox drummondii Hook. (2n=14) and Zea mays L. (2n=20) endosperms were studied by labelling experiments with tritiated thymidine and uridine. The incorporation of thymidine and uridine was identical in both diploid and giant endopolyploid nuclei of the roots of H. vulgare. The endosperm cells of P. drummondii and Z. mays, however, exhibit markedly different labelling pattern in normal (i.e. triploid) and endopolyploid nuclei where both replication and transcription were rather high. The nutritive function of the endosperm is probably responsible for this high degree of activity. (author). 14 refs., 10 figs., 3 tables

  4. Differentiation of normal pressure hydrocephalus and cerebral atrophy by computed tomography and spinal infusion test

    Energy Technology Data Exchange (ETDEWEB)

    Tans, J T.J. [Nijverheidsorganisatie TNO, The Hague (Netherlands). Dept. of Neurology and Research Unit TNO for Clinical Neurophysiology

    1979-01-01

    The diagnostic value of computed tomography (CT) and spinal infusion test (SIT) was investigated in 27 patients with normal pressure hydrocephalus (NPH) and 35 patients with cerebral atrophy. The most consistent CT finding of NPH was dilatation of the temporal horns, that of cerebral atrophy widening of the convexity sulci. However, 43% of patients with cerebral atrophy demonstrated no cortical atrophy. The SIT showed an excellent relation with isotope cisternography and continuous intracranial pressure recording. NPH and cerebral atrophy were correctly differentiated in 71% by CT and SIT. A normal SIT and a CT scan without the typical features of NPH exclude impairment of cerebrospinal fluid absorption. An abnormal SIT and a CT scan showing ventricular enlargement without dilatation of convexity sulci, require isotope cisternography and possibly intracranial pressure recording to determine the degree of the absorption deficit.

  5. Diagnosing dementia and normal aging: clinical relevance of brain ratios and cognitive performance in a Brazilian sample

    Directory of Open Access Journals (Sweden)

    Chaves M.L.F.

    1999-01-01

    Full Text Available The main objective of the present study was to evaluate the diagnostic value (clinical application of brain measures and cognitive function. Alzheimer and multiinfarct patients (N = 30 and normal subjects over the age of 50 (N = 40 were submitted to a medical, neurological and cognitive investigation. The cognitive tests applied were Mini-Mental, word span, digit span, logical memory, spatial recognition span, Boston naming test, praxis, and calculation tests. The brain ratios calculated were the ventricle-brain, bifrontal, bicaudate, third ventricle, and suprasellar cistern measures. These data were obtained from a brain computer tomography scan, and the cutoff values from receiver operating characteristic curves. We analyzed the diagnostic parameters provided by these ratios and compared them to those obtained by cognitive evaluation. The sensitivity and specificity of cognitive tests were higher than brain measures, although dementia patients presented higher ratios, showing poorer cognitive performances than normal individuals. Normal controls over the age of 70 presented higher measures than younger groups, but similar cognitive performance. We found diffuse losses of tissue from the central nervous system related to distribution of cerebrospinal fluid in dementia patients. The likelihood of case identification by functional impairment was higher than when changes of the structure of the central nervous system were used. Cognitive evaluation still seems to be the best method to screen individuals from the community, especially for developing countries, where the cost of brain imaging precludes its use for screening and initial assessment of dementia.

  6. Effect of simvastatin on CSF Alzheimer disease biomarkers in cognitively normal adults.

    Science.gov (United States)

    Li, Ge; Mayer, Cynthia L; Morelli, Daniel; Millard, Steven P; Raskind, Wendy H; Petrie, Eric C; Cherrier, Monique; Fagan, Anne M; Raskind, Murray A; Peskind, Elaine R

    2017-09-19

    To examine potential disease-modifying effects of statin drugs, we conducted a 12-month randomized, placebo-controlled clinical trial of simvastatin in cognitively normal adults using change in CSF Alzheimer disease biomarkers as primary outcome measure. Participants were 45-64 years old and statin-naive with normal cognition and normal or mildly elevated cholesterol. Forty-six participants completed the 1-year study per protocol (25 in the simvastatin and 21 in the placebo group). Simvastatin was titrated to 40 mg/d. CSF Aβ 42 , total tau, and p-tau 181 were measured at baseline and after 12 months of treatment using the INNO-BIA AlzBio3 assay. We used analysis of covariance to assess differences in biomarker change from baseline between treatment groups, adjusting for age, sex, and APOE ε4 status. Changes from baseline did not differ significantly between treatment groups for any CSF biomarker, with p values of 0.53, 0.36, and 0.25 for CSF Aβ 42 , total tau, and p-tau 181 , respectively. There was no significant modifying effect of sex, APOE ε4, or baseline high-density lipoprotein or triglycerides on treatment group for any of the biomarkers (all p > 0.18). However, a significant interaction between treatment group and baseline low-density lipoprotein (LDL) was observed for p-tau 181 ( p = 0.003), where greater decreases from baseline in CSF p-tau 181 concentrations were associated with higher baseline LDL level for the simvastatin group. Simvastatin-related reductions in CSF p-tau 181 concentrations may be modulated by LDL cholesterol. The potential disease-modifying effects of simvastatin on CSF phospho-tau should be further investigated in persons with hypercholesterolemia. © 2017 American Academy of Neurology.

  7. Differentiation and Integration: Guiding Principles for Analyzing Cognitive Change

    Science.gov (United States)

    Siegler, Robert S.; Chen, Zhe

    2008-01-01

    Differentiation and integration played large roles within classic developmental theories but have been relegated to obscurity within contemporary theories. However, they may have a useful role to play in modern theories as well, if conceptualized as guiding principles for analyzing change rather than as real-time mechanisms. In the present study,…

  8. Calculus for cognitive scientists partial differential equation models

    CERN Document Server

    Peterson, James K

    2016-01-01

    This book shows cognitive scientists in training how mathematics, computer science and science can be usefully and seamlessly intertwined. It is a follow-up to the first two volumes on mathematics for cognitive scientists, and includes the mathematics and computational tools needed to understand how to compute the terms in the Fourier series expansions that solve the cable equation. The latter is derived from first principles by going back to cellular biology and the relevant biophysics.  A detailed discussion of ion movement through cellular membranes, and an explanation of how the equations that govern such ion movement leading to the standard transient cable equation are included. There are also solutions for the cable model using separation of variables, as well an explanation of why Fourier series converge and a description of the implementation of MatLab tools to compute the solutions. Finally, the standard Hodgkin - Huxley model is developed for an excitable neuron and is solved using MatLab.

  9. Increased expression of enhancer of Zeste Homolog 2 (EZH2) differentiates squamous cell carcinoma from normal skin and actinic keratosis.

    Science.gov (United States)

    Xie, Qiang; Wang, Hongbei; Heilman, Edward R; Walsh, Michael G; Haseeb, M A; Gupta, Raavi

    2014-01-01

    Enhancer of Zeste Homolog 2 (EZH2) is a polycomb group protein that has been shown to be involved in the progression of multiple human cancers including melanoma. The expression of EZH2 in normal skin and in pre-malignant and malignant cutaneous squamous cell carcinoma (SCC) has not been studied. We examined the expression of EZH2 in normal skin, actinic keratosis (AK), SCC in situ, well-differentiated (SCC-WD), moderately-differentiated (SCC-MD) and poorly-differentiated SCC (SCC-PD) to ascertain whether EZH2 expression differentiates these conditions. Immunohistochemical staining for EZH2 was performed on formalin-fixed paraffin-embedded biopsies and a tissue microarray containing normal skin, AK, SCC in situ, and SCC of different grades. In comparison to the normal skin, EZH2 expression in actinic keratosis was increased (p=0.03). Similarly, EZH2 expression in all of the neoplastic conditions studied (SCC in situ, SCC-WD, SCC-MD and SCC-PD) was greatly increased in comparison to both the normal skin and actinic keratosis (p≤0.001). EZH2 expression increases incrementally from normal skin to AK and further to SCC, suggesting a role for EZH2 in the progression and differentiation of SCC. EZH2 expression may be used as a diagnostic marker for differentiating SCC from AK or normal skin.

  10. Cognitive Function in Normal-Weight, Overweight, and Obese Older Adults: An Analysis of the Advanced Cognitive Training for Independent and Vital Elderly Cohort

    Science.gov (United States)

    Kuo, Hsu-Ko; Jones, Richard N.; Milberg, William P.; Tennstedt, Sharon; Talbot, Laura; Morris, John N.; Lipsitz, Lewis A.

    2010-01-01

    OBJECTIVES To assess how elevated body mass index (BMI) affects cognitive function in elderly people. DESIGN Cross-sectional study. SETTING Data for this cross-sectional study were taken from a multicenter randomized controlled trial, the Advanced Cognitive Training for Independent and Vital Elderly trial. PARTICIPANTS The analytic sample included 2,684 normal-weight, overweight, or obese subjects aged 65 to 94. MEASUREMENTS Evaluation of cognitive abilities was performed in several domains: global cognition, memory, reasoning, and speed of processing. Cross-sectional association between body weight status and cognitive functions was analyzed using multiple linear regression. RESULTS Overweight subjects had better performance on a reasoning task (β = 0.23, standard error (SE) = 0.11, P = .04) and the Useful Field of View (UFOV) measure (β = −39.46, SE = 12.95, P = .002), a test of visuospatial speed of processing, after controlling for age, sex, race, years of education, intervention group, study site, and cardiovascular risk factors. Subjects with class I (BMI 30.0–34.9 kg/m2) and class II (BMI>35.0 kg/m2) obesity had better UFOV measure scores (β = −38.98, SE = 14.77, P = .008; β = −35.75, SE = 17.65, and P = .04, respectively) in the multivariate model than normal-weight subjects. The relationships between BMI and individual cognitive domains were nonlinear. CONCLUSION Overweight participants had better cognitive performance in terms of reasoning and visuospatial speed of processing than normal-weight participants. Obesity was associated with better performance in visuospatial speed of processing than normal weight. The relationship between BMI and cognitive function should be studied prospectively. PMID:16420204

  11. Hypoxia and hydrogen sulfide differentially affect normal and tumor-derived vascular endothelium

    Directory of Open Access Journals (Sweden)

    Serena Bianco

    2017-08-01

    Full Text Available Background: endothelial cells play a key role in vessels formation both under physiological and pathological conditions. Their behavior is influenced by blood components including gasotransmitters (H2S, NO and CO. Tumor cells are subjected to a cyclic shift between pro-oxidative and hypoxic state and, in this scenario, H2S can be both cytoprotective and detrimental depending on its concentration. H2S effects on tumors onset and development is scarcely studied, particularly concerning tumor angiogenesis. We previously demonstrated that H2S is proangiogenic for tumoral but not for normal endothelium and this may represent a target for antiangiogenic therapeutical strategies. Methods: in this work, we investigate cell viability, migration and tubulogenesis on human EC derived from two different tumors, breast and renal carcinoma (BTEC and RTEC, compared to normal microvascular endothelium (HMEC under oxidative stress, hypoxia and treatment with exogenous H2S. Results: all EC types are similarly sensitive to oxidative stress induced by hydrogen peroxide; chemical hypoxia differentially affects endothelial viability, that results unaltered by real hypoxia. H2S neither affects cell viability nor prevents hypoxia and H2O2-induced damage. Endothelial migration is enhanced by hypoxia, while tubulogenesis is inhibited for all EC types. H2S acts differentially on EC migration and tubulogenesis. Conclusions: these data provide evidence for a great variability of normal and altered endothelium in response to the environmental conditions. Keywords: Hydrogen sulfide, Human microvascular endothelial cells, Human breast carcinoma-derived EC, Human renal carcinoma-derived EC, Tumor angiogenesis

  12. The Impact of Memory Change on Daily Life in Normal Aging and Mild Cognitive Impairment.

    Science.gov (United States)

    Parikh, Preeyam K; Troyer, Angela K; Maione, Andrea M; Murphy, Kelly J

    2016-10-01

    Older adults with age-normal memory changes and those with amnestic mild cognitive impairment (aMCI) report mild memory difficulties with everyday problems such as learning new names or remembering past events. Although the type and extent of memory changes in these populations have been well documented, little is known about how memory changes impact their everyday lives. Using a qualitative research design, data were collected from three focus groups of older adults with normal memory changes (n = 23) and two focus groups of older adults with aMCI (n = 14). A thematic analysis using the constant comparative method was used to identify the impacts of memory change on key life domains. Four major themes emerged from the two groups, including changes in feelings and views of the self, changes in relationships and social interactions, changes in work and leisure activities, and deliberate increases in compensatory behaviors. Participants described both positive and negative consequences of memory change, and these were more substantial and generally more adverse for individuals with aMCI than for those with age-normal memory changes. There are similarities and important differences in the impact of mild memory change on the everyday lives of older adults with age-normal memory changes and those with aMCI. Findings underscore the need for clinical interventions that aim to minimize the emotional impact of memory changes and that increase leisure and social activity in individuals with aMCI. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. Cognitive Deficits in Healthy Elderly Population With "Normal" Scores on the Mini-Mental State Examination.

    Science.gov (United States)

    Votruba, Kristen L; Persad, Carol; Giordani, Bruno

    2016-05-01

    This study investigated whether healthy older adults with Mini-Mental State Examination (MMSE) scores above 23 exhibit cognitive impairment on neuropsychological tests. Participants completed the MMSE and a neuropsychological battery including tests of 10 domains. Results were compared to published normative data. On neuropsychological testing, participants performed well on measures of naming and recall but showed mild to moderate impairment in working memory and processing speed and marked impairment in inhibition, sustained attention, and executive functioning. Almost everyone (91%) scored at least 1 standard deviation (SD) below the mean in at least 1 domain. The median number of domains in which individuals scored below 1 SD was 3.0 of 10.0, whereas over 21% scored below 1 SD in 5 domains or more. With the strictest of definitions for impairment, 20% of this population scored below 2.0 SDs below the norm in at least 2 domains, a necessary condition for a diagnosis of dementia. The finding that cognitive impairment, particularly in attention and executive functioning, is found in healthy older persons who perform well on the MMSE has clinical and research implications in terms of emphasizing normal variability in performance and early identification of possible impairment. © The Author(s) 2016.

  14. Disrupted functional and structural networks in cognitively normal elderly subjects with the APOE ɛ4 allele.

    Science.gov (United States)

    Chen, Yaojing; Chen, Kewei; Zhang, Junying; Li, Xin; Shu, Ni; Wang, Jun; Zhang, Zhanjun; Reiman, Eric M

    2015-03-13

    As the Apolipoprotein E (APOE) ɛ4 allele is a major genetic risk factor for sporadic Alzheimer's disease (AD), which has been suggested as a disconnection syndrome manifested by the disruption of white matter (WM) integrity and functional connectivity (FC), elucidating the subtle brain structural and functional network changes in cognitively normal ɛ4 carriers is essential for identifying sensitive neuroimaging based biomarkers and understanding the preclinical AD-related abnormality development. We first constructed functional network on the basis of resting-state functional magnetic resonance imaging and a structural network on the basis of diffusion tensor image. Using global, local and nodal efficiencies of these two networks, we then examined (i) the differences of functional and WM structural network between cognitively normal ɛ4 carriers and non-carriers simultaneously, (ii) the sensitivity of these indices as biomarkers, and (iii) their relationship to behavior measurements, as well as to cholesterol level. For ɛ4 carriers, we found reduced global efficiency significantly in WM and marginally in FC, regional FC dysfunctions mainly in medial temporal areas, and more widespread for WM network. Importantly, the right parahippocampal gyrus (PHG.R) was the only region with simultaneous functional and structural damage, and the nodal efficiency of PHG.R in WM network mediates the APOE ɛ4 effect on memory function. Finally, the cholesterol level correlated with WM network differently than with the functional network in ɛ4 carriers. Our results demonstrated ɛ4-specific abnormal structural and functional patterns, which may potentially serve as biomarkers for early detection before the onset of the disease.

  15. Effects of Delay Duration on the WMS Logical Memory Performance of Older Adults with Probable Alzheimer's Disease, Probable Vascular Dementia, and Normal Cognition.

    Science.gov (United States)

    Montgomery, Valencia; Harris, Katie; Stabler, Anthony; Lu, Lisa H

    2017-05-01

    To examine how the duration of time delay between Wechsler Memory Scale (WMS) Logical Memory I and Logical Memory II (LM) affected participants' recall performance. There are 46,146 total Logical Memory administrations to participants diagnosed with either Alzheimer's disease (AD), vascular dementia (VaD), or normal cognition in the National Alzheimer's Disease Coordinating Center's Uniform Data Set. Only 50% of the sample was administered the standard 20-35 min of delay as specified by WMS-R and WMS-III. We found a significant effect of delay time duration on proportion of information retained for the VaD group compared to its control group, which remained after adding LMI raw score as a covariate. There was poorer retention of information with longer delay for this group. This association was not as strong for the AD and cognitively normal groups. A 24.5-min delay was most optimal for differentiating AD from VaD participants (47.7% classification accuracy), an 18.5-min delay was most optimal for differentiating AD versus normal participants (51.7% classification accuracy), and a 22.5-min delay was most optimal for differentiating VaD versus normal participants (52.9% classification accuracy). Considering diagnostic implications, our findings suggest that test administration should incorporate precise tracking of delay periods. We recommend a 20-min delay with 18-25-min range. Poor classification accuracy based on LM data alone is a reminder that story memory performance is only one piece of data that contributes to complex clinical decisions. However, strict adherence to the recommended range yields optimal data for diagnostic decisions. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  16. Self-rated driving habits among older adults with clinically-defined mild cognitive impairment, clinically-defined dementia, and normal cognition.

    Science.gov (United States)

    O'Connor, Melissa L; Edwards, Jerri D; Bannon, Yvonne

    2013-12-01

    Older adults with clinically-defined dementia may report reducing their driving more than cognitively normal controls. However, it is unclear how these groups compare to individuals with clinically-defined mild cognitive impairment (MCI) in terms of driving behaviors. The current study investigated self-reported driving habits among adults age 60 and older with clinical MCI (n=41), clinical mild dementia (n=40), and normal cognition (n=43). Participants reported their driving status, driving frequency (days per week), and how often they avoided accessing the community, making left turns, driving at night, driving in unfamiliar areas, driving on high-traffic roads, and driving in bad weather. After adjusting for education, a MANCOVA revealed that participants with MCI and dementia avoided unfamiliar areas and high-traffic roads significantly more than normal participants. Participants with dementia also avoided left turns and accessing the community more than those with normal cognition and MCI (pdriving variables did not significantly differ between groups. Thus, older adults with clinically-defined MCI, as well as those with dementia, avoided some complex driving situations more than cognitively intact adults. However, all diagnostic groups had similar rates of driving cessation and frequency. Future research should examine the safety implications of such findings. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Insulin-like Growth Factor 1 (IGF-1) as a marker of cognitive decline in normal ageing: A review.

    Science.gov (United States)

    Frater, Julanne; Lie, David; Bartlett, Perry; McGrath, John J

    2018-03-01

    Insulin-like Growth Factor 1 (IGF-1) and its signaling pathway play a primary role in normal growth and ageing, however serum IGF-1 is known to reduce with advancing age. Recent findings suggest IGF-1 is essential for neurogenesis in the adult brain, and this reduction of IGF-1 with ageing may contribute to age-related cognitive decline. Experimental studies have shown manipulation of the GH/GF-1 axis can slow rates of cognitive decline in animals, making IGF-1 a potential biomarker of cognition, and/or its signaling pathway a possible therapeutic target to prevent or slow age-related cognitive decline. A systematic literature review and qualitative narrative summary of current evidence for IGF-1 as a biomarker of cognitive decline in the ageing brain was undertaken. Results indicate IGF-1 concentrations do not confer additional diagnostic information for those with cognitive decline, and routine clinical measurement of IGF-1 is not currently justified. In cases of established cognitive impairment, it remains unclear whether increasing circulating or brain IGF-1 may reverse or slow down the rate of further decline. Advances in neuroimaging, genetics, neuroscience and the availability of large well characterized biobanks will facilitate research exploring the role of IGF-1 in both normal ageing and age-related cognitive decline. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Children with High-Functioning Autism and Asperger's Syndrome: Can We Differentiate Their Cognitive Profiles?

    Science.gov (United States)

    Planche, Pascale; Lemonnier, Eric

    2012-01-01

    The aim of this study was to investigate whether children with high-functioning autism (HFA) and Asperger's syndrome (AS) can be differentiated from each other and from typically developing children on their cognitive profiles. The present study included a total of 45 participants: children with autism (high-functioning autism or Asperger's…

  19. Neuronal glycosylation differentials in normal, injured and chondroitinase-treated environments

    International Nuclear Information System (INIS)

    Kilcoyne, Michelle; Sharma, Shashank; McDevitt, Niamh; O’Leary, Claire; Joshi, Lokesh; McMahon, Siobhán S.

    2012-01-01

    Highlights: ► Carbohydrates are important in the CNS and ChABC has been used for spinal cord injury (SCI) treatment. ► Neuronal glycosylation in injury and after ChABC treatment is unknown. ► In silico mining verified that glyco-related genes were differentially regulated after SCI. ► In vitro model system revealed abnormal sialylation in an injured environment. ► The model indicated a return to normal neuronal glycosylation after ChABC treatment. -- Abstract: Glycosylation is found ubiquitously throughout the central nervous system (CNS). Chondroitin sulphate proteoglycans (CSPGs) are a group of molecules heavily substituted with glycosaminoglycans (GAGs) and are found in the extracellular matrix (ECM) and cell surfaces. Upon CNS injury, a glial scar is formed, which is inhibitory for axon regeneration. Several CSPGs are up-regulated within the glial scar, including NG2, and these CSPGs are key inhibitory molecules of axonal regeneration. Treatment with chondroitinase ABC (ChABC) can neutralise the inhibitory nature of NG2. A gene expression dataset was mined in silico to verify differentially regulated glycosylation-related genes in neurons after spinal cord injury and identify potential targets for further investigation. To establish the glycosylation differential of neurons that grow in a healthy, inhibitory and ChABC-treated environment, we established an indirect co-culture system where PC12 neurons were grown with primary astrocytes, Neu7 astrocytes (which overexpress NG2) and Neu7 astrocytes treated with ChABC. After 1, 4 and 8 days culture, lectin cytochemistry of the neurons was performed using five fluorescently-labelled lectins (ECA MAA, PNA, SNA-I and WFA). Usually α-(2,6)-linked sialylation scarcely occurs in the CNS but this motif was observed on the neurons in the injured environment only at day 8. Treatment with ChABC was successful in returning neuronal glycosylation to normal conditions at all timepoints for MAA, PNA and SNA-I staining

  20. Neuronal glycosylation differentials in normal, injured and chondroitinase-treated environments

    Energy Technology Data Exchange (ETDEWEB)

    Kilcoyne, Michelle; Sharma, Shashank [Glycoscience Group, National Centre for Biomedical Engineering Science, National University of Ireland, Galway (Ireland); McDevitt, Niamh; O' Leary, Claire [Anatomy, School of Medicine, National University of Ireland, Galway (Ireland); Joshi, Lokesh [Glycoscience Group, National Centre for Biomedical Engineering Science, National University of Ireland, Galway (Ireland); McMahon, Siobhan S., E-mail: siobhan.mcmahon@nuigalway.ie [Anatomy, School of Medicine, National University of Ireland, Galway (Ireland)

    2012-04-13

    Highlights: Black-Right-Pointing-Pointer Carbohydrates are important in the CNS and ChABC has been used for spinal cord injury (SCI) treatment. Black-Right-Pointing-Pointer Neuronal glycosylation in injury and after ChABC treatment is unknown. Black-Right-Pointing-Pointer In silico mining verified that glyco-related genes were differentially regulated after SCI. Black-Right-Pointing-Pointer In vitro model system revealed abnormal sialylation in an injured environment. Black-Right-Pointing-Pointer The model indicated a return to normal neuronal glycosylation after ChABC treatment. -- Abstract: Glycosylation is found ubiquitously throughout the central nervous system (CNS). Chondroitin sulphate proteoglycans (CSPGs) are a group of molecules heavily substituted with glycosaminoglycans (GAGs) and are found in the extracellular matrix (ECM) and cell surfaces. Upon CNS injury, a glial scar is formed, which is inhibitory for axon regeneration. Several CSPGs are up-regulated within the glial scar, including NG2, and these CSPGs are key inhibitory molecules of axonal regeneration. Treatment with chondroitinase ABC (ChABC) can neutralise the inhibitory nature of NG2. A gene expression dataset was mined in silico to verify differentially regulated glycosylation-related genes in neurons after spinal cord injury and identify potential targets for further investigation. To establish the glycosylation differential of neurons that grow in a healthy, inhibitory and ChABC-treated environment, we established an indirect co-culture system where PC12 neurons were grown with primary astrocytes, Neu7 astrocytes (which overexpress NG2) and Neu7 astrocytes treated with ChABC. After 1, 4 and 8 days culture, lectin cytochemistry of the neurons was performed using five fluorescently-labelled lectins (ECA MAA, PNA, SNA-I and WFA). Usually {alpha}-(2,6)-linked sialylation scarcely occurs in the CNS but this motif was observed on the neurons in the injured environment only at day 8. Treatment

  1. Expression profiling of genes regulated by TGF-beta: Differential regulation in normal and tumour cells

    Directory of Open Access Journals (Sweden)

    Takahashi Takashi

    2007-04-01

    Full Text Available Abstract Background TGF-beta is one of the key cytokines implicated in various disease processes including cancer. TGF-beta inhibits growth and promotes apoptosis in normal epithelial cells and in contrast, acts as a pro-tumour cytokine by promoting tumour angiogenesis, immune-escape and metastasis. It is not clear if various actions of TGF-beta on normal and tumour cells are due to differential gene regulations. Hence we studied the regulation of gene expression by TGF-beta in normal and cancer cells. Results Using human 19 K cDNA microarrays, we show that 1757 genes are exclusively regulated by TGF-beta in A549 cells in contrast to 733 genes exclusively regulated in HPL1D cells. In addition, 267 genes are commonly regulated in both the cell-lines. Semi-quantitative and real-time qRT-PCR analysis of some genes agrees with the microarray data. In order to identify the signalling pathways that influence TGF-beta mediated gene regulation, we used specific inhibitors of p38 MAP kinase, ERK kinase, JNK kinase and integrin signalling pathways. The data suggest that regulation of majority of the selected genes is dependent on at least one of these pathways and this dependence is cell-type specific. Interestingly, an integrin pathway inhibitor, RGD peptide, significantly affected TGF-beta regulation of Thrombospondin 1 in A549 cells. Conclusion These data suggest major differences with respect to TGF-beta mediated gene regulation in normal and transformed cells and significant role of non-canonical TGF-beta pathways in the regulation of many genes by TGF-beta.

  2. Analysis of a renormalization group method and normal form theory for perturbed ordinary differential equations

    Science.gov (United States)

    DeVille, R. E. Lee; Harkin, Anthony; Holzer, Matt; Josić, Krešimir; Kaper, Tasso J.

    2008-06-01

    For singular perturbation problems, the renormalization group (RG) method of Chen, Goldenfeld, and Oono [Phys. Rev. E. 49 (1994) 4502-4511] has been shown to be an effective general approach for deriving reduced or amplitude equations that govern the long time dynamics of the system. It has been applied to a variety of problems traditionally analyzed using disparate methods, including the method of multiple scales, boundary layer theory, the WKBJ method, the Poincaré-Lindstedt method, the method of averaging, and others. In this article, we show how the RG method may be used to generate normal forms for large classes of ordinary differential equations. First, we apply the RG method to systems with autonomous perturbations, and we show that the reduced or amplitude equations generated by the RG method are equivalent to the classical Poincaré-Birkhoff normal forms for these systems up to and including terms of O(ɛ2), where ɛ is the perturbation parameter. This analysis establishes our approach and generalizes to higher order. Second, we apply the RG method to systems with nonautonomous perturbations, and we show that the reduced or amplitude equations so generated constitute time-asymptotic normal forms, which are based on KBM averages. Moreover, for both classes of problems, we show that the main coordinate changes are equivalent, up to translations between the spaces in which they are defined. In this manner, our results show that the RG method offers a new approach for deriving normal forms for nonautonomous systems, and it offers advantages since one can typically more readily identify resonant terms from naive perturbation expansions than from the nonautonomous vector fields themselves. Finally, we establish how well the solution to the RG equations approximates the solution of the original equations on time scales of O(1/ɛ).

  3. Envelhecimento cerebral: o problema dos limites entre o normal e o patológico Brain ageing: problems of differential diagnosis between normal and pathologic

    Directory of Open Access Journals (Sweden)

    BENITO PEREIRA DAMASCENO

    1999-03-01

    Full Text Available O autor relata três casos de pseudodemência e discute o problema dos limites entre o normal e o patológico no sujeito idoso. O envelhecimento cerebral acompanha-se de alterações mentais e neuropatológicas superponíveis às da demência de Alzheimer (DA, levando a problemas de diagnóstico diferencial. Ainda não existe um marcador biológico seguro de DA e os testes psicométricos podem dar resultados falso-positivos ou falso-negativos. No idoso normal, o declínio da memória operacional e memória secundária é maior que o das memórias primária e terciária, de modo similar ao encontrado nas fases iniciais da DA. Os testes de evocação retardada de lista de palavras, memória lógica, pensamento categórico, destreza visuo-motora-espacial e o Teste de Nomeação de Boston têm sido apontados como os mais discriminativos entre demência incipiente e normalidade. Na neuroimagem, os achados de atrofia ou hipoperfusão em regiões entorrinais-hipocampais ou temporo-parietais são sugestivos de DA, mas podem estar ausentes nas fases iniciais desta doença. O autor conclui sugerindo passos decisivos para o diagnóstico diferencial: avaliação neuropsicológica e comportamental abrangente (com levantamento do nível pré-mórbido de funcionamento cognitivo e sócio-ocupacional do paciente, bem como exames laboratoriais e de neuroimagem; e, se preciso, reavaliação após 4 a 6 meses, para verificar a consistência dos achados.The author reports three cases of pseudodementia and discuss the difficulties in establishing limits between normality and illness in the elderly. The mental and neuropathological changes that accompany the normal ageing of the brain are similar to those of early Alzheimer's dementia (AD. These similarities often lead to difficulties in the differential diagnosis, hence the search for consensus criteria. The decline of working and secondary memory is greater than that of primary and tertiary memory, as is found in AD

  4. Different effects of adding white noise on cognitive performance of sub-, normal and super-attentive school children.

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    Suzannah K Helps

    Full Text Available Noise often has detrimental effects on performance. However, because of the phenomenon of stochastic resonance (SR, auditory white noise (WN can alter the "signal to noise" ratio and improve performance. The Moderate Brain Arousal (MBA model postulates different levels of internal "neural noise" in individuals with different attentional capacities. This in turn determines the particular WN level most beneficial in each individual case-with one level of WN facilitating poor attenders but hindering super-attentive children. The objective of the present study is to find out if added WN affects cognitive performance differently in children that differ in attention ability.Participants were teacher-rated super- (N = 25; normal- (N = 29 and sub-attentive (N = 36 children (aged 8 to 10 years. Two non-executive function (EF tasks (a verbal episodic recall task and a delayed verbal recognition task and two EF tasks (a visuo-spatial working memory test and a Go-NoGo task were performed under three WN levels. The non-WN condition was only used to control for potential differences in background noise in the group testing situations.There were different effects of WN on performance in the three groups-adding moderate WN worsened the performance of super-attentive children for both task types and improved EF performance in sub-attentive children. The normal-attentive children's performance was unaffected by WN exposure. The shift from moderate to high levels of WN had little further effect on performance in any group.The predicted differential effect of WN on performance was confirmed. However, the failure to find evidence for an inverted U function challenges current theories. Alternative explanations are discussed. We propose that WN therapy should be further investigated as a possible non-pharmacological treatment for inattention.

  5. Different effects of adding white noise on cognitive performance of sub-, normal and super-attentive school children.

    Science.gov (United States)

    Helps, Suzannah K; Bamford, Susan; Sonuga-Barke, Edmund J S; Söderlund, Göran B W

    2014-01-01

    Noise often has detrimental effects on performance. However, because of the phenomenon of stochastic resonance (SR), auditory white noise (WN) can alter the "signal to noise" ratio and improve performance. The Moderate Brain Arousal (MBA) model postulates different levels of internal "neural noise" in individuals with different attentional capacities. This in turn determines the particular WN level most beneficial in each individual case-with one level of WN facilitating poor attenders but hindering super-attentive children. The objective of the present study is to find out if added WN affects cognitive performance differently in children that differ in attention ability. Participants were teacher-rated super- (N = 25); normal- (N = 29) and sub-attentive (N = 36) children (aged 8 to 10 years). Two non-executive function (EF) tasks (a verbal episodic recall task and a delayed verbal recognition task) and two EF tasks (a visuo-spatial working memory test and a Go-NoGo task) were performed under three WN levels. The non-WN condition was only used to control for potential differences in background noise in the group testing situations. There were different effects of WN on performance in the three groups-adding moderate WN worsened the performance of super-attentive children for both task types and improved EF performance in sub-attentive children. The normal-attentive children's performance was unaffected by WN exposure. The shift from moderate to high levels of WN had little further effect on performance in any group. The predicted differential effect of WN on performance was confirmed. However, the failure to find evidence for an inverted U function challenges current theories. Alternative explanations are discussed. We propose that WN therapy should be further investigated as a possible non-pharmacological treatment for inattention.

  6. Size evolution of ultrafine particles: Differential signatures of normal and episodic events.

    Science.gov (United States)

    Joshi, Manish; Khan, Arshad; Anand, S; Sapra, B K

    2016-01-01

    The effect of fireworks on the aerosol number characteristics of atmosphere was studied for an urban mega city. Measurements were made at 50 m height to assess the local changes around the festival days. Apart from the increase in total number concentration and characteristic accumulation mode, short-term increase of ultrafine particle concentration was noted. Total number concentration varies an order of magnitude during the measurement period in which peak occurs at a frequency of approximately one per day. On integral scale, it seems not possible to distinguish an episodic (e.g. firework bursting induced aerosol emission) and a normal (ambient atmospheric changes) event. However these events could be differentiated on the basis of size evolution analysis around number concentration peaks. The results are discussed relative to past studies and inferences are drawn towards aerosol signatures of firework bursting. The short-term burst in ultrafine particle concentration can pose an inhalation hazard. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Distinct and shared cognitive functions mediate event- and time-based prospective memory impairment in normal ageing

    Science.gov (United States)

    Gonneaud, Julie; Kalpouzos, Grégoria; Bon, Laetitia; Viader, Fausto; Eustache, Francis; Desgranges, Béatrice

    2011-01-01

    Prospective memory (PM) is the ability to remember to perform an action at a specific point in the future. Regarded as multidimensional, PM involves several cognitive functions that are known to be impaired in normal aging. In the present study, we set out to investigate the cognitive correlates of PM impairment in normal aging. Manipulating cognitive load, we assessed event- and time-based PM, as well as several cognitive functions, including executive functions, working memory and retrospective episodic memory, in healthy subjects covering the entire adulthood. We found that normal aging was characterized by PM decline in all conditions and that event-based PM was more sensitive to the effects of aging than time-based PM. Whatever the conditions, PM was linked to inhibition and processing speed. However, while event-based PM was mainly mediated by binding and retrospective memory processes, time-based PM was mainly related to inhibition. The only distinction between high- and low-load PM cognitive correlates lays in an additional, but marginal, correlation between updating and the high-load PM condition. The association of distinct cognitive functions, as well as shared mechanisms with event- and time-based PM confirms that each type of PM relies on a different set of processes. PMID:21678154

  8. Genetic variants in the choline acetyltransferase (ChAT) gene are modestly associated with normal cognitive function in the elderly

    DEFF Research Database (Denmark)

    Mengel-From, J; Christensen, K; Thinggaard, M

    2011-01-01

    Genetic variants in the choline acetyltransferase (ChAT) gene have been suggested as risk factors for neurodegenerative Alzheimer's disease (AD). Here we tested the importance of genetic variants in the ChAT gene in normal cognitive function of elderly in a study sample of Danish twins...... and singletons (N = 2070). The ChAT rs3810950 A allele, which has been associated with increased risk for AD, was found to be associated with a decrease cognitive status evaluated by a five-component cognitive composite score [P = 0.03, regression coefficient -0.30, 95% confidence interval (CI) -0.57 to -0...

  9. Language experience differentiates prefrontal and subcortical activation of the cognitive control network in novel word learning.

    Science.gov (United States)

    Bradley, Kailyn A L; King, Kelly E; Hernandez, Arturo E

    2013-02-15

    The purpose of this study was to examine the cognitive control mechanisms in adult English speaking monolinguals compared to early sequential Spanish-English bilinguals during the initial stages of novel word learning. Functional magnetic resonance imaging during a lexico-semantic task after only 2h of exposure to novel German vocabulary flashcards showed that monolinguals activated a broader set of cortical control regions associated with higher-level cognitive processes, including the supplementary motor area (SMA), anterior cingulate (ACC), and dorsolateral prefrontal cortex (DLPFC), as well as the caudate, implicated in cognitive control of language. However, bilinguals recruited a more localized subcortical network that included the putamen, associated more with motor control of language. These results suggest that experience managing multiple languages may differentiate the learning strategy and subsequent neural mechanisms of cognitive control used by bilinguals compared to monolinguals in the early stages of novel word learning. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Quantitative Analysis of Differential Proteome Expression in Bladder Cancer vs. Normal Bladder Cells Using SILAC Method.

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    Ganglong Yang

    Full Text Available The best way to increase patient survival rate is to identify patients who are likely to progress to muscle-invasive or metastatic disease upfront and treat them more aggressively. The human cell lines HCV29 (normal bladder epithelia, KK47 (low grade nonmuscle invasive bladder cancer, NMIBC, and YTS1 (metastatic bladder cancer have been widely used in studies of molecular mechanisms and cell signaling during bladder cancer (BC progression. However, little attention has been paid to global quantitative proteome analysis of these three cell lines. We labeled HCV29, KK47, and YTS1 cells by the SILAC method using three stable isotopes each of arginine and lysine. Labeled proteins were analyzed by 2D ultrahigh-resolution liquid chromatography LTQ Orbitrap mass spectrometry. Among 3721 unique identified and annotated proteins in KK47 and YTS1 cells, 36 were significantly upregulated and 74 were significantly downregulated with >95% confidence. Differential expression of these proteins was confirmed by western blotting, quantitative RT-PCR, and cell staining with specific antibodies. Gene ontology (GO term and pathway analysis indicated that the differentially regulated proteins were involved in DNA replication and molecular transport, cell growth and proliferation, cellular movement, immune cell trafficking, and cell death and survival. These proteins and the advanced proteome techniques described here will be useful for further elucidation of molecular mechanisms in BC and other types of cancer.

  11. Differentiating normal and disordered personality using the General Assessment of Personality Disorder (GAPD).

    Science.gov (United States)

    Hentschel, Annett G; John Livesley, W

    2013-05-01

    Criteria to differentiate personality disorder from extremes of normal personality variations are important given growing interest in dimensional classification because an extreme level of a personality dimension does not necessarily indicate disorder. The DSM-5 proposed classification of personality disorder offers a definition of general personality disorder based on chronic interpersonal and self/identity pathology. The ability of this approach to differentiate personality disorder from other mental disorders was evaluated using a self-report questionnaire, the General Assessment of Personality Disorder (GAPD). This measure was administered to a sample of psychiatric patients (N = 149) from different clinical sub-sites. Patients were divided into personality disordered and non-personality disordered groups on the basis of the Structured Clinical Interview for DSM-IV Axis II Disorders (SCID-II). The results showed a hit rate of 82% correct identified patients and a good accuracy of the predicted model. There was a substantial agreement between SCID-II interview and GAPD personality disorder diagnoses. The GAPD appears to predict personality disorder in general, which provides support of the DSM-5 general diagnostic criteria of personality disorder. Copyright © 2012 John Wiley & Sons, Ltd.

  12. Differential diagnosis of normal pressure hydrocephalus by MRI mean diffusivity histogram analysis.

    Science.gov (United States)

    Ivkovic, M; Liu, B; Ahmed, F; Moore, D; Huang, C; Raj, A; Kovanlikaya, I; Heier, L; Relkin, N

    2013-01-01

    Accurate diagnosis of normal pressure hydrocephalus is challenging because the clinical symptoms and radiographic appearance of NPH often overlap those of other conditions, including age-related neurodegenerative disorders such as Alzheimer and Parkinson diseases. We hypothesized that radiologic differences between NPH and AD/PD can be characterized by a robust and objective MR imaging DTI technique that does not require intersubject image registration or operator-defined regions of interest, thus avoiding many pitfalls common in DTI methods. We collected 3T DTI data from 15 patients with probable NPH and 25 controls with AD, PD, or dementia with Lewy bodies. We developed a parametric model for the shape of intracranial mean diffusivity histograms that separates brain and ventricular components from a third component composed mostly of partial volume voxels. To accurately fit the shape of the third component, we constructed a parametric function named the generalized Voss-Dyke function. We then examined the use of the fitting parameters for the differential diagnosis of NPH from AD, PD, and DLB. Using parameters for the MD histogram shape, we distinguished clinically probable NPH from the 3 other disorders with 86% sensitivity and 96% specificity. The technique yielded 86% sensitivity and 88% specificity when differentiating NPH from AD only. An adequate parametric model for the shape of intracranial MD histograms can distinguish NPH from AD, PD, or DLB with high sensitivity and specificity.

  13. Statistical mechanics of normal grain growth in one dimension: A partial integro-differential equation model

    International Nuclear Information System (INIS)

    Ng, Felix S.L.

    2016-01-01

    We develop a statistical-mechanical model of one-dimensional normal grain growth that does not require any drift-velocity parameterization for grain size, such as used in the continuity equation of traditional mean-field theories. The model tracks the population by considering grain sizes in neighbour pairs; the probability of a pair having neighbours of certain sizes is determined by the size-frequency distribution of all pairs. Accordingly, the evolution obeys a partial integro-differential equation (PIDE) over ‘grain size versus neighbour grain size’ space, so that the grain-size distribution is a projection of the PIDE's solution. This model, which is applicable before as well as after statistically self-similar grain growth has been reached, shows that the traditional continuity equation is invalid outside this state. During statistically self-similar growth, the PIDE correctly predicts the coarsening rate, invariant grain-size distribution and spatial grain size correlations observed in direct simulations. The PIDE is then reducible to the standard continuity equation, and we derive an explicit expression for the drift velocity. It should be possible to formulate similar parameterization-free models of normal grain growth in two and three dimensions.

  14. Kinematic differentiation of prosodic categories in normal and disordered language development.

    Science.gov (United States)

    Goffman, Lisa

    2004-10-01

    Prosody is complex and hierarchically organized but is realized as rhythmic movement sequences. Thus, observations of the development of rhythmic aspects of movement can provide insight into links between motor and language processes, specifically whether prosodic distinctions (e.g., feet and prosodic words) are instantiated in rhythmic movement output. This experiment examined 4-7-year-old children's (both normally developing and specifically language impaired) and adults' productions of prosodic sequences that were controlled for phonetic content but differed in morphosyntactic structure (i.e., content vs. function words). Primary analyses included kinematic measures of rhythmic structure (i.e., amplitude and duration of movements in weak vs. strong syllables) across content and function contexts. Findings showed that at the level of articulatory movement, adults produced distinct rhythmic categories across content and function word contexts, whereas children did not. Children with specific language impairment differed from normally developing peers only in their ability to produce well-organized and stable rhythmic movements, not in the differentiation of prosodic categories.

  15. Circadian Clock Genes Are Essential for Normal Adult Neurogenesis, Differentiation, and Fate Determination.

    Directory of Open Access Journals (Sweden)

    Astha Malik

    proliferation during differentiation, but they generated normal percentages of neuronal cells. Neuronal fate commitment therefore appears to be controlled through a non-clock function of BMAL1. This study provides insight into how cell autonomous circadian clocks and clock genes regulate adult neural stem cells with implications for treating neurodegenerative disorders and impaired brain functions by manipulating neurogenesis.

  16. Differences in knowledge of dementia among older adults with normal cognition, mild cognitive impairment, and dementia: A representative nationwide sample of Korean elders.

    Science.gov (United States)

    Lee, Jun-Young; Park, Soowon; Kim, Ki Woong; Kwon, Ji Eyon; Park, Joon Hyuk; Kim, Moon Doo; Kim, Bong-Jo; Kim, Jeong Lan; Moon, Seok Woo; Bae, Jae Nam; Ryu, Seung-Ho; Yoon, Jong Chul; Lee, Nam-Jin; Lee, Dong Young; Lee, Dong Woo; Lee, Seok Bum; Lee, Jung Jae; Lee, Chang-Uk; Jhoo, Jin Hyeong; Cho, Maeng Je

    2016-01-01

    Lack of knowledge about a disease could impede early diagnosis and may lead to delays in seeking appropriate medical care. The aim of this study was to explore knowledge of dementia (KOD) and to find the determinants of KOD among three groups: older adults with normal cognition, mild cognitive impairment (MCI), and dementia. A representative nationwide sample of 6141 Korean elders aged 65 years or older participated in face-to-face interviews and answered 14 questions pertaining to general information, etiology, symptoms, and treatment of dementia. Stepwise multiple regressions and path analyses probed the relationships between various sociodemographic variables and KOD. The percentage of correct responses was only 62%. The item 'A person who remembers things that happened in the past does not have dementia' was answered correctly (false) by only 24.8-27% of the respondents in all groups. Older adults with normal cognition had higher KOD scores than those with MCI or dementia. In the normal-cognition group, KOD scores were higher among highly educated, younger, and literate women with no depression and a family history of dementia. In contrast with the determinants in the normal-cognition group, only the ability to read and write predicted KOD scores in the dementia group. Efforts to enhance KOD in elder adults are needed. Public education regarding the differences between dementia and healthy aging may increase KOD among normal elders and those with MCI. Among elders with dementia, educational materials that do not require literacy may be more helpful in increasing KOD with the aim of preventing treatment delay. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  17. Predicting recovery of cognitive function soon after stroke: differential modeling of logarithmic and linear regression.

    Science.gov (United States)

    Suzuki, Makoto; Sugimura, Yuko; Yamada, Sumio; Omori, Yoshitsugu; Miyamoto, Masaaki; Yamamoto, Jun-ichi

    2013-01-01

    Cognitive disorders in the acute stage of stroke are common and are important independent predictors of adverse outcome in the long term. Despite the impact of cognitive disorders on both patients and their families, it is still difficult to predict the extent or duration of cognitive impairments. The objective of the present study was, therefore, to provide data on predicting the recovery of cognitive function soon after stroke by differential modeling with logarithmic and linear regression. This study included two rounds of data collection comprising 57 stroke patients enrolled in the first round for the purpose of identifying the time course of cognitive recovery in the early-phase group data, and 43 stroke patients in the second round for the purpose of ensuring that the correlation of the early-phase group data applied to the prediction of each individual's degree of cognitive recovery. In the first round, Mini-Mental State Examination (MMSE) scores were assessed 3 times during hospitalization, and the scores were regressed on the logarithm and linear of time. In the second round, calculations of MMSE scores were made for the first two scoring times after admission to tailor the structures of logarithmic and linear regression formulae to fit an individual's degree of functional recovery. The time course of early-phase recovery for cognitive functions resembled both logarithmic and linear functions. However, MMSE scores sampled at two baseline points based on logarithmic regression modeling could estimate prediction of cognitive recovery more accurately than could linear regression modeling (logarithmic modeling, R(2) = 0.676, PLogarithmic modeling based on MMSE scores could accurately predict the recovery of cognitive function soon after the occurrence of stroke. This logarithmic modeling with mathematical procedures is simple enough to be adopted in daily clinical practice.

  18. A triple network connectivity study of large-scale brain systems in cognitively normal APOE4 carriers

    Directory of Open Access Journals (Sweden)

    Xia Wu

    2016-09-01

    Full Text Available The triple network model, consisting of the central executive network, salience network and default mode network, has been recently employed to understand dysfunction in core networks across various disorders. Here we used the triple network model to investigate the large-scale brain networks in cognitively normal APOE4 carriers who are at risk of Alzheimer’s disease (AD. To explore the functional connectivity for each of the three networks and the effective connectivity among them, we evaluated 17 cognitively normal individuals with a family history of AD and at least one copy of the apolipoprotein e4 (APOE4 allele and compared the findings to those of 12 individuals who did not carry the APOE4 gene or have a family history of AD, using independent component analysis and Bayesian network approach. Our findings indicated altered within-network connectivity that suggests future cognitive decline risk, and preserved between-network connectivity that may support their current preserved cognition in the cognitively normal APOE4 allele carries. The study provides novel sights into our understanding of the risk factors for AD and their influence on the triple network model of major psychopathology.

  19. Association between memory complaints and incident Alzheimer's disease in elderly people with normal baseline cognition

    NARCIS (Netherlands)

    Geerlings, M. I.; Jonker, C.; Bouter, L. M.; Adèr, H. J.; Schmand, B.

    1999-01-01

    Results of previous studies suggest that memory complaints may predict cognitive decline and dementia among elderly people in whom cognitive impairment is already apparent. However, cognitive decline is often a gradual process, and elderly people may notice that their memory deteriorates before

  20. Cognitive functioning and its influence on sexual behavior in normal aging and dementia

    NARCIS (Netherlands)

    Hartmans, C.; Comijs, H.; Jonker, C.

    2014-01-01

    Objective Motivational aspects, emotional factors, and cognition, all of which require intact cognitive functioning may be essential in sexual functioning. However, little is known about the association between cognitive functioning and sexual behavior. The aim of this article is to review the

  1. HIGHER PREVALENCE OF TDP-43 PROTEINOPATHY IN COGNITIVELY NORMAL ASIANS: A CLINICOPATHOLOGICAL STUDY ON A MULTIETHNIC SAMPLE

    Science.gov (United States)

    Nascimento, Camila; Suemoto, Claudia K.; Rodriguez, Roberta D.; Di Lorenzo Alho, Ana Tereza; Leite, Renata P.; Farfel, Jose Marcelo; Pasqualucci, Carlos Alberto; Jacob-Filho, Wilson; Grinberg, Lea T.

    2015-01-01

    Transactive response DNA binding-protein 43 (TDP-43) proteinopathy is the major hallmark of frontotemporal lobar degeneration and amyotrophic lateral sclerosis. It is also present in a subset of Alzheimer’s disease cases. Recently, few reports showed TDP-43 changes in cognitively normal elderly. In Caucasians, TDP-43 proteinopathy independently correlate with cognitive decline. However, it is challenging to establish direct links between cognitive and/or neuropsychiatric symptoms and protein inclusions in neurodegenerative diseases because individual cognitive reserves modify the threshold for clinical disease expression. Cognitive reserve is influenced by demographic, environmental and genetic factors. We investigated the relationships between demographic, clinical, and neuropathological variables and TDP-43 proteinopathy in a large multiethnic sample of cognitively normal elderly. TDP-43 proteinopathy were identified in 10.5%, independently associated with older age (p = 0.03) and Asian ethnicity (p = 0.002). Asians showed a higher prevalence of TDP-43 proteinopathy than Caucasians, even after adjustment for sex, age, Braak stage, and schooling (odds ratio = 3.50, confidence interval 1.41–8.69, p = 0.007). These findings suggested Asians older adults may be protected from the clinical manifestation of brain TDP-43 proteinopathy. Future studies are needed to identify possible race-related protective factors against clinical expression of TDP-43 proteinopathies. PMID:26260327

  2. The Utility of the Wisconsin Card Sorting Test in Differential Diagnosis of Cognitive Disorders in Iranian Psychiatric Patients and Healthy Subjects

    Directory of Open Access Journals (Sweden)

    Razieh Hashemi, MA

    2011-09-01

    Full Text Available Objective: The Wisconsin Test Card Sorting Test (WCST is a neuropsychological test that has been suggested as a more specific test for frontal lobes dysfunctions. This study was designed to determine whether WCST is able to differentiate between Iranian psychiatric patients with cognitive disorders and normal subjects, and whether WCST scores are related to severity of symptoms in depressive and schizophrenic patients.Method: Participants were four groups: schizophrenics with positive symptoms (n=25; schizophrenics with negative symptoms (n=25; major depressives (n=25; and normal subjects (n=25. All subjects were tested individually using WCST. To analyze the data, various descriptive statistics, ANOVA, t-test and multiple regression analysis were used.Results: Regarding the number of categories (P<0.001 and the rate of perseverative errors (P<0.01, according to the results, the normal subjects performed significantly better than patient groups on WCST, although the differences between patient groups were not significant. Our results also showed that greater positive or depressive symptoms were not associated with poorer scores on WCST performance. Only the level of severity of negative symptoms predicted scores on perseverative errors.Conclusion: It is concluded that WCST can differentiate Iranian psychiatric patients with cognitive disorders from normal subjects, but it is not able to clearly differentiate schizophrenic patients with negative symptoms from those with positive symptoms and depressives. Only severity of negative symptoms affects WCST performance

  3. Association Between Serum Triglycerides and Cerebral Amyloidosis in Cognitively Normal Elderly.

    Science.gov (United States)

    Choi, Hyo Jung; Byun, Min Soo; Yi, Dahyun; Choe, Young Min; Sohn, Bo Kyung; Baek, Hye Won; Lee, Jun Ho; Kim, Hyun Jung; Han, Ji Young; Yoon, Eun Jin; Kim, Yu Kyeong; Woo, Jong Inn; Lee, Dong Young

    2016-08-01

    Although many preclinical studies have suggested the possible linkage between dyslipidemia and cerebral amyloid deposition, the association between serum lipid measures and cerebral amyloid-beta (Aβ) deposition in human brain is still poorly known. We aimed to investigate the association in cognitively normal (CN) elderly individuals. Cross-sectional study. University hospital dementia clinic. 59 CN elderly. The study measures included comprehensive clinical and neuropsychological assessment based on the CERAD protocol, magnetic resonance imaging and (11)C-labelled Pittsburgh Compound B positron emission tomography scans, and quantification for serum lipid biomarkers. Multiple linear regression analyses showed that a higher serum triglycerides level was associated with heavier global cerebral Aβ deposition even after controlling age, sex, and apolipoprotein E ε4 genotype. Serum apolipoprotein B also showed significant positive association with global cerebral Aβ deposition, but the significance disappeared after controlling serum triglycerides level. No association was found between other lipid measures and global cerebral Aβ deposition. The findings suggest that serum triglycerides are closely associated with cerebral amyloidosis, although population-based prospective studies are needed to provide further evidence of the causative effect of triglycerides on cerebral amyloidosis. Copyright © 2016 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

  4. Cognitive Decline in Patients with Chronic Hydrocephalus and Normal Aging: ‘Growing into Deficits'

    Directory of Open Access Journals (Sweden)

    Marlijn H. de Beer

    2016-10-01

    Full Text Available Background/Aim: To explore the theory of ‘growing into deficits', a concept known from developmental neurology, in a series of cases with chronic hydrocephalus (CH. Methods: Patients were selected from the Amsterdam Dementia Cohort and underwent extensive dementia screening. Results: Twelve patients with CH were selected, in whom Alzheimer's disease was considered unlikely, based on biomarker information and follow-up. Mean Mini-Mental State Examination score was 24 (range 7-30. Most patients were functioning on a level of mild dementia [Clinical Dementia Rating score of 0.5 in 8/11 (66.7% patients]. On neuropsychological examination, memory and executive functions, as well as processing speed were most frequently impaired. Conclusion: In our opinion, the theory of ‘growing into deficits' shows a parallel with the clinical course of CH and normal aging when Alzheimer's disease was considered very unlikely, because most of these patients were functioning well for a very large part of their lives. The altered cerebrospinal fluid dynamics might make the brain more vulnerable to aging-related changes, leading to a faster cognitive decline in CH patients compared to healthy subjects, especially in case of concomitant brain damage such as traumatic brain injury or meningitis.

  5. Amyloid burden and incident depressive symptoms in cognitively normal older adults.

    Science.gov (United States)

    Harrington, Karra D; Gould, Emma; Lim, Yen Ying; Ames, David; Pietrzak, Robert H; Rembach, Alan; Rainey-Smith, Stephanie; Martins, Ralph N; Salvado, Olivier; Villemagne, Victor L; Rowe, Christopher C; Masters, Colin L; Maruff, Paul

    2017-04-01

    Several studies have reported that non-demented older adults with clinical depression show changes in amyloid-β (Aβ) levels in blood, cerebrospinal fluid and on neuroimaging that are consistent with those observed in patients with Alzheimer's disease. These findings suggest that Aβ may be one of the mechanisms underlying the relation between the two conditions. We sought to determine the relation between elevated cerebral Aβ and the presence of depression across a 54-month prospective observation period. Cognitively normal older adults from the Australian Imaging Biomarkers and Lifestyle study who were not depressed and had undergone a positron emission tomography scan to classify them as either high Aβ (n = 81) or low Aβ (n = 278) participated. Depressive symptoms were assessed using the Geriatric Depression Scale - Short Form at 18-month intervals over 54 months. Whilst there was no difference in probable depression between groups at baseline, incidence was 4.5 (95% confidence interval [CI] 1.3-16.4) times greater within the high Aβ group (9%) than the low Aβ group (2%) by the 54-month assessment. Results of this study suggest that elevated Aβ levels are associated with a 4.5-fold increased likelihood of developing clinically significant depressive symptoms on follow-up in preclinical Alzheimer's disease. This underscores the importance of assessing, monitoring and treating depressive symptoms in older adults with elevated Aβ. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  6. Investigating the relationship between FMR1 allele length and cognitive ability in children: a subtle effect of the normal allele range on the normal ability range?

    Science.gov (United States)

    Loat, C S; Craig, G; Plomin, R; Craig, I W

    2006-09-01

    The FMR1 gene contains a trinucleotide repeat tract which can expand from a normal size of around 30 repeats to over 200 repeats, causing mental retardation (Fragile X Syndrome). Evidence suggests that premutation males (55-200 repeats) are susceptible to a late-onset tremor/ataxia syndrome and females to premature ovarian failure, and that intermediate alleles ( approximately 41-55 repeats) and premutations may be in excess in samples with special educational needs. We explored the relationship between FMR1 allele length and cognitive ability in 621 low ability and control children assessed at 4 and 7 years, as well as 122 students with high IQ. The low and high ability and control samples showed no between-group differences in incidence of longer alleles. In males there was a significant negative correlation between allele length and non-verbal ability at 4 years (p = 0.048), academic achievement in maths (p = 0.003) and English (p = 0.011) at 7 years, and IQ in the high ability group (p = 0.018). There was a significant negative correlation between allele length and a standardised score for IQ and general cognitive ability at age 7 in the entire male sample (p = 0.002). This suggests that, within the normal spectrum of allele length, increased repeat numbers may have a limiting influence on cognitive performance.

  7. n-3 Fatty acids, Mediterranean diet and cognitive function in normal aging: A systematic review.

    Science.gov (United States)

    Masana, Maria F; Koyanagi, Ai; Haro, Josep Maria; Tyrovolas, Stefanos

    2017-05-01

    Intake of n-3 fatty acids and adherence to the Mediterranean diet (MedDiet) have been shown to slow the progression of age-related cognitive decline, but the results are mixed. We summarized and evaluated the effect of n-3 fatty acids and MedDiet on cognitive outcomes in a cognitively healthy aged population. Relevant published studies from January 2000 to May 2015 were identified by searching three electronic databases: Pubmed, Web of Science/MEDLINE, and CINHAL. Observational studies and randomized controlled trials (RCTs) were considered. Twenty-four studies were included for the systematic review. n-3 fatty acids were associated with better global cognition and some specific cognitive domains though some results were conflicting. Adherence to the MedDiet was also significantly associated with better cognitive performance and less cognitive decline. Finally, better cognitive performance was observed in men compared to women and mixed results were also found for the influence of APOE4 genotype on the association between n-3 fatty acids or MedDiet and cognition. Studies suggest that n-3 fatty acids in the diet and adherence to the MedDiet are beneficial in slowing age-related cognitive decline. However, more high-quality RCTs would be useful to clarify the effect of n-3 fatty acid supplements on cognition. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. ERP C250 shows the elderly (cognitively normal, Alzheimer's disease) store more stimuli in short-term memory than Young Adults do.

    Science.gov (United States)

    Chapman, Robert M; Gardner, Margaret N; Mapstone, Mark; Klorman, Rafael; Porsteinsson, Anton P; Dupree, Haley M; Antonsdottir, Inga M; Kamalyan, Lily

    2016-06-01

    To determine how aging and dementia affect the brain's initial storing of task-relevant and irrelevant information in short-term memory. We used brain Event-Related Potentials (ERPs) to measure short-term memory storage (ERP component C250) in 36 Young Adults, 36 Normal Elderly, and 36 early-stage AD subjects. Participants performed the Number-Letter task, a cognitive paradigm requiring memory storage of a first relevant stimulus to compare it with a second stimulus. In Young Adults, C250 was more positive for the first task-relevant stimulus compared to all other stimuli. C250 in Normal Elderly and AD subjects was roughly the same to relevant and irrelevant stimuli in Intratrial Parts 1-3 but not 4. The AD group had lower C250 to relevant stimuli in part 1. Both normal aging and dementia cause less differentiation of relevant from irrelevant information in initial storage. There was a large aging effect involving differences in the pattern of C250 responses of the Young Adult versus the Normal Elderly/AD groups. Also, a potential dementia effect was obtained. C250 is a candidate tool for measuring short-term memory performance on a biological level, as well as a potential marker for memory changes due to normal aging and dementia. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  9. Aging and insulin signaling differentially control normal and tumorous germline stem cells.

    Science.gov (United States)

    Kao, Shih-Han; Tseng, Chen-Yuan; Wan, Chih-Ling; Su, Yu-Han; Hsieh, Chang-Che; Pi, Haiwei; Hsu, Hwei-Jan

    2015-02-01

    Aging influences stem cells, but the processes involved remain unclear. Insulin signaling, which controls cellular nutrient sensing and organismal aging, regulates the G2 phase of Drosophila female germ line stem cell (GSC) division cycle in response to diet; furthermore, this signaling pathway is attenuated with age. The role of insulin signaling in GSCs as organisms age, however, is also unclear. Here, we report that aging results in the accumulation of tumorous GSCs, accompanied by a decline in GSC number and proliferation rate. Intriguingly, GSC loss with age is hastened by either accelerating (through eliminating expression of Myt1, a cell cycle inhibitory regulator) or delaying (through mutation of insulin receptor (dinR) GSC division, implying that disrupted cell cycle progression and insulin signaling contribute to age-dependent GSC loss. As flies age, DNA damage accumulates in GSCs, and the S phase of the GSC cell cycle is prolonged. In addition, GSC tumors (which escape the normal stem cell regulatory microenvironment, known as the niche) still respond to aging in a similar manner to normal GSCs, suggesting that niche signals are not required for GSCs to sense or respond to aging. Finally, we show that GSCs from mated and unmated females behave similarly, indicating that female GSC-male communication does not affect GSCs with age. Our results indicate the differential effects of aging and diet mediated by insulin signaling on the stem cell division cycle, highlight the complexity of the regulation of stem cell aging, and describe a link between ovarian cancer and aging. © 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  10. Differential psychophysiological effects of operant and cognitive behavioural treatments in women with fibromyalgia.

    Science.gov (United States)

    Thieme, K; Turk, D C; Gracely, R H; Flor, H

    2016-10-01

    Determination of psychophysiological effects of operant behavioural (OBT) and cognitive behavioural treatment (CBT) for fibromyalgia patients. One hundred and fifteen female patients randomized to OBT (N = 43), CBT (N = 42), or whole-body infrared heat (IH) (N = 30) were compared before and after group treatment as well as at 6- and 12-month follow-ups using intent-to-treat analysis (12 drop-outs). Thirty matched pain-free controls (CON) served as reference group for the initial psychophysiological analysis. Surface electromyogram (EMG), blood pressure, heart rate (HR) and skin conductance levels (SCL) were continuously recorded during adaptation, baseline, social conflict, mental arithmetic and relaxation tasks. At baseline, fibromyalgia patients showed higher SCL and HR, lower diastolic blood pressure and EMG in comparison to controls. OBT and CBT compared to IH significantly reduced pain intensity [OBT: effect size (ES) = 1.21 CI: 0.71-1.71, CBT: ES = 1.23, CI: 0.72-1.74]. OBT increased diastolic blood pressure [ES = 1.13, CI: 0.63-1.63 and CBT reduced SCL (ES) = -0.66, CI: -1.14-0.18] 12 months after treatment. Both CBT and OBT significantly increased EMG levels (OBT: ES = 0.97, CI: 0.48-1.46, CBT: ES = 1.17, CI: 0.67-1.68). In contrast, the IH group did not show any significant changes in the psychophysiological parameters. Increased diastolic blood pressure and decreased pain after OBT suggest a reactivation of baroreflex-mechanisms in fibromyalgia and a normalization of the blood pressure and pain functional relationship. Reduced SCL following CBT may indicate reduced general arousal levels. Increased muscle tension after CBT and OBT suggest a normalization of physical parameters. The reduction in pain seems to be mediated by different psychophysiological processes, providing support for mechanism-based treatments might be indicated for CBT and OBT. WHAT DOES THIS STUDY ADD?: Differential physiological stress responses followed different

  11. Differential MR/GR Activation in Mice Results in Emotional States Beneficial or Impairing for Cognition

    Directory of Open Access Journals (Sweden)

    Vera Brinks

    2007-01-01

    Full Text Available Corticosteroids regulate stress response and influence emotion, learning, and memory via two receptors in the brain, the high‐affinity mineralocorticoid (MR and low‐affinity glucocorticoid receptor (GR. We test the hypothesis that MR- and GR-mediated effects interact in emotion and cognition when a novel situation is encountered that is relevant for a learning process. By adrenalectomy and additional constant corticosterone supplement we obtained four groups of male C57BL/6J mice with differential chronic MR and GR activations. Using a hole board task, we found that mice with continuous predominant MR and moderate GR activations were fast learners that displayed low anxiety and arousal together with high directed explorative behavior. Progressive corticosterone concentrations with predominant action via GR induced strong emotional arousal at the expense of cognitive performance. These findings underline the importance of a balanced MR/GR system for emotional and cognitive functioning that is critical for mental health.

  12. Cognitive-style characteristics as criteria for differential diagnosis of delirium

    Directory of Open Access Journals (Sweden)

    I.V. Kuznetsov

    2014-08-01

    Full Text Available We present a psychological study of the relationship of cognitive styles with the development of delusional formations, overvalued ideas and simulative products in order to develop criteria of delirium differential diagnosis. We examined 118 men, ordered at forensic psychological and psychiatric examination, among them delusional symptoms were found in 68 people, and overvalued ideas in 26 people, 24 people simulated delirium. As a method of research, we used pathopsychological experiment and projective techniques and methods that identify particular cognitive style (TAT, Rorschach, Torrance. We found that delusional patients, unlike those simulating a mental disorder, show field independence cognitive style combined with the rigidity that is characteristic also for patients with endogenous overvalued ideas. In personality disorders, we found combination of field independence with the flexibility or with rigidity.

  13. Serum cholinesterases are differentially regulated in normal and dystrophin-deficient mutant mice

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    Andrea R. Durrant

    2012-06-01

    Full Text Available The cholinesterases, acetylcholinesterase and butyrylcholinesterase (pseudocholinesterase, are abundant in the nervous system and in other tissues. The role of acetylcholinesterase in terminating transmitter action in the peripheral and central nervous system is well understood. However, both knowledge of the function(s of the cholinesterases in serum, and of their metabolic and endocrine regulation under normal and pathological conditions, is limited. This study investigates acetylcholinesterase and butyrylcholinesterase in sera of dystrophin-deficient mdx mutant mice, an animal model for the human Duchenne muscular dystrophy and in control healthy mice. The data show systematic and differential variations in the concentrations of both enzymes in the sera, and specific changes dictated by alteration of hormonal balance in both healthy and dystrophic mice. While acetylcholinesterase in mdx-sera is elevated, butyrylcholinesterase is markedly diminished, resulting in an overall cholinesterase decrease compared to sera of healthy controls. The androgen testosterone (T is a negative modulator of butyrylcholinesterase, but not of acetylcholinesterase, in male mouse sera. T-removal elevated both butyrylcholinesterase activity and the butyrylcholinesterase/acetylcholinesterase ratio in mdx male sera to values resembling those in healthy control male mice. Mechanisms of regulation of the circulating cholinesterases and their impairment in the dystrophic mice are suggested, and clinical implications for diagnosis and treatment are considered.

  14. Normal proliferation and differentiation of Hoxc-8 transgenic chondrocytes in vitro

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    Mello Maria

    2003-04-01

    Full Text Available Abstract Background Hox genes encode transcription factors that are involved in pattern formation in the skeleton, and recent evidence suggests that they also play a role in the regulation of endochondral ossification. To analyze the role of Hoxc-8 in this process in more detail, we applied in vitro culture systems, using high density cultures of primary chondrocytes from neonatal mouse ribs. Results Cultured cells were characterized on the basis of morphology (light microscopy and production of cartilage-specific extracellular matrix (sulfated proteoglycans and type II Collagen. Hypertrophy was demonstrated by increase in cell size, alkaline phosphatase activity and type X Collagen immunohistochemistry. Proliferation was assessed by BrdU uptake and flow cytometry. Unexpectedly, chondrocytes from Hoxc-8 transgenic mice, which exhibit delayed cartilage maturation in vivo 1, were able to proliferate and differentiate normally in our culture systems. This was the case even though freshly isolated Hoxc-8 transgenic chondrocytes exhibited significant molecular differences as measured by real-time quantitative PCR. Conclusions The results demonstrate that primary rib chondrocytes behave similar to published reports for chondrocytes from other sources, validating in vitro approaches for studies of Hox genes in the regulation of endochondral ossification. Our analysis of cartilage-producing cells from Hoxc-8 transgenic mice provides evidence that the cellular phenotype induced by Hoxc-8 overexpression in vivo is reversible in vitro.

  15. Neural implementation of musical expertise and cognitive transfers: Could they be promising in the framework of normal cognitive aging?

    Directory of Open Access Journals (Sweden)

    Baptiste eFAUVEL

    2013-10-01

    Full Text Available Brain plasticity allows the central nervous system of a given organism to cope with environmental demands. Therefore, the quality of mental processes relies partly on the interaction between the brain’s physiological maturation and individual daily experiences.In this review, we focus on the neural implementation of musical expertise at both an anatomical and a functional level. We then discuss how this neural implementation can explain transfers from musical learning to a broad range of nonmusical cognitive functions, including language, especially during child development. Finally, given that brain plasticity is still present in aging, we gather arguments to propose that musical practice could be a good environmental enrichment to promote cerebral and cognitive reserves, thereby reducing the deleterious effect of aging on cognitive functions.

  16. Connectivity Neurofeedback Training Can Differentially Change Functional Connectivity and Cognitive Performance.

    Science.gov (United States)

    Yamashita, Ayumu; Hayasaka, Shunsuke; Kawato, Mitsuo; Imamizu, Hiroshi

    2017-10-01

    Advances in functional magnetic resonance imaging have made it possible to provide real-time feedback on brain activity. Neurofeedback has been applied to therapeutic interventions for psychiatric disorders. Since many studies have shown that most psychiatric disorders exhibit abnormal brain networks, a novel experimental paradigm named connectivity neurofeedback, which can directly modulate a brain network, has emerged as a promising approach to treat psychiatric disorders. Here, we investigated the hypothesis that connectivity neurofeedback can induce the aimed direction of change in functional connectivity, and the differential change in cognitive performance according to the direction of change in connectivity. We selected the connectivity between the left primary motor cortex and the left lateral parietal cortex as the target. Subjects were divided into 2 groups, in which only the direction of change (an increase or a decrease in correlation) in the experimentally manipulated connectivity differed between the groups. As a result, subjects successfully induced the expected connectivity changes in either of the 2 directions. Furthermore, cognitive performance significantly and differentially changed from preneurofeedback to postneurofeedback training between the 2 groups. These findings indicate that connectivity neurofeedback can induce the aimed direction of change in connectivity and also a differential change in cognitive performance. © The Author 2017. Published by Oxford University Press.

  17. Cell-surface glycoproteins of human sarcomas: differential expression in normal and malignant tissues and cultured cells

    International Nuclear Information System (INIS)

    Rettig, W.F.; Garin-Chesa, P.; Beresford, H.R.; Oettgen, H.F.; Melamed, M.R.; Old, L.J.

    1988-01-01

    Normal differentiation and malignant transformation of human cells are characterized by specific changes in surface antigen phenotype. In the present study, the authors have defined six cell-surface antigens of human sarcomas and normal mesenchymal cells, by using mixed hemadsorption assays and immunochemical methods for the analysis of cultured cells and immunohistochemical staining for the analysis of normal tissues and > 200 tumor specimens. Differential patterns of F19, F24, G171, G253, S5, and Thy-1 antigen expression were found to characterize (i) subsets of cultured sarcoma cell lines, (ii) cultured fibroblasts derived from various organs, (iii) normal resting and activated mesenchymal tissues, and (iv) sarcoma and nonmesenchymal tumor tissues. These results provide a basic surface antigenic map for cultured mesenchymal cells and mesenchymal tissues and permit the classification of human sarcomas according to their antigenic phenotypes

  18. Displacement of the normal pituitary gland by sellar and juxtasellar tumours: surgical-MRI correlation and use in differential diagnosis

    International Nuclear Information System (INIS)

    Sumida, M.; Uozumi, T.; Yamanaka, M.; Mukada, K.; Arita, K.; Kurisu, K.; Satoh, H.; Ikawa, F.

    1994-01-01

    We compared the position of the normal pituitary gland as estimated by gadolinium (Gd)-DTPA-enhanced MRI, with its position at surgery in 40 patients with intra- and juxtasellar tumours: 22 pituitary adenomas, 4 craniopharyngiomas, 7 meningiomas, 2 germinomas, and 5 Rathke cleft cysts. In 37 of these, the normal gland showed more intense contrast enhancement than the adjacent tumour, from which it could be differentiated by Gd-DTPA-enhanced MRI, especially in the sagittal plane. The direction of displacement of the normal pituitary gland correlated well with tumour type, so that its position proved helpful in the differential diagnosis. The normal gland was typically displaced superiorly by pituitary adenomas, inferiorly by craniopharyngiomas, and anteriorly by germinomas. It showed variable displacement by Rathke cleft cysts, and was not usually displaced by meningiomas. (orig.)

  19. Sleep, Cognition, and Normal Aging: Integrating a Half-Century of Multidisciplinary Research

    Science.gov (United States)

    Scullin, Michael K.; Bliwise, Donald L.

    2014-01-01

    Sleep is implicated in cognitive functioning in young adults. With increasing age there are substantial changes to sleep quantity and quality including changes to slow wave sleep, spindle density, and sleep continuity/fragmentation. A provocative question for the field of cognitive aging is whether such changes in sleep physiology affect cognition (e.g., memory consolidation). We review nearly a half-century of research studies across 7 diverse correlational and experimental literature domains, which historically have had little crosstalk. Broadly speaking, sleep and cognitive functions are often related in advancing age, though the prevalence of null effects (including correlations in the unexpected, negative direction) in healthy older adults indicates that age may be an effect modifier of these associations. We interpret the literature as suggesting that maintaining good sleep quality, at least in young adulthood and middle age, promotes better cognitive functioning and serves to protect against age-related cognitive declines. PMID:25620997

  20. Episodic memory deficits slow down the dynamics of cognitive procedural learning in normal ageing

    Science.gov (United States)

    Beaunieux, Hélène; Hubert, Valérie; Pitel, Anne Lise; Desgranges, Béatrice; Eustache, Francis

    2009-01-01

    Cognitive procedural learning is characterized by three phases, each involving distinct processes. Considering the implication of the episodic memory in the first cognitive stage, the impairment of this memory system might be responsible for a slowing down of the cognitive procedural learning dynamics in the course of aging. Performances of massed cognitive procedural learning were evaluated in older and younger participants using the Tower of Toronto task. Nonverbal intelligence and psychomotor abilities were used to analyze procedural dynamics, while episodic memory and working memory were assessed to measure their respective contributions to learning strategies. This experiment showed that older participants did not spontaneously invoke episodic memory and presented a slowdown in the cognitive procedural learning associated with a late involvement of working memory. These findings suggest that the slowdown in the cognitive procedural learning may be linked with the implementation of different learning strategies less involving episodic memory in older subjects. PMID:18654928

  1. Differential effects of water-based exercise on the cognitive function in independent elderly adults.

    Science.gov (United States)

    Sato, Daisuke; Seko, Chihiro; Hashitomi, Tatsuya; Sengoku, Yasuo; Nomura, Takeo

    2015-04-01

    Physical exercise has been reported to be the most effective method to improve cognitive function and brain health, but there is as yet no research on the effect of water-based exercise. The aim of the present study was to compare the effects of water-based exercise with and without cognitive stimuli on cognitive and physical functions. The design is a single-blind randomized controlled study. Twenty-one participants were randomly assigned to a normal water-based exercise (Nor-WE) group or a cognitive water-based exercise (Cog-WE) group. The exercise sessions were divided into two exercise series: a 10-min series of land-based warm-up, consisting of flexibility exercises, and a 50-min series of exercises in water. The Nor-WE consisted of 10 min of walking, 30 min of strength and stepping exercise, including stride over, and 10 min of stretching and relaxation in water. The Cog-WE consisted of 10 min of walking, 30 min of water-cognitive exercises, and 10 min of stretching and relaxation in water. Cognitive function, physical function, and ADL were measured before the exercise intervention (pre-intervention) and 10 weeks after the intervention (post-intervention). Participation in the Cog-WE performed significantly better on the pegboard test and the choice stepping reaction test and showed a significantly improved attention, memory, and learning, and in the general cognitive function (measured as the total score in the 5-Cog test). Participation in the Nor-WE dramatically improved walking ability and lower limb muscle strength. Our results reveal that the benefits elderly adults may obtain from water-based exercise depend on the characteristics of each specific exercise program. These findings highlight the importance of prescription for personalized water-based exercises to elderly adults to improve cognitive function.

  2. Performance in normal subjects on a novel battery of driving-related sensory-motor and cognitive tests.

    Science.gov (United States)

    Innes, Carrie R H; Jones, Richard D; Anderson, Tim J; Hollobon, Susan G; Dalrymple-Alford, John C

    2009-05-01

    Currently, there is no international standard for the assessment of fitness to drive for cognitively or physically impaired persons. A computerized battery of driving-related sensory-motor and cognitive tests (SMCTests) has been developed, comprising tests of visuoperception, visuomotor ability, complex attention, visual search, decision making, impulse control, planning, and divided attention. Construct validity analysis was conducted in 60 normal, healthy subjects and showed that, overall, the novel cognitive tests assessed cognitive functions similar to a set of standard neuropsychological tests. The novel tests were found to have greater perceived face validity for predicting on-road driving ability than was found in the equivalent standard tests. Test-retest stability and reliability of SMCTests measures, as well as correlations between SMCTests and on-road driving, were determined in a subset of 12 subjects. The majority of test measures were stable and reliable across two sessions, and significant correlations were found between on-road driving scores and measures from ballistic movement, footbrake reaction, hand-control reaction, and complex attention. The substantial face validity, construct validity, stability, and reliability of SMCTests, together with the battery's level of correlation with on-road driving in normal subjects, strengthen our confidence in the ability of SMCTests to detect and identify sensory-motor and cognitive deficits related to unsafe driving and increased risk of accidents.

  3. Glucose hypometabolism is highly localized, but lower cortical thickness and brain atrophy are widespread in cognitively normal older adults.

    Science.gov (United States)

    Nugent, Scott; Castellano, Christian-Alexandre; Goffaux, Philippe; Whittingstall, Kevin; Lepage, Martin; Paquet, Nancy; Bocti, Christian; Fulop, Tamas; Cunnane, Stephen C

    2014-06-01

    Several studies have suggested that glucose hypometabolism may be present in specific brain regions in cognitively normal older adults and could contribute to the risk of subsequent cognitive decline. However, certain methodological shortcomings, including a lack of partial volume effect (PVE) correction or insufficient cognitive testing, confound the interpretation of most studies on this topic. We combined [(18)F]fluorodeoxyglucose ([(18)F]FDG) positron emission tomography (PET) and magnetic resonance (MR) imaging to quantify cerebral metabolic rate of glucose (CMRg) as well as cortical volume and thickness in 43 anatomically defined brain regions from a group of cognitively normal younger (25 ± 3 yr old; n = 25) and older adults (71 ± 9 yr old; n = 31). After correcting for PVE, we observed 11-17% lower CMRg in three specific brain regions of the older group: the superior frontal cortex, the caudal middle frontal cortex, and the caudate (P ≤ 0.01 false discovery rate-corrected). In the older group, cortical volumes and cortical thickness were 13-33 and 7-18% lower, respectively, in multiple brain regions (P ≤ 0.01 FDR correction). There were no differences in CMRg between individuals who were or were not prescribed antihypertensive medication. There were no significant correlations between CMRg and cognitive performance or metabolic parameters measured in fasting plasma. We conclude that highly localized glucose hypometabolism and widespread cortical thinning and atrophy can be present in older adults who are cognitively normal, as assessed using age-normed neuropsychological testing measures. Copyright © 2014 the American Physiological Society.

  4. Differential impairment of social cognition factors in bipolar disorder with and without psychotic features and schizophrenia.

    Science.gov (United States)

    Thaler, Nicholas S; Allen, Daniel N; Sutton, Griffin P; Vertinski, Mary; Ringdahl, Erik N

    2013-12-01

    While it is well-established that patients with schizophrenia and bipolar disorder exhibit deficits in social cognition, few studies have separately examined bipolar disorder with and without psychotic features. The current study addressed this gap by comparing patients with bipolar disorder with (BD+) and without (BD-) psychotic features, patients with schizophrenia (SZ), and healthy controls (NC) across social cognitive measures. Principal factor analysis on five social cognition tasks extracted a two-factor structure comprised of social/emotional processing and theory of mind. Factor scores were compared among the four groups. Results identified differential patterns of impairment between the BD+ and BD- group on the social/emotional processing factor while all clinical groups performed poorer than controls on the theory of mind factor. This provides evidence that a history of psychosis should be taken into account while evaluating social cognition in patients with bipolar disorder and also raises hypotheses about the relationship between social cognition and psychosis. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Folate and S-adenosylmethionine modulate synaptic activity in cultured cortical neurons: acute differential impact on normal and apolipoprotein-deficient mice

    International Nuclear Information System (INIS)

    Serra, Michael; Chan, Amy; Dubey, Maya; Shea, Thomas B; Gilman, Vladimir

    2008-01-01

    Folate deficiency is accompanied by a decline in the cognitive neurotransmitter acetylcholine and a decline in cognitive performance in mice lacking apolipoprotein E (ApoE−/− mice), a low-density lipoprotein that regulates aspects of lipid metabolism. One direct consequence of folate deficiency is a decline in S-adenosylmethionine (SAM). Since dietary SAM supplementation maintains acetylcholine levels and cognitive performance in the absence of folate, we examined herein the impact of folate and SAM on neuronal synaptic activity. Embryonic cortical neurons from mice expressing or lacking ApoE (ApoE+/+ or −/−, respectively) were cultured for 1 month on multi-electrode arrays, and signaling was recorded. ApoE+/+ cultures displayed significantly more frequent spontaneous signals than ApoE−/− cultures. Supplementation with 166 µm SAM (not normally present in culture medium) increased signal frequency and decreased signal amplitude in ApoE+/+ cultures. SAM also increased the frequency of tightly clustered signal bursts. Folate deprivation reversibly reduced signal frequency in ApoE+/+ cultures; SAM supplementation maintained signal frequency despite folate deprivation. These findings support the importance of dietary supplementation with folate and SAM on neuronal health. Supplementation with 166 µm SAM did not alter signaling in ApoE−/− cultures, which may be a reflection of the reduced SAM levels in ApoE−/− mice. The differential impact of SAM on ApoE+/+ and −/− neurons underscores the combined impact of nutritional and genetic deficiencies on neuronal homeostasis. (communication)

  6. Differential regulation of renal Klotho and FGFR1 in normal and uremic rats.

    Science.gov (United States)

    Muñoz-Castañeda, Juan R; Herencia, Carmen; Pendón-Ruiz de Mier, Maria Victoria; Rodriguez-Ortiz, Maria Encarnación; Diaz-Tocados, Juan M; Vergara, Noemi; Martínez-Moreno, Julio M; Salmerón, Maria Dolores; Richards, William G; Felsenfeld, Arnold; Kuro-O, Makoto; Almadén, Yolanda; Rodríguez, Mariano

    2017-09-01

    In renal failure, hyperphosphatemia occurs despite a marked elevation in serum fibroblast growth factor (FGF)-23. Abnormal regulation of the FGFR1-Klotho receptor complex may cause a resistance to the phosphaturic action of FGF23. The purpose of the present study was to investigate the regulation of renal Klotho and FGF receptor (FEFR)-1 in healthy and uremic rats induced by 5/6 nephrectomy. In normal rats, the infusion of rat recombinant FGF23 enhanced phosphaturia and increased renal FGFR1 expression; however, Klotho expression was reduced. Uremic rats on a high-phosphate (HP) diet presented hyperphosphatemia with marked elevation of FGF23 and an increased fractional excretion of phosphate (P) that was associated with a marked reduction of Klotho expression and an increase in FGFR1. After neutralization of FGF23 by anti-FGF23 administration, phosphaturia was still abundant, Klotho expression remained low, and the FGFR1 level was reduced. These results suggest that the expression of renal Klotho is modulated by phosphaturia, whereas the FGFR1 expression is regulated by FGF23. Calcitriol (CTR) administration prevented a decrease in renal Klotho expression. In HEK293 cells HP produced nuclear translocation of β-catenin, together with a reduction in Klotho. Wnt/β-catenin inhibition with Dkk-1 prevented the P-induced down-regulation of Klotho. The addition of CTR to HP medium was able to recover Klotho expression. In summary, high FGF23 levels increase FGFR1, whereas phosphaturia decreases Klotho expression through the activation of Wnt/β-catenin pathway.-Muñoz-Castañeda, J. R., Herencia, C., Pendón-Ruiz de Mier, M. V., Rodriguez-Ortiz, M. E., Diaz-Tocados, J. M., Vergara, N., Martínez-Moreno, J. M., Salmerón, M. D., Richards, W. G., Felsenfeld, A., Kuro-O, M., Almadén, Y., Rodríguez, M. Differential regulation of renal Klotho and FGFR1 in normal and uremic rats. © FASEB.

  7. Clinical relevance of specific cognitive complaints in determining Mild Cognitive Impairment from Cognitively Normal States in a study of Healthy Elderly Controls

    Directory of Open Access Journals (Sweden)

    Marina Avila Villanueva

    2016-10-01

    Full Text Available Introduction: Subjective memory complaints in the elderly have been suggested as an early sign of dementia. This study aims at investigating whether specific cognitive complaints are more useful than others to discriminate Mild Cognitive Impairment (MCI by examining the dimensional structure of the Everyday Memory Questionnaire (EMQ.Material and Methods: A sample of community-dwelling elderly individuals was recruited (766 controls and 78 MCI. The Everyday Memory Questionnaire (EMQ was administered to measure self-perception of cognitive complaints. All participants also underwent a comprehensive clinical and neuropsychological battery. Combined exploratory factor analysis and item response theory were performed to identify the underlying structure of the EMQ. Furthermore, logistic regression analyses were conducted to study whether single cognitive complaints were able to predict MCI.Results: A suitable five-factor solution was found. Each factor focused on a different cognitive domain. Interestingly, just three of them, namely forgetfulness of immediate information, executive functions and prospective memory proved to be effective in distinguishing between cognitively healthy individuals and MCI. Based on these results we propose a shortened EMQ version comprising 10 items (EMQ-10.Discussion: Not all cognitive complaints have the same clinical relevance. Only subjective complaints on specific cognitive domains are able to discriminate MCI. We encourage clinicians to the EMQ-10 as a useful tool to quantify and monitor the progression of individuals who report cognitive complaints.

  8. Differentiating os acromiale from normally developing acromial ossification centers using magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Winfeld, Matthew [Children' s National Medical Center, Department of Radiology, Washington, DC (United States); Rosenberg, Zehava Sadka; Wang, Annie; Bencardino, Jenny [New York University School of Medicine, New York, NY (United States)

    2015-05-01

    Acromial fusion may not be complete until age 18-25, making it questionable to diagnose os acromiale in adolescents. Os acromiale may exist in adolescents and can be differentiated from a developing acromial ossification center based on MRI findings. A total of 128 MRIs of the shoulder were randomly and blindly reviewed retrospectively by two musculoskeletal radiologists. The MRIs consisted of two groups: (1) 56 of os acromiale in adults (25-74 years old, mean, 50) and (2) 72 consecutive of adolescents (12-17 years old, mean, 14.5). The following were assessed at the interface between the distal acromion and os acromiale/developing ossification center(s): presence of os acromiale vs. developing acromion, orientation, margins, and edema within and adjacent to it. Fifty-one adults and 49 adolescents were included. Exclusions were due to poor image quality or confounding findings (n = 7) or complete acromial fusion (n = 21 adolescents). Utilizing accepted definitions of os acromiale, all adult cases (100 %) were accurately diagnosed as os acromiale, with transverse interface orientation and irregular margins (94 %, R = 0.86, p < 0.00001). Forty-five (92 %) adolescent cases were accurately diagnosed as normally developing acromion with arched interface and lobulated margins (92 %, R = 0.92, p < 0.000001). Four (8 %) adolescent cases were diagnosed as having os acromiale, with transverse orientation and irregular margins. Thirty-five (69 %) and 46 (90 %) adults had marrow and interface edema, respectively. Six (12 %) and eight (16 %) adolescents had marrow and interface edema, respectively, including the four concluded to be os acromiale. Adolescents may have imaging findings consistent with os acromiale. The diagnosis of os acromiale should be based on imaging features and not limited by age. (orig.)

  9. Regulation of normal B-cell differentiation and malignant B-cell survival by OCT2.

    Science.gov (United States)

    Hodson, Daniel J; Shaffer, Arthur L; Xiao, Wenming; Wright, George W; Schmitz, Roland; Phelan, James D; Yang, Yandan; Webster, Daniel E; Rui, Lixin; Kohlhammer, Holger; Nakagawa, Masao; Waldmann, Thomas A; Staudt, Louis M

    2016-04-05

    The requirement for the B-cell transcription factor OCT2 (octamer-binding protein 2, encoded by Pou2f2) in germinal center B cells has proved controversial. Here, we report that germinal center B cells are formed normally after depletion of OCT2 in a conditional knockout mouse, but their proliferation is reduced and in vivo differentiation to antibody-secreting plasma cells is blocked. This finding led us to examine the role of OCT2 in germinal center-derived lymphomas. shRNA knockdown showed that almost all diffuse large B-cell lymphoma (DLBCL) cell lines are addicted to the expression of OCT2 and its coactivator OCA-B. Genome-wide chromatin immunoprecipitation (ChIP) analysis and gene-expression profiling revealed the broad transcriptional program regulated by OCT2 that includes the expression of STAT3, IL-10, ELL2, XBP1, MYC, TERT, and ADA. Importantly, genetic alteration of OCT2 is not a requirement for cellular addiction in DLBCL. However, we detected amplifications of the POU2F2 locus in DLBCL tumor biopsies and a recurrent mutation of threonine 223 in the DNA-binding domain of OCT2. This neomorphic mutation subtly alters the DNA-binding preference of OCT2, leading to the transactivation of noncanonical target genes including HIF1a and FCRL3 Finally, by introducing mutations designed to disrupt the OCT2-OCA-B interface, we reveal a requirement for this protein-protein interface that ultimately might be exploited therapeutically. Our findings, combined with the predominantly B-cell-restricted expression of OCT2 and the absence of a systemic phenotype in our knockout mice, suggest that an OCT2-targeted therapeutic strategy would be efficacious in both major subtypes of DLBCL while avoiding systemic toxicity.

  10. Differentiating os acromiale from normally developing acromial ossification centers using magnetic resonance imaging

    International Nuclear Information System (INIS)

    Winfeld, Matthew; Rosenberg, Zehava Sadka; Wang, Annie; Bencardino, Jenny

    2015-01-01

    Acromial fusion may not be complete until age 18-25, making it questionable to diagnose os acromiale in adolescents. Os acromiale may exist in adolescents and can be differentiated from a developing acromial ossification center based on MRI findings. A total of 128 MRIs of the shoulder were randomly and blindly reviewed retrospectively by two musculoskeletal radiologists. The MRIs consisted of two groups: (1) 56 of os acromiale in adults (25-74 years old, mean, 50) and (2) 72 consecutive of adolescents (12-17 years old, mean, 14.5). The following were assessed at the interface between the distal acromion and os acromiale/developing ossification center(s): presence of os acromiale vs. developing acromion, orientation, margins, and edema within and adjacent to it. Fifty-one adults and 49 adolescents were included. Exclusions were due to poor image quality or confounding findings (n = 7) or complete acromial fusion (n = 21 adolescents). Utilizing accepted definitions of os acromiale, all adult cases (100 %) were accurately diagnosed as os acromiale, with transverse interface orientation and irregular margins (94 %, R = 0.86, p < 0.00001). Forty-five (92 %) adolescent cases were accurately diagnosed as normally developing acromion with arched interface and lobulated margins (92 %, R = 0.92, p < 0.000001). Four (8 %) adolescent cases were diagnosed as having os acromiale, with transverse orientation and irregular margins. Thirty-five (69 %) and 46 (90 %) adults had marrow and interface edema, respectively. Six (12 %) and eight (16 %) adolescents had marrow and interface edema, respectively, including the four concluded to be os acromiale. Adolescents may have imaging findings consistent with os acromiale. The diagnosis of os acromiale should be based on imaging features and not limited by age. (orig.)

  11. Flow-regulated versus differential pressure-regulated shunt valves for adult patients with normal pressure hydrocephalus

    DEFF Research Database (Denmark)

    Ziebell, Morten; Wetterslev, Jørn; Tisell, Magnus

    2013-01-01

    Since 1965 many ventriculo-peritoneal shunt systems have been inserted worldwide to treat hydrocephalus. The most frequent indication in adults is normal pressure hydrocephalus (NPH), a condition that can be difficult to diagnose precisely. Surgical intervention with flow-regulated and differential...

  12. Clinical Utility of Short Social Cognitive Tests in Early Differentiation of Behavioral Variant Frontotemporal Dementia from Alzheimer’s Disease

    DEFF Research Database (Denmark)

    Buhl, Christian; Stokholm, Jette; Gade, Anders

    2013-01-01

    Traditional cognitive tests used in clinical practice may not be sensitive enough for the early differentiation of behavioral variant frontotemporal dementia (bvFTD) from Alzheimer's disease (AD). A growing body of literature has shown that deficits in various aspects of social cognition can be f...

  13. Cortical Thickness, Surface Area and Subcortical Volume Differentially Contribute to Cognitive Heterogeneity in Parkinson's Disease.

    Science.gov (United States)

    Gerrits, Niels J H M; van Loenhoud, Anita C; van den Berg, Stan F; Berendse, Henk W; Foncke, Elisabeth M J; Klein, Martin; Stoffers, Diederick; van der Werf, Ysbrand D; van den Heuvel, Odile A

    2016-01-01

    Parkinson's disease (PD) is often associated with cognitive deficits, although their severity varies considerably between patients. Recently, we used voxel-based morphometry (VBM) to show that individual differences in gray matter (GM) volume relate to cognitive heterogeneity in PD. VBM does, however, not differentiate between cortical thickness (CTh) and surface area (SA), which might be independently affected in PD. We therefore re-analyzed our cohort using the surface-based method FreeSurfer, and investigated (i) CTh, SA, and (sub)cortical GM volume differences between 93 PD patients and 45 matched controls, and (ii) the relation between these structural measures and cognitive performance on six neuropsychological tasks within the PD group. We found cortical thinning in PD patients in the left pericalcarine gyrus, extending to cuneus, precuneus and lingual areas and left inferior parietal cortex, bilateral rostral middle frontal cortex, and right cuneus, and increased cortical surface area in the left pars triangularis. Within the PD group, we found negative correlations between (i) CTh of occipital areas and performance on a verbal memory task, (ii) SA and volume of the frontal cortex and visuospatial memory performance, and, (iii) volume of the right thalamus and scores on two verbal fluency tasks. Our primary findings illustrate that i) CTh and SA are differentially affected in PD, and ii) VBM and FreeSurfer yield non-overlapping results in an identical dataset. We argue that this discrepancy is due to technical differences and the subtlety of the PD-related structural changes.

  14. Alzheimer’s disease cerebrospinal fluid biomarker in cognitively normal subjects

    Science.gov (United States)

    Toledo, Jon B.; Zetterberg, Henrik; van Harten, Argonde C.; Glodzik, Lidia; Martinez-Lage, Pablo; Bocchio-Chiavetto, Luisella; Rami, Lorena; Hansson, Oskar; Sperling, Reisa; Engelborghs, Sebastiaan; Osorio, Ricardo S.; Vanderstichele, Hugo; Vandijck, Manu; Hampel, Harald; Teipl, Stefan; Moghekar, Abhay; Albert, Marilyn; Hu, William T.; Monge Argilés, Jose A.; Gorostidi, Ana; Teunissen, Charlotte E.; De Deyn, Peter P.; Hyman, Bradley T.; Molinuevo, Jose L.; Frisoni, Giovanni B.; Linazasoro, Gurutz; de Leon, Mony J.; van der Flier, Wiesje M.; Scheltens, Philip; Blennow, Kaj; Shaw, Leslie M.

    2015-01-01

    In a large multicentre sample of cognitively normal subjects, as a function of age, gender and APOE genotype, we studied the frequency of abnormal cerebrospinal fluid levels of Alzheimer’s disease biomarkers including: total tau, phosphorylated tau and amyloid-β1-42. Fifteen cohorts from 12 different centres with either enzyme-linked immunosorbent assays or Luminex® measurements were selected for this study. Each centre sent nine new cerebrospinal fluid aliquots that were used to measure total tau, phosphorylated tau and amyloid-β1-42 in the Gothenburg laboratory. Seven centres showed a high correlation with the new Gothenburg measurements; therefore, 10 cohorts from these centres are included in the analyses here (1233 healthy control subjects, 40–84 years old). Amyloid-β amyloid status (negative or positive) and neurodegeneration status (negative or positive) was established based on the pathological cerebrospinal fluid Alzheimer’s disease cut-off values for cerebrospinal fluid amyloid-β1-42 and total tau, respectively. While gender did not affect these biomarker values, APOE genotype modified the age-associated changes in cerebrospinal fluid biomarkers such that APOE ε4 carriers showed stronger age-related changes in cerebrospinal fluid phosphorylated tau, total tau and amyloid-β1-42 values and APOE ε2 carriers showed the opposite effect. At 40 years of age, 76% of the subjects were classified as amyloid negative, neurodegeneration negative and their frequency decreased to 32% at 85 years. The amyloid-positive neurodegeneration-negative group remained stable. The amyloid-negative neurodegeneration-positive group frequency increased slowly from 1% at 44 years to 16% at 85 years, but its frequency was not affected by APOE genotype. The amyloid-positive neurodegeneration-positive frequency increased from 1% at 53 years to 28% at 85 years. Abnormally low cerebrospinal fluid amyloid-β1-42 levels were already frequent in midlife and APOE genotype

  15. Normalized Mini-Mental State Examination for assessing cognitive change in population-based brain aging studies.

    Science.gov (United States)

    Philipps, Viviane; Amieva, Hélène; Andrieu, Sandrine; Dufouil, Carole; Berr, Claudine; Dartigues, Jean-François; Jacqmin-Gadda, Hélène; Proust-Lima, Cécile

    2014-01-01

    The Mini-Mental State Examination (MMSE) is widely used in population-based longitudinal studies to quantify cognitive change. However, its poor metrological properties, mainly ceiling/floor effects and varying sensitivity to change, have largely restricted its usefulness. We propose a normalizing transformation that corrects these properties, and makes possible the use of standard statistical methods to analyze change in MMSE scores. The normalizing transformation designed to correct at best the metrological properties of MMSE was estimated and validated on two population-based studies (n = 4,889, 20-year follow-up) by cross-validation. The transformation was also validated on two external studies with heterogeneous samples mixing normal and pathological aging, and samples including only demented subjects. The normalizing transformation provided correct inference in contrast with models analyzing the change in crude MMSE that most often lead to biased estimates of risk factors and incorrect conclusions. Cognitive change can be easily and properly assessed with the normalized MMSE using standard statistical methods such as linear (mixed) models. © 2014 S. Karger AG, Basel.

  16. Differential cognitive profiles of intimate partner violence perpetrators based on alcohol consumption.

    Science.gov (United States)

    Vitoria-Estruch, Sara; Romero-Martínez, Angel; Lila, Marisol; Moya-Albiol, Luis

    2018-08-01

    Despite extensive evidence of heterogeneity in intimate partner violence (IPV) perpetrator profiles, there has been little research into neuropsychological deficits that might help us understand differences within this violent population. Moreover, studies on this topic have not paid much attention to the role of alcohol abuse in neuropsychological domains of IPV perpetrators. Hence, the current study was designed to examine neuropsychological differences among individuals who have committed domestic violence with high (n = 28, HA) and low (n = 35, LA) levels of alcohol consumption, and non-violent individuals (n = 37) to establish differential neuropsychological profiles. An exhaustive neuropsychological assessment battery was employed which combined the computer-based Cambridge Neuropsychological Test Automated Battery with pencil-and-paper measures. Compared to controls, HA IPV perpetrators had slower processing speed and significantly more impairments in attentional set-shifting or switch attention, working and long-term memory, cognitive flexibility, planning, decision-making, emotion decoding skills, and perspective taking. Furthermore, there were differences between IPV perpetrator subgroups in attentional set-shifting or switch attention and cognitive empathy, with HA IPV perpetrators displaying more severe impairments in both cognitive domains than LA IPV perpetrators. Finally, the LA IPV perpetrators had significantly more impairments in working and long-term memory, executive functioning, and emotion decoding skills than controls, but they did not differ in processing speed, attentional set-shifting or switch attention, decision making, or perspective taking. Thus, the current findings suggest that IPV perpetrators with neuropsychological difficulties, especially those who are heavy drinkers, may have the greatest need for cognitive interventions. These cognitive deficits could be employed as targets for developing specific cognitive rehabilitation

  17. The importance of being subtle: small changes in calcium homeostasis control cognitive decline in normal aging

    Czech Academy of Sciences Publication Activity Database

    Toescu, E.C.; Verkhratsky, Alexei

    2007-01-01

    Roč. 6, - (2007), s. 267-273 ISSN 1474-9718 Institutional research plan: CEZ:AV0Z50390512 Keywords : Aging * Ca homeostasis * Cognitive decline Subject RIV: FH - Neurology Impact factor: 5.854, year: 2007

  18. On the Comparison of Cognitive Function in Substance Abusers and Addicts under Methadone Treatment with Normal Individuals

    Directory of Open Access Journals (Sweden)

    reza mohammadzadeghan

    2015-09-01

    Full Text Available Objective: This study was an attempt to compare cognitive functioning in substance abusers and addicts under methadone treatment with normal individuals. Method: The current study was a causal-comparative one. The statistical population of this research consisted of all male substance abusers who had referred to addiction treatment centers of Khoy city in 2013. The total of 40 addicts under methadone treatment, 40 active drug users, and 40 non-addicts were selected as the participants of this study via convenience sampling method. Wisconsin Card Sorting Test and Wechsler Memory Scale were administered to the three groups for data collection purposes. Results: The results showed that the substance abusers’ scores in Wisconsin card sorting test and Wechsler memory scale were significantly different from those of addicts under methadone treatment and normal individuals. In the same way, there was a significant difference between addicts under methadone treatment and normal individuals in terms of cognitive function however, there was no significant difference between these two groups in terms of perseveration error. Conclusion: It can be concluded that chronic use of psychoactive substances causes damage to multiple brain regions such as prefrontal cortex and hippocampus and, thereby, it leads to cognitive malfunctioning in these areas.

  19. Differentially Severe Cognitive Effects of Compromised Cerebral Blood Flow in Aged Mice: Association with Myelin Degradation and Microglia Activation

    Directory of Open Access Journals (Sweden)

    Gilly Wolf

    2017-06-01

    Full Text Available Bilateral common carotid artery stenosis (BCAS models the effects of compromised cerebral blood flow on brain structure and function in mice. We compared the effects of BCAS in aged (21 month and young adult (3 month female mice, anticipating a differentially more severe effect in the older mice. Four weeks after surgery there was a significant age by time by treatment interaction on the radial-arm water maze (RAWM; p = 0.014: on the first day of the test, latencies of old mice were longer compared to the latencies of young adult mice, independent of BCAS. However, on the second day of the test, latencies of old BCAS mice were significantly longer than old control mice (p = 0.049, while latencies of old controls were similar to those of the young adult mice, indicating more severe impairment of hippocampal dependent learning and working memory by BCAS in the older mice. Fluorescence staining of myelin basic protein (MBP showed that old age and BCAS both induced a significant decrease in fluorescence intensity. Evaluation of the number oligodendrocyte precursor cells demonstrated augmented myelin replacement in old BCAS mice (p < 0.05 compared with young adult BCAS and old control mice. While microglia morphology was assessed as normal in young adult control and young adult BCAS mice, microglia of old BCAS mice exhibited striking activation in the area of degraded myelin compared to young adult BCAS (p < 0.01 and old control mice (p < 0.05. These findings show a differentially more severe effect of cerebral hypoperfusion on cognitive function, myelin integrity and inflammatory processes in aged mice. Hypoperfusion may exacerbate degradation initiated by aging, which may induce more severe neuronal and cognitive phenotypes.

  20. Plasma polyunsaturated fatty acids are directly associated with cognition in overweight children but not in normal weight children.

    Science.gov (United States)

    Haapala, E A; Viitasalo, A; Venäläinen, T; Eloranta, A-M; Ågren, J; Lindi, V; Lakka, T A

    2016-12-01

    Polyunsaturated fatty acids are essential nutrients for the normal development of the brain. We investigated the associations between plasma polyunsaturated fatty acids and cognition in normal weight and overweight children. The study recruited 386 normal weight children and 58 overweight children aged six to eight years and blood samples were drawn after a 12-hour fast. We assessed plasma polyunsaturated fatty acids using gas chromatography, cognition using Raven's Coloured Progressive Matrices, and overweight and obesity using the age-specific and sex-specific cut-offs from the International Obesity Task Force. The data were analysed by linear regression analyses adjusted for age and sex. Higher proportions of eicosapentaenoic acid in plasma triacylglycerols (β = 0.311, p = 0.020, p = 0.029 for interaction) and docosahexaenoic acid in plasma triacylglycerols (β = 0.281, p = 0.038, p = 0.049 for interaction) were both associated with higher Raven's scores in overweight children but not in normal weight children. Higher eicosapentaenoic acid to arachidonic acid ratios in triacylglycerols (β = 0.317, p = 0.019) and phospholipids (β = 0.273, p = 0.046) were directly associated with the Raven's score in overweight children but not in normal weight children. These findings suggest that increasing the consumption of fish and other sources of eicosapentaenoic acid and docosahexaenoic acid may improve cognition among overweight children. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  1. Normal differential renal function does not indicate a normal kidney after partial ureteropelvic obstruction and subsequent relief in 2-week-old piglets

    Energy Technology Data Exchange (ETDEWEB)

    Dissing, Thomas H.; Mikkelsen, Mette Marie; Pedersen, Michael; Froekiaer, Joergen; Djurhuus, Jens Christian [University of Aarhus, Institute of Clinical Medicine, Aarhus (Denmark); Eskild-Jensen, Anni [Aarhus University Hospital, Department of Nuclear Medicine, Aarhus Sygehus, Aarhus (Denmark); Gordon, Isky [University College London, Institute of Child Health, London (United Kingdom); University College London, Radiology and Physics Unit, Institute of Child Health, London (United Kingdom)

    2008-09-15

    We investigated the functional consequences of relieving ureteric obstruction in young pigs with experimental hydronephrosis (HN) induced by partial unilateral ureteropelvic obstruction. Three groups of animals were followed from the age of 2 weeks to the age of 14 weeks: Eight animals had severe or grades 3-4 HN throughout the study. Six animals had relief of the obstruction after 4 weeks. Six animals received sham operations at both ages. Morphological and functional examinations were performed at age 6 weeks and again at age 14 weeks and consisted of magnetic resonance imaging (MRI), technetium-diethylenetriaminepentaaceticacid ({sup 99m}Tc-DTPA) renography, renal technetium-dimercaptosuccinicacid ({sup 99m}Tc-DMSA) scintigraphy, and glomerular filtration rate (GFR) measurement. After relief of the partial obstruction, there was reduction of the pelvic diameter and improvement of urinary drainage. Global and relative kidney function was not significantly affected by either obstruction or its relief. Renal {sup 99m}Tc-DMSA scintigraphy showed a change in both the appearance of the kidney and a change in the distribution within kidneys even after relief of obstruction. This study shows that partial ureteric obstruction in young pigs may be associated with little effect on global and differential kidney function. However, even after relief of HN, the distribution of {sup 99m}Tc-DMSA in the kidney remains abnormal suggesting that a normal differential renal function may not represent a normal kidney. (orig.)

  2. Differentiation of prostate cancer from normal prostate tissue in an animal model: conventional MRI and dynamic contrast-enhanced MRI

    International Nuclear Information System (INIS)

    Gemeinhardt, O.; Prochnow, D.; Taupitz, M.; Hamm, B.; Beyersdorff, D.; Luedemann, L.; Abramjuk, C.

    2005-01-01

    Purpose: to differentiate orthotopically implanted prostate cancer from normal prostate tissue using magnetic resonance imaging (MRI) and Gd-DTPA-BMA-enhanced dynamic MRI in the rat model. Material and methods: tumors were induced in 15 rats by orthotopic implantation of G subline Dunning rat prostatic tumor cells. MRI was performed 56 to 60 days after tumor cell implantation using T1-weighted spin-echo, T2-weighted turbo SE sequences, and a 2D FLASH sequence for the contrast medium based dynamic study. The interstitial leakage volume, normalized permeability and the permeability surface area product of tumor and healthy prostate were determined quantitatively using a pharmacokinetic model. The results were confirmed by histologic examination. Results: axial T2-weighted TSE images depicted low-intensity areas suspicious for tumor in all 15 animals. The mean tumor volume was 46.5 mm3. In the dynamic study, the suspicious areas in all animals displayed faster and more pronounced signal enhancement than surrounding prostate tissue. The interstitial volume and the permeability surface area product of the tumors increased significantly by 420% (p<0.001) and 424% (p<0.001), respectively, compared to normal prostate tissue, while no significant difference was seen for normalized permeability alone. Conclusion: the results of the present study demonstrate that quantitative analysis of contrast-enhanced dynamic MRI data enables differentiation of small, slowly growing orthotopic prostate cancer from normal prostate tissue in the rat model. (orig.)

  3. Profound Effect of Profiling Platform and Normalization Strategy on Detection of Differentially Expressed MicroRNAs – A Comparative Study

    Science.gov (United States)

    Meyer, Swanhild U.; Kaiser, Sebastian; Wagner, Carola; Thirion, Christian; Pfaffl, Michael W.

    2012-01-01

    Background Adequate normalization minimizes the effects of systematic technical variations and is a prerequisite for getting meaningful biological changes. However, there is inconsistency about miRNA normalization performances and recommendations. Thus, we investigated the impact of seven different normalization methods (reference gene index, global geometric mean, quantile, invariant selection, loess, loessM, and generalized procrustes analysis) on intra- and inter-platform performance of two distinct and commonly used miRNA profiling platforms. Methodology/Principal Findings We included data from miRNA profiling analyses derived from a hybridization-based platform (Agilent Technologies) and an RT-qPCR platform (Applied Biosystems). Furthermore, we validated a subset of miRNAs by individual RT-qPCR assays. Our analyses incorporated data from the effect of differentiation and tumor necrosis factor alpha treatment on primary human skeletal muscle cells and a murine skeletal muscle cell line. Distinct normalization methods differed in their impact on (i) standard deviations, (ii) the area under the receiver operating characteristic (ROC) curve, (iii) the similarity of differential expression. Loess, loessM, and quantile analysis were most effective in minimizing standard deviations on the Agilent and TLDA platform. Moreover, loess, loessM, invariant selection and generalized procrustes analysis increased the area under the ROC curve, a measure for the statistical performance of a test. The Jaccard index revealed that inter-platform concordance of differential expression tended to be increased by loess, loessM, quantile, and GPA normalization of AGL and TLDA data as well as RGI normalization of TLDA data. Conclusions/Significance We recommend the application of loess, or loessM, and GPA normalization for miRNA Agilent arrays and qPCR cards as these normalization approaches showed to (i) effectively reduce standard deviations, (ii) increase sensitivity and accuracy of

  4. Patterns of proliferation and differentiation of irradiated haemopoietic stem cells cultured on normal 'stromal' cell colonies in vitro

    International Nuclear Information System (INIS)

    Mori, K.J.

    1981-01-01

    Experiments were designed to elucidate whether or not the irradiated bone marrow cells receive any stimulation for the self-replication and differentiation from normal 'stromal' cell colonies in the bone marrow cell culture in vitro. When irradiated or unirradiated bone marrow cells were overlaid on the normal adherent cell colonies, the proliferation of haemopoietic stem cells was supported, the degree of the stimulation depending on the starting cellular concentration. There was, however, no significant changes in the concentration of either CFUs or CFUc regardless of the dose of irradiation on the bone marrow cells overlaid. This was a great contrast to the dose-dependent decrease of CFUs or CFUc within the culture in which both the stem cells and stromal cells were simultaneously irradiated. These results suggest that the balance of self-replication and differentiation of the haemopoietic stem cells is affected only when haemopoietic microenvironment is perturbed. (author)

  5. Confirmatory factor analysis reveals a latent cognitive structure common to bipolar disorder, schizophrenia, and normal controls.

    Science.gov (United States)

    Schretlen, David J; Peña, Javier; Aretouli, Eleni; Orue, Izaskun; Cascella, Nicola G; Pearlson, Godfrey D; Ojeda, Natalia

    2013-06-01

    We sought to determine whether a single hypothesized latent factor structure would characterize cognitive functioning in three distinct groups. We assessed 576 adults (340 community controls, 126 adults with bipolar disorder, and 110 adults with schizophrenia) using 15 measures derived from nine cognitive tests. Confirmatory factor analysis (CFA) was conducted to examine the fit of a hypothesized six-factor model. The hypothesized factors included attention, psychomotor speed, verbal memory, visual memory, ideational fluency, and executive functioning. The six-factor model provided an excellent fit for all three groups [for community controls, root mean square error of approximation (RMSEA) schizophrenia, RMSEA = 0.06 and CFI = 0.98]. Alternate models that combined fluency with processing speed or verbal and visual memory reduced the goodness of fit. Multi-group CFA results supported factor invariance across the three groups. Confirmatory factor analysis supported a single six-factor structure of cognitive functioning among patients with schizophrenia or bipolar disorder and community controls. While the three groups clearly differ in level of performance, they share a common underlying architecture of information processing abilities. These cognitive factors could provide useful targets for clinical trials of treatments that aim to enhance information processing in persons with neurological and neuropsychiatric disorders. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Changes of cognition and regional cerebral activity during acute hypoglycemia in normal subjects

    DEFF Research Database (Denmark)

    Bie-Olsen, Lise G; Kjaer, Troels W; Pedersen-Bjergaard, Ulrik

    2009-01-01

    cerebral blood flow (rCBF) as a marker of cerebral activity. Hypoglycemia was induced by intravenous insulin infusion in 19 healthy men performing two different cognitive tasks of varying complexity. The hypoglycemic stimulus [plasma glucose 2.2 mmol/liter (0.4)] produced a significant hormonal...

  7. Normal weight children have higher cognitive performance – Independent of physical activity, sleep, and diet

    DEFF Research Database (Denmark)

    Hjorth, Mads F.; Sørensen, Louise B.; Andersen, Rikke

    2016-01-01

    % of expected learning within one school year (P breakfast consumption, fewer sleep problems, higher CRF, less total physical activity, more sedentary time, and less light physical activity were associated with higher cognitive performance independently of each other in at least one of the three...

  8. Addenbrooke's Cognitive Examination (ACE) for the diagnosis and differential diagnosis of dementia.

    Science.gov (United States)

    Larner, A J

    2007-07-01

    The Addenbrooke's Cognitive Examination (ACE) is reported to be a highly sensitive and specific "bedside" test for the diagnosis of dementia, but large pragmatic studies of its use in day-to-day clinical practice are lacking. This study measured diagnostic accuracy of ACE in a large cohort of consecutive patients referred to a dedicated Cognitive Function Clinic. Consecutive new referrals over a 3.5-year period were administered the ACE (n=285). ACE scores and subscores (VLOM ratio) were compared to clinical diagnoses of dementia and dementia subtype, established on the basis of widely accepted diagnostic criteria and at least 12-month follow-up. ACE had good sensitivity, specificity, and positive predictive value for the diagnosis of dementia, with excellent diagnostic accuracy as measured by area under the receiver operating characteristic curve. However, a lower cutoff than that used in the index paper was required for optimum test sensitivity and specificity. ACE VLOM ratio subscore for the differential diagnosis of Alzheimer's disease and frontotemporal dementia proved less accurate. This study suggests that ACE is useful for the diagnosis of dementia in routine clinical practice but that other instruments may be required for the differential diagnosis of the dementia syndrome.

  9. Autobiographical memory for the differential diagnosis of cognitive pathology in aging.

    Science.gov (United States)

    Meléndez, Juan C; Redondo, Rita; Torres, Marta; Mayordomo, Teresa; Sales, Alicia

    2016-11-01

    The present study distinguishes three memory stages across the lifespan, and aims to compare episodic and semantic autobiographical memory in healthy older adults, with amnesic mild cognitive impairment, and with Alzheimer's disease. This information can offer evidence about the way semantic and episodic autobiographical memory work, and how the disease affects them. The sample was composed of 56 people, all aged over 60 years; 15 with amnestic mild cognitive impairment, 12 with Alzheimer's disease and 29 healthy older people. Participants were evaluated with the Autobiographical Memory Interview. A mixed anova showed significant main effects of memory and time-period, and significant interactions of memory × group, time-period × group and memory × time × group. Assessment of autobiographical memory provides information to differentiate amnestic mild cognitive impairment patients from Alzheimer's disease patients. Although the decline in episodic memory starts with the onset of the disease, semantic memory is maintained until moderate stages of dementia. Geriatr Gerontol Int 2016; 16:1220-1225. © 2015 Japan Geriatrics Society.

  10. Differential impairments underlying decision making in anorexia nervosa and bulimia nervosa: a cognitive modeling analysis.

    Science.gov (United States)

    Chan, Trista Wai Sze; Ahn, Woo-Young; Bates, John E; Busemeyer, Jerome R; Guillaume, Sebastien; Redgrave, Graham W; Danner, Unna N; Courtet, Philippe

    2014-03-01

    This study examined the underlying processes of decision-making impairments in individuals with anorexia nervosa (AN) and bulimia nervosa (BN). We deconstructed their performance on the widely used decision task, the Iowa Gambling Task (IGT) into cognitive, motivational, and response processes using cognitive modeling analysis. We hypothesized that IGT performance would be characterized by impaired memory functions and heightened punishment sensitivity in AN, and by elevated sensitivity to reward as opposed to punishment in BN. We analyzed trial-by-trial data of IGT obtained from 224 individuals: 94 individuals with AN, 63 with BN, and 67 healthy comparison individuals (HC). The prospect valence learning model was used to assess cognitive, motivational, and response processes underlying IGT performance. Individuals with AN showed marginally impaired IGT performance compared to HC. Their performance was characterized by impairments in memory functions. Individuals with BN showed significantly impaired IGT performance compared to HC. They showed greater relative sensitivity to gains as opposed to losses than HC. Memory functions in AN were positively correlated with body mass index. This study identified differential impairments underlying IGT performance in AN and BN. Findings suggest that impaired decision making in AN might involve impaired memory functions. Impaired decision making in BN might involve altered reward and punishment sensitivity. Copyright © 2013 Wiley Periodicals, Inc.

  11. Site-Specific Differentiation of Fibroblasts in Normal and Scleroderma Skin

    National Research Council Canada - National Science Library

    Chang, Howard Y

    2008-01-01

    The results from year I of funding suggest that appropriate markers and technologies are in place for systematic investigation of the positional identity of fibroblasts both in normal and diseased tissues...

  12. The Addenbrooke's Cognitive Examination for the differential diagnosis and longitudinal assessment of patients with parkinsonian disorders.

    Science.gov (United States)

    Rittman, Timothy; Ghosh, Boyd C; McColgan, Peter; Breen, David P; Evans, Jonathan; Williams-Gray, Caroline H; Barker, Roger A; Rowe, James B

    2013-05-01

    Differentiating idiopathic Parkinson's disease from atypical parkinsonian syndromes is challenging, especially in the early stages. We assessed whether the Revised Addenbrooke's Cognitive Examination (ACE-R) could differentiate between parkinsonian syndromes and reflect longitudinal changes in cognition in these disorders. The ACE-R was administered at baseline and after approximately 18 months to 135 patients with parkinsonian disorders: 86 with idiopathic Parkinson's disease (PD), 30 with progressive supranuclear palsy (PSP), 19 with corticobasal degeneration (CBD). We assessed differences between groups for ACE-R, ACE-R subscores and Mini Mental State Examination (MMSE) scores at baseline (analyses of variance, receiver operating characteristics curves), and the interaction between diagnosis and change in ACE-R scores between visits (analyses of variance). The ACE-R verbal fluency subscore distinguished between PSP and PD with a high sensitivity (0.92) and specificity (0.87); total ACE-R score and the visuospatial subscore were less specific (0.87 and 0.84 respectively) and sensitive (0.70 and 0.73). Significant group level differences were found between PD and PSP for MMSE and ACE-R (total score and subscores for attention and concentration, fluency, language, and visuospatial function), and between PD and CBD for the ACE-R visuospatial subscore. Performance worsened between visits for ACE-R score in PD (p=0.001) and CBD (p=0.001); visuospatial subscore in PD (p=0.003), PSP (p=0.022) and CBD (p=0.0002); and MMSE in CBD (p=0.004). We propose the ACE-R, particularly the verbal fluency subscore, as a valuable contributor to the differential diagnosis of parkinsonian syndromes in the correct clinical context. The ACE-R may reflect disease progression in PD and CBD.

  13. Differentiation between mild cognitive impairment, Alzheimer's disease and depression by means of cued recall.

    Science.gov (United States)

    Dierckx, E; Engelborghs, S; De Raedt, R; De Deyn, P P; Ponjaert-Kristoffersen, I

    2007-05-01

    Discriminating Alzheimer's disease (AD) and mild cognitive impairment (MCI) from depression is a challenge in psychogeriatric medicine. A study was set up to ascertain whether cued recall could be useful in differentiating early AD and MCI from depression among elderly individuals. The Visual Association Test (VAT) and the Memory Impairment Screen-plus (MIS-plus) were administered together with the Mini-Mental State Examination (MMSE) and the Geriatric Depression Scale (GDS) to 40 MCI patients, 35 mild AD patients, 46 depressed patients and 52 healthy control subjects. A one-way analysis of variance (ANOVA) followed by post-hoc Scheffé tests showed that AD patients had significantly lower cued recall scores (i.e. combined VAT and MIS-plus scores) than MCI patients, who in turn had lower scores than depressed patients. The scores of depressed patients and controls were not significantly different. Discriminant analysis revealed that 94% of the AD patients and 96% of the depressed patients could be classified correctly by means of the GDS and the cued recall sores. Receiver operating characteristic (ROC) curves identified an optimal cut-off score of 8 (maximum score 12) for differentiating AD and MCI patients from depressed elderly patients and controls. Applying this cut-off, a sensitivity of 83% (58%) and a specificity of 85% (85%) was obtained when differentiating AD (MCI) from depression. Cued recall, operationalized by the combined scores of VAT and MIS-plus, is a useful method for differentiating AD patients from depressed individuals and healthy controls. Probably because of the great heterogeneity among MCI patients, the diagnostic power of cued recall decreases when applied to differentiate MCI from depression.

  14. 18F-FDG PET in Parkinsonism: Differential Diagnosis and Evaluation of Cognitive Impairment.

    Science.gov (United States)

    Meyer, Philipp T; Frings, Lars; Rücker, Gerta; Hellwig, Sabine

    2017-12-01

    Accurate differential diagnosis of parkinsonism is of paramount therapeutic and prognostic importance. In addition, with the development of invasive therapies and novel disease-specific therapies, strategies for patient enrichment in trial populations are of growing importance. Imaging disease-specific patterns of regional glucose metabolism with PET and 18 F-FDG allows for a highly accurate distinction between Parkinson disease (PD) and atypical parkinsonian syndromes, including multiple-system atrophy, progressive supranuclear palsy, and corticobasal degeneration. On the basis of a preliminary metaanalysis of currently available studies with inclusion of multiple disease groups, we estimated that the diagnostic sensitivity and specificity for visual PET readings supported by voxel-based statistical analyses for diagnosis of atypical parkinsonian syndromes are 91.4% and 90.6%, respectively. The diagnostic specificity of 18 F-FDG PET for diagnosing multiple-system atrophy, progressive supranuclear palsy, and corticobasal degeneration was consistently shown to be high (>90%), whereas sensitivity was more variable (>75%). It is increasingly acknowledged that cognitive impairment represents a major challenge in PD, with mild cognitive impairment being a prodromal stage of PD with dementia (PDD). In line with clinical and neuropsychologic studies, recent PET studies demonstrated that posterior cortical dysfunction in nondemented PD patients precedes cognitive decline and the development of PDD by several years. Taken together, the current literature underscores the utility of 18 F-FDG PET for diagnostic evaluation of parkinsonism and the promising role of 18 F-FDG PET for assessment and risk stratification of cognitive impairment in PD. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

  15. A score based on screening tests to differentiate mild cognitive impairment from subjective memory complaints

    Directory of Open Access Journals (Sweden)

    Fábio Henrique de Gobbi Porto

    2013-09-01

    Full Text Available It is not easy to differentiate patients with mild cognitive impairment (MCI from subjective memory complainers (SMC. Assessments with screening cognitive tools are essential, particularly in primary care where most patients are seen. The objective of this study was to evaluate the diagnostic accuracy of screening cognitive tests and to propose a score derived from screening tests. Elderly subjects with memory complaints were evaluated using the Mini Mental State Examination (MMSE and the Brief Cognitive Battery (BCB. We added two delayed recalls in the MMSE (a delayed recall and a late-delayed recall, LDR, and also a phonemic fluency test of letter P fluency (LPF. A score was created based on these tests. The diagnoses were made on the basis of clinical consensus and neuropsychological testing. Receiver operating characteristic curve analyses were used to determine area under the curve (AUC, the sensitivity and specificity for each test separately and for the final proposed score. MMSE, LDR, LPF and delayed recall of BCB scores reach statistically significant differences between groups (P=0.000, 0.03, 0.001 and 0.01, respectively. Sensitivity, specificity and AUC were MMSE: 64%, 79% and 0.75 (cut off <29; LDR: 56%, 62% and 0.62 (cut off <3; LPF: 71%, 71% and 0.71 (cut off <14; delayed recall of BCB: 56%, 82% and 0.68 (cut off <9. The proposed score reached a sensitivity of 88% and 76% and specificity of 62% and 75% for cut off over 1 and over 2, respectively. AUC were 0.81. In conclusion, a score created from screening tests is capable of discriminating MCI from SMC with moderate to good accurancy.

  16. White matter correlates of cognitive domains in normal aging with diffusion tensor imaging

    Directory of Open Access Journals (Sweden)

    Efrat eSasson

    2013-03-01

    Full Text Available The ability to perform complex as well as simple cognitive tasks engages a network of brain regions that is mediated by the white matter fiber bundles connecting them. Different cognitive tasks employ distinctive white matter fiber bundles. The temporal lobe and its projections subserve a variety of key functions known to deteriorate during aging. In a cohort of 52 healthy subjects (ages 25-82 years, we performed voxel-wise regression analysis correlating performance in higher-order cognitive domains (executive function, information processing speed, and memory with white matter integrity, as measured by diffusion tensor imaging (DTI fiber tracking in the temporal lobe projections (uncinate fasciculus (UF, fornix, cingulum, inferior longitudinal fasciculus (ILF, and superior longitudinal fasciculus (SLF. The fiber tracts were spatially registered and statistical parametric maps were produced to spatially localize the significant correlations. Results showed that performance in the executive function domain is correlated with DTI parameters in the left SLF and right UF; performance in the information processing speed domain is correlated with fractional anisotropy (FA in the left cingulum, left fornix, right and left ILF and SLF; and the memory domain shows significant correlations with DTI parameters in the right fornix, right cingulum, left ILF, left SLF and right UF. These findings suggest that DTI tractography enables anatomical definition of region of interest for correlation of behavioral parameters with diffusion indices, and functionality can be correlated with white matter integrity.

  17. Differentiation of purified malignant B cells induced by PMA or by activated normal T cells

    NARCIS (Netherlands)

    van Kooten, C.; Rensink, I.; Aarden, L.; van Oers, R.

    1993-01-01

    We studied the in vitro differentiation (immunoglobulin production) of purified malignant B cells of 21 patients with different B-cell malignancies, including chronic lymphocytic leukemia (CLL), prolymphocytic leukemia (PLL), hairy cell leukemia (HCL) and non-Hodgkin lymphoma (NHL). Direct

  18. Site-Specific Differentiation of Fibroblasts in Normal and Scleroderma Skin

    Science.gov (United States)

    2009-06-01

    the accordance in the structure and growth of animals and plants . London: The Syden- ham Society, 1–268 Sessa L, Breiling A, Lavorgna G, Silvestri L...targets. Heredity 97:88–96 Wolpert L (1969) Positional information and the spatial pattern of cellular differentiation. J Theor Biol 25:1–47 Yamaguchi Y

  19. Mild cognitive disorders are associated with different patterns of brain asymmetry than normal ageing: the PATH through life study

    Directory of Open Access Journals (Sweden)

    Nicolas Cherbuin

    2010-05-01

    Full Text Available Background and Purpose: Defining how brain structures differ in pre-clinical dementia is important to better understand the pathological processes involved and to inform clinical practice. The aim of this study was to identify significant brain correlates (volume and asymmetry in volume of mild cognitive disorders when compared to normal controls in a large community-based sample of young-old individuals who were assessed for cognitive impairment. Methods: Cortical and sub-cortical volumes were measured using a semi-automated method in 398 participants aged 65-70 years who were selected from a larger randomly sampled cohort and who agreed to undergo an MRI scan. Diagnoses were reached based on established protocols for MCI and a more inclusive category of any Mild Cognitive Disorder (any-MCD: which includes AAMI, AACD, OCD, MNC, CDR, MCI. Logistic regression analyses were used to assess the relationship between volume and asymmetry of theoretically relevant cerebral structures (predictors and MCI or any-MCD while controlling for age, sex, and intra-cranial volume. Results: The main correlates of cognitive impairment assessed in multivariate analyses were hippocampal asymmetry (more to left, MCI: OR 0.83, 95%CI 0.71-0.96, p = .013; MCD: OR 0.86, 95%CI 0.77-0.97, p = .011, lateral ventricle asymmetry (more to left, MCI: OR 0.95, 95%CI 0.91-0.99, p = .009; MCD: OR 0.95, 95%CI 0.92-0.98, p = .004, and cerebellar cortex asymmetry (more to left, MCI: OR 1.51, 95%CI 1.13-2.01, p = .005. Conclusions: In this population-based cohort stronger associations were found between asymmetry measures, rather than raw volumes in cerebral structures, and mild cognitive disorders.

  20. Patterns of brain structural connectivity differentiate normal weight from overweight subjects.

    Science.gov (United States)

    Gupta, Arpana; Mayer, Emeran A; Sanmiguel, Claudia P; Van Horn, John D; Woodworth, Davis; Ellingson, Benjamin M; Fling, Connor; Love, Aubrey; Tillisch, Kirsten; Labus, Jennifer S

    2015-01-01

    Alterations in the hedonic component of ingestive behaviors have been implicated as a possible risk factor in the pathophysiology of overweight and obese individuals. Neuroimaging evidence from individuals with increasing body mass index suggests structural, functional, and neurochemical alterations in the extended reward network and associated networks. To apply a multivariate pattern analysis to distinguish normal weight and overweight subjects based on gray and white-matter measurements. Structural images (N = 120, overweight N = 63) and diffusion tensor images (DTI) (N = 60, overweight N = 30) were obtained from healthy control subjects. For the total sample the mean age for the overweight group (females = 32, males = 31) was 28.77 years (SD = 9.76) and for the normal weight group (females = 32, males = 25) was 27.13 years (SD = 9.62). Regional segmentation and parcellation of the brain images was performed using Freesurfer. Deterministic tractography was performed to measure the normalized fiber density between regions. A multivariate pattern analysis approach was used to examine whether brain measures can distinguish overweight from normal weight individuals. 1. White-matter classification: The classification algorithm, based on 2 signatures with 17 regional connections, achieved 97% accuracy in discriminating overweight individuals from normal weight individuals. For both brain signatures, greater connectivity as indexed by increased fiber density was observed in overweight compared to normal weight between the reward network regions and regions of the executive control, emotional arousal, and somatosensory networks. In contrast, the opposite pattern (decreased fiber density) was found between ventromedial prefrontal cortex and the anterior insula, and between thalamus and executive control network regions. 2. Gray-matter classification: The classification algorithm, based on 2 signatures with 42 morphological features, achieved 69

  1. Patterns of brain structural connectivity differentiate normal weight from overweight subjects

    Science.gov (United States)

    Gupta, Arpana; Mayer, Emeran A.; Sanmiguel, Claudia P.; Van Horn, John D.; Woodworth, Davis; Ellingson, Benjamin M.; Fling, Connor; Love, Aubrey; Tillisch, Kirsten; Labus, Jennifer S.

    2015-01-01

    Background Alterations in the hedonic component of ingestive behaviors have been implicated as a possible risk factor in the pathophysiology of overweight and obese individuals. Neuroimaging evidence from individuals with increasing body mass index suggests structural, functional, and neurochemical alterations in the extended reward network and associated networks. Aim To apply a multivariate pattern analysis to distinguish normal weight and overweight subjects based on gray and white-matter measurements. Methods Structural images (N = 120, overweight N = 63) and diffusion tensor images (DTI) (N = 60, overweight N = 30) were obtained from healthy control subjects. For the total sample the mean age for the overweight group (females = 32, males = 31) was 28.77 years (SD = 9.76) and for the normal weight group (females = 32, males = 25) was 27.13 years (SD = 9.62). Regional segmentation and parcellation of the brain images was performed using Freesurfer. Deterministic tractography was performed to measure the normalized fiber density between regions. A multivariate pattern analysis approach was used to examine whether brain measures can distinguish overweight from normal weight individuals. Results 1. White-matter classification: The classification algorithm, based on 2 signatures with 17 regional connections, achieved 97% accuracy in discriminating overweight individuals from normal weight individuals. For both brain signatures, greater connectivity as indexed by increased fiber density was observed in overweight compared to normal weight between the reward network regions and regions of the executive control, emotional arousal, and somatosensory networks. In contrast, the opposite pattern (decreased fiber density) was found between ventromedial prefrontal cortex and the anterior insula, and between thalamus and executive control network regions. 2. Gray-matter classification: The classification algorithm, based on 2 signatures with 42

  2. Smart Aging Platform for Evaluating Cognitive Functions in Aging: A Comparison with the MoCA in a Normal Population

    Directory of Open Access Journals (Sweden)

    Sara Bottiroli

    2017-11-01

    Full Text Available Background: Smart Aging is a Serious games (SGs platform in a 3D virtual environment in which users perform a set of screening tests that address various cognitive skills. The tests are structured as 5 tasks of activities of daily life in a familiar environment. The main goal of the present study is to compare a cognitive evaluation made with Smart Aging with those of a classic standardized screening test, the Montreal Cognitive Assessment (MoCA.Methods: One thousand one-hundred thirty-one healthy adults aged between 50 and 80 (M = 64.3 ± 8.3 were enrolled in the study. They received a cognitive evaluation with the MoCA and the Smart Aging platform. Participants were grouped according to their MoCA global and specific cognitive domain (i.e., memory, executive functions, working memory, visual spatial elaboration, language, and orientation scores and we explored differences among these groups in the Smart Aging indices.Results: One thousand eighty-six older adults (M = 64.0 ± 8.0 successfully completed the study and were stratified according to their MoCA score: Group 1 with MoCA < 27 (n = 360; Group 2 with 27 ≥ MoCA < 29 (n = 453; and Group 3 with MoCA ≥ 29 (n = 273. MoCA groups significantly differed in most of the Smart Aging indices considered, in particular as concerns accuracy (ps < 0.001 and time (ps < 0.001 for completing most of the platform tasks. Group 1 was outperformed by the other two Groups and was slower than them in these tasks, which were those supposed to assess memory and executive functions. In addition, significant differences across groups also emerged when considering the single cognitive domains of the MoCA and the corresponding performances in each Smart Aging task. In particular, this platform seems to be a good proxy for assessing memory, executive functions, working memory, and visual spatial processes.Conclusion: These findings demonstrate the validity of Smart Aging for assessing cognitive functions in normal

  3. Comparing the normalization methods for the differential analysis of Illumina high-throughput RNA-Seq data.

    Science.gov (United States)

    Li, Peipei; Piao, Yongjun; Shon, Ho Sun; Ryu, Keun Ho

    2015-10-28

    , Med, TMM, DESeq, and Q did not noticeably improve gene expression normalization, regardless of read length. Other normalization methods were more efficient when alignment accuracy was low; Sailfish with RPKM gave the best normalization results. When alignment accuracy was high, RC was sufficient for gene expression calculation. And we suggest ignoring poly-A tail during differential gene expression analysis.

  4. Differential geometry of CR-submanifolds of a normal almost para contact manifold

    International Nuclear Information System (INIS)

    Shahid, M.H.

    1992-12-01

    The aim of this paper is to study the geometry of CR-submanifolds of a normal almost para contact manifold. We discuss the integrability conditions of distributions involved in the definition and geometry of leaves of CR-submanifolds, some results on CR-submanifolds with parallel structures and contact CR-product are also given. (author). 10 refs

  5. Cognitive Machine-Learning Algorithm for Cardiac Imaging: A Pilot Study for Differentiating Constrictive Pericarditis From Restrictive Cardiomyopathy.

    Science.gov (United States)

    Sengupta, Partho P; Huang, Yen-Min; Bansal, Manish; Ashrafi, Ali; Fisher, Matt; Shameer, Khader; Gall, Walt; Dudley, Joel T

    2016-06-01

    Associating a patient's profile with the memories of prototypical patients built through previous repeat clinical experience is a key process in clinical judgment. We hypothesized that a similar process using a cognitive computing tool would be well suited for learning and recalling multidimensional attributes of speckle tracking echocardiography data sets derived from patients with known constrictive pericarditis and restrictive cardiomyopathy. Clinical and echocardiographic data of 50 patients with constrictive pericarditis and 44 with restrictive cardiomyopathy were used for developing an associative memory classifier-based machine-learning algorithm. The speckle tracking echocardiography data were normalized in reference to 47 controls with no structural heart disease, and the diagnostic area under the receiver operating characteristic curve of the associative memory classifier was evaluated for differentiating constrictive pericarditis from restrictive cardiomyopathy. Using only speckle tracking echocardiography variables, associative memory classifier achieved a diagnostic area under the curve of 89.2%, which improved to 96.2% with addition of 4 echocardiographic variables. In comparison, the area under the curve of early diastolic mitral annular velocity and left ventricular longitudinal strain were 82.1% and 63.7%, respectively. Furthermore, the associative memory classifier demonstrated greater accuracy and shorter learning curves than other machine-learning approaches, with accuracy asymptotically approaching 90% after a training fraction of 0.3 and remaining flat at higher training fractions. This study demonstrates feasibility of a cognitive machine-learning approach for learning and recalling patterns observed during echocardiographic evaluations. Incorporation of machine-learning algorithms in cardiac imaging may aid standardized assessments and support the quality of interpretations, particularly for novice readers with limited experience. © 2016

  6. A Cognitive Machine Learning Algorithm for Cardiac Imaging: A Pilot Study for Differentiating Constrictive Pericarditis from Restrictive Cardiomyopathy

    Science.gov (United States)

    Sengupta, Partho P.; Huang, Yen-Min; Bansal, Manish; Ashrafi, Ali; Fisher, Matt; Shameer, Khader; Gall, Walt; Dudley, Joel T

    2016-01-01

    Background Associating a patient’s profile with the memories of prototypical patients built through previous repeat clinical experience is a key process in clinical judgment. We hypothesized that a similar process using a cognitive computing tool would be well suited for learning and recalling multidimensional attributes of speckle tracking echocardiography (STE) data sets derived from patients with known constrictive pericarditis (CP) and restrictive cardiomyopathy (RCM). Methods and Results Clinical and echocardiographic data of 50 patients with CP and 44 with RCM were used for developing an associative memory classifier (AMC) based machine learning algorithm. The STE data was normalized in reference to 47 controls with no structural heart disease, and the diagnostic area under the receiver operating characteristic curve (AUC) of the AMC was evaluated for differentiating CP from RCM. Using only STE variables, AMC achieved a diagnostic AUC of 89·2%, which improved to 96·2% with addition of 4 echocardiographic variables. In comparison, the AUC of early diastolic mitral annular velocity and left ventricular longitudinal strain were 82.1% and 63·7%, respectively. Furthermore, AMC demonstrated greater accuracy and shorter learning curves than other machine learning approaches with accuracy asymptotically approaching 90% after a training fraction of 0·3 and remaining flat at higher training fractions. Conclusions This study demonstrates feasibility of a cognitive machine learning approach for learning and recalling patterns observed during echocardiographic evaluations. Incorporation of machine learning algorithms in cardiac imaging may aid standardized assessments and support the quality of interpretations, particularly for novice readers with limited experience. PMID:27266599

  7. Gray matter network disruptions and amyloid beta in cognitively normal adults.

    Science.gov (United States)

    Tijms, Betty M; Kate, Mara Ten; Wink, Alle Meije; Visser, Pieter Jelle; Ecay, Mirian; Clerigue, Montserrat; Estanga, Ainara; Garcia Sebastian, Maite; Izagirre, Andrea; Villanua, Jorge; Martinez Lage, Pablo; van der Flier, Wiesje M; Scheltens, Philip; Sanz Arigita, Ernesto; Barkhof, Frederik

    2016-01-01

    Gray matter networks are disrupted in Alzheimer's disease (AD). It is unclear when these disruptions start during the development of AD. Amyloid beta 1-42 (Aβ42) is among the earliest changes in AD. We studied, in cognitively healthy adults, the relationship between Aβ42 levels in cerebrospinal fluid (CSF) and single-subject cortical gray matter network measures. Single-subject gray matter networks were extracted from structural magnetic resonance imaging scans in a sample of cognitively healthy adults (N = 185; age range 39-79, mini-mental state examination >25, N = 12 showed abnormal Aβ42 level and for 90 anatomical areas. Associations between continuous Aβ42 CSF levels and single-subject cortical gray matter network measures were tested. Smoothing splines were used to determine whether a linear or nonlinear relationship gave a better fit to the data. Lower Aβ42 CSF levels were linearly associated at whole brain level with lower connectivity density, and nonlinearly with lower clustering values and higher path length values, which is indicative of a less-efficient network organization. These relationships were specific to medial temporal areas, precuneus, and the middle frontal gyrus (all p levels can be related to gray matter networks disruptions. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Cognitive skills and the effect of noise on perceived effort in employees with aided hearing impairment and normal hearing

    Directory of Open Access Journals (Sweden)

    Håkan Hua

    2014-01-01

    Full Text Available The aim of the following study was to examine the relationship between working memory capacity (WMC, executive functions (EFs and perceived effort (PE after completing a work-related task in quiet and in noise in employees with aided hearing impairment (HI and normal hearing. The study sample consisted of 20 hearing-impaired and 20 normally hearing participants. Measures of hearing ability, WMC and EFs were tested prior to performing a work-related task in quiet and in simulated traffic noise. PE of the work-related task was also measured. Analysis of variance was used to analyze within- and between-group differences in cognitive skills, performance on the work-related task and PE. The presence of noise yielded a significantly higher PE for both groups. However, no significant group differences were observed in WMC, EFs, PE and performance in the work-related task. Interestingly, significant negative correlations were only found between PE in the noise condition and the ability to update information for both groups. In summary, noise generates a significantly higher PE and brings explicit processing capacity into play, irrespective of hearing. This suggest that increased PE involves other factors such as type of task that is to be performed, performance in the cognitive skill required solving the task at hand and whether noise is present. We therefore suggest that special consideration in hearing care should be made to the individual′s prerequisites on these factors in the labor market.

  9. Differentiation in boron distribution in adult male and female rats' normal brain: A BNCT approach

    International Nuclear Information System (INIS)

    Goodarzi, Samereh; Pazirandeh, Ali; Jameie, Seyed Behnamedin; Baghban Khojasteh, Nasrin

    2012-01-01

    Boron distribution in adult male and female rats' normal brain after boron carrier injection (0.005 g Boric Acid+0.005 g Borax+10 ml distilled water, pH: 7.4) was studied in this research. Coronal sections of control and trial animal tissue samples were irradiated with thermal neutrons. Using alpha autoradiography, significant differences in boron concentration were seen in forebrain, midbrain and hindbrain sections of male and female animal groups with the highest value, four hours after boron compound injection. - Highlights: ► Boron distribution in male and female rats' normal brain was studied in this research. ► Coronal sections of animal tissue samples were irradiated with thermal neutrons. ► Alpha and Lithium tracks were counted using alpha autoradiography. ► Different boron concentration was seen in brain sections of male and female rats. ► The highest boron concentration was seen in 4 h after boron compound injection.

  10. Differential Expression of Cytochrome P450 Enzymes in Normal and Tumor Tissues from Childhood Rhabdomyosarcoma

    Science.gov (United States)

    Molina-Ortiz, Dora; Camacho-Carranza, Rafael; González-Zamora, José Francisco; Shalkow-Kalincovstein, Jaime; Cárdenas-Cardós, Rocío; Ností-Palacios, Rosario; Vences-Mejía, Araceli

    2014-01-01

    Intratumoral expression of genes encoding Cytochrome P450 enzymes (CYP) might play a critical role not only in cancer development but also in the metabolism of anticancer drugs. The purpose of this study was to compare the mRNA expression patterns of seven representative CYPs in paired tumor and normal tissue of child patients with rabdomyosarcoma (RMS). Using real time quantitative RT-PCR, the gene expression pattern of CYP1A1, CYP1A2, CYP1B1, CYP2E1, CYP2W1, CYP3A4, and CYP3A5 were analyzed in tumor and adjacent non-tumor tissues from 13 child RMS patients. Protein concentration of CYPs was determined using Western blot. The expression levels were tested for correlation with the clinical and pathological data of the patients. Our data showed that the expression levels of CYP1A1 and CYP1A2 were negligible. Elevated expression of CYP1B1 mRNA and protein was detected in most RMS tumors and adjacent normal tissues. Most cancerous samples exhibit higher levels of both CYP3A4 and CYP3A5 compared with normal tissue samples. Expression of CYP2E1 mRNA was found to be significantly higher in tumor tissue, however no relation was found with protein levels. CYP2W1 mRNA and/or protein are mainly expressed in tumors. In conclusion, we defined the CYP gene expression profile in tumor and paired normal tissue of child patients with RMS. The overexpression of CYP2W1, CYP3A4 and CYP3A5 in tumor tissues suggests that they may be involved in RMS chemoresistance; furthermore, they may be exploited for the localized activation of anticancer prodrugs. PMID:24699256

  11. Cognitive impairments in patients with intractable temporal lobe epilepsy

    Directory of Open Access Journals (Sweden)

    Mahgol Tavakoli

    2011-01-01

    Conclusions: These findings indicated that WMS-III and WAIS-R can differentiate patients with refractory temporal lobe epilepsy from normal subjects. However, the obtained cognitive profile could not differentiate between the right and the left TLE.

  12. GC-MS-Based Endometabolome Analysis Differentiates Prostate Cancer from Normal Prostate Cells

    Directory of Open Access Journals (Sweden)

    Ana Rita Lima

    2018-03-01

    Full Text Available Prostate cancer (PCa is an important health problem worldwide. Diagnosis and management of PCa is very complex because the detection of serum prostate specific antigen (PSA has several drawbacks. Metabolomics brings promise for cancer biomarker discovery and for better understanding PCa biochemistry. In this study, a gas chromatography–mass spectrometry (GC-MS based metabolomic profiling of PCa cell lines was performed. The cell lines include 22RV1 and LNCaP from PCa with androgen receptor (AR expression, DU145 and PC3 (which lack AR expression, and one normal prostate cell line (PNT2. Regarding the metastatic potential, PC3 is from an adenocarcinoma grade IV with high metastatic potential, DU145 has a moderate metastatic potential, and LNCaP has a low metastatic potential. Using multivariate analysis, alterations in levels of several intracellular metabolites were detected, disclosing the capability of the endometabolome to discriminate all PCa cell lines from the normal prostate cell line. Discriminant metabolites included amino acids, fatty acids, steroids, and sugars. Six stood out for the separation of all the studied PCa cell lines from the normal prostate cell line: ethanolamine, lactic acid, β-Alanine, L-valine, L-leucine, and L-tyrosine.

  13. Cortical Amyloid Beta in Cognitively Normal Elderly Adults is Associated with Decreased Network Efficiency within the Cerebro-Cerebellar System.

    Science.gov (United States)

    Steininger, Stefanie C; Liu, Xinyang; Gietl, Anton; Wyss, Michael; Schreiner, Simon; Gruber, Esmeralda; Treyer, Valerie; Kälin, Andrea; Leh, Sandra; Buck, Alfred; Nitsch, Roger M; Prüssmann, Klaas P; Hock, Christoph; Unschuld, Paul G

    2014-01-01

    Deposition of cortical amyloid beta (Aβ) is a correlate of aging and a risk factor for Alzheimer disease (AD). While several higher order cognitive processes involve functional interactions between cortex and cerebellum, this study aims to investigate effects of cortical Aβ deposition on coupling within the cerebro-cerebellar system. We included 15 healthy elderly subjects with normal cognitive performance as assessed by neuropsychological testing. Cortical Aβ was quantified using (11)carbon-labeled Pittsburgh compound B positron-emission-tomography late frame signals. Volumes of brain structures were assessed by applying an automated parcelation algorithm to three dimensional magnetization-prepared rapid gradient-echo T1-weighted images. Basal functional network activity within the cerebro-cerebellar system was assessed using blood-oxygen-level dependent resting state functional magnetic resonance imaging at the high field strength of 7 T for measuring coupling between cerebellar seeds and cerebral gray matter. A bivariate regression approach was applied for identification of brain regions with significant effects of individual cortical Aβ load on coupling. Consistent with earlier reports, a significant degree of positive and negative coupling could be observed between cerebellar seeds and cerebral voxels. Significant positive effects of cortical Aβ load on cerebro-cerebellar coupling resulted for cerebral brain regions located in inferior temporal lobe, prefrontal cortex, hippocampus, parahippocampal gyrus, and thalamus. Our findings indicate that brain amyloidosis in cognitively normal elderly subjects is associated with decreased network efficiency within the cerebro-cerebellar system. While the identified cerebral regions are consistent with established patterns of increased sensitivity for Aβ-associated neurodegeneration, additional studies are needed to elucidate the relationship between dysfunction of the cerebro-cerebellar system and risk for AD.

  14. First-order systems of linear partial differential equations: normal forms, canonical systems, transform methods

    Directory of Open Access Journals (Sweden)

    Heinz Toparkus

    2014-04-01

    Full Text Available In this paper we consider first-order systems with constant coefficients for two real-valued functions of two real variables. This is both a problem in itself, as well as an alternative view of the classical linear partial differential equations of second order with constant coefficients. The classification of the systems is done using elementary methods of linear algebra. Each type presents its special canonical form in the associated characteristic coordinate system. Then you can formulate initial value problems in appropriate basic areas, and you can try to achieve a solution of these problems by means of transform methods.

  15. Biomarker clusters are differentially associated with longitudinal cognitive decline in late midlife

    Science.gov (United States)

    Racine, Annie M.; Koscik, Rebecca L.; Berman, Sara E.; Nicholas, Christopher R.; Clark, Lindsay R.; Okonkwo, Ozioma C.; Rowley, Howard A.; Asthana, Sanjay; Bendlin, Barbara B.; Blennow, Kaj; Zetterberg, Henrik; Gleason, Carey E.; Carlsson, Cynthia M.

    2016-01-01

    The ability to detect preclinical Alzheimer’s disease is of great importance, as this stage of the Alzheimer’s continuum is believed to provide a key window for intervention and prevention. As Alzheimer’s disease is characterized by multiple pathological changes, a biomarker panel reflecting co-occurring pathology will likely be most useful for early detection. Towards this end, 175 late middle-aged participants (mean age 55.9 ± 5.7 years at first cognitive assessment, 70% female) were recruited from two longitudinally followed cohorts to undergo magnetic resonance imaging and lumbar puncture. Cluster analysis was used to group individuals based on biomarkers of amyloid pathology (cerebrospinal fluid amyloid-β42/amyloid-β40 assay levels), magnetic resonance imaging-derived measures of neurodegeneration/atrophy (cerebrospinal fluid-to-brain volume ratio, and hippocampal volume), neurofibrillary tangles (cerebrospinal fluid phosphorylated tau181 assay levels), and a brain-based marker of vascular risk (total white matter hyperintensity lesion volume). Four biomarker clusters emerged consistent with preclinical features of (i) Alzheimer’s disease; (ii) mixed Alzheimer’s disease and vascular aetiology; (iii) suspected non-Alzheimer’s disease aetiology; and (iv) healthy ageing. Cognitive decline was then analysed between clusters using longitudinal assessments of episodic memory, semantic memory, executive function, and global cognitive function with linear mixed effects modelling. Cluster 1 exhibited a higher intercept and greater rates of decline on tests of episodic memory. Cluster 2 had a lower intercept on a test of semantic memory and both Cluster 2 and Cluster 3 had steeper rates of decline on a test of global cognition. Additional analyses on Cluster 3, which had the smallest hippocampal volume, suggest that its biomarker profile is more likely due to hippocampal vulnerability and not to detectable specific volume loss exceeding the rate of normal

  16. Cognitive function predicts listening effort performance during complex tasks in normally aging adults

    Directory of Open Access Journals (Sweden)

    Jennine Harvey

    2017-01-01

    Full Text Available Purpose: This study examines whether cognitive function, as measured by the subtests of the Woodcock–Johnson III (WCJ-III assessment, predicts listening-effort performance during dual tasks across the adults of varying ages. Materials and Methods: Participants were divided into two groups. Group 1 consisted of 14 listeners (number of females = 11 who were 41–61 years old [mean = 53.18; standard deviation (SD = 5.97]. Group 2 consisted of 15 listeners (number of females = 9 who were 63–81 years old (mean = 72.07; SD = 5.11. Participants were administered the WCJ-III Memory for Words, Auditory Working Memory, Visual Matching, and Decision Speed subtests. All participants were tested in each of the following three dual-task experimental conditions, which were varying in complexity: (1 auditory word recognition + visual processing, (2 auditory working memory (word + visual processing, and (3 auditory working memory (sentence + visual processing in noise. Results: A repeated measures analysis of variance revealed that task complexity significantly affected the performance measures of auditory accuracy, visual accuracy, and processing speed. Linear regression revealed that the cognitive subtests of the WCJ-III test significantly predicted performance across dependent variable measures. Conclusion: Listening effort is significantly affected by task complexity, regardless of age. Performance on the WCJ-III test may predict listening effort in adults and may assist speech-language pathologist (SLPs to understand challenges faced by participants when subjected to noise.

  17. Disinhibited social engagement in postinstitutionalized children: differentiating normal from atypical behavior.

    Science.gov (United States)

    Lawler, Jamie M; Hostinar, Camelia E; Mliner, Shanna B; Gunnar, Megan R

    2014-05-01

    The most commonly reported socially aberrant behavior in postinstitutionalized (PI) children is disinhibited social engagement (DSE; also known as indiscriminate friendliness). There is no gold standard for measurement of this phenomenon nor agreement on how to differentiate it from normative behavior. We adopted a developmental psychopathology approach (Cicchetti, 1984) to study this phenomenon by comparing it to normative social development and by studying its patterns over time in 50 newly adopted PI children (16-36 months at adoption) compared with 41 children adopted early from foster care overseas and 47 nonadopted (NA) controls. Using coded behavioral observations of the child's interaction with an unfamiliar adult, atypical behaviors were differentiated from normative behaviors. Principal components analysis identified two dimensions of social disinhibition. The nonphysical social dimension (e.g., initiations, proximity) showed wide variation in NA children and is therefore considered a typical form of sociability. Displays of physical contact and intimacy were rare in NA children, suggesting that they represent an atypical pattern of behavior. Both adopted groups demonstrated more physical DSE behavior than NA children. There were no group differences on the nonphysical factor, and it increased over time in all groups. Implications for understanding the etiology of DSE and future directions are discussed.

  18. Differential metabolism and leakage of protein in an inherited cataract and a normal lens cultured with ouabain

    International Nuclear Information System (INIS)

    Piatigorsky, J.; Fukui, H.N.; Kinoshita, J.H.

    1978-01-01

    Ocular lenses in Nakano mice showed marked changes in synthesis, degradation and leakage of protein during cataractogenesis. The cataract-associated changes included the differential lowering of crystalline synthesis, the cleavage of crystallin polypeptides to lower molecular weight forms and the leakage of crystallins from cultured lenses. Ouabain treatment of normal lenses induced these alterations, suggesting that changes in the intracellular levels of Na + and K + affect the anabolism and catabolism of protein during cataract formation. 35 S-methionine was used during the course of the experiments as a method of protein identification. (author)

  19. The method of normal forms for singularly perturbed systems of Fredholm integro-differential equations with rapidly varying kernels

    Energy Technology Data Exchange (ETDEWEB)

    Bobodzhanov, A A; Safonov, V F [National Research University " Moscow Power Engineering Institute" , Moscow (Russian Federation)

    2013-07-31

    The paper deals with extending the Lomov regularization method to classes of singularly perturbed Fredholm-type integro-differential systems, which have not so far been studied. In these the limiting operator is discretely noninvertible. Such systems are commonly known as problems with unstable spectrum. Separating out the essential singularities in the solutions to these problems presents great difficulties. The principal one is to give an adequate description of the singularities induced by 'instability points' of the spectrum. A methodology for separating singularities by using normal forms is developed. It is applied to the above type of systems and is substantiated in these systems. Bibliography: 10 titles.

  20. Differential influences of unilateral tDCS over the intraparietal cortex on numerical cognition

    Directory of Open Access Journals (Sweden)

    Christina eArtemenko

    2015-03-01

    Full Text Available Recent neuro-imaging research identified the bilateral intraparietal sulcus (IPS to be a key area associated with number processing. However, causal structure-function relationships are hard to evaluate from neuro-imaging techniques such as fMRI. Nevertheless, brain stimulation methods like transcranial direct current stimulation (tDCS allow for investigating the functional relevance of the IPS for number processing. Following up on a study using bilateral bi-cephalic tDCS over the IPS, the current study aimed at evaluating the differential lateralized functional contributions of the left and right IPS to number processing using unilateral bi-cephalic tDCS over either the left or right IPS. Results indicated a right lateralization for the processing of the place-value structure of the Arabic number system. Importantly, the processing of number magnitude information was not affected by unilateral IPS corroborating the assumption that number magnitude is processed in the bilateral IPS. Taken together, these data suggest that even though number magnitude is represented bilaterally, the left and right IPS seem to contribute differentially to numerical cognition with respect to the processing of specific other aspects of numerical information.

  1. Differential transferrin expression in placentae from normal and abnormal pregnancies: a pilot study

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    Bukovsky Antonin

    2008-07-01

    Full Text Available Abstract Background The placenta is an important site for iron metabolism in humans. It transfers iron from the mother to the fetus. One of the major iron transport proteins is transferrin, which is a blood plasma protein crucial for iron uptake. Its localization and expression may be one of the markers to distinguish placental dysfunction. Methods In the experimental study we used antibody preparation, mass spectrometric analysis, biochemical and immunocytochemical methods for characterization of transferrin expression on the human choriocarcinoma cell line JAR (JAR cells, placental lysates, and cryostat sections. Newly designed monoclonal antibody TRO-tf-01 to human transferrin was applied on human placentae from normal (n = 3 and abnormal (n = 9 pregnancies. Results Variations of transferrin expression were detected in villous syncytiotrophoblast, which is in direct contact with maternal blood. In placentae from normal pregnancies, the expression of transferrin in the syncytium was significantly lower (p Conclusion These observations suggest that in the case of abnormal pregnancies, the fetus may require higher levels of transferrin in order to prevent iron depletion due to the stress from the placental dysfunction.

  2. Differential effects of mental stress on plasma homovanillic acid in schizophrenia and normal controls.

    Science.gov (United States)

    Sumiyoshi, T; Saitoh, O; Yotsutsuji, T; Itoh, H; Kurokawa, K; Kurachi, M

    1999-04-01

    We previously reported that mental stress by Kraepelin's arithmetic test decreases plasma homovanillic acid (pHVA) levels in psychiatrically normal healthy human subjects. The present study was undertaken to determine whether this pattern of changes in pHVA concentrations resulting from mental stress is altered in patients with schizophrenia. Fourteen male patients with schizophrenia including those under ongoing neuroleptic treatment and 14 normal male volunteers participated in the study. Following overnight fast and restricted physical activity, the subjects performed Kraepelin's arithmetic test for 30 minutes. Plasma samples were collected immediately before and after the test for measurement of pHVA levels. A significant diagnosis by Kraepelin's test effect was observed due to a decrease in pHVA levels by the Kraepelin test in control subjects but not in patients with schizophrenia. Changes in pHVA levels during the Kraepelin test positively correlated with pre-test pHVA levels in control subjects, while this correlation was not observed in patients with schizophrenia. These results may be further support for the presence of a dopamine-dependent restitutive system in the brain. The absence of response of pHVA levels to mental stress in patients with schizophrenia may indicate that the dopamine restitutive system in these patients is disrupted or already down-regulated, as previously predicted.

  3. Differentiating Patients with Parkinson's Disease from Normal Controls Using Gray Matter in the Cerebellum.

    Science.gov (United States)

    Zeng, Ling-Li; Xie, Liang; Shen, Hui; Luo, Zhiguo; Fang, Peng; Hou, Yanan; Tang, Beisha; Wu, Tao; Hu, Dewen

    2017-02-01

    Parkinson's disease (PD) is one of the most common neurodegenerative disorders in the world. Previous studies have focused on the basal ganglia and cerebral cortices. To date, the cerebellum has not been systematically investigated in patients with PD. In the current study, 45 probable PD patients and 40 age- and gender-matched healthy controls underwent structural magnetic resonance imaging, and we used support vector machines combining with voxel-based morphometry to explore the cerebellar structural changes in the probable PD patients relative to healthy controls. The results revealed that the gray matter alterations were primarily located within the cerebellar Crus I, implying a possible important role of this region in PD. Furthermore, the gray matter alterations in the cerebellum could differentiate the probable PD patients from healthy controls with accuracies of more than 95 % (p cerebellum in the clinical diagnosis of PD.

  4. Ubiquitin specific protease 21 is dispensable for normal development, hematopoiesis and lymphocyte differentiation.

    Directory of Open Access Journals (Sweden)

    Jaspreet Pannu

    Full Text Available USP21 is a ubiquitin specific protease that catalyzes protein deubiquitination, however the identification of its physiological substrates remains challenging. USP21 is known to deubiquitinate transcription factor GATA3 and death-domain kinase RIPK1 in vitro, however the in vivo settings where this regulation plays a biologically significant role remain unknown. In order to determine whether USP21 is an essential and non-redundant regulator of GATA3 or RIPK1 activity in vivo, we characterized Usp21-deficient mice, focusing on mouse viability and development, hematopoietic stem cell function, and lymphocyte differentiation. The Usp21-knockout mice were found to be viable and fertile, with no significant dysmorphology, in contrast to the GATA3 and RIPK1 knockout lines that exhibit embryonic or perinatal lethality. Loss of USP21 also had no effect on hematopoietic stem cell function, lymphocyte development, or the responses of antigen presenting cells to TLR and TNFR stimulation. GATA3 levels in hematopoietic stem cells or T lymphocytes remained unchanged. We observed that aged Usp21-knockout mice exhibited spontaneous T cell activation, however this was not linked to altered GATA3 levels in the affected cells. The contrast in the phenotype of the Usp21-knockout line with the previously characterized GATA3 and RIPK1 knockout mice strongly indicates that USP21 is redundant for the regulation of GATA3 and RIPK1 activity during mouse development, in hematopoietic stem cells, and in lymphocyte differentiation. The Usp21-deficient mouse line characterized in this study may serve as a useful tool for the future characterization of USP21 physiological functions.

  5. Distinct Thalamic Reticular Cell Types Differentially Modulate Normal and Pathological Cortical Rhythms

    Directory of Open Access Journals (Sweden)

    Alexandra Clemente-Perez

    2017-06-01

    Full Text Available Integrative brain functions depend on widely distributed, rhythmically coordinated computations. Through its long-ranging connections with cortex and most senses, the thalamus orchestrates the flow of cognitive and sensory information. Essential in this process, the nucleus reticularis thalami (nRT gates different information streams through its extensive inhibition onto other thalamic nuclei, however, we lack an understanding of how different inhibitory neuron subpopulations in nRT function as gatekeepers. We dissociated the connectivity, physiology, and circuit functions of neurons within rodent nRT, based on parvalbumin (PV and somatostatin (SOM expression, and validated the existence of such populations in human nRT. We found that PV, but not SOM, cells are rhythmogenic, and that PV and SOM neurons are connected to and modulate distinct thalamocortical circuits. Notably, PV, but not SOM, neurons modulate somatosensory behavior and disrupt seizures. These results provide a conceptual framework for how nRT may gate incoming information to modulate brain-wide rhythms.

  6. Interactions of the Salience Network and Its Subsystems with the Default-Mode and the Central-Executive Networks in Normal Aging and Mild Cognitive Impairment.

    Science.gov (United States)

    Chand, Ganesh B; Wu, Junjie; Hajjar, Ihab; Qiu, Deqiang

    2017-09-01

    Previous functional magnetic resonance imaging (fMRI) investigations suggest that the intrinsically organized large-scale networks and the interaction between them might be crucial for cognitive activities. A triple network model, which consists of the default-mode network, salience network, and central-executive network, has been recently used to understand the connectivity patterns of the cognitively normal brains versus the brains with disorders. This model suggests that the salience network dynamically controls the default-mode and central-executive networks in healthy young individuals. However, the patterns of interactions have remained largely unknown in healthy aging or those with cognitive decline. In this study, we assess the patterns of interactions between the three networks using dynamical causal modeling in resting state fMRI data and compare them between subjects with normal cognition and mild cognitive impairment (MCI). In healthy elderly subjects, our analysis showed that the salience network, especially its dorsal subnetwork, modulates the interaction between the default-mode network and the central-executive network (Mann-Whitney U test; p control correlated significantly with lower overall cognitive performance measured by Montreal Cognitive Assessment (r = 0.295; p control, especially the dorsal salience network, over other networks provides a neuronal basis for cognitive decline and may be a candidate neuroimaging biomarker of cognitive impairment.

  7. Differential effects of physical activity and sleep duration on cognitive function in young adults

    Directory of Open Access Journals (Sweden)

    Kazuko Kato

    2018-04-01

    Full Text Available Purpose: Although exercise and sleep duration habits are associated with cognitive function, their beneficial effects on cognitive function remain unclear. We aimed to examine the effect of sleep duration and daily physical activity on cognitive function, elucidating the neural mechanisms using near-infrared spectroscopy (NIRS. Methods: A total of 23 healthy young adults (age 22.0 ± 2.2 years participated in this study. Exercise amount was assessed using a uniaxial accelerometer. We evaluated total sleep time (TST and sleep efficiency by actigraphy. Cognitive function was tested using the N-back task, the Wisconsin Card Sorting Test (WCST, and the Continuous Performance Test–Identical Pairs (CPT-IP, and the cortical oxygenated hemoglobin levels during a word fluency task were measured with NIRS. Results: Exercise amount was significantly correlated with reaction time on 0- and 1-back tasks (r = −0.602, p = 0.002; r = −0.446, p = 0.033, respectively, whereas TST was significantly correlated with % corrects on the 2-back task (r = 0.486, p = 0.019. Multiple regression analysis, including exercise amount, TST, and sleep efficiency, revealed that exercise amount was the most significant factor for reaction time on 0- and 1-back tasks (β = −0.634, p = 0.002; β = −0.454, p = 0.031, respectively, and TST was the most significant factor for % corrects on the 2-back task (β = 0.542, p = 0.014. The parameter measured by WCST and CPT-IP was not significantly correlated with TST or exercise amount. Exercise amount, but not TST, was significantly correlated with the mean area under the NIRS curve in the prefrontal area (r = 0.492, p = 0.017. Conclusion: Exercise amount and TST had differential effects on working memory and cortical activation in the prefrontal area. Daily physical activity and appropriate sleep duration may play an important role in working memory. Keywords: Cortical

  8. Do cognitive measures of response inhibition differentiate between attention deficit/hyperactivity disorder and borderline personality disorder?

    NARCIS (Netherlands)

    Dijk, F.E. van; Schellekens, A.F.A.; Broek, P.J.A. van den; Kan, C.C.; Verkes, R.J.; Buitelaar, J.K.

    2014-01-01

    This study examined whether cognitive measures of response inhibition derived from the AX-CPT are able to differentiate between adult attention deficit/hyperactivity disorder (ADHD), borderline personality disorder (BPD), and healthy controls (HC). Current DSM-IV-TR symptoms of ADHD and BPD were

  9. Differentiating fibroadenoma and ductal carcinoma in situ from normal breast tissue by multiphoton microscopy

    Science.gov (United States)

    Nie, Yuting; Wu, Yan; Lian, Yuane; Fu, Fangmeng; Wang, Chuan; Chen, Jianxin

    2014-09-01

    Fibroadenoma (FA) is the most common benign tumor of the female breast and several studies have reported that women with it have increased risk of breast cancer. While the ductal carcinoma in situ (DCIS) is a very early form of breast cancer. Thus, early detections of FA and DCIS are critical for improving breast tumor outcome and survival. In this paper, we use multiphoton microscopy (MPM) to obtain the high-contrast images of fresh, unfixed, unstained human breast specimens (normal breast tissue, FA and DCIS). Our results show that MPM has the ability to identify the characteristics of FA and DCIS including changes of duct architecture and collagen morphology. These results are consistent with the histological results. With the advancement of MPM, the technique has potential ability to serve as a real-time noninvasive imaging tool for early detection of breast tumor.

  10. Uninstructed BIAT faking when ego depleted or in normal state: differential effect on brain and behavior.

    Science.gov (United States)

    Wolff, Wanja; Schindler, Sebastian; Englert, Christoph; Brand, Ralf; Kissler, Johanna

    2016-05-03

    Deception can distort psychological tests on socially sensitive topics. Understanding the cerebral processes that are involved in such faking can be useful in detection and prevention of deception. Previous research shows that faking a brief implicit association test (BIAT) evokes a characteristic ERP response. It is not yet known whether temporarily available self-control resources moderate this response. We randomly assigned 22 participants (15 females, 24.23 ± 2.91 years old) to a counterbalanced repeated-measurements design. Participants first completed a Brief-IAT (BIAT) on doping attitudes as a baseline measure and were then instructed to fake a negative doping attitude both when self-control resources were depleted and non-depleted. Cerebral activity during BIAT performance was assessed using high-density EEG. Compared to the baseline BIAT, event-related potentials showed a first interaction at the parietal P1, while significant post hoc differences were found only at the later occurring late positive potential. Here, significantly decreased amplitudes were recorded for 'normal' faking, but not in the depletion condition. In source space, enhanced activity was found for 'normal' faking in the bilateral temporoparietal junction. Behaviorally, participants were successful in faking the BIAT successfully in both conditions. Results indicate that temporarily available self-control resources do not affect overt faking success on a BIAT. However, differences were found on an electrophysiological level. This indicates that while on a phenotypical level self-control resources play a negligible role in deliberate test faking the underlying cerebral processes are markedly different.

  11. Differential Cortical Neurotrophin and Cytogenetic Adaptation after Voluntary Exercise in Normal and Amnestic Rats

    Science.gov (United States)

    Hall, Joseph M.; Vetreno, Ryan P.; Savage, Lisa M.

    2013-01-01

    Voluntary exercise (VEx) has profound effects on neural and behavioral plasticity, including recovery of CNS trauma and disease. However, the unique regional cortical adaption to VEx has not been elucidated. In a series of experiments, we first examined whether VEx would restore and retain neurotrophin levels in several cortical regions (frontal cortex [FC], retrosplenial cortex [RSC], occipital cortex [OC]) in an animal model (pyrithiamine-induced thiamine deficiency [PTD]) of the amnestic disorder Wernicke-Korsakoff syndrome. In addition, we assessed the time-dependent effect of VEx to rescue performance on a spontaneous alternation task. Following 2-weeks of VEx or stationary housing conditions (Stat), rats were behaviorally tested and brains were harvested either the day after VEx (24-h) or after an additional two-week period (2-wk). In both control pair-fed (PF) rats and PTD rats, all neurotrophin levels (brain-derived neurotrophic factor [BDNF], nerve growth factor [NGF], and vascular endothelial growth factor [VEGF]) increased at the 24-h period after VEx in the FC and RSC, but not OC. Two-weeks following VEx, BDNF remained elevated in both FC and RSC, whereas NGF remained elevated in only the FC. Interestingly, VEx only recovered cognitive performance in amnestic rats when there was an additional 2-wk adaptation period after VEx. Given this unique temporal profile, Experiment 2 examined the cortical cytogenetic responses in all three cortical regions following a 2-wk adaptation period after VEx. In healthy (PF) rats, VEx increased the survival of progenitor cells in both the FC and RSC, but only increased oligodendrocyte precursor cells in the FC. Furthermore, VEx had a selective effect of only recovering oligodendrocyte precursor cells in the FC in PTD rats. These data reveal the therapeutic potential of exercise to restore cortical plasticity in the amnestic brain, and that the FC is one of the most responsive cortical regions to VEx. PMID:24215977

  12. The clinical utility of naturalistic action test in differentiating mild cognitive impairment from early dementia in memory clinic.

    Science.gov (United States)

    Bruce, Irene; Ntlholang, Ontefetse; Crosby, Lisa; Cunningham, Conal; Lawlor, Brian

    2016-03-01

    This study aimed to examine the validity of the Naturalistic Action Test in differentiating Mild Cognitive Impairment from early dementia compared to clinical diagnosis and ascertain Naturalistic Action Test cut-off points. This was a cross-sectional study of 70 consecutive patients diagnosed with Mild Cognitive Impairment attending the memory clinic in St James's Hospital, Dublin, Ireland. Patients with a diagnosis of Mild Cognitive Impairment who attended for routine annual assessment were asked to participate in the study. The Naturalistic Action Test was carried out after the patient had completed their routine assessment in the clinic. The Area under the Curve, AUC ± SE was 0.808 ± 0.058, p Cognitive Impairment in our study (PPV 50%, NPV 91%, sensitivity 78%, specificity 73% and accuracy of 74%). There was discrepancy in 18 patients using the new cut-off point (≥11 for Mild Cognitive Impairment vs ≤10 for dementia). The Naturalistic Action Test is a useful tool that can increase diagnostic accuracy in differentiating Mild Cognitive Impairment from early dementia. Copyright © 2015 John Wiley & Sons, Ltd.

  13. ChIPnorm: a statistical method for normalizing and identifying differential regions in histone modification ChIP-seq libraries.

    Science.gov (United States)

    Nair, Nishanth Ulhas; Sahu, Avinash Das; Bucher, Philipp; Moret, Bernard M E

    2012-01-01

    The advent of high-throughput technologies such as ChIP-seq has made possible the study of histone modifications. A problem of particular interest is the identification of regions of the genome where different cell types from the same organism exhibit different patterns of histone enrichment. This problem turns out to be surprisingly difficult, even in simple pairwise comparisons, because of the significant level of noise in ChIP-seq data. In this paper we propose a two-stage statistical method, called ChIPnorm, to normalize ChIP-seq data, and to find differential regions in the genome, given two libraries of histone modifications of different cell types. We show that the ChIPnorm method removes most of the noise and bias in the data and outperforms other normalization methods. We correlate the histone marks with gene expression data and confirm that histone modifications H3K27me3 and H3K4me3 act as respectively a repressor and an activator of genes. Compared to what was previously reported in the literature, we find that a substantially higher fraction of bivalent marks in ES cells for H3K27me3 and H3K4me3 move into a K27-only state. We find that most of the promoter regions in protein-coding genes have differential histone-modification sites. The software for this work can be downloaded from http://lcbb.epfl.ch/software.html.

  14. Screening for Internet dependence: do the proposed diagnostic criteria differentiate normal from dependent Internet use?

    Science.gov (United States)

    Dowling, Nicki A; Quirk, Kelly L

    2009-02-01

    There is continued discussion of including Internet dependence as a diagnosis in future editions of the Diagnostic and Statistical Manual of Mental Disorders. The primary aim of the study was to evaluate the utility of the proposed diagnostic criteria for Internet dependence as measured by Young's Diagnostic Questionnaire (YDQ). Although the YDQ does not provide any measure of severity, there is emerging recognition that some Internet users may display less severe or at risk Internet dependence. The degree to which the cutoff of 5 out of 8 criteria is appropriate to differentiate nondependent from dependent Internet use was evaluated by comparing the Internet usage and psychological dysfunction of 424 university students endorsing 3 and 4 diagnostic criteria (at-risk Internet dependence) to those endorsing less than 3 criteria (nondependent) and those endorsing 5 or more criteria (Internet dependence). The findings suggest that the proposed diagnostic criteria do not adequately discriminate individuals scoring 3 or 4 from those currently classified as Internet dependent. The implications of the findings for the assessment, diagnosis, and treatment of Internet dependence are discussed.

  15. MRI Volumetry of Hippocampus and Amygdala in Normal Aging, Mild Cognitive Impairment and Alzheimer's Disease Subjects

    International Nuclear Information System (INIS)

    Suphaphong, S.; Tritanon, O.; Laothamatas, J.; Sungkarat, W.

    2012-01-01

    The Alzheimer's disease (AD) and mild cognitive impairment (MCI) can affect memory and daily living. Non- invasive diagnostic tools such as MRI can be useful to discriminate the patients from normal group.This study aims to compare the relative volumes of hippocampus and amygdala, to suggest the relative normal volumes, and to evaluate MRI automatic volumetry as a diagnostic tool. The MRI images of 130 subjects were retrospectively studied (Turbo field echo (TFE), acquired with a 3-Tesla Philips scanner). The image data were processed with Free Surfer (automatic segmentation and volumetry). The resultant volumes were corrected for brain size differences with intracranial volumes (ICV), and then analysed with SPSS (v. 17.0). There are differences of hippocampus and amygdala relative volumes between normal, MCI, and AD subjects at p < 0.001. The volume reductions of hippocampus in MCI and AD groups compared to normal group are about 8 % and 28 %, while those of amygdala are about 10 % and 34 %, respectively. The relative volumes of hippocampus (compared to ICV) in normal aging are 0.002617 ± 0.000278 (right) and 0.002553 ± 0.000257 (left), while those of amygdala are 0.001231 ± 0.000165 (right) and 0.001096 ± 0.000144 (left). There are no differences of relative volumes affected by gender in normal, MCI, and AD. There is a highly significant difference of relative volume affected by brain side in normal group (p < 0.001) but not in MCI (p = 0.119 and 0.077) and AD (p = 0.713 and 0.250), for hippocampus and amygdala, respectively. These results demonstrate that there are volume losses of hippocampus and amygdala in both diseases. Automatically measured hippocampus and amygdala volumes can be used as a measure indicating MCI and AD. The abnormal disturbance of volume affected by brain side may indicate the progression of both diseases. The hippocampus and amygdala volumes can be used as one of diagnostic tools to confirm the diagnosis of MCI or AD. The volume

  16. Open-type congenital cholesteatoma: differential diagnosis for conductive hearing loss with a normal tympanic membrane.

    Science.gov (United States)

    Kim, Se-Hyung; Cho, Yang-Sun; Chu, Ho-Suk; Jang, Jeon-Yeob; Chung, Won-Ho; Hong, Sung Hwa

    2012-06-01

    In patients with progressive conductive hearing loss and a normal tympanic membrane (TM), and with soft tissue density in the middle ear cavity (MEC) on temporal bone computed tomography (TBCT) scan, open-type congenital cholesteatoma (OCC) should be highly suspected and a proper surgical plan that includes mastoid exploration and second-stage operation is required. The clinical presentation of OCC is very similar to congenital ossicular anomaly (COA) presenting with a conductive hearing loss with intact TM. Therefore, it is challenging to make a correct preoperative diagnosis in patients with OCC. We evaluated the clinical characteristics of OCC compared with those of COA to find diagnostic clues useful in diagnosis of OCC. The medical records of 12 patients with surgically proven OCC and 14 patients with surgically proven COA were reviewed for demographic data, otologic history, preoperative TBCT findings, intraoperative findings, and pre- and postoperative audiologic data. There was no difference between OCC and COA based on demographic data, preoperative hearing, and ossicular status on TBCT. However, the presence of progressive hearing loss, soft tissue density in the MEC on TBCT scan, and the need for mastoid surgery and second-stage operation were significantly more frequent in OCC patients.

  17. Detection of colorectal masses in CT colonography: application of deep residual networks for differentiating masses from normal colon anatomy

    Science.gov (United States)

    Näppi, Janne J.; Hironaka, Toru; Yoshida, Hiroyuki

    2018-02-01

    Even though the clinical consequences of a missed colorectal cancer far outweigh those of a missed polyp, there has been little work on computer-aided detection (CADe) for colorectal masses in CT colonography (CTC). One of the problems is that it is not clear how to manually design mathematical image-based features that could be used to differentiate effectively between masses and certain types of normal colon anatomy such as ileocecal valves (ICVs). Deep learning has demonstrated ability to automatically determine effective discriminating features in many image-based problems. Recently, residual networks (ResNets) were developed to address the practical problems of constructing deep network architectures for optimizing the performance of deep learning. In this pilot study, we compared the classification performance of a conventional 2D-convolutional ResNet (2D-ResNet) with that of a volumetric 3D-convolutional ResNet (3D-ResNet) in differentiating masses from normal colon anatomy in CTC. For the development and evaluation of the ResNets, 695 volumetric images of biopsy-proven colorectal masses, ICVs, haustral folds, and rectal tubes were sampled from 196 clinical CTC cases and divided randomly into independent training, validation, and test datasets. The training set was expanded by use of volumetric data augmentation. Our preliminary results on the 140 test samples indicate that it is feasible to train a deep volumetric 3D-ResNet for performing effective image-based discriminations in CTC. The 3D-ResNet slightly outperformed the 2D-ResNet in the discrimination of masses and normal colon anatomy, but the statistical difference between their very high classification accuracies was not significant. The highest classification accuracy was obtained by combining the mass-likelihood estimates of the 2D- and 3D-ResNets, which enabled correct classification of all of the masses.

  18. Mice with Sort1 deficiency display normal cognition but elevated anxiety-like behavior.

    Science.gov (United States)

    Ruan, Chun-Sheng; Yang, Chun-Rui; Li, Jia-Yi; Luo, Hai-Yun; Bobrovskaya, Larisa; Zhou, Xin-Fu

    2016-07-01

    Exposure to stressful life events plays a central role in the development of mood disorders in vulnerable individuals. However, the mechanisms that link mood disorders to stress are poorly understood. Brain-derived neurotrophic factor (BDNF) has long been implicated in positive regulation of depression and anxiety, while its precursor (proBDNF) recently showed an opposing effect on such mental illnesses. P75(NTR) and sortilin are co-receptors of proBDNF, however, the role of these receptors in mood regulation is not established. Here, we aimed to investigate the role of sortilin in regulating mood-related behaviors and its role in the proBDNF-mediated mood abnormality in mice. We found that sortilin was up-regulated in neocortex (by 78.3%) and hippocampus (by 111%) of chronically stressed mice as assessed by western blot analysis. These changes were associated with decreased mobility in the open field test and increased depression-like behavior in the forced swimming test. We also found that sortilin deficiency in mice resulted in hyperlocomotion in the open field test and increased anxiety-like behavior in both the open field and elevated plus maze tests. No depression-like behavior in the forced swimming test and no deficit in spatial cognition in the Morris water maze test were found in the Sort1-deficient mice. Moreover, the intracellular and extracellular levels of mature BDNF and proBDNF were not changed when sortilin was absent in vivo and in vitro. Finally, we found that both WT and Sort1-deficient mice injected with proBDNF in lateral ventricle displayed increased depression-like behavior in the forced swimming test but not anxiety-like behaviors in the open field and elevated plus maze tests. The present study suggests that sortilin functions as a negative regulator of mood performance and can be a therapeutic target for the treatment of mental illness. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  19. Impaired cognitive functions in mild traumatic brain injury patients with normal and pathologic magnetic resonance imaging

    International Nuclear Information System (INIS)

    Kurca, E.; Sivak, S.; Kucera, P.

    2006-01-01

    Mild traumatic brain injury (MTBI) is a common neurological (neurotraumatological) diagnosis. As well as different subjective symptoms, many patients develop neuropsychological dysfunction with objective impairment of attention, memory and certain executive functions. Magnetic resonance imaging (MRI) is not routinely used in MTBI patients despite its proven greater sensitivity and specificity in comparison with computed tomography (CT). The patient group consisted of 30 persons with MTBI and the control group consisted of 30 sex- and age-matched healthy volunteers. Both groups underwent neurological examination, neuropsychological testing (including the Postconcussion Symptoms Scale questionnaire, PCSS) and brain MRI (the patient group within 96 h after injury). The analyzed groups did not differ significantly in terms of sex, age, or level or duration of education. MRI pathological findings (traumatic and nonspecific) were present in nine patients. Traumatic lesions were found in seven patients. Nonspecific white matter lesions were found in five healthy controls. There were significant differences between MTBI patients and controls in terms of subjective symptoms (PCSS) and selected neuropsychological tests. Statistically significant neuropsychological differences were found between MTBI patients with true traumatic lesions and MTBI patients with nonspecific lesions. There is evidence that MTBI patients with true traumatic MRI lesions are neuropsychologically different from MTBI patients with nonspecific MRI lesions or normal brain MRI. These results support the hypothesis that some acute MTBI signs and symptoms have a real organic basis which can be detected by selected new MRI modalities. (orig.)

  20. Brain Microstructural Correlates of Cognitive Dysfunction in Clinically and Biochemically Normal Hepatitis C Virus Infection.

    Science.gov (United States)

    Kumar, Ajay; Deep, Amar; Gupta, Rakesh K; Atam, Virendra; Mohindra, Samir

    2017-09-01

    This study examined correlates of the brain's neurocognitive performance among clinically and biochemically normal adult patient with hepatitis C virus (HCV). We hypothesized that anti-HCV positive individuals would demonstrate structural brain abnormalities and neurocognitive dysfunction as well as the changes in cell component and extracellular space in the white matter regions of brain in asymptomatic HCV infection by using diffusion tensor tractrography (DTT) metrics. Anti-HCV positive patient ( n  = 40), and healthy controls ( n  = 31), fulfilling inclusion criteria (incidentally detected anti-HCV positive) and able to provide informed consent were screened and recruited for the study. All these subjects and controls underwent subjective assessment of their quality of life related symptoms, neuropsychometric tests (NPT) and magnetic resonance imaging. The patients were subjected to neuroimaging as well as psychological testing. There was no significant difference in basic laboratory parameters in these two groups. Independent t -test reveals significantly lower neuropsychological functioning as compared to healthy control. A significantly decreased FA values and myoinsitol were observed in HCV subjects on sensory, inferior longitudinal fascicules, and STR fiber bundles as compared to healthy control. Bivariate correlation analysis reveals that neuropsychological scores are significantly positive. Our result show that HCV positive individuals would demonstrate structural brain abnormalities and neurocognitive dysfunction as well as the changes in cell component and extracellular space in the white matter regions of brain in asymptomatic HCV infection by using DTT metrics.

  1. Impaired cognitive functions in mild traumatic brain injury patients with normal and pathologic magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kurca, E.; Sivak, S. [Comenius University, Clinic of Neurology, Jessenius Faculty of Medicine, Martin (Slovakia); Kucera, P. [Comenius University, 1st Clinic of Neurology, Faculty of Medicine, Bratislava (Slovakia)

    2006-09-15

    Mild traumatic brain injury (MTBI) is a common neurological (neurotraumatological) diagnosis. As well as different subjective symptoms, many patients develop neuropsychological dysfunction with objective impairment of attention, memory and certain executive functions. Magnetic resonance imaging (MRI) is not routinely used in MTBI patients despite its proven greater sensitivity and specificity in comparison with computed tomography (CT). The patient group consisted of 30 persons with MTBI and the control group consisted of 30 sex- and age-matched healthy volunteers. Both groups underwent neurological examination, neuropsychological testing (including the Postconcussion Symptoms Scale questionnaire, PCSS) and brain MRI (the patient group within 96 h after injury). The analyzed groups did not differ significantly in terms of sex, age, or level or duration of education. MRI pathological findings (traumatic and nonspecific) were present in nine patients. Traumatic lesions were found in seven patients. Nonspecific white matter lesions were found in five healthy controls. There were significant differences between MTBI patients and controls in terms of subjective symptoms (PCSS) and selected neuropsychological tests. Statistically significant neuropsychological differences were found between MTBI patients with true traumatic lesions and MTBI patients with nonspecific lesions. There is evidence that MTBI patients with true traumatic MRI lesions are neuropsychologically different from MTBI patients with nonspecific MRI lesions or normal brain MRI. These results support the hypothesis that some acute MTBI signs and symptoms have a real organic basis which can be detected by selected new MRI modalities. (orig.)

  2. Androgen receptor signalling in peritubular myoid cells is essential for normal differentiation and function of adult Leydig cells

    DEFF Research Database (Denmark)

    Welsh, M.; Moffat, L.; Belling, Kirstine Christensen

    2012-01-01

    Testosterone synthesis depends on normal Leydig cell (LC) development, but the mechanisms controlling this development remain unclear. We recently demonstrated that androgen receptor (AR) ablation from a proportion of testicular peritubular myoid cells (PTM-ARKO) did not affect LC number, but res......Testosterone synthesis depends on normal Leydig cell (LC) development, but the mechanisms controlling this development remain unclear. We recently demonstrated that androgen receptor (AR) ablation from a proportion of testicular peritubular myoid cells (PTM-ARKO) did not affect LC number......’ subpopulation that had arrested development and only weakly expressed INSL3, luteinizing hormone receptor, and several steroidogenic enzymes. Furthermore, unlike ‘normal’ LCs in PTM-ARKOs, the ‘abnormal’ LCs did not involute as expected in response to exogenous testosterone. Differential function of these LC...... sub-populations is likely to mean that the ‘normal’ LCs work harder to compensate for the ‘abnormal’ LCs to maintain normal serum testosterone. These findings reveal new paracrine mechanisms underlying adult LC development, which can be further investigated using PTM-ARKOs....

  3. Follicular localization of growth differentiation factor 8 and its receptors in normal and polycystic ovary syndrome ovaries.

    Science.gov (United States)

    Lin, Ting-Ting; Chang, Hsun-Ming; Hu, Xiao-Ling; Leung, Peter C K; Zhu, Yi-Min

    2018-05-01

    Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age and its etiology has not been characterized. Growth differentiation factor 8 (GDF8) is a member of the transforming growth factor-β superfamily that plays a critical role in the regulation of ovarian functions. However, the expression pattern of GDF8 in the human ovary is not yet clear. This study examined the cellular distribution of GDF8 and its putative cellular receptors (ACVR2A, ACVR2B, and ALK5) in a series of normal (n = 34) and PCOS ovaries (n = 14). The immunostaining of GDF8, ACVR2A, ACVR2B, and ALK5 was detected in the oocytes regardless of the developmental stage. All these proteins were localized in antral follicles in normal and PCOS ovaries, and the expression of these proteins increased with increasing follicle diameter. A significantly higher expression of GDF8 was detected in the granulosa cells than in the matched theca cells (TCs). These proteins were also localized in the luteal cells of the corpus luteum. Granulosa cells and TCs of large antral follicles in PCOS ovaries display a higher expression of these proteins. The higher expression levels of GDF8 and its functional receptors (ACVR2A, ACVR2B, and ALK5) in antral follicles of PCOS ovaries than those in normal ovaries suggest the possible involvement of dysregulated GDF8 in the pathogenesis of PCOS.

  4. Relationship of metabolic and endocrine parameters to brain glucose metabolism in older adults: do cognitively-normal older adults have a particular metabolic phenotype?

    Science.gov (United States)

    Nugent, S; Castellano, C A; Bocti, C; Dionne, I; Fulop, T; Cunnane, S C

    2016-02-01

    Our primary objective in this study was to quantify whole brain and regional cerebral metabolic rates of glucose (CMRg) in young and older adults in order to determine age-normalized reference CMRg values for healthy older adults with normal cognition for age. Our secondary objectives were to--(i) report a broader range of metabolic and endocrine parameters including body fat composition that could form the basis for the concept of a 'metabolic phenotype' in cognitively normal, older adults, and (ii) to assess whether medications commonly used to control blood lipids, blood pressure or thyroxine affect CMRg values in older adults. Cognition assessed by a battery of tests was normal for age and education in both groups. Compared to the young group (25 years old; n = 34), the older group (72 years old; n = 41) had ~14% lower CMRg (μmol/100 g/min) specifically in the frontal cortex, and 18% lower CMRg in the caudate. Lower grey matter volume and cortical thickness was widespread in the older group. These differences in CMRg, grey matter volume and cortical thickness were present in the absence of any known evidence for prodromal Alzheimer's disease (AD). Percent total body fat was positively correlated with CMRg in many brain regions but only in the older group. Before and after controlling for body fat, HOMA2-IR was significantly positively correlated to CMRg in several brain regions in the older group. These data show that compared to a healthy younger adult, the metabolic phenotype of a cognitively-normal 72 year old person includes similar plasma glucose, insulin, cholesterol, triglycerides and TSH, higher hemoglobin A1c and percent body fat, lower CMRg in the superior frontal cortex and caudate, but the same CMRg in the hippocampus and white matter. Age-normalization of cognitive test results is standard practice and we would suggest that regional CMRg in cognitively healthy older adults should also be age-normalized.

  5. DTI studies in patients with Alzheimer's disease, mild cognitive impairment, or normal cognition with evaluation of the intrinsic background gradients

    Energy Technology Data Exchange (ETDEWEB)

    Jahng, Geon-Ho [Kyung Hee University, Department of Radiology, Kyung Hee University Hospital-Gangdong, School of Medicine, Seoul (Korea, Republic of); Xu, Songfan [Graduate School of Kyung Hee University, Department of Biomedical Science, Seoul (Korea, Republic of); Weiner, Micheal W.; Meyerhoff, Dieter J.; Schuff, Norbert [University of California-San Francisco, Center for Imaging of Neurodegenerative Diseases, VA Medical Center and the Department of Radiology, San Francisco, CA (United States); Park, Seungjoon [Graduate School of Kyung Hee University, Department of Biomedical Science, Seoul (Korea, Republic of); Kyung Hee University, Department of Pharmacology and the Medical Research Center for Bioreaction to ROS and the Biomedical Science Institute, School of Medicine, Seoul (Korea, Republic of)

    2011-10-15

    The objective of the study was to explore the impact of the background gradients on diffusion tensor (DT) magnetic resonance imaging (DT-MRI) in patients with Alzheimer's disease (AD), mild cognitive impairment (MCI), or cognitively normal (CN) aging. Two DT-MRI sets with positive and negative polarities of the diffusion-sensitizing gradients were obtained in 15 AD patients, 18 MCI patients, and 16 CN control subjects. The maps of mean diffusivity (MD) and fractional anisotropy (FA) were computed separately for positive (p: pMD and pFA) and negative (n: nMD and nFA) polarities, and we computed the geometric mean (gm) of the DT-MRI to obtain the gmFA and gmMD with reducing the background gradient effects. Regional variations were assessed across the groups using one-way analysis of variance. Increased regional gmMD values in the AD subjects, as compared to the regional gmMD values in the MCI and CN subjects, were found primarily in the frontal, limbic, and temporal lobe regions. We also found increased nMD and pMD values in the AD subjects compared to those values in the MCI and CN subjects, including in the temporal lobe and the left limbic parahippocampal gyrus white matter. Results of comparisons among the three methods showed that the left limbic parahippocampal gyrus and right temporal gyrus were the increased MD in the AD patients for all three methods. Background gradients affect the DT-MRI measurements in AD patients. Geometric average diffusion measures can be useful to minimize the intrinsic local magnetic susceptibility variations in brain tissue. (orig.)

  6. Using functional Magnetic Resonance Imaging to differentiate between healthy aging subjects, Mild Cognitive Impairment, and Alzheimer′s patients

    Directory of Open Access Journals (Sweden)

    Mohammad Ali Oghabian

    2010-01-01

    Full Text Available Background: Alzheimer′s disease is the most common form of dementia which is still difficult to be differentiated from other types of brain disorders. Moreover, Mild Cognitive Impairment refers to the presence of cognitive impairments that is not severe enough to meet the criteria of Alzheimer′s, and its diagnosis in early stages is so critical. There is currently no distinct method available for diagnosing Alzheimer′s or Mild Cognitive Impairment, and their diagnosis needs a combination of different methods and assessments. Methods: The aim of this study was to evaluate the effectiveness of functional Magnetic Resonance Imaging (fMRI in differentiating between Alzheimer′s, Mild Cognitive Impairment (MCI and healthy aging. To prove fMRI′s ability, resting-state brain activation patterns between these three groups of subjects were compared using Independent Component Analysis (ICA algorithm. Forty age- and sex-matched subjects, 15 elderly, 11 MCI and 14 Alzheimer′s subjects were examined. Results: The results showed that during a certain resting-state session, healthy aging brain benefits from larger area and greater intensity of activation (compared with MCI and Alzheimer′s group in Posterior Cingulate Cortex (PCC region of the brain, as part of Default Mode Network. Conclusions: This difference in activation pattern can be used as a diagnostic criterion in using fMRI for differentiating between Alzheimer′s Disease (AD, MCI and healthy aging.

  7. Vesicles mimicking normal and cancer cell membranes exhibit differential responses to the cell-penetrating peptide Pep-1.

    Science.gov (United States)

    Almarwani, Bashiyar; Phambu, Esther Nzuzi; Alexander, Christopher; Nguyen, Ha Aimee T; Phambu, Nsoki; Sunda-Meya, Anderson

    2018-06-01

    The cell-penetrating peptide (CPP) Pep-1 presents a great potential in drug delivery due to its intrinsic property to cross plasma membrane. However, its mechanism of entry into the cell remains unresolved. In this study, we compare the selectivity of Pep-1 towards vesicles mimicking normal and cancer cell membranes. The interaction was performed in a wide range of peptide-to-lipid molar ratios using infrared (IR), fluorescence, scanning electron microscopy (SEM), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) techniques. At low peptide concentration, fluorescence experiments show that lipid-phosphatidylserine (PS) seems to enable Pep-1 translocation into cancer cell membrane as evidenced by the blue shift of its maximal emission wavelength. DSC data show that Pep-1 induces segregation of lipids. At high peptide concentration, IR data indicate that the interaction of Pep-1 is relatively stronger with normal cell membrane than with cancer cell membrane through the phosphate groups, while the interaction is weaker with normal cell membrane than with cancer cell membrane through the carbonyl groups. TGA and DSC data reveal that vesicles of normal cell membrane are thermally more stable than vesicles of cancer cell membrane. This suggests that the additional lipid PS included in cancer cell membrane has a destabilizing effect on the membrane structure. SEM images reveal that Pep-1 form superstructures including spherical particles and fibrils in the presence of both model membranes. PS seems to enhance peptide transport across cellular membranes. The biophysical techniques in this study provide valuable insights into the properties of CPPs in drug delivery systems. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. High "normal" blood glucose is associated with decreased brain volume and cognitive performance in the 60s: the PATH through life study.

    Directory of Open Access Journals (Sweden)

    Moyra E Mortby

    Full Text Available Type 2 diabetes is associated with cerebral atrophy, cognitive impairment and dementia. We recently showed higher glucose levels in the normal range not to be free of adverse effects and to be associated with greater hippocampal and amygdalar atrophy in older community-dwelling individuals free of diabetes.This study aimed to determine whether blood glucose levels in the normal range (<6.1 mmol/L were associated with cerebral volumes in structures other than the hippocampus and amygdale, and whether these glucose-related regional volumes were associated with cognitive performance.210 cognitively healthy individuals (68-73 years without diabetes, glucose intolerance or metabolic syndrome were assessed in the large, community-based Personality and Total Health Through Life (PATH study.Baseline blood glucose levels in the normal range (3.2-6.1 mmol/l were used to determine regional brain volumes and associated cognitive function at wave 3.Higher blood glucose levels in the normal range were associated with lower grey/white matter regional volumes in the frontal cortices (middle frontal gyrus, inferior frontal gyrus precentral gyrus. Moreover, identified cerebral regions were associated with poorer cognitive performance and the structure-function associations were gender specific to men.These findings stress the need to re-evaluate what is considered as healthy blood glucose levels, and consider the role of higher normal blood glucose as a risk factor for cerebral health, cognitive function and dementia. A better lifetime management of blood glucose levels may contribute to improved cerebral and cognitive health in later life and possibly protect against dementia.

  9. Differentiation of semantic dementia and Alzheimer's disease using the Addenbrooke's Cognitive Examination (ACE).

    Science.gov (United States)

    Davies, R Rhys; Dawson, Kate; Mioshi, Eneida; Erzinçlioğlu, Sharon; Hodges, John R

    2008-04-01

    The Addenbrooke's Cognitive Examination (ACE) is a simple diagnostic tool bridging the gap between the very brief Mini Mental State Exam (MMSE) and much longer test batteries used by neuropsychologists which has proven extremely popular internationally. We aimed to assess the ability of the ACE to differentiate semantic dementia (SD) from Alzheimer's disease (AD). The ACE was administered to three groups: SD patients (n = 40) and two separate groups of AD patients (n = 40 in each), matched for overall ACE or MMSE score. Significant differences were found between SD and both AD groups for the ACE sub-scores of naming, reading and orientation in time. Discriminant analysis (SD versus AD) led to the formulation of a 'semantic index' (naming plus reading minus scores for serial-7s, orientation in time and drawing). Application of the semantic index to the patient data found values of less than zero to be predictive of SD rather than AD with 88% sensitivity and 90% specificity. Validation analysis in an independent sample of 24 SD and AD patients proved even more favourable. The overall ACE score is known to be a sensitive, and specific, indicator of early neurodegenerative dementia; this study shows that the ACE can also be used to detect SD through application of the semantic index.

  10. Loss of Gnas imprinting differentially affects REM/NREM sleep and cognition in mice.

    Directory of Open Access Journals (Sweden)

    Glenda Lassi

    Full Text Available It has been suggested that imprinted genes are important in the regulation of sleep. However, the fundamental question of whether genomic imprinting has a role in sleep has remained elusive up to now. In this work we show that REM and NREM sleep states are differentially modulated by the maternally expressed imprinted gene Gnas. In particular, in mice with loss of imprinting of Gnas, NREM and complex cognitive processes are enhanced while REM and REM-linked behaviors are inhibited. This is the first demonstration that a specific overexpression of an imprinted gene affects sleep states and related complex behavioral traits. Furthermore, in parallel to the Gnas overexpression, we have observed an overexpression of Ucp1 in interscapular brown adipose tissue (BAT and a significant increase in thermoregulation that may account for the REM/NREM sleep phenotypes. We conclude that there must be significant evolutionary advantages in the monoallelic expression of Gnas for REM sleep and for the consolidation of REM-dependent memories. Conversely, biallelic expression of Gnas reinforces slow wave activity in NREM sleep, and this results in a reduction of uncertainty in temporal decision-making processes.

  11. Multiphoton microscopic imaging of histological sections without hematoxylin and eosin staining differentiates carcinoma in situ lesion from normal oesophagus

    Science.gov (United States)

    Chen, Jianxin; Xu, Jian; Kang, Deyong; Xu, Meifang; Zhuo, Shuangmu; Zhu, Xiaoqin; Jiang, Xingshan

    2013-10-01

    Multiphoton microscopy (MPM) has become a powerful, important tool for tissues imaging at the molecular level. In this paper, this technique was extended to histological investigations, differentiating carcinoma in situ (CIS) lesion from normal oesophagus by imaging histological sections without hematoxylin and eosin (H&E) staining. The results show that the histology procedures of dehydration, paraffin embedding, and de-paraffinizing highlighted two photon excited fluorescence of cytoplasm and nucleolus of epithelial cell and collagen in stroma. MPM has the ability to identify the characteristics of CIS lesion including changes of squamous cells and full epithelium, identification of basement membrane, especially prominent nucleolus. The studies described here show that MPM has the potential for future retrospective studies of tumor staging by employing on histological section specimens without H&E staining.

  12. The differential radiological impact of plutonium recycle in the light-water reactor fuel cycle: effluent discharges during normal operation

    International Nuclear Information System (INIS)

    Bouville, A.; Guetat, P.; Jones, J.A.; Kelly, G.N.; Legrand, J.; White, I.F.

    1980-01-01

    The radiological impact of a light-water reactor fuel cycle utilizing enriched uranium fuel may be altered by the recycle of plutonium. Differences in impact may arise during various operations in the fuel cycle: those which arise from effluents discharged during normal operation of the various installations comprising the fuel cycle are evaluated in this study. The differential radiological impact on the population of the European Communities (EC) of effluents discharged during the recycling of 10 tonnes of fissile plutonium metal is evaluated. The contributions from each stage of the fuel cycle, i.e. fuel fabrication, reactor operation and fuel reprocessing and conversion, are identified. Separate consideration is given to airborne and liquid effluents and account is taken of a wide range of environmental conditions, representative of the EC, in estimating the radiological impact. The recycle of plutonium is estimated to result in a reduction in the radiological impact from effluents of about 30% of that when using enriched uranium fuel

  13. Comparison of microarray platforms for measuring differential microRNA expression in paired normal/cancer colon tissues.

    Directory of Open Access Journals (Sweden)

    Maurizio Callari

    Full Text Available BACKGROUND: Microarray technology applied to microRNA (miRNA profiling is a promising tool in many research fields; nevertheless, independent studies characterizing the same pathology have often reported poorly overlapping results. miRNA analysis methods have only recently been systematically compared but only in few cases using clinical samples. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the inter-platform reproducibility of four miRNA microarray platforms (Agilent, Exiqon, Illumina, and Miltenyi, comparing nine paired tumor/normal colon tissues. The most concordant and selected discordant miRNAs were further studied by quantitative RT-PCR. Globally, a poor overlap among differentially expressed miRNAs identified by each platform was found. Nevertheless, for eight miRNAs high agreement in differential expression among the four platforms and comparability to qRT-PCR was observed. Furthermore, most of the miRNA sets identified by each platform are coherently enriched in data from the other platforms and the great majority of colon cancer associated miRNA sets derived from the literature were validated in our data, independently from the platform. Computational integration of miRNA and gene expression profiles suggested that anti-correlated predicted target genes of differentially expressed miRNAs are commonly enriched in cancer-related pathways and in genes involved in glycolysis and nutrient transport. CONCLUSIONS: Technical and analytical challenges in measuring miRNAs still remain and further research is required in order to increase consistency between different microarray-based methodologies. However, a better inter-platform agreement was found by looking at miRNA sets instead of single miRNAs and through a miRNAs - gene expression integration approach.

  14. Differential effects of psychopathy and antisocial personality disorder symptoms on cognitive and fear processing in female offenders.

    Science.gov (United States)

    Anton, Marja E; Baskin-Sommers, Arielle R; Vitale, Jennifer E; Curtin, John J; Newman, Joseph P

    2012-12-01

    Psychopathy and antisocial personality disorder (APD) have long been considered important risk factors for criminal behavior and incarceration. However, little is known about the psychobiological underpinnings that give rise to the disinhibited behavior of female offenders. Using an instructed fear-conditioning paradigm and a sample of incarcerated female offenders, we manipulated attentional focus and cognitive load to characterize and differentiate between the dysfunctional cognitive and affective processes associated with these syndromes. We used fear-potentiated startle (FPS) and event-related potentials as measures of affective and cognitive processing, respectively. After controlling for APD symptoms, psychopathic women displayed greater FPS while attending directly to threat-relevant stimuli and displayed less FPS while performing a demanding task that directed attention to threat-irrelevant information. Conversely, controlling for psychopathy, women with high APD symptoms displayed less overall FPS, especially when instructed to focus on threat-relevant stimuli. However, as the demands on cognitive resources increased, they displayed greater FPS. For both psychopathy and APD, analysis of the event-related potentials qualified these findings and further specified the abnormal cognitive processes associated with these two syndromes. Overall, simultaneous analysis of psychopathy and APD revealed distinct patterns of cognitive processing and fear reactivity.

  15. Differential effects of psychopathy and antisocial personality disorder symptoms on cognitive and fear processing in female offenders

    Science.gov (United States)

    Anton, Marja E.; Vitale, Jennifer E.; Curtin, John J.; Newman, Joseph P.

    2012-01-01

    Psychopathy and antisocial personality disorder (APD) have long been considered important risk factors for criminal behavior and incarceration. However, little is known about the psychobiological underpinnings that give rise to the disinhibited behavior of female offenders. Using an instructed fear-conditioning paradigm and a sample of incarcerated female offenders, we manipulated attentional focus and cognitive load to characterize and differentiate between the dysfunctional cognitive and affective processes associated with these syndromes. We used fear-potentiated startle (FPS) and event-related potentials as measures of affective and cognitive processing, respectively. After controlling for APD symptoms, psychopathic women displayed greater FPS while attending directly to threat-relevant stimuli and displayed less FPS while performing a demanding task that directed attention to threat-irrelevant information. Conversely, controlling for psychopathy, women with high APD symptoms displayed less overall FPS, especially when instructed to focus on threat-relevant stimuli. However, as the demands on cognitive resources increased, they displayed greater FPS. For both psychopathy and APD, analysis of the event-related potentials qualified these findings and further specified the abnormal cognitive processes associated with these two syndromes. Overall, simultaneous analysis of psychopathy and APD revealed distinct patterns of cognitive processing and fear reactivity. PMID:22886692

  16. The clinical utility of MR diffusion tensor imaging and spatially normalized PET to evaluate traumatic brain injury patients with memory and cognitive impairments

    International Nuclear Information System (INIS)

    Okumura, Ayumi; Yasokawa, Yuuto; Nakayama, Noriyuki; Miwa, Kazuhiro; Shinoda, Jun; Iwama, Toru

    2005-01-01

    We detected and compared abnormal brain areas using both MR diffusion tensor imaging (DTI) and easy Z score imaging system (eZIS) of fluorodeoxyglucose (FDG)-PET for traumatic brain injury patients with memory and cognitive impairments. Twenty normal subjects and eighteen diffuse axonal injury patients with memory and cognitive impairments were studied with DTI and eZIS of 18 F-FDG-PET. DTI contained fractional anisotorophy (FA) analysis and the tractography for the corpus callosum. After PET imaging was performed, statistical analysis using eZIS was undergone with followed processing steps, including smoothing, normalization and z transformation with respect to normal database. Z score map was superimposed on 3D MRI brain. Group analysis was performed using statistical parametric mapping (SPM). In diffuse axonal injury patients, the decline of FA was observed around the corpus callosum in comparison with normal subjects and the reduction of glucose metabolism was shown in the cingulated association. These results suggest that the reduction of metabolism within the cingulated cortex indicated deprived neuronal activation caused by the impaired neuronal connectivity that was revealed with DTI. Furthermore, the metabolic abnormalities within the cingulated cortex may be responsible for memory and cognitive impairments. DTI and spatially normalized PET have a role in neuroimaging interpretation for patients with memory and cognition impairments be cause its 3D better visualization allows objective and systematic investigation. (author)

  17. Differential expression of GPR30 in preeclampsia placenta tissue and normal placenta tissue and its clinical significance

    Directory of Open Access Journals (Sweden)

    Ben-Zhou Feng

    2016-04-01

    Full Text Available Objective: To study the differential expression of GPR30 in preeclampsia placenta tissue and normal placenta tissue and its clinical significance. Methods: Preeclampsia placenta tissue and normal placenta tissue were collected and GPR30 expression levels were detected; human umbilical vein endothelial cells were cultured and processed with GRP30 inhibitor and GRP30 agonist combined with hypoxia-reoxygenation respectively, and cell apoptosis as well as pro-angiogenesis molecule and apoptosis molecule contents were detected. Results: mRNA content and protein content of GRP30 in preeclampsia placenta tissue were significantly lower than those in normal placenta tissue; apoptosis rate of G15 group was significantly higher than that of control group, VEGF and bFGF contents in supernatant were significantly lower than those of control group, and mRNA contents of Bax, Caspase-3 and Caspase-9 in cells were significantly higher than those of control group; apoptosis rate of H/R group was significantly higher than that of control group, VEGF and bFGF contents in supernatant were significantly lower than those of control group, and mRNA contents of Bax, Caspase-3 and Caspase-9 in cells were significantly higher than those of control group; apoptosis rate of G1 group was significantly lower than that of H/R group, VEGF and bFGF contents in supernatant were significantly higher than those of H/R group, and mRNA contents of Bax, Caspase-3 and Caspase-9 in cells were significantly lower than those of H/R group. Conclusions: Low expression of GPR30 in placenta tissue is closely associated with the occurrence of preeclampsia, enhancing GPR function can reduce endothelial cell apoptosis and increase the contents of pro-angiogenesis factors, and it has endothelial protection effect.

  18. Using functional Magnetic Resonance Imaging to differentiate between Healthy Aging subjects, Mild Cognitive Impairment, and Alzheimer’s Patients

    Directory of Open Access Journals (Sweden)

    Mohammad Ali Oghabian

    2010-01-01

    Full Text Available

    Back ground: Alzheimer's disease is the most common form of dementia which is still difficult to be differentiated from other types of brain disorders. Moreover, Mild Cognitive Impairment refers to the presence of cognitive impairments that is not severe enough to meet the criteria of dementia, and its diagnosis in early stages is so critical. There is currently no distinct method available for diagnosing Alzheimer's or Mild Cognitive Impairment, and their diagnosis needs a combination of different methods and assessments.

    Methods: Our goal in this study was to evaluate the effectiveness of fMRI imaging in differentiating between Alzheimer's, Mild Cognitive Impairment (MCI and Healthy Aging. To prove fMRI's ability, we compared resting-state brain activation patterns between these three groups of subjects using Independent Component Algorithm (ICA. We examined 40 age- and sex-matched subjects, 15 elderly, 11 MCI and 14 Alzheimer's subjects.

    Results: The results show that during a certain resting-state session, healthy aging brain benefits from larger area and greater intensity of activation (compared with MCI and Alzheimer's group in Posterior Cingulate Cortex (PCC region of the brain, as part of Default Mode Network.

    Conclusion: This difference in activation pattern can be used as a diagnostic criterion in using fMRI for differentiating between Alzheimer's disease (AD, MCI and Healthy Aging.


    Keywords: fMRI, Default Mode Network, Alzheimer's, Mild Cognitive Impairment, Resting-State

  19. Modeling Differentiation of Cognitive Abilities within the Higher-Order Factor Model Using Moderated Factor Analysis

    Science.gov (United States)

    Molenaar, Dylan; Dolan, Conor V.; Wicherts, Jelte M.; van der Maas, Han L. J.

    2010-01-01

    The general differentiation hypothesis states that the strength of the correlations among a set of IQ subtests varies with a given variable. Instances of the general differentiation hypothesis that have been considered in the literature include age and ability differentiation. Traditionally, the differentiation effect is attributed to the varying…

  20. Cortical thinning in cognitively normal elderly cohort of 60 to 89 year old from AIBL database and vulnerable brain areas

    Science.gov (United States)

    Lin, Zhongmin S.; Avinash, Gopal; Yan, Litao; McMillan, Kathryn

    2014-03-01

    Age-related cortical thinning has been studied by many researchers using quantitative MR images for the past three decades and vastly differing results have been reported. Although results have shown age-related cortical thickening in elderly cohort statistically in some brain regions under certain conditions, cortical thinning in elderly cohort requires further systematic investigation. This paper leverages our previously reported brain surface intensity model (BSIM)1 based technique to measure cortical thickness to study cortical changes due to normal aging. We measured cortical thickness of cognitively normal persons from 60 to 89 years old using Australian Imaging Biomarkers and Lifestyle Study (AIBL) data. MRI brains of 56 healthy people including 29 women and 27 men were selected. We measured average cortical thickness of each individual in eight brain regions: parietal, frontal, temporal, occipital, visual, sensory motor, medial frontal and medial parietal. Unlike the previous published studies, our results showed consistent age-related thinning of cerebral cortex in all brain regions. The parietal, medial frontal and medial parietal showed fastest thinning rates of 0.14, 0.12 and 0.10 mm/decade respectively while the visual region showed the slowest thinning rate of 0.05 mm/decade. In sensorimotor and parietal areas, women showed higher thinning (0.09 and 0.16 mm/decade) than men while in all other regions men showed higher thinning than women. We also created high resolution cortical thinning rate maps of the cohort and compared them to typical patterns of PET metabolic reduction of moderate AD and frontotemporal dementia (FTD). The results seemed to indicate vulnerable areas of cortical deterioration that may lead to brain dementia. These results validate our cortical thickness measurement technique by demonstrating the consistency of the cortical thinning and prediction of cortical deterioration trend with AIBL database.

  1. Differentiating SCT and inattentive symptoms in ADHD using fMRI measures of cognitive control.

    Science.gov (United States)

    Fassbender, Catherine; Krafft, Cynthia E; Schweitzer, Julie B

    2015-01-01

    Attention Deficit/Hyperactivity Disorder (ADHD) is associated with different impairment profiles in the symptom domains of hyperactivity/impulsivity and/or inattention. An additional symptom domain of sluggish cognitive tempo (SCT) has also been proposed. Although there is a degree of correlation between the SCT symptom domain and inattention, it has been proposed as a distinct disorder independent of ADHD. The objective of this study was to examine the neural substrates of cue-related preparatory processes associated with SCT symptoms versus inattentive symptoms in a group of adolescents with ADHD. We also compared cue-related effects in the entire ADHD group compared with a group of typically developing (TD) peers. A modified cued flanker paradigm and fMRI examined brain activity associated with attention preparation and motor response preparation. Between group contrasts between the ADHD and TD group revealed significant hypoactivity in the ADHD group during general attention preparation in the supplementary motor area (SMA) and in the right superior parietal lobe (SPL) during response preparation. In the ADHD group, greater numbers of SCT symptoms were associated with hypoactivity in the left SPL to cues in general whereas greater numbers of inattentive symptoms were associated with greater activity in the SMA to cues that provided no information and less activity in the thalamus during response preparation. Hypoactivity in the SPL with increasing SCT symptoms may be associated with impaired reorienting or shifting of attention. Altered activity in the SMA and thalamus with increasing inattention may be associated with a general problem with response preparation, which may also reflect inefficient processing of the response preparation cue. Our results support a degree of differentiation between SCT and inattentive symptom profiles within adolescents with ADHD.

  2. Cartilage T2 assessment: differentiation of normal hyaline cartilage and reparative tissue after arthroscopic cartilage repair in equine subjects.

    Science.gov (United States)

    White, Lawrence M; Sussman, Marshall S; Hurtig, Mark; Probyn, Linda; Tomlinson, George; Kandel, Rita

    2006-11-01

    To prospectively assess T2 mapping characteristics of normal articular cartilage and of cartilage at sites of arthroscopic repair, including comparison with histologic results and collagen organization assessed at polarized light microscopy (PLM). Study protocol was compliant with the Canadian Council on Animal Care Guidelines and approved by the institutional animal care committee. Arthroscopic osteochondral autograft transplantation (OAT) and microfracture arthroplasty (MFx) were performed in knees of 10 equine subjects (seven female, three male; age range, 3-5 years). A site of arthroscopically normal cartilage was documented in each joint as a control site. Joints were harvested at 12 (n = 5) and 24 (n = 5) weeks postoperatively and were imaged at 1.5-T magnetic resonance (MR) with a 10-echo sagittal fast spin-echo acquisition. T2 maps of each site (21 OAT harvest, 10 MFx, 12 OAT plug, and 10 control sites) were calculated with linear least-squares curve fitting. Cartilage T2 maps were qualitatively graded as "organized" (normal transition of low-to-high T2 signal from deep to superficial cartilage zones) or "disorganized." Quantitative mean T2 values were calculated for deep, middle, and superficial cartilage at each location. Results were compared with histologic and PLM assessments by using kappa analysis. T2 maps were qualitatively graded as organized at 20 of 53 sites and as disorganized at 33 sites. Perfect agreement was seen between organized T2 and histologic findings of hyaline cartilage and between disorganized T2 and histologic findings of fibrous reparative tissue (kappa = 1.0). Strong agreement was seen between organized T2 and normal PLM findings and between disorganized T2 and abnormal PLM findings (kappa = .92). Quantitative assessment of the deep, middle, and superficial cartilage, respectively, showed mean T2 values of 53.3, 58.6, and 54.9 msec at reparative fibrous tissue sites and 40.7, 53.6, and 61.6 msec at hyaline cartilage sites. A

  3. Ambient Persuasive Technology Needs Little Cognitive Effort: The Differential Effects of Cognitive Load on Lighting Feedback versus Factual Feedback

    Science.gov (United States)

    Ham, Jaap; Midden, Cees

    Persuasive technology can influence behavior or attitudes by for example providing interactive factual feedback about energy conservation. However, people often lack motivation or cognitive capacity to consciously process such relative complex information (e.g., numerical consumption feedback). Extending recent research that indicates that ambient persuasive technology can persuade the user without receiving the user's conscious attention, we argue here that Ambient Persuasive Technology can be effective while needing only little cognitive resources, and in general can be more influential than more focal forms of persuasive technology. In an experimental study, some participants received energy consumption feedback by means of a light changing color (more green=lower energy consumption, vs. more red=higher energy consumption) and others by means of numbers indicating kWh consumption. Results indicated that ambient feedback led to more conservation than factual feedback. Also, as expected, only for participants processing factual feedback, additional cognitive load lead to slower processing of that feedback. This research sheds light on fundamental characteristics of Ambient Persuasive Technology and Persuasive Lighting, and suggests that it can have important advantages over more focal persuasive technologies without losing its persuasive potential.

  4. Apolipoprotein E Genotype and educational attainment predict the rate of cognitive decline in normal aging? A 12-year follow-up of the Maastricht Aging Study

    NARCIS (Netherlands)

    van Gerven, P.W.; van Boxtel, M.P.J.; Bekers, O.; Ausems, E.E.B.; Jolles, J.

    2012-01-01

    Objective: We investigated suspected longitudinal interaction effects of apolipoprotein E (APOE) genotype and educational attainment on cognitive decline in normal aging. Method: Our sample consisted of 571 healthy, nondemented adults aged between 49 and 82 years. Linear mixed-models analyses were

  5. The "weakest link" as an indicator of cognitive vulnerability differentially predicts symptom dimensions of anxiety in adolescents in China.

    Science.gov (United States)

    Wang, Junyi; Wang, Danyang; Cui, Lixia; McWhinnie, Chad M; Wang, Li; Xiao, Jing

    2017-08-01

    This multiwave longitudinal study examined the cognitive vulnerability-stress component of hopelessness theory to differentially predict symptom dimensions of anxiety using a "weakest link" approach in a sample of adolescents from Hunan Province, China. Baseline and 6-month follow-up data were obtained from 553 middle-school students. During an initial assessment, participants completed measures of assessing their weakest links, anxious symptoms, and the occurrence of stress. Participants subsequently completed measures assessing stress, and anxious symptoms one a month for six months. Higher weakest link scores were associated with greater increases in the harm avoidance and separation anxiety/panic dimensions, but not the physical or social anxiety dimension, of anxious symptoms following stress in Chinese adolescents. These results support the applicability of the "weakest link" approach, derived from hopelessness theory, in Chinese adolescents. Weakest link scores as cognitive vulnerability factors may play a role in the development of anxious symptoms, especially in the cognitive dimensions (e.g., harm avoidance and separation anxiety/panic). Our findings also have potential value in explaining the effectiveness of cognitive relevant therapy in treating the cognitive dimensions of anxious symptoms. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Gene expression analysis of skin grafts and cultured keratinocytes using synthetic RNA normalization reveals insights into differentiation and growth control.

    Science.gov (United States)

    Katayama, Shintaro; Skoog, Tiina; Jouhilahti, Eeva-Mari; Siitonen, H Annika; Nuutila, Kristo; Tervaniemi, Mari H; Vuola, Jyrki; Johnsson, Anna; Lönnerberg, Peter; Linnarsson, Sten; Elomaa, Outi; Kankuri, Esko; Kere, Juha

    2015-06-25

    Keratinocytes (KCs) are the most frequent cells in the epidermis, and they are often isolated and cultured in vitro to study the molecular biology of the skin. Cultured primary cells and various immortalized cells have been frequently used as skin models but their comparability to intact skin has been questioned. Moreover, when analyzing KC transcriptomes, fluctuation of polyA+ RNA content during the KCs' lifecycle has been omitted. We performed STRT RNA sequencing on 10 ng samples of total RNA from three different sample types: i) epidermal tissue (split-thickness skin grafts), ii) cultured primary KCs, and iii) HaCaT cell line. We observed significant variation in cellular polyA+ RNA content between tissue and cell culture samples of KCs. The use of synthetic RNAs and SAMstrt in normalization enabled comparison of gene expression levels in the highly heterogenous samples and facilitated discovery of differences between the tissue samples and cultured cells. The transcriptome analysis sensitively revealed genes involved in KC differentiation in skin grafts and cell cycle regulation related genes in cultured KCs and emphasized the fluctuation of transcription factors and non-coding RNAs associated to sample types. The epidermal keratinocytes derived from tissue and cell culture samples showed highly different polyA+ RNA contents. The use of SAMstrt and synthetic RNA based normalization allowed the comparison between tissue and cell culture samples and thus proved to be valuable tools for RNA-seq analysis with translational approach. Transciptomics revealed clear difference both between tissue and cell culture samples and between primary KCs and immortalized HaCaT cells.

  7. The normal breast microenvironment of premenopausal women differentially influences the behavior of breast cancer cells in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Ginsburg Erika

    2010-05-01

    Full Text Available Abstract Background Breast cancer studies frequently focus on the role of the tumor microenvironment in the promotion of cancer; however, the influence of the normal breast microenvironment on cancer cells remains relatively unknown. To investigate the role of the normal breast microenvironment on breast cancer cell tumorigenicity, we examined whether extracellular matrix molecules (ECM derived from premenopausal African-American (AA or Caucasian-American (CAU breast tissue would affect the tumorigenicity of cancer cells in vitro and in vivo. We chose these two populations because of the well documented predisposition of AA women to develop aggressive, highly metastatic breast cancer compared to CAU women. Methods The effects of primary breast fibroblasts on tumorigenicity were analyzed via real-time PCR arrays and mouse xenograft models. Whole breast ECM was isolated, analyzed via zymography, and its effects on breast cancer cell aggressiveness were tested in vitro via soft agar and invasion assays, and in vivo via xenograft models. Breast ECM and hormone metabolites were analyzed via mass spectrometry. Results Mouse mammary glands humanized with premenopausal CAU fibroblasts and injected with primary breast cancer cells developed significantly larger tumors compared to AA humanized glands. Examination of 164 ECM molecules and cytokines from CAU-derived fibroblasts demonstrated a differentially regulated set of ECM proteins and increased cytokine expression. Whole breast ECM was isolated; invasion and soft agar assays demonstrated that estrogen receptor (ER-, progesterone receptor (PR/PR- cells were significantly more aggressive when in contact with AA ECM, as were ER+/PR+ cells with CAU ECM. Using zymography, protease activity was comparatively upregulated in CAU ECM. In xenograft models, CAU ECM significantly increased the tumorigenicity of ER+/PR+ cells and enhanced metastases. Mass spectrometry analysis of ECM proteins showed that only 1

  8. Common chromosomal fragile sites (CFS) may be involved in normal and traumatic cognitive stress memory consolidation and altered nervous system immunity.

    Science.gov (United States)

    Gericke, G S

    2010-05-01

    Previous reports of specific patterns of increased fragility at common chromosomal fragile sites (CFS) found in association with certain neurobehavioural disorders did not attract attention at the time due to a shift towards molecular approaches to delineate neuropsychiatric disorder candidate genes. Links with miRNA, altered methylation and the origin of copy number variation indicate that CFS region characteristics may be part of chromatinomic mechanisms that are increasingly linked with neuroplasticity and memory. Current reports of large-scale double-stranded DNA breaks in differentiating neurons and evidence of ongoing DNA demethylation of specific gene promoters in adult hippocampus may shed new light on the dynamic epigenetic changes that are increasingly appreciated as contributing to long-term memory consolidation. The expression of immune recombination activating genes in key stress-induced memory regions suggests the adoption by the brain of this ancient pattern recognition and memory system to establish a structural basis for long-term memory through controlled chromosomal breakage at highly specific genomic regions. It is furthermore considered that these mechanisms for management of epigenetic information related to stress memory could be linked, in some instances, with the transfer of the somatically acquired information to the germline. Here, rearranged sequences can be subjected to further selection and possible eventual retrotranscription to become part of the more stable coding machinery if proven to be crucial for survival and reproduction. While linkage of cognitive memory with stress and fear circuitry and memory establishment through structural DNA modification is proposed as a normal process, inappropriate activation of immune-like genomic rearrangement processes through traumatic stress memory may have the potential to lead to undesirable activation of neuro-inflammatory processes. These theories could have a significant impact on the

  9. Cortical Thickness, Surface Area and Subcortical Volume Differentially Contribute to Cognitive Heterogeneity in Parkinson's Disease

    NARCIS (Netherlands)

    Gerrits, Niels J H M; van Loenhoud, Anita C; van den Berg, Stan F; Berendse, Henk W; Foncke, Elisabeth M J; Klein, Martin; Stoffers, Diederick; van der Werf, Ysbrand D; van den Heuvel, Odile A

    2016-01-01

    Parkinson's disease (PD) is often associated with cognitive deficits, although their severity varies considerably between patients. Recently, we used voxel-based morphometry (VBM) to show that individual differences in gray matter (GM) volume relate to cognitive heterogeneity in PD. VBM does,

  10. Differentiating Processes of Control and Understanding in the Early Development of Emotion and Cognition

    Science.gov (United States)

    Blankson, A. Nayena; O'Brien, Marion; Leerkes, Esther M.; Marcovitch, Stuart; Calkins, Susan D.

    2012-01-01

    In this study, we examined the hypothesis that preschoolers' performance on emotion and cognitive tasks is organized into discrete processes of control and understanding within the domains of emotion and cognition. Additionally, we examined the relations among component processes using mother report, behavioral observation, and physiological…

  11. Differential action on cancer and normal tissue by adrenochrome monoaminoguanidine methanesulfonate and cytochrome C combined with radiotherapy

    International Nuclear Information System (INIS)

    Nakatsugawa, S.; Sugahara, T.

    1994-01-01

    The possibility that radioprotective effects on potent natural killer (NK) cells by adrenochrome monoaminoguanidine methanesulfonate (AMM) + cytochrome C during radiotherapy (RT) for lung cancer might result in the radiosensitization of human lung cancer cells in vivo is examined. Human lung cancer xenografts in the right hind legs of KSN mice (10 weeks old) were locally irradiated with 20 Gy of X ray. AMM (10 mg/kg/day) and/or cytochrome C (CCC) (5 mg/kg/day) were given intraperitoneally immediately before or after RT, followed by daily administration for 4 days. Natural killer activities of host splenocytes were also tested with the standard 51 Cr releasing assay with YAC-1 cells as target cells. In a clinical study, 65 patients with lung cancer were treated with more than 50 Gy of RT with or without combination with AMM + CCC, OK-432 or AMM + CCC + OK-432. Before and after RT, lymphocyte subsets in the peripheral blood were examined with dichromatic analysis using an Ortho Spectrum IIIFCM system and fluorescent MABs. In this study, the change in the absolute number of each subset was investigated. AMM + cytochrome C augumented NK activity in KSN nude mice, protected potent NK cells in patients with lung cancer against RT and sensitized the human lung cancer xenografts to RT. AMM + cytochrome C may have potential as a differential modulator of radiosensitivity of normal tissues and of tumors. 8 refs., 2 figs., 1 tab

  12. Chemical peeling by SA-PEG remodels photo-damaged skin: suppressing p53 expression and normalizing keratinocyte differentiation.

    Science.gov (United States)

    Dainichi, Teruki; Amano, Satoshi; Matsunaga, Yukiko; Iriyama, Shunsuke; Hirao, Tetsuji; Hariya, Takeshi; Hibino, Toshihiko; Katagiri, Chika; Takahashi, Motoji; Ueda, Setsuko; Furue, Masutaka

    2006-02-01

    Chemical peeling with salicylic acid in polyethylene glycol vehicle (SA-PEG), which specifically acts on the stratum corneum, suppresses the development of skin tumors in UVB-irradiated hairless mice. To elucidate the mechanism through which chemical peeling with SA-PEG suppresses skin tumor development, the effects of chemical peeling on photodamaged keratinocytes and cornified envelopes (CEs) were evaluated in vivo. Among UVB-irradiated hairless mice, the structural atypia and expression of p53 protein in keratinocytes induced by UVB irradiation were intensely suppressed in the SA-PEG-treated mice 28 days after the start of weekly SA-PEG treatments when compared to that in the control UVB-irradiated mice. Incomplete expression of filaggrin and loricrin in keratinocytes from the control mice was also improved in keratinocytes from the SA-PEG-treated mice. In photo-exposed human facial skin, immature CEs were replaced with mature CEs 4 weeks after treatment with SA-PEG. Restoration of photodamaged stratum corneum by treatment with SA-PEG, which may affect remodeling of the structural environment of the keratinocytes, involved the normalization of keratinocyte differentiation and suppression of skin tumor development. These results suggest that the stratum corneum plays a protective role against carcinogenesis, and provide a novel strategy for the prevention of photo-induced skin tumors.

  13. Regional Fluid-Attenuated Inversion Recovery (FLAIR at 7 Tesla correlates with Amyloid beta in Hippocampus and Brainstem of cognitively normal elderly subjects.

    Directory of Open Access Journals (Sweden)

    Simon J Schreiner

    2014-09-01

    Full Text Available Background: Accumulation of amyloid beta (Aβ may occur during healthy aging and is a risk factor for Alzheimer Disease (AD. While individual Aβ-accumulation can be measured non-invasively using Pittsburgh compound-B positron-emission-tomography (PiB-PET, Fluid-Attenuated Inversion Recovery (FLAIR is a Magnetic Resonance Imaging (MRI sequence, capable of indicating heterogeneous age-related brain pathologies associated with tissue-edema. In the current study cognitively normal elderly subjects were investigated for regional correlation of PiB- and FLAIR- intensity. Methods: 14 healthy elderly subjects without known history of cognitive impairment received 11C-PiB-PET for estimation of regional Aβ-load. In addition, whole brain T1-MPRAGE and FLAIR-MRI sequences were acquired at high field strength of 7 Tesla (7T. Volume-normalized intensities of brain regions were assessed by applying an automated subcortical segmentation algorithm for spatial definition of brain structures. Statistical dependence between FLAIR- and PiB-PET intensities was tested using Spearman's rank correlation coefficient (rho, followed by Holm-Bonferroni correction for multiple testing. Results: Neuropsychological testing revealed normal cognitive performance levels in all participants. Mean regional PiB-PET and FLAIR intensities were normally distributed and independent. Significant correlation between volume-normalized PiB-PET signals and FLAIR intensities resulted for Hippocampus (right:rho=0.86; left:rho=0.84, Brainstem (rho=0.85 and left Basal Ganglia vessel region (rho=0.82. Conclusions: Our finding of a significant relationship between PiB- and FLAIR-intensity mainly observable in the Hippocampus and Brainstem, indicates regional Aβ associated tissue-edema in cognitively normal elderly subjects. Further studies including clinical populations are necessary to clarify the relevance of our findings for estimating individual risk for age-related neurodegenerative

  14. Regional Fluid-Attenuated Inversion Recovery (FLAIR) at 7 Tesla correlates with amyloid beta in hippocampus and brainstem of cognitively normal elderly subjects

    Science.gov (United States)

    Schreiner, Simon J.; Liu, Xinyang; Gietl, Anton F.; Wyss, Michael; Steininger, Stefanie C.; Gruber, Esmeralda; Treyer, Valerie; Meier, Irene B.; Kälin, Andrea M.; Leh, Sandra E.; Buck, Alfred; Nitsch, Roger M.; Pruessmann, Klaas P.; Hock, Christoph; Unschuld, Paul G.

    2014-01-01

    Background: Accumulation of amyloid beta (Aβ) may occur during healthy aging and is a risk factor for Alzheimer Disease (AD). While individual Aβ-accumulation can be measured non-invasively using Pittsburgh Compund-B positron emission tomography (PiB-PET), Fluid-attenuated inversion recovery (FLAIR) is a Magnetic Resonance Imaging (MRI) sequence, capable of indicating heterogeneous age-related brain pathologies associated with tissue-edema. In the current study cognitively normal elderly subjects were investigated for regional correlation of PiB- and FLAIR intensity. Methods: Fourteen healthy elderly subjects without known history of cognitive impairment received 11C-PiB-PET for estimation of regional Aβ-load. In addition, whole brain T1-MPRAGE and FLAIR-MRI sequences were acquired at high field strength of 7 Tesla (7T). Volume-normalized intensities of brain regions were assessed by applying an automated subcortical segmentation algorithm for spatial definition of brain structures. Statistical dependence between FLAIR- and PiB-PET intensities was tested using Spearman's rank correlation coefficient (rho), followed by Holm–Bonferroni correction for multiple testing. Results: Neuropsychological testing revealed normal cognitive performance levels in all participants. Mean regional PiB-PET and FLAIR intensities were normally distributed and independent. Significant correlation between volume-normalized PiB-PET signals and FLAIR intensities resulted for Hippocampus (right: rho = 0.86; left: rho = 0.84), Brainstem (rho = 0.85) and left Basal Ganglia vessel region (rho = 0.82). Conclusions: Our finding of a significant relationship between PiB- and FLAIR intensity mainly observable in the Hippocampus and Brainstem, indicates regional Aβ associated tissue-edema in cognitively normal elderly subjects. Further studies including clinical populations are necessary to clarify the relevance of our findings for estimating individual risk for age-related neurodegenerative

  15. A combination of supplements may reduce the risk of Alzheimer's disease in elderly Japanese with normal cognition.

    Science.gov (United States)

    Bun, Shogyoku; Ikejima, Chiaki; Kida, Jiro; Yoshimura, Atsuko; Lebowitz, Adam Jon; Kakuma, Tatsuyuki; Asada, Takashi

    2015-01-01

    A number of studies have examined the effect of a single supplement against Alzheimer's disease (AD) with conflicting results. Taking into account the complex and multifactorial nature of AD pathogenesis, multiple supplements may be more effective. Physical activity is another prospect against AD. An open-label intervention study was conducted to explore a potential protective effect of multiple supplements and physical activity. Their interaction was also examined. Participants were community-dwelling volunteers aged 65 or older as of May 2001 in a rural area of Japan. Among 918 cognitively normal participants included in the analyses, 171 took capsules daily for three years that contained n-3 polyunsaturated fatty acid, Ginkgo biloba leaf dry extracts, and lycopene. Two hundred and forty one participants joined the two-year exercise intervention that included a community center-based and a home-based exercise program. One-hundred and forty eight participated in both interventions. A standardized neuropsychological battery was administered at baseline in 2001, the first follow-up in 2004-2005, and the second in 2008-2009. The primary outcome was AD diagnosis at follow-ups. A complementary log-log model was used for survival analysis. A total of 76 participants were diagnosed with AD during follow-up periods. Higher adherence to supplementation intervention was associated with lower AD incidence in both unadjusted and adjusted models. Exercise intervention was also associated with lower AD incidence in the unadjusted model, but not in the adjusted model. We hypothesized that the combination of supplements acted in a complementary and synergistic fashion to bring significant effects against AD occurrence.

  16. White matter measures are near normal in controlled HIV infection except in those with cognitive impairment and longer HIV duration.

    Science.gov (United States)

    Cysique, Lucette A; Soares, James R; Geng, Guangqiang; Scarpetta, Maia; Moffat, Kirsten; Green, Michael; Brew, Bruce J; Henry, Roland G; Rae, Caroline

    2017-08-01

    The objective of the current study was to quantify the degree of white matter (WM) abnormalities in chronic and virally suppressed HIV-infected (HIV+) persons while carefully taking into account demographic and disease factors. Diffusion tensor imaging (DTI) was conducted in 40 HIV- and 82 HIV+ men with comparable demographics and life style factors. The HIV+ sample was clinically stable with successful viral control. Diffusion was measured across 32 non-colinear directions with a b-value of 1000 s/mm 2 ; fractional anisotropy (FA) and mean diffusivity (MD) maps were quantified with Itrack IDL. Using the ENIGMA DTI protocol, FA and MD values were extracted for each participant and in 11 skeleton regions of interest (SROI) from standard labels in the JHU ICBM-81 atlas covering major striato-frontal and parietal tracks. We found no major differences in FA and MD values across the 11 SROI between study groups. Within the HIV+ sample, we found that a higher CNS penetrating antiretroviral treatment, higher current CD4+ T cell count, and immune recovery from the nadir CD4+ T cell count were associated with increased FA and decreased MD (p < 0.05-0.006), while HIV duration, symptomatic, and asymptomatic cognitive impairment were associated with decreased FA and increased MD (p < 0.01-0.004). Stability of HIV treatment and antiretroviral CNS penetration efficiency in addition to current and historical immune recovery were related to higher FA and lower MD (p = 0.04-p < 0.01). In conclusion, WM DTI measures are near normal except for patients with neurocognitive impairment and longer HIV disease duration.

  17. Association between educational attainment and amyloid deposition across the spectrum from normal cognition to dementia: neuroimaging evidence for protection and compensation.

    Science.gov (United States)

    Arenaza-Urquijo, Eider M; Bejanin, Alexandre; Gonneaud, Julie; Wirth, Miranka; La Joie, Renaud; Mutlu, Justine; Gaubert, Malo; Landeau, Brigitte; de la Sayette, Vincent; Eustache, Francis; Chételat, Gaël

    2017-11-01

    The brain mechanisms underlying the effect of intellectual enrichment may evolve along the normal aging Alzheimer's disease (AD) cognitive spectrum and may include both protective and compensatory mechanisms. We assessed the association between early intellectual enrichment (education, years) and average cortical florbetapir standardized uptake value ratio as well as performed voxel-wise analyses in a total of 140 participants, including cognitively normal older adults, mild cognitive impairment (MCI), and AD patients. Higher education was associated with lower cortical florbetapir positron emission tomography (florbetapir-PET) uptake, notably in the frontal lobe in normal older adults, but with higher uptake in frontal, temporal, and parietal regions in MCI after controlling for global cognitive status. No association was found in AD. In MCI, we observed an increased fluorodeoxyglucose positron emission tomography (FDG-PET) uptake with education within the regions of higher florbetapir-PET uptake, suggesting a compensatory increase. Early intellectual enrichment may be associated with protection and compensation for amyloid beta (Aβ) deposition later in life, before the onset of dementia. Previous investigations have been controversial as regard to the effects of intellectual enrichment variables on Aβ deposition; the present findings call for approaches aiming to evaluate mechanisms of resilience across disease stages. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Differential neural substrates of working memory and cognitive skill learning in healthy young volunteers

    International Nuclear Information System (INIS)

    Cho, Sang Soo; Lee, Eun Ju; Yoon, Eun Jin; Kim, Yu Kyeong; Lee, Won Woo; Kim, Sang Eun

    2005-01-01

    It is known that different neural circuits are involved in working memory and cognitive skill learning that represent explicit and implicit memory functions, respectively. In the present study, we investigated the metabolic correlates of working memory and cognitive skill learning with correlation analysis of FDG PET images. Fourteen right-handed healthy subjects (age, 24 ± 2 yr; 5 males and 9 females) underwent brain FDG PET and neuropsychological testing. Two-back task and weather prediction task were used for the evaluation of working memory and cognitive skill learning, respectively, Correlation between regional glucose metabolism and cognitive task performance was examined using SPM99. A significant positive correlation between 2-back task performance and regional glucose metabolism was found in the prefrontal regions and superior temporal gyri bilaterally. In the first term of weather prediction task the task performance correlated positively with glucose metabolism in the bilateral prefrontal areas, left middle temporal and posterior cingulate gyri, and left thalamus. In the second and third terms of the task, the correlation found in the prefrontal areas, superior temporal and anterior cingulate gyri bilaterally, right insula, left parahippocampal gyrus, and right caudate nucleus. We identified the neural substrates that are related with performance of working memory and cognitive skill learning. These results indicate that brain regions associated with the explicit memory system are recruited in early periods of cognitive skill learning, but additional brain regions including caudate nucleus are involved in late periods of cognitive skill learning

  19. Residual Negative Symptoms Differentiate Cognitive Performance in Clinically Stable Patients with Schizophrenia and Bipolar Disorder

    Directory of Open Access Journals (Sweden)

    Rajeev Krishnadas

    2014-01-01

    Full Text Available Cognitive deficits in various domains have been shown in patients with bipolar disorder and schizophrenia. The purpose of the present study was to examine if residual psychopathology explained the difference in cognitive function between clinically stable patients with schizophrenia and bipolar disorder. We compared the performance on tests of attention, visual and verbal memory, and executive function of 25 patients with schizophrenia in remission and 25 euthymic bipolar disorder patients with that of 25 healthy controls. Mediation analysis was used to see if residual psychopathology could explain the difference in cognitive function between the patient groups. Both patient groups performed significantly worse than healthy controls on most cognitive tests. Patients with bipolar disorder displayed cognitive deficits that were milder but qualitatively similar to those of patients with schizophrenia. Residual negative symptoms mediated the difference in performance on cognitive tests between the two groups. Neither residual general psychotic symptoms nor greater antipsychotic doses explained this relationship. The shared variance explained by the residual negative and cognitive deficits that the difference between patient groups may be explained by greater frontal cortical neurophysiological deficits in patients with schizophrenia, compared to bipolar disorder. Further longitudinal work may provide insight into pathophysiological mechanisms that underlie these deficits.

  20. Differential neural substrates of working memory and cognitive skill learning in healthy young volunteers

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Sang Soo; Lee, Eun Ju; Yoon, Eun Jin; Kim, Yu Kyeong; Lee, Won Woo; Kim, Sang Eun [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    2005-07-01

    It is known that different neural circuits are involved in working memory and cognitive skill learning that represent explicit and implicit memory functions, respectively. In the present study, we investigated the metabolic correlates of working memory and cognitive skill learning with correlation analysis of FDG PET images. Fourteen right-handed healthy subjects (age, 24 {+-} 2 yr; 5 males and 9 females) underwent brain FDG PET and neuropsychological testing. Two-back task and weather prediction task were used for the evaluation of working memory and cognitive skill learning, respectively, Correlation between regional glucose metabolism and cognitive task performance was examined using SPM99. A significant positive correlation between 2-back task performance and regional glucose metabolism was found in the prefrontal regions and superior temporal gyri bilaterally. In the first term of weather prediction task the task performance correlated positively with glucose metabolism in the bilateral prefrontal areas, left middle temporal and posterior cingulate gyri, and left thalamus. In the second and third terms of the task, the correlation found in the prefrontal areas, superior temporal and anterior cingulate gyri bilaterally, right insula, left parahippocampal gyrus, and right caudate nucleus. We identified the neural substrates that are related with performance of working memory and cognitive skill learning. These results indicate that brain regions associated with the explicit memory system are recruited in early periods of cognitive skill learning, but additional brain regions including caudate nucleus are involved in late periods of cognitive skill learning.

  1. Differential Prescribing of Antimuscarinic Agents in Older Adults with Cognitive Impairment.

    Science.gov (United States)

    Vouri, Scott Martin; Schootman, Mario; Strope, Seth A; Birge, Stanley J; Olsen, Margaret A

    2018-04-01

    Oral oxybutynin has been associated with the development of cognitive impairment. The objective of this study was to describe the use of oral oxybutynin versus other antimuscarinics (e.g., tolterodine, darifenacin, solifenacin, trospium, fesoterodine, transdermal oxybutynin) in older adults with documented cognitive impairment. This is a population-based retrospective analysis of antimuscarinic new users aged ≥ 66 years from January 2008 to December 2011 (n = 42,886) using a 5% random sample of Medicare claims linked with Part D data. Cognitive impairment was defined as a diagnosis of mild cognitive impairment, dementia, use of antidementia medication, and memory loss/drug-induced cognitive conditions in the year prior to the initial antimuscarinic claim. We used multivariable generalized linear models to assess indicators of cognitive impairment associated with initiation of oral oxybutynin versus other antimuscarinics after adjusting for comorbid conditions. In total, 33% received oral oxybutynin as initial therapy. Cognitive impairment was documented in 10,259 (23.9%) patients prior to antimuscarinic therapy. Patients with cognitive impairment were 5% more likely to initiate another antimuscarinic versus oral oxybutynin (relative risk [RR] 1.05; 95% confidence interval [CI] 1.03-1.06). The proportion of patients with cognitive impairment initiated on oral oxybutynin increased from 24.1% in 2008 to 41.1% in 2011. The total cost of oral oxybutynin, in $US, year 2011 values, decreased by 10.5%, whereas the total cost of other antimuscarinics increased by 50.3% from 2008 to 2011. Our findings suggest opportunities for quality improvement of antimuscarinic prescribing in older adults, but this may be hampered by cost and formulary restrictions.

  2. Increased psychopathology and maladaptive personality traits, but normal cognitive functioning, in patients after long-term cure of acromegaly

    NARCIS (Netherlands)

    Tiemensma, Jitske; Biermasz, Nienke R.; van der Mast, Roos C.; Wassenaar, Moniek J. E.; Middelkoop, Huub A. M.; Pereira, Alberto M.; Romijn, Johannes A.

    2010-01-01

    Active acromegaly is associated with psychopathology, personality changes, and cognitive dysfunction. It is unknown whether, and to what extent, these effects are present after long-term cure of acromegaly. The aim of the study was to assess psychopathology, personality traits, and cognitive

  3. Triple SILAC quantitative proteomic analysis reveals differential abundance of cell signaling proteins between normal and lung cancer-derived exosomes.

    Science.gov (United States)

    Clark, David J; Fondrie, William E; Yang, Austin; Mao, Li

    2016-02-05

    Exosomes are 30-100 nm sized membrane vesicles released by cells into the extracellular space that mediate intercellular communication via transfer of proteins and other biological molecules. To better understand the role of these microvesicles in lung carcinogenesis, we employed a Triple SILAC quantitative proteomic strategy to examine the differential protein abundance between exosomes derived from an immortalized normal bronchial epithelial cell line and two non-small cell lung cancer (NSCLC) cell lines harboring distinct activating mutations in the cell signaling molecules: Kirsten rat sarcoma viral oncogene homolog (KRAS) or epidermal growth factor receptor (EGFR). In total, we were able to quantify 721 exosomal proteins derived from the three cell lines. Proteins associated with signal transduction, including EGFR, GRB2 and SRC, were enriched in NSCLC exosomes, and could actively regulate cell proliferation in recipient cells. This study's investigation of the NSCLC exosomal proteome has identified enriched protein cargo that can contribute to lung cancer progression, which may have potential clinical implications in biomarker development for patients with NSCLC. The high mortality associated with lung cancer is a result of late-stage diagnosis of the disease. Current screening techniques used for early detection of lung cancer lack the specificity for accurate diagnosis. Exosomes are nano-sized extracellular vesicles, and the increased abundance of select protein cargo in exosomes derived from cancer cells may be used for diagnostic purposes. In this paper, we applied quantitative proteomic analysis to elucidate abundance differences in exosomal protein cargo between two NSCLC cell lines with distinctive oncogene mutations and an immortalized normal bronchial epithelial cell line. This study revealed proteins associated with cell adhesion, the extracellular matrix, and a variety of signaling molecules were enriched in NSCLC exosomes. The present data reveals

  4. [Differentiating early dementia from major depression with the Spanish version of the Addenbrooke's Cognitive Examination].

    Science.gov (United States)

    Roca, M; Torralva, T; López, P; Marengo, J; Cetkovich, M; Manes, F

    In clinical practice it is often difficult to establish whether cognitive impairment is secondary to an affective disorder or a dementing process. To describe the cognitive performance on the Spanish version of the Addenbrooke's Cognitive Examination (ACE) of patients with early dementia and depression. 77 patients with early dementia (53 Alzheimer disease; 24 frontotemporal dementia), 17 patients with major depression and 54 healthy volunteers were tested with the Spanish version of the ACE. Alzheimer disease and frontotemporal dementia groups were significantly lower than the control group and the major depression group. When the major depression group was compared with the control group no significant differences were found. The cognitive performance in the ACE is different in patients with early dementia and patient with depression.

  5. Effective connectivity within the frontoparietal control network differentiates cognitive control and working memory.

    Science.gov (United States)

    Harding, Ian H; Yücel, Murat; Harrison, Ben J; Pantelis, Christos; Breakspear, Michael

    2015-02-01

    Cognitive control and working memory rely upon a common fronto-parietal network that includes the inferior frontal junction (IFJ), dorsolateral prefrontal cortex (dlPFC), pre-supplementary motor area/dorsal anterior cingulate cortex (pSMA/dACC), and intraparietal sulcus (IPS). This network is able to flexibly adapt its function in response to changing behavioral goals, mediating a wide range of cognitive demands. Here we apply dynamic causal modeling to functional magnetic resonance imaging data to characterize task-related alterations in the strength of network interactions across distinct cognitive processes. Evidence in favor of task-related connectivity dynamics was accrued across a very large space of possible network structures. Cognitive control and working memory demands were manipulated using a factorial combination of the multi-source interference task and a verbal 2-back working memory task, respectively. Both were found to alter the sensitivity of the IFJ to perceptual information, and to increase IFJ-to-pSMA/dACC connectivity. In contrast, increased connectivity from the pSMA/dACC to the IPS, as well as from the dlPFC to the IFJ, was uniquely driven by cognitive control demands; a task-induced negative influence of the dlPFC on the pSMA/dACC was specific to working memory demands. These results reflect a system of both shared and unique context-dependent dynamics within the fronto-parietal network. Mechanisms supporting cognitive engagement, response selection, and action evaluation may be shared across cognitive domains, while dynamic updating of task and context representations within this network are potentially specific to changing demands on cognitive control. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Structural plasticity of the social brain: Differential change after socio-affective and cognitive mental training.

    Science.gov (United States)

    Valk, Sofie L; Bernhardt, Boris C; Trautwein, Fynn-Mathis; Böckler, Anne; Kanske, Philipp; Guizard, Nicolas; Collins, D Louis; Singer, Tania

    2017-10-01

    Although neuroscientific research has revealed experience-dependent brain changes across the life span in sensory, motor, and cognitive domains, plasticity relating to social capacities remains largely unknown. To investigate whether the targeted mental training of different cognitive and social skills can induce specific changes in brain morphology, we collected longitudinal magnetic resonance imaging (MRI) data throughout a 9-month mental training intervention from a large sample of adults between 20 and 55 years of age. By means of various daily mental exercises and weekly instructed group sessions, training protocols specifically addressed three functional domains: (i) mindfulness-based attention and interoception, (ii) socio-affective skills (compassion, dealing with difficult emotions, and prosocial motivation), and (iii) socio-cognitive skills (cognitive perspective-taking on self and others and metacognition). MRI-based cortical thickness analyses, contrasting the different training modules against each other, indicated spatially diverging changes in cortical morphology. Training of present-moment focused attention mostly led to increases in cortical thickness in prefrontal regions, socio-affective training induced plasticity in frontoinsular regions, and socio-cognitive training included change in inferior frontal and lateral temporal cortices. Module-specific structural brain changes correlated with training-induced behavioral improvements in the same individuals in domain-specific measures of attention, compassion, and cognitive perspective-taking, respectively, and overlapped with task-relevant functional networks. Our longitudinal findings indicate structural plasticity in well-known socio-affective and socio-cognitive brain networks in healthy adults based on targeted short daily mental practices. These findings could promote the development of evidence-based mental training interventions in clinical, educational, and corporate settings aimed at

  7. Recovery from Proactive Semantic Interference in Mild Cognitive Impairment and Normal Aging: Relationship to Atrophy in Brain Regions Vulnerable to Alzheimer's Disease.

    Science.gov (United States)

    Loewenstein, David A; Curiel, Rosie E; Wright, Clinton; Sun, Xiaoyan; Alperin, Noam; Crocco, Elzabeth; Czaja, Sara J; Raffo, Arlene; Penate, Ailyn; Melo, Jose; Capp, Kimberly; Gamez, Monica; Duara, Ranjan

    2017-01-01

    There is growing evidence that proactive semantic interference (PSI) and failure to recover from PSI may represent early features of Alzheimer's disease (AD). This study investigated the association between PSI, recovery from PSI, and reduced MRI volumes in AD signature regions among cognitively impaired and unimpaired older adults. Performance on the LASSI-L (a novel test of PSI and recovery from PSI) and regional brain volumetric measures were compared between 38 cognitively normal (CN) elders and 29 older participants with amnestic mild cognitive impairment (MCI). The relationship between MRI measures and performance on the LASSI-L as well as traditional memory and non-memory cognitive measures was also evaluated in both diagnostic groups. Relative to traditional neuropsychological measures, MCI patients' failure to recover from PSI was associated with reduced volumes in the hippocampus (rs = 0.48), precuneus (rs = 0.50); rostral middle frontal lobules (rs = 0.54); inferior temporal lobules (rs = 0.49), superior parietal lobules (rs = 0.47), temporal pole (rs = 0.44), and increased dilatation of the inferior lateral ventricle (rs = -0.49). For CN elders, only increased inferior lateral ventricular size was associated with vulnerability to PSI (rs = -0.49), the failure to recover from PSI (rs = -0.57), and delayed recall on the Hopkins Verbal Learning Test-Revised (rs = -0.48). LASSI-L indices eliciting failure to recover from PSI were more highly associated with more MRI regional biomarkers of AD than other traditional cognitive measures. These results as well as recent amyloid imaging studies with otherwise cognitively normal subjects, suggest that recovery from PSI may be a sensitive marker of preclinical AD and deserves further investigation.

  8. Is "Learning" episodic memory? Distinct cognitive and neuroanatomic correlates of immediate recall during learning trials in neurologically normal aging and neurodegenerative cohorts.

    Science.gov (United States)

    Casaletto, K B; Marx, G; Dutt, S; Neuhaus, J; Saloner, R; Kritikos, L; Miller, B; Kramer, J H

    2017-07-28

    Although commonly interpreted as a marker of episodic memory during neuropsychological exams, relatively little is known regarding the neurobehavior of "total learning" immediate recall scores. Medial temporal lobes are clearly associated with delayed recall performances, yet immediate recall may necessitate networks beyond traditional episodic memory. We aimed to operationalize cognitive and neuroanatomic correlates of total immediate recall in several aging syndromes. Demographically-matched neurologically normal adults (n=91), individuals with Alzheimer's disease (n=566), logopenic variant primary progressive aphasia (PPA) (n=34), behavioral variant frontotemporal dementia (n=97), semantic variant PPA (n=71), or nonfluent/agrammatic variant PPA (n=39) completed a neurocognitive battery, including the CVLT-Short Form trials 1-4 Total Immediate Recall; a majority subset also completed a brain MRI. Regressions covaried for age and sex, and MMSE in cognitive and total intracranial volume in neuroanatomic models. Neurologically normal adults demonstrated a heterogeneous pattern of cognitive associations with total immediate recall (executive, speed, delayed recall), such that no singular cognitive or neuroanatomic correlate uniquely predicted performance. Within the clinical cohorts, there were syndrome-specific cognitive and neural associations with total immediate recall; e.g., semantic processing was the strongest cognitive correlate in svPPA (partial r=0.41), while frontal volumes was the only meaningful neural correlate in bvFTD (partial r=0.20). Medial temporal lobes were not independently associated with total immediate recall in any group (ps>0.05). Multiple neurobehavioral systems are associated with "total learning" immediate recall scores that importantly differ across distinct clinical syndromes. Conventional memory networks may not be sufficient or even importantly contribute to total immediate recall in many syndromes. Interpreting learning scores as

  9. Effects of glucose, insulin, and insulin resistance on cerebral 18F-FDG distribution in cognitively normal older subjects

    Science.gov (United States)

    Onishi, Airin; Fujiwara, Yoshinori; Ishiwata, Kiichi; Ishii, Kenji

    2017-01-01

    Background Increasing plasma glucose levels and insulin resistance can alter the distribution pattern of fluorine-18-labeled fluorodeoxyglucose (18F-FDG) in the brain and relatively reduce 18F-FDG uptake in Alzheimer's disease (AD)-related hypometabolic regions, leading to the appearance of an AD-like pattern. However, its relationship with plasma insulin levels is unclear. We aimed to compare the effects of plasma glucose levels, plasma insulin levels and insulin resistance on the appearance of the AD-like pattern in 18F-FDG images. Methods Fifty-nine cognitively normal older subjects (age = 75.7 ± 6.4 years) underwent 18F-FDG positron emission tomography along with measurement of plasma glucose and insulin levels. As an index of insulin resistance, the Homeostasis model assessment of Insulin Resistance (HOMA-IR) was calculated. Results Plasma glucose levels, plasma insulin levels, and HOMA-IR were 102.2 ± 8.1 mg/dL, 4.1 ± 1.9 μU/mL, and 1.0 ± 0.5, respectively. Whole-brain voxelwise analysis showed a negative correlation of 18F-FDG uptake with plasma glucose levels in the precuneus and lateral parietotemporal regions (cluster-corrected p < 0.05), and no correlation with plasma insulin levels or HOMA-IR. In the significant cluster, 18F-FDG uptake decreased by approximately 4–5% when plasma glucose levels increased by 20 mg/dL. In the precuneus region, volume-of-interest analysis confirmed a negative correlation of 18F-FDG uptake with plasma glucose levels (r = -0.376, p = 0.002), and no correlation with plasma insulin levels (r = 0.156, p = 0.12) or HOMA-IR (r = 0.096, p = 0.24). Conclusion This study suggests that, of the three parameters, plasma glucose levels have the greatest effect on the appearance of the AD-like pattern in 18F-FDG images. PMID:28715453

  10. Effects of glucose, insulin, and insulin resistance on cerebral 18F-FDG distribution in cognitively normal older subjects.

    Directory of Open Access Journals (Sweden)

    Kenji Ishibashi

    Full Text Available Increasing plasma glucose levels and insulin resistance can alter the distribution pattern of fluorine-18-labeled fluorodeoxyglucose (18F-FDG in the brain and relatively reduce 18F-FDG uptake in Alzheimer's disease (AD-related hypometabolic regions, leading to the appearance of an AD-like pattern. However, its relationship with plasma insulin levels is unclear. We aimed to compare the effects of plasma glucose levels, plasma insulin levels and insulin resistance on the appearance of the AD-like pattern in 18F-FDG images.Fifty-nine cognitively normal older subjects (age = 75.7 ± 6.4 years underwent 18F-FDG positron emission tomography along with measurement of plasma glucose and insulin levels. As an index of insulin resistance, the Homeostasis model assessment of Insulin Resistance (HOMA-IR was calculated.Plasma glucose levels, plasma insulin levels, and HOMA-IR were 102.2 ± 8.1 mg/dL, 4.1 ± 1.9 μU/mL, and 1.0 ± 0.5, respectively. Whole-brain voxelwise analysis showed a negative correlation of 18F-FDG uptake with plasma glucose levels in the precuneus and lateral parietotemporal regions (cluster-corrected p < 0.05, and no correlation with plasma insulin levels or HOMA-IR. In the significant cluster, 18F-FDG uptake decreased by approximately 4-5% when plasma glucose levels increased by 20 mg/dL. In the precuneus region, volume-of-interest analysis confirmed a negative correlation of 18F-FDG uptake with plasma glucose levels (r = -0.376, p = 0.002, and no correlation with plasma insulin levels (r = 0.156, p = 0.12 or HOMA-IR (r = 0.096, p = 0.24.This study suggests that, of the three parameters, plasma glucose levels have the greatest effect on the appearance of the AD-like pattern in 18F-FDG images.

  11. Insulin is Differentially Related to Cognitive Decline and Atrophy in Alzheimer’s Disease and Aging

    Science.gov (United States)

    Burns, Jeffrey M.; Honea, Robyn A.; Vidoni, Eric D.; Hutfles, Lewis; Brooks, William M.; Swerdlow, Russell H.

    2012-01-01

    We assessed the relationship of insulin resistance with cognitive decline and brain atrophy over two years in early Alzheimer’s disease (AD, n=48) and nondemented controls (n=61). Intravenous glucose tolerance tests were conducted at baseline to determine insulin area-under-the-curve (AUC). A standard battery of cognitive tasks and MRI were conducted at baseline and 2-year follow-up. In nondemented controls, higher baseline insulin AUC was associated with 2-year decline in global cognitive performance (beta=−0.36, p=0.005). In early AD, however, higher insulin AUC was associated with less decline in global cognitive performance (beta=0.26, p=0.06), slower global brain atrophy (beta=0.40, p=0.01) and less regional atrophy in the bilateral hippocampi and cingulate cortices. While insulin resistance is associated with cognitive decline in nondemented aging, higher peripheral insulin may have AD-specific benefits or insulin signaling may be affected by systemic physiologic changes associated with AD. PMID:21745566

  12. Differential effects of cognitive load on emotion: Emotion maintenance versus passive experience.

    Science.gov (United States)

    DeFraine, William C

    2016-06-01

    Two separate lines of research have examined the effects of cognitive load on emotional processing with similar tasks but seemingly contradictory results. Some research has shown that the emotions elicited by passive viewing of emotional images are reduced by subsequent cognitive load. Other research has shown that such emotions are not reduced by cognitive load if the emotions are actively maintained. The present study sought to compare and resolve these 2 lines of research. Participants either passively viewed negative emotional images or maintained the emotions elicited by the images, and after a delay rated the intensity of the emotion they were feeling. Half of trials included a math task during the delay to induce cognitive load, and the other half did not. Results showed that cognitive load reduced the intensity of negative emotions during passive-viewing of emotional images but not during emotion maintenance. The present study replicates the findings of both lines of research, and shows that the key factor is whether or not emotions are actively maintained. Also, in the context of previous emotion maintenance research, the present results support the theoretical idea of a separable emotion maintenance process. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  13. Socio-Cognitive Phenotypes Differentially Modulate Large-Scale Structural Covariance Networks.

    Science.gov (United States)

    Valk, Sofie L; Bernhardt, Boris C; Böckler, Anne; Trautwein, Fynn-Mathis; Kanske, Philipp; Singer, Tania

    2017-02-01

    Functional neuroimaging studies have suggested the existence of 2 largely distinct social cognition networks, one for theory of mind (taking others' cognitive perspective) and another for empathy (sharing others' affective states). To address whether these networks can also be dissociated at the level of brain structure, we combined behavioral phenotyping across multiple socio-cognitive tasks with 3-Tesla MRI cortical thickness and structural covariance analysis in 270 healthy adults, recruited across 2 sites. Regional thickness mapping only provided partial support for divergent substrates, highlighting that individual differences in empathy relate to left insular-opercular thickness while no correlation between thickness and mentalizing scores was found. Conversely, structural covariance analysis showed clearly divergent network modulations by socio-cognitive and -affective phenotypes. Specifically, individual differences in theory of mind related to structural integration between temporo-parietal and dorsomedial prefrontal regions while empathy modulated the strength of dorsal anterior insula networks. Findings were robust across both recruitment sites, suggesting generalizability. At the level of structural network embedding, our study provides a double dissociation between empathy and mentalizing. Moreover, our findings suggest that structural substrates of higher-order social cognition are reflected rather in interregional networks than in the the local anatomical markup of specific regions per se. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  14. Cognitive-Behavioral Therapy for Depression Using Mind Over Mood: CBT Skill Use and Differential Symptom Alleviation.

    Science.gov (United States)

    Hawley, Lance L; Padesky, Christine A; Hollon, Steven D; Mancuso, Enza; Laposa, Judith M; Brozina, Karen; Segal, Zindel V

    2017-01-01

    Cognitive-behavioral therapy (CBT) for depression is highly effective. An essential element of this therapy involves acquiring and utilizing CBT skills; however, it is unclear whether the type of CBT skill used is associated with differential symptom alleviation. Outpatients (N = 356) diagnosed with a primary mood disorder received 14 two-hour group sessions of CBT for depression, using the Mind Over Mood protocol. In each session, patients completed the Beck Depression Inventory and throughout the week they reported on their use of CBT skills: behavioral activation (BA), cognitive restructuring (CR), and core belief (CB) strategies. Bivariate latent difference score (LDS) longitudinal analyses were used to examine patterns of differential skill use and subsequent symptom change, and multigroup LDS analyses were used to determine whether longitudinal associations differed as a function of initial depression severity. Higher levels of BA use were associated with a greater subsequent decrease in depressive symptoms for patients with mild to moderate initial depression symptoms relative to those with severe symptoms. Higher levels of CR use were associated with a greater subsequent decrease in depressive symptoms, whereas higher levels of CB use were followed by a subsequent increase in depressive symptoms, regardless of initial severity. Results indicated that the type of CBT skill used is associated with differential patterns of subsequent symptom change. BA use was associated with differential subsequent change as a function of initial severity (patients with less severe depression symptoms demonstrated greater symptom improvement), whereas CR use was associated with symptom alleviation and CB use with an increase in subsequent symptoms as related to initial severity. Copyright © 2016. Published by Elsevier Ltd.

  15. Volumetric correlates of memory and executive function in normal elderly, mild cognitive impairment and Alzheimer’s disease

    Science.gov (United States)

    Duarte, Audrey; Hayasaka, Satoru; Du, Antao; Schuff, Norbert; Jahng, Geon-Ho; Kramer, Joel; Miller, Bruce; Weiner, Michael

    2007-01-01

    In Alzheimer’s disease (AD), atrophy negatively impacts cognition while in healthy adults, inverse relationships between brain volume and cognition may occur. We investigated correlations between gray matter volume and cognition in elderly controls, AD and mild cognitive impairment (MCI) patients with memory and executive deficits. AD demonstrated substantial loss in temporal, parietal and frontal regions while MCI exhibited moderate volume loss in temporal and frontal regions. In controls, memory and executive function were negatively correlated with frontal regions, while in AD, memory was positively correlated with temporal and frontal gyri, and executive function with frontal regions. The combination of the two patterns may explain the lack of correlations in MCI. Developmental versus pathological contributions to these relationships are discussed. PMID:16904823

  16. Associations between apolipoprotein E genotypes and serum levels of glucose, cholesterol, and triglycerides in a cognitively normal aging Han Chinese population.

    Science.gov (United States)

    Tao, Qing-Qing; Chen, Yan; Liu, Zhi-Jun; Sun, Yi-Min; Yang, Ping; Lu, Shen-Ji; Xu, Miao; Dong, Qin-Yun; Yang, Jia-Jun; Wu, Zhi-Ying

    2014-01-01

    To determine the associations between apolipoprotein E (APOE) genotypes and serum levels of glucose, total cholesterol, and triglycerides in a cognitively normal aging Han Chinese population. There were 1,003 cognitively normal aging subjects included in this study. APOE genotypes were analyzed and biochemical parameters were tested. All the subjects were divided into three groups according to APOE genotypes: (1) E2/2 or E2/3 (APOE E2); (2) E3/3 (APOE E3); and (3) E2/4, E3/4, or E4/4 (APOE E4). Correlations of serum levels of glucose, total cholesterol, and triglycerides with APOE genotypes were assessed. E2, E3, and E4 allele frequencies were found to be 6.2%, 82.1%, and 11.7%, respectively. Serum levels of total cholesterol were higher in the APOE E4 group (Ptriglycerides (adjusted odds ratio 1.042, 95% confidence interval 0.759-1.429, P=0.800). A higher serum level of total cholesterol was significantly correlated with APOE E4 status in a cognitively normal, nondiabetic aging population. However, there was no correlation between APOE genotypes and serum levels of glucose or total triglycerides.

  17. Differential effects of enriched environment at work on cognitive decline in old age.

    Science.gov (United States)

    Then, Francisca S; Luck, Tobias; Luppa, Melanie; König, Hans-Helmut; Angermeyer, Matthias C; Riedel-Heller, Steffi G

    2015-05-26

    The aim of the present study was to investigate how different mentally demanding work conditions during the professional life-i.e., enriched environments at work-might influence the rate of cognitive decline in old age. Individuals (n = 1,054) of the Leipzig Longitudinal Study of the Aged, a representative population-based cohort study of individuals aged 75 years and older, underwent cognitive testing via the Mini-Mental State Examination (MMSE) in up to 6 measurement waves. Type and level of mentally demanding work conditions in the participants' former professional life were classified based on the O*NET job descriptor database. In multivariate mixed-model analyses (controlling for sociodemographic and health-related factors), a high level of mentally demanding work tasks stimulating verbal intelligence was significantly associated with a better cognitive functioning at baseline (on average 5 MMSE points higher) as well as a lower rate of cognitive decline (on average 2 MMSE points less) over the 8-year follow-up period compared with a low level. The rate of cognitive decline in old age was also significantly lower (on average 3 MMSE points less) in individuals who had a high level of mentally demanding work tasks stimulating executive functions than those who had a low level. The results suggest that a professional life enriched with work tasks stimulating verbal intelligence and executive functions may help to sustain a good cognitive functioning in old age (75+ years). The findings thus emphasize that today's challenging work conditions may also promote positive health effects. © 2015 American Academy of Neurology.

  18. Aromas of rosemary and lavender essential oils differentially affect cognition and mood in healthy adults.

    Science.gov (United States)

    Moss, Mark; Cook, Jenny; Wesnes, Keith; Duckett, Paul

    2003-01-01

    This study was designed to assess the olfactory impact of the essential oils of lavender (Lavandula angustifolia) and rosemary (Rosmarlnus officinalis) on cognitive performance and mood in healthy volunteers. One hundred and forty-four participants were randomly assigned to one of three independent groups, and subsequently performed the Cognitive Drug Research (CDR) computerized cognitive assessment battery in a cubicle containing either one of the two odors or no odor (control). Visual analogue mood questionnaires were completed prior to exposure to the odor, and subsequently after completion of the test battery. The participants were deceived as to the genuine aim of the study until the completion of testing to prevent expectancy effects from possibly influencing the data. The outcome variables from the nine tasks that constitute the CDR core battery feed into six factors that represent different aspects of cognitive functioning. Analysis of performance revealed that lavender produced a significant decrement in performance of working memory, and impaired reaction times for both memory and attention based tasks compared to controls. In contrast, rosemary produced a significant enhancement of performance for overall quality of memory and secondary memory factors, but also produced an impairment of speed of memory compared to controls. With regard to mood, comparisons of the change in ratings from baseline to post-test revealed that following the completion of the cognitive assessment battery, both the control and lavender groups were significantly less alert than the rosemary condition; however, the control group was significantly less content than both rosemary and lavender conditions. These findings indicate that the olfactory properties of these essential oils can produce objective effects on cognitive performance, as well as subjective effects on mood.

  19. Measurement of normalized differential $t\\bar{t}$ cross sections in the dilepton channel from pp collisions at 13 TeV

    CERN Document Server

    Roh, Youn

    2017-01-01

    Measurements of normalized differential cross sections for top quark pair production are performed in the dilepton decay channels in proton-proton collisions at a center-of-mass energy of 13~TeV. The differential cross sections are measured with data corresponding to an integrated luminosity of 2.1~fb$^{-1}$ recorded by the CMS experiment at the LHC. We have measured the cross sections differentially as a function of the kinematic properties of the leptons (electron or muon), jets from bottom quark hadronization, top quarks, and top quark pairs at the particle and parton levels. The $t\\bar{t}$ differential cross section measurements are compared to several Monte Carlo generators that implement calculations up to next-to-leading order in perturbative quantum chromodynamics interfaced with parton showering, and also to fixed-order theoretical calculations of top quark pair production beyond next-to-leading order accuracy.

  20. Do apolipoprotein E genotype and educational attainment predict the rate of cognitive decline in normal aging? A 12-year follow-up of the Maastricht Aging Study.

    Science.gov (United States)

    Van Gerven, Pascal W M; Van Boxtel, Martin P J; Ausems, Eleonora E B; Bekers, Otto; Jolles, Jelle

    2012-07-01

    We investigated suspected longitudinal interaction effects of apolipoprotein E (APOE) genotype and educational attainment on cognitive decline in normal aging. Our sample consisted of 571 healthy, nondemented adults aged between 49 and 82 years. Linear mixed-models analyses were performed with four measurement time points: baseline, 3-year, 6-year, and 12-year follow-up. Covariates included age at baseline, sex, and self-perceived physical and mental health. Dependent measures were global cognitive functioning (Mini-Mental State Examination; Folstein, Folstein, & McHugh, 1975), Stroop performance (Stroop Color-Word Test; Van der Elst, Van Boxtel, Van Breukelen, & Jolles, 2006a), set-shifting performance (Concept Shifting Test; Van der Elst, Van Boxtel, Van Breukelen, & Jolles, 2006b), cognitive speed (Letter-Digit Substitution Test; Van der Elst, Van Boxtel, Van Breukelen, & Jolles, 2006c), verbal learning (Verbal Learning Test: Sum of five trials; Van der Elst, Van Boxtel, Van Breukelen, & Jolles, 2005), and long-term memory (Verbal Learning Test: Delayed recall). We found only faint evidence that older, high-educated carriers of the APOE-ε4 allele (irrespective of zygosity) show a more pronounced decline than younger, low-educated carriers and noncarriers (irrespective of educational attainment). Moreover, this outcome was confined to concept-shifting performance and was especially observable between 6- and 12-year follow-ups. No protective effects of higher education were found on any of the six cognitive measures. We conclude that the combination of APOE-ε4 allele and high educational attainment may be a risk factor for accelerated cognitive decline in older age, as has been reported before, but only to a very limited extent. Moreover, we conclude that, within the cognitive reserve framework, education does not have significant protective power against age-related cognitive decline.

  1. Integrating the Differentiated: A Review of the Personal Construct Approach to Cognitive Complexity

    Czech Academy of Sciences Publication Activity Database

    Kovářová, Marie; Filip, Miroslav

    2015-01-01

    Roč. 28, č. 4 (2015), s. 342-366 ISSN 1072-0537 R&D Projects: GA ČR(CZ) GAP407/12/2432 Institutional support: RVO:68081740 Keywords : cognitive complexity * psychology of personal constructs * repertory grid technique Subject RIV: AN - Psychology Impact factor: 0.333, year: 2015

  2. Cognitive benefit and cost of acute stress is differentially modulated by individual brain state

    NARCIS (Netherlands)

    Kohn, N.; Hermans, E.J.; Fernandez, G.

    2017-01-01

    Acute stress is associated with beneficial as well as detrimental effects on cognition in different individuals. However, it is not yet known how stress can have such opposing effects. Stroop-like tasks typically show this dissociation: stress diminishes speed, but improves accuracy. We investigated

  3. The differential effects of tangible rewards and praise on intrinsic motivation: A comparison of cognitive evaluation theory and operant theory.

    Science.gov (United States)

    Carton, J S

    1996-01-01

    Substantial research indicates that tangible rewards, such as money, prizes, and tokens, decrease response rates by undermining intrinsic motivation. In contrast, praise appears to increase response rates by enhancing intrinsic motivation. Based on their interpretation of available evidence, many social-cognitive researchers warn not to use tangible rewards in applied settings and to use praise instead. Furthermore, they suggest that the differential effects of the two types of rewards on intrinsic motivation cannot be explained using principles of operant psychology. Cognitive evaluation theory provides one of the most recent and widely cited social-cognitive explanations for the different effects of the two types of rewards on intrinsic motivation (Deci & Ryan, 1985). However, a review of existing research found little support for the explanations based on this theory and revealed three potential confounding effects: (a) temporal contiguity, (b) the number of reward administrations, and (c) discriminative stimuli associated with reward availability. These three confounding factors provide explanations for the effects of tangible rewards and praise on intrinsic motivation that are consistent with principles of operant psychology.

  4. Differential spontaneous recovery across cognitive abilities during detoxification period in alcohol-dependence.

    Directory of Open Access Journals (Sweden)

    Géraldine Petit

    Full Text Available There is a lack of consensus regarding the extent to which cognitive dysfunctions may recover upon cessation of alcohol intake by alcohol-dependents (AD, and the divergent findings are most likely due to methodological differences between the various studies. The present study was aimed at conducting a very strict longitudinal study of cognitive recovery in terms of assessment points, the duration of abstinence, control of age and duration of the addiction, and by use of individual analyses in addition to mean group comparisons. Our study further focused on the 2-3 week phase of alcohol detoxification that is already known to positively affect many biological, emotional, motivational, as well as neural variables, followed by longer-term therapies for which good cognitive functioning is needed.41 AD inpatients undergoing a detoxification program, and 41 matched controls, were evaluated twice in terms of five cognitive functions (i.e., short-term memory, working memory, inhibition, cognitive flexibility, and verbal fluency within a three-week interval [on the first day (T1 and the 18th day (T2 of abstinence for AD patients]. Emotional (positive and negative affectivity and depression and motivational (craving variables were also measured at both evaluation times.Although verbal fluency, short-term memory, and cognitive flexibility did not appear to be affected, the patients exhibited impaired inhibition and working memory at T1. While no recovery of inhibition was found to occur, the average working memory performance of the patients was comparable to that of the controls at T2. Improvements in emotional and motivational dimensions were also observed, although they did not correlate with the ones in working memory. Individual analysis showed that not all participants were impaired or recover the same functions.While inhibition deficits appear to persist after 18 days of detoxification, deficits in working memory, which is a central component of

  5. Phase- and size-adjusted CT cut-off for differentiating neoplastic lesions from normal colon in contrast-enhanced CT colonography

    International Nuclear Information System (INIS)

    Luboldt, W.; Kroll, M.; Wetter, A.; Vogl, T.J.; Toussaint, T.L.; Hoepffner, N.; Holzer, K.; Kluge, A.

    2004-01-01

    A computed tomography (CT) cut-off for differentiating neoplastic lesions (polyps/carcinoma) from normal colon in contrast-enhanced CT colonography (CTC) relating to the contrast phase and lesion size is determined. CT values of 64 colonic lesions (27 polyps 0 . The slope m was determined by linear regression in the correlation (lesion ∝[xA + (1 - x)V]//H) and the Y-intercept y 0 by the minimal shift of the line needed to maximize the accuracy of separating the colonic wall from the lesions. The CT value of the lesions correlated best with the intermediate phase: 0.4A+ 0.6V(r=0.8 for polyps ≥10 mm, r=0.6 for carcinomas, r=0.4 for polyps <10 mm). The accuracy in the differentiation between lesions and normal colonic wall increased with the height implemented as divisor, reached 91% and was obtained by the dynamic cut-off described by the formula: cut-off(A,V,H) = 1.1[0.4A + 0.6V]/H + 69.8. The CT value of colonic polyps or carcinomas can be increased extrinsically by scanning in the phase in which 0.4A + 0.6V reaches its maximum. Differentiating lesions from normal colon based on CT values is possible in contrast-enhanced CTC and improves when the cut-off is adjusted (normalized) to the contrast phase and lesion size. (orig.)

  6. Differential diagnosis of depression and Alzheimer's disease with the Addenbrooke's Cognitive Examination-Revised (ACE-R).

    Science.gov (United States)

    Rotomskis, Augustinas; Margevičiūtė, Ramunė; Germanavičius, Arūnas; Kaubrys, Gintaras; Budrys, Valmantas; Bagdonas, Albinas

    2015-04-17

    One of the usual problems psychologists and clinicians face in clinical practice is differential diagnostics of Alzheimer's disease and depression. It has been reported that the ACE and ACE-R could discriminate the cognitive dysfunctions due to depression from that due to dementia, although this is not uniform in all studies. The current study aimed to evaluate the utility of the ACE-R to differentiate late-life onset depression (with severe episode) from mild-moderate Alzheimer's Disease (AD). This study received approval from the Lithuanian Bioethics Committee. All participants were older than 50 years (mean age = 66.52 (±8.76) years). The study sample consisted of 295 individuals: 117 with severe depression, 85 with mild-moderate Alzheimer's disease (AD), and 94 age, gender and education matched participants of control group. The ACE-R had high sensitivity (100%) and specificity (81%) at detecting cognitive impairments related to AD. Patients with late-life onset depression (ACE-R mean 76.82, SD = 7.36) performed worse than controls (ACE-R mean 85.08, SD = 7.2), but better than the AD group (ACE-R mean 54.74, SD = 12.19). Participants with late-life onset depression were differentiated by mild impairment in the ACE-R total score with mild memory (13.79, SD = 6.29) and greater deficits in letter fluency (3.65, SD = 1.21) than in semantic fluency (4.68, SD = 1.23). Participants with AD were differentiated by severely impaired performance on attention and orientation (11.80, SD = 2.93), memory (8.25, SD = 3.47) and language subtests (17.21, SD = 4.04), and moderately impaired performance on verbal fluency (6.07, SD = 2.74). ACE-R has diagnostic accuracy in detecting people with AD and can be used in differential diagnostics of late-life onset depression (severe episode) and AD. Diagnostic accuracy may be improved by analyzing the neuropsychological profiles and using lower cutoffs for different age groups.

  7. White matter hyperintensities and cognitive reserve during a working memory task: a functional magnetic resonance imaging study in cognitively normal older adults.

    Science.gov (United States)

    Fernández-Cabello, Sara; Valls-Pedret, Cinta; Schurz, Matthias; Vidal-Piñeiro, Dídac; Sala-Llonch, Roser; Bargallo, Nuria; Ros, Emilio; Bartrés-Faz, David

    2016-12-01

    Cognitive reserve (CR) models posit that lifestyle factors such as education modulate the relationship between brain damage and cognition. However, the functional correlates of CR in healthy aging are still under investigation. White matter hyperintensities (WMHs) are a common age-associated finding that impacts cognition. In this study, we used functional magnetic resonance imaging to characterize the patterns of brain activation during a working memory task in older participants with high and low levels of education (as a proxy of CR) and high and low WMH volumes. Ninety older volunteers (aged 63-76 years) and 16 young adults (aged 21-27) completed the study. We found that older adults with higher education had better working memory performance than their less educated peers. Among the highly educated participants, those with WMH over-recruited areas engaged by young volunteers and showed activation in additional cortical and subcortical structures. However, those with low WMH differed little with respect to their younger counterparts. Our findings demonstrate that the functional mechanisms subtending the effects of education, as a proxy of CR, are modulated according to the WMH burden. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Cognitive functioning differentially predicts different dimensions of older drivers' on-road safety.

    Science.gov (United States)

    Aksan, Nazan; Anderson, Steve W; Dawson, Jeffrey; Uc, Ergun; Rizzo, Matthew

    2015-02-01

    The extent to which deficits in specific cognitive domains contribute to older drivers' safety risk in complex real-world driving tasks is not well understood. We selected 148 drivers older than 70 years of age both with and without neurodegenerative diseases (Alzheimer disease-AD and Parkinson disease-PD) from an existing driving database of older adults. Participant assessments included on-road driving safety and cognitive functioning in visuospatial construction, speed of processing, memory, and executive functioning. The standardized on-road drive test was designed to examine multiple facets of older driver safety including navigation performance (e.g., following a route, identifying landmarks), safety errors while concurrently performing secondary navigation tasks ("on-task" safety errors), and safety errors in the absence of any secondary navigation tasks ("baseline" safety errors). The inter-correlations of these outcome measures were fair to moderate supporting their distinctiveness. Participants with diseases performed worse than the healthy aging group on all driving measures and differences between those with AD and PD were minimal. In multivariate analyses, different domains of cognitive functioning predicted distinct facets of driver safety on road. Memory and set-shifting predicted performance in navigation-related secondary tasks, speed of processing predicted on-task safety errors, and visuospatial construction predicted baseline safety errors. These findings support broad assessments of cognitive functioning to inform decisions regarding older driver safety on the road and suggest navigation performance may be useful in evaluating older driver fitness and restrictions in licensing. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Differential cognitive effects of energy drink ingredients: caffeine, taurine, and glucose.

    Science.gov (United States)

    Giles, Grace E; Mahoney, Caroline R; Brunyé, Tad T; Gardony, Aaron L; Taylor, Holly A; Kanarek, Robin B

    2012-10-01

    Energy drinks containing caffeine, taurine, and glucose may improve mood and cognitive performance. However, there are no studies assessing the individual and interactive effects of these ingredients. We evaluated the effects of caffeine, taurine, and glucose alone and in combination on cognitive performance and mood in 24-hour caffeine-abstained habitual caffeine consumers. Using a randomized, double-blind, mixed design, 48 habitual caffeine consumers (18 male, 30 female) who were 24-hour caffeine deprived received one of four treatments (200 mg caffeine/0 mg taurine, 0 mg caffeine/2000 mg taurine, 200 mg caffeine/2000 mg taurine, 0 mg caffeine/0 mg taurine), on each of four separate days, separated by a 3-day wash-out period. Between-participants treatment was a glucose drink (50 g glucose, placebo). Salivary cortisol, mood and heart rate were measured. An attention task was administered 30-minutes post-treatment, followed by a working memory and reaction time task 60-minutes post-treatment. Caffeine enhanced executive control and working memory, and reduced simple and choice reaction time. Taurine increased choice reaction time but reduced reaction time in the working memory tasks. Glucose alone slowed choice reaction time. Glucose in combination with caffeine, enhanced object working memory and in combination with taurine, enhanced orienting attention. Limited glucose effects may reflect low task difficulty relative to subjects' cognitive ability. Caffeine reduced feelings of fatigue and increased tension and vigor. Taurine reversed the effects of caffeine on vigor and caffeine-withdrawal symptoms. No effects were found for salivary cortisol or heart rate. Caffeine, not taurine or glucose, is likely responsible for reported changes in cognitive performance following consumption of energy drinks, especially in caffeine-withdrawn habitual caffeine consumers. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Korean Addenbrooke's Cognitive Examination Revised (K-ACER) for differential diagnosis of Alzheimer's disease and subcortical ischemic vascular dementia.

    Science.gov (United States)

    Kwak, Yong Tae; Yang, Youngsoon; Kim, Gyung Whan

    2010-10-01

    Sensitive, specific neuropsychological screening tests, such as the Addenbrooke's Cognitive Examination Revised (ACE-R), are essential for dementia diagnosis. We aimed to validate the use of the Korean version of ACE-R (K-ACER) to differentiate Alzheimer's disease (AD) from subcortical ischemic vascular dementia (SIVD). Standard tests for dementia screening were applied to 156 subjects (84 controls, 30 AD, 42 SIVD), and total and sub-domain scores on the K-ACER, as well as the sub-domain ratio (VLOM), were compared. The reliability of the K-ACER was very good (α-coefficient 0.84), and cut-off score for dementia was determined (cut-off value 78, sensitivity 0.93, specificity 0.95). The likelihood ratio for dementia was calculated as between 78 and 82. At a cut-off of 78, the likelihood of dementia was 18.6:1. Although a comparison of K-ACER scores between AD and SIVD patients revealed significant differences in verbal fluency, language domain and VLOM ratio, sensitivity and specificity for differential diagnosis between AD and SVID proved less accurate. The K-ACER is a rapid, sensitive and specific dementia screening test. Though sub-domains of items may be useful for differentiating between AD and SIVD, sensitivity and specificity is less accurate than dementia screening itself. © 2010 Japan Geriatrics Society.

  11. QoS Differential Scheduling in Cognitive-Radio-Based Smart Grid Networks: An Adaptive Dynamic Programming Approach.

    Science.gov (United States)

    Yu, Rong; Zhong, Weifeng; Xie, Shengli; Zhang, Yan; Zhang, Yun

    2016-02-01

    As the next-generation power grid, smart grid will be integrated with a variety of novel communication technologies to support the explosive data traffic and the diverse requirements of quality of service (QoS). Cognitive radio (CR), which has the favorable ability to improve the spectrum utilization, provides an efficient and reliable solution for smart grid communications networks. In this paper, we study the QoS differential scheduling problem in the CR-based smart grid communications networks. The scheduler is responsible for managing the spectrum resources and arranging the data transmissions of smart grid users (SGUs). To guarantee the differential QoS, the SGUs are assigned to have different priorities according to their roles and their current situations in the smart grid. Based on the QoS-aware priority policy, the scheduler adjusts the channels allocation to minimize the transmission delay of SGUs. The entire transmission scheduling problem is formulated as a semi-Markov decision process and solved by the methodology of adaptive dynamic programming. A heuristic dynamic programming (HDP) architecture is established for the scheduling problem. By the online network training, the HDP can learn from the activities of primary users and SGUs, and adjust the scheduling decision to achieve the purpose of transmission delay minimization. Simulation results illustrate that the proposed priority policy ensures the low transmission delay of high priority SGUs. In addition, the emergency data transmission delay is also reduced to a significantly low level, guaranteeing the differential QoS in smart grid.

  12. Interactive Associations of Vascular Risk and β-Amyloid Burden With Cognitive Decline in Clinically Normal Elderly Individuals: Findings From the Harvard Aging Brain Study.

    Science.gov (United States)

    Rabin, Jennifer S; Schultz, Aaron P; Hedden, Trey; Viswanathan, Anand; Marshall, Gad A; Kilpatrick, Emily; Klein, Hannah; Buckley, Rachel F; Yang, Hyun-Sik; Properzi, Michael; Rao, Vaishnavi; Kirn, Dylan R; Papp, Kathryn V; Rentz, Dorene M; Johnson, Keith A; Sperling, Reisa A; Chhatwal, Jasmeer P

    2018-05-21

    Identifying asymptomatic individuals at high risk of impending cognitive decline because of Alzheimer disease is crucial for successful prevention of dementia. Vascular risk and β-amyloid (Aβ) pathology commonly co-occur in older adults and are significant causes of cognitive impairment. To determine whether vascular risk and Aβ burden act additively or synergistically to promote cognitive decline in clinically normal older adults; and, secondarily, to evaluate the unique influence of vascular risk on prospective cognitive decline beyond that of commonly used imaging biomarkers, including Aβ burden, hippocampal volume, fludeoxyglucose F18-labeled (FDG) positron emission tomography (PET), and white matter hyperintensities, a marker of cerebrovascular disease. In this longitudinal observational study, we examined clinically normal older adults from the Harvard Aging Brain Study. Participants were required to have baseline imaging data (FDG-PET, Aβ-PET, and magnetic resonance imaging), baseline medical data to quantify vascular risk, and at least 1 follow-up neuropsychological visit. Data collection began in 2010 and is ongoing. Data analysis was performed on data collected between 2010 and 2017. Vascular risk was quantified using the Framingham Heart Study general cardiovascular disease (FHS-CVD) risk score. We measured Aβ burden with Pittsburgh Compound-B PET. Cognition was measured annually with the Preclinical Alzheimer Cognitive Composite. Models were corrected for baseline age, sex, years of education, and apolipoprotein E ε4 status. Of the 223 participants, 130 (58.3%) were women. The mean (SD) age was 73.7 (6.0) years, and the mean (SD) follow-up time was 3.7 (1.2) years. Faster cognitive decline was associated with both a higher FHS-CVD risk score (β = -0.064; 95% CI, -0.094 to -0.033; P < .001) and higher Aβ burden (β = -0.058; 95% CI, -0.079 to -0.037; P < .001). The interaction of the FHS-CVD risk score and Aβ burden with time

  13. Transfer and maintenance effects of online working-memory training in normal ageing and mild cognitive impairment

    NARCIS (Netherlands)

    Vermeij, A.; Claassen, J.A.; Dautzenberg, P.L.; Kessels, R.P.C.

    2016-01-01

    Working memory (WM) is one of the cognitive functions that is susceptible to ageing-related decline. Interventions that are able to improve WM functioning at older age are thus highly relevant. In this pilot study, we explored the transfer effects of core WM training on the WM domain and other

  14. Circulating microRNAs disclose biology of normal cognitive function in healthy elderly people – a discovery twin study

    DEFF Research Database (Denmark)

    Mengel-From, Jonas; Feddersen, Søren; Halekoh, Ulrich

    2018-01-01

    Neurobiology is regulated by miRNA. Here circulating plasma miRNAs were assayed on a 754 miRNA OpenArray platform using 90 monozygotic elderly twins (73–95 year of age) and associated with mini mental state examination (MMSE) and a five-component cognitive score (CCS) in an explorative study. Bot...

  15. [From acute victimization at chronic victimization: socio-cognitive approach of differential tolerance threshold].

    Science.gov (United States)

    Forte, M; Przygodzki-Lionet, N; Masclet, G

    2006-01-01

    own resources. These modulators would correspond to the social evaluation of the stressor and the adjustment strategies adopted by the victims. We then postulate the fact that these interfering variables would determine a connection between the type of victimization and the series of signs and symptoms generated. In other words, the aversive modes would refer to a process of significance via these interpolated socio-cognitive factors, thus forming a trace of the traumatic event according to the tolerance threshold expressed. More precisely, our assumption consists in postulating that the insidious and latent aspect of harassment which is supposed to support a dispositional attribution of the harasser's intrigues as well as the preferential adoption of coping strategies centred on emotional control, would lower the victims' tolerance threshold further, than a visible and instantaneous hold-up which is supposed to condition an essentially situational perception and the adoption of strategies mainly directed towards the problem. Since this study is the subject of a comparative research strategy, its required the constitution of three independent samples: ten harassment victims; seven armed attack victims; ten witnesses, all salaried employees; they had not been subjected to either type of attack but were questioned about a working life event seen as stressful. The three groups, set up according to sex and age considerations, agreed to be subjected to a semi-directive interview. Considering the exploratory nature of this present research, the process proved to be most suitable since, through the filter of the people's subjectivity, it clearly determined the meaning granted by the victim to the aversive situation. In order to comply with a standardization preoccupation, each interview was identically structured using a preset question grid and similar operating conditions. The data collected were then subjected to four levels of analysis. An analysis of contents, centred

  16. Motor-evoked potential amplitudes elicited by transcranial magnetic stimulation do not differentiate between patients and normal controls.

    Science.gov (United States)

    Grunhaus, Leon; Polak, Dana; Amiaz, Revital; Dannon, Pinhas N

    2003-12-01

    Transcranial magnetic stimulation (TMS) applied over the motor cortex depolarizes neurons and leads to motor-evoked potentials (MEP). To assess cortico-spinal excitability we compared the motor threshold (MT) and the averaged MEP amplitude generated by TMS in patients with major depression (MD) and matched controls. Nineteen patients, who where participants in a protocol comparing the antidepressant effects of rTMS with those of ECT, and thirteen age- and gender-matched normal controls were studied. MT was similar between patients and normal controls. The MEP amplitude response was significantly increased by rTMS, however, the magnitude of the response was similar in patients and normal controls. Correlations between the averaged MEP amplitude and age revealed that older subjects demonstrated significantly lower responses at all time-points. We conclude that cortico-spinal excitability is increased following rTMS, however, differences between patients and normal controls were not apparent with the paradigm used.

  17. Differentiation between chronic hepatitis and normal liver of grayscale ultrasound tissue quantification using adobe photoshop(5.0)

    International Nuclear Information System (INIS)

    Choi, Jong Cheol; Oh, Jong Young; Lim, Jong Uk; Nam, Kyung Jin

    2001-01-01

    To evaluate whether was any difference in the brightness of echogenicity on gray scale ultrasound imaging between the liver with chronic hepatitis and the normal liver using Adobe photoshop 5.0 Seventy-five patients with pathologically proven chronic hepatitis and twenty normal volunteers were included in this study. Adobe photoshop 5.0 histogram was used to measure the brightness of image. The measured brightness of the liver was divided by the brightness of the kidney, and the radio was calculated and compared between patients with chronic hepatitis and the normal control groups. In addition, the degree of fibrosis was also evaluated. The difference in brightness between the normal liver and live with chronic hepatitis was statistically significant, but no statistically significant difference was observed between the brightness of the liver and the degree of fibrosis in the liver. Tissue echo quantification using Adobe Photoshop 5.0 may be a helpful diagnostic methods for the patients with chronic hepatitis.

  18. Gender differentiations of cognitive-motor functioning in prepubertal and pubertal children.

    Science.gov (United States)

    Katić, Ratko; Bala, Gustav; Barović, Zdenka

    2012-06-01

    The aim of this study was to determine cognitive and motor status factors in female and male children aged 10-14, as well as developmental and/or integration functions according to gender. The study included 162 girls and 134 boys aged 10-14, divided into four groups: 84 girls aged 10-12 (mean age 11.26, SD 0.68), 84 boys aged 10-12 (mean age 11.41, SD 0.50), 78 girls aged 13-14 (mean age 13.52, SD 0.63) and 50 boys aged 13-14 (mean age 13.21, SD 0.53). The significance of quantitative differences between boys and girls in the overall system of variables was defined based on the results of canonic discriminant analysis of variance, and within each variable based on the results on univariate analysis of variance (ANOVA). In the younger age group (10-12 years), girls were superior to boys in a test assessing flexibility (Seated straddle stretch), whereas, compared to girls, boys had greater strength of the trunk (Crossed-arm sit-ups), greater explosive strength ofjump and sprint type (Standing broad jump and 20 m dash), and coordination (Obstacle course backwards and Steps laterally). In the older age group (13-14 years) differences in flexibility were even more prominent in favor of girls, whereas the differences in explosive strength increased in favor of boys, especially of the throwing type with better agility (Steps laterally), balance (Board balance) and greater static strength of arms and shoulders (Bent-arm hang). In order to determine qualitative differences between pubertal and prepubertal girls and boys, the matrix of variable inter-correlations was factorized by the procedure of principal components procedure, that were then transformed to promax solution. The results showed that cognitive functioning had a significant role in the motor efficacy of girls and boys aged 10 to 14. In the age group of 10-12 years, in females, cognitive functioning is related to the motor system which integrates the regulation of muscle tone with agility/coordination, whereas

  19. Combination of MRI hippocampal volumetry and arterial spin labeling MR perfusion at 3-Tesla improves the efficacy in discriminating Alzheimer's disease from cognitively normal elderly adults.

    Science.gov (United States)

    Mak, Henry Ka-Fung; Qian, Wenshu; Ng, Kwok Sing; Chan, Queenie; Song, You-Qiang; Chu, Leung Wing; Yau, Kelvin Kai-Wing

    2014-01-01

    Structural magnetic resonance imaging has been employed for evaluation of medial temporal atrophy in patients with Alzheimer's disease (AD). Arterial spin labeling (ASL) technique could detect cerebral perfusion abnormalities in AD. We hypothesized that combination of hippocampal volumetry and cerebral blood flow yield higher accuracy than either method alone in discriminating AD patients from cognitively normal elderly adults. 13 AD patients and 15 healthy controls were studied using a 3-tesla scanner. Standardized T1W 3D volumetric Fast Field Echo and QUASAR ASL sequences were employed for cerebral volumetry and perfusion respectively. Manual Right and left hippocampal volumetry was performed manually by ANALYZE software, with total intracranial volume normalization. ASL data were analyzed by institutional specially-design software to calculate cerebral blood flow of region-of-interests placed at the middle and posterior cingulate gyri. Right and left hippocampal volumes and middle and posterior cingulate gyri cerebral blood flows were significantly lower in the patients than in the controls (independent-samples t-tests, p volumetry and cerebral perfusion has improved efficacy in discriminating AD patients from cognitively normal elderly adults.

  20. Differential effects of acute and regular physical exercise on cognition and affect.

    Science.gov (United States)

    Hopkins, M E; Davis, F C; Vantieghem, M R; Whalen, P J; Bucci, D J

    2012-07-26

    The effects of regular exercise versus a single bout of exercise on cognition, anxiety, and mood were systematically examined in healthy, sedentary young adults who were genotyped to determine brain-derived neurotrophic factor (BDNF) allelic status (i.e., Val-Val or Val66Met polymorphism). Participants were evaluated on novel object recognition (NOR) memory and a battery of mental health surveys before and after engaging in either (a) a 4-week exercise program, with exercise on the final test day, (b) a 4-week exercise program, without exercise on the final test day, (c) a single bout of exercise on the final test day, or (d) remaining sedentary between test days. Exercise enhanced object recognition memory and produced a beneficial decrease in perceived stress, but only in participants who exercised for 4 weeks including the final day of testing. In contrast, a single bout of exercise did not affect recognition memory and resulted in increased perceived stress levels. An additional novel finding was that the improvements on the NOR task were observed exclusively in participants who were homozygous for the BDNF Val allele, indicating that altered activity-dependent release of BDNF in Met allele carriers may attenuate the cognitive benefits of exercise. Importantly, exercise-induced changes in cognition were not correlated with changes in mood/anxiety, suggesting that separate neural systems mediate these effects. These data in humans mirror recent data from our group in rodents. Taken together, these current findings provide new insights into the behavioral and neural mechanisms that mediate the effects of physical exercise on memory and mental health in humans. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

  1. Differential Effects of Acute and Regular Physical Exercise on Cognition and Affect

    Science.gov (United States)

    Hopkins, Michael E.; Davis, F. Caroline; VanTieghem, Michelle R.; Whalen, Paul J.; Bucci, David J.

    2012-01-01

    The effects of regular exercise versus a single bout of exercise on cognition, anxiety, and mood were systematically examined in healthy, sedentary young adults who were genotyped to determine brain-derived neurotrophic factor (BDNF) allelic status (i.e., Val-Val or Val66Met polymorphism). Participants were evaluated on novel object recognition (NOR) memory and a battery of mental health surveys before and after engaging in either a) a four-week exercise program, with exercise on the final test day, b) a four-week exercise program, without exercise on the final test day, c) a single bout of exercise on the final test day, or d) remaining sedentary between test days. Exercise enhanced object recognition memory and produced a beneficial decrease in perceived stress, but only in participants who exercised for four weeks including the final day of testing. In contrast, a single bout of exercise did not affect recognition memory and resulted in increased perceived stress levels. An additional novel finding was that the improvements on the NOR task were observed exclusively in participants who were homozygous for the BDNF Val allele, indicating that altered activity-dependent release of BDNF in Met allele carriers may attenuate the cognitive benefits of exercise. Importantly, exercise-induced changes in cognition were not correlated with changes in mood/anxiety, suggesting that separate neural systems mediate these effects. These data in humans mirror recent data from our group in rodents. Taken together, these current findings provide new insights into the behavioral and neural mechanisms that mediate the effects of physical exercise on memory and mental health in humans. PMID:22554780

  2. Intelligence, creativity, and cognitive control: The common and differential involvement of executive functions in intelligence and creativity

    Science.gov (United States)

    Benedek, Mathias; Jauk, Emanuel; Sommer, Markus; Arendasy, Martin; Neubauer, Aljoscha C.

    2014-01-01

    Intelligence and creativity are known to be correlated constructs suggesting that they share a common cognitive basis. The present study assessed three specific executive abilities – updating, shifting, and inhibition – and examined their common and differential relations to fluid intelligence and creativity (i.e., divergent thinking ability) within a latent variable model approach. Additionally, it was tested whether the correlation of fluid intelligence and creativity can be explained by a common executive involvement. As expected, fluid intelligence was strongly predicted by updating, but not by shifting or inhibition. Creativity was predicted by updating and inhibition, but not by shifting. Moreover, updating (and the personality factor openness) was found to explain a relevant part of the shared variance between intelligence and creativity. The findings provide direct support for the executive involvement in creative thought and shed further light on the functional relationship between intelligence and creativity. PMID:25278640

  3. Personality and Differential Treatment Response in Major Depression: A Randomized Controlled Trial Comparing Cognitive-Behavioural Therapy and Pharmacotherapy

    Science.gov (United States)

    Bagby, R Michael; Quilty, Lena C; Segal, Zindel V; McBride, Carolina C; Kennedy, Sidney H; Costa, Paul T

    2008-01-01

    Objective Effective treatments for major depressive disorder exist, yet some patients fail to respond, or achieve only partial response. One approach to optimizing treatment success is to identify which patients are more likely to respond best to which treatments. The objective of this investigation was to determine if patient personality characteristics are predictive of response to either cognitive-behavioural therapy (CBT) or pharmacotherapy (PHT). Method Depressed patients completed the Revised NEO Personality Inventory, which measures the higher-order domain and lower-order facet traits of the Five-Factor Model of Personality, and were randomized to receive either CBT or PHT. Result Four personality traits—the higher-order domain neuroticism and 3 lower-order facet traits: trust, straightforwardness, and tendermindedness—were able to distinguish a differential response rate to CBT, compared with PHT. Conclusion The assessment of patient dimensional personality traits can assist in the selection and optimization of treatment response for depressed patients. PMID:18616856

  4. Emotional and cognitive stimuli differentially engage the default network during inductive reasoning

    OpenAIRE

    Eldaief, Mark C.; Deckersbach, Thilo; Carlson, Lindsay E.; Beucke, Jan C.; Dougherty, Darin D.

    2011-01-01

    The brain’s default network (DN) is comprised of several cortical regions demonstrating robust intrinsic connectivity at rest. The authors sought to examine the differential effects of emotional reasoning and reasoning under certainty upon the DN through the employment of an event-related fMRI design in healthy participants. Participants were presented with syllogistic arguments which were organized into a 2 × 2 factorial design in which the first factor was emotional salience and the second ...

  5. Effort testing in children: can cognitive and symptom validity measures differentiate malingered performances?

    Science.gov (United States)

    Rambo, Philip L; Callahan, Jennifer L; Hogan, Lindsey R; Hullmann, Stephanie; Wrape, Elizabeth

    2015-01-01

    Recent efforts have contributed to significant advances in the detection of malingered performances in adults during cognitive assessment. However, children's ability to purposefully underperform has received relatively little attention. The purpose of the present investigation was to examine children's performances on common intellectual measures, as well as two symptom validity measures: the Test of Memory Malingering and the Dot-Counting Test. This was accomplished through the administration of measures to children ages 6 to 12 years old in randomly assigned full-effort (control) and poor-effort (treatment) conditions. Prior to randomization, children's general intellectual functioning (i.e., IQ) was estimated via administration of the Kaufman Brief Intellectual Battery-Second Edition (KBIT-2). Multivariate analyses revealed that the conditions significantly differed on some but not all administered measures. Specifically, children's estimated IQ in the treatment condition significantly differed from the full-effort IQ initially obtained from the same children on the KBIT-2, as well as from the IQs obtained in the full-effort control condition. These findings suggest that children are fully capable of willfully underperforming during cognitive testing; however, consistent with prior investigations, some measures evidence greater sensitivity than others in evaluating effort.

  6. Heterogeneity in Red Wine Polyphenolic Contents Differentially Influences Alzheimer's Disease-type Neuropathology and Cognitive Deterioration

    Science.gov (United States)

    Ho, Lap; Chen, Ling Hong; Wang, Jun; Zhao, Wei; Talcott, Stephen T.; Ono, Kenjiro; Teplow, David; Humala, Nelson; Cheng, Alice; Percival, Susan S.; Ferruzzi, Mario; Janle, Elsa; Dickstein, Dara L.; Pasinetti, Giulio Maria

    2009-01-01

    We recently found that moderate consumption of two unrelated red wines generate from different grape species, a Cabernet Sauvignon and a muscadine wine that are characterized by distinct component composition of polyphenolic compounds, significantly attenuated the development of Alzheimer's disease (AD)-type brain pathology and memory deterioration in a transgenic AD mouse model. Interestingly, our evidence suggests that the two red wines attenuated AD phenotypes through independent mechanisms. In particular, we previously found that treatment with Cabernet Sauvignon reduced the generation of AD-type amyloid-β (Aβ) peptides. In contrast, evidence from our present study suggests that muscadine treatment attenuates Aβ neuropathology and Aβ-related cognitive deterioration in Tg2576 mice by interfering with the oligomerization of Aβ molecules to soluble high-molecular-weight Aβ oligomer species that are responsible for initiating a cascade of cellular events resulting in cognitive decline. Collectively, our observations suggest that distinct polyphenolic compounds from red wines may be bioavailable at the organism level and beneficially modulate AD phenotypes through multiple Aβ-related mechanisms. Results from these studies suggest the possibility of developing a “combination” of dietary polyphenolic compounds for AD prevention and/or therapy by modulating multiple Aβ-related mechanisms. PMID:19158422

  7. Cognitive benefit and cost of acute stress is differentially modulated by individual brain state.

    Science.gov (United States)

    Kohn, Nils; Hermans, Erno J; Fernández, Guillén

    2017-07-01

    Acute stress is associated with beneficial as well as detrimental effects on cognition in different individuals. However, it is not yet known how stress can have such opposing effects. Stroop-like tasks typically show this dissociation: stress diminishes speed, but improves accuracy. We investigated accuracy and speed during a stroop-like task of 120 healthy male subjects after an experimental stress induction or control condition in a randomized, counter-balanced cross-over design; we assessed brain-behavior associations and determined the influence of individual brain connectivity patterns on these associations, which may moderate the effect and help identify stress resilience factors. In the mean, stress was associated to increase in accuracy, but decrease in speed. Accuracy was associated to brain activation in a distributed set of brain regions overlapping with the executive control network (ECN) and speed to temporo-parietal activation. In line with a stress-related large-scale network reconfiguration, individuals showing an upregulation of the salience and down-regulation of the executive-control network under stress displayed increased speed, but decreased performance. In contrast, individuals who upregulate their ECN under stress show improved performance. Our results indicate that the individual large-scale brain network balance under acute stress moderates cognitive consequences of threat. © The Author (2017). Published by Oxford University Press.

  8. Cognitive benefit and cost of acute stress is differentially modulated by individual brain state

    Science.gov (United States)

    Hermans, Erno J.; Fernández, Guillén

    2017-01-01

    Abstract Acute stress is associated with beneficial as well as detrimental effects on cognition in different individuals. However, it is not yet known how stress can have such opposing effects. Stroop-like tasks typically show this dissociation: stress diminishes speed, but improves accuracy. We investigated accuracy and speed during a stroop-like task of 120 healthy male subjects after an experimental stress induction or control condition in a randomized, counter-balanced cross-over design; we assessed brain–behavior associations and determined the influence of individual brain connectivity patterns on these associations, which may moderate the effect and help identify stress resilience factors. In the mean, stress was associated to increase in accuracy, but decrease in speed. Accuracy was associated to brain activation in a distributed set of brain regions overlapping with the executive control network (ECN) and speed to temporo-parietal activation. In line with a stress-related large-scale network reconfiguration, individuals showing an upregulation of the salience and down-regulation of the executive-control network under stress displayed increased speed, but decreased performance. In contrast, individuals who upregulate their ECN under stress show improved performance. Our results indicate that the individual large-scale brain network balance under acute stress moderates cognitive consequences of threat. PMID:28402480

  9. The differential item functioning and structural equivalence of a nonverbal cognitive ability test for five language groups

    Directory of Open Access Journals (Sweden)

    Pieter Schaap

    2011-10-01

    Research purpose: The aim of the study was to determine the differential item functioning (DIF and structural equivalence of a nonverbal cognitive ability test (the PiB/SpEEx Observance test [401] for five South African language groups. Motivation for study: Cultural and language group sensitive tests can lead to unfair discrimination and is a contentious workplace issue in South Africa today. Misconceptions about psychometric testing in industry can cause tests to lose credibility if industries do not use a scientifically sound test-by-test evaluation approach. Research design, approach and method: The researcher used a quasi-experimental design and factor analytic and logistic regression techniques to meet the research aims. The study used a convenience sample drawn from industry and an educational institution. Main findings: The main findings of the study show structural equivalence of the test at a holistic level and nonsignificant DIF effect sizes for most of the comparisons that the researcher made. Practical/managerial implications: This research shows that the PIB/SpEEx Observance Test (401 is not completely language insensitive. One should see it rather as a language-reduced test when people from different language groups need testing. Contribution/value-add: The findings provide supporting evidence that nonverbal cognitive tests are plausible alternatives to verbal tests when one compares people from different language groups.

  10. Medicalising normality? Using a simulated dataset to assess the performance of different diagnostic criteria of HIV-associated cognitive impairment

    Science.gov (United States)

    De Francesco, Davide; Leech, Robert; Sabin, Caroline A.; Winston, Alan

    2018-01-01

    Objective The reported prevalence of cognitive impairment remains similar to that reported in the pre-antiretroviral therapy era. This may be partially artefactual due to the methods used to diagnose impairment. In this study, we evaluated the diagnostic performance of the HIV-associated neurocognitive disorder (Frascati criteria) and global deficit score (GDS) methods in comparison to a new, multivariate method of diagnosis. Methods Using a simulated ‘normative’ dataset informed by real-world cognitive data from the observational Pharmacokinetic and Clinical Observations in PeoPle Over fiftY (POPPY) cohort study, we evaluated the apparent prevalence of cognitive impairment using the Frascati and GDS definitions, as well as a novel multivariate method based on the Mahalanobis distance. We then quantified the diagnostic properties (including positive and negative predictive values and accuracy) of each method, using bootstrapping with 10,000 replicates, with a separate ‘test’ dataset to which a pre-defined proportion of ‘impaired’ individuals had been added. Results The simulated normative dataset demonstrated that up to ~26% of a normative control population would be diagnosed with cognitive impairment with the Frascati criteria and ~20% with the GDS. In contrast, the multivariate Mahalanobis distance method identified impairment in ~5%. Using the test dataset, diagnostic accuracy [95% confidence intervals] and positive predictive value (PPV) was best for the multivariate method vs. Frascati and GDS (accuracy: 92.8% [90.3–95.2%] vs. 76.1% [72.1–80.0%] and 80.6% [76.6–84.5%] respectively; PPV: 61.2% [48.3–72.2%] vs. 29.4% [22.2–36.8%] and 33.9% [25.6–42.3%] respectively). Increasing the a priori false positive rate for the multivariate Mahalanobis distance method from 5% to 15% resulted in an increase in sensitivity from 77.4% (64.5–89.4%) to 92.2% (83.3–100%) at a cost of specificity from 94.5% (92.8–95.2%) to 85.0% (81.2–88

  11. Switching from reaching to navigation: differential cognitive strategies for spatial memory in children and adults.

    Science.gov (United States)

    Belmonti, Vittorio; Cioni, Giovanni; Berthoz, Alain

    2015-07-01

    Navigational and reaching spaces are known to involve different cognitive strategies and brain networks, whose development in humans is still debated. In fact, high-level spatial processing, including allocentric location encoding, is already available to very young children, but navigational strategies are not mature until late childhood. The Magic Carpet (MC) is a new electronic device translating the traditional Corsi Block-tapping Test (CBT) to navigational space. In this study, the MC and the CBT were used to assess spatial memory for navigation and for reaching, respectively. Our hypothesis was that school-age children would not treat MC stimuli as navigational paths, assimilating them to reaching sequences. Ninety-one healthy children aged 6 to 11 years and 18 adults were enrolled. Overall short-term memory performance (span) on both tests, effects of sequence geometry, and error patterns according to a new classification were studied. Span increased with age on both tests, but relatively more in navigational than in reaching space, particularly in males. Sequence geometry specifically influenced navigation, not reaching. The number of body rotations along the path affected MC performance in children more than in adults, and in women more than in men. Error patterns indicated that navigational sequences were increasingly retained as global paths across development, in contrast to separately stored reaching locations. A sequence of spatial locations can be coded as a navigational path only if a cognitive switch from a reaching mode to a navigation mode occurs. This implies the integration of egocentric and allocentric reference frames, of visual and idiothetic cues, and access to long-term memory. This switch is not yet fulfilled at school age due to immature executive functions. © 2014 John Wiley & Sons Ltd.

  12. Apraxia for differentiating Alzheimer’s disease from subcortical vascular dementia and mild cognitive impairment

    Directory of Open Access Journals (Sweden)

    Ozkan S

    2013-07-01

    Full Text Available Serhat Ozkan,1 Demet Ozbabalik Adapinar,1 Nese Tuncer Elmaci,2 Didem Arslantas31Department of Neurology, Eskisehir Osmangazi University Medical Faculty, Eskisehir, Turkey; 2Department of Neurology, Marmara University Medical Faculty, Istanbul, Turkey; 3Department of Public Health, Eskisehir Osmangazi University Medical Faculty, Eskisehir, TurkeyAbstract: Although ideomotor limb apraxia is considered to be a typical sign of cortical pathologies such as Alzheimer’s disease (AD, it has been also reported in subcortical neurodegenerative diseases and vascular lesions. We aimed to investigate the difference between AD, subcortical vascular dementia (SVaD and mild cognitive impairment (MCI patients by means of ideomotor limb apraxia frequency and severity. Ninety-six AD, 72 SVaD, and 84 MCI patients were assessed with the mini-mental status examination (MMSE, clinical dementia rating (CDR and the apraxia screening test of TULIA (AST. Apraxia was significantly more frequent in the AD patients (32.3% than in both of the SVaD (16.7% and MCI (4.8% patients. The frequency of apraxia was also significantly higher in SVaD patients than in MCI patients. AD patients had significantly lower apraxia scores than both SVaD and MCI patients. In addition, a significant difference was found between SVaD and MCI patients in terms of apraxia scores. These results suggest that the widespread belief of the association between apraxia and cortical dementias is not exactly correct. The significant difference between both of the dementia groups and the MCI patients suggests that the absence of apraxia can be an indicator for MCI diagnosis.Keywords: apraxia, Alzheimer’s disease, subcortical vascular dementia, mild cognitive impairment

  13. Comparison of Cognitive, Psychological and Social Characteristics, between Parents Who Have More Than One Exceptional Child with Parents of Normal Child

    Directory of Open Access Journals (Sweden)

    Mohammad Mousavy-Khatat

    2011-10-01

    Full Text Available Normal 0 false false false EN-US X-NONE FA /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal" mso-tstyle-rowband-size:0 mso-tstyle-colband-size:0 mso-style-noshow:yes mso-style-priority:99 mso-style-parent:"" mso-padding-alt:0mm 5.4pt 0mm 5.4pt mso-para-margin-top:0mm mso-para-margin-right:0mm mso-para-margin-bottom:10.0pt mso-para-margin-left:0mm line-height:115% mso-pagination:widow-orphan font-size:11.0pt font-family:"Times New Roman","serif" mso-ascii-font-family:"Times New Roman" mso-ascii-theme-font:minor-latin mso-hansi-font-family:"Times New Roman" mso-hansi-theme-font:minor-latin mso-bidi-font-family:"XB Niloofar" mso-bidi-theme-font:minor-bidi} Objective: The purpose of this study was to compare the cognitive, psychological and social characteristics between parents who have more than one exceptional child and those parents with normal child. Materials & Methods: In this cross sectional and comparative study, 80 families who had more than one exceptional child were conveniently selected and 53 families with normal child were selected using multi-stage sampling in schools of Uromia city, western Iran. The Cognitive, Psychological and Social Characteristics of Parents with more than One Special Child Questionnaire, General Health Questionnaire (GHQ and Evaluation and Nurturing Relationship Issues Communication and Happiness (ENRICH were used. Compromise Xi Chi, Yu-Man Whitney and t tests were used for data analysis. Results: Among cognitive, psychological and social variables, job (Father and Mother (P<0.001 education (Father & Mother time of disability awareness (P<0.001 parents' level of interest to marriage (P<0.001 parents' relationship before birth (P<0.001 parents' relationship during pregnancy (P<0.001 Mothers' mental health (physical symptoms P=0.037, depression P=0.041, social dysfunction P=0.04, anxiety and insomnia P=0.001 and marital satisfaction (P=0.030 were statistically significant between the two

  14. Differential expression of splicing variants of the human caldesmon gene (CALD1) in glioma neovascularization versus normal brain microvasculature

    NARCIS (Netherlands)

    P.P. Zheng (Pingpin); A.M. Sieuwerts (Anieta); T.M. Luider (Theo); M.M. van der Weiden (Marcel); J.M. Kros (Johan); P.A.E. Sillevis Smitt (Peter)

    2004-01-01

    textabstractCaldesmon is a cytoskeleton-associated protein which has not yet been related to neoplastic angiogenesis. In this study we investigated the expression of the caldesmon gene (CALD1) splicing variants and the protein expression level in glioma microvessels versus normal

  15. CDK2 differentially controls normal cell senescence and cancer cell proliferation upon exposure to reactive oxygen species

    International Nuclear Information System (INIS)

    Hwang, Chae Young; Lee, Seung-Min; Park, Sung Sup; Kwon, Ki-Sun

    2012-01-01

    Highlights: ► H 2 O 2 differently adjusted senescence and proliferation in normal and cancer cells. ► H 2 O 2 exposure transiently decreased PCNA levels in normal cells. ► H 2 O 2 exposure transiently increased CDK2 activity in cancer cells. ► p21 Cip1 is likely dispensable when H 2 O 2 induces senescence in normal cells. ► Suggestively, CDK2 and PCNA play critical roles in H 2 O 2 -induced cell fate decision. -- Abstract: Reactive oxygen species modulate cell fate in a context-dependent manner. Sublethal doses of H 2 O 2 decreased the level of proliferating cell nuclear antigen (PCNA) in normal cells (including primary human dermal fibroblasts and IMR-90 cells) without affecting cyclin-dependent kinase 2 (CDK2) activity, leading to cell cycle arrest and subsequent senescence. In contrast, exposure of cancer cells (such as HeLa and MCF7 cells) to H 2 O 2 increased CDK2 activity with no accompanying change in the PCNA level, leading to cell proliferation. A CDK2 inhibitor, CVT-313, prevented H 2 O 2 -induced cancer cell proliferation. These results support the notion that the cyclin/CDK2/p21 Cip1 /PCNA complex plays an important role as a regulator of cell fate decisions.

  16. Normal spectrum of pulmonary parametric response map to differentiate lung collapsibility: distribution of densitometric classifications in healthy adult volunteers

    International Nuclear Information System (INIS)

    Silva, Mario; Nemec, Stefan F.; Dufresne, Valerie; Occhipinti, Mariaelena; Heidinger, Benedikt H.; Bankier, Alexander A.; Chamberlain, Ryan

    2016-01-01

    Pulmonary parametric response map (PRM) was proposed for quantitative densitometric phenotypization of chronic obstructive pulmonary disease. However, little is known about this technique in healthy subjects. The purpose of this study was to describe the normal spectrum of densitometric classification of pulmonary PRM in a group of healthy adults. 15 healthy volunteers underwent spirometrically monitored chest CT at total lung capacity (TLC) and functional residual capacity (FRC). The paired CT scans were analyzed by PRM for voxel-by-voxel characterization of lung parenchyma according to 4 densitometric classifications: normal lung (TLC ≥ -950 HU, FRC ≥ -856 HU); expiratory low attenuation area (LAA) (TLC ≥ -950 HU, FRC < -856 HU); dual LAA (TLC<-950 HU, FRC < -856 HU); uncharacterized (TLC < -950 HU, FRC ≥ -856 HU). PRM spectrum was 78 % ± 10 % normal lung, 20 % ± 8 % expiratory LAA, and 1 % ± 1 % dual LAA. PRM was similar between genders, there was moderate correlation between dual LAA and spirometrically assessed TLC (R = 0.531; p = 0.042), and between expiratory LAA and Vol Exp/Insp ratio (R = -0.572; p = 0.026). PRM reflects the predominance of normal lung parenchyma in a group of healthy volunteers. However, PRM also confirms the presence of physiological expiratory LAA seemingly related to air trapping and a minimal amount of dual LAA likely reflecting emphysema. (orig.)

  17. Artichoke compound cynarin differentially affects the survival, growth and stress response of normal, immortalized and cancerous human cells

    DEFF Research Database (Denmark)

    Gezer, Ceren; Yücecan, Sevinç; Rattan, Suresh Inder Singh

    2015-01-01

    of CYN on the proliferative potential, survival, morphology, and stress response (SR) markers haemoxygenase-1 (HO-1) and heat shock protein-70 (HSP70) in normal human skin fibroblasts (FSF-1), telomerase-immortalized mesenchymal stem cells (hTERT-MSC) and cervical cancer cells, HeLa. Effects of CYN...

  18. Amyloid imaging in cognitively normal older adults: comparison between 18F-flutemetamol and 11C-Pittsburgh compound B

    International Nuclear Information System (INIS)

    Adamczuk, Katarzyna; Schaeverbeke, Jolien; Neyens, Veerle; Dupont, Patrick; Nelissen, Natalie; Vandenbulcke, Mathieu; Goffin, Karolien; Lilja, Johan; Hilven, Kelly; Laere, Koen van; Vandenberghe, Rik

    2016-01-01

    Preclinical, or asymptomatic, Alzheimer's disease (AD) refers to the presence of positive AD biomarkers in the absence of cognitive deficits. This research concept is being applied to define target populations for clinical drug development. In a prospective community-recruited cohort of cognitively intact older adults, we compared two amyloid imaging markers within subjects: 18 F-flutemetamol and 11 C-Pittsburgh compound B (PIB). In 32 community-recruited cognitively intact older adults aged between 65 and 80 years, we determined the concordance between binary classification based on 18 F-flutemetamol versus 11 C-PIB according to semiquantitative assessment (standardized uptake value ratio in composite cortical volume, SUVR comp ) and, alternatively, according to visual reads. We also determined the correlation between 18 F-flutemetamol and 11 C-PIB SUVR and evaluated how this was affected by the reference region chosen (cerebellar grey matter versus pons) and the use of partial volume correction (PVC) in this population. Binary classification based on semiquantitative assessment was concordant between 18 F-flutemetamol and 11 C-PIB in 94 % of cases. Concordance of blinded binary visual reads between tracers was 84 %. The Spearman correlation between 18 F-flutemetamol and 11 C-PIB SUVR comp with cerebellar grey matter as reference region was 0.84, with a slope of 0.98. Correlations in neocortical regions were significantly lower with the pons as reference region. PVC improved the correlation in striatum and medial temporal cortex. For the definition of preclinical AD based on 18 F-flutemetamol, concordance with 11 C-PIB was highest using semiquantitative assessment with cerebellar grey matter as reference region. (orig.)

  19. Using virtual reality to distinguish subjects with multiple- but not single-domain amnestic mild cognitive impairment from normal elderly subjects.

    Science.gov (United States)

    Mohammadi, Alireza; Kargar, Mahmoud; Hesami, Ehsan

    2018-03-01

    Spatial disorientation is a hallmark of amnestic mild cognitive impairment (aMCI) and Alzheimer's disease. Our aim was to use virtual reality to determine the allocentric and egocentric memory deficits of subjects with single-domain aMCI (aMCIsd) and multiple-domain aMCI (aMCImd). For this purpose, we introduced an advanced virtual reality navigation task (VRNT) to distinguish these deficits in mild Alzheimer's disease (miAD), aMCIsd, and aMCImd. The VRNT performance of 110 subjects, including 20 with miAD, 30 with pure aMCIsd, 30 with pure aMCImd, and 30 cognitively normal controls was compared. Our newly developed VRNT consists of a virtual neighbourhood (allocentric memory) and virtual maze (egocentric memory). Verbal and visuospatial memory impairments were also examined with Rey Auditory-Verbal Learning Test and Rey-Osterrieth Complex Figure Test, respectively. We found that miAD and aMCImd subjects were impaired in both allocentric and egocentric memory, but aMCIsd subjects performed similarly to the normal controls on both tasks. The miAD, aMCImd, and aMCIsd subjects performed worse on finding the target or required more time in the virtual environment than the aMCImd, aMCIsd, and normal controls, respectively. Our findings indicated the aMCImd and miAD subjects, as well as the aMCIsd subjects, were more impaired in egocentric orientation than allocentric orientation. We concluded that VRNT can distinguish aMCImd subjects, but not aMCIsd subjects, from normal elderly subjects. The VRNT, along with the Rey Auditory-Verbal Learning Test and Rey-Osterrieth Complex Figure Test, can be used as a valid diagnostic tool for properly distinguishing different forms of aMCI. © 2018 Japanese Psychogeriatric Society.

  20. Cognitive Factors in the Choice of Syntactic Form by Aphasic and Normal Speakers of English and Japanese: The Speaker's Impulse.

    Science.gov (United States)

    Menn, Lise; And Others

    This study examined the role of empathy in the choice of syntactic form and the degree of independence of pragmatic and syntactic abilities in a range of aphasic patients. Study 1 involved 9 English-speaking and 9 Japanese-speaking aphasic subjects with 10 English-speaking and 4 Japanese normal controls. Study 2 involved 14 English- and 6…

  1. [The delayed word recall task using ADAS-Jcog word booklet effectively divides patients with mild cognitive impairment from normal elderly people].

    Science.gov (United States)

    Kawano, Naoko; Umegaki, Hiroyuki; Suzuki, Yusuke; Yamamoto, Sayaka; Mogi, Nanaka; Iguchi, Akihisa

    2007-07-01

    A new screening test for detecting mild cognitive impairment (MCI) with higher sensitivity that can easily be administered at the bedside is necessary. In this study, we proposed the delayed recall task using the word booklet of Alzheimer's Disease Assessment Scale-cognitive component-Japanese version (ADAS-Jcog) and compared the score of the task in patients with MCI with that of cognitive normal elderly (NE) and patients with AD. Thirty six patients with MCI, 13 very mild AD, 104 mild AD, 13 moderate AD, and age- and education-matched 19 NE, recruited from the memory clinic of Nagoya University Hospital, were evaluated by the ADAS-Jcog word recall task which consisted of immediate recall (IR), a classical method on ADAS-Jcog, and delayed recall (DR) that has been newly introduced. Compared with controls, patients with MCI were significantly impaired on both IR and DR. On the other hand, DR is more sensitive than IR for distinguishing MCI from NE. The highest sensitivity (94.4%) and specificity (68.4%) were achieved when the results of IR were combined with those of DR. The result suggests that the delayed word recall task using the word booklet of ADAS-Jcog may be a useful tool as a screening method for the detection of MCI.

  2. Effects of level of processing at encoding and types of retrieval task in mild cognitive impairment and normal aging.

    Science.gov (United States)

    Froger, Charlotte; Taconnat, Laurence; Landré, Lionel; Beigneux, Katia; Isingrini, Michel

    2009-04-01

    A total of 16 young (M = 27.25 years), 13 healthy elderly (M = 75.38 years), and 10 older adults with probable mild cognitive impairment (MCI; M = 78.6 years) carried out a task under two different encoding conditions (shallow vs. semantic) and two retrieval conditions (free recall vs. recognition). For the shallow condition, participants had to decide whether the first or last letter of each word in a list was "E." For the semantic condition, they had to decide whether each word represented a concrete or abstract entity. The MCI group was only able to benefit from semantic encoding to the same extent as the healthy older adults in the recognition task, whereas the younger and healthy older adults benefited in both retrieval tasks. These results suggest that the MCI group required cognitive support at retrieval to make effective use of semantic processing carried out at encoding. In the discussion, we suggest that adults with MCI engage more in deep processing, using the semantic network, than hitherto thought.

  3. Diffusion Tensor Imaging of Normal-Appearing White Matter as Biomarker for Radiation-Induced Late Delayed Cognitive Decline

    International Nuclear Information System (INIS)

    Chapman, Christopher H.; Nagesh, Vijaya; Sundgren, Pia C.; Buchtel, Henry; Chenevert, Thomas L.; Junck, Larry; Lawrence, Theodore S.; Tsien, Christina I.; Cao, Yue

    2012-01-01

    Purpose: To determine whether early assessment of cerebral white matter degradation can predict late delayed cognitive decline after radiotherapy (RT). Methods and Materials: Ten patients undergoing conformal fractionated brain RT participated in a prospective diffusion tensor magnetic resonance imaging study. Magnetic resonance imaging studies were acquired before RT, at 3 and 6 weeks during RT, and 10, 30, and 78 weeks after starting RT. The diffusivity variables in the parahippocampal cingulum bundle and temporal lobe white matter were computed. A quality-of-life survey and neurocognitive function tests were administered before and after RT at the magnetic resonance imaging follow-up visits. Results: In both structures, longitudinal diffusivity (λ ‖ ) decreased and perpendicular diffusivity (λ ⊥ ) increased after RT, with early changes correlating to later changes (p ⊥ at 3 weeks, and patients with >50% of cingula volume receiving >12 Gy had a greater increase in λ ⊥ at 3 and 6 weeks (p ‖ (30 weeks, p ‖ changes predicted for post-RT changes in verbal recall scores (3 and 6 weeks, p < .05). The neurocognitive test scores correlated significantly with the quality-of-life survey results. Conclusions: The correlation between early diffusivity changes in the parahippocampal cingulum and the late decline in verbal recall suggests that diffusion tensor imaging might be useful as a biomarker for predicting late delayed cognitive decline.

  4. Differential production of proteolytic enzymes by normal human fibroblasts and their counterparts transformed by treatment with 60Co gamma rays

    International Nuclear Information System (INIS)

    Nishitani, Koji; Namba, Masayoshi; Ohkubo, Shigeki; Kimoto, Tetsuo

    1985-01-01

    Production of proteolytic enzymes by human fibroblasts in the process of transformation was investigated. The cells used were normal human fibroblasts (KSM-6) and their in vitro counterparts transformed by treatment with 60 Co gamma rays (KMST-6). Cells seeded by treatment with EDTA were cultured in a serum free medium. Proteolytic enzymes in the culture medium of cells were assayed using a synthetic substrate, N-α-(p-tosyl)-L-arginine ( 3 H) methyl ester hydrochloride. The transformed cells (KMST-6) produced a larger amount of enzymes than normal cells (KMS-6). The enzyme production in both cell lines was high in the exponential growth stage and then decreased as the cells reached confluency. The proteolytic enzymes produced by these cells were trypsin- and thrombin-like enzymes. Cell growth of KMST-6 or KMS-6 was not inhibited by the addition of protease inhibitors to the culture medium. (author)

  5. Adenomatous polyposis coli is required for early events in the normal growth and differentiation of the developing cerebral cortex

    Directory of Open Access Journals (Sweden)

    Price David J

    2009-01-01

    Full Text Available Abstract Background Adenomatous polyposis coli (Apc is a large multifunctional protein known to be important for Wnt/β-catenin signalling, cytoskeletal dynamics, and cell polarity. In the developing cerebral cortex, Apc is expressed in proliferating cells and its expression increases as cells migrate to the cortical plate. We examined the consequences of loss of Apc function for the early development of the cerebral cortex. Results We used Emx1Cre to inactivate Apc specifically in proliferating cerebral cortical cells and their descendents starting from embryonic day 9.5. We observed reduction in the size of the mutant cerebral cortex, disruption to its organisation, and changes in the molecular identity of its cells. Loss of Apc leads to a decrease in the size of the proliferative pool, disrupted interkinetic nuclear migration, and increased apoptosis. β-Catenin, pericentrin, and N-cadherin proteins no longer adopt their normal high concentration at the apical surface of the cerebral cortical ventricular zone, indicating that cell polarity is disrupted. Consistent with enhanced Wnt/β-catenin signalling resulting from loss of Apc we found increased levels of TCF/LEF-dependent transcription and expression of endogenous Wnt/β-catenin target genes (Axin2 (conductin, Lef1, and c-myc in the mutant cerebral cortex. In the Apc mutant cerebral cortex the expression of transcription factors Foxg1, Pax6, Tbr1, and Tbr2 is drastically reduced compared to normal and many cells ectopically express Pax3, Wnt1, and Wt1 (but not Wnt2b, Wnt8b, Ptc, Gli1, Mash1, Olig2, or Islet1. This indicates that loss of Apc function causes cerebral cortical cells to lose their normal identity and redirect to fates normally found in more posterior-dorsal regions of the central nervous system. Conclusion Apc is required for multiple aspects of early cerebral cortical development, including the regulation of cell number, interkinetic nuclear migration, cell polarity, and

  6. Cognitive neuropsychological analysis of differential reading and spelling disorder mechanisms in a patient with aphasia.

    Science.gov (United States)

    Hashimoto, Kosei; Uno, Akira

    2016-06-01

    The purpose of this study was to determine if differential reading and spelling mechanisms were involved in a Japanese patient with aphasia. In our case, the patient scored low on all of the administered reading tasks, suggesting that both the reading lexical and non-lexical routes were impaired. In contrast, his writing-to-dictation score for Kana nonwords was high, suggesting that the spelling non-lexical route was intact. However, the patient scored low on a writing-to-dictation task comprised of high-familiarity Kanji words. The spelling lexical route was thought to be impaired. Therefore, the mechanism(s) involved in reading and spelling may differ in this case.

  7. Measurement of normalized differential t-tbar cross sections in the dilepton channel from pp collisions at sqrt(s) = 13 TeV

    Energy Technology Data Exchange (ETDEWEB)

    Sirunyan, Albert M; et al.

    2017-08-25

    Normalized differential cross sections for top quark pair production are measured in the dilepton (e-e, mu-mu, and mu-e) decay channels in proton-proton collisions at a center-of-mass energy of 13 TeV. The measurements are performed with data corresponding to an integrated luminosity of 2.1 inverse-femtobarns using the CMS detector at the LHC. The cross sections are measured differentially as a function of the kinematic properties of the leptons, jets from bottom quark hadronization, top quarks, and top quark pairs at the particle and parton levels. The results are compared to several Monte Carlo generators that implement calculations up to next-to-leading order in perturbative quantum chromodynamics interfaced with parton showering, and also to fixed-order theoretical calculations of top quark pair production up to next-to-next-to-leading order.

  8. Measurement of normalized differential t\\overline{t} cross sections in the dilepton channel from pp collisions at √{s}=13 TeV

    Science.gov (United States)

    Sirunyan, A. M.; Tumasyan, A.; Adam, W.; Ambrogi, F.; Asilar, E.; Bergauer, T.; Brandstetter, J.; Brondolin, E.; Dragicevic, M.; Erö, J.; Flechl, M.; Friedl, M.; Frühwirth, R.; Ghete, V. M.; Grossmann, J.; Hrubec, J.; Jeitler, M.; König, A.; Krammer, N.; Krätschmer, I.; Liko, D.; Madlener, T.; Mikulec, I.; Pree, E.; Rabady, D.; Rad, N.; Rohringer, H.; Schieck, J.; Schöfbeck, R.; Spanring, M.; Spitzbart, D.; Strauss, J.; Waltenberger, W.; Wittmann, J.; Wulz, C.-E.; Zarucki, M.; Chekhovsky, V.; Mossolov, V.; Suarez Gonzalez, J.; De Wolf, E. 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H.; Barney, D.; Bianco, M.; Bloch, P.; Bocci, A.; Botta, C.; Camporesi, T.; Castello, R.; Cepeda, M.; Cerminara, G.; Chapon, E.; Chen, Y.; d'Enterria, D.; Dabrowski, A.; Daponte, V.; David, A.; De Gruttola, M.; De Roeck, A.; Di Marco, E.; Dobson, M.; Dorney, B.; du Pree, T.; Dünser, M.; Dupont, N.; Elliott-Peisert, A.; Everaerts, P.; Franzoni, G.; Fulcher, J.; Funk, W.; Gigi, D.; Gill, K.; Glege, F.; Gulhan, D.; Gundacker, S.; Guthoff, M.; Harris, P.; Hegeman, J.; Innocente, V.; Janot, P.; Karacheban, O.; Kieseler, J.; Kirschenmann, H.; Knünz, V.; Kornmayer, A.; Kortelainen, M. J.; Krammer, M.; Lange, C.; Lecoq, P.; Lourenço, C.; Lucchini, M. T.; Malgeri, L.; Mannelli, M.; Martelli, A.; Meijers, F.; Merlin, J. A.; Mersi, S.; Meschi, E.; Milenovic, P.; Moortgat, F.; Mulders, M.; Neugebauer, H.; Orfanelli, S.; Orsini, L.; Pape, L.; Perez, E.; Peruzzi, M.; Petrilli, A.; Petrucciani, G.; Pfeiffer, A.; Pierini, M.; Racz, A.; Reis, T.; Rolandi, G.; Rovere, M.; Sakulin, H.; Schäfer, C.; Schwick, C.; Seidel, M.; Selvaggi, M.; Sharma, A.; Silva, P.; Sphicas, P.; Steggemann, J.; Stoye, M.; Tosi, M.; Treille, D.; Triossi, A.; Tsirou, A.; Veckalns, V.; Veres, G. I.; Verweij, M.; Wardle, N.; Zeuner, W. D.; Bertl, W.; Deiters, K.; Erdmann, W.; Horisberger, R.; Ingram, Q.; Kaestli, H. C.; Kotlinski, D.; Langenegger, U.; Rohe, T.; Wiederkehr, S. A.; Bachmair, F.; Bäni, L.; Berger, P.; Bianchini, L.; Casal, B.; Dissertori, G.; Dittmar, M.; Donegà, M.; Grab, C.; Heidegger, C.; Hits, D.; Hoss, J.; Kasieczka, G.; Klijnsma, T.; Lustermann, W.; Mangano, B.; Marionneau, M.; Meinhard, M. T.; Meister, D.; Micheli, F.; Musella, P.; Nessi-Tedaldi, F.; Pandolfi, F.; Pata, J.; Pauss, F.; Perrin, G.; Perrozzi, L.; Quittnat, M.; Rossini, M.; Schönenberger, M.; Shchutska, L.; Starodumov, A.; Tavolaro, V. R.; Theofilatos, K.; Vesterbacka Olsson, M. L.; Wallny, R.; Zagozdzinska, A.; Zhu, D. H.; Aarrestad, T. K.; Amsler, C.; Caminada, L.; Canelli, M. F.; De Cosa, A.; Donato, S.; Galloni, C.; Hinzmann, A.; Hreus, T.; Kilminster, B.; Ngadiuba, J.; Pinna, D.; Rauco, G.; Robmann, P.; Salerno, D.; Seitz, C.; Zucchetta, A.; Candelise, V.; Doan, T. H.; Jain, Sh.; Khurana, R.; Konyushikhin, M.; Kuo, C. M.; Lin, W.; Pozdnyakov, A.; Yu, S. S.; Kumar, Arun; Chang, P.; Chao, Y.; Chen, K. F.; Chen, P. H.; Fiori, F.; Hou, W.-S.; Hsiung, Y.; Liu, Y. F.; Lu, R.-S.; Miñano Moya, M.; Paganis, E.; Psallidas, A.; Tsai, J. f.; Asavapibhop, B.; Kovitanggoon, K.; Singh, G.; Srimanobhas, N.; Adiguzel, A.; Boran, F.; Cerci, S.; Damarseckin, S.; Demiroglu, Z. S.; Dozen, C.; Dumanoglu, I.; Girgis, S.; Gokbulut, G.; Guler, Y.; Hos, I.; Kangal, E. E.; Kara, O.; Kayis Topaksu, A.; Kiminsu, U.; Oglakci, M.; Onengut, G.; Ozdemir, K.; Sunar Cerci, D.; Topakli, H.; Turkcapar, S.; Zorbakir, I. S.; Zorbilmez, C.; Bilin, B.; Karapinar, G.; Ocalan, K.; Yalvac, M.; Zeyrek, M.; Gülmez, E.; Kaya, M.; Kaya, O.; Tekten, S.; Yetkin, E. A.; Agaras, M. N.; Atay, S.; Cakir, A.; Cankocak, K.; Grynyov, B.; Levchuk, L.; Sorokin, P.; Aggleton, R.; Ball, F.; Beck, L.; Brooke, J. J.; Burns, D.; Clement, E.; Cussans, D.; Flacher, H.; Goldstein, J.; Grimes, M.; Heath, G. P.; Heath, H. F.; Jacob, J.; Kreczko, L.; Lucas, C.; Newbold, D. M.; Paramesvaran, S.; Poll, A.; Sakuma, T.; Seif El Nasr-storey, S.; Smith, D.; Smith, V. J.; Bell, K. W.; Belyaev, A.; Brew, C.; Brown, R. M.; Calligaris, L.; Cieri, D.; Cockerill, D. J. A.; Coughlan, J. A.; Harder, K.; Harper, S.; Olaiya, E.; Petyt, D.; Shepherd-Themistocleous, C. H.; Thea, A.; Tomalin, I. R.; Williams, T.; Baber, M.; Bainbridge, R.; Breeze, S.; Buchmuller, O.; Bundock, A.; Casasso, S.; Citron, M.; Colling, D.; Corpe, L.; Dauncey, P.; Davies, G.; De Wit, A.; Della Negra, M.; Di Maria, R.; Dunne, P.; Elwood, A.; Futyan, D.; Haddad, Y.; Hall, G.; Iles, G.; James, T.; Lane, R.; Laner, C.; Lyons, L.; Magnan, A.-M.; Malik, S.; Mastrolorenzo, L.; Matsushita, T.; Nash, J.; Nikitenko, A.; Pela, J.; Pesaresi, M.; Raymond, D. M.; Richards, A.; Rose, A.; Scott, E.; Seez, C.; Shtipliyski, A.; Summers, S.; Tapper, A.; Uchida, K.; Vazquez Acosta, M.; Virdee, T.; Winterbottom, D.; Wright, J.; Zenz, S. C.; Cole, J. E.; Hobson, P. R.; Khan, A.; Kyberd, P.; Reid, I. D.; Symonds, P.; Teodorescu, L.; Turner, M.; Borzou, A.; Call, K.; Dittmann, J.; Hatakeyama, K.; Liu, H.; Pastika, N.; Bartek, R.; Dominguez, A.; Buccilli, A.; Cooper, S. I.; Henderson, C.; Rumerio, P.; West, C.; Arcaro, D.; Avetisyan, A.; Bose, T.; Gastler, D.; Rankin, D.; Richardson, C.; Rohlf, J.; Sulak, L.; Zou, D.; Benelli, G.; Cutts, D.; Garabedian, A.; Hakala, J.; Heintz, U.; Hogan, J. M.; Kwok, K. H. M.; Laird, E.; Landsberg, G.; Mao, Z.; Narain, M.; Pazzini, J.; Piperov, S.; Sagir, S.; Syarif, R.; Yu, D.; Band, R.; Brainerd, C.; Burns, D.; Calderon De La Barca Sanchez, M.; Chertok, M.; Conway, J.; Conway, R.; Cox, P. T.; Erbacher, R.; Flores, C.; Funk, G.; Gardner, M.; Ko, W.; Lander, R.; Mclean, C.; Mulhearn, M.; Pellett, D.; Pilot, J.; Shalhout, S.; Shi, M.; Smith, J.; Squires, M.; Stolp, D.; Tos, K.; Tripathi, M.; Wang, Z.; Bachtis, M.; Bravo, C.; Cousins, R.; Dasgupta, A.; Florent, A.; Hauser, J.; Ignatenko, M.; Mccoll, N.; Saltzberg, D.; Schnaible, C.; Valuev, V.; Bouvier, E.; Burt, K.; Clare, R.; Ellison, J.; Gary, J. W.; Ghiasi Shirazi, S. M. A.; Hanson, G.; Heilman, J.; Jandir, P.; Kennedy, E.; Lacroix, F.; Long, O. R.; Olmedo Negrete, M.; Paneva, M. I.; Shrinivas, A.; Si, W.; Wei, H.; Wimpenny, S.; Yates, B. R.; Branson, J. G.; Cerati, G. B.; Cittolin, S.; Derdzinski, M.; Gerosa, R.; Hashemi, B.; Holzner, A.; Klein, D.; Kole, G.; Krutelyov, V.; Letts, J.; Macneill, I.; Masciovecchio, M.; Olivito, D.; Padhi, S.; Pieri, M.; Sani, M.; Sharma, V.; Simon, S.; Tadel, M.; Vartak, A.; Wasserbaech, S.; Wood, J.; Würthwein, F.; Yagil, A.; Zevi Della Porta, G.; Amin, N.; Bhandari, R.; Bradmiller-Feld, J.; Campagnari, C.; Dishaw, A.; Dutta, V.; Franco Sevilla, M.; George, C.; Golf, F.; Gouskos, L.; Gran, J.; Heller, R.; Incandela, J.; Mullin, S. D.; Ovcharova, A.; Qu, H.; Richman, J.; Stuart, D.; Suarez, I.; Yoo, J.; Anderson, D.; Bendavid, J.; Bornheim, A.; Lawhorn, J. M.; Newman, H. B.; Nguyen, T.; Pena, C.; Spiropulu, M.; Vlimant, J. R.; Xie, S.; Zhang, Z.; Zhu, R. Y.; Andrews, M. B.; Ferguson, T.; Mudholkar, T.; Paulini, M.; Russ, J.; Sun, M.; Vogel, H.; Vorobiev, I.; Weinberg, M.; Cumalat, J. P.; Ford, W. T.; Jensen, F.; Johnson, A.; Krohn, M.; Leontsinis, S.; Mulholland, T.; Stenson, K.; Wagner, S. R.; Alexander, J.; Chaves, J.; Chu, J.; Dittmer, S.; Mcdermott, K.; Mirman, N.; Patterson, J. R.; Rinkevicius, A.; Ryd, A.; Skinnari, L.; Soffi, L.; Tan, S. M.; Tao, Z.; Thom, J.; Tucker, J.; Wittich, P.; Zientek, M.; Abdullin, S.; Albrow, M.; Apollinari, G.; Apresyan, A.; Apyan, A.; Banerjee, S.; Bauerdick, L. A. T.; Beretvas, A.; Berryhill, J.; Bhat, P. C.; Bolla, G.; Burkett, K.; Butler, J. N.; Canepa, A.; Cheung, H. W. K.; Chlebana, F.; Cremonesi, M.; Duarte, J.; Elvira, V. D.; Freeman, J.; Gecse, Z.; Gottschalk, E.; Gray, L.; Green, D.; Grünendahl, S.; Gutsche, O.; Harris, R. M.; Hasegawa, S.; Hirschauer, J.; Hu, Z.; Jayatilaka, B.; Jindariani, S.; Johnson, M.; Joshi, U.; Klima, B.; Kreis, B.; Lammel, S.; Lincoln, D.; Lipton, R.; Liu, M.; Liu, T.; Lopes De Sá, R.; Lykken, J.; Maeshima, K.; Magini, N.; Marraffino, J. M.; Maruyama, S.; Mason, D.; McBride, P.; Merkel, P.; Mrenna, S.; Nahn, S.; O'Dell, V.; Pedro, K.; Prokofyev, O.; Rakness, G.; Ristori, L.; Schneider, B.; Sexton-Kennedy, E.; Soha, A.; Spalding, W. J.; Spiegel, L.; Stoynev, S.; Strait, J.; Strobbe, N.; Taylor, L.; Tkaczyk, S.; Tran, N. V.; Uplegger, L.; Vaandering, E. W.; Vernieri, C.; Verzocchi, M.; Vidal, R.; Wang, M.; Weber, H. A.; Whitbeck, A.; Acosta, D.; Avery, P.; Bortignon, P.; Brinkerhoff, A.; Carnes, A.; Carver, M.; Curry, D.; Das, S.; Field, R. D.; Furic, I. K.; Konigsberg, J.; Korytov, A.; Kotov, K.; Ma, P.; Matchev, K.; Mei, H.; Mitselmakher, G.; Rank, D.; Sperka, D.; Terentyev, N.; Thomas, L.; Wang, J.; Wang, S.; Yelton, J.; Joshi, Y. R.; Linn, S.; Markowitz, P.; Martinez, G.; Rodriguez, J. L.; Ackert, A.; Adams, T.; Askew, A.; Hagopian, S.; Hagopian, V.; Johnson, K. F.; Kolberg, T.; Perry, T.; Prosper, H.; Santra, A.; Yohay, R.; Baarmand, M. M.; Bhopatkar, V.; Colafranceschi, S.; Hohlmann, M.; Noonan, D.; Roy, T.; Yumiceva, F.; Adams, M. R.; Apanasevich, L.; Berry, D.; Betts, R. R.; Cavanaugh, R.; Chen, X.; Evdokimov, O.; Gerber, C. E.; Hangal, D. A.; Hofman, D. J.; Jung, K.; Kamin, J.; Sandoval Gonzalez, I. D.; Tonjes, M. B.; Trauger, H.; Varelas, N.; Wang, H.; Wu, Z.; Zhang, J.; Bilki, B.; Clarida, W.; Dilsiz, K.; Durgut, S.; Gandrajula, R. P.; Haytmyradov, M.; Khristenko, V.; Merlo, J.-P.; Mermerkaya, H.; Mestvirishvili, A.; Moeller, A.; Nachtman, J.; Ogul, H.; Onel, Y.; Ozok, F.; Penzo, A.; Snyder, C.; Tiras, E.; Wetzel, J.; Yi, K.; Blumenfeld, B.; Cocoros, A.; Eminizer, N.; Fehling, D.; Feng, L.; Gritsan, A. V.; Maksimovic, P.; Roskes, J.; Sarica, U.; Swartz, M.; Xiao, M.; You, C.; Al-bataineh, A.; Baringer, P.; Bean, A.; Boren, S.; Bowen, J.; Castle, J.; Khalil, S.; Kropivnitskaya, A.; Majumder, D.; Mcbrayer, W.; Murray, M.; Royon, C.; Sanders, S.; Schmitz, E.; Stringer, R.; Tapia Takaki, J. D.; Wang, Q.; Ivanov, A.; Kaadze, K.; Maravin, Y.; Mohammadi, A.; Saini, L. K.; Skhirtladze, N.; Toda, S.; Rebassoo, F.; Wright, D.; Anelli, C.; Baden, A.; Baron, O.; Belloni, A.; Calvert, B.; Eno, S. C.; Ferraioli, C.; Hadley, N. J.; Jabeen, S.; Jeng, G. Y.; Kellogg, R. G.; Kunkle, J.; Mignerey, A. C.; Ricci-Tam, F.; Shin, Y. H.; Skuja, A.; Tonwar, S. C.; Abercrombie, D.; Allen, B.; Azzolini, V.; Barbieri, R.; Baty, A.; Bi, R.; Brandt, S.; Busza, W.; Cali, I. A.; D'Alfonso, M.; Demiragli, Z.; Gomez Ceballos, G.; Goncharov, M.; Hsu, D.; Iiyama, Y.; Innocenti, G. M.; Klute, M.; Kovalskyi, D.; Lai, Y. S.; Lee, Y.-J.; Levin, A.; Luckey, P. D.; Maier, B.; Marini, A. C.; Mcginn, C.; Mironov, C.; Narayanan, S.; Niu, X.; Paus, C.; Roland, C.; Roland, G.; Salfeld-Nebgen, J.; Stephans, G. S. F.; Tatar, K.; Velicanu, D.; Wang, J.; Wang, T. W.; Wyslouch, B.; Benvenuti, A. C.; Chatterjee, R. M.; Evans, A.; Hansen, P.; Kalafut, S.; Kubota, Y.; Lesko, Z.; Mans, J.; Nourbakhsh, S.; Ruckstuhl, N.; Rusack, R.; Turkewitz, J.; Acosta, J. G.; Oliveros, S.; Avdeeva, E.; Bloom, K.; Claes, D. R.; Fangmeier, C.; Gonzalez Suarez, R.; Kamalieddin, R.; Kravchenko, I.; Monroy, J.; Siado, J. E.; Snow, G. R.; Stieger, B.; Alyari, M.; Dolen, J.; Godshalk, A.; Harrington, C.; Iashvili, I.; Nguyen, D.; Parker, A.; Rappoccio, S.; Roozbahani, B.; Alverson, G.; Barberis, E.; Hortiangtham, A.; Massironi, A.; Morse, D. M.; Nash, D.; Orimoto, T.; Teixeira De Lima, R.; Trocino, D.; Wang, R.-J.; Wood, D.; Bhattacharya, S.; Charaf, O.; Hahn, K. A.; Mucia, N.; Odell, N.; Pollack, B.; Schmitt, M. H.; Sung, K.; Trovato, M.; Velasco, M.; Dev, N.; Hildreth, M.; Hurtado Anampa, K.; Jessop, C.; Karmgard, D. J.; Kellams, N.; Lannon, K.; Loukas, N.; Marinelli, N.; Meng, F.; Mueller, C.; Musienko, Y.; Planer, M.; Reinsvold, A.; Ruchti, R.; Smith, G.; Taroni, S.; Wayne, M.; Wolf, M.; Woodard, A.; Alimena, J.; Antonelli, L.; Bylsma, B.; Durkin, L. S.; Flowers, S.; Francis, B.; Hart, A.; Hill, C.; Ji, W.; Liu, B.; Luo, W.; Puigh, D.; Winer, B. L.; Wulsin, H. W.; Benaglia, A.; Cooperstein, S.; Driga, O.; Elmer, P.; Hardenbrook, J.; Hebda, P.; Lange, D.; Luo, J.; Marlow, D.; Mei, K.; Ojalvo, I.; Olsen, J.; Palmer, C.; Piroué, P.; Stickland, D.; Svyatkovskiy, A.; Tully, C.; Malik, S.; Norberg, S.; Barker, A.; Barnes, V. E.; Folgueras, S.; Gutay, L.; Jha, M. K.; Jones, M.; Jung, A. W.; Khatiwada, A.; Miller, D. H.; Neumeister, N.; Schulte, J. F.; Sun, J.; Wang, F.; Xie, W.; Cheng, T.; Parashar, N.; Stupak, J.; Adair, A.; Akgun, B.; Chen, Z.; Ecklund, K. M.; Geurts, F. J. M.; Guilbaud, M.; Li, W.; Michlin, B.; Northup, M.; Padley, B. P.; Roberts, J.; Rorie, J.; Tu, Z.; Zabel, J.; Bodek, A.; de Barbaro, P.; Demina, R.; Duh, Y. t.; Ferbel, T.; Galanti, M.; Garcia-Bellido, A.; Han, J.; Hindrichs, O.; Khukhunaishvili, A.; Lo, K. H.; Tan, P.; Verzetti, M.; Ciesielski, R.; Goulianos, K.; Mesropian, C.; Agapitos, A.; Chou, J. P.; Gershtein, Y.; Gómez Espinosa, T. A.; Halkiadakis, E.; Heindl, M.; Hughes, E.; Kaplan, S.; Kunnawalkam Elayavalli, R.; Kyriacou, S.; Lath, A.; Montalvo, R.; Nash, K.; Osherson, M.; Saka, H.; Salur, S.; Schnetzer, S.; Sheffield, D.; Somalwar, S.; Stone, R.; Thomas, S.; Thomassen, P.; Walker, M.; Foerster, M.; Heideman, J.; Riley, G.; Rose, K.; Spanier, S.; Thapa, K.; Bouhali, O.; Castaneda Hernandez, A.; Celik, A.; Dalchenko, M.; De Mattia, M.; Delgado, A.; Dildick, S.; Eusebi, R.; Gilmore, J.; Huang, T.; Kamon, T.; Mueller, R.; Pakhotin, Y.; Patel, R.; Perloff, A.; Perniè, L.; Rathjens, D.; Safonov, A.; Tatarinov, A.; Ulmer, K. A.; Akchurin, N.; Damgov, J.; De Guio, F.; Dudero, P. R.; Faulkner, J.; Gurpinar, E.; Kunori, S.; Lamichhane, K.; Lee, S. W.; Libeiro, T.; Peltola, T.; Undleeb, S.; Volobouev, I.; Wang, Z.; Greene, S.; Gurrola, A.; Janjam, R.; Johns, W.; Maguire, C.; Melo, A.; Ni, H.; Sheldon, P.; Tuo, S.; Velkovska, J.; Xu, Q.; Arenton, M. W.; Barria, P.; Cox, B.; Hirosky, R.; Ledovskoy, A.; Li, H.; Neu, C.; Sinthuprasith, T.; Sun, X.; Wang, Y.; Wolfe, E.; Xia, F.; Clarke, C.; Harr, R.; Karchin, P. E.; Sturdy, J.; Zaleski, S.; Buchanan, J.; Caillol, C.; Dasu, S.; Dodd, L.; Duric, S.; Gomber, B.; Grothe, M.; Herndon, M.; Hervé, A.; Hussain, U.; Klabbers, P.; Lanaro, A.; Levine, A.; Long, K.; Loveless, R.; Pierro, G. A.; Polese, G.; Ruggles, T.; Savin, A.; Smith, N.; Smith, W. H.; Taylor, D.; Woods, N.

    2018-04-01

    Normalized differential cross sections for top quark pair production are measured in the dilepton (e+e-, μ + μ -, and μ ∓e±) decay channels in proton-proton collisions at a center-of-mass energy of 13 TeV. The measurements are performed with data corresponding to an integrated luminosity of 2.1 fb-1 using the CMS detector at the LHC. The cross sections are measured differentially as a function of the kinematic properties of the leptons, jets from bottom quark hadronization, top quarks, and top quark pairs at the particle and parton levels. The results are compared to several Monte Carlo generators that implement calculations up to next-to-leading order in perturbative quantum chromodynamics interfaced with parton showering, and also to fixed-order theoretical calculations of top quark pair production up to next-to-next-to-leading order. [Figure not available: see fulltext.

  9. Keratin 8/18 regulation of glucose metabolism in normal versus cancerous hepatic cells through differential modulation of hexokinase status and insulin signaling

    Energy Technology Data Exchange (ETDEWEB)

    Mathew, Jasmin; Loranger, Anne; Gilbert, Stéphane [Centre de recherche en cancérologie de l' Université Laval and Centre de recherche du CHUQ (L' Hôtel-Dieu de Québec), 9 McMahon, Québec, Qc, Canada G1R 2J6 (Canada); Faure, Robert [Département de Pédiatrie, Université Laval and Centre de recherche du CHUQ (Centre Mère-Enfant), Québec, Qc, Canada G1V 4G2 (Canada); Marceau, Normand, E-mail: normand.marceau@crhdq.ulaval.ca [Centre de recherche en cancérologie de l' Université Laval and Centre de recherche du CHUQ (L' Hôtel-Dieu de Québec), 9 McMahon, Québec, Qc, Canada G1R 2J6 (Canada)

    2013-02-15

    As differentiated cells, hepatocytes primarily metabolize glucose for ATP production through oxidative phosphorylation of glycolytic pyruvate, whereas proliferative hepatocellular carcinoma (HCC) cells undergo a metabolic shift to aerobic glycolysis despite oxygen availability. Keratins, the intermediate filament (IF) proteins of epithelial cells, are expressed as pairs in a lineage/differentiation manner. Hepatocyte and HCC (hepatoma) cell IFs are made solely of keratins 8/18 (K8/K18), thus providing models of choice to address K8/K18 IF functions in normal and cancerous epithelial cells. Here, we demonstrate distinctive increases in glucose uptake, glucose-6-phosphate formation, lactate release, and glycogen formation in K8/K18 IF-lacking hepatocytes and/or hepatoma cells versus their respective IF-containing counterparts. We also show that the K8/K18-dependent glucose uptake/G6P formation is linked to alterations in hexokinase I/II/IV content and localization at mitochondria, with little effect on GLUT1 status. In addition, we find that the insulin-stimulated glycogen formation in normal hepatocytes involves the main PI-3 kinase-dependent signaling pathway and that the K8/K18 IF loss makes them more efficient glycogen producers. In comparison, the higher insulin-dependent glycogen formation in K8/K18 IF-lacking hepatoma cells is associated with a signaling occurring through a mTOR-dependent pathway, along with an augmentation in cell proliferative activity. Together, the results uncover a key K8/K18 regulation of glucose metabolism in normal and cancerous hepatic cells through differential modulations of mitochondrial HK status and insulin-mediated signaling.

  10. Interleukin 22 early affects keratinocyte differentiation, but not proliferation, in a three-dimensional model of normal human skin

    Energy Technology Data Exchange (ETDEWEB)

    Donetti, Elena, E-mail: elena.donetti@unimi.it [Department of Biomedical Sciences for Health, Università degli Studi di Milano, 20133 Milan (Italy); Cornaghi, Laura; Arnaboldi, Francesca; Landoni, Federica [Department of Biomedical Sciences for Health, Università degli Studi di Milano, 20133 Milan (Italy); Romagnoli, Paolo [Department of Experimental and Clinical Medicine, Università degli Studi di Firenze, 50125 Florence (Italy); Mastroianni, Nicolino [Department of Biomedical Sciences for Health, Università degli Studi di Milano, 20133 Milan (Italy); Pescitelli, Leonardo [Department of Surgery and Translational Medicine, Università degli Studi di Firenze, 50125 Florence (Italy); Baruffaldi Preis, Franz W. [I.R.C.C.S. Istituto Ortopedico Galeazzi, 20161 Milan (Italy); Prignano, Francesca [Department of Surgery and Translational Medicine, Università degli Studi di Firenze, 50125 Florence (Italy)

    2016-07-15

    Interleukin (IL)-22 is a pro-inflammatory cytokine driving the progression of the psoriatic lesion with other cytokines, as Tumor Necrosis Factor (TNF)-alpha and IL-17. Our study was aimed at evaluating the early effect of IL-22 alone or in combination with TNF-alpha and IL-17 by immunofluorescence on i) keratinocyte (KC) proliferation, ii) terminal differentiation biomarkers as keratin (K) 10 and 17 expression, iii) intercellular junctions. Transmission electron microscopy (TEM) analysis was performed. A model of human skin culture reproducing a psoriatic microenvironment was used. Plastic surgery explants were obtained from healthy young women (n=7) after informed consent. Fragments were divided before adding IL-22 or a combination of the three cytokines, and harvested 24 (T24), 48 (T48), and 72 (T72) h later. From T24, in IL-22 samples we detected a progressive decrease in K10 immunostaining in the spinous layer paralleled by K17 induction. By TEM, after IL-22 incubation, keratin aggregates were evident in the perinuclear area. Occludin immunostaining was not homogeneously distributed. Conversely, KC proliferation was not inhibited by IL-22 alone, but only by the combination of cytokines. Our results suggest that IL-22 affects keratinocyte terminal differentiation, whereas, in order to induce a proliferation impairment, a more complex psoriatic-like microenvironment is needed.

  11. Interleukin 22 early affects keratinocyte differentiation, but not proliferation, in a three-dimensional model of normal human skin

    International Nuclear Information System (INIS)

    Donetti, Elena; Cornaghi, Laura; Arnaboldi, Francesca; Landoni, Federica; Romagnoli, Paolo; Mastroianni, Nicolino; Pescitelli, Leonardo; Baruffaldi Preis, Franz W.; Prignano, Francesca

    2016-01-01

    Interleukin (IL)-22 is a pro-inflammatory cytokine driving the progression of the psoriatic lesion with other cytokines, as Tumor Necrosis Factor (TNF)-alpha and IL-17. Our study was aimed at evaluating the early effect of IL-22 alone or in combination with TNF-alpha and IL-17 by immunofluorescence on i) keratinocyte (KC) proliferation, ii) terminal differentiation biomarkers as keratin (K) 10 and 17 expression, iii) intercellular junctions. Transmission electron microscopy (TEM) analysis was performed. A model of human skin culture reproducing a psoriatic microenvironment was used. Plastic surgery explants were obtained from healthy young women (n=7) after informed consent. Fragments were divided before adding IL-22 or a combination of the three cytokines, and harvested 24 (T24), 48 (T48), and 72 (T72) h later. From T24, in IL-22 samples we detected a progressive decrease in K10 immunostaining in the spinous layer paralleled by K17 induction. By TEM, after IL-22 incubation, keratin aggregates were evident in the perinuclear area. Occludin immunostaining was not homogeneously distributed. Conversely, KC proliferation was not inhibited by IL-22 alone, but only by the combination of cytokines. Our results suggest that IL-22 affects keratinocyte terminal differentiation, whereas, in order to induce a proliferation impairment, a more complex psoriatic-like microenvironment is needed.

  12. Cognitive-affective depression and somatic symptoms clusters are differentially associated with maternal parenting and coparenting.

    Science.gov (United States)

    Lamela, Diogo; Jongenelen, Inês; Morais, Ana; Figueiredo, Bárbara

    2017-09-01

    Both depressive and somatic symptoms are significant predictors of parenting and coparenting problems. However, despite clear evidence of their co-occurrence, no study to date has examined the association between depressive-somatic symptoms clusters and parenting and coparenting. The current research sought to identify and cross-validate clusters of cognitive-affective depressive symptoms and nonspecific somatic symptoms, as well as to test whether clusters would differ on parenting and coparenting problems across three independent samples of mothers. Participants in Studies 1 and 3 consisted of 409 and 652 community mothers, respectively. Participants in Study 2 consisted of 162 mothers exposed to intimate partner violence. All participants prospectively completed self-report measures of depressive and nonspecific somatic symptoms and parenting (Studies 1 and 2) or coparenting (Study 3). Across studies, three depression-somatic symptoms clusters were identified: no symptoms, high depression and low nonspecific somatic symptoms, and high depression and nonspecific somatic symptoms. The high depression-somatic symptoms cluster was associated with the highest levels of child physical maltreatment risk (Study 1) and overt-conflict coparenting (Study 3). No differences in perceived maternal competence (Study 2) and cooperative and undermining coparenting (Study 3) were found between the high depression and low somatic symptoms cluster and the high depression-somatic symptoms cluster. The results provide novel evidence for the strong associations between clusters of depression and nonspecific somatic symptoms and specific parenting and coparenting problems. Cluster stability across three independent samples suggest that they may be generalizable. The results inform preventive approaches and evidence-based psychotherapeutic treatments. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Quarter-Sweep Iteration Concept on Conjugate Gradient Normal Residual Method via Second Order Quadrature - Finite Difference Schemes for Solving Fredholm Integro-Differential Equations

    International Nuclear Information System (INIS)

    Aruchunan, E.

    2015-01-01

    In this paper, we have examined the effectiveness of the quarter-sweep iteration concept on conjugate gradient normal residual (CGNR) iterative method by using composite Simpson's (CS) and finite difference (FD) discretization schemes in solving Fredholm integro-differential equations. For comparison purposes, Gauss- Seidel (GS) and the standard or full- and half-sweep CGNR methods namely FSCGNR and HSCGNR are also presented. To validate the efficacy of the proposed method, several analyses were carried out such as computational complexity and percentage reduction on the proposed and existing methods. (author)

  14. Differentiation of the mRNA transcripts originating from the alpha 1- and alpha 2-globin loci in normals and alpha-thalassemics.

    OpenAIRE

    Liebhaber, S A; Kan, Y W

    1981-01-01

    The alpha-globin polypeptide is encoded by two adjacent genes, alpha 1 and alpha 2. In the normal diploid state (alpha alpha/alpha alpha) all four alpha-globin genes are expressed. Loss or dysfunction of one or more of these genes leads to deficient alpha-globin production and results in alpha-thalassemia. We present a technique to differentially assess the steady-state levels of the alpha 1- and alpha-2-globin messenger RNA (mRNA) transcripts and thus delineate the relative level of expressi...

  15. Differentials in health-related quality of life of employed and unemployed women with normal vaginal delivery

    OpenAIRE

    Chinweuba, Anthonia U.; Okoronkwo, Ijeoma L.; Anarado, Agnes N.; Agbapuonwu, Noreen E.; Ogbonnaya, Ngozi P.; Ihudiebube-Splendor, Chikaodili N.

    2018-01-01

    Background The combination of child care and domestic work demands on both housewives and the employed (hired) women may impact their health-related quality-of-life. There is paucity of studies to ascertain this. This study investigated the differences in health-related quality of life of employed and unemployed women with normal vaginal delivery and associated socio-demographic variables. Methods This longitudinal study was done from March, 2012 to June, 2013. Modified SF-36v2™ health-relate...

  16. Emotional and cognitive stimuli differentially engage the default network during inductive reasoning.

    Science.gov (United States)

    Eldaief, Mark C; Deckersbach, Thilo; Carlson, Lindsay E; Beucke, Jan C; Dougherty, Darin D

    2012-04-01

    The brain's default network (DN) is comprised of several cortical regions demonstrating robust intrinsic connectivity at rest. The authors sought to examine the differential effects of emotional reasoning and reasoning under certainty upon the DN through the employment of an event-related fMRI design in healthy participants. Participants were presented with syllogistic arguments which were organized into a 2 × 2 factorial design in which the first factor was emotional salience and the second factor was certainty/uncertainty. We demonstrate that regions of the DN were activated both during reasoning that is emotionally salient and during reasoning which is more certain, suggesting that these processes are neurally instantiated on a network level. In addition, we present evidence that emotional reasoning preferentially activates the dorsomedial (dMPFC) subsystem of the DN, whereas reasoning in the context of certainty activates areas specific to the DN's medial temporal (MTL) subsystem. We postulate that emotional reasoning mobilizes the dMPFC subsystem of the DN because this type of reasoning relies upon the recruitment of introspective and self-relevant data such as personal bias and temperament. In contrast, activation of the MTL subsystem during certainty argues that this form of reasoning involves the recruitment of mnemonic and semantic associations to derive conclusions.

  17. Extended flow cytometry characterization of normal bone marrow progenitor cells by simultaneous detection of aldehyde dehydrogenase and early hematopoietic antigens: implication for erythroid differentiation studies

    Directory of Open Access Journals (Sweden)

    Pascariello Caterina

    2008-05-01

    Full Text Available Abstract Background Aldehyde dehydrogenase (ALDH is a cytosolic enzyme highly expressed in hematopoietic precursors from cord blood and granulocyte-colony stimulating factor mobilized peripheral blood, as well as in bone marrow from patients with acute myeloblastic leukemia. As regards human normal bone marrow, detailed characterization of ALDH+ cells has been addressed by one single study (Gentry et al, 2007. The goal of our work was to provide new information about the dissection of normal bone marrow progenitor cells based upon the simultaneous detection by flow cytometry of ALDH and early hematopoietic antigens, with particular attention to the expression of ALDH on erythroid precursors. To this aim, we used three kinds of approach: i multidimensional analytical flow cytometry, detecting ALDH and early hematopoietic antigens in normal bone marrow; ii fluorescence activated cell sorting of distinct subpopulations of progenitor cells, followed by in vitro induction of erythroid differentiation; iii detection of ALDH+ cellular subsets in bone marrow from pure red cell aplasia patients. Results In normal bone marrow, we identified three populations of cells, namely ALDH+CD34+, ALDH-CD34+ and ALDH+CD34- (median percentages were 0.52, 0.53 and 0.57, respectively. As compared to ALDH-CD34+ cells, ALDH+CD34+ cells expressed the phenotypic profile of primitive hematopoietic progenitor cells, with brighter expression of CD117 and CD133, accompanied by lower display of CD38 and CD45RA. Of interest, ALDH+CD34- population disclosed a straightforward erythroid commitment, on the basis of three orders of evidences. First of all, ALDH+CD34- cells showed a CD71bright, CD105+, CD45- phenotype. Secondly, induction of differentiation experiments evidenced a clear-cut expression of glycophorin A (CD235a. Finally, ALDH+CD34- precursors were not detectable in patients with pure red cell aplasia (PRCA. Conclusion Our study, comparing surface antigen expression of

  18. Differentiation of isomeric N-glycan structures by normal-phase liquid chromatography-MALDI-TOF/TOF tandem mass spectrometry.

    Science.gov (United States)

    Maslen, Sarah; Sadowski, Pawel; Adam, Alex; Lilley, Kathryn; Stephens, Elaine

    2006-12-15

    The detailed characterization of protein N-glycosylation is very demanding given the many different glycoforms and structural isomers that can exist on glycoproteins. Here we report a fast and sensitive method for the extensive structure elucidation of reducing-end labeled N-glycan mixtures using a combination of capillary normal-phase HPLC coupled off-line to matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and TOF/TOF-MS/MS. Using this method, isobaric N-glycans released from honey bee phospholipase A2 and Arabidopsis thaliana glycoproteins were separated by normal-phase chromatography and subsequently identified by key fragment ions in the MALDI-TOF/TOF tandem mass spectra. In addition, linkage and branching information were provided by abundant cross-ring and "elimination" fragment ions in the MALDI-CID spectra that gave extensive structural information. Furthermore, the fragmentation characteristics of N-glycans reductively aminated with 2-aminobenzoic acid and 2-aminobenzamide were compared. The identification of N-glycans containing 3-linked core fucose was facilitated by distinctive ions present only in the MALDI-CID spectra of 2-aminobenzoic acid-labeled oligosaccharides. To our knowledge, this is the first MS/MS-based technique that allows confident identification of N-glycans containing 3-linked core fucose, which is a major allergenic determinant on insect and plant glycoproteins.

  19. Differential effects of approach bias and eating style on unhealthy food consumption in overweight and normal weight women.

    Science.gov (United States)

    Kakoschke, Naomi; Kemps, Eva; Tiggemann, Marika

    2017-11-01

    The current study aimed to examine the effects of approach bias for unhealthy food and trait eating style on consumption of unhealthy food in overweight and normal weight individuals. Participants were 245 undergraduate women aged 17 - 26 years. They completed an Approach-Avoidance Task, the Dutch Eating Behaviour Questionnaire (to assess restrained, emotional, and external eating), and a taste test to measure consumption of unhealthy food. An external eating style predicted increased consumption of unhealthy food. Among overweight participants, external and emotional eating style individually moderated the relationship between approach bias for unhealthy food and subsequent consumption. Specifically, approach bias was positively related to consumption in high external and emotional eaters, but negatively related to consumption in low emotional eaters. These interactions were not observed among normal weight participants. Practically, the results suggest that overweight individuals who are external or emotional eaters may benefit from interventions that aim to modify approach bias towards unhealthy food cues to reduce problematic eating behaviour.

  20. Differentiation in boron distribution in adult male and female rats' normal brain: A BNCT approach

    Energy Technology Data Exchange (ETDEWEB)

    Goodarzi, Samereh, E-mail: samere.g@gmail.com [Department of Nuclear Engineering, Science and Research Branch, Islamic Azad University, PO Box 19395-1943, Tehran (Iran, Islamic Republic of); Pazirandeh, Ali, E-mail: paziran@yahoo.com [Department of Nuclear Engineering, Science and Research Branch, Islamic Azad University, PO Box 19395-1943, Tehran (Iran, Islamic Republic of); Jameie, Seyed Behnamedin, E-mail: behnamjameie@tums.ac.ir [Basic Science Department, Faculty of Allied Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Department of Anatomy, Faculty of Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Baghban Khojasteh, Nasrin, E-mail: khojasteh_n@yahoo.com [Department of Nuclear Engineering, Science and Research Branch, Islamic Azad University, PO Box 19395-1943, Tehran (Iran, Islamic Republic of)

    2012-06-15

    Boron distribution in adult male and female rats' normal brain after boron carrier injection (0.005 g Boric Acid+0.005 g Borax+10 ml distilled water, pH: 7.4) was studied in this research. Coronal sections of control and trial animal tissue samples were irradiated with thermal neutrons. Using alpha autoradiography, significant differences in boron concentration were seen in forebrain, midbrain and hindbrain sections of male and female animal groups with the highest value, four hours after boron compound injection. - Highlights: Black-Right-Pointing-Pointer Boron distribution in male and female rats' normal brain was studied in this research. Black-Right-Pointing-Pointer Coronal sections of animal tissue samples were irradiated with thermal neutrons. Black-Right-Pointing-Pointer Alpha and Lithium tracks were counted using alpha autoradiography. Black-Right-Pointing-Pointer Different boron concentration was seen in brain sections of male and female rats. Black-Right-Pointing-Pointer The highest boron concentration was seen in 4 h after boron compound injection.

  1. Differentiating the two main histologic categories of fibroadenoma tissue from normal breast tissue by using multiphoton microscopy.

    Science.gov (United States)

    Nie, Y T; Wu, Y; Fu, F M; Lian, Y E; Zhuo, S M; Wang, C; Chen, J X

    2015-04-01

    Multiphoton microscopy has become a novel biological imaging technique that allows cellular and subcellular microstructure imaging based on two-photon excited fluorescence and second harmonic generation. In this work, we used multiphoton microscopy to obtain the high-contrast images of human normal breast tissue and two main histologic types of fibroadenoma (intracanalicular, pericanalicular). Moreover, quantitative image analysis was performed to characterize the changes of collagen morphology (collagen content, collagen orientation). The results show that multiphoton microscopy combined with quantitative method has the ability to identify the characteristics of fibroadenoma including changes of the duct architecture and collagen morphology in stroma. With the advancement of multiphoton microscopy, we believe that the technique has great potential to be a real-time histopathological diagnostic tool for intraoperative detection of fibroadenoma in the future. © 2015 The Authors Journal of Microscopy © 2015 Royal Microscopical Society.

  2. Quantitative assessment of cerebral hemodynamic parameters by QUASAR arterial spin labeling in Alzheimer's disease and cognitively normal Elderly adults at 3-tesla.

    Science.gov (United States)

    Mak, Henry K F; Chan, Queenie; Zhang, Zhipeng; Petersen, Esben T; Qiu, Deqiang; Zhang, Linda; Yau, Kelvin K W; Chu, Leung-Wing; Golay, Xavier

    2012-01-01

    QUASAR arterial spin labeling (ASL) was used to investigate the role of vascular impairment in Alzheimer's disease (AD). We hypothesized that the hemodynamic parameters monitoring cerebrovascular integrity, i.e., cerebral blood flow (CBF), arterial blood volume (aBV), and arterial transit time (aTT), would be affected. 13 AD patients and 15 healthy control (HC) subjects underwent 3T MRI scanning. Two separate blood flow acquisitions were obtained with 1 slice overlap for whole brain coverage. CBF, aBV, and aTT maps were calculated using in-house software. Preprocessing and statistical analyses were performed on SPM5. Region-of-interest (ROI) studies of ten selected cerebral regions were also conducted. There were significant differences in mini mental status exam (MMSE) (AD: 16.3 ± 4.55, HC: 28.5 ± 2.00) and Alzheimer's disease assessment scale-cognitive subscale (ADAS-cog) scores (AD: 25.25 ± 9.64, HC: 5.51 ± 2.62) between the 2 groups (p QUASAR ASL, we found patterns of regional hemodynamic impairment typical of moderate AD, suggesting underlying vascular abnormality. As potential biomarkers, these hemodynamic parameters could differentiate patients from volunteers, and possibly indicate the conversion from healthy aging to mild cognitive impairment to AD.

  3. Tubular urate transporter gene polymorphisms differentiate patients with gout who have normal and decreased urinary uric acid excretion.

    Science.gov (United States)

    Torres, Rosa J; de Miguel, Eugenio; Bailén, Rebeca; Banegas, José R; Puig, Juan G

    2014-09-01

    Primary gout has been associated with single-nucleotide polymorphisms (SNP) in several tubular urate transporter genes. No study has assessed the association of reabsorption and secretion urate transporter gene SNP with gout in a single cohort of documented primary patients with gout carefully subclassified as normoexcretors or underexcretors. Three reabsorption SNP (SLC22A12/URAT1, SLC2A9/GLUT9, and SLC22A11/OAT4) and 2 secretion transporter SNP (SLC17A1/NPT1 and ABCG2/BRCP) were studied in 104 patients with primary gout and in 300 control subjects. The patients were subclassified into normoexcretors and underexcretors according to their serum and 24-h urinary uric acid levels under strict conditions of dietary control. Compared with control subjects, patients with gout showed different allele distributions of the 5 SNP analyzed. However, the diagnosis of underexcretor was only positively associated with the presence of the T allele of URAT1 rs11231825, the G allele of GLUT9 rs16890979, and the A allele of ABCG2 rs2231142. The association of the A allele of ABCG2 rs2231142 in normoexcretors was 10 times higher than in underexcretors. The C allele of NPT1 rs1165196 was only significantly associated with gout in patients with normal uric acid excretion. Gout with uric acid underexcretion is associated with transporter gene SNP related mainly to tubular reabsorption, whereas uric acid normoexcretion is associated only with tubular secretion SNP. This finding supports the concept of distinctive mechanisms to account for hyperuricemia in patients with gout with reduced or normal uric acid excretion.

  4. NIMROD: a program for inference via a normal approximation of the posterior in models with random effects based on ordinary differential equations.

    Science.gov (United States)

    Prague, Mélanie; Commenges, Daniel; Guedj, Jérémie; Drylewicz, Julia; Thiébaut, Rodolphe

    2013-08-01

    Models based on ordinary differential equations (ODE) are widespread tools for describing dynamical systems. In biomedical sciences, data from each subject can be sparse making difficult to precisely estimate individual parameters by standard non-linear regression but information can often be gained from between-subjects variability. This makes natural the use of mixed-effects models to estimate population parameters. Although the maximum likelihood approach is a valuable option, identifiability issues favour Bayesian approaches which can incorporate prior knowledge in a flexible way. However, the combination of difficulties coming from the ODE system and from the presence of random effects raises a major numerical challenge. Computations can be simplified by making a normal approximation of the posterior to find the maximum of the posterior distribution (MAP). Here we present the NIMROD program (normal approximation inference in models with random effects based on ordinary differential equations) devoted to the MAP estimation in ODE models. We describe the specific implemented features such as convergence criteria and an approximation of the leave-one-out cross-validation to assess the model quality of fit. In pharmacokinetics models, first, we evaluate the properties of this algorithm and compare it with FOCE and MCMC algorithms in simulations. Then, we illustrate NIMROD use on Amprenavir pharmacokinetics data from the PUZZLE clinical trial in HIV infected patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  5. Mode of effective connectivity within a putative neural network differentiates moral cognitions related to care and justice ethics.

    Science.gov (United States)

    Cáceda, Ricardo; James, G Andrew; Ely, Timothy D; Snarey, John; Kilts, Clinton D

    2011-02-25

    Moral sensitivity refers to the interpretive awareness of moral conflict and can be justice or care oriented. Justice ethics is associated primarily with human rights and the application of moral rules, whereas care ethics is related to human needs and a situational approach involving social emotions. Among the core brain regions involved in moral issue processing are: medial prefrontal cortex, anterior (ACC) and posterior (PCC) cingulate cortex, posterior superior temporal sulcus (pSTS), insula and amygdala. This study sought to inform the long standing debate of whether care and justice moral ethics represent one or two different forms of cognition. Model-free and model-based connectivity analysis were used to identify functional neural networks underlying care and justice ethics for a moral sensitivity task. In addition to modest differences in patterns of associated neural activity, distinct modes of functional and effective connectivity were observed for moral sensitivity for care and justice issues that were modulated by individual variation in moral ability. These results support a neurobiological differentiation between care and justice ethics and suggest that human moral behavior reflects the outcome of integrating opposing rule-based, self-other perspectives, and emotional responses.

  6. Mode of Effective Connectivity within a Putative Neural Network Differentiates Moral Cognitions Related to Care and Justice Ethics

    Science.gov (United States)

    Cáceda, Ricardo; James, G. Andrew; Ely, Timothy D.; Snarey, John; Kilts, Clinton D.

    2011-01-01

    Background Moral sensitivity refers to the interpretive awareness of moral conflict and can be justice or care oriented. Justice ethics is associated primarily with human rights and the application of moral rules, whereas care ethics is related to human needs and a situational approach involving social emotions. Among the core brain regions involved in moral issue processing are: medial prefrontal cortex, anterior (ACC) and posterior (PCC) cingulate cortex, posterior superior temporal sulcus (pSTS), insula and amygdala. This study sought to inform the long standing debate of whether care and justice moral ethics represent one or two different forms of cognition. Methodology/Principal Findings Model-free and model-based connectivity analysis were used to identify functional neural networks underlying care and justice ethics for a moral sensitivity task. In addition to modest differences in patterns of associated neural activity, distinct modes of functional and effective connectivity were observed for moral sensitivity for care and justice issues that were modulated by individual variation in moral ability. Conclusions/Significance These results support a neurobiological differentiation between care and justice ethics and suggest that human moral behavior reflects the outcome of integrating opposing rule-based, self-other perspectives, and emotional responses. PMID:21364916

  7. Mode of effective connectivity within a putative neural network differentiates moral cognitions related to care and justice ethics.

    Directory of Open Access Journals (Sweden)

    Ricardo Cáceda

    Full Text Available BACKGROUND: Moral sensitivity refers to the interpretive awareness of moral conflict and can be justice or care oriented. Justice ethics is associated primarily with human rights and the application of moral rules, whereas care ethics is related to human needs and a situational approach involving social emotions. Among the core brain regions involved in moral issue processing are: medial prefrontal cortex, anterior (ACC and posterior (PCC cingulate cortex, posterior superior temporal sulcus (pSTS, insula and amygdala. This study sought to inform the long standing debate of whether care and justice moral ethics represent one or two different forms of cognition. METHODOLOGY/PRINCIPAL FINDINGS: Model-free and model-based connectivity analysis were used to identify functional neural networks underlying care and justice ethics for a moral sensitivity task. In addition to modest differences in patterns of associated neural activity, distinct modes of functional and effective connectivity were observed for moral sensitivity for care and justice issues that were modulated by individual variation in moral ability. CONCLUSIONS/SIGNIFICANCE: These results support a neurobiological differentiation between care and justice ethics and suggest that human moral behavior reflects the outcome of integrating opposing rule-based, self-other perspectives, and emotional responses.

  8. Differential cognitive processing of Kanji and Kana words: do orthographic and semantic codes function in parallel in word matching task.

    Science.gov (United States)

    Kawakami, A; Hatta, T; Kogure, T

    2001-12-01

    Relative engagements of the orthographic and semantic codes in Kanji and Hiragana word recognition were investigated. In Exp. 1, subjects judged whether the pairs of Kanji words (prime and target) presented sequentially were physically identical to each other in the word condition. In the sentence condition, subjects decided whether the target word was valid for the prime sentence presented in advance. The results showed that the response times to the target swords orthographically similar (to the prime) were significantly slower than to semantically related target words in the word condition and that this was also the case in the sentence condition. In Exp. 2, subjects judged whether the target word written in Hiragana was physically identical to the prime word in the word condition. In the sentence condition, subjects decided if the target word was valid for the previously presented prime sentence. Analysis indicated that response times to orthographically similar words were slower than to semantically related words in the word condition but not in the sentence condition wherein the response times to the semantically and orthographically similar words were largely the same. Based on these results, differential contributions of orthographic and semantic codes in cognitive processing of Japanese Kanji and Hiragana words was discussed.

  9. Nonsuppressing normal thymus on chemical-shift MR imaging and anterior mediastinal lymphoma. Differentiation with diffusion-weighted MR imaging by using the apparent diffusion coefficient

    International Nuclear Information System (INIS)

    Priola, Adriano Massimiliano; Priola, Sandro Massimo; Gned, Dario; Veltri, Andrea; Giraudo, Maria Teresa

    2018-01-01

    To prospectively evaluate usefulness of the apparent diffusion coefficient (ADC) in differentiating anterior mediastinal lymphoma from nonsuppressing normal thymus on chemical-shift MR, and to look at the relationship between patient age and ADC. Seventy-three young subjects (25 men, 48 women; age range, 9-29 years), who underwent chemical-shift MR and diffusion-weighted MR were divided into a normal thymus group (group A, 40 subjects), and a lymphoma group (group B, 33 patients). For group A, all subjects had normal thymus with no suppression on opposed-phase chemical-shift MR. Two readers measured the signal intensity index (SII) and ADC. Differences in SII and ADC between groups were tested using t-test. ADC was correlated with age using Pearson correlation coefficient. Mean SII±standard deviation was 2.7±1.8% for group A and 2.2±2.4% for group B, with no significant difference between groups (P=.270). Mean ADC was 2.48±0.38 x 10 -3 mm 2 /s for group A and 1.24±0.23 x 10 -3 mm 2 /s for group B. A significant difference between groups was found (P<.001), with no overlap in range. Lastly, significant correlation was found between age and ADC (r=0.935, P<.001) in group A. ADC of diffusion-weighted MR is a noninvasive and accurate parameter for differentiating lymphoma from nonsuppressing thymus on chemical-shift MR in young subjects. (orig.)

  10. Differential effects of erythropoietin on neural and cognitive measures of executive function 3 and 7 days post-administration

    DEFF Research Database (Denmark)

    Miskowiak, Kamilla; Inkster, Becky; O'Sullivan, Ursula

    2008-01-01

    Erythropoietin (Epo) has neuroprotective and neurotrophic effects and improves cognitive function in animal models of neurodegenerative and neuropsychiatric illness. In humans, weekly Epo administration over 3 months improves cognitive function in schizophrenia. The neural underpinnings and time...

  11. 99mTc-glucarate kinetics differentiate normal, stunned, hibernating, and nonviable myocardium in a perfused rat heart model

    International Nuclear Information System (INIS)

    Okada, David R.; Liu, Zhonglin; Johnson, Gerald; Okada, Robert D.; Beju, Delia; Khaw, Ban An

    2010-01-01

    99m Tc-glucarate is an infarct-avid imaging agent. However, patients may have mixtures of normal, irreversibly injured, stunned, and hibernating myocardium. The purposes were to determine 99m Tc-glucarate uptake and clearance kinetics in these four conditions, and its ability to determine the extent of injury. Twenty-two perfused rat hearts were studied: controls (n = 5), stunned (n = 5; 20-min no-flow followed by 5-min reflow), hibernating (n = 6; 120-min low flow at 4 ml/min), and ischemic-reperfused (n = 6; 120-min no-flow followed by reflow). 99m Tc-glucarate was then infused. Tracer activity was monitored using a NaI scintillation detector and a multichannel analyzer. Creatine kinase, electron microscopy, and triphenyltetrazolium chloride determined viability. 99m Tc-glucarate 10-min myocardial uptake was significantly greater in ischemic-reperfused (2.50 ± 0.09) (cpm, SEM) than in control (1.74 ± 0.07), stunned (1.68 ± 0.11), and hibernating (1.59 ± 0.11) (p 99m Tc-glucarate 60-min myocardial uptake was significantly greater in ischemic-reperfused (7.60 ± 0.63) than in control (1.98 ± 0.15), stunned (1.79 ± 0.08), and hibernating (2.33 ± 0.15) (p 99m Tc-glucarate activity continually and progressively increased in irreversibly injured myocardium. 99m Tc-glucarate uptake was strongly correlated with myocardial necrosis as determined by three independent assessments of viability. There were minimal and similar 99m Tc-glucarate uptakes in control, stunned, and hibernating myocardium. (orig.)

  12. Acute aerobic exercise differentially alters acylated ghrelin and perceived fullness in normal-weight and obese individuals.

    Science.gov (United States)

    Heden, Timothy D; Liu, Ying; Park, Youngmin; Dellsperger, Kevin C; Kanaley, Jill A

    2013-09-01

    Adiposity alters acylated ghrelin concentrations, but it is unknown whether adiposity alters the effect of exercise and feeding on acylated ghrelin responses. Therefore, the purpose of this study was to determine whether adiposity [normal-weight (NW) vs. obese (Ob)] influences the effect of exercise and feeding on acylated ghrelin, hunger, and fullness. Fourteen NW and 14 Ob individuals completed two trials in a randomized counterbalanced fashion, including a prior exercise trial (EX) and a no exercise trial (NoEX). During the EX trial, the participants performed 1 h of treadmill walking (55-60% peak O2 uptake) during the evening, 12 h before a 4-h standardized mixed meal test. Frequent blood samples were taken and analyzed for acylated ghrelin, and a visual analog scale was used to assess perceived hunger and fullness. In NW individuals, EX, compared with NoEX, reduced fasting acylated ghrelin concentrations by 18% (P = 0.03), and, in response to feeding, the change in acylated ghrelin (P = 0.02) was attenuated by 39%, but perceived hunger and fullness were unaltered. In Ob individuals, despite no changes in fasting or postprandial acylated ghrelin concentrations with EX, postprandial fullness was attenuated by 46% compared with NoEX (P = 0.05). In summary, exercise performed the night before a meal suppresses acylated ghrelin concentrations in NW individuals without altering perceived hunger or fullness. In Ob individuals, despite no changes in acylated ghrelin concentrations, EX reduced the fullness response to the test meal. Acylated ghrelin and perceived fullness responses are differently altered by acute aerobic exercise in NW and Ob individuals.

  13. Cell biological effects of total body irradiation on growth and differentiation of acute myelogenous leukemia cells compared to normal bone marrow

    Energy Technology Data Exchange (ETDEWEB)

    Greenberger, J S; Weichselbaum, R R; Botnick, L E; Sakakeeny, M; Moloney, W C

    1979-01-01

    Radiation therapy is used as total body treatment in preparation of the acute myelogenous leukemia (AML) patient for bone marrow transplantation. Many AML patients will have residual leukemia cells at the time of total body irradiation (TBI). In the present study, the effect of TBI on leukemic myeloid cells was compared to the effect on normal marrow granulocytic stem cells (CFUc) in vitro. Little difference from that of normal CFUc was found in the radiosensitivity of two mouse myeloid leukemia cell lines. The effect of TBI on growth of WEHI-3 or J774 cells in millipore diffusion chambers was stimulatory. These AML cell lines as well as others derived from Friend or Abelson virus infected in vitro long term mouse marrow cultures showed some morphologic differentiation by 7 days growth in diffusion chambers in irradiated heterologous rat hosts, but immature cells predominated by day 21. Thus, evidence in murine models of AML indicates that residual AML cells surviving chemotherapy will show no greater susceptibility to radiation killing compared to normal stem cells and will rapidly repopulate the irradiated host.

  14. Capability of differentiating smokers with normal pulmonary function from COPD patients: a comparison of CT pulmonary volume analysis and MR perfusion imaging

    Energy Technology Data Exchange (ETDEWEB)

    Fan, Li; Xia, Yi; Guan, Yu; Yu, Hong; Liu, Shi-yuan [Changzheng Hospital of the Second Military Medical University, Department of Radiology, Shanghai (China); Zhang, Tie-feng; Li, Bing [Changzheng Hospital of the Second Military Medical University, Department of Respiration Medicine, Shanghai (China)

    2013-05-15

    To compare CT volume analysis with MR perfusion imaging in differentiating smokers with normal pulmonary function (controls) from COPD patients. Sixty-two COPD patients and 17 controls were included. The total lung volume (TLV), total emphysema volume (TEV) and emphysema index (EI) were quantified by CT. MR perfusion evaluated positive enhancement integral (PEI), maximum slope of increase (MSI), maximum slope of decrease (MSD), signal enhancement ratio (SER) and signal intensity ratio (R{sub SI}) of perfusion defects to normal lung. There were 19 class I, 17 class II, 14 class III and 12 class IV COPD patients. No differences were observed in TLV, TEV and EI between control and class I COPD. The control was different from class II, III and IV COPD in TEV and EI. The control was different from each class of COPD in R{sub SI,} MSI, PEI and MSD. Differences were found in R{sub SI} between class I and III, I and IV, and II and IV COPD. Amongst controls, MR detected perfusion defects more frequently than CT detected emphysema. Compared with CT, MR perfusion imaging shows higher potential to distinguish controls from mild COPD and appears more sensitive in identifying abnormalities amongst smokers with normal pulmonary function (controls). (orig.)

  15. Capability of differentiating smokers with normal pulmonary function from COPD patients: a comparison of CT pulmonary volume analysis and MR perfusion imaging

    International Nuclear Information System (INIS)

    Fan, Li; Xia, Yi; Guan, Yu; Yu, Hong; Liu, Shi-yuan; Zhang, Tie-feng; Li, Bing

    2013-01-01

    To compare CT volume analysis with MR perfusion imaging in differentiating smokers with normal pulmonary function (controls) from COPD patients. Sixty-two COPD patients and 17 controls were included. The total lung volume (TLV), total emphysema volume (TEV) and emphysema index (EI) were quantified by CT. MR perfusion evaluated positive enhancement integral (PEI), maximum slope of increase (MSI), maximum slope of decrease (MSD), signal enhancement ratio (SER) and signal intensity ratio (R SI ) of perfusion defects to normal lung. There were 19 class I, 17 class II, 14 class III and 12 class IV COPD patients. No differences were observed in TLV, TEV and EI between control and class I COPD. The control was different from class II, III and IV COPD in TEV and EI. The control was different from each class of COPD in R SI, MSI, PEI and MSD. Differences were found in R SI between class I and III, I and IV, and II and IV COPD. Amongst controls, MR detected perfusion defects more frequently than CT detected emphysema. Compared with CT, MR perfusion imaging shows higher potential to distinguish controls from mild COPD and appears more sensitive in identifying abnormalities amongst smokers with normal pulmonary function (controls). (orig.)

  16. Cultural Factors Affecting the Differential Performance of Israeli and Palestinian Children on the Loewenstein Occupational Therapy Cognitive Assessment

    Science.gov (United States)

    Josman, Naomi; Abdallah, Taisir M.; Engel-Yeger, Batya

    2010-01-01

    Cognitive performance is essential for children's functioning and may also predict school readiness. The suitability of Western standardized assessments for cognitive performance among children from different cultures needs to be elaborated. This study referred to the existence of differences in cognitive performance between and within children…

  17. Stroke and TIA survivors’ cognitive beliefs and affective responses regarding treatment and future stroke risk differentially predict medication adherence and categorised stroke risk

    Science.gov (United States)

    Phillips, L. Alison; Diefenbach, Michael A.; Abrams, Jessica; Horowitz, Carol R.

    2014-01-01

    Cognitive beliefs and affective responses to illness and treatment are known to independently predict health behaviours. The purpose of the current study is to assess the relative importance of four psychological domains – specifically, affective illness, cognitive illness, affective treatment and cognitive treatment – for predicting stroke and transient ischemic attack (TIA) survivors’ adherence to stroke prevention medications as well as their objective, categorised stroke risk. We assessed these domains among stroke/TIA survivors (n = 600), and conducted correlation and regression analyses with concurrent and prospective outcomes to determine the relative importance of each cognitive and affective domain for adherence and stroke risk. As hypothesised, patients’ affective treatment responses explained the greatest unique variance in baseline and six-month adherence reports (8 and 5%, respectively, of the variance in adherence, compared to 1–3% explained by other domains). Counter to hypotheses, patients’ cognitive illness beliefs explained the greatest unique variance in baseline and six-month objective categorised stroke risk (3 and 2%, respectively, compared to 0–1% explained by other domains). Results indicate that domain type (i.e. cognitive and affective) and domain referent (illness and treatment) may be differentially important for providers to assess when treating patients for stroke/TIA. More research is required to further distinguish between these domains and their relative importance for stroke prevention. PMID:25220292

  18. Stroke and TIA survivors' cognitive beliefs and affective responses regarding treatment and future stroke risk differentially predict medication adherence and categorised stroke risk.

    Science.gov (United States)

    Phillips, L Alison; Diefenbach, Michael A; Abrams, Jessica; Horowitz, Carol R

    2015-01-01

    Cognitive beliefs and affective responses to illness and treatment are known to independently predict health behaviours. The purpose of the current study is to assess the relative importance of four psychological domains - specifically, affective illness, cognitive illness, affective treatment and cognitive treatment - for predicting stroke and transient ischemic attack (TIA) survivors' adherence to stroke prevention medications as well as their objective, categorised stroke risk. We assessed these domains among stroke/TIA survivors (n = 600), and conducted correlation and regression analyses with concurrent and prospective outcomes to determine the relative importance of each cognitive and affective domain for adherence and stroke risk. As hypothesised, patients' affective treatment responses explained the greatest unique variance in baseline and six-month adherence reports (8 and 5%, respectively, of the variance in adherence, compared to 1-3% explained by other domains). Counter to hypotheses, patients' cognitive illness beliefs explained the greatest unique variance in baseline and six-month objective categorised stroke risk (3 and 2%, respectively, compared to 0-1% explained by other domains). Results indicate that domain type (i.e. cognitive and affective) and domain referent (illness and treatment) may be differentially important for providers to assess when treating patients for stroke/TIA. More research is required to further distinguish between these domains and their relative importance for stroke prevention.

  19. {sup 99m}Tc-glucarate kinetics differentiate normal, stunned, hibernating, and nonviable myocardium in a perfused rat heart model

    Energy Technology Data Exchange (ETDEWEB)

    Okada, David R. [University of Pennsylvania School of Medicine, Philadelphia, PA (United States); Liu, Zhonglin [University of Arizona School of Medicine, Tucson, AZ (United States); Johnson, Gerald; Okada, Robert D. [University of Oklahoma Health Sciences Center, Oklahoma, OK (United States); University of Tulsa, Tulsa, OK (United States); Beju, Delia [Oklahoma State University School of Medicine, Tulsa, OK (United States); Khaw, Ban An [Northeastern University, Boston, MA (United States)

    2010-10-15

    {sup 99m}Tc-glucarate is an infarct-avid imaging agent. However, patients may have mixtures of normal, irreversibly injured, stunned, and hibernating myocardium. The purposes were to determine {sup 99m}Tc-glucarate uptake and clearance kinetics in these four conditions, and its ability to determine the extent of injury. Twenty-two perfused rat hearts were studied: controls (n = 5), stunned (n = 5; 20-min no-flow followed by 5-min reflow), hibernating (n = 6; 120-min low flow at 4 ml/min), and ischemic-reperfused (n = 6; 120-min no-flow followed by reflow). {sup 99m}Tc-glucarate was then infused. Tracer activity was monitored using a NaI scintillation detector and a multichannel analyzer. Creatine kinase, electron microscopy, and triphenyltetrazolium chloride determined viability. {sup 99m}Tc-glucarate 10-min myocardial uptake was significantly greater in ischemic-reperfused (2.50 {+-} 0.09) (cpm, SEM) than in control (1.74 {+-} 0.07), stunned (1.68 {+-} 0.11), and hibernating (1.59 {+-} 0.11) (p < 0.05). Tracer retention curves for ischemic-reperfused were elevated at all time points as compared with the other groups. {sup 99m}Tc-glucarate 60-min myocardial uptake was significantly greater in ischemic-reperfused (7.60 {+-} 0.63) than in control (1.98 {+-} 0.15), stunned (1.79 {+-} 0.08), and hibernating (2.33 {+-} 0.15) (p < 0.05). The 60-min well-counted tracer activity ratio of ischemic-reperfused to control was 9:1 and corroborated the NaI detector results. Creatine kinase, triphenyltetrazolium chloride, and electron microscopy all demonstrated significantly greater injury in ischemic-reperfused compared to the other groups. An excellent correlation was observed between viability markers and tracer activity (r = 0.99 triphenyltetrazolium chloride; r = 0.90 creatine kinase). {sup 99m}Tc-glucarate activity continually and progressively increased in irreversibly injured myocardium. {sup 99m}Tc-glucarate uptake was strongly correlated with myocardial necrosis as

  20. Differentials in health-related quality of life of employed and unemployed women with normal vaginal delivery.

    Science.gov (United States)

    Chinweuba, Anthonia U; Okoronkwo, Ijeoma L; Anarado, Agnes N; Agbapuonwu, Noreen E; Ogbonnaya, Ngozi P; Ihudiebube-Splendor, Chikaodili N

    2018-01-10

    The combination of child care and domestic work demands on both housewives and the employed (hired) women may impact their health-related quality-of-life. There is paucity of studies to ascertain this. This study investigated the differences in health-related quality of life of employed and unemployed women with normal vaginal delivery and associated socio-demographic variables. This longitudinal study was done from March, 2012 to June, 2013. Modified SF-36v2™ health-related quality of life questionnaire was administered to 234 newly delivered women drawn from six selected hospitals in Enugu, Southeast Nigeria at 6, 12 and 18 weeks postpartum. Respondents were reached for data collection through personal contacts initially at the hospitals of delivery, and subsequently by visits to their homes/workplaces or cell-phone calls. Women were asked to indicate how each of 36 items applied to them at each of the three times. Data collection lasted for six calendar months and 17 days (from September 3rd 2012 to 20th March, 2013). All the women had their best HrQoL at 12 weeks postpartum. Employed women reported lower health-related quality-of-life than the unemployed at the three time-points, the lowest mean score being at 18 weeks postpartum (Mean = 73.9). Multiple comparison of scores of the two groups using Tukey HSD Repeated Mean showed significant variation on the eight subscales of the health-related quality-of-life. Physical functioning (p = 0.045), Physical role limitation (p = 0.000), bodily pain (p = 0.000), social functioning (p = 0.000) and general health (p = 0.000) were unequal guaranteeing type 1 error. Women with higher education and personal income reported higher health-related quality-of-life (p women have more problems with physical health components and are more negatively affected by increasing age except those with higher education and personal income. Increased responsibilities combined with increasing age and low socio

  1. Correlation between Urothelial Differentiation and Sensory Proteins P2X3, P2X5, TRPV1, and TRPV4 in Normal Urothelium and Papillary Carcinoma of Human Bladder

    Directory of Open Access Journals (Sweden)

    Igor Sterle

    2014-01-01

    Full Text Available Terminal differentiation of urothelium is a prerequisite for blood-urine barrier formation and enables normal sensory function of the urinary bladder. In this study, urothelial differentiation of normal human urothelium and of low and high grade papillary urothelial carcinomas was correlated with the expression and localization of purinergic receptors (P2X3, and P2X5 and transient receptor potential vanilloid channels (TRPV1, and TRPV4. Western blotting and immunofluorescence of uroplakins together with scanning electron microscopy of urothelial apical surface demonstrated terminal differentiation of normal urothelium, partial differentiation of low grade carcinoma, and poor differentiation of high grade carcinoma. P2X3 was expressed in normal urothelium as well as in low grade carcinoma and in both cases immunolabeling was stronger in the superficial cells. P2X3 expression decreased in high grade carcinoma. P2X5 expression was detected in normal urothelium and in high grade carcinoma, while in low grade carcinoma its expression was diminished. The expression of TRPV1 decreased in low grade and even more in high grade carcinoma when compared with normal urothelium, while TRPV4 expression was unchanged in all samples. Our results suggest that sensory proteins P2X3 and TRPV1 are in correlation with urothelial differentiation, while P2X5 and TRPV4 have unique expression patterns.

  2. Semantic error patterns on the Boston Naming Test in normal aging, amnestic mild cognitive impairment, and mild Alzheimer's disease: is there semantic disruption?

    Science.gov (United States)

    Balthazar, Marcio Luiz Figueredo; Cendes, Fernando; Damasceno, Benito Pereira

    2008-11-01

    Naming difficulty is common in Alzheimer's disease (AD), but the nature of this problem is not well established. The authors investigated the presence of semantic breakdown and the pattern of general and semantic errors in patients with mild AD, patients with amnestic mild cognitive impairment (aMCI), and normal controls by examining their spontaneous answers on the Boston Naming Test (BNT) and verifying whether they needed or were benefited by semantic and phonemic cues. The errors in spontaneous answers were classified in four mutually exclusive categories (semantic errors, visual paragnosia, phonological errors, and omission errors), and the semantic errors were further subclassified as coordinate, superordinate, and circumlocutory. Patients with aMCI performed normally on the BNT and needed fewer semantic and phonemic cues than patients with mild AD. After semantic cues, subjects with aMCI and control subjects gave more correct answers than patients with mild AD, but after phonemic cues, there was no difference between the three groups, suggesting that the low performance of patients with AD cannot be completely explained by semantic breakdown. Patterns of spontaneous naming errors and subtypes of semantic errors were similar in the three groups, with decreasing error frequency from coordinate to superordinate to circumlocutory subtypes.

  3. Semi-quantitative analysis of perfusion of Brodmann areas in the differential diagnosis of cognitive impairment in Alzheimer's disease, fronto-temporal dementia and mild cognitive impairment.

    Science.gov (United States)

    Tranfaglia, Cristina; Palumbo, Barbara; Siepi, Donatella; Sinzinger, Helmut; Parnetti, Lucilla

    2009-01-01

    Different perfusion defects reflect neurological damage characteristics of different kinds of dementia. Our aim was to investigate the role of brain single photon emission tomography (SPET) with semiquantitative analysis of Brodmann areas in dementia, by technetium-99m - hexamethyl-propylenamine- oxime ((99m)Tc-HMPAO) brain SPET with semiquantitative analysis of Brodmann areas in patients with Alzheimer's disease (AD), frontotemporal dementia (FTD) and mild cognitive impairment (MCI). We studied 75 patients, 25 with AD (NiNCDS ADRDA criteria), 25 with FTD (Lund and Manchester criteria), 25 with MCI (EADC criteria). After i.v. injection of 740MBq of (99m)Tc-HMPAO, each patient underwent brain SPET. A software application was used able to map the SPET brain image to a stereotaxic atlas (Talairach), providing an affine co-registration by blocks of data defined in the Talairach space. A normal database calculating voxel by voxel the mean and the standard deviation of the measured values was built. Functional SPET data of 3D regions of interest (ROI) of predefined Brodmann's area templates were compared with those of a database of healthy subjects of the same age and gender. Mean values obtained in the Brodmann area ROI in the different groups of patients studied were evaluated. Our results showed that different Brodmann areas were significantly impaired in the different categories of dementia subjects. Both areas 37 (temporal gyrus) and 39 (angular gyrus) of AD patients (mean+/-SD: 37L= -1.6+/-1.0; 37R= -1.5+/-1.1; 39L= -2.3+/-1.3; 39R= -1.9+/-1.2) showed significant hypoperfusion (Pareas 40 (supramarginal gyrus) (40L= -2.6+/-1.0; 40R= -2.3+/-1.1) with respect to MCI patients (40L= -1.8+/-0.9; 40R= -1.7+/-1.2). Finally, FTD patients showed significant hypoperfusion (Pareas 47 (frontal association cortex) (47L= -1.8+/-0.8; 47R= -1.1+/-0.8) in comparison with MCI subjects (47L= -1.2+/-0.9; 47R= -0.9+/-0.9). In conclusion, our results suggest that semiquantitative

  4. Eyes with Suspicious Appearance of the Optic Disc and Normal Intraocular Pressure: Using Clinical and Epidemiological Characteristics to Differentiate Those with and without Glaucoma.

    Directory of Open Access Journals (Sweden)

    Diego T Dias

    Full Text Available Among all glaucoma suspects, eyes with optic nerve head features suspicious or suggestive of early glaucoma are probably those that offer the greatest challenge for clinicians. In contrast with the robust longitudinal data published on ocular hypertension, there is no specific management guideline for these patients. Therefore, evaluating eyes with suspicious optic disc appearance and normal intraocular pressure (IOP, we sought to investigate potential differences in clinical and epidemiological characteristics to differentiate those with normal-tension glaucoma (NTG from those with presumed large physiological optic disc cups (pLPC. In this observational case-control study, we consecutively enrolled individuals with pLPC and NTG. All eyes had vertical cup-to-disc ratio (VCDR≥0.6 and untreated IOP<21 mmHg. Glaucomatous eyes had reproducible visual field defects. Eyes with pLPC required normal visual fields and ≥30 months of follow-up with no evidence of glaucomatous neuropathy. Clinical and epidemiological parameters were compared between groups. Eighty-four individuals with pLPC and 40 NTG patients were included. Regarding our main results, NTG patients were significantly older and with a higher prevalence of Japanese descendants (p<0.01. Not only did pLPC eyes have smaller mean VCDR, but also larger optic discs (p≤0.04. There were no significant differences for gender, central corneal thickness, and spherical equivalent (p≥0.38. Significant odds ratios (OR were found for race (OR = 2.42; for Japanese ancestry, age (OR = 1.05, VCDR (OR = 5.03, and disc size (OR = 0.04; p≤0.04. In conclusion, in patients with suspicious optic disc and normal IOP, those with older age, Japanese ancestry, smaller optic discs, and larger VCDR are more likely to have NTG, and therefore, deserve deeper investigation and closer monitoring.

  5. Differential immunotoxic effects of ethanol on murine EL-4 lymphoma and normal lymphocytes is mediated through increased ROS production and activation of p38MAPK.

    Science.gov (United States)

    Premachandran, Sudha; Khan, Nazir M; Thakur, Vikas S; Shukla, Jyoti; Poduval, T B

    2012-08-01

    Ethanol has been used to achieve thymic depletion in myasthenia gravis patients. Ethanol (95%) has also been used widely in the therapy of many tumors including hepatocellular carcinoma. In light of these findings, we delineated the differential immunotoxic behavior and mechanism of lower concentration of ethanol towards murine EL-4 lymphoma and its normal counterpart lymphocytes. EL-4 lymphoma and normal lymphocytes were cultured with ethanol (0%-5%) for 6 h and cytotoxicity was measured by various methods. EL-4 cells treated with ethanol showed concentration-dependent loss of viability at 2%-5% ethanol concentration and exhibit proliferative arrest at preG1 stage. Acridine-orange and ethidium-bromide staining indicated that ethanol induced death in EL-4 cells, by induction of both apoptosis and necrosis which was further supported by findings of DNA-fragmentation and trypan blue dye exclusion test. However, treatment of lymphocytes with similar concentration of ethanol did not show any death-associated parameters. Furthermore, ethanol induced significantly higher ROS generation in EL-4 cells as compared to lymphocytes and caused PARP cleavage and activation of apoptotic proteins like p53 and Bax, in EL-4 cells and not in normal lymphocytes. In addition, ethanol exposure to EL-4 cells led to phosphorylation of p38MAPK, and upregulation of death receptor Fas (CD95). Taken together, these results suggest that ethanol upto a concentration of 5% caused no significant immunotoxicity towards normal lymphocytes and induced cell death in EL-4 cells via phosphorylation of p38MAPK and regulation of p53 leading to further activation of both extrinsic (Fas) and intrinsic (Bax) apoptotic markers.

  6. Apparent diffusion coefficient in the analysis of prostate cancer: determination of optimal b-value pair to differentiate normal from malignant tissue.

    Science.gov (United States)

    Adubeiro, Nuno; Nogueira, Maria Luísa; Nunes, Rita G; Ferreira, Hugo Alexandre; Ribeiro, Eduardo; La Fuente, José Maria Ferreira

    Determining optimal b-value pair for differentiation between normal and prostate cancer (PCa) tissues. Forty-three patients with diagnosis or PCa symptoms were included. Apparent diffusion coefficient (ADC) was estimated using minimum and maximum b-values of 0, 50, 100, 150, 200, 500s/mm2 and 500, 800, 1100, 1400, 1700 and 2000s/mm2, respectively. Diagnostic performances were evaluated when Area-under-the-curve (AUC)>95%. 15 of the 35 b-values pair surpassed this AUC threshold. The pair (50, 2000s/mm2) provided the highest AUC (96%) with ADC cutoff 0.89×10- 3 mm 2 /s, sensitivity 95.5%, specificity 93.2% and accuracy 94.4%. The best b-value pair was b=50, 2000s/mm2. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Differential lexical correlates of social cognition and metacognition in schizophrenia; a study of spontaneously-generated life narratives.

    Science.gov (United States)

    Buck, Benjamin; Minor, Kyle S; Lysaker, Paul H

    2015-04-01

    Social cognition and metacognition have been identified as important cognitive domains in schizophrenia, which are separable from general neurocognition and predictive of functional and treatment outcomes. However, one challenge to improved models of schizophrenia has been the conceptual overlap between the two. One tool used in previous research to develop cognitive models of psychopathology is language analysis. In this article we aimed to clarify distinctions between social cognition and metacognition in schizophrenia using computerized language software. Fifty-eight (n=58) individuals with schizophrenia completed the Metacognitive Assessment Scale Abbreviated and measures of social cognition using the Hinting, Eyes, BLERT and Picture Arrangement test. A lexical analysis of participants' speech using Language Inquiry and Word Count software was conducted to examine relative frequencies of word types. Lexical characteristics were examined for their relationships to social cognition and metacognition. We found that lexical characteristics indicative of cognitive complexity were significantly related to level of metacognitive capacity while social cognition was related to second-person pronoun use, articles, and prepositions, and pronoun use overall. The relationships between lexical variables and metacognition persisted after controlling for demographics, verbal intelligence, and overall word count, but the same was not true for social cognition. Our findings provided support for the view that metacognition requires more synthetic and complex verbal and linguistic operations, while social cognition is associated with the representation and clear identification of others. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Differentiating between Glioblastoma and Primary CNS Lymphoma Using Combined Whole-tumor Histogram Analysis of the Normalized Cerebral Blood Volume and the Apparent Diffusion Coefficient.

    Science.gov (United States)

    Bao, Shixing; Watanabe, Yoshiyuki; Takahashi, Hiroto; Tanaka, Hisashi; Arisawa, Atsuko; Matsuo, Chisato; Wu, Rongli; Fujimoto, Yasunori; Tomiyama, Noriyuki

    2018-05-31

    This study aimed to determine whether whole-tumor histogram analysis of normalized cerebral blood volume (nCBV) and apparent diffusion coefficient (ADC) for contrast-enhancing lesions can be used to differentiate between glioblastoma (GBM) and primary central nervous system lymphoma (PCNSL). From 20 patients, 9 with PCNSL and 11 with GBM without any hemorrhagic lesions, underwent MRI, including diffusion-weighted imaging and dynamic susceptibility contrast perfusion-weighted imaging before surgery. Histogram analysis of nCBV and ADC from whole-tumor voxels in contrast-enhancing lesions was performed. An unpaired t-test was used to compare the mean values for each type of tumor. A multivariate logistic regression model (LRM) was performed to classify GBM and PCNSL using the best parameters of ADC and nCBV. All nCBV histogram parameters of GBMs were larger than those of PCNSLs, but only average nCBV was statistically significant after Bonferroni correction. Meanwhile, ADC histogram parameters were also larger in GBM compared to those in PCNSL, but these differences were not statistically significant. According to receiver operating characteristic curve analysis, the nCBV average and ADC 25th percentile demonstrated the largest area under the curve with values of 0.869 and 0.838, respectively. The LRM combining these two parameters differentiated between GBM and PCNSL with a higher area under the curve value (Logit (P) = -21.12 + 10.00 × ADC 25th percentile (10 -3 mm 2 /s) + 5.420 × nCBV mean, P histogram analysis of nCBV and ADC combined can be a valuable objective diagnostic method for differentiating between GBM and PCNSL.

  9. The Differential Expression of Aqueous Soluble Proteins in Breast Normal and Cancerous Tissues in Relation to Ethnicity of the Patients; Chinese, Malay and Indian

    Directory of Open Access Journals (Sweden)

    Seng Liang

    2010-01-01

    Full Text Available Female breast cancer is one of the leading causes of female mortality worldwide. In Malaysia, breast cancer is the most commonly diagnosed cancer in women. Of the women in Malaysia, the Chinese have the highest number of breast cancer cases, followed by the Indian and the Malay. The most common type of breast cancer is infiltrating ductal carcinoma (IDC. A proteomic approach was applied in this study to identify changes in the protein profile of cancerous tissues compared with normal tissues from 18 patients; 8 Chinese, 6 Malay and 4 Indian were analysed. Twenty-four differentially expressed hydrophilic proteins were identified. We evaluated the potential of these proteins as biomarkers for infiltrating ductal carcinoma based on their ethnic-specific expressions. Three of the upregulated proteins, calreticulin, 14-3-3 protein zeta and 14-3-3 protein eta, were found to be expressed at a significantly higher level in the cancerous breast tissues when compared with the normal tissues in cases of infiltrating ductal carcinoma. The upregulation in expression was particularly dominant in the Malay cohort.

  10. Mild Cognitive Impairment (MCI)

    Science.gov (United States)

    Mild cognitive impairment (MCI) Overview Mild cognitive impairment (MCI) is an intermediate stage between the expected cognitive decline of normal aging and the more-serious decline of dementia. It ...

  11. Development and validation of a new cognitive screening test: The Hong Kong Brief Cognitive Test (HKBC).

    Science.gov (United States)

    Chiu, Helen F K; Zhong, Bao-Liang; Leung, Tony; Li, S W; Chow, Paulina; Tsoh, Joshua; Yan, Connie; Xiang, Yu-Tao; Wong, Mike

    2018-07-01

    To develop and examine the validity of a new brief cognitive test with less educational bias for screening cognitive impairment. A new cognitive test, Hong Kong Brief Cognitive Test (HKBC), was developed based on review of the literature, as well as the views of an expert panel. Three groups of subjects aged 65 or above were recruited after written consent: normal older people recruited in elderly centres, people with mild NCD (neurocognitive disorder), and people with major NCD. The brief cognitive test, Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment Scale (MoCA), were administered to the subjects. The performance of HKBC in differentiating subjects with major NCD, mild NCD, and normal older people were compared with the clinical diagnosis, as well as the MMSE and MoCA scores. In total, 359 subjects were recruited, with 99 normal controls, 132 subjects with major NCD, and 128 with mild NCD. The mean MMSE, MoCA, and HKBC scores showed significant differences among the 3 groups of subjects. In the receiving operating characteristic curve analysis of the HKBC in differentiating normal subjects from those with cognitive impairment (mild NCD + major NCD), the area under the curve was 0.955 with an optimal cut-off score of 21/22. The performances of MMSE and MoCA in differentiating normal from cognitively impaired subjects are slightly inferior to the HKBC. The HKBC is a brief instrument useful for screening cognitive impairment in older adults and is also useful in populations with low educational level. Copyright © 2018 John Wiley & Sons, Ltd.

  12. Emotional based cognition in mice is differentially influenced by dose and lipid origin of dietary docosahexaenoic acid

    Science.gov (United States)

    Docosahexaenoic acid (DHA) is a major constituent, and primary omega-3 fatty acid, in the brain. Evidence suggests that DHA consumption may promote cognitive functioning and prevent cognitive decline, and these effects may be particularly relevant in the context of fear or stress. However, the pot...

  13. A SEMantic and EPisodic Memory Test (SEMEP) Developed within the Embodied Cognition Framework: Application to Normal Aging, Alzheimer's Disease and Semantic Dementia.

    Science.gov (United States)

    Vallet, Guillaume T; Hudon, Carol; Bier, Nathalie; Macoir, Joël; Versace, Rémy; Simard, Martine

    2017-01-01

    Embodiment has highlighted the importance of sensory-motor components in cognition. Perception and memory are thus very tightly bound together, and episodic and semantic memories should rely on the same grounded memory traces. Reduced perception should then directly reduce the ability to encode and retrieve an episodic memory, as in normal aging. Multimodal integration deficits, as in Alzheimer's disease, should lead to more severe episodic memory impairment. The present study introduces a new memory test developed to take into account these assumptions. The SEMEP (SEMantic-Episodic) memory test proposes to assess conjointly semantic and episodic knowledge across multiple tasks: semantic matching, naming, free recall, and recognition. The performance of young adults is compared to healthy elderly adults (HE), patients with Alzheimer's disease (AD), and patients with semantic dementia (SD). The results show specific patterns of performance between the groups. HE commit memory errors only for presented but not to be remembered items. AD patients present the worst episodic memory performance associated with intrusion errors (recall or recognition of items never presented). They were the only group to not benefit from a visual isolation (addition of a yellow background), a method known to increase the distinctiveness of the memory traces. Finally, SD patients suffer from the most severe semantic impairment. To conclude, confusion errors are common across all the elderly groups, whereas AD was the only group to exhibit regular intrusion errors and SD patients to show severe semantic impairment.

  14. A SEMantic and EPisodic Memory Test (SEMEP Developed within the Embodied Cognition Framework: Application to Normal Aging, Alzheimer's Disease and Semantic Dementia

    Directory of Open Access Journals (Sweden)

    Guillaume T. Vallet

    2017-09-01

    Full Text Available Embodiment has highlighted the importance of sensory-motor components in cognition. Perception and memory are thus very tightly bound together, and episodic and semantic memories should rely on the same grounded memory traces. Reduced perception should then directly reduce the ability to encode and retrieve an episodic memory, as in normal aging. Multimodal integration deficits, as in Alzheimer's disease, should lead to more severe episodic memory impairment. The present study introduces a new memory test developed to take into account these assumptions. The SEMEP (SEMantic-Episodic memory test proposes to assess conjointly semantic and episodic knowledge across multiple tasks: semantic matching, naming, free recall, and recognition. The performance of young adults is compared to healthy elderly adults (HE, patients with Alzheimer's disease (AD, and patients with semantic dementia (SD. The results show specific patterns of performance between the groups. HE commit memory errors only for presented but not to be remembered items. AD patients present the worst episodic memory performance associated with intrusion errors (recall or recognition of items never presented. They were the only group to not benefit from a visual isolation (addition of a yellow background, a method known to increase the distinctiveness of the memory traces. Finally, SD patients suffer from the most severe semantic impairment. To conclude, confusion errors are common across all the elderly groups, whereas AD was the only group to exhibit regular intrusion errors and SD patients to show severe semantic impairment.

  15. Differential Aging Trajectories of Modulation of Activation to Cognitive Challenge in APOE ε4 Groups: Reduced Modulation Predicts Poorer Cognitive Performance.

    Science.gov (United States)

    Foster, Chris M; Kennedy, Kristen M; Rodrigue, Karen M

    2017-07-19

    The present study was designed to investigate the effect of a genetic risk factor for Alzheimer's disease (AD), ApolipoproteinE ε4 (APOEε4), on the ability of the brain to modulate activation in response to cognitive challenge in a lifespan sample of healthy human adults. A community-based sample of 181 cognitively intact, healthy adults were recruited from the Dallas-Fort Worth metroplex. Thirty-one APOEε4+ individuals (48% women), derived from the parent sample, were matched based on sex, age, and years of education to 31 individuals who were APOEε4-negative (APOEε4-). Ages ranged from 20 to 86 years of age. Blood oxygen level-dependent functional magnetic resonance imaging was collected during the performance of a visuospatial distance judgment task with three parametric levels of difficulty. Multiple regression was used in a whole-brain analysis with age, APOE group, and their interaction predicting functional brain modulation in response to difficulty. Results revealed an interaction between age and APOE in a large cluster localized primarily to the bilateral precuneus. APOEε4- individuals exhibited age-invariant modulation in response to task difficulty, whereas APOEε4+ individuals showed age-related reduction of modulation in response to increasing task difficulty compared with ε4- individuals. Decreased modulation in response to cognitive challenge was associated with reduced task accuracy as well as poorer name-face associative memory performance. Findings suggest that APOEε4 is associated with a reduction in the ability of the brain to dynamically modulate in response to cognitive challenge. Coupled with a significant genetic risk factor for AD, changes in modulation may provide additional information toward identifying individuals potentially at risk for cognitive decline associated with preclinical AD. SIGNIFICANCE STATEMENT Understanding how risk factors for Alzheimer's disease (AD) affect brain function and cognition in healthy adult samples

  16. Scientific Opinion on the substantiation of a health claim related to glycaemic carbohydrates and contribution to normal cognitive function pursuant to Article 13(5) of Regulation (EC) No 1924/2006

    DEFF Research Database (Denmark)

    Tetens, Inge

    2015-01-01

    an opinion on the scientific substantiation of a health claim related to glycaemic carbohydrates and contribution to normal cognitive function. The scope of the application was proposed to fall under a health claim based on newly developed scientific evidence. The Panel considers that the food constituent....... Such amounts can be consumed as part of a balanced diet. The target population is the general population....

  17. Comprehensive processing of high-throughput small RNA sequencing data including quality checking, normalization, and differential expression analysis using the UEA sRNA Workbench.

    Science.gov (United States)

    Beckers, Matthew; Mohorianu, Irina; Stocks, Matthew; Applegate, Christopher; Dalmay, Tamas; Moulton, Vincent

    2017-06-01

    Recently, high-throughput sequencing (HTS) has revealed compelling details about the small RNA (sRNA) population in eukaryotes. These 20 to 25 nt noncoding RNAs can influence gene expression by acting as guides for the sequence-specific regulatory mechanism known as RNA silencing. The increase in sequencing depth and number of samples per project enables a better understanding of the role sRNAs play by facilitating the study of expression patterns. However, the intricacy of the biological hypotheses coupled with a lack of appropriate tools often leads to inadequate mining of the available data and thus, an incomplete description of the biological mechanisms involved. To enable a comprehensive study of differential expression in sRNA data sets, we present a new interactive pipeline that guides researchers through the various stages of data preprocessing and analysis. This includes various tools, some of which we specifically developed for sRNA analysis, for quality checking and normalization of sRNA samples as well as tools for the detection of differentially expressed sRNAs and identification of the resulting expression patterns. The pipeline is available within the UEA sRNA Workbench, a user-friendly software package for the processing of sRNA data sets. We demonstrate the use of the pipeline on a H. sapiens data set; additional examples on a B. terrestris data set and on an A. thaliana data set are described in the Supplemental Information A comparison with existing approaches is also included, which exemplifies some of the issues that need to be addressed for sRNA analysis and how the new pipeline may be used to do this. © 2017 Beckers et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  18. Epidermal cell-shape regulation and subpopulation kinetics during butyrate-induced terminal maturation of normal and SV40-transformed human keratinocytes: epithelial models of differentiation therapy.

    Science.gov (United States)

    Staiano-Coico, L; Steinberg, M; Higgins, P J

    1990-10-15

    Recent data indicate that malignant human epidermal cells may be appropriate targets for sodium butyrate (NaB)-mediated differentiation therapy. The response of pre- and post-crisis populations of SV40-transformed human keratinocytes (SVKs) to this differentiation-inducing agent was assessed, therefore, within the framework of NaB-directed normal human keratinocyte (NHK) maturation. NaB augmented cornified envelope (CE) production in NHK and pre-crisis SVK cultures; the time-course and efficiency of induced maturation were similar in the 2 cell systems. In NHKs, the percentage of amplifying ("B" substate) cells decreased with time in NaB correlating with increases in both "C" stage keratinocytes and CEs. The latter formed over one or 2 layers of nucleated basal-like cells. Inductions were accompanied by immediate cell cycle blocks (in both the G1 and G2/M phases), reorganization within the actin cytoskeleton, and transient early increases in cellular actin content. Increased NHK and pre-crisis SVK cytoskeletal-associated actin reached a maximum approximately 48 hr after NaB addition and preceded development of CEs. The CE precursors, thus, probably reside in the "B" substate. Post-crisis SVKs, in contrast, were refractive to NaB-induced terminal maturation or cell-cycle perturbation, failed to initiate actin filament rearrangements, and retained a basal cell-like phenotype. Stable transformation of human SVKs in post-crisis phase, therefore, appears to be associated with loss of maturation "competence" within the "B" keratinocyte subpopulation.

  19. MO-F-CAMPUS-I-04: Characterization of Fan Beam Coded Aperture Coherent Scatter Spectral Imaging Methods for Differentiation of Normal and Neoplastic Breast Structures

    Energy Technology Data Exchange (ETDEWEB)

    Morris, R; Albanese, K; Lakshmanan, M; Greenberg, J; Kapadia, A [Duke University Medical Center, Durham, NC, Carl E Ravin Advanced Imaging Laboratories, Durham, NC (United States)

    2015-06-15

    Purpose: This study intends to characterize the spectral and spatial resolution limits of various fan beam geometries for differentiation of normal and neoplastic breast structures via coded aperture coherent scatter spectral imaging techniques. In previous studies, pencil beam raster scanning methods using coherent scatter computed tomography and selected volume tomography have yielded excellent results for tumor discrimination. However, these methods don’t readily conform to clinical constraints; primarily prolonged scan times and excessive dose to the patient. Here, we refine a fan beam coded aperture coherent scatter imaging system to characterize the tradeoffs between dose, scan time and image quality for breast tumor discrimination. Methods: An X-ray tube (125kVp, 400mAs) illuminated the sample with collimated fan beams of varying widths (3mm to 25mm). Scatter data was collected via two linear-array energy-sensitive detectors oriented parallel and perpendicular to the beam plane. An iterative reconstruction algorithm yields images of the sample’s spatial distribution and respective spectral data for each location. To model in-vivo tumor analysis, surgically resected breast tumor samples were used in conjunction with lard, which has a form factor comparable to adipose (fat). Results: Quantitative analysis with current setup geometry indicated optimal performance for beams up to 10mm wide, with wider beams producing poorer spatial resolution. Scan time for a fixed volume was reduced by a factor of 6 when scanned with a 10mm fan beam compared to a 1.5mm pencil beam. Conclusion: The study demonstrates the utility of fan beam coherent scatter spectral imaging for differentiation of normal and neoplastic breast tissues has successfully reduced dose and scan times whilst sufficiently preserving spectral and spatial resolution. Future work to alter the coded aperture and detector geometries could potentially allow the use of even wider fans, thereby making coded

  20. EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies), 20 13 . Scientific Opinion on the substantiatio n of a health claim related to iron and contribution to normal cognitive development pursuant to Article 14 of Regulation (EC ) No 1924/2006

    DEFF Research Database (Denmark)

    Tetens, Inge

    to iron and contribution to normal cognitive development. The food constituent, iron, which is the subject of the health claim, is sufficiently characterised. Contribution to normal cognitive development is a beneficial physiological effect for infants and young children. A claim on iron and cognitive...... development in children (up to 18 years) has already been assessed with a favourable outcome. The Panel notes that the role of iron in normal cognitive development also applies to infants and young children (from birth to three years). The Panel concludes that a cause and effect relationship has been...... established between dietary intake of iron and contribution to normal cognitive development. The following wording reflects the scientific evidence: “Iron contributes to normal cognitive development”. The target population is infants and children up to three years. © European Food Safety Authority, 2013...

  1. Cognitive Impairment, Depression, and Cooccurrence of Both among the Elderly in Panama: Differential Associations with Multimorbidity and Functional Limitations

    Directory of Open Access Journals (Sweden)

    Alcibiades E. Villarreal

    2015-01-01

    Full Text Available Cognitive impairment and depression are common mental health problems among the elderly, although few studies have examined their cooccurrence in older adults in Latin America. The purpose of this study was to examine cognitive impairment, depression, and cooccurrence of the two conditions and associated factors in a sample of older adults in Panama. This study included 304 community-dwelling elderly (≥65 years individuals. Participants underwent a clinical interview and assessments of cognitive function by the Minimental State Examination and depressive symptoms by the Geriatric Depression Scale. Limitations in basic (BADL and instrumental (IADL activities in daily living and the presence of chronic illnesses were recorded. Multinomial regression analysis revealed that cooccurrence of cognitive impairment and depressive symptoms was explained by increasing age (OR: 3.2, 95% CI: 1.20, 8.30, low education (OR: 3.3, 95% CI: 1.33, 8.38, having four or more chronic conditions (OR: 11.5, 95% CI: 2.84, 46.63, and BADL limitations (OR: 5.0, 95% CI: 1.26, 19.68. Less education and limitations in BADL and IADL increased the odds of cognitive impairment alone, while less education and three or more chronic conditions increased the odds of depression alone. These findings underscore the relevance of assessing cognitive impairment in the elderly as part of a long-term approach to managing depression and vice versa.

  2. Global diffusion tensor imaging derived metrics differentiate glioblastoma multiforme vs. normal brains by using discriminant analysis: introduction of a novel whole-brain approach.

    Science.gov (United States)

    Roldan-Valadez, Ernesto; Rios, Camilo; Cortez-Conradis, David; Favila, Rafael; Moreno-Jimenez, Sergio

    2014-06-01

    Histological behavior of glioblastoma multiforme suggests it would benefit more from a global rather than regional evaluation. A global (whole-brain) calculation of diffusion tensor imaging (DTI) derived tensor metrics offers a valid method to detect the integrity of white matter structures without missing infiltrated brain areas not seen in conventional sequences. In this study we calculated a predictive model of brain infiltration in patients with glioblastoma using global tensor metrics. Retrospective, case and control study; 11 global DTI-derived tensor metrics were calculated in 27 patients with glioblastoma multiforme and 34 controls: mean diffusivity, fractional anisotropy, pure isotropic diffusion, pure anisotropic diffusion, the total magnitude of the diffusion tensor, linear tensor, planar tensor, spherical tensor, relative anisotropy, axial diffusivity and radial diffusivity. The multivariate discriminant analysis of these variables (including age) with a diagnostic test evaluation was performed. The simultaneous analysis of 732 measures from 12 continuous variables in 61 subjects revealed one discriminant model that significantly differentiated normal brains and brains with glioblastoma: Wilks' λ = 0.324, χ(2) (3) = 38.907, p tensor and linear tensor. These metrics might be clinically applied for diagnosis, follow-up, and the study of other neurological diseases.

  3. Characterization of six small HSP genes from Chironomus riparius (Diptera, Chironomidae): Differential expression under conditions of normal growth and heat-induced stress.

    Science.gov (United States)

    Martín-Folgar, Raquel; de la Fuente, Mercedes; Morcillo, Gloria; Martínez-Guitarte, José-Luis

    2015-10-01

    Small heat shock proteins (sHSPs) comprise the most numerous, structurally diverse, and functionally uncharacterized family of heat shock proteins. Several Hsp genes (Hsp 90, 70, 40, and 27) from the insect Chironomus riparius are widely used in aquatic toxicology as biomarkers for environmental toxins. Here, we conducted a comparative study and characterized secondary structure of the six newly identified sHsp genes Hsp17, Hsp21, Hsp22, Hsp23, Hsp24, and Hsp34. A characteristic α-crystallin domain is predicted in all the new proteins. Phylogenetic analysis suggests a strong relation to other sHSPs from insects and interesting evidence regarding evolutionary origin and duplication events. Comparative analysis of transcription profiles for Hsp27, Hsp70, and the six newly identified genes revealed that Hsp17, Hsp21, and Hsp22 are constitutively expressed under normal conditions, while under two different heat shock conditions these genes are either not activated or are even repressed (Hsp22). In contrast, Hsp23, Hsp24, and Hsp34 are significantly activated along with Hsp27 and Hsp70 during heat stress. These results strongly suggest functional differentiation within the small HSP subfamily and provide new data to help understand the coping mechanisms induced by stressful environmental stimuli. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Measurements of normalized differential cross-sections for $t\\bar{t}$ production in $pp$ collisions at $\\sqrt{s}$=7 TeV using the ATLAS detector

    CERN Document Server

    Aad, Georges; Abbott, Brad; Abdallah, Jalal; Abdel Khalek, Samah; Abdinov, Ovsat; Aben, Rosemarie; Abi, Babak; Abolins, Maris; AbouZeid, Ossama; Abramowicz, Halina; Abreu, Henso; Abulaiti, Yiming; Acharya, Bobby Samir; Adamczyk, Leszek; Adams, David; Adelman, Jahred; Adomeit, Stefanie; Adye, Tim; Agatonovic-Jovin, Tatjana; Aguilar-Saavedra, Juan Antonio; Agustoni, Marco; Ahlen, Steven; Ahmadov, Faig; Aielli, Giulio; Åkesson, Torsten Paul Ake; Akimoto, Ginga; Akimov, Andrei; Albert, Justin; Albrand, Solveig; Alconada Verzini, Maria Josefina; Aleksa, Martin; Aleksandrov, Igor; Alexa, Calin; Alexander, Gideon; Alexandre, Gauthier; Alexopoulos, Theodoros; Alhroob, Muhammad; Alimonti, Gianluca; Alio, Lion; Alison, John; Allbrooke, Benedict; Allison, Lee John; Allport, Phillip; Allwood-Spiers, Sarah; Almond, John; Aloisio, Alberto; Alon, Raz; Alonso, Alejandro; Alonso, Francisco; Alpigiani, Cristiano; Altheimer, Andrew David; Alvarez Gonzalez, Barbara; Alviggi, Mariagrazia; Amako, Katsuya; Amaral Coutinho, Yara; Amelung, Christoph; Amidei, Dante; Ammosov, Vladimir; Amor Dos Santos, Susana Patricia; Amorim, Antonio; Amoroso, Simone; Amram, Nir; Amundsen, Glenn; Anastopoulos, Christos; Ancu, Lucian Stefan; Andari, Nansi; Andeen, Timothy; Anders, Christoph Falk; Anders, Gabriel; Anderson, Kelby; Andreazza, Attilio; Andrei, George Victor; Anduaga, Xabier; Angelidakis, Stylianos; Anger, Philipp; Angerami, Aaron; Anghinolfi, Francis; Anisenkov, Alexey; Anjos, Nuno; Annovi, Alberto; Antonaki, Ariadni; Antonelli, Mario; Antonov, Alexey; Antos, Jaroslav; Anulli, Fabio; Aoki, Masato; Aperio Bella, Ludovica; Apolle, Rudi; Arabidze, Giorgi; Aracena, Ignacio; Arai, Yasuo; Araque, Juan Pedro; Arce, Ayana; Arguin, Jean-Francois; Argyropoulos, Spyridon; Arik, Metin; Armbruster, Aaron James; Arnaez, Olivier; Arnal, Vanessa; Arslan, Ozan; Artamonov, Andrei; Artoni, Giacomo; Asai, Shoji; Asbah, Nedaa; Ashkenazi, Adi; Ask, Stefan; Åsman, Barbro; Asquith, Lily; Assamagan, Ketevi; Astalos, Robert; Atkinson, Markus; Atlay, Naim Bora; Auerbach, Benjamin; Auge, Etienne; Augsten, Kamil; Aurousseau, Mathieu; Avolio, Giuseppe; Azuelos, Georges; Azuma, Yuya; Baak, Max; Bacci, Cesare; Bachacou, Henri; Bachas, Konstantinos; Backes, Moritz; Backhaus, Malte; Backus Mayes, John; Badescu, Elisabeta; Bagiacchi, Paolo; Bagnaia, Paolo; Bai, Yu; Bailey, David; Bain, Travis; Baines, John; Baker, Oliver Keith; Baker, Sarah; Balek, Petr; Balli, Fabrice; Banas, Elzbieta; Banerjee, Swagato; Bangert, Andrea Michelle; Bannoura, Arwa A E; Bansal, Vikas; Bansil, Hardeep Singh; Barak, Liron; Baranov, Sergei; Barber, Tom; Barberio, Elisabetta Luigia; Barberis, Dario; Barbero, Marlon; Barillari, Teresa; Barisonzi, Marcello; Barklow, Timothy; Barlow, Nick; Barnett, Bruce; Barnett, Michael; Barnovska, Zuzana; Baroncelli, Antonio; Barone, Gaetano; Barr, Alan; Barreiro, Fernando; Barreiro Guimarães da Costa, João; Bartoldus, Rainer; Barton, Adam Edward; Bartos, Pavol; Bartsch, Valeria; Bassalat, Ahmed; Basye, Austin; Bates, Richard; Batkova, Lucia; Batley, Richard; Battistin, Michele; Bauer, Florian; Bawa, Harinder Singh; Beau, Tristan; Beauchemin, Pierre-Hugues; Beccherle, Roberto; Bechtle, Philip; Beck, Hans Peter; Becker, Anne Kathrin; Becker, Sebastian; Beckingham, Matthew; Becot, Cyril; Beddall, Andrew; Beddall, Ayda; Bedikian, Sourpouhi; Bednyakov, Vadim; Bee, Christopher; Beemster, Lars; Beermann, Thomas; Begel, Michael; Behr, Katharina; Belanger-Champagne, Camille; Bell, Paul; Bell, William; Bella, Gideon; Bellagamba, Lorenzo; Bellerive, Alain; Bellomo, Massimiliano; Belloni, Alberto; Belotskiy, Konstantin; Beltramello, Olga; Benary, Odette; Benchekroun, Driss; Bendtz, Katarina; Benekos, Nektarios; Benhammou, Yan; Benhar Noccioli, Eleonora; Benitez Garcia, Jorge-Armando; Benjamin, Douglas; Bensinger, James; Benslama, Kamal; Bentvelsen, Stan; Berge, David; Bergeaas Kuutmann, Elin; Berger, Nicolas; Berghaus, Frank; Berglund, Elina; Beringer, Jürg; Bernard, Clare; Bernat, Pauline; Bernius, Catrin; Bernlochner, Florian Urs; Berry, Tracey; Berta, Peter; Bertella, Claudia; Bertolucci, Federico; Besana, Maria Ilaria; Besjes, Geert-Jan; Bessidskaia, Olga; Besson, Nathalie; Betancourt, Christopher; Bethke, Siegfried; Bhimji, Wahid; Bianchi, Riccardo-Maria; Bianchini, Louis; Bianco, Michele; Biebel, Otmar; Bieniek, Stephen Paul; Bierwagen, Katharina; Biesiada, Jed; Biglietti, Michela; Bilbao De Mendizabal, Javier; Bilokon, Halina; Bindi, Marcello; Binet, Sebastien; Bingul, Ahmet; Bini, Cesare; Black, Curtis; Black, James; Black, Kevin; Blackburn, Daniel; Blair, Robert; Blanchard, Jean-Baptiste; Blazek, Tomas; Bloch, Ingo; Blocker, Craig; Blum, Walter; Blumenschein, Ulrike; Bobbink, Gerjan; Bobrovnikov, Victor; Bocchetta, Simona Serena; Bocci, Andrea; Boddy, Christopher Richard; Boehler, Michael; Boek, Jennifer; Boek, Thorsten Tobias; Bogaerts, Joannes Andreas; Bogdanchikov, Alexander; Bogouch, Andrei; Bohm, Christian; Bohm, Jan; Boisvert, Veronique; Bold, Tomasz; Boldea, Venera; Boldyrev, Alexey; Bolnet, Nayanka Myriam; Bomben, Marco; Bona, Marcella; Boonekamp, Maarten; Borisov, Anatoly; Borissov, Guennadi; Borri, Marcello; Borroni, Sara; Bortfeldt, Jonathan; Bortolotto, Valerio; Bos, Kors; Boscherini, Davide; Bosman, Martine; Boterenbrood, Hendrik; Boudreau, Joseph; Bouffard, Julian; Bouhova-Thacker, Evelina Vassileva; Boumediene, Djamel Eddine; Bourdarios, Claire; Bousson, Nicolas; Boutouil, Sara; Boveia, Antonio; Boyd, James; Boyko, Igor; Bozovic-Jelisavcic, Ivanka; Bracinik, Juraj; Branchini, Paolo; Brandt, Andrew; Brandt, Gerhard; Brandt, Oleg; Bratzler, Uwe; Brau, Benjamin; Brau, James; Braun, Helmut; Brazzale, Simone Federico; Brelier, Bertrand; Brendlinger, Kurt; Brennan, Amelia Jean; Brenner, Richard; Bressler, Shikma; Bristow, Kieran; Bristow, Timothy Michael; Britton, Dave; Brochu, Frederic; Brock, Ian; Brock, Raymond; Bromberg, Carl; Bronner, Johanna; Brooijmans, Gustaaf; Brooks, Timothy; Brooks, William; Brosamer, Jacquelyn; Brost, Elizabeth; Brown, Gareth; Brown, Jonathan; Bruckman de Renstrom, Pawel; Bruncko, Dusan; Bruneliere, Renaud; Brunet, Sylvie; Bruni, Alessia; Bruni, Graziano; Bruschi, Marco; Bryngemark, Lene; Buanes, Trygve; Buat, Quentin; Bucci, Francesca; Buchholz, Peter; Buckingham, Ryan; Buckley, Andrew; Buda, Stelian Ioan; Budagov, Ioulian; Buehrer, Felix; Bugge, Lars; Bugge, Magnar Kopangen; Bulekov, Oleg; Bundock, Aaron Colin; Burckhart, Helfried; Burdin, Sergey; Burghgrave, Blake; Burke, Stephen; Burmeister, Ingo; Busato, Emmanuel; Büscher, Volker; Bussey, Peter; Buszello, Claus-Peter; Butler, Bart; Butler, John; Butt, Aatif Imtiaz; Buttar, Craig; Butterworth, Jonathan; Butti, Pierfrancesco; Buttinger, William; Buzatu, Adrian; Byszewski, Marcin; Cabrera Urbán, Susana; Caforio, Davide; Cakir, Orhan; Calafiura, Paolo; Calderini, Giovanni; Calfayan, Philippe; Calkins, Robert; Caloba, Luiz; Calvet, David; Calvet, Samuel; Camacho Toro, Reina; Camarda, Stefano; Cameron, David; Caminada, Lea Michaela; Caminal Armadans, Roger; Campana, Simone; Campanelli, Mario; Campoverde, Angel; Canale, Vincenzo; Canepa, Anadi; Cantero, Josu; Cantrill, Robert; Cao, Tingting; Capeans Garrido, Maria Del Mar; Caprini, Irinel; Caprini, Mihai; Capua, Marcella; Caputo, Regina; Cardarelli, Roberto; Carli, Tancredi; Carlino, Gianpaolo; Carminati, Leonardo; Caron, Sascha; Carquin, Edson; Carrillo-Montoya, German D; Carter, Janet; Carvalho, João; Casadei, Diego; Casado, Maria Pilar; Castaneda-Miranda, Elizabeth; Castelli, Angelantonio; Castillo Gimenez, Victoria; Castro, Nuno Filipe; Catastini, Pierluigi; Catinaccio, Andrea; Catmore, James; Cattai, Ariella; Cattani, Giordano; Caughron, Seth; Cavaliere, Viviana; Cavalli, Donatella; Cavalli-Sforza, Matteo; Cavasinni, Vincenzo; Ceradini, Filippo; Cerio, Benjamin; Cerny, Karel; Santiago Cerqueira, Augusto; Cerri, Alessandro; Cerrito, Lucio; Cerutti, Fabio; Cerv, Matevz; Cervelli, Alberto; Cetin, Serkant Ali; Chafaq, Aziz; Chakraborty, Dhiman; Chalupkova, Ina; Chan, Kevin; Chang, Philip; Chapleau, Bertrand; Chapman, John Derek; Charfeddine, Driss; Charlton, Dave; Chau, Chav Chhiv; Chavez Barajas, Carlos Alberto; Cheatham, Susan; Chegwidden, Andrew; Chekanov, Sergei; Chekulaev, Sergey; Chelkov, Gueorgui; Chelstowska, Magda Anna; Chen, Chunhui; Chen, Hucheng; Chen, Karen; Chen, Liming; Chen, Shenjian; Chen, Xin; Chen, Yujiao; Cheng, Hok Chuen; Cheng, Yangyang; Cheplakov, Alexander; Cherkaoui El Moursli, Rajaa; Chernyatin, Valeriy; Cheu, Elliott; Chevalier, Laurent; Chiarella, Vitaliano; Chiefari, Giovanni; Childers, John Taylor; Chilingarov, Alexandre; Chiodini, Gabriele; Chisholm, Andrew; Chislett, Rebecca Thalatta; Chitan, Adrian; Chizhov, Mihail; Chouridou, Sofia; Chow, Bonnie Kar Bo; Christidi, Ilektra-Athanasia; Chromek-Burckhart, Doris; Chu, Ming-Lee; Chudoba, Jiri; Chytka, Ladislav; Ciapetti, Guido; Ciftci, Abbas Kenan; Ciftci, Rena; Cinca, Diane; Cindro, Vladimir; Ciocio, Alessandra; Cirkovic, Predrag; Citron, Zvi Hirsh; Citterio, Mauro; Ciubancan, Mihai; Clark, Allan G; Clark, Philip James; Clarke, Robert; Cleland, Bill; Clemens, Jean-Claude; Clement, Benoit; Clement, Christophe; Coadou, Yann; Cobal, Marina; Coccaro, Andrea; Cochran, James H; Coffey, Laurel; Cogan, Joshua Godfrey; Coggeshall, James; Cole, Brian; Cole, Stephen; Colijn, Auke-Pieter; Collins-Tooth, Christopher; Collot, Johann; Colombo, Tommaso; Colon, German; Compostella, Gabriele; Conde Muiño, Patricia; Coniavitis, Elias; Conidi, Maria Chiara; Connell, Simon Henry; Connelly, Ian; Consonni, Sofia Maria; Consorti, Valerio; Constantinescu, Serban; Conta, Claudio; Conti, Geraldine; Conventi, Francesco; Cooke, Mark; Cooper, Ben; Cooper-Sarkar, Amanda; Cooper-Smith, Neil; Copic, Katherine; Cornelissen, Thijs; Corradi, Massimo; Corriveau, Francois; Corso-Radu, Alina; Cortes-Gonzalez, Arely; Cortiana, Giorgio; Costa, Giuseppe; Costa, María José; Costanzo, Davide; Côté, David; Cottin, Giovanna; Cowan, Glen; Cox, Brian; Cranmer, Kyle; Cree, Graham; Crépé-Renaudin, Sabine; Crescioli, Francesco; Crispin Ortuzar, Mireia; Cristinziani, Markus; Crosetti, Giovanni; Cuciuc, Constantin-Mihai; Cuhadar Donszelmann, Tulay; Cummings, Jane; Curatolo, Maria; Cuthbert, Cameron; Czirr, Hendrik; Czodrowski, Patrick; Czyczula, Zofia; D'Auria, Saverio; D'Onofrio, Monica; Da Cunha Sargedas De Sousa, Mario Jose; Da Via, Cinzia; Dabrowski, Wladyslaw; Dafinca, Alexandru; Dai, Tiesheng; Dale, Orjan; Dallaire, Frederick; Dallapiccola, Carlo; Dam, Mogens; Daniells, Andrew Christopher; Dano Hoffmann, Maria; Dao, Valerio; Darbo, Giovanni; Darlea, Georgiana Lavinia; Darmora, Smita; Dassoulas, James; Davey, Will; David, Claire; Davidek, Tomas; Davies, Eleanor; Davies, Merlin; Davignon, Olivier; Davison, Adam; Davison, Peter; Davygora, Yuriy; Dawe, Edmund; Dawson, Ian; Daya-Ishmukhametova, Rozmin; De, Kaushik; de Asmundis, Riccardo; De Castro, Stefano; De Cecco, Sandro; de Graat, Julien; De Groot, Nicolo; de Jong, Paul; De La Taille, Christophe; De la Torre, Hector; De Lorenzi, Francesco; De Nooij, Lucie; De Pedis, Daniele; De Salvo, Alessandro; De Sanctis, Umberto; De Santo, Antonella; De Vivie De Regie, Jean-Baptiste; De Zorzi, Guido; Dearnaley, William James; Debbe, Ramiro; Debenedetti, Chiara; Dechenaux, Benjamin; Dedovich, Dmitri; Degenhardt, James; Deigaard, Ingrid; Del Peso, Jose; Del Prete, Tarcisio; Deliot, Frederic; Delitzsch, Chris Malena; Deliyergiyev, Maksym; Dell'Acqua, Andrea; Dell'Asta, Lidia; Dell'Orso, Mauro; Della Pietra, Massimo; della Volpe, Domenico; Delmastro, Marco; Delsart, Pierre-Antoine; Deluca, Carolina; Demers, Sarah; Demichev, Mikhail; Demilly, Aurelien; Denisov, Sergey; Derendarz, Dominik; Derkaoui, Jamal Eddine; Derue, Frederic; Dervan, Paul; Desch, Klaus Kurt; Deterre, Cecile; Deviveiros, Pier-Olivier; Dewhurst, Alastair; Dhaliwal, Saminder; Di Ciaccio, Anna; Di Ciaccio, Lucia; Di Domenico, Antonio; Di Donato, Camilla; Di Girolamo, Alessandro; Di Girolamo, Beniamino; Di Mattia, Alessandro; Di Micco, Biagio; Di Nardo, Roberto; Di Simone, Andrea; Di Sipio, Riccardo; Di Valentino, David; Diaz, Marco Aurelio; Diehl, Edward; Dietrich, Janet; Dietzsch, Thorsten; Diglio, Sara; Dimitrievska, Aleksandra; Dingfelder, Jochen; Dionisi, Carlo; Dita, Petre; Dita, Sanda; Dittus, Fridolin; Djama, Fares; Djobava, Tamar; Barros do Vale, Maria Aline; Do Valle Wemans, André; Doan, Thi Kieu Oanh; Dobos, Daniel; Dobson, Ellie; Doglioni, Caterina; Doherty, Tom; Dohmae, Takeshi; Dolejsi, Jiri; Dolezal, Zdenek; Dolgoshein, Boris; Donadelli, Marisilvia; Donati, Simone; Dondero, Paolo; Donini, Julien; Dopke, Jens; Doria, Alessandra; Dova, Maria-Teresa; Doyle, Tony; Dris, Manolis; Dubbert, Jörg; Dube, Sourabh; Dubreuil, Emmanuelle; Duchovni, Ehud; Duckeck, Guenter; Ducu, Otilia Anamaria; Duda, Dominik; Dudarev, Alexey; Dudziak, Fanny; Duflot, Laurent; Duguid, Liam; Dührssen, Michael; Dunford, Monica; Duran Yildiz, Hatice; Düren, Michael; Durglishvili, Archil; Dwuznik, Michal; Dyndal, Mateusz; Ebke, Johannes; Edson, William; Edwards, Nicholas Charles; Ehrenfeld, Wolfgang; Eifert, Till; Eigen, Gerald; Einsweiler, Kevin; Ekelof, Tord; El Kacimi, Mohamed; Ellert, Mattias; Elles, Sabine; Ellinghaus, Frank; Ellis, Nicolas; Elmsheuser, Johannes; Elsing, Markus; Emeliyanov, Dmitry; Enari, Yuji; Endner, Oliver Chris; Endo, Masaki; Engelmann, Roderich; Erdmann, Johannes; Ereditato, Antonio; Eriksson, Daniel; Ernis, Gunar; Ernst, Jesse; Ernst, Michael; Ernwein, Jean; Errede, Deborah; Errede, Steven; Ertel, Eugen; Escalier, Marc; Esch, Hendrik; Escobar, Carlos; Esposito, Bellisario; Etienvre, Anne-Isabelle; Etzion, Erez; Evans, Hal; Fabbri, Laura; Facini, Gabriel; Fakhrutdinov, Rinat; Falciano, Speranza; Faltova, Jana; Fang, Yaquan; Fanti, Marcello; Farbin, Amir; Farilla, Addolorata; Farooque, Trisha; Farrell, Steven; Farrington, Sinead; Farthouat, Philippe; Fassi, Farida; Fassnacht, Patrick; Fassouliotis, Dimitrios; Favareto, Andrea; Fayard, Louis; Federic, Pavol; Fedin, Oleg; Fedorko, Wojciech; Fehling-Kaschek, Mirjam; Feigl, Simon; Feligioni, Lorenzo; Feng, Cunfeng; Feng, Eric; Feng, Haolu; Fenyuk, Alexander; Fernandez Perez, Sonia; Ferrag, Samir; Ferrando, James; Ferrara, Valentina; Ferrari, Arnaud; Ferrari, Pamela; Ferrari, Roberto; Ferreira de Lima, Danilo Enoque; Ferrer, Antonio; Ferrere, Didier; Ferretti, Claudio; Ferretto Parodi, Andrea; Fiascaris, Maria; Fiedler, Frank; Filipčič, Andrej; Filipuzzi, Marco; Filthaut, Frank; Fincke-Keeler, Margret; Finelli, Kevin Daniel; Fiolhais, Miguel; Fiorini, Luca; Firan, Ana; Fischer, Julia; Fisher, Matthew; Fisher, Wade Cameron; Fitzgerald, Eric Andrew; Flechl, Martin; Fleck, Ivor; Fleischmann, Philipp; Fleischmann, Sebastian; Fletcher, Gareth Thomas; Fletcher, Gregory; Flick, Tobias; Floderus, Anders; Flores Castillo, Luis; Florez Bustos, Andres Carlos; Flowerdew, Michael; Formica, Andrea; Forti, Alessandra; Fortin, Dominique; Fournier, Daniel; Fox, Harald; Fracchia, Silvia; Francavilla, Paolo; Franchini, Matteo; Franchino, Silvia; Francis, David; Franklin, Melissa; Franz, Sebastien; Fraternali, Marco; French, Sky; Friedrich, Conrad; Friedrich, Felix; Froidevaux, Daniel; Frost, James; Fukunaga, Chikara; Fullana Torregrosa, Esteban; Fulsom, Bryan Gregory; Fuster, Juan; Gabaldon, Carolina; Gabizon, Ofir; Gabrielli, Alessandro; Gabrielli, Andrea; Gadatsch, Stefan; Gadomski, Szymon; Gagliardi, Guido; Gagnon, Pauline; Galea, Cristina; Galhardo, Bruno; Gallas, Elizabeth; Gallo, Valentina Santina; Gallop, Bruce; Gallus, Petr; Galster, Gorm Aske Gram Krohn; Gan, KK; Gandrajula, Reddy Pratap; Gao, Jun; Gao, Yongsheng; Garay Walls, Francisca; Garberson, Ford; García, Carmen; García Navarro, José Enrique; Garcia-Sciveres, Maurice; Gardner, Robert; Garelli, Nicoletta; Garonne, Vincent; Gatti, Claudio; Gaudio, Gabriella; Gaur, Bakul; Gauthier, Lea; Gauzzi, Paolo; Gavrilenko, Igor; Gay, Colin; Gaycken, Goetz; Gazis, Evangelos; Ge, Peng; Gecse, Zoltan; Gee, Norman; Geerts, Daniël Alphonsus Adrianus; Geich-Gimbel, Christoph; Gellerstedt, Karl; Gemme, Claudia; Gemmell, Alistair; Genest, Marie-Hélène; Gentile, Simonetta; George, Matthias; George, Simon; Gerbaudo, Davide; Gershon, Avi; Ghazlane, Hamid; Ghodbane, Nabil; Giacobbe, Benedetto; Giagu, Stefano; Giangiobbe, Vincent; Giannetti, Paola; Gianotti, Fabiola; Gibbard, Bruce; Gibson, Stephen; Gilchriese, Murdock; Gillam, Thomas; Gillberg, Dag; Gilles, Geoffrey; Gingrich, Douglas; Giokaris, Nikos; Giordani, MarioPaolo; Giordano, Raffaele; Giorgi, Francesco Michelangelo; Giraud, Pierre-Francois; Giugni, Danilo; Giuliani, Claudia; Giulini, Maddalena; Gjelsten, Børge Kile; Gkialas, Ioannis; Gladilin, Leonid; Glasman, Claudia; Glatzer, Julian; Glaysher, Paul; Glazov, Alexandre; Glonti, George; Goblirsch-Kolb, Maximilian; Goddard, Jack Robert; Godfrey, Jennifer; Godlewski, Jan; Goeringer, Christian; Goldfarb, Steven; Golling, Tobias; Golubkov, Dmitry; Gomes, Agostinho; Gomez Fajardo, Luz Stella; Gonçalo, Ricardo; Goncalves Pinto Firmino Da Costa, Joao; Gonella, Laura; González de la Hoz, Santiago; Gonzalez Parra, Garoe; Gonzalez Silva, Laura; Gonzalez-Sevilla, Sergio; Goossens, Luc; Gorbounov, Petr Andreevich; Gordon, Howard; Gorelov, Igor; Gorini, Benedetto; Gorini, Edoardo; Gorišek, Andrej; Gornicki, Edward; Goshaw, Alfred; Gössling, Claus; Gostkin, Mikhail Ivanovitch; Gouighri, Mohamed; Goujdami, Driss; Goulette, Marc Phillippe; Goussiou, Anna; Goy, Corinne; Gozpinar, Serdar; Grabas, Herve Marie Xavier; Graber, Lars; Grabowska-Bold, Iwona; Grafström, Per; Grahn, Karl-Johan; Gramling, Johanna; Gramstad, Eirik; Grancagnolo, Francesco; Grancagnolo, Sergio; Grassi, Valerio; Gratchev, Vadim; Gray, Heather; Graziani, Enrico; Grebenyuk, Oleg; Greenwood, Zeno Dixon; Gregersen, Kristian; Gregor, Ingrid-Maria; Grenier, Philippe; Griffiths, Justin; Grillo, Alexander; Grimm, Kathryn; Grinstein, Sebastian; Gris, Philippe Luc Yves; Grishkevich, Yaroslav; Grivaz, Jean-Francois; Grohs, Johannes Philipp; Grohsjean, Alexander; Gross, Eilam; Grosse-Knetter, Joern; Grossi, Giulio Cornelio; Groth-Jensen, Jacob; Grout, Zara Jane; Grybel, Kai; Guan, Liang; Guescini, Francesco; Guest, Daniel; Gueta, Orel; Guicheney, Christophe; Guido, Elisa; Guillemin, Thibault; Guindon, Stefan; Gul, Umar; Gumpert, Christian; Gunther, Jaroslav; Guo, Jun; Gupta, Shaun; Gutierrez, Phillip; Gutierrez Ortiz, Nicolas Gilberto; Gutschow, Christian; Guttman, Nir; Guyot, Claude; Gwenlan, Claire; Gwilliam, Carl; Haas, Andy; Haber, Carl; Hadavand, Haleh Khani; Haddad, Nacim; Haefner, Petra; Hageböck, Stephan; Hajduk, Zbigniew; Hakobyan, Hrachya; Haleem, Mahsana; Hall, David; Halladjian, Garabed; Hamacher, Klaus; Hamal, Petr; Hamano, Kenji; Hamer, Matthias; Hamilton, Andrew; Hamilton, Samuel; Hamnett, Phillip George; Han, Liang; Hanagaki, Kazunori; Hanawa, Keita; Hance, Michael; Hanke, Paul; Hansen, Jørgen Beck; Hansen, Jorn Dines; Hansen, Peter Henrik; Hara, Kazuhiko; Hard, Andrew; Harenberg, Torsten; Harkusha, Siarhei; Harper, Devin; Harrington, Robert; Harris, Orin; Harrison, Paul Fraser; Hartjes, Fred; Hasegawa, Satoshi; Hasegawa, Yoji; Hasib, A; Hassani, Samira; Haug, Sigve; Hauschild, Michael; Hauser, Reiner; Havranek, Miroslav; Hawkes, Christopher; Hawkings, Richard John; Hawkins, Anthony David; Hayashi, Takayasu; Hayden, Daniel; Hays, Chris; Hayward, Helen; Haywood, Stephen; Head, Simon; Heck, Tobias; Hedberg, Vincent; Heelan, Louise; Heim, Sarah; Heim, Timon; Heinemann, Beate; Heinrich, Lukas; Heisterkamp, Simon; Hejbal, Jiri; Helary, Louis; Heller, Claudio; Heller, Matthieu; Hellman, Sten; Hellmich, Dennis; Helsens, Clement; Henderson, James; Henderson, Robert; Hengler, Christopher; Henrichs, Anna; Henriques Correia, Ana Maria; Henrot-Versille, Sophie; Hensel, Carsten; Herbert, Geoffrey Henry; Hernández Jiménez, Yesenia; Herrberg-Schubert, Ruth; Herten, Gregor; Hertenberger, Ralf; Hervas, Luis; Hesketh, Gavin Grant; Hessey, Nigel; Hickling, Robert; Higón-Rodriguez, Emilio; Hill, John; Hiller, Karl Heinz; Hillert, Sonja; Hillier, Stephen; Hinchliffe, Ian; Hines, Elizabeth; Hirose, Minoru; Hirschbuehl, Dominic; Hobbs, John; Hod, Noam; Hodgkinson, Mark; Hodgson, Paul; Hoecker, Andreas; Hoeferkamp, Martin; Hoffman, Julia; Hoffmann, Dirk; Hofmann, Julia Isabell; Hohlfeld, Marc; Holmes, Tova Ray; Hong, Tae Min; Hooft van Huysduynen, Loek; Hostachy, Jean-Yves; Hou, Suen; Hoummada, Abdeslam; Howard, Jacob; Howarth, James; Hrabovsky, Miroslav; Hristova, Ivana; Hrivnac, Julius; Hryn'ova, Tetiana; Hsu, Pai-hsien Jennifer; Hsu, Shih-Chieh; Hu, Diedi; Hu, Xueye; Huang, Yanping; Hubacek, Zdenek; Hubaut, Fabrice; Huegging, Fabian; Huffman, Todd Brian; Hughes, Emlyn; Hughes, Gareth; Huhtinen, Mika; Hülsing, Tobias Alexander; Hurwitz, Martina; Huseynov, Nazim; Huston, Joey; Huth, John; Iacobucci, Giuseppe; Iakovidis, Georgios; Ibragimov, Iskander; Iconomidou-Fayard, Lydia; Ideal, Emma; Iengo, Paolo; Igonkina, Olga; Iizawa, Tomoya; Ikegami, Yoichi; Ikematsu, Katsumasa; Ikeno, Masahiro; Iliadis, Dimitrios; Ilic, Nikolina; Inamaru, Yuki; Ince, Tayfun; Ioannou, Pavlos; Iodice, Mauro; Iordanidou, Kalliopi; Ippolito, Valerio; Irles Quiles, Adrian; Isaksson, Charlie; Ishino, Masaya; Ishitsuka, Masaki; Ishmukhametov, Renat; Issever, Cigdem; Istin, Serhat; Iturbe Ponce, Julia Mariana; Ivashin, Anton; Iwanski, Wieslaw; Iwasaki, Hiroyuki; Izen, Joseph; Izzo, Vincenzo; Jackson, Brett; Jackson, John; Jackson, Matthew; Jackson, Paul; Jaekel, Martin; Jain, Vivek; Jakobs, Karl; Jakobsen, Sune; Jakoubek, Tomas; Jakubek, Jan; Jamin, David Olivier; Jana, Dilip; Jansen, Eric; Jansen, Hendrik; Janssen, Jens; Janus, Michel; Jarlskog, Göran; Javůrek, Tomáš; Jeanty, Laura; Jeng, Geng-yuan; Jennens, David; Jenni, Peter; Jentzsch, Jennifer; Jeske, Carl; Jézéquel, Stéphane; Ji, Haoshuang; Ji, Weina; Jia, Jiangyong; Jiang, Yi; Jimenez Belenguer, Marcos; Jin, Shan; Jinaru, Adam; Jinnouchi, Osamu; Joergensen, Morten Dam; Johansson, Erik; Johansson, Per; Johns, Kenneth; Jon-And, Kerstin; Jones, Graham; Jones, Roger; Jones, Tim; Jongmanns, Jan; Jorge, Pedro; Joshi, Kiran Daniel; Jovicevic, Jelena; Ju, Xiangyang; Jung, Christian; Jungst, Ralph Markus; Jussel, Patrick; Juste Rozas, Aurelio; Kaci, Mohammed; Kaczmarska, Anna; Kado, Marumi; Kagan, Harris; Kagan, Michael; Kajomovitz, Enrique; Kama, Sami; Kanaya, Naoko; Kaneda, Michiru; Kaneti, Steven; Kanno, Takayuki; Kantserov, Vadim; Kanzaki, Junichi; Kaplan, Benjamin; Kapliy, Anton; Kar, Deepak; Karakostas, Konstantinos; Karastathis, Nikolaos; Karnevskiy, Mikhail; Karpov, Sergey; Karthik, Krishnaiyengar; Kartvelishvili, Vakhtang; Karyukhin, Andrey; Kashif, Lashkar; Kasieczka, Gregor; Kass, Richard; Kastanas, Alex; Kataoka, Yousuke; Katre, Akshay; Katzy, Judith; Kaushik, Venkatesh; Kawagoe, Kiyotomo; Kawamoto, Tatsuo; Kawamura, Gen; Kazama, Shingo; Kazanin, Vassili; Kazarinov, Makhail; Keeler, Richard; Kehoe, Robert; Keil, Markus; Keller, John; Keoshkerian, Houry; Kepka, Oldrich; Kerševan, Borut Paul; Kersten, Susanne; Kessoku, Kohei; Keung, Justin; Khalil-zada, Farkhad; Khandanyan, Hovhannes; Khanov, Alexander; Khodinov, Alexander; Khomich, Andrei; Khoo, Teng Jian; Khoriauli, Gia; Khoroshilov, Andrey; Khovanskiy, Valery; Khramov, Evgeniy; Khubua, Jemal; Kim, Hee Yeun; Kim, Hyeon Jin; Kim, Shinhong; Kimura, Naoki; Kind, Oliver; King, Barry; King, Matthew; King, Robert Steven Beaufoy; King, Samuel Burton; Kirk, Julie; Kiryunin, Andrey; Kishimoto, Tomoe; Kisielewska, Danuta; Kiss, Florian; Kitamura, Takumi; Kittelmann, Thomas; Kiuchi, Kenji; Kladiva, Eduard; Klein, Max; Klein, Uta; Kleinknecht, Konrad; Klimek, Pawel; Klimentov, Alexei; Klingenberg, Reiner; Klinger, Joel Alexander; Klinkby, Esben; Klioutchnikova, Tatiana; Klok, Peter; Kluge, Eike-Erik; Kluit, Peter; Kluth, Stefan; Kneringer, Emmerich; Knoops, Edith; Knue, Andrea; Kobayashi, Tomio; Kobel, Michael; Kocian, Martin; Kodys, Peter; Koevesarki, Peter; Koffas, Thomas; Koffeman, Els; Kogan, Lucy Anne; Kohlmann, Simon; Kohout, Zdenek; Kohriki, Takashi; Koi, Tatsumi; Kolanoski, Hermann; Koletsou, Iro; Koll, James; Komar, Aston; Komori, Yuto; Kondo, Takahiko; Kondrashova, Nataliia; Köneke, Karsten; König, Adriaan; König, Sebastian; Kono, Takanori; Konoplich, Rostislav; Konstantinidis, Nikolaos; Kopeliansky, Revital; Koperny, Stefan; Köpke, Lutz; Kopp, Anna Katharina; Korcyl, Krzysztof; Kordas, Kostantinos; Korn, Andreas; Korol, Aleksandr; Korolkov, Ilya; Korolkova, Elena; Korotkov, Vladislav; Kortner, Oliver; Kortner, Sandra; Kostyukhin, Vadim; Kotov, Vladislav; Kotwal, Ashutosh; Kourkoumelis, Christine; Kouskoura, Vasiliki; Koutsman, Alex; Kowalewski, Robert Victor; Kowalski, Tadeusz; Kozanecki, Witold; Kozhin, Anatoly; Kral, Vlastimil; Kramarenko, Viktor; Kramberger, Gregor; Krasnopevtsev, Dimitriy; Krasny, Mieczyslaw Witold; Krasznahorkay, Attila; Kraus, Jana; Kravchenko, Anton; Kreiss, Sven; Kretz, Moritz; Kretzschmar, Jan; Kreutzfeldt, Kristof; Krieger, Peter; Kroeninger, Kevin; Kroha, Hubert; Kroll, Joe; Kroseberg, Juergen; Krstic, Jelena; Kruchonak, Uladzimir; Krüger, Hans; Kruker, Tobias; Krumnack, Nils; Krumshteyn, Zinovii; Kruse, Amanda; Kruse, Mark; Kruskal, Michael; Kubota, Takashi; Kuday, Sinan; Kuehn, Susanne; Kugel, Andreas; Kuhl, Andrew; Kuhl, Thorsten; Kukhtin, Victor; Kulchitsky, Yuri; Kuleshov, Sergey; Kuna, Marine; Kunkle, Joshua; Kupco, Alexander; Kurashige, Hisaya; Kurochkin, Yurii; Kurumida, Rie; Kus, Vlastimil; Kuwertz, Emma Sian; Kuze, Masahiro; Kvita, Jiri; La Rosa, Alessandro; La Rotonda, Laura; Labarga, Luis; Lacasta, Carlos; Lacava, Francesco; Lacey, James; Lacker, Heiko; Lacour, Didier; Lacuesta, Vicente Ramón; Ladygin, Evgueni; Lafaye, Remi; Laforge, Bertrand; Lagouri, Theodota; Lai, Stanley; Laier, Heiko; Lambourne, Luke; Lammers, Sabine; Lampen, Caleb; Lampl, Walter; Lançon, Eric; Landgraf, Ulrich; Landon, Murrough; Lang, Valerie Susanne; Lange, Clemens; Lankford, Andrew; Lanni, Francesco; Lantzsch, Kerstin; Laplace, Sandrine; Lapoire, Cecile; Laporte, Jean-Francois; Lari, Tommaso; Lassnig, Mario; Laurelli, Paolo; Lavorini, Vincenzo; Lavrijsen, Wim; Law, Alexander; Laycock, Paul; Le, Bao Tran; Le Dortz, Olivier; Le Guirriec, Emmanuel; Le Menedeu, Eve; LeCompte, Thomas; Ledroit-Guillon, Fabienne Agnes Marie; Lee, Claire Alexandra; Lee, Hurng-Chun; Lee, Jason; Lee, Shih-Chang; Lee, Lawrence; Lefebvre, Guillaume; Lefebvre, Michel; Legger, Federica; Leggett, Charles; Lehan, Allan; Lehmacher, Marc; Lehmann Miotto, Giovanna; Lei, Xiaowen; Leister, Andrew Gerard; Leite, Marco Aurelio Lisboa; Leitner, Rupert; Lellouch, Daniel; Lemmer, Boris; Leney, Katharine; Lenz, Tatjana; Lenzen, Georg; Lenzi, Bruno; Leone, Robert; Leonhardt, Kathrin; Leontsinis, Stefanos; Leroy, Claude; Lester, Christopher; Lester, Christopher Michael; Levêque, Jessica; Levin, Daniel; Levinson, Lorne; Levy, Mark; Lewis, Adrian; Lewis, George; Leyko, Agnieszka; Leyton, Michael; Li, Bing; Li, Bo; Li, Haifeng; Li, Ho Ling; Li, Shu; Li, Xuefei; Li, Yichen; Liang, Zhijun; Liao, Hongbo; Liberti, Barbara; Lichard, Peter; Lie, Ki; Liebal, Jessica; Liebig, Wolfgang; Limbach, Christian; Limosani, Antonio; Limper, Maaike; Lin, Simon; Linde, Frank; Lindquist, Brian Edward; Linnemann, James; Lipeles, Elliot; Lipniacka, Anna; Lisovyi, Mykhailo; Liss, Tony; Lissauer, David; Lister, Alison; Litke, Alan; Liu, Bo; Liu, Dong; Liu, Jianbei; Liu, Kun; Liu, Lulu; Liu, Miaoyuan; Liu, Minghui; Liu, Yanwen; Livan, Michele; Livermore, Sarah; Lleres, Annick; Llorente Merino, Javier; Lloyd, Stephen; Lo Sterzo, Francesco; Lobodzinska, Ewelina; Loch, Peter; Lockman, William; Loddenkoetter, Thomas; Loebinger, Fred; Loevschall-Jensen, Ask Emil; Loginov, Andrey; Loh, Chang Wei; Lohse, Thomas; Lohwasser, Kristin; Lokajicek, Milos; Lombardo, Vincenzo Paolo; Long, Jonathan; Long, Robin Eamonn; Lopes, Lourenco; Lopez Mateos, David; Lopez Paredes, Brais; Lorenz, Jeanette; Lorenzo Martinez, Narei; Losada, Marta; Loscutoff, Peter; Lou, XinChou; Lounis, Abdenour; Love, Jeremy; Love, Peter; Lowe, Andrew; Lu, Feng; Lubatti, Henry; Luci, Claudio; Lucotte, Arnaud; Luehring, Frederick; Lukas, Wolfgang; Luminari, Lamberto; Lundberg, Olof; Lund-Jensen, Bengt; Lungwitz, Matthias; Lynn, David; Lysak, Roman; Lytken, Else; Ma, Hong; Ma, Lian Liang; Maccarrone, Giovanni; Macchiolo, Anna; Maček, Boštjan; Machado Miguens, Joana; Macina, Daniela; Madaffari, Daniele; Madar, Romain; Maddocks, Harvey Jonathan; Mader, Wolfgang; Madsen, Alexander; Maeno, Mayuko; Maeno, Tadashi; Magradze, Erekle; Mahboubi, Kambiz; Mahlstedt, Joern; Mahmoud, Sara; Maiani, Camilla; Maidantchik, Carmen; Maio, Amélia; Majewski, Stephanie; Makida, Yasuhiro; Makovec, Nikola; Mal, Prolay; Malaescu, Bogdan; Malecki, Pawel; Maleev, Victor; Malek, Fairouz; Mallik, Usha; Malon, David; Malone, Caitlin; Maltezos, Stavros; Malyshev, Vladimir; Malyukov, Sergei; Mamuzic, Judita; Mandelli, Beatrice; Mandelli, Luciano; Mandić, Igor; Mandrysch, Rocco; Maneira, José; Manfredini, Alessandro; Manhaes de Andrade Filho, Luciano; Manjarres Ramos, Joany Andreina; Mann, Alexander; Manning, Peter; Manousakis-Katsikakis, Arkadios; Mansoulie, Bruno; Mantifel, Rodger; Mapelli, Livio; March, Luis; Marchand, Jean-Francois; Marchiori, Giovanni; Marcisovsky, Michal; Marino, Christopher; Marques, Carlos; Marroquim, Fernando; Marsden, Stephen Philip; Marshall, Zach; Marti, Lukas Fritz; Marti-Garcia, Salvador; Martin, Brian; Martin, Brian Thomas; Martin, Tim; Martin, Victoria Jane; Martin dit Latour, Bertrand; Martinez, Homero; Martinez, Mario; Martin-Haugh, Stewart; Martyniuk, Alex; Marx, Marilyn; Marzano, Francesco; Marzin, Antoine; Masetti, Lucia; Mashimo, Tetsuro; Mashinistov, Ruslan; Masik, Jiri; Maslennikov, Alexey; Massa, Ignazio; Massol, Nicolas; Mastrandrea, Paolo; Mastroberardino, Anna; Masubuchi, Tatsuya; Matsunaga, Hiroyuki; Matsushita, Takashi; Mättig, Peter; Mättig, Stefan; Mattmann, Johannes; Maurer, Julien; Maxfield, Stephen; Maximov, Dmitriy; Mazini, Rachid; Mazzaferro, Luca; Mc Goldrick, Garrin; Mc Kee, Shawn Patrick; McCarn, Allison; McCarthy, Robert; McCarthy, Tom; McCubbin, Norman; McFarlane, Kenneth; Mcfayden, Josh; Mchedlidze, Gvantsa; Mclaughlan, Tom; McMahon, Steve; McPherson, Robert; Meade, Andrew; Mechnich, Joerg; Medinnis, Michael; Meehan, Samuel; Meera-Lebbai, Razzak; Mehlhase, Sascha; Mehta, Andrew; Meier, Karlheinz; Meineck, Christian; Meirose, Bernhard; Melachrinos, Constantinos; Mellado Garcia, Bruce Rafael; Meloni, Federico; Mengarelli, Alberto; Menke, Sven; Meoni, Evelin; Mercurio, Kevin Michael; Mergelmeyer, Sebastian; Meric, Nicolas; Mermod, Philippe; Merola, Leonardo; Meroni, Chiara; Merritt, Frank; Merritt, Hayes; Messina, Andrea; Metcalfe, Jessica; Mete, Alaettin Serhan; Meyer, Carsten; Meyer, Christopher; Meyer, Jean-Pierre; Meyer, Jochen; Middleton, Robin; Migas, Sylwia; Mijović, Liza; Mikenberg, Giora; Mikestikova, Marcela; Mikuž, Marko; Miller, David; Mills, Corrinne; Milov, Alexander; Milstead, David; Milstein, Dmitry; Minaenko, Andrey; Miñano Moya, Mercedes; Minashvili, Irakli; Mincer, Allen; Mindur, Bartosz; Mineev, Mikhail; Ming, Yao; Mir, Lluisa-Maria; Mirabelli, Giovanni; Mitani, Takashi; Mitrevski, Jovan; Mitsou, Vasiliki A; Mitsui, Shingo; Miucci, Antonio; Miyagawa, Paul; Mjörnmark, Jan-Ulf; Moa, Torbjoern; Mochizuki, Kazuya; Moeller, Victoria; Mohapatra, Soumya; Mohr, Wolfgang; Molander, Simon; Moles-Valls, Regina; Mönig, Klaus; Monini, Caterina; Monk, James; Monnier, Emmanuel; Montejo Berlingen, Javier; Monticelli, Fernando; Monzani, Simone; Moore, Roger; Mora Herrera, Clemencia; Moraes, Arthur; Morange, Nicolas; Morel, Julien; Moreno, Deywis; Moreno Llácer, María; Morettini, Paolo; Morgenstern, Marcus; Morii, Masahiro; Moritz, Sebastian; Morley, Anthony Keith; Mornacchi, Giuseppe; Morris, John; Morvaj, Ljiljana; Moser, Hans-Guenther; Mosidze, Maia; Moss, Josh; Mount, Richard; Mountricha, Eleni; Mouraviev, Sergei; Moyse, Edward; Muanza, Steve; Mudd, Richard; Mueller, Felix; Mueller, James; Mueller, Klemens; Mueller, Thibaut; Mueller, Timo; Muenstermann, Daniel; Munwes, Yonathan; Murillo Quijada, Javier Alberto; Murray, Bill; Musheghyan, Haykuhi; Musto, Elisa; Myagkov, Alexey; Myska, Miroslav; Nackenhorst, Olaf; Nadal, Jordi; Nagai, Koichi; Nagai, Ryo; Nagai, Yoshikazu; Nagano, Kunihiro; Nagarkar, Advait; Nagasaka, Yasushi; Nagel, Martin; Nairz, Armin Michael; Nakahama, Yu; Nakamura, Koji; Nakamura, Tomoaki; Nakano, Itsuo; Namasivayam, Harisankar; Nanava, Gizo; Narayan, Rohin; Nattermann, Till; Naumann, Thomas; Navarro, Gabriela; Nayyar, Ruchika; Neal, Homer; Nechaeva, Polina; Neep, Thomas James; Negri, Andrea; Negri, Guido; Negrini, Matteo; Nektarijevic, Snezana; Nelson, Andrew; Nelson, Timothy Knight; Nemecek, Stanislav; Nemethy, Peter; Nepomuceno, Andre Asevedo; Nessi, Marzio; Neubauer, Mark; Neumann, Manuel; Neves, Ricardo; Nevski, Pavel; Newman, Paul; Nguyen, Duong Hai; Nickerson, Richard; Nicolaidou, Rosy; Nicquevert, Bertrand; Nielsen, Jason; Nikiforou, Nikiforos; Nikiforov, Andriy; Nikolaenko, Vladimir; Nikolic-Audit, Irena; Nikolics, Katalin; Nikolopoulos, Konstantinos; Nilsson, Paul; Ninomiya, Yoichi; Nisati, Aleandro; Nisius, Richard; Nobe, Takuya; Nodulman, Lawrence; Nomachi, Masaharu; Nomidis, Ioannis; Norberg, Scarlet; Nordberg, Markus; Nowak, Sebastian; Nozaki, Mitsuaki; Nozka, Libor; Ntekas, Konstantinos; Nunes Hanninger, Guilherme; Nunnemann, Thomas; Nurse, Emily; Nuti, Francesco; O'Brien, Brendan Joseph; O'grady, Fionnbarr; O'Neil, Dugan; O'Shea, Val; Oakham, Gerald; Oberlack, Horst; Obermann, Theresa; Ocariz, Jose; Ochi, Atsuhiko; Ochoa, Ines; Oda, Susumu; Odaka, Shigeru; Ogren, Harold; Oh, Alexander; Oh, Seog; Ohm, Christian; Ohman, Henrik; Ohshima, Takayoshi; Okamura, Wataru; Okawa, Hideki; Okumura, Yasuyuki; Okuyama, Toyonobu; Olariu, Albert; Olchevski, Alexander; Olivares Pino, Sebastian Andres; Oliveira Damazio, Denis; Oliver Garcia, Elena; Olivito, Dominick; Olszewski, Andrzej; Olszowska, Jolanta; Onofre, António; Onyisi, Peter; Oram, Christopher; Oreglia, Mark; Oren, Yona; Orestano, Domizia; Orlando, Nicola; Oropeza Barrera, Cristina; Orr, Robert; Osculati, Bianca; Ospanov, Rustem; Otero y Garzon, Gustavo; Otono, Hidetoshi; Ouchrif, Mohamed; Ouellette, Eric; Ould-Saada, Farid; Ouraou, Ahmimed; Oussoren, Koen Pieter; Ouyang, Qun; Ovcharova, Ana; Owen, Mark; Ozcan, Veysi Erkcan; Ozturk, Nurcan; Pachal, Katherine; Pacheco Pages, Andres; Padilla Aranda, Cristobal; 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Sanchez Martinez, Victoria; Sandaker, Heidi; Sander, Heinz Georg; Sanders, Michiel; Sandhoff, Marisa; Sandoval, Tanya; Sandoval, Carlos; Sandstroem, Rikard; Sankey, Dave; Sansoni, Andrea; Santoni, Claudio; Santonico, Rinaldo; Santos, Helena; Santoyo Castillo, Itzebelt; Sapp, Kevin; Sapronov, Andrey; Saraiva, João; Sarrazin, Bjorn; Sartisohn, Georg; Sasaki, Osamu; Sasaki, Yuichi; Sauvage, Gilles; Sauvan, Emmanuel; Savard, Pierre; Savu, Dan Octavian; Sawyer, Craig; Sawyer, Lee; Saxon, David; Saxon, James; Sbarra, Carla; Sbrizzi, Antonio; Scanlon, Tim; Scannicchio, Diana; Scarcella, Mark; Schaarschmidt, Jana; Schacht, Peter; Schaefer, Douglas; Schaefer, Ralph; Schaelicke, Andreas; Schaepe, Steffen; Schaetzel, Sebastian; Schäfer, Uli; Schaffer, Arthur; Schaile, Dorothee; Schamberger, R. Dean; Scharf, Veit; Schegelsky, Valery; Scheirich, Daniel; Schernau, Michael; Scherzer, Max; Schiavi, Carlo; Schieck, Jochen; Schillo, Christian; Schioppa, Marco; Schlenker, Stefan; Schmidt, Evelyn; Schmieden, Kristof; Schmitt, Christian; Schmitt, Christopher; Schmitt, Sebastian; Schneider, Basil; Schnellbach, Yan Jie; Schnoor, Ulrike; Schoeffel, Laurent; Schoening, Andre; Schoenrock, Bradley Daniel; Schorlemmer, Andre Lukas; Schott, Matthias; Schouten, Doug; Schovancova, Jaroslava; Schramm, Steven; Schreyer, Manuel; Schroeder, Christian; Schuh, Natascha; Schultens, Martin Johannes; Schultz-Coulon, Hans-Christian; Schulz, Holger; Schumacher, Markus; Schumm, Bruce; Schune, Philippe; Schwartzman, Ariel; Schwegler, Philipp; Schwemling, Philippe; Schwienhorst, Reinhard; Schwindling, Jerome; Schwindt, Thomas; Schwoerer, Maud; Sciacca, Gianfranco; Scifo, Estelle; Sciolla, Gabriella; Scott, Bill; Scuri, Fabrizio; Scutti, Federico; Searcy, Jacob; Sedov, George; Sedykh, Evgeny; Seidel, Sally; Seiden, Abraham; Seifert, Frank; Seixas, José; Sekhniaidze, Givi; Sekula, Stephen; Selbach, Karoline Elfriede; Seliverstov, Dmitry; Sellers, Graham; Semprini-Cesari, Nicola; Serfon, Cedric; Serin, Laurent; Serkin, Leonid; Serre, Thomas; Seuster, Rolf; Severini, Horst; Sforza, Federico; Sfyrla, Anna; Shabalina, Elizaveta; Shamim, Mansoora; Shan, Lianyou; Shank, James; Shao, Qi Tao; Shapiro, Marjorie; Shatalov, Pavel; Shaw, Kate; Sherwood, Peter; Shimizu, Shima; Shimmin, Chase Owen; Shimojima, Makoto; Shiyakova, Mariya; Shmeleva, Alevtina; Shochet, Mel; Short, Daniel; Shrestha, Suyog; Shulga, Evgeny; Shupe, Michael; Shushkevich, Stanislav; Sicho, Petr; Sidorov, Dmitri; Sidoti, Antonio; Siegert, Frank; Sijacki, Djordje; Silbert, Ohad; Silva, José; Silver, Yiftah; Silverstein, Daniel; Silverstein, Samuel; Simak, Vladislav; Simard, Olivier; Simic, Ljiljana; Simion, Stefan; Simioni, Eduard; Simmons, Brinick; Simoniello, Rosa; Simonyan, Margar; Sinervo, Pekka; Sinev, Nikolai; Sipica, Valentin; Siragusa, Giovanni; Sircar, Anirvan; Sisakyan, Alexei; Sivoklokov, Serguei; Sjölin, Jörgen; Sjursen, Therese; Skinnari, Louise Anastasia; Skottowe, Hugh Philip; Skovpen, Kirill; Skubic, Patrick; Slater, Mark; Slavicek, Tomas; Sliwa, Krzysztof; Smakhtin, Vladimir; Smart, Ben; Smestad, Lillian; Smirnov, Sergei; Smirnov, Yury; Smirnova, Lidia; Smirnova, Oxana; Smith, Kenway; Smizanska, Maria; Smolek, Karel; Snesarev, Andrei; Snidero, Giacomo; Snyder, Scott; Sobie, Randall; Socher, Felix; Soffer, Abner; Soh, Dart-yin; Solans, Carlos; Solar, Michael; Solc, Jaroslav; Soldatov, Evgeny; Soldevila, Urmila; Solfaroli Camillocci, Elena; Solodkov, Alexander; Solovyanov, Oleg; Solovyev, Victor; Sommer, Philip; Song, Hong Ye; Soni, Nitesh; Sood, Alexander; Sopko, Bruno; Sopko, Vit; Sorin, Veronica; Sosebee, Mark; Soualah, Rachik; Soueid, Paul; Soukharev, Andrey; South, David; Spagnolo, Stefania; Spanò, Francesco; Spearman, William Robert; Spighi, Roberto; Spigo, Giancarlo; Spousta, Martin; Spreitzer, Teresa; Spurlock, Barry; St Denis, Richard Dante; Staerz, Steffen; Stahlman, Jonathan; Stamen, Rainer; Stanecka, Ewa; Stanek, Robert; Stanescu, Cristian; Stanescu-Bellu, Madalina; Stanitzki, Marcel Michael; Stapnes, Steinar; Starchenko, Evgeny; Stark, Jan; Staroba, Pavel; Starovoitov, Pavel; Staszewski, Rafal; Stavina, Pavel; Steele, Genevieve; Steinberg, Peter; Stelzer, Bernd; Stelzer, Harald Joerg; Stelzer-Chilton, Oliver; Stenzel, Hasko; Stern, Sebastian; Stewart, Graeme; Stillings, Jan Andre; Stockton, Mark; Stoebe, Michael; Stoerig, Kathrin; Stoicea, Gabriel; Stolte, Philipp; Stonjek, Stefan; Stradling, Alden; Straessner, Arno; Strandberg, Jonas; Strandberg, Sara; Strandlie, Are; Strauss, Emanuel; Strauss, Michael; Strizenec, Pavol; Ströhmer, Raimund; Strom, David; Stroynowski, Ryszard; Stucci, Stefania Antonia; Stugu, Bjarne; Styles, Nicholas Adam; Su, Dong; Su, Jun; Subramania, Halasya Siva; Subramaniam, Rajivalochan; Succurro, Antonella; Sugaya, Yorihito; Suhr, Chad; Suk, Michal; Sulin, Vladimir; Sultansoy, Saleh; Sumida, Toshi; Sun, Xiaohu; Sundermann, Jan Erik; Suruliz, Kerim; Susinno, Giancarlo; Sutton, Mark; Suzuki, Yu; Svatos, Michal; Swedish, Stephen; Swiatlowski, Maximilian; Sykora, Ivan; Sykora, Tomas; Ta, Duc; Tackmann, Kerstin; Taenzer, Joe; Taffard, Anyes; Tafirout, Reda; Taiblum, Nimrod; Takahashi, Yuta; Takai, Helio; Takashima, Ryuichi; Takeda, Hiroshi; Takeshita, Tohru; Takubo, Yosuke; Talby, Mossadek; Talyshev, Alexey; Tam, Jason; Tamsett, Matthew; Tan, Kong Guan; Tanaka, Junichi; Tanaka, Reisaburo; Tanaka, Satoshi; Tanaka, Shuji; Tanasijczuk, Andres Jorge; Tani, Kazutoshi; Tannoury, Nancy; Tapprogge, Stefan; Tarem, Shlomit; Tarrade, Fabien; Tartarelli, Giuseppe Francesco; Tas, Petr; Tasevsky, Marek; Tashiro, Takuya; Tassi, Enrico; Tavares Delgado, Ademar; Tayalati, Yahya; Taylor, Christopher; Taylor, Frank; Taylor, Geoffrey; Taylor, Wendy; Teischinger, Florian Alfred; Teixeira Dias Castanheira, Matilde; Teixeira-Dias, Pedro; Temming, Kim Katrin; Ten Kate, Herman; Teng, Ping-Kun; Terada, Susumu; Terashi, Koji; Terron, Juan; Terzo, Stefano; Testa, Marianna; Teuscher, Richard; Therhaag, Jan; Theveneaux-Pelzer, Timothée; Thoma, Sascha; Thomas, Juergen; Thomas-Wilsker, Joshuha; Thompson, Emily; Thompson, Paul; Thompson, Peter; Thompson, Stan; Thomsen, Lotte Ansgaard; Thomson, Evelyn; Thomson, Mark; Thong, Wai Meng; Thun, Rudolf; Tian, Feng; Tibbetts, Mark James; Tikhomirov, Vladimir; Tikhonov, Yury; Timoshenko, Sergey; Tiouchichine, Elodie; Tipton, Paul; Tisserant, Sylvain; Todorov, Theodore; Todorova-Nova, Sharka; Toggerson, Brokk; Tojo, Junji; Tokár, Stanislav; Tokushuku, Katsuo; Tollefson, Kirsten; Tomlinson, Lee; Tomoto, Makoto; Tompkins, Lauren; Toms, Konstantin; Topilin, Nikolai; Torrence, Eric; Torres, Heberth; Torró Pastor, Emma; Toth, Jozsef; Touchard, Francois; Tovey, Daniel; Tran, Huong Lan; Trefzger, Thomas; Tremblet, Louis; Tricoli, Alessandro; Trigger, Isabel Marian; Trincaz-Duvoid, Sophie; Tripiana, Martin; Triplett, Nathan; Trischuk, William; Trocmé, Benjamin; Troncon, Clara; Trottier-McDonald, Michel; Trovatelli, Monica; True, Patrick; Trzebinski, Maciej; Trzupek, Adam; Tsarouchas, Charilaos; Tseng, Jeffrey; Tsiareshka, Pavel; Tsionou, Dimitra; Tsipolitis, Georgios; Tsirintanis, Nikolaos; Tsiskaridze, Shota; Tsiskaridze, Vakhtang; Tskhadadze, Edisher; Tsukerman, Ilya; Tsulaia, Vakhtang; Tsuno, Soshi; Tsybychev, Dmitri; Tua, Alan; Tudorache, Alexandra; Tudorache, Valentina; Tuna, Alexander Naip; Tupputi, Salvatore; Turchikhin, Semen; Turecek, Daniel; Turk Cakir, Ilkay; Turra, Ruggero; Tuts, Michael; Tykhonov, Andrii; Tylmad, Maja; Tyndel, Mike; Uchida, Kirika; Ueda, Ikuo; Ueno, Ryuichi; Ughetto, Michael; Ugland, Maren; Uhlenbrock, Mathias; Ukegawa, Fumihiko; Unal, Guillaume; Undrus, Alexander; Unel, Gokhan; Ungaro, Francesca; Unno, Yoshinobu; Urbaniec, Dustin; Urquijo, Phillip; Usai, Giulio; Usanova, Anna; Vacavant, Laurent; Vacek, Vaclav; Vachon, Brigitte; Valencic, Nika; Valentinetti, Sara; Valero, Alberto; Valery, Loic; Valkar, Stefan; Valladolid Gallego, Eva; Vallecorsa, Sofia; Valls Ferrer, Juan Antonio; Van Der Deijl, Pieter; van der Geer, Rogier; van der Graaf, Harry; Van Der Leeuw, Robin; van der Ster, Daniel; van Eldik, Niels; van Gemmeren, Peter; Van Nieuwkoop, Jacobus; van Vulpen, Ivo; van Woerden, Marius Cornelis; Vanadia, Marco; Vandelli, Wainer; Vanguri, Rami; Vaniachine, Alexandre; Vankov, Peter; Vannucci, Francois; Vardanyan, Gagik; Vari, Riccardo; Varnes, Erich; Varol, Tulin; Varouchas, Dimitris; Vartapetian, Armen; Varvell, Kevin; Vazeille, Francois; Vazquez Schroeder, Tamara; Veatch, Jason; Veloso, Filipe; Veneziano, Stefano; Ventura, Andrea; Ventura, Daniel; Venturi, Manuela; Venturi, Nicola; Venturini, Alessio; Vercesi, Valerio; Verducci, Monica; Verkerke, Wouter; Vermeulen, Jos; Vest, Anja; Vetterli, Michel; Viazlo, Oleksandr; Vichou, Irene; Vickey, Trevor; Vickey Boeriu, Oana Elena; Viehhauser, Georg; Viel, Simon; Vigne, Ralph; Villa, Mauro; Villaplana Perez, Miguel; Vilucchi, Elisabetta; Vincter, Manuella; Vinogradov, Vladimir; Virzi, Joseph; Vitells, Ofer; Vivarelli, Iacopo; Vives Vaque, Francesc; Vlachos, Sotirios; Vladoiu, Dan; Vlasak, Michal; Vogel, Adrian; Vokac, Petr; Volpi, Guido; Volpi, Matteo; von der Schmitt, Hans; von Radziewski, Holger; von Toerne, Eckhard; Vorobel, Vit; Vorobev, Konstantin; Vos, Marcel; Voss, Rudiger; Vossebeld, Joost; Vranjes, Nenad; Vranjes Milosavljevic, Marija; Vrba, Vaclav; Vreeswijk, Marcel; Vu Anh, Tuan; Vuillermet, Raphael; Vukotic, Ilija; Vykydal, Zdenek; Wagner, Peter; Wagner, Wolfgang; Wahrmund, Sebastian; Wakabayashi, Jun; Walder, James; Walker, Rodney; Walkowiak, Wolfgang; Wall, Richard; Waller, Peter; Walsh, Brian; Wang, Chao; Wang, Chiho; Wang, Fuquan; Wang, Haichen; Wang, Hulin; Wang, Jike; Wang, Jin; Wang, Kuhan; Wang, Rui; Wang, Song-Ming; Wang, Tan; Wang, Xiaoxiao; Warburton, Andreas; Ward, Patricia; Wardrope, David Robert; Warsinsky, Markus; Washbrook, Andrew; Wasicki, Christoph; Watanabe, Ippei; Watkins, Peter; Watson, Alan; Watson, Ian; Watson, Miriam; Watts, Gordon; Watts, Stephen; Waugh, Ben; Webb, Samuel; Weber, Michele; Weber, Stefan Wolf; Webster, Jordan S; Weidberg, Anthony; Weigell, Philipp; Weinert, Benjamin; Weingarten, Jens; Weiser, Christian; Weits, Hartger; Wells, Phillippa; Wenaus, Torre; Wendland, Dennis; Weng, Zhili; Wengler, Thorsten; Wenig, Siegfried; Wermes, Norbert; Werner, Matthias; Werner, Per; Wessels, Martin; Wetter, Jeffrey; Whalen, Kathleen; White, Andrew; White, Martin; White, Ryan; White, Sebastian; Whiteson, Daniel; Wicke, Daniel; Wickens, Fred; Wiedenmann, Werner; Wielers, Monika; Wienemann, Peter; Wiglesworth, Craig; Wiik-Fuchs, Liv Antje Mari; Wijeratne, Peter Alexander; Wildauer, Andreas; Wildt, Martin Andre; Wilkens, Henric George; Will, Jonas Zacharias; Williams, Hugh; Williams, Sarah; Willis, Christopher; Willocq, Stephane; Wilson, Alan; Wilson, John; Wingerter-Seez, Isabelle; Winkelmann, Stefan; Winklmeier, Frank; Wittgen, Matthias; Wittig, Tobias; Wittkowski, Josephine; Wollstadt, Simon Jakob; Wolter, Marcin Wladyslaw; 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Zanzi, Daniele; Zaytsev, Alexander; Zeitnitz, Christian; Zeman, Martin; Zemla, Andrzej; Zengel, Keith; Zenin, Oleg; Ženiš, Tibor; Zerwas, Dirk; Zevi della Porta, Giovanni; Zhang, Dongliang; Zhang, Fangzhou; Zhang, Huaqiao; Zhang, Jinlong; Zhang, Lei; Zhang, Xueyao; Zhang, Zhiqing; Zhao, Zhengguo; Zhemchugov, Alexey; Zhong, Jiahang; Zhou, Bing; Zhou, Lei; Zhou, Ning; Zhu, Cheng Guang; Zhu, Hongbo; Zhu, Junjie; Zhu, Yingchun; Zhuang, Xuai; Zibell, Andre; Zieminska, Daria; Zimine, Nikolai; Zimmermann, Christoph; Zimmermann, Robert; Zimmermann, Simone; Zimmermann, Stephanie; Zinonos, Zinonas; Ziolkowski, Michael; Zitoun, Robert; Zobernig, Georg; Zoccoli, Antonio; zur Nedden, Martin; Zurzolo, Giovanni; Zutshi, Vishnu; Zwalinski, Lukasz

    2014-10-13

    Measurements of normalized differential cross-sections for top-quark pair production are presented as a~function of the top-quark transverse momentum, and of the mass, transverse momentum, and rapidity of the $t\\bar{t}$ system, in proton--proton collisions at a~center-of-mass energy of $\\sqrt{s}$ = 7 TeV. The dataset corresponds to an integrated luminosity of 4.6 fb$^{-1}$, recorded in 2011 with the ATLAS detector at the CERN Large Hadron Collider. Events are selected in the lepton+jets channel, requiring exactly one lepton and at least four jets with at least one of the jets tagged as originating from a~$b$-quark. The measured spectra are corrected for detector efficiency and resolution effects and are compared to several Monte Carlo simulations and theory calculations. The results are in fair agreement with the predictions in a~wide kinematic range. Nevertheless, data distributions are softer than predicted for higher values of the mass of the $t\\bar{t}$ system and of the top-quark transverse momentum. The ...

  5. When Cognitive Decline and Depression Coexist in the Elderly: CSF Biomarkers Analysis Can Differentiate Alzheimer's Disease from Late-Life Depression.

    Science.gov (United States)

    Liguori, Claudio; Pierantozzi, Mariangela; Chiaravalloti, Agostino; Sancesario, Giulia M; Mercuri, Nicola B; Franchini, Flaminia; Schillaci, Orazio; Sancesario, Giuseppe

    2018-01-01

    Late-life depression (LLD) and Alzheimer's Disease (AD) are the two most frequent neuropsychiatric disorders affecting elderly. LLD and AD may clinically present with depressive and cognitive symptoms. Therefore, when cognitive decline is coupled with depression in the elderly, the differential diagnosis between LLD and AD could be challenging. The aim of the present study was to evaluate in a population of elderly patients affected by depression and dementia the usefulness of CSF AD biomarkers (tau proteins and β-amyloid 42 -Aβ 42 ) and 2-[18F]fluoro-2-deoxy-d-glucose positron emission tomography (18FFDG-PET) in early differentiating LLD from AD. Two hundred and fifty-six depressed and demented patients, after performing CSF AD biomarkers and 18FFDG-PET, were distributed in two groups on the basis of the current diagnostic guidelines for AD ( n = 201) and LLD ( n = 55). Patients were then observed for 2 years to verify the early diagnosis. After the 2 year follow-up we compared AD and LLD patients' CSF and 18FFDG-PET data obtained at baseline to a group of age- and sex-matched controls. We found CSF Aβ 42 levels significantly higher in LLD compared to AD patients. Remarkably, CSF Aβ 42 levels of LLD patients (range between 550 and 1204 pg/mL) did not overlap with those of AD patients (range between 82 and 528 pg/mL). Moreover, we documented no differences in CSF AD biomarkers (Aβ 42 and tau proteins) when comparing LLD patients to controls. In addition, AD patients showed the significant reduction of 18FFDG-PET uptake in temporo-parietal regions compared to both controls and LLD. Conversely, LLD and control groups did not differ at 18FFDG-PET analysis, although LLD patients showed heterogeneous patterns of glucose hypometabolism involving cortical and subcortical brain areas. It is noteworthy that at the end of the clinical follow-up, patients owing to AD group showed the expected significant decline of cognitive performances, whereas patients assigned to LLD

  6. When Cognitive Decline and Depression Coexist in the Elderly: CSF Biomarkers Analysis Can Differentiate Alzheimer's Disease from Late-Life Depression

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    Claudio Liguori

    2018-02-01

    Full Text Available Late-life depression (LLD and Alzheimer's Disease (AD are the two most frequent neuropsychiatric disorders affecting elderly. LLD and AD may clinically present with depressive and cognitive symptoms. Therefore, when cognitive decline is coupled with depression in the elderly, the differential diagnosis between LLD and AD could be challenging. The aim of the present study was to evaluate in a population of elderly patients affected by depression and dementia the usefulness of CSF AD biomarkers (tau proteins and β-amyloid42–Aβ42 and 2-[18F]fluoro-2-deoxy-d-glucose positron emission tomography (18FFDG-PET in early differentiating LLD from AD. Two hundred and fifty-six depressed and demented patients, after performing CSF AD biomarkers and 18FFDG-PET, were distributed in two groups on the basis of the current diagnostic guidelines for AD (n = 201 and LLD (n = 55. Patients were then observed for 2 years to verify the early diagnosis. After the 2 year follow-up we compared AD and LLD patients' CSF and 18FFDG-PET data obtained at baseline to a group of age- and sex-matched controls. We found CSF Aβ42 levels significantly higher in LLD compared to AD patients. Remarkably, CSF Aβ42 levels of LLD patients (range between 550 and 1204 pg/mL did not overlap with those of AD patients (range between 82 and 528 pg/mL. Moreover, we documented no differences in CSF AD biomarkers (Aβ42 and tau proteins when comparing LLD patients to controls. In addition, AD patients showed the significant reduction of 18FFDG-PET uptake in temporo-parietal regions compared to both controls and LLD. Conversely, LLD and control groups did not differ at 18FFDG-PET analysis, although LLD patients showed heterogeneous patterns of glucose hypometabolism involving cortical and subcortical brain areas. It is noteworthy that at the end of the clinical follow-up, patients owing to AD group showed the expected significant decline of cognitive performances, whereas patients assigned to

  7. Assessing normative cut points through differential item functioning analysis: An example from the adaptation of the Middlesex Elderly Assessment of Mental State (MEAMS for use as a cognitive screening test in Turkey

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    Kutlay Sehim

    2006-03-01

    Full Text Available Abstract Background The Middlesex Elderly Assessment of Mental State (MEAMS was developed as a screening test to detect cognitive impairment in the elderly. It includes 12 subtests, each having a 'pass score'. A series of tasks were undertaken to adapt the measure for use in the adult population in Turkey and to determine the validity of existing cut points for passing subtests, given the wide range of educational level in the Turkish population. This study focuses on identifying and validating the scoring system of the MEAMS for Turkish adult population. Methods After the translation procedure, 350 normal subjects and 158 acquired brain injury patients were assessed by the Turkish version of MEAMS. Initially, appropriate pass scores for the normal population were determined through ANOVA post-hoc tests according to age, gender and education. Rasch analysis was then used to test the internal construct validity of the scale and the validity of the cut points for pass scores on the pooled data by using Differential Item Functioning (DIF analysis within the framework of the Rasch model. Results Data with the initially modified pass scores were analyzed. DIF was found for certain subtests by age and education, but not for gender. Following this, pass scores were further adjusted and data re-fitted to the model. All subtests were found to fit the Rasch model (mean item fit 0.184, SD 0.319; person fit -0.224, SD 0.557 and DIF was then found to be absent. Thus the final pass scores for all subtests were determined. Conclusion The MEAMS offers a valid assessment of cognitive state for the adult Turkish population, and the revised cut points accommodate for age and education. Further studies are required to ascertain the validity in different diagnostic groups.

  8. Assessing normative cut points through differential item functioning analysis: an example from the adaptation of the Middlesex Elderly Assessment of Mental State (MEAMS) for use as a cognitive screening test in Turkey.

    Science.gov (United States)

    Tennant, Alan; Küçükdeveci, Ayse A; Kutlay, Sehim; Elhan, Atilla H

    2006-03-23

    The Middlesex Elderly Assessment of Mental State (MEAMS) was developed as a screening test to detect cognitive impairment in the elderly. It includes 12 subtests, each having a 'pass score'. A series of tasks were undertaken to adapt the measure for use in the adult population in Turkey and to determine the validity of existing cut points for passing subtests, given the wide range of educational level in the Turkish population. This study focuses on identifying and validating the scoring system of the MEAMS for Turkish adult population. After the translation procedure, 350 normal subjects and 158 acquired brain injury patients were assessed by the Turkish version of MEAMS. Initially, appropriate pass scores for the normal population were determined through ANOVA post-hoc tests according to age, gender and education. Rasch analysis was then used to test the internal construct validity of the scale and the validity of the cut points for pass scores on the pooled data by using Differential Item Functioning (DIF) analysis within the framework of the Rasch model. Data with the initially modified pass scores were analyzed. DIF was found for certain subtests by age and education, but not for gender. Following this, pass scores were further adjusted and data re-fitted to the model. All subtests were found to fit the Rasch model (mean item fit 0.184, SD 0.319; person fit -0.224, SD 0.557) and DIF was then found to be absent. Thus the final pass scores for all subtests were determined. The MEAMS offers a valid assessment of cognitive state for the adult Turkish population, and the revised cut points accommodate for age and education. Further studies are required to ascertain the validity in different diagnostic groups.

  9. Regional analysis of FDG and PIB-PET images in normal aging, mild cognitive impairment, and Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yi [New York University School of Medicine, New York, NY (United States); Qilu hospital Shandong University, Jinan (China); HN400 NYU School of Medicine, Center for Brain Health, Department of Psychiatry, New York, NY (United States); Rinne, Juha O.; Kemppainen, Nina; Naagren, Kjell [Turku PET Centre, University of Turku, Turku (Finland); Mosconi, Lisa; Pirraglia, Elizabeth; Rusinek, Henry; DeSanti, Susan [New York University School of Medicine, New York, NY (United States); Kim, Byeong-Chae [New York University School of Medicine, New York, NY (United States); Chonnam National University Medical School, Department of Neurology, Gwangju (Korea); Tsui, Wai [New York University School of Medicine, New York, NY (United States); Nathan Kline Institute, Orangeburg, NY (United States); Leon, Mony J. de [New York University School of Medicine, New York, NY (United States); Nathan Kline Institute, Orangeburg, NY (United States); HN400 NYU School of Medicine, Center for Brain Health, Department of Psychiatry, New York, NY (United States)

    2008-12-15

    The objective of the study is to compare the diagnostic value of regional sampling of the cerebral metabolic rate of glucose metabolism (MRglc) using [18F]-fluoro-2-deoxyglucose ([18F]FDG)-positron emission tomography (PET) and amyloid-beta pathology using Pittsburgh Compound-B ([11C]PIB)-PET in the evaluation of patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) compared to normal elderly (NL). AD patients, 7NL, 13MCI, and 17, received clinical, neuropsychological, magnetic resonance imaging (MRI), FDG, and PIB-PET exams. Parametric images of PIB uptake and MRglc were sampled using automated regions-of-interest (ROI). AD showed global MRglc reductions, and MCI showed reduced hippocampus (HIP) and inferior parietal lobe (IP) MRglc compared to NL. On PIB, AD patients showed significantly increased uptake in the middle frontal gyrus (MFG), posterior cingulate cortex (PCC), and IP (ps<0.05). PIB uptake in MCI subjects was either AD or NL-like. HIP MRglc and MFG PIB uptake were the best discriminators of NL from MCI and NL from AD. These two best measures showed high diagnostic agreement for AD (94%) and poor agreement for MCI (54%). For the NL vs. MCI discrimination, combining the two best measures increased the accuracy for PIB (75%) and for FDG (85%) to 90%. For AD, the pattern of regional involvement for FDG and PIB differ, but both techniques show high diagnostic accuracy and 94% case by case agreement. In the classification of NL and MCI, FDG is superior to PIB, but there is only 54% agreement at a case level. Combining the two modalities improves the diagnostic accuracy for MCI. (orig.)

  10. Differential Effects of Awake Glioma Surgery in “Critical” Language Areas on Cognition: 4 Case Studies

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    Djaina Satoer

    2017-01-01

    Full Text Available Awake surgery with electrocorticosubcortical stimulation is the golden standard treatment for gliomas in eloquent areas. Preoperatively, mostly mild cognitive disturbances are observed with postoperative deterioration. We describe pre- and postoperative profiles of 4 patients (P1–P4 with gliomas in “critical” language areas (“Broca,” “Wernicke,” and the arcuate fasciculus undergoing awake surgery to get insight into the underlying mechanism of neuroplasticity. Neuropsychological examination was carried out preoperatively (at T1 and postoperatively (at T2, T3. At T1, cognition of P1 was intact and remained stable. P2 had impairments in all cognitive domains at T1 with further deterioration at T2 and T3. At T1, P3 had impairments in memory and executive functions followed by stable recovery. P4 was intact at T1, followed by a decline in a language test at T2 and recovery at T3. Intraoperatively, in all patients language positive sites were identified. Patients with gliomas in “critical” language areas do not necessarily present cognitive disturbances. Surgery can either improve or deteriorate (existing cognitive impairments. Several factors may underlie the plastic potential of the brain, for example, corticosubcortical networks and tumor histopathology. Our findings illustrate the complexity of the underlying mechanism of neural plasticity and provide further support for a “hodotopical” viewpoint.