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Sample records for severely impaired spatial

  1. Validation of the Korean Version of the Spatial Hearing Questionnaire for Assessing the Severity and Symmetry of Hearing Impairment.

    Science.gov (United States)

    Kong, Tae Hoon; Park, Yoon Ah; Bong, Jeong Pyo; Park, Sang Yoo

    2017-07-01

    Spatial hearing refers to the ability to understand speech and identify sounds in various environments. We assessed the validity of the Korean version of the Spatial Hearing Questionnaire (K-SHQ). We performed forward translation of the original English SHQ to Korean and backward translation from the Korean to English. Forty-eight patients who were able to read and understand Korean and received a score of 24 or higher on the Mini-Mental Status Examination were included in the study. Patients underwent pure tone audiometry (PTA) using a standard protocol and completed the K-SHQ. Internal consistency was evaluated using Cronbach's alpha, and factor analysis was performed to prove reliability. Construct validity was tested by comparing K-SHQ scores from patients with normal hearing to those with hearing impairment. Scores were compared between subjects with unilateral or bilateral hearing loss and between symmetrical and asymmetrical hearing impairment. Cronbach's alpha showed good internal consistency (0.982). Two factors were identified by factor analysis: There was a significant difference in K-SHQ scores for patients with normal hearing compared to those with hearing impairment. Patients with asymmetric hearing impairment had higher K-SHQ scores than those with symmetric hearing impairment. This is related to a lower threshold of PTA in the better ear of subjects. The hearing ability of the better ear is correlated with K-SHQ score. The K-SHQ is a reliable and valid tool with which to assess spatial hearing in patients who speak and read Korean. K-SHQ score reflects the severity and symmetry of hearing impairment. © Copyright: Yonsei University College of Medicine 2017

  2. Gene Network Construction from Microarray Data Identifies a Key Network Module and Several Candidate Hub Genes in Age-Associated Spatial Learning Impairment.

    Science.gov (United States)

    Uddin, Raihan; Singh, Shiva M

    2017-01-01

    As humans age many suffer from a decrease in normal brain functions including spatial learning impairments. This study aimed to better understand the molecular mechanisms in age-associated spatial learning impairment (ASLI). We used a mathematical modeling approach implemented in Weighted Gene Co-expression Network Analysis (WGCNA) to create and compare gene network models of young (learning unimpaired) and aged (predominantly learning impaired) brains from a set of exploratory datasets in rats in the context of ASLI. The major goal was to overcome some of the limitations previously observed in the traditional meta- and pathway analysis using these data, and identify novel ASLI related genes and their networks based on co-expression relationship of genes. This analysis identified a set of network modules in the young, each of which is highly enriched with genes functioning in broad but distinct GO functional categories or biological pathways. Interestingly, the analysis pointed to a single module that was highly enriched with genes functioning in "learning and memory" related functions and pathways. Subsequent differential network analysis of this "learning and memory" module in the aged (predominantly learning impaired) rats compared to the young learning unimpaired rats allowed us to identify a set of novel ASLI candidate hub genes. Some of these genes show significant repeatability in networks generated from independent young and aged validation datasets. These hub genes are highly co-expressed with other genes in the network, which not only show differential expression but also differential co-expression and differential connectivity across age and learning impairment. The known function of these hub genes indicate that they play key roles in critical pathways, including kinase and phosphatase signaling, in functions related to various ion channels, and in maintaining neuronal integrity relating to synaptic plasticity and memory formation. Taken together, they

  3. Nutrition of patients with severe neurologic impairment

    Directory of Open Access Journals (Sweden)

    Orel Anija

    2017-12-01

    Full Text Available Commercial enteral formulas are generally recommended for gastrostomy feeding in patients with severe neurologic impairment. However, pureed food diets are still widely used and even gaining popularity among certain groups. We tried to compare the effectiveness of gastrostomy feeding for treatment of severe malnutrition with either enteral formulas or pureed feeds.

  4. Eating disorder severity and functional impairment

    DEFF Research Database (Denmark)

    Davidsen, Annika Helgadóttir; Hoyt, William T.; Poulsen, Stig Bernt

    2017-01-01

    Purpose: The aim was to examine duration of illness and body mass index as possible moderators of the relationship between eating disorder severity and functional impairment, as well as psychological distress as a possible mediator of this relationship. Methods: The study included 159 patients...... was measured with the Sheehan Disability Scale, and psychological distress was measured with the Symptom Check List-90-R. Duration of illness and body mass index were assessed clinically. Results: Duration of illness significantly moderated the relationship between eating disorder severity and functional...... impairment; the relationship was strongest for patients with a shorter duration of illness. Psychological distress partly mediated the relationship between eating disorder severity and functional impairment. Duration of illness significantly moderated the relationship between psychological distress...

  5. Multiple sclerosis with predominant, severe cognitive impairment

    Science.gov (United States)

    Staff, Nathan P.; Lucchinetti, Claudia F.; Keegan, B. Mark

    2009-01-01

    Objective To describe the characteristics of multiple sclerosis (MS) presenting with severe cognitive impairment as its primary disabling manifestation. Design Retrospective case series. Setting Tertiary referral center. Patients Patients were identified through the Mayo Clinic data retrieval system (1996–2008) with definite MS (McDonald criteria) and severe cognitive impairment as their primary neurological symptom without accompanying significant MS-related impairment or alternative diagnosis for cognitive dysfunction. Twenty-three patients meeting inclusion criteria were compared regarding demographics, clinical course and radiological features. Main Outcome Measures Demographic, clinical, and radiological characteristics of the disease. Results Twelve patients were men. The median age of the first clinical symptom suggestive of CNS demyelination was 33 years, and severe MS-related cognitive impairment developed at a median of 39 years. Cognitive impairment could be dichotomized as subacute fulminant (n=9) or chronic progressive (n=14) in presentation, which corresponded to subsequent relapsing or progressive MS courses. Study patients commonly exhibited psychiatric (65%), mild cerebellar (57%) and cortical symptoms and signs (e.g. seizure, aphasia, apraxia) (39%). Fourteen of 21 (67%), where documented, smoked cigarettes. Brain MRI demonstrated diffuse cerebral atrophy in 16 and gadolinium enhancing lesions in 11. Asymptomatic spinal cord MRI lesions were present in 12 of 16 patients (75%). Immunomodulatory therapies were generally ineffective in improving these patients. Conclusions We describe patients with MS whose clinical phenotype is characterized by severe cognitive dysfunction and prominent cortical and psychiatric signs presenting as a subacute fulminant or chronic progressive clinical course. Cigarette smokers may be over represented in this phenotype. PMID:19752304

  6. Histone deacetylase inhibition abolishes stress-induced spatial memory impairment.

    Science.gov (United States)

    Vargas-López, Viviana; Lamprea, Marisol R; Múnera, Alejandro

    2016-10-01

    Acute stress induced before spatial training impairs memory consolidation. Although non-epigenetic underpinning of such effect has been described, the epigenetic mechanisms involved have not yet been studied. Since spatial training and intense stress have opposite effects on histone acetylation balance, it is conceivable that disruption of such balance may underlie acute stress-induced spatial memory consolidation impairment and that inhibiting histone deacetylases prevents such effect. Trichostatin-A (TSA, a histone deacetylase inhibitor) was used to test its effectiveness in preventing stress' deleterious effect on memory. Male Wistar rats were trained in a spatial task in the Barnes maze; 1-h movement restraint was applied to half of them before training. Immediately after training, stressed and non-stressed animals were randomly assigned to receive either TSA (1mg/kg) or vehicle intraperitoneal injection. Twenty-four hours after training, long-term spatial memory was tested; plasma and brain tissue were collected immediately after the memory test to evaluate corticosterone levels and histone H3 acetylation in several brain areas. Stressed animals receiving vehicle displayed memory impairment, increased plasma corticosterone levels and markedly reduced histone H3 acetylation in prelimbic cortex and hippocampus. Such effects did not occur in stressed animals treated with TSA. The aforementioned results support the hypothesis that acute stress induced-memory impairment is related to histone deacetylation. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Spatial Coding of Individuals with Visual Impairments

    Science.gov (United States)

    Papadopoulos, Konstantinos; Koustriava, Eleni; Kartasidou, Lefkothea

    2012-01-01

    The aim of this study is to examine the ability of children and adolescents with visual impairments to code and represent near space. Moreover, it examines the impact of the strategies they use and individual differences in their performance. A total of 30 individuals with visual impairments up to the age of 18 were given eight different object…

  8. Validity of the Severe Impairment Battery Short Version.

    NARCIS (Netherlands)

    Jonghe, J.F. de; Wetzels, R.B.; Mulders, A.; Zuidema, S.U.; Koopmans, R.T.C.M.

    2009-01-01

    BACKGROUND: Efficient neuropsychological tests are needed to measure cognitive impairment in moderate to severe dementia. OBJECTIVE: To examine construct validity of the Severe Impairment Battery Short Version (SIB-S) in nursing home patients with moderate to severe dementia, and to examine

  9. Assessing depression related severity and functional impairment: the Overall Depression Severity and Impairment Scale (ODSIS.

    Directory of Open Access Journals (Sweden)

    Masaya Ito

    Full Text Available The Overall Depression Severity and Impairment Scale (ODSIS is a brief, five-item measure for assessing the frequency and intensity of depressive symptoms, as well as functional impairments in pleasurable activities, work or school, and interpersonal relationships due to depression. Although this scale is expected to be useful in various psychiatric and mental health settings, the reliability, validity, and interpretability have not yet been fully examined. This study was designed to examine the reliability, factorial, convergent, and discriminant validity of a Japanese version of the ODSIS, as well as its ability to distinguish between individuals with and without a major depressive disorder diagnosis.From a pool of registrants at an internet survey company, 2830 non-clinical and clinical participants were selected randomly (619 with major depressive disorder, 619 with panic disorder, 576 with social anxiety disorder, 645 with obsessive-compulsive disorder, and 371 non-clinical panelists. Participants were asked to respond to the ODSIS and conventional measures of depression, functional impairment, anxiety, neuroticism, satisfaction with life, and emotion regulation.Exploratory and confirmatory factor analysis of three split subsamples indicated the unidimensional factor structure of ODSIS. Multi-group confirmatory factor analysis showed invariance of factor loadings between non-clinical and clinical subsamples. The ODSIS also showed excellent internal consistency and test-retest intraclass correlation coefficients. Convergence and discriminance of the ODSIS with various measures were in line with our expectations. Receiver operating characteristic curve analyses showed that the ODSIS was able to detect a major depressive syndrome accurately.This study supports the reliability and validity of ODSIS in a non-western population, which can be interpreted as demonstrating cross-cultural validity.

  10. Severe hypothyroidism masquerading as renal impairment

    DEFF Research Database (Denmark)

    Bistrup, C; Jensen, Dorte Møller; Kvetny, J

    1996-01-01

    A case of severe hypothyroidism in a 51-year old male is presented. The patient was especially complaining of weakness, stiffness and moderate pain in the proximal muscle groups together with rhinorrhea and nasal stenosis. Because of severely elevated S-creatine-kinase combined with reduced...

  11. Distinguishing Motor Weakness From Impaired Spatial Awareness: A Helping Hand!

    Science.gov (United States)

    Raju, Suneil A; Swift, Charles R; Bardhan, Karna Dev

    2017-01-01

    Our patient, aged 73 years, had background peripheral neuropathy of unknown cause, stable for several years, which caused some difficulty in walking on uneven ground. He attended for a teaching session but now staggered in, a new development. He had apparent weakness of his right arm, but there was difficulty in distinguishing motor weakness from impaired spatial awareness suggestive of parietal lobe dysfunction. With the patient seated, eyes closed, and left arm outstretched, S.A.R. lifted the patient's right arm and asked him to indicate when both were level. This confirmed motor weakness. Urgent computed tomographic scan confirmed left subdural haematoma and its urgent evacuation rapidly resolved the patient's symptoms. Intrigued by our patient's case, we explored further and learnt that in rehabilitation medicine, the awareness of limb position is commonly viewed in terms of joint position sense. We present recent literature evidence indicating that the underlying mechanisms are more subtle.

  12. Language and Spatial Reorientation: Evidence from Severe Aphasia

    Science.gov (United States)

    Bek, Judith; Blades, Mark; Siegal, Michael; Varley, Rosemary

    2010-01-01

    Investigating spatial cognition in individuals with acquired language impairments can inform our understanding of how components of language are involved in spatial representation. Using the reorientation paradigm of Hermer-Vazquez, Spelke, and Katsnelson (1999), we examined spatial cue integration (landmark-geometry conjunctions) in individuals…

  13. Factors associated with the severity of motor impairment in children ...

    African Journals Online (AJOL)

    The purpose of this study was to assess the relation between the severity of gross motor dysfunction (GMD) and certain factors such as the type of CP, aetiology of CP, nutrition, socioeconomic class (SEC), and the frequency of these accompanying impairments like visual, auditory, cognitive and speech impairments.

  14. Spatial memory impairment in Morris water maze after electroconvulsive seizures.

    Science.gov (United States)

    Svensson, Maria; Hallin, Thord; Broms, Jonas; Ekstrand, Joakim; Tingström, Anders

    2017-02-01

    Electroconvulsive therapy (ECT) is one of the most efficient treatments for severe major depression, but some patients suffer from retrograde memory loss after treatment. Electroconvulsive seizures (ECS), an animal model of ECT, have repeatedly been shown to increase hippocampal neurogenesis, and multiple ECS treatments cause retrograde amnesia in hippocampus-dependent memory tasks. Since recent studies propose that addition of newborn hippocampal neurons might degrade existing memories, we investigated whether the memory impairment after multiple ECS treatments is a cumulative effect of repeated treatments, or if it is the result of a delayed effect after a single ECS. We used the hippocampus-dependent memory task Morris water maze (MWM) to evaluate spatial memory. Rats were exposed to an 8-day training paradigm before receiving either a single ECS or sham treatment and tested in the MWM 24 h, 72 h, or 7 days after this treatment, or multiple (four) ECS or sham treatments and tested 7 days after the first treatment. A single ECS treatment was not sufficient to cause retrograde amnesia whereas multiple ECS treatments strongly disrupted spatial memory in the MWM. The retrograde amnesia after multiple ECS is a cumulative effect of repeated treatments rather than a delayed effect after a single ECS.

  15. Processing of spatial sounds in the impaired auditory system

    DEFF Research Database (Denmark)

    Arweiler, Iris

    with an intelligibility-weighted “efficiency factor” which revealed that the spectral characteristics of the ER’s caused the reduced benefit. Hearing-impaired listeners were able to utilize the ER energy as effectively as normal-hearing listeners, most likely because binaural processing was not required...... implications for speech perception models and the development of compensation strategies in future generations of hearing instruments.......Understanding speech in complex acoustic environments presents a challenge for most hearing-impaired listeners. In conditions where normal-hearing listeners effortlessly utilize spatial cues to improve speech intelligibility, hearing-impaired listeners often struggle. In this thesis, the influence...

  16. Gait disorder as a predictor of spatial learning and memory impairment in aged mice

    Directory of Open Access Journals (Sweden)

    Xin Wang

    2017-01-01

    Full Text Available Objective To investigate whether gait dysfunction is a predictor of severe spatial learning and memory impairment in aged mice. Methods A total of 100 12-month-old male mice that had no obvious abnormal motor ability and whose Morris water maze performances were not significantly different from those of two-month-old male mice were selected for the study. The selected aged mice were then divided into abnormal or normal gait groups according to the results from the quantitative gait assessment. Gaits of aged mice were defined as abnormal when the values of quantitative gait parameters were two standard deviations (SD lower or higher than those of 2-month-old male mice. Gait parameters included stride length, variability of stride length, base of support, cadence, and average speed. After nine months, mice exhibiting severe spatial learning and memory impairment were separated from mice with mild or no cognitive dysfunction. The rate of severe spatial learning and memory impairment in the abnormal and normal gait groups was tested by a chi-square test and the correlation between gait dysfunction and decline in cognitive function was tested using a diagnostic test. Results The 12-month-old aged mice were divided into a normal gait group (n = 75 and an abnormal gait group (n = 25. Nine months later, three mice in the normal gait group and two mice in the abnormal gait group had died. The remaining mice were subjected to the Morris water maze again, and 17 out of 23 mice in the abnormal gait group had developed severe spatial learning and memory impairment, including six with stride length deficits, 15 with coefficient of variation (CV in stride length, two with base of support (BOS deficits, five with cadence dysfunction, and six with average speed deficits. In contrast, only 15 out of 72 mice in the normal gait group developed severe spatial learning and memory impairment. The rate of severe spatial learning and memory impairment was

  17. Spatial short-term memory in children with nonverbal learning disabilities: impairment in encoding spatial configuration.

    Science.gov (United States)

    Narimoto, Tadamasa; Matsuura, Naomi; Takezawa, Tomohiro; Mitsuhashi, Yoshinori; Hiratani, Michio

    2013-01-01

    The authors investigated whether impaired spatial short-term memory exhibited by children with nonverbal learning disabilities is due to a problem in the encoding process. Children with or without nonverbal learning disabilities performed a simple spatial test that required them to remember 3, 5, or 7 spatial items presented simultaneously in random positions (i.e., spatial configuration) and to decide if a target item was changed or all items including the target were in the same position. The results showed that, even when the spatial positions in the encoding and probe phases were similar, the mean proportion correct of children with nonverbal learning disabilities was 0.58 while that of children without nonverbal learning disabilities was 0.84. The authors argue with the results that children with nonverbal learning disabilities have difficulty encoding relational information between spatial items, and that this difficulty is responsible for their impaired spatial short-term memory.

  18. Developmental dyscalculia is related to visuo-spatial memory and inhibition impairment.

    Science.gov (United States)

    Szucs, Denes; Devine, Amy; Soltesz, Fruzsina; Nobes, Alison; Gabriel, Florence

    2013-01-01

    Developmental dyscalculia is thought to be a specific impairment of mathematics ability. Currently dominant cognitive neuroscience theories of developmental dyscalculia suggest that it originates from the impairment of the magnitude representation of the human brain, residing in the intraparietal sulcus, or from impaired connections between number symbols and the magnitude representation. However, behavioral research offers several alternative theories for developmental dyscalculia and neuro-imaging also suggests that impairments in developmental dyscalculia may be linked to disruptions of other functions of the intraparietal sulcus than the magnitude representation. Strikingly, the magnitude representation theory has never been explicitly contrasted with a range of alternatives in a systematic fashion. Here we have filled this gap by directly contrasting five alternative theories (magnitude representation, working memory, inhibition, attention and spatial processing) of developmental dyscalculia in 9-10-year-old primary school children. Participants were selected from a pool of 1004 children and took part in 16 tests and nine experiments. The dominant features of developmental dyscalculia are visuo-spatial working memory, visuo-spatial short-term memory and inhibitory function (interference suppression) impairment. We hypothesize that inhibition impairment is related to the disruption of central executive memory function. Potential problems of visuo-spatial processing and attentional function in developmental dyscalculia probably depend on short-term memory/working memory and inhibition impairments. The magnitude representation theory of developmental dyscalculia was not supported. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  19. 20 CFR 220.102 - Non-severe impairment(s), defined.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Non-severe impairment(s), defined. 220.102 Section 220.102 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT... these include— (1) Physical functions such as walking, standing, sitting, lifting, pushing, pulling...

  20. Working while unwell: Workplace impairment in people with severe asthma.

    Science.gov (United States)

    Hiles, Sarah A; Harvey, Erin S; McDonald, Vanessa M; Peters, Matthew; Bardin, Philip; Reynolds, Paul N; Upham, John W; Baraket, Melissa; Bhikoo, Zaheerodin; Bowden, Jeffrey; Brockway, Ben; Chung, Li Ping; Cochrane, Belinda; Foxley, Gloria; Garrett, Jeffrey; Hew, Mark; Jayaram, Lata; Jenkins, Christine; Katelaris, Constance; Katsoulotos, Gregory; Koh, Mariko S; Kritikos, Vicky; Lambert, Marina; Langton, David; Rivero, Alexis Lara; Marks, Guy B; Middleton, Peter G; Nanguzgambo, Aldoph; Radhakrishna, Naghmeh; Reddel, Helen; Rimmer, Janet; Southcott, Anne Marie; Sutherland, Michael; Thien, Francis; Wark, Peter Ab; Yang, Ian A; Yap, Elaine; Gibson, Peter G

    2018-04-20

    Severe asthma affects quality of life; however, its impact on workplace productivity is poorly understood. To compare workplace productivity - absenteeism and presenteeism - and impairment in daily activities in severe and non-severe asthma over time and identify characteristics associated with presenteeism in severe asthma. The Severe Asthma Web-based Database (SAWD) is an ongoing observational registry from Australia, New Zealand and Singapore. At April 2017, 434 patients with severe asthma and 102 with non-severe asthma were enrolled (18 to 88 years; 59% female). Participants provided comprehensive clinical and questionnaire data at baseline and were followed-up every 6 months for 24 months. Absenteeism (percentage of time not at work), presenteeism (self-reported impairment at work) and impairment in daily activities outside work due to health problems in the last week were calculated. At baseline, 61.4% of participants with severe asthma and 66.2% with non-severe asthma under 65 years were employed. At younger ages (30-50 years), fewer severe asthma participants were employed (69% vs 100%). Presenteeism and impairment in daily activity were more frequently reported in severe asthma and in participants with poorer asthma control, poorer lung function and more past-year exacerbations (pworkplace. Improving asthma control and mental health may be important targets for optimising workplace productivity in severe asthma. Presenteeism and absenteeism may represent key metrics for assessing intervention efficacy in people with severe asthma of working age. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  1. Distinguishing Motor Weakness From Impaired Spatial Awareness: A Helping Hand!

    Directory of Open Access Journals (Sweden)

    Suneil A Raju

    2017-05-01

    Full Text Available Our patient, aged 73 years, had background peripheral neuropathy of unknown cause, stable for several years, which caused some difficulty in walking on uneven ground. He attended for a teaching session but now staggered in, a new development. He had apparent weakness of his right arm, but there was difficulty in distinguishing motor weakness from impaired spatial awareness suggestive of parietal lobe dysfunction. With the patient seated, eyes closed, and left arm outstretched, S.A.R. lifted the patient’s right arm and asked him to indicate when both were level. This confirmed motor weakness. Urgent computed tomographic scan confirmed left subdural haematoma and its urgent evacuation rapidly resolved the patient’s symptoms. Intrigued by our patient’s case, we explored further and learnt that in rehabilitation medicine, the awareness of limb position is commonly viewed in terms of joint position sense. We present recent literature evidence indicating that the underlying mechanisms are more subtle.

  2. 20 CFR 416.921 - What we mean by a not severe impairment(s) in an adult.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false What we mean by a not severe impairment(s) in an adult. 416.921 Section 416.921 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL... Disability § 416.921 What we mean by a not severe impairment(s) in an adult. (a) Non-severe impairment(s). An...

  3. Hippocampal Volume Reduction in Humans Predicts Impaired Allocentric Spatial Memory in Virtual-Reality Navigation.

    Science.gov (United States)

    Guderian, Sebastian; Dzieciol, Anna M; Gadian, David G; Jentschke, Sebastian; Doeller, Christian F; Burgess, Neil; Mishkin, Mortimer; Vargha-Khadem, Faraneh

    2015-10-21

    The extent to which navigational spatial memory depends on hippocampal integrity in humans is not well documented. We investigated allocentric spatial recall using a virtual environment in a group of patients with severe hippocampal damage (SHD), a group of patients with "moderate" hippocampal damage (MHD), and a normal control group. Through four learning blocks with feedback, participants learned the target locations of four different objects in a circular arena. Distal cues were present throughout the experiment to provide orientation. A circular boundary as well as an intra-arena landmark provided spatial reference frames. During a subsequent test phase, recall of all four objects was tested with only the boundary or the landmark being present. Patients with SHD were impaired in both phases of this task. Across groups, performance on both types of spatial recall was highly correlated with memory quotient (MQ), but not with intelligence quotient (IQ), age, or sex. However, both measures of spatial recall separated experimental groups beyond what would be expected based on MQ, a widely used measure of general memory function. Boundary-based and landmark-based spatial recall were both strongly related to bilateral hippocampal volumes, but not to volumes of the thalamus, putamen, pallidum, nucleus accumbens, or caudate nucleus. The results show that boundary-based and landmark-based allocentric spatial recall are similarly impaired in patients with SHD, that both types of recall are impaired beyond that predicted by MQ, and that recall deficits are best explained by a reduction in bilateral hippocampal volumes. In humans, bilateral hippocampal atrophy can lead to profound impairments in episodic memory. Across species, perhaps the most well-established contribution of the hippocampus to memory is not to episodic memory generally but to allocentric spatial memory. However, the extent to which navigational spatial memory depends on hippocampal integrity in humans is

  4. Severe neurological impairment: legal aspects of decisions to reduce care.

    Science.gov (United States)

    Beresford, H R

    1984-05-01

    Decisions to reduce care for patients with severe neurological impairment may raise legal questions. The laws of most states now authorize physicians to stop care for those who have suffered irreversible cessation of all functions of the brain ("brain death"). Where state law is not explicit, it is nevertheless probably lawful to regard brain death as death for legal purposes so long as currently accepted criteria are satisfied. Several courts have ruled that it is lawful to reduce care for patients in vegetative states, but have prescribed differing standards and procedures for implementing such decisions. The issue of whether parents can authorize physicians to reduce care for neurologically impaired children is the focus of current litigation. Implicit in this litigation is the question of how severe neurological impairment must be before parents and physicians may lawfully agree to reduce care. For severely impaired but not vegetative adults, there is some legal authority to justify certain decisions to reduce care. The issue of whether withholding feeding from a severely demented patient with life-threatening medical problems constitutes criminal behavior is now being considered by a state supreme court.

  5. Spatial navigation deficit in amnestic mild cognitive impairment

    Czech Academy of Sciences Publication Activity Database

    Hort, J.; Laczó, J.; Vyhnálek, M.; Bojar, M.; Bureš, Jan; Vlček, Kamil

    2007-01-01

    Roč. 104, č. 10 (2007), s. 4042-4047 ISSN 0027-8424 R&D Projects: GA ČR(CZ) GA309/06/1231; GA MŠk(CZ) 1M0517; GA ČR(CZ) GA309/05/0693 Institutional research plan: CEZ:AV0Z50110509 Keywords : Mild cognitive impairment * spatial navigation * Alzheimer’s Disease Subject RIV: FH - Neuro logy Impact factor: 9.598, year: 2007

  6. Spatial Navigation and APOE in Amnestic Mild Cognitive Impairment

    Czech Academy of Sciences Publication Activity Database

    Laczó, J.; Andel, R.; Vlček, Kamil; Maťoška, V.; Vyhnálek, M.; Tolar, M.; Bojar, M.; Hort, J.

    2011-01-01

    Roč. 8, č. 4 (2011), s. 169-177 ISSN 1660-2854 R&D Projects: GA ČR(CZ) GA309/09/0286; GA ČR(CZ) GA309/09/1053; GA MŠk(CZ) 1M0517; GA MŠk(CZ) LC554 Institutional research plan: CEZ:AV0Z50110509 Keywords : mild cognitive impairment * spatial navigation * Alzheimer's disease Subject RIV: FH - Neurology Impact factor: 3.056, year: 2011

  7. Encoding audio motion: spatial impairment in early blind individuals

    Directory of Open Access Journals (Sweden)

    Sara eFinocchietti

    2015-09-01

    Full Text Available The consequence of blindness on auditory spatial localization has been an interesting issue of research in the last decade providing mixed results. Enhanced auditory spatial skills in individuals with visual impairment have been reported by multiple studies, while some aspects of spatial hearing seem to be impaired in the absence of vision. In this study, the ability to encode the trajectory of a 2 dimensional sound motion, reproducing the complete movement, and reaching the correct end-point sound position, is evaluated in 12 early blind individuals, 8 late blind individuals, and 20 age-matched sighted blindfolded controls. Early blind individuals correctly determine the direction of the sound motion on the horizontal axis, but show a clear deficit in encoding the sound motion in the lower side of the plane. On the contrary, late blind individuals and blindfolded controls perform much better with no deficit in the lower side of the plane. In fact the mean localization error resulted 271 ± 10 mm for early blind individuals, 65 ± 4 mm for late blind individuals, and 68 ± 2 mm for sighted blindfolded controls.These results support the hypothesis that i it exists a trade-off between the development of enhanced perceptual abilities and role of vision in the sound localization abilities of early blind individuals, and ii the visual information is fundamental in calibrating some aspects of the representation of auditory space in the brain.

  8. Cognitive impairment, clinical severity and MRI changes in MELAS syndrome.

    Science.gov (United States)

    Kraya, Torsten; Neumann, Lena; Paelecke-Habermann, Yvonne; Deschauer, Marcus; Stoevesandt, Dietrich; Zierz, Stephan; Watzke, Stefan

    2017-12-29

    To examine clinical severity, cognitive impairment, and MRI changes in patients with MELAS syndrome. Cognitive-mnestic functions, brain MRI (lesion load, cella media index) and clinical severity of ten patients with MELAS syndrome were examined. All patients carried the m.3243A>G mutation. The detailed neuropsychological assessment revealed cognitive deficits in attention, executive function, visuoperception, and -construction. There were significant correlations between these cognitive changes, lesion load in MRI, disturbances in everyday life (clinical scale), and high scores in NMDAS. Patients with MELAS syndrome showed no global neuropsychological deficit, but rather distinct cognitive deficits. Copyright © 2018 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

  9. The communicative performance of a severely hearing-impaired adolescent

    Directory of Open Access Journals (Sweden)

    Ann Russel

    1981-11-01

    Full Text Available This study describes the communicative performance of a severely hearing-impaired adolescent.The experimenter taught the subject how to play Russian Backgammon. The subject conversed with, and afterwards taught his mother, speech therapist, and a peer how to play the game. Each dyad played the game once. Videotape recordings were made of each dyadic situation. The channels of communication, both verbal and nonverbal, used by each speaker, were determined. A relational communication coding scheme, involving the analysis of requests and subsequent responses, was applied to the data. Results indicate that the hearing-impaired adolescent, though not always able to hold a dominant position in a dyadic situation, was capable of expressing the same types of control as normal adults. Moreover, the types of control expressed varied as a function of each contextual setting. Whenever the subject did hold a dominant position, the combined verbal plus nonverbal channel was his predominant mode of  communication. These findings  suggest that a sociolinguistic approach provides important information regarding a hearing-impaired adolescent's communicative performance.

  10. Working memory limitations in children with severe language impairment.

    Science.gov (United States)

    van Daal, John; Verhoeven, Ludo; van Leeuwe, Jan; van Balkom, Hans

    2008-01-01

    In the present study, the relations of various aspects of working memory to various aspects of language problems in a clinical sample of 97 Dutch speaking 5-year-old children with severe language problems were studied. The working memory and language abilities of the children were examined using an extensive battery of tests. Working memory was operationalized according to the model of Baddeley. Confirmative factor analyses revealed three memory factors: phonological, visual and central executive. Language was construed as a multifactorial construct, and confirmative factor analyses revealed four factors: lexical-semantic abilities, phonological abilities, syntactic abilities and speech production abilities. Moderate to high correlations were found between the memory and language factors. Structural equation modelling was used to further explore the relations between the different factors. Phonological memory was found to predict phonological abilities; central-executive memory predicted lexical-semantic abilities; and visual memory predicted speech production abilities. Phonological abilities also predicted syntactic abilities. Both the theoretical and clinical implications of the findings are discussed. The reader will be introduced to the concepts of multifactorial components of working memory as well as language impairment. Secondly the reader will recognize that working memory and language impairment factors can be related. Particular emphasis will be placed on phonological memory, central-executive memory and visual memory and their possible prediction of specific components of language impairment.

  11. Spatial Analysis of Accident Spots Using Weighted Severity Index ...

    African Journals Online (AJOL)

    ADOWIE PERE

    Spatial Analysis of Accident Spots Using Weighted Severity Index (WSI) and ... pedestrians avoiding the use of pedestrian bridges/aid even when they are available. ..... not minding an unforeseen obstruction, miscalculations and wrong break.

  12. MGlu5 antagonism impairs exploration and memory of spatial and non-spatial stimuli in rats

    DEFF Research Database (Denmark)

    Christoffersen, Gert Rene Juul; Simonyi, Agnes; Schachtman, Todd R.

    2008-01-01

    and it was found that: 1) Locomotion during exploration of spatial environments and exploration time at novel objects were reduced by i.p. but not by prelimbic administration of MPEP, 2) spatial short-term memory was impaired in cross-maze and object discrimination was reduced after both types of administration, 3......) long-term retention of spatial conditioning in the cross-maze was inhibited after i.p. applications which 4) also inhibited spontaneous alternation performance during maze-exploration. Reduced exploratory locomotion and exploration time after i.p. injections may have contributed to the observed......Metabotropic glutamate receptor subtype 5 (mGlu5) has been implicated in memory processing in some but not all learning tasks.  The reason why this receptor is involved in some tasks but not in others remains to be determined.  The present experiments using rats examined effects of the mGlu5...

  13. Mobile communication jacket for people with severe speech impairment.

    Science.gov (United States)

    Lampe, Renée; Blumenstein, Tobias; Turova, Varvara; Alves-Pinto, Ana

    2018-04-01

    Cerebral palsy is a movement disorder caused by damage to motor control areas of the developing brain during early childhood. Motor disorders can also affect the ability to produce clear speech and to communicate. The aim of this study was to develop and to test a prototype of an assistive tool with an embedded mobile communication device to support patients with severe speech impairments. A prototype was developed by equipping a cycling jacket with a display, a small keyboard, a LED and an alarm system, all controlled by a microcontroller. Functionality of the prototype was tested in six participants (aged 7-20 years) with cerebral palsy and global developmental disorder and three healthy persons. A patient questionnaire consisting of seven items was used as an evaluation tool. A working prototype of the communication jacket was developed and tested. The questionnaire elicited positive responses from participants. Improvements to correct revealed weaknesses were proposed. Enhancements like voice output of pre-selected phrases and enlarged display were implemented. Integration in a jacket makes the system mobile and continuously available to the user. The communication jacket may be of great benefit to patients with motor and speech impairments. Implications for Rehabilitation The communication jacket developed can be easily used by people with movement and speech impairment. All technical components are integrated in a garment and do not have to be held with the hands or transported separately. The system is adaptable to individual use. Both expected and unexpected events can be dealt with, which contributes to the quality of life and self-fulfilment.

  14. Severe hearing impairment among military veterans--United States, 2010.

    Science.gov (United States)

    2011-07-22

    A substantial proportion of hearing loss in the United States is attributable to employment-related exposure to noise. Among military veterans, the most common service-connected disabilities are hearing impairments, suggesting that occupational noise exposure during military service might cause more veterans to have hearing loss than nonveterans. However, a recent analysis of data from the 1993-1995 Epidemiology of Hearing Loss Study did not find significant differences between the two groups. To further investigate hearing loss among veterans, specifically the prevalence of severe hearing impairment (SHI), data from the 2010 Annual Social and Economic Supplement (ASEC) to the Current Population Survey (CPS) were analyzed. This report describes the results of those analyses, which indicated that the prevalence of SHI among veterans was significantly greater than among nonveterans. Veterans were 30% more likely to have SHI than nonveterans after adjusting for age and current occupation, and veterans who served in the United States or overseas during September 2001-March 2010, the era of overseas contingency operations (including Operations Enduring Freedom and Iraqi Freedom), were four times more likely than nonveterans to have SHI. These findings suggest a need for increased emphasis on improving military hearing conservation programs (HCPs) and on hearing loss surveillance in military and veterans' health systems.

  15. Inhibition of connexin43 hemichannels impairs spatial short-term memory without affecting spatial working memory

    Directory of Open Access Journals (Sweden)

    Laura Walrave

    2016-12-01

    Full Text Available Astrocytes are active players in higher brain function as they can release gliotransmitters, which are essential for synaptic plasticity. Various mechanisms have been proposed for gliotransmission, including vesicular mechanisms as well as non-vesicular ones, for example by passive diffusion via connexin hemichannels (HCs. We here investigated whether interfering with connexin43 (Cx43 HCs influenced hippocampal spatial memory. We made use of the peptide Gap19 that blocks HCs but not gap junction channels and is specific for Cx43. To this end, we microinfused transactivator of transcription linked Gap19 (TAT-Gap19 into the brain ventricle of male NMRI mice and assessed spatial memory in a Y maze. We found that the in vivo blockade of Cx43 HCs did not affect the locomotor activity or spatial working memory in a spontaneous alternation Y maze task. Cx43 blockade did however significantly impair the spatial short-term memory in a delayed spontaneous alternation Y maze task. These results indicate that Cx43 HCs play a role in spatial short-term memory.

  16. Spatial compression impairs prism-adaptation in healthy individuals

    Directory of Open Access Journals (Sweden)

    Rachel J Scriven

    2013-05-01

    Full Text Available Neglect patients typically present with gross inattention to one side of space following damage to the contralateral hemisphere. While prism-adaptation is effective in ameliorating some neglect behaviours, the mechanisms involved and their relationship to neglect remain unclear. Recent studies have shown that conscious strategic control processes in prism-adaptation may be impaired in neglect patients, who are also reported to show extraordinarily long aftereffects compared to healthy participants. Determining the underlying cause of these effects may be the key to understanding therapeutic benefits. Alternative accounts suggest that reduced strategic control might result from a failure to detect prism-induced reaching errors properly either because a the size of the error is underestimated in compressed visual space or b pathologically increased error detection thresholds reduce the requirement for error correction. The purpose of this study was to model these two alternatives in healthy participants and to examine whether strategic control and subsequent aftereffects were abnormal compared to standard prism adaptation. Each participant completed three prism-adaptation procedures within a MIRAGE mediated reality environment with direction errors recorded before, during and after adaptation. During prism-adaptation, visual-feedback of the reach could be compressed, perturbed by noise or represented veridically. Compressed visual space significantly reduced strategic control and aftereffects compared to control and noise conditions. These results support recent observations in neglect patients, suggesting that a distortion of spatial representation may successfully model neglect and explain neglect performance while adapting to prisms.

  17. The Impact of Residual Vision in Spatial Skills of Individuals with Visual Impairments

    Science.gov (United States)

    Papadopoulos, Konstantinos; Koustriava, Eleni; Kartasidou, Lefkothea

    2011-01-01

    Loss of vision is believed to have a great impact on the acquisition of spatial knowledge. The aims of the present study are to examine the performance of individuals with visual impairments on spatial tasks and the impact of residual vision on processing these tasks. In all, 28 individuals with visual impairments--blindness or low…

  18. Cognitive impairment in patients with AIDS – prevalence and severity

    Directory of Open Access Journals (Sweden)

    Watkins CC

    2015-01-01

    Full Text Available Crystal C Watkins,1,2 Glenn J Treisman2 1The Memory Center in Neuropsychiatry, Sheppard Pratt Health System, 2Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, USA Abstract: The advent of highly active antiretroviral therapy has prolonged the life expectancy of HIV patients and decreased the number of adults who progress to AIDS and HIV-associated dementia. However, neurocognitive deficits remain a pronounced consequence of HIV/AIDS. HIV-1 infection targets the central nervous system in subcortical brain areas and leads to high rates of delirium, depression, opportunistic central nervous system infections, and dementia. Long-term HIV replication in the brain occurs in astrocytes and microglia, allowing the virus to hide from antiviral medication and later compromise neuronal function. The associated cognitive disturbance is linked to both viral activity and inflammatory and other mediators from these immune cells that lead to the damage associated with HIV-associated neurocognitive disorders, a general term given for these disturbances. We review the severity and prevalence of the neuropsychiatric complications of HIV including delirium, neurobehavioral impairments (depression, minor cognitive-motor dysfunction, and HIV-associated dementia. Keywords: HIV, delirium, depression, HAND, dementia; HIV-associated neurocognitive disorder

  19. Model Interpretation of Topological Spatial Analysis for the Visually Impaired (Blind Implemented in Google Maps

    Directory of Open Access Journals (Sweden)

    Marcelo Franco Porto

    2013-06-01

    Full Text Available The technological innovations promote the availability of geographic information on the Internet through Web GIS such as Google Earth and Google Maps. These systems contribute to the teaching and diffusion of geographical knowledge that instigates the recognition of the space we live in, leading to the creation of a spatial identity. In these products available on the Web, the interpretation and analysis of spatial information gives priority to one of the human senses: vision. Due to the fact that this representation of information is transmitted visually (image and vectors, a portion of the population is excluded from part of this knowledge because categories of analysis of geographic data such as borders, territory, and space can only be understood by people who can see. This paper deals with the development of a model of interpretation of topological spatial analysis based on the synthesis of voice and sounds that can be used by the visually impaired (blind.The implementation of a prototype in Google Maps and the usability tests performed are also examined. For the development work it was necessary to define the model of topological spatial analysis, focusing on computational implementation, which allows users to interpret the spatial relationships of regions (countries, states and municipalities, recognizing its limits, neighborhoods and extension beyond their own spatial relationships . With this goal in mind, several interface and usability guidelines were drawn up to be used by the visually impaired (blind. We conducted a detailed study of the Google Maps API (Application Programming Interface, which was the environment selected for prototype development, and studied the information available for the users of that system. The prototype was developed based on the synthesis of voice and sounds that implement the proposed model in C # language and in .NET environment. To measure the efficiency and effectiveness of the prototype, usability

  20. Prevention of Severe Hypoglycemia-Induced Brain Damage and Cognitive Impairment with Verapamil.

    Science.gov (United States)

    Jackson, David A; Michael, Trevin; Vieira de Abreu, Adriana; Agrawal, Rahul; Bortolato, Marco; Fisher, Simon J

    2018-05-03

    People with insulin-treated diabetes are uniquely at risk for severe hypoglycemia-induced brain damage. Since calcium influx may mediate brain damage, we tested the hypothesis that the calcium channel blocker, verapamil, would significantly reduce brain damage and cognitive impairment caused by severe hypoglycemia. Ten-week-old Sprague-Dawley rats were randomly assigned to one of three treatments; 1) control hyperinsulinemic (200 mU.kg -1 min -1 ) euglycemic (80-100mg/dl) clamps (n=14), 2) hyperinsulinemic hypoglycemic (10-15mg/dl) clamps (n=16), or 3) hyperinsulinemic hypoglycemic clamps followed by a single treatment with verapamil (20mg/kg) (n=11). As compared to euglycemic controls, hypoglycemia markedly increased dead/dying neurons in the hippocampus and cortex, by 16-fold and 14-fold, respectively. Verapamil treatment strikingly decreased hypoglycemia-induced hippocampal and cortical damage, by 87% and 94%, respectively. Morris Water Maze probe trial results demonstrated that hypoglycemia induced a retention, but not encoding, memory deficit (noted by both abolished target quadrant preference and reduced target quadrant time). Verapamil treatment significantly rescued spatial memory as noted by restoration of target quadrant preference and target quadrant time. In summary, a one-time treatment with verapamil following severe hypoglycemia prevented neural damage and memory impairment caused by severe hypoglycemia. For people with insulin treated diabetes, verapamil may be a useful drug to prevent hypoglycemia-induced brain damage. © 2018 by the American Diabetes Association.

  1. High prevalence of seasonal affective disorder among persons with severe visual impairment

    DEFF Research Database (Denmark)

    Madsen, Helle Østergaard; Dam, Henrik; Hageman, Ida

    2016-01-01

    BACKGROUND: Light severely affects the occurrence of seasonal affective disorder (SAD). AIMS: To compare the prevalence of SAD in persons with severe visual impairment and persons with full sight, and in persons with severe visual impairment with or without light perception. METHOD: This cross......-sectional study assessed the Global Seasonality Score (GSS) and the prevalence of SAD among 2781 persons with visual impairment and 4099 persons with full sight using the Seasonal Pattern Assessment Questionnaire (SPAQ). RESULTS: Respondents with visual impairment had significantly higher GSS and prevalence...... of SAD compared with full sight controls, Pvisual impairment and SPAQ-defined SAD parameters...

  2. Severe Impairments of Social Interaction and Associated Abnormalities in Children: Epidemiology and Classification.

    Science.gov (United States)

    Wing, Lorna; Gould, Judith

    1979-01-01

    The prevalence of severe impairments of social interaction, language abnormalities, and repetitive stereotyped behaviors was investigated in a group of 132 children under 15 years old, consisting of a socially impaired group (more than half of whom were severely retarded) and a comparison group of sociable severely mentally retarded. Author/DLS)

  3. [GLIATILIN CORRECTION OF WORKING AND REFERENCE SPATIAL MEMORY IMPAIRMENT IN AGED RATS].

    Science.gov (United States)

    Tyurenkov, I N; Volotova, E V; Kurkin, D V

    2015-01-01

    This work was aimed at evaluating the influence of gliatilin administration on the spatial memory in aged rats. Cognitive function and spatial memory in animals was evaluated using radial (8-beam) maze test. Errors of working spatial memory and reference memory were used as indicators of impaired cognitive function. It was found that aged (24-month) rats compared with younger (6-months) age group exhibited cognitive impairment, as manifested by deterioration of short- and long-term memory processes. Course administration of gliatilin in rats of the older age group at a dose of 100 mg/kg resulted in significant improvement of the working and reference spatial memory in aged rats.

  4. Eating disorder severity and functional impairment: moderating effects of illness duration in a clinical sample.

    Science.gov (United States)

    Davidsen, Annika Helgadóttir; Hoyt, William T; Poulsen, Stig; Waaddegaard, Mette; Lau, Marianne

    2017-09-01

    The aim was to examine duration of illness and body mass index as possible moderators of the relationship between eating disorder severity and functional impairment, as well as psychological distress as a possible mediator of this relationship. The study included 159 patients diagnosed with bulimia nervosa, binge eating disorder or eating disorder not otherwise specified. Regression analysis was applied to assess the effect of the hypothesized moderators and mediators. Eating disorder severity was measured with the Eating Disorder Examination Questionnaire, functional impairment was measured with the Sheehan Disability Scale, and psychological distress was measured with the Symptom Check List-90-R. Duration of illness and body mass index were assessed clinically. Duration of illness significantly moderated the relationship between eating disorder severity and functional impairment; the relationship was strongest for patients with a shorter duration of illness. Psychological distress partly mediated the relationship between eating disorder severity and functional impairment. Duration of illness significantly moderated the relationship between psychological distress and functional impairment; the strongest relationship was seen for patients with a shorter duration of illness. Body mass index was not a significant moderator of the relationship between ED severity and functional impairment. Overall, this study established a link between ED severity, psychological distress and functional impairment indicating that both eating disorder severity and psychological distress are more strongly related to impaired role functioning for patients with more recent onset of an eating disorder. More research in the complex relationship between ED severity and functional impairment is needed.

  5. Children with Chromosome 22q11.2 Deletion Syndrome Exhibit Impaired Spatial Working Memory

    Science.gov (United States)

    Wong, Ling M.; Riggins, Tracy; Harvey, Danielle; Cabaral, Margarita; Simon, Tony J.

    2014-01-01

    Individuals with chromosome 22q11.2 deletion syndrome (22q11.2DS) have been shown to have impairments in processing spatiotemporal information. The authors examined whether children with 22q11.2DS exhibit impairments in spatial working memory performance due to these weaknesses, even when controlling for maintenance of attention. Children with…

  6. Neural correlates of spatial navigation changes in mild cognitive impairment and Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Kamil eVlček

    2014-03-01

    Full Text Available Although the memory impairment is a hallmark of Alzheimer’s disease (AD, AD has also been characterized by spatial disorientation, which is present from its early stages. Spatial disorientation in AD manifests itself in getting lost in familiar and unfamiliar places and have been characterized more specifically using spatial navigation tests in both real space and virtual environments as an impairment in multiple spatial abilities, including allocentric and egocentric navigation strategies, visuospatial perception or selection of relevant information for successful navigation. Patients suffering mild cognitive impairment (MCI, who are at a high risk of development of dementia, show impairment in a subset of these abilities, mainly connected with allocentric and egocentric processing. While spatial disorientation in typical AD patients probably reflects neurodegenerative changes in medial and posterior temporal, parietal and frontal lobes and retrosplenial cortex, the impairment of spatial navigation in MCI seem to be connected mainly with the medial temporal and also parietal brain changes. In this review we will summarize the signs of brain disease in most MCI and AD patients showing in various tasks of spatial memory and navigation.

  7. Selective impairments in spatial memory after ischaemic stroke

    NARCIS (Netherlands)

    Kessels, RPC; de Haan, EHF; Kappelle, LJ; Postma, A

    2002-01-01

    There is evidence that object-location memory consists of three separate processes, that is, positional memory, binding of objects to locations, and a possible integration mechanism. A group of 26 patients with lesions following ischaemic stroke was studied to find evidence for selective impairments

  8. Developmental dyscalculia is related to visuo-spatial memory and inhibition impairment

    OpenAIRE

    Szucs, Denes; Devine, Amy; Soltesz, Fruzsina; Nobes, Alison; Gabriel, Florence

    2013-01-01

    Developmental dyscalculia is thought to be a specific impairment of mathematics ability. Currently dominant cognitive neuroscience theories of developmental dyscalculia suggest that it originates from the impairment of the magnitude representation of the human brain, residing in the intraparietal sulcus, or from impaired connections between number symbols and the magnitude representation. However, behavioral research offers several alternative theories for developmental dyscalculia and neuro-...

  9. 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)

  10. Impaired temporal, not just spatial, resolution in amblyopia.

    Science.gov (United States)

    Spang, Karoline; Fahle, Manfred

    2009-11-01

    In amblyopia, neuronal deficits deteriorate spatial vision including visual acuity, possibly because of a lack of use-dependent fine-tuning of afferents to the visual cortex during infancy; but temporal processing may deteriorate as well. Temporal, rather than spatial, resolution was investigated in patients with amblyopia by means of a task based on time-defined figure-ground segregation. Patients had to indicate the quadrant of the visual field where a purely time-defined square appeared. The results showed a clear decrease in temporal resolution of patients' amblyopic eyes compared with the dominant eyes in this task. The extent of this decrease in figure-ground segregation based on time of motion onset only loosely correlated with the decrease in spatial resolution and spanned a smaller range than did the spatial loss. Control experiments with artificially induced blur in normal observers confirmed that the decrease in temporal resolution was not simply due to the acuity loss. Amblyopia not only decreases spatial resolution, but also temporal factors such as time-based figure-ground segregation, even at high stimulus contrasts. This finding suggests that the realm of neuronal processes that may be disturbed in amblyopia is larger than originally thought.

  11. Spirometry quality in adults with very severe lung function impairment.

    Science.gov (United States)

    Torre-Bouscoulet, Luis; Velázquez-Uncal, Mónica; García-Torrentera, Rogelio; Gochicoa-Rangel, Laura; Fernández-Plata, Rosario; Enright, Paul; Pérez-Padilla, Rogelio

    2015-05-01

    Some technologists worry that patients with very severe lung disease are unable to complete several spirometry maneuvers, which require considerable effort. We retrospectively selected all spirometry tests with an FEV1 30,000 subjects tested during the 3-y period) had adequate quality spirometry. Subjects with airway obstruction were less likely to meet FVC repeatability goals. A poor spirometry quality grade was associated with a very low FVC and a low body mass index, but not older age. Severe lung disease should not be used as an excuse for not meeting spirometry quality goals. Copyright © 2015 by Daedalus Enterprises.

  12. Monocyte function is severely impaired by the fluorochrome calcein acetomethylester

    International Nuclear Information System (INIS)

    Czepluch, Frauke S.; Olieslagers, Serve J.F.; Waltenberger, Johannes

    2007-01-01

    For rapid chemotaxis quantification, cell prelabelling is often performed with the fluorochrome calcein acetomethylester (calcein AM). We investigated whether calcein AM-prelabelling is reliable for monocyte migration analysis. Human monocytes were either preexposed to calcein AM or unlabelled. Monocyte migration towards the potent chemoattractants transforming growth factor-β1 (TGF-β1) and N-formyl-Methionin-Leucin-Phenylalanin (fMLP) was assessed using a 48-well micro-chemotaxis chamber. For quantification, cells were visualized by light microscopy and counted. Surprisingly, random migration of calcein AM-prelabelled cells was significantly impaired compared to the unlabelled control. Accordingly, monocyte chemotaxis towards either TGF-β1 or fMLP dramatically declined. Adherence of calcein AM-labelled monocytes on plastic was also significantly decreased compared to control cells. As adhesion is regarded as an essential component of monocyte migration, the reduced migration observed in calcein AM-labelled monocytes might be explained by a fluorochrome-induced adhesion defect. Therefore, use of the fluorochrome calcein AM cannot be recommended for functional testing of monocytes

  13. Nucleus incertus inactivation impairs spatial learning and memory in rats.

    Science.gov (United States)

    Nategh, Mohsen; Nikseresht, Sara; Khodagholi, Fariba; Motamedi, Fereshteh

    2015-02-01

    Nucleus incertus (NI) is a pontine nucleus which releases mainly GABA and relaxin-3 in rats. Its suggested functions include response to stress, arousal, and modulation of hippocampal theta rhythm. Since the role of NI in learning and memory has not been well characterized, therefore the involvement of this nucleus in spatial learning and memory and the aftermath hippocampal levels of c-fos and pCREB were evaluated. NI was targeted by implanting cannula in male rats. For reference memory, NI was inactivated by lidocaine (0.4 μl, 4%) at three stages of acquisition, consolidation and retrieval in Morris water maze paradigm. For working memory, NI was inactivated in acquisition and retrieval phases. Injection of lidocaine prior to the first training session of reference memory significantly increased the distance moved, suggesting that inactivation of NI delays acquisition in this spatial task. Inactivation also interfered with the retrieval phase of spatial reference memory, as the time in target quadrant for lidocaine group was less, and the escape latency was higher compared to the control group. However, no difference was observed in the consolidation phase. In the working memory task, with inter-trial intervals of 75 min, the escape latency was higher when NI was inactivated in the retrieval phase. In addition, c-fos and pCREB/CREB levels decreased in NI-inhibited rats. This study suggests that nucleus incertus might participate in acquisition of spatial reference, and retrieval of both spatial reference and working memory. Further studies should investigate possible roles of NI in the hippocampal plasticity. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Working memory limitations in children with severe language impairment

    NARCIS (Netherlands)

    Daal, J.G.H.L. van; Verhoeven, L.T.W.; Leeuwe, J.F.J. van; Balkom, L.J.M. van

    2008-01-01

    In the present study, the relations of various aspects of working memory to various aspects of language problems in a clinical sample of 97 Dutch speaking 5-year-old children with severe language problems were studied. The working memory and language abilities of the children were examined using an

  15. Visuo-Spatial Imagery Impairment in Posterior Cortical Atrophy: A Cognitive and SPECT Study

    Directory of Open Access Journals (Sweden)

    Simona Gardini

    2011-01-01

    Full Text Available This study investigated the cognitive profile and the cerebral perfusion pattern in a highly educated 70 year old gentleman with posterior cortical atrophy (PCA. Visuo-perceptual abilities, spatial memory, spatial representation and navigation, visuo-spatial mental imagery, semantic and episodic-autobiographical memory were assessed. Regional cerebral blood flow (rCBF was imaged with SPECT. Cognitive testing showed visual-perceptual impairment, apperceptive visual and landmark agnosia, topographical disorientation with way-finding deficits, impaired map learning and poor mental image generation. Semantic memory was normal, while episodic-autobiographical memory was impaired. Reduced rCBF was found mainly in the right hemisphere, in the precentral gyrus, posterior cingulate and middle temporal gyri, cuneus and precuneus, in the left superior temporal and lingual gyri and in the parahippocampus bilaterally. Hypoperfusion in occipito-parietal regions was associated with visuo-spatial deficits, whereas deficits in visuo-spatial mental imagery might reflect dysfunction related to hypoperfusion in the parahippocampus and precuneus, structures which are responsible for spatial and imagery processing. Dissociating performance between preserved semantic memory and poor episodic-autobiographical recall is consistent with a pattern of normal perfusion in frontal and anterior temporal regions but abnormal rCBF in the parahippocampi. The present findings indicate that PCA involves visuo-spatial imagery deficits and provide further validation to current neuro-cognitive models of spatial representation and topographical disorientation.

  16. Spatial navigation impairment is proportional to right hippocampal volume

    Czech Academy of Sciences Publication Activity Database

    Nedelská, Z.; Andel, R.; Laczó, J.; Vlček, Kamil; Hořínek, D.; Lisý, J.; Sheardová, K.; Bureš, Jan; Hort, J.

    2012-01-01

    Roč. 109, č. 7 (2012), s. 2590-2594 ISSN 0027-8424 R&D Projects: GA ČR(CZ) GA309/09/1053; GA ČR(CZ) GA309/09/0286; GA MŠk(CZ) 1M0517; GA MŠk(CZ) LC554 Grant - others:GA MZd(CZ) NS10331 Institutional research plan: CEZ:AV0Z50110509 Keywords : spatial navigation * Alzheimer’s Disease * hippocampal volume Subject RIV: FH - Neurology Impact factor: 9.737, year: 2012

  17. Self-Concept of Severely to Profoundly Hearing-Impaired Children.

    Science.gov (United States)

    Warren, Charlotte; Hasenstab, Suzanne

    1986-01-01

    A study examined demographic, impairment-related, and parental variables that best predicted self-concept among 49 severely to profoundly hearing-impaired 5- to 11-year-olds. A strong relationship was observed between self-concept and parental indulgence, parental rejection, parental protection, parental discipline, and extent of language…

  18. Isoflurane-induced spatial memory impairment in mice is prevented by the acetylcholinesterase inhibitor donepezil.

    Directory of Open Access Journals (Sweden)

    Diansan Su

    Full Text Available Although many studies have shown that isoflurane exposure impairs spatial memory in aged animals, there are no clinical treatments available to prevent this memory deficit. The anticholinergic properties of volatile anesthetics are a biologically plausible cause of cognitive dysfunction in elderly subjects. We hypothesized that pretreatment with the acetylcholinesterase inhibitor donepezil, which has been approved by the Food and Drug Administration (FDA for the treatment of Alzheimer's disease, prevents isoflurane-induced spatial memory impairment in aged mice. In present study, eighteen-month-old mice were administered donepezil (5 mg/kg or an equal volume of saline by oral gavage with a feeding needle for four weeks. Then the mice were exposed to isoflurane (1.2% for six hours. Two weeks later, mice were subjected to the Morris water maze to examine the impairment of spatial memory after exposure to isoflurane. After the behavioral test, the mice were sacrificed, and the protein expression level of acetylcholinesterase (AChE, choline acetylase (ChAT and α7 nicotinic receptor (α7-nAChR were measured in the brain. Each group consisted of 12 mice. We found that isoflurane exposure for six hours impaired the spatial memory of the mice. Compared with the control group, isoflurane exposure dramatically decreased the protein level of ChAT, but not AChE or α7-nAChR. Donepezil prevented isoflurane-induced spatial memory impairments and increased ChAT levels, which were downregulated by isoflurane. In conclusions, pretreatment with the AChE inhibitor donepezil prevented isoflurane-induced spatial memory impairment in aged mice. The mechanism was associated with the upregulation of ChAT, which was decreased by isoflurane.

  19. Subhypnotic doses of propofol impair spatial memory retrieval in rats

    Directory of Open Access Journals (Sweden)

    Hu Liu

    2016-01-01

    Full Text Available Abundant evidence indicates that propofol profoundly affects memory processes, although its specific effects on memory retrieval have not been clarified. A recent study has indicated that hippocampal glycogen synthase kinase-3β (GSK-3β activity affects memory. Constitutively active GSK-3β is required for memory retrieval, and propofol has been shown to inhibit GSK-3β. Thus, the present study examined whether propofol affects memory retrieval, and, if so, whether that effect is mediated through altered GSK-3β activity. Adult Sprague-Dawley rats were trained on a Morris water maze task (eight acquisition trials in one session and subjected under the influence of a subhypnotic dose of propofol to a 24-hour probe trial memory retrieval test. The results showed that rats receiving pretest propofol (25 mg/kg spent significantly less time in the target quadrant but showed no change in locomotor activity compared with those in the control group. Memory retrieval was accompanied by reduced phosphorylation of the serine-9 residue of GSK-3β in the hippocampus, whereas phosphorylation of the tyrosine-216 residue was unaffected. However, propofol blocked this retrieval-associated serine-9 phosphorylation. These findings suggest that subhypnotic propofol administration impairs memory retrieval and that the amnestic effects of propofol may be mediated by attenuated GSK-3β signaling in the hippocampus.

  20. Physical Performance Is Associated with Working Memory in Older People with Mild to Severe Cognitive Impairment

    NARCIS (Netherlands)

    Volkers, K. M.; Scherder, E. J. A.

    2014-01-01

    Background. Physical performances and cognition are positively related in cognitively healthy people. The aim of this study was to examine whether physical performances are related to specific cognitive functioning in older people with mild to severe cognitive impairment. Methods. This

  1. Measuring body composition and energy expenditure in children with severe neurologic impairment and intellectual disability

    NARCIS (Netherlands)

    Rieken, Rob; van Goudoever, Johannes B.; Schierbeek, Henk; Willemsen, Sten P.; Calis, Elsbeth A. C.; Tibboel, Dick; Evenhuis, Heleen M.; Penning, Corine

    2011-01-01

    Accurate prediction equations for estimating body composition and total energy expenditure (TEE) in children with severe neurologic impairment and intellectual disability are currently lacking. The objective was to develop group-specific equations to predict body composition by using

  2. Recovery-related indicators of motor network plasticity according to impairment severity after stroke.

    Science.gov (United States)

    Lee, J; Park, E; Lee, A; Chang, W H; Kim, D-S; Kim, Y-H

    2017-10-01

    Brain connectivity analysis has been widely used to investigate brain plasticity and recovery-related indicators of patients with stroke. However, results remain controversial because of interindividual variability of initial impairment and subsequent recovery of function. In this study, we aimed to investigate the differences in network plasticity and motor recovery-related indicators according to initial severity. We divided participants (16 males and 14 females, aged 54.2 ± 12.0 years) into groups of different severity by Fugl-Mayer Assessment score, i.e. moderate (50-84), severe (20-49) and extremely severe (impairment groups. Longitudinal resting-state functional magnetic resonance imaging data were acquired at 2 weeks and 3 months after onset. The differences in network plasticity and recovery-related indicators between groups were investigated using network distance and graph measurements. As the level of impairment increased, the network balance was more disrupted. Network balance, interhemispheric connectivity and network efficiency were recovered at 3 months only in the moderate impairment group. However, this was not the case in the extremely severe impairment group. A single connection strength between the ipsilesional primary motor cortex and ventral premotor cortex was implicated in the recovery of motor function for the extremely severe impairment group. The connections of the ipsilesional primary motor cortex-ventral premotor cortex were positively associated with motor recovery as the patients were more severely impaired. Differences in plasticity and recovery-related indicators of motor networks were noted according to impairment severity. Our results may suggest meaningful implications for recovery prediction and treatment strategies in future stroke research. © 2017 EAN.

  3. Neural correlates of spatial navigation changes in mild cognitive impairment and Alzheimer's disease

    Czech Academy of Sciences Publication Activity Database

    Vlček, Kamil; Laczó, J.

    2014-01-01

    Roč. 8, Mar 17 (2014), s. 89 ISSN 1662-5153 R&D Projects: GA MZd(CZ) NT13386 Grant - others:GA MŠk(CZ) ED1.100/02/0123 Institutional support: RVO:67985823 Keywords : spatial navigation * Alzheimer’s disease * spatial disorientation * brain changes * mild cognitive impairment Subject RIV: FH - Neurology Impact factor: 3.270, year: 2014

  4. Impaired spatial body representation in complex regional pain syndrome type 1 (CRPS I).

    Science.gov (United States)

    Reinersmann, Annika; Landwehrt, Julia; Krumova, Elena K; Ocklenburg, Sebastian; Güntürkün, Onur; Maier, Christoph

    2012-11-01

    Recently, a shift of the visual subjective body midline (vSM), a correlate of the egocentric reference frame, towards the affected side was reported in patients with complex regional pain syndrome (CRPS). However, the specificity of this finding is as yet unclear. This study compares 24 CRPS patients to 21 patients with upper limb pain of other origin (pain control) and to 24 healthy subjects using a comprehensive test battery, including assessment of the vSM in light and dark, line bisection, hand laterality recognition, neglect-like severity symptoms, and motor impairment (disability of the arm, shoulder, and hand). 1-way analysis of variance, t-tests, significance level: 0.05. In the dark, CRPS patients displayed a significantly larger leftward spatial bias when estimating their vSM, compared to pain controls and healthy subjects, and also reported lower motor function than pain controls. For right-affected CRPS patients only, the deviation of the vSM correlated significantly with the severity of distorted body perception. Results confirm previous findings of impaired visuospatial perception in CRPS patients, which might be the result of the involvement of supraspinal mechanisms in this pain syndrome. These mechanisms might accentuate the leftward bias that results from a right-hemispheric dominance in visuospatial processing and is known as pseudoneglect. Pseudoneglect reveals itself in the tendency to perceive the midpoint of horizontal lines or the subjective body midline left of the centre. It was observable in all 3 groups, but most pronounced in CRPS patients, which might be due to the cortical reorganisation processes associated with this syndrome. Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  5. Risk indicators for severe impaired oral health among indigenous Australian young adults

    Directory of Open Access Journals (Sweden)

    Roberts-Thomson Kaye F

    2010-01-01

    Full Text Available Abstract Background Oral health impairment comprises three conceptual domains; pain, appearance and function. This study sought to: (1 estimate the prevalence of severe oral health impairment as assessed by a summary oral health impairment measure, including aspects of dental pain, dissatisfaction with dental appearance and difficulty eating, among a birth cohort of Indigenous Australian young adults (n = 442, age range 16-20 years; (2 compare prevalence according to demographic, socio-economic, behavioural, dental service utilisation and oral health outcome risk indicators; and (3 ascertain the independent contribution of those risk indicators to severe oral health impairment in this population. Methods Data were from the Aboriginal Birth Cohort (ABC study, a prospective longitudinal investigation of Aboriginal individuals born 1987-1990 at an Australian regional hospital. Data for this analysis pertained to Wave-3 of the study only. Severe oral health impairment was defined as reported experience of toothache, poor dental appearance and food avoidance in the last 12 months. Logistic regression models were used to evaluate effects of demographic, socio-economic, behavioural, dental service utilisation and clinical oral disease indicators on severe oral health impairment. Effects were quantified as odds ratios (OR. Results The percent of participants with severe oral health impairment was 16.3 (95% CI 12.9-19.7. In the multivariate model, severe oral health impairment was associated with untreated dental decay (OR 4.0, 95% CI 1.6-9.6. In addition to that clinical indicator, greater odds of severe oral health impairment were associated with being female (OR 2.0, 95% CI 1.2-3.6, being aged 19-20 years (OR 2.1, 95% CI 1.2-3.6, soft drink consumption every day or a few days a week (OR 2.6, 95% 1.2-5.6 and non-ownership of a toothbrush (OR 1.9, 95% CI 1.1-3.4. Conclusions Severe oral health impairment was prevalent among this population. The findings

  6. Blindness and severe visual impairment in pupils at schools for the blind in Burundi.

    Science.gov (United States)

    Ruhagaze, Patrick; Njuguna, Kahaki Kimani Margaret; Kandeke, Lévi; Courtright, Paul

    2013-01-01

    To determine the causes of childhood blindness and severe visual impairment in pupils attending schools for the blind in Burundi in order to assist planning for services in the country. All pupils attending three schools for the blind in Burundi were examined. A modified WHO/PBL eye examination record form for children with blindness and low vision was used to record the findings. Data was analyzed for those who became blind or severely visually impaired before the age of 16 years. Overall, 117 pupils who became visually impaired before 16 years of age were examined. Of these, 109 (93.2%) were blind or severely visually impaired. The major anatomical cause of blindness or severe visual impairment was cornea pathology/phthisis (23.9%), followed by lens pathology (18.3%), uveal lesions (14.7%) and optic nerve lesions (11.9%). In the majority of pupils with blindness or severe visual impairment, the underlying etiology of visual loss was unknown (74.3%). More than half of the pupils with lens related blindness had not had surgery; among those who had surgery, outcomes were generally poor. The causes identified indicate the importance of continuing preventive public health strategies, as well as the development of specialist pediatric ophthalmic services in the management of childhood blindness in Burundi. The geographic distribution of pupils at the schools for the blind indicates a need for community-based programs to identify and refer children in need of services.

  7. Spatial memory impairment is associated with hippocampal insulin signals in ovariectomized rats.

    Science.gov (United States)

    Wang, Fang; Song, Yan-Feng; Yin, Jie; Liu, Zi-Hua; Mo, Xiao-Dan; Wang, De-Gui; Gao, Li-Ping; Jing, Yu-Hong

    2014-01-01

    Estrogen influences memory formation and insulin sensitivity. Meanwhile, glucose utilization directly affects learning and memory, which are modulated by insulin signals. Therefore, this study investigated whether or not the effect of estrogen on memory is associated with the regulatory effect of this hormone on glucose metabolism. The relative expression of estrogen receptor β (ERβ) and glucose transporter type 4 (GLUT4) in the hippocampus of rats were evaluated by western blot. Insulin level was assessed by ELISA and quantitative RT-PCR, and spatial memory was tested by the Morris water maze. Glucose utilization in the hippocampus was measured by 2-NBDG uptake analysis. Results showed that ovariectomy impaired the spatial memory of rats. These impairments are similar as the female rats treated with the ERβ antagonist tamoxifen (TAM). Estrogen blockade by ovariectomy or TAM treatment obviously decreased glucose utilization. This phenomenon was accompanied by decreased insulin level and GLUT4 expression in the hippocampus. The female rats were neutralized with hippocampal insulin with insulin antibody, which also impaired memory and local glucose consumption. These results indicated that estrogen blockade impaired the spatial memory of the female rats. The mechanisms by which estrogen blockade impaired memory partially contributed to the decline in hippocampal insulin signals, which diminished glucose consumption.

  8. Lanthanum chloride impairs spatial memory through ERK/MSK1 signaling pathway of hippocampus in rats.

    Science.gov (United States)

    Liu, Huiying; Yang, Jinghua; Liu, Qiufang; Jin, Cuihong; Wu, Shengwen; Lu, Xiaobo; Zheng, Linlin; Xi, Qi; Cai, Yuan

    2014-12-01

    Rare earth elements (REEs) are used in many fields for their diverse physical and chemical properties. Surveys have shown that REEs can impair learning and memory in children and cause neurobehavioral defects in animals. However, the mechanism underlying these impairments has not yet been completely elucidated. Lanthanum (La) is often selected to study the effects of REEs. The aim of this study was to investigate the spatial memory impairments induced by lanthanum chloride (LaCl3) and the probable underlying mechanism. Wistar rats were exposed to LaCl3 in drinking water at 0 % (control, 0 mM), 0.25 % (18 mM), 0.50 % (36 mM), and 1.00 % (72 mM) from birth to 2 months after weaning. LaCl3 considerably impaired the spatial learning and memory of rats in the Morris water maze test, damaged the synaptic ultrastructure and downregulated the expression of p-MEK1/2, p-ERK1/2, p-MSK1, p-CREB, c-FOS and BDNF in the hippocampus. These results indicate that LaCl3 exposure impairs the spatial learning and memory of rats, which may be attributed to disruption of the synaptic ultrastructure and inhibition of the ERK/MSK1 signaling pathway in the hippocampus.

  9. Extensive Lesions of Cholinergic Basal Forebrain Neurons Do Not Impair Spatial Working Memory

    Science.gov (United States)

    Vuckovich, Joseph A.; Semel, Mara E.; Baxter, Mark G.

    2004-01-01

    A recent study suggests that lesions to all major areas of the cholinergic basal forebrain in the rat (medial septum, horizontal limb of the diagonal band of Broca, and nucleus basalis magnocellularis) impair a spatial working memory task. However, this experiment used a surgical technique that may have damaged cerebellar Purkinje cells. The…

  10. The experiences of severely visually impaired students in higher music education

    OpenAIRE

    Ball, Natalie

    2017-01-01

    The aim of this research was to investigate the experiences of severely visually impaired students in higher music education. Higher education should be accessible to all and therefore policies must be created and implemented to ensure this. The experiences of students with impairments best show where barriers exist for such students and how they can be removed. This studied is based on the social model of disability and the emancipatory research paradigm which is linked to critical pedagogy....

  11. Postural Care for People with Intellectual Disabilities and Severely Impaired Motor Function: A Scoping Review

    Science.gov (United States)

    Robertson, Janet; Baines, Susannah; Emerson, Eric; Hatton, Chris

    2018-01-01

    Background: Poor postural care can have severe and life-threatening complications. This scoping review aims to map and summarize existing evidence regarding postural care for people with intellectual disabilities and severely impaired motor function. Method: Studies were identified via electronic database searches (MEDLINE, CINAHL, PsycINFO and…

  12. Emergency Department Use by Nursing Home Residents: Effect of Severity of Cognitive Impairment

    Science.gov (United States)

    Stephens, Caroline E.; Newcomer, Robert; Blegen, Mary; Miller, Bruce; Harrington, Charlene

    2012-01-01

    Purpose: To examine the 1-year prevalence and risk of emergency department (ED) use and ambulatory care-sensitive (ACS) ED use by nursing home (NH) residents with different levels of severity of cognitive impairment (CI). Design and Methods: We used multinomial logistic regression to estimate the effect of CI severity on the odds of any ED visit…

  13. Risk factors for spatial memory impairment in patients with temporal lobe epilepsy.

    Science.gov (United States)

    Amlerova, Jana; Laczo, Jan; Vlcek, Kamil; Javurkova, Alena; Andel, Ross; Marusic, Petr

    2013-01-01

    At present, the risk factors for world-centered (allocentric) navigation impairment in patients with temporal lobe epilepsy (TLE) are not known. There is some evidence on the importance of the right hippocampus but other clinical features have not been investigated yet. In this study, we used an experimental human equivalent to the Morris water maze to examine spatial navigation performance in patients with drug-refractory unilateral TLE. We included 47 left-hemisphere speech dominant patients (25 right sided; 22 left sided). The aim of our study was to identify clinical and demographic characteristics of TLE patients who performed poorly in allocentric spatial memory tests. Our results demonstrate that poor spatial navigation is significantly associated with younger age at epilepsy onset, longer disease duration, and lower intelligence level. Allocentric navigation in TLE patients was impaired irrespective of epilepsy lateralization. Good and poor navigators did not differ in their age, gender, or preoperative/postoperative status. This study provides evidence on risk factors that increase the likelihood of allocentric navigation impairment in TLE patients. The results indicate that not only temporal lobe dysfunction itself but also low general cognitive abilities may contribute to the navigation impairment. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Zinc deficiency with reduced mastication impairs spatial memory in young adult mice.

    Science.gov (United States)

    Kida, Kumiko; Tsuji, Tadataka; Tanaka, Susumu; Kogo, Mikihiko

    2015-12-01

    Sufficient oral microelements such as zinc and fully chewing of foods are required to maintain cognitive function despite aging. No knowledge exists about the combination of factors such as zinc deficiency and reduced mastication on learning and memory. Here we show that tooth extraction only in 8-week-old mice did not change the density of glial fibrillary acidic protein-labeled astrocytes in the hippocampus or spatial memory parameters. However, tooth extraction followed by zinc deprivation strongly impaired spatial memory and led to an increase in astrocytic density in the hippocampal CA1 region. The impaired spatial performance in the zinc-deficient only (ZD) mice also coincided well with the increase in the astrocytic density in the hippocampal CA1 region. After switching both zinc-deficient groups to a normal diet with sufficient zinc, spatial memory recovered, and more time was spent in the quadrant with the goal in the probe test in the mice with tooth extraction followed by zinc deprivation (EZD) compared to the ZD mice. Interestingly, we found no differences in astrocytic density in the CA1 region among all groups at 22 weeks of age. Furthermore, the escape latency in a visible probe test at all times was longer in zinc-deficient groups than the others and demonstrated a negative correlation with body weight. No significant differences in escape latency were observed in the visible probe test among the ZD, EZD, and normal-fed control at 4 weeks (CT4w) groups in which body weight was standardized to that of the EZD group, or in the daily reduction in latency between the normal-fed control and CT4w groups. Our data showed that zinc-deficient feeding during a young age impairs spatial memory performance and leads to an increase in astrocytic density in the hippocampal CA1 region and that zinc-sufficient feeding is followed by recovery of the impaired spatial memory along with changes in astrocytic density. The combination of the two factors, zinc deficiency

  15. Impairments of spatial working memory and attention following acute psychosocial stress.

    Science.gov (United States)

    Olver, James S; Pinney, Myra; Maruff, Paul; Norman, Trevor R

    2015-04-01

    Few studies have investigated the effect of an acute psychosocial stress paradigm on impaired attention and working memory in humans. Further, the duration of any stress-related cognitive impairment remains unclear. The aim of this study was to examine the effect of an acute psychosocial stress paradigm, the Trier Social Stress, on cognitive function in healthy volunteers. Twenty-three healthy male and female subjects were exposed to an acute psychosocial stress task. Physiological measures (salivary cortisol, heart rate and blood pressure) and subjective stress ratings were measured at baseline, in anticipation of stress, immediately post-stress and after a period of rest. A neuropsychological test battery including spatial working memory and verbal memory was administered at each time point. Acute psychosocial stress produced significant increases in cardiovascular and subjective measures in the anticipatory and post-stress period, which recovered to baseline after rest. Salivary cortisol steadily declined over the testing period. Acute psychosocial stress impaired delayed verbal recall, attention and spatial working memory. Attention remained impaired, and delayed verbal recall continued to decline after rest. Acute psychosocial stress is associated with an impairment of a broad range of cognitive functions in humans and with prolonged abnormalities in attention and memory. Copyright © 2014 John Wiley & Sons, Ltd.

  16. Peripheral inflammation acutely impairs human spatial memory via actions on medial temporal lobe glucose metabolism.

    Science.gov (United States)

    Harrison, Neil A; Doeller, Christian F; Voon, Valerie; Burgess, Neil; Critchley, Hugo D

    2014-10-01

    Inflammation impairs cognitive performance and is implicated in the progression of neurodegenerative disorders. Rodent studies demonstrated key roles for inflammatory mediators in many processes critical to memory, including long-term potentiation, synaptic plasticity, and neurogenesis. They also demonstrated functional impairment of medial temporal lobe (MTL) structures by systemic inflammation. However, human data to support this position are limited. Sequential fluorodeoxyglucose positron emission tomography together with experimentally induced inflammation was used to investigate effects of a systemic inflammatory challenge on human MTL function. Fluorodeoxyglucose positron emission tomography scanning was performed in 20 healthy participants before and after typhoid vaccination and saline control injection. After each scanning session, participants performed a virtual reality spatial memory task analogous to the Morris water maze and a mirror-tracing procedural memory control task. Fluorodeoxyglucose positron emission tomography data demonstrated an acute reduction in human MTL glucose metabolism after inflammation. The inflammatory challenge also selectively compromised human spatial, but not procedural, memory; this effect that was independent of actions on motivation or psychomotor response. Effects of inflammation on parahippocampal and rhinal glucose metabolism directly mediated actions of inflammation on spatial memory. These data demonstrate acute sensitivity of human MTL to mild peripheral inflammation, giving rise to associated functional impairment in the form of reduced spatial memory performance. Our findings suggest a mechanism for the observed epidemiologic link between inflammation and risk of age-related cognitive decline and progression of neurodegenerative disorders including Alzheimer's disease. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  17. Deletion of PEA-15 in mice is associated with specific impairments of spatial learning abilities

    Directory of Open Access Journals (Sweden)

    Hale Gregory

    2009-11-01

    Full Text Available Abstract Background PEA-15 is a phosphoprotein that binds and regulates ERK MAP kinase and RSK2 and is highly expressed throughout the brain. PEA-15 alters c-Fos and CREB-mediated transcription as a result of these interactions. To determine if PEA-15 contributes to the function of the nervous system we tested mice lacking PEA-15 in a series of experiments designed to measure learning, sensory/motor function, and stress reactivity. Results We report that PEA-15 null mice exhibited impaired learning in three distinct spatial tasks, while they exhibited normal fear conditioning, passive avoidance, egocentric navigation, and odor discrimination. PEA-15 null mice also had deficient forepaw strength and in limited instances, heightened stress reactivity and/or anxiety. However, these non-cognitive variables did not appear to account for the observed spatial learning impairments. The null mice maintained normal weight, pain sensitivity, and coordination when compared to wild type controls. Conclusion We found that PEA-15 null mice have spatial learning disabilities that are similar to those of mice where ERK or RSK2 function is impaired. We suggest PEA-15 may be an essential regulator of ERK-dependent spatial learning.

  18. Physical Performance Is Associated with Working Memory in Older People with Mild to Severe Cognitive Impairment

    Directory of Open Access Journals (Sweden)

    K. M. Volkers

    2014-01-01

    Full Text Available Background. Physical performances and cognition are positively related in cognitively healthy people. The aim of this study was to examine whether physical performances are related to specific cognitive functioning in older people with mild to severe cognitive impairment. Methods. This cross-sectional study included 134 people with a mild to severe cognitive impairment (mean age 82 years. Multiple linear regression was performed, after controlling for covariates and the level of global cognition, with the performances on mobility, strength, aerobic fitness, and balance as predictors and working memory and episodic memory as dependent variables. Results. The full models explain 49–57% of the variance in working memory and 40–43% of episodic memory. Strength, aerobic fitness, and balance are significantly associated with working memory, explaining 3–7% of its variance, irrespective of the severity of the cognitive impairment. Physical performance is not related to episodic memory in older people with mild to severe cognitive impairment. Conclusions. Physical performance is associated with working memory in older people with cognitive impairment. Future studies should investigate whether physical exercise for increased physical performance can improve cognitive functioning. This trial is registered with ClinicalTrials.gov NTR1482.

  19. Communication impairment and activity limitation in stroke patients with severe aphasia.

    Science.gov (United States)

    Darrigrand, Benedicte; Dutheil, Sabine; Michelet, Valerie; Rereau, Stephanie; Rousseaux, Marc; Mazaux, Jean-Michel

    2011-01-01

    This study investigated how patients with severe aphasia communicated in daily living, which verbal and non-verbal communication skills were spared and which were impaired, and whether activity limitations in communication are related to verbal impairments. Twenty-seven patients with severe aphasia and 9 with moderate aphasia originating from a sample of 102 aphasic persons followed up in a French regional survey were assessed with a communication test and a communication activity limitation questionnaire 12-18 months after a first stroke. Patients with severe aphasia suffered severe activity limitations in communication, with performance 3-fold lower than that of patients with moderate aphasia, and 4-fold lower than scores attained by normals. Both aphasia severity and communication disability at follow-up were related to the initial severity of aphasia. Using a phone, credit card and a chequebook, reading and filling in administrative documents, and communication behaviours involved in social life were the most severely impaired. Non-verbal communication performance was not related to aphasia severity. We conclude that there is a great need for speech therapy research to develop new compensatory or alternative strategies for patients with severe aphasia.

  20. The chemotherapeutic agent paclitaxel selectively impairs learning while sparing source memory and spatial memory.

    Science.gov (United States)

    Smith, Alexandra E; Slivicki, Richard A; Hohmann, Andrea G; Crystal, Jonathon D

    2017-03-01

    Chemotherapeutic agents are widely used to treat patients with systemic cancer. The efficacy of these therapies is undermined by their adverse side-effect profiles such as cognitive deficits that have a negative impact on the quality of life of cancer survivors. Cognitive side effects occur across a variety of domains, including memory, executive function, and processing speed. Such impairments are exacerbated under cognitive challenges and a subgroup of patients experience long-term impairments. Episodic memory in rats can be examined using a source memory task. In the current study, rats received paclitaxel, a taxane-derived chemotherapeutic agent, and learning and memory functioning was examined using the source memory task. Treatment with paclitaxel did not impair spatial and episodic memory, and paclitaxel treated rats were not more susceptible to cognitive challenges. Under conditions in which memory was not impaired, paclitaxel treatment impaired learning of new rules, documenting a decreased sensitivity to changes in experimental contingencies. These findings provide new information on the nature of cancer chemotherapy-induced cognitive impairments, particularly regarding the incongruent vulnerability of episodic memory and new learning following treatment with paclitaxel. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Visual-motor integration performance in children with severe specific language impairment.

    Science.gov (United States)

    Nicola, K; Watter, P

    2016-09-01

    This study investigated (1) the visual-motor integration (VMI) performance of children with severe specific language impairment (SLI), and any effect of age, gender, socio-economic status and concomitant speech impairment; and (2) the relationship between language and VMI performance. It is hypothesized that children with severe SLI would present with VMI problems irrespective of gender and socio-economic status; however, VMI deficits will be more pronounced in younger children and those with concomitant speech impairment. Furthermore, it is hypothesized that there will be a relationship between VMI and language performance, particularly in receptive scores. Children enrolled between 2000 and 2008 in a school dedicated to children with severe speech-language impairments were included, if they met the criteria for severe SLI with or without concomitant speech impairment which was verified by a government organization. Results from all initial standardized language and VMI assessments found during a retrospective review of chart files were included. The final study group included 100 children (males = 76), from 4 to 14 years of age with mean language scores at least 2SD below the mean. For VMI performance, 52% of the children scored below -1SD, with 25% of the total group scoring more than 1.5SD below the mean. Age, gender and the addition of a speech impairment did not impact on VMI performance; however, children living in disadvantaged suburbs scored significantly better than children residing in advantaged suburbs. Receptive language scores of the Clinical Evaluation of Language Fundamentals was the only score associated with and able to predict VMI performance. A small subgroup of children with severe SLI will also have poor VMI skills. The best predictor of poor VMI is receptive language scores on the Clinical Evaluation of Language Fundamentals. Children with poor receptive language performance may benefit from VMI assessment and multidisciplinary

  2. Long-term heavy ketamine use is associated with spatial memory impairment and altered hippocampal activation

    Directory of Open Access Journals (Sweden)

    Celia J A Morgan

    2014-12-01

    Full Text Available Ketamine, a non-competitive N-methyl-D-aspartate receptor antagonist, is rising in popularity as a drug of abuse. Preliminary evidence suggests that chronic, heavy ketamine use may have profound effects on spatial memory but the mechanism of these deficits is as yet unclear. This study aimed to examine the neural mechanism by which heavy ketamine use impairs spatial memory processing. In a sample of 11 frequent ketamine users and 15 polydrug controls, matched for IQ, age and years in education. We used fMRI utilising an ROI approach to examine the neural activity of three regions known to support successful navigation; the hippocampus, parahippocampal gyrus and the caudate nucleus during a virtual reality task of spatial memory. Frequent ketamine users displayed spatial memory deficits, accompanied by and related to, reduced activation in both the right hippocampus and left parahippocampal gyrus during navigation from memory, and in the left caudate during memory updating, compared to controls. Ketamine users also exhibited schizotypal and dissociative symptoms that were related to hippocampal activation. Impairments in spatial memory observed in ketamine users are related to changes in medial temporal lobe activation. Disrupted medial temporal lobe function may be a consequence of chronic ketamine abuse and may relate to schizophrenia-like symptomatology observed in ketamine users.

  3. Spatial navigation impairment in the development of Alzheimer´s disease

    Czech Academy of Sciences Publication Activity Database

    Vlček, Kamil; Ort, Michael; Laczó, J.; Vajnerová, O.; Blahna, Karel; Vyhnálek, M.; Hort, J.

    2007-01-01

    Roč. 11, Suppl.3 (2007), s. 44-48 ISSN 1211-7579 R&D Projects: GA MŠk(CZ) 1M0517; GA ČR(CZ) GA309/05/0693; GA ČR(CZ) GA309/06/1231 Institutional research plan: CEZ:AV0Z50110509 Keywords : mild cognitive impairment * spatial navigation * Alzheimer ’s Disease Subject RIV: FH - Neurology

  4. Impairment of the spatial learning and memory induced by learned helplessness and chronic mild stress.

    Science.gov (United States)

    Song, Li; Che, Wang; Min-Wei, Wang; Murakami, Yukihisa; Matsumoto, Kinzo

    2006-02-01

    Increasing evidences indicate the concurrence and interrelationship of depression and cognitive impairments. The present study was undertaken to investigate the effects of two depressive animal models, learned helplessness (LH) and chronic mild stress (CMS), on the cognitive functions of mice in the Morris water maze task. Our results demonstrated that both LH and CMS significantly decreased the cognitive performance of stressed mice in the water maze task. The escaping latency to the platform was prolonged and the probe test percentage in the platform quadrant was reduced. These two models also increased the plasma corticosterone concentration and decreased the brain derived neurotrophic factor (BDNF) and cAMP-response element-biding protein (CREB) messenger ribonucleic acid (mRNA) levels in hippocampus, which might cause the spatial cognition deficits. Repeated treatment with antidepressant drugs, imipramine (Imi) and fluoxetine (Flu), significantly reduced the plasma corticosterone concentration and enhanced the BDNF and CREB levels. Furthermore, antidepressant treated animals showed an ameliorated cognitive performance compared with the vehicle treated stressed animals. These data suggest that both LH and CMS impair the spatial cognitive function and repeated treatment with antidepressant drugs decreases the prevalence of cognitive impairments induced by these two animal models. Those might in part be attributed to the reduced plasma corticosterone and enhanced hippocampal BDNF and CREB expressions. This study provided a better understanding of molecular mechanisms underlying interactions of depression and cognitive impairments, although animal models used in this study can mimic only some aspects of depression or cognition of human.

  5. Select overexpression of homer1a in dorsal hippocampus impairs spatial working memory

    Directory of Open Access Journals (Sweden)

    Tansu Celikel

    2007-10-01

    Full Text Available Long Homer proteins forge assemblies of signaling components involved in glutamate receptor signaling in postsynaptic excitatory neurons, including those underlying synaptic transmission and plasticity. The short immediate-early gene (IEG Homer1a can dynamically uncouple these physical associations by functional competition with long Homer isoforms. To examine the consequences of Homer1amediated uncoupling for synaptic plasticity and behavior, we generated forebrain-specific tetracycline (tet controlled expression of Venus-tagged Homer1a (H1aV in mice. We report that sustained overexpression of H1aV impaired spatial working but not reference memory. Most notably, a similar impairment was observed when H1aV expression was restricted to the dorsal hippocampus (HP, which identifies this structure as the principal cortical area for spatial working memory. Interestingly, H1aV overexpression also abolished maintenance of CA3-CA1 long-term potentiation (LTP. These impairments, generated by sustained high Homer1a levels, identify a requirement for long Homer forms in synaptic plasticity and temporal encoding of spatial memory.

  6. Patterns of preserved and impaired spatial memory in a case of developmental amnesia

    Directory of Open Access Journals (Sweden)

    R Shayna eRosenbaum

    2015-05-01

    Full Text Available The hippocampus is believed to have evolved to support allocentric spatial representations of environments as well as the details of personal episodes that occur within them, whereas other brain structures are believed to support complementary egocentric spatial representations. Studies of patients with adult-onset lesions lend support to these distinctions for newly encountered places but suggest that with time and/or experience, schematic aspects of environments can exist independent of the hippocampus. Less clear is the quality of spatial memories acquired in individuals with impaired episodic memory in the context of a hippocampal system that did not develop normally. Here we describe a detailed investigation of the integrity of spatial representations of environments navigated repeatedly over many years in the rare case of H.C., a person with congenital absence of the mammillary bodies and abnormal hippocampal and fornix development. H.C. and controls who had extensive experience navigating the residential and downtown areas known to H.C. were tested on mental navigation tasks that assess the identity, location, and spatial relations among landmarks, and the ability to represent routes. H.C. was able to represent distances and directions between familiar landmarks and provide accurate, though inefficient, route descriptions. However, difficulties producing detailed spatial features on maps and accurately ordering more than two landmarks that are in close proximity to one another along a route suggest a spatial representation that includes only coarse, schematic information that lacks coherence and that cannot be used flexibly. This pattern of performance is considered in the context of other areas of preservation and impairment exhibited by H.C. and suggests that the allocentric-egocentric dichotomy with respect to hippocampal and extended hippocampal system function may need to be reconsidered.

  7. Parent and Teacher Ratings of Communication among Children with Severe Disabilities and Visual Impairment/Blindness

    Science.gov (United States)

    Cascella, Paul W.; Trief, Ellen; Bruce, Susan M.

    2012-01-01

    Three trends emerged from independent parent and teacher ratings of receptive communication and expressive forms and functions among students with severe disabilities and visual impairment/blindness. Parents had higher ratings than teachers, receptive communication was rated the highest, and no skills occurred often. Implications are discussed for…

  8. Culturally Responsive Instruction for Students with Multiple or Severe Physical Impairments

    Science.gov (United States)

    Glimps, Blanche Jackson; Ford, Theron

    2006-01-01

    Are there students with physical disabilities who are so severely impaired that their culture can not be taken into consideration? Growing numbers of preschool and school age children with such disabilities are from non-European countries including Africa, South America, East Asia, and the Caribbean Islands. In addition, children who are American…

  9. Literacy Instruction for Young Children with Severe Speech and Physical Impairments: A Systematic Review

    Science.gov (United States)

    Stauter, Donna W.; Myers, Sarah R.; Classen, Audra I.

    2017-01-01

    Children with severe speech and physical impairment who use augmentative and alternative communication (AAC) present unique challenges in literacy development. Traditional reading instruction has not met these students' needs. Occupational therapy and speech therapy provide supports to mediate limitations to literacy instruction. A systematic…

  10. Eye disorder differentiates seasonality outcomes in persons with severe visual impairment

    DEFF Research Database (Denmark)

    Madsen, Heller; Dam, Henrik; Hageman, Ida

    2017-01-01

    Background Light plays a crucial role in both the pathogenesis and treatment of seasonal affective disorder (SAD). Consequently decreased retinal sensitivity to light has been suggested to be a risk factor for SAD. In a population of persons with severe visual impairment we recently found a highly...

  11. Severe carotid stenosis and impaired cerebral hemodynamics can influence cognitive deterioration.

    Science.gov (United States)

    Balestrini, Simona; Perozzi, Cecilia; Altamura, Claudia; Vernieri, Fabrizio; Luzzi, Simona; Bartolini, Marco; Provinciali, Leandro; Silvestrini, Mauro

    2013-06-04

    To evaluate whether severe carotid stenosis and related hemodynamics impairment may increase the risk of cognitive deterioration in asymptomatic subjects. A total of 210 subjects with unilateral asymptomatic severe carotid stenosis and 109 healthy controls were included and prospectively evaluated for a 36-month period. At entry, demographics, vascular risk profile, and pharmacologic treatments were defined. Cerebral hemodynamics was assessed by transcranial Doppler-based breath-holding index (BHI) test. Cognitive status was evaluated with the Mini-Mental State Examination (MMSE) at entry and at the end of the follow-up period. Cognitive deterioration was defined as a decrease in the MMSE score of 3 points or more during the overall follow-up period. Subjects with carotid stenosis showed an increased probability of developing cognitive deterioration compared with the group without stenosis (odds ratio [OR] 4.16 [95% confidence interval (CI) 1.89-9.11]; p < 0.001). The presence of an impaired BHI ipsilateral to the stenosis was associated with an increased incidence of reduction in cognitive performance (OR 14.66 [95% CI 7.51-28.59]; p < 0.001). Our findings show that the presence of a severe carotid stenosis influences cognitive deterioration over a 36-month period in asymptomatic subjects. An associated hemodynamic impairment significantly increases the risk. Evaluation of functional consequences of carotid stenosis may offer the opportunity to select a group with an increased risk of developing cognitive impairment from subjects with asymptomatic severe carotid stenosis.

  12. Psychotic reactions to daily life stress and dopamine function in people with severe hearing impairment

    NARCIS (Netherlands)

    Gevonden, M. J.; Myin-Germeys, I.; van den Brink, W.; van Os, J.; Selten, J. P.; Booij, J.

    2015-01-01

    Minor stresses measured in daily life have repeatedly been associated with increased momentary psychotic experiences, both in individuals with psychotic disorders and in persons who are genetically at an increased risk for these disorders. Severe hearing impairment (SHI) is an environmental risk

  13. Application of the Mitrofanoff principle in children with severe impairment of bladder function

    NARCIS (Netherlands)

    Heij, H. A.; Ekkelkamp, S.; Moorman-Voestermans, C. G.; Vos, A.

    1997-01-01

    Treatment of children with severe impairment of bladder function requires a large-volume, low-pressure reservoir combined with a continent, easily catheterizable valve. The Mitrofanoff principle (MP) appears to meet these requirements. Between 1986 and 1993, the MP was applied in 15 children (4

  14. A NOVEL EFFECT OF DIOXIN: EXPOSURE DURING PREGNANCY SEVERELY IMPAIRS MAMMARY GLAND DIFFERENTIATION

    Science.gov (United States)

    A novel effect of dioxin: Exposure during pregnancy severely impairs mammary gland differentiation.Beth A. Vorderstrasse1, Suzanne E. Fenton2, Andrea A. Bohn3, Jennifer A. Cundiff1, and B. Paige Lawrence1,3,4 1Department of Pharmaceutical Sciences, Washington State Universi...

  15. Visual impairments in people with severe and profound multiple disabilities: An inventory of visual functioning

    NARCIS (Netherlands)

    van den Broek, E.G.C.; Janssen, C.G.C.; van Ramshorst, T.; Deen, L.

    2006-01-01

    Background: The prevalence of visual impairments in people with severe and profound multiple disabilities (SPMD) is the subject of considerable debate and is difficult to assess. Methods: In a typical Dutch care organization, all clients with SPMD (n = 76) participated in the study and specific

  16. Using electronic storybooks to support word learning in children with severe language impairments

    NARCIS (Netherlands)

    Smeets, Daisy J. H.; van Dijken, Marianne J.; Bus, Adriana G

    2012-01-01

    Novel word learning is reported to be problematic for children with severe language impairments (SLI). In this study, we tested electronic storybooks as a tool to support vocabulary acquisition in SLI children. In Experiment 1, 29 kindergarten SLI children heard four e-books each four times: (a) two

  17. The severity of the visual impairment and practice matter for drawing ability in children.

    Science.gov (United States)

    Vinter, Annie; Bonin, Patrick; Morgan, Pascal

    2018-07-01

    Astonishing drawing capacities have been reported in children with early visual impairments. However, most of the evidence relies on single case studies. Hitherto, no study has systematically jointly investigated, in these children, the role of (1) the severity of the visual handicap, (2) age and (3) practice in drawing. The study aimed at revealing the specificities of the drawing in children deprived from vision, as compared to children with less severe visual handicap and to sighted children performing under haptic or usual visual control. 148 children aged 6-14 years had to produce 12 drawings of familiar objects. 38 had a severe visual impairment, 41 suffered from low vision, and 69 were sighted children performing either under visual condition or blindfolded under haptic control. Recognizability and other characteristics of the drawings were highly dependent on the child's degree of vision and level of drawing practice, and progressed with chronological age more clearly in the sighted children or those with low vision than in those deprived of vision. The study confirmed that all groups showed significant drawing ability, even the group totally deprived of visual experience. Furthermore, the specificities of the drawings produced by visually-impaired children appeared clearly related to their practice and the severity of their visual impairment. This should incite parents and professionals to encourage these children to practice drawing as early as possible. Copyright © 2018 Elsevier Ltd. All rights reserved.

  18. Severe Visual Impairments in Infants and Toddlers in the United States

    Science.gov (United States)

    Hatton, Deborah D.; Ivy, Sarah E.; Boyer, Charles

    2013-01-01

    Introduction: This article describes the most prevalent visual conditions and other demographic characteristics of 5,931 young children with severe visual impairments in 28 states in the United States, the largest sample reported to date. The information presented in this article can assist in planning and implementing programs. Method: The data…

  19. Gender dimorphism in aspartame-induced impairment of spatial cognition and insulin sensitivity.

    Directory of Open Access Journals (Sweden)

    Kate S Collison

    Full Text Available Previous studies have linked aspartame consumption to impaired retention of learned behavior in rodents. Prenatal exposure to aspartame has also been shown to impair odor-associative learning in guinea pigs; and recently, aspartame-fed hyperlipidemic zebrafish exhibited weight gain, hyperglycemia and acute swimming defects. We therefore investigated the effects of chronic lifetime exposure to aspartame, commencing in utero, on changes in blood glucose parameters, spatial learning and memory in C57BL/6J mice. Morris Water Maze (MWM testing was used to assess learning and memory, and a random-fed insulin tolerance test was performed to assess glucose homeostasis. Pearson correlation analysis was used to investigate the associations between body characteristics and MWM performance outcome variables. At 17 weeks of age, male aspartame-fed mice exhibited weight gain, elevated fasting glucose levels and decreased insulin sensitivity compared to controls (P<0.05. Females were less affected, but had significantly raised fasting glucose levels. During spatial learning trials in the MWM (acquisition training, the escape latencies of male aspartame-fed mice were consistently higher than controls, indicative of learning impairment. Thigmotactic behavior and time spent floating directionless was increased in aspartame mice, who also spent less time searching in the target quadrant of the maze (P<0.05. Spatial learning of female aspartame-fed mice was not significantly different from controls. Reference memory during a probe test was affected in both genders, with the aspartame-fed mice spending significantly less time searching for the former location of the platform. Interestingly, the extent of visceral fat deposition correlated positively with non-spatial search strategies such as floating and thigmotaxis, and negatively with time spent in the target quadrant and swimming across the location of the escape platform. These data suggest that lifetime

  20. SPATIAL MEMORY IMPAIRMENT AND HIPPOCAMPAL CELL LOSS INDUCED BY OKADAIC ACID (EXPERIMENTAL STUDY).

    Science.gov (United States)

    Chighladze, M; Dashniani, M; Beselia, G; Kruashvili, L; Naneishvili, T

    2016-01-01

    In the present study, we evaluated and compared effect of intracerebroventricular (ICV) and intrahippocampal bilateral microinjection of okadaic acid (OA) on spatial memory function assessed in one day water maze paradigm and hippocampal structure in rats. Rats were divided in following groups: Control(icv) - rats injected with ICV and aCSF; Control(hipp) - rats injected intrahippocampally with aCSF; OAicv - rats injected with ICV and OA; OAhipp - rats injected intrahippocampally with OA. Nissl staining of hippocampal sections showed that the pyramidal cell loss in OAhipp group is significantly higher than that in the OAicv. The results of behavioral experiments showed that ICV or intrahippocampal bilateral microinjection of OA did not affect learning process and short-term spatial memory but induced impairment in spatial long-term memory assessed in probe test performance 24 h after training. OA-induced spatial memory impairment may be attributed to the hippocampal cell death. Based on these results OA induced memory deficit and hippocampal cell loss in rat may be considered as a potential animal model for preclinical evaluation of antidementic drug activity.

  1. Static and Dynamic Balance in Congenital Severe to Profound Hearing-Impaired Children

    Directory of Open Access Journals (Sweden)

    Farideh HajiHeydari

    2011-09-01

    Full Text Available Background and Aim: Research conducted since the early 1900s has consistently identified differences between deaf and hearing children on performance of a wide variety of motor tasks, most notably balance. Our study was performed to test static and dynamic balance skills in congenital severe to profound hearing impaired children in comparison with normal age-matched children.Methods: This cross-sectional study was conducted on 30 severe to profound hearing impaired and 40 normal children with age 6 to 10 years old. Bruininks-Oseretsky test of motor proficiency 2, balance subset with 9 parts was used for evaluation of balance skills.Results: Hearing-impaired children showed 16.7 to 100% fail results in 7 parts of the balance subset. In normal children fail result was revealed just in 3 parts of the balance subset from 2.5 to 57.5%, and differences between two groups were significant (p<0.0001. There was a significant difference between two groups in two static balance skills of standing on one leg on a line and standing on one leg on a balance beam with eyes closed (p<0.0001.conclusion: It seems that development of static balance skills are longer than dynamic ones. Because severe to profound hearing-impaired children showed more weakness than normal children in both static and dynamic balance abilities, functional tests of balance proficiency can help to identify balance disorders in these children.

  2. Sleep deprivation impairs spatial retrieval but not spatial learning in the non-human primate grey mouse lemur.

    Directory of Open Access Journals (Sweden)

    Anisur Rahman

    Full Text Available A bulk of studies in rodents and humans suggest that sleep facilitates different phases of learning and memory process, while sleep deprivation (SD impairs these processes. Here we tested the hypothesis that SD could alter spatial learning and memory processing in a non-human primate, the grey mouse lemur (Microcebus murinus, which is an interesting model of aging and Alzheimer's disease (AD. Two sets of experiments were performed. In a first set of experiments, we investigated the effects of SD on spatial learning and memory retrieval after one day of training in a circular platform task. Eleven male mouse lemurs aged between 2 to 3 years were tested in three different conditions: without SD as a baseline reference, 8 h of SD before the training and 8 h of SD before the testing. The SD was confirmed by electroencephalographic recordings. Results showed no effect of SD on learning when SD was applied before the training. When the SD was applied before the testing, it induced an increase of the amount of errors and of the latency prior to reach the target. In a second set of experiments, we tested the effect of 8 h of SD on spatial memory retrieval after 3 days of training. Twenty male mouse lemurs aged between 2 to 3 years were tested in this set of experiments. In this condition, the SD did not affect memory retrieval. This is the first study that documents the disruptive effects of the SD on spatial memory retrieval in this primate which may serve as a new validated challenge to investigate the effects of new compounds along physiological and pathological aging.

  3. Severe hindrance of viral infection propagation in spatially extended hosts.

    Directory of Open Access Journals (Sweden)

    José A Capitán

    Full Text Available The production of large progeny numbers affected by high mutation rates is a ubiquitous strategy of viruses, as it promotes quick adaptation and survival to changing environments. However, this situation often ushers in an arms race between the virus and the host cells. In this paper we investigate in depth a model for the dynamics of a phenotypically heterogeneous population of viruses whose propagation is limited to two-dimensional geometries, and where host cells are able to develop defenses against infection. Our analytical and numerical analyses are developed in close connection to directed percolation models. In fact, we show that making the space explicit in the model, which in turn amounts to reducing viral mobility and hindering the infective ability of the virus, connects our work with similar dynamical models that lie in the universality class of directed percolation. In addition, we use the fact that our model is a multicomponent generalization of the Domany-Kinzel probabilistic cellular automaton to employ several techniques developed in the past in that context, such as the two-site approximation to the extinction transition line. Our aim is to better understand propagation of viral infections with mobility restrictions, e.g., in crops or in plant leaves, in order to inspire new strategies for effective viral control.

  4. Impaired early visual response modulations to spatial information in chronic schizophrenia

    Science.gov (United States)

    Knebel, Jean-François; Javitt, Daniel C.; Murray, Micah M.

    2011-01-01

    Early visual processing stages have been demonstrated to be impaired in schizophrenia patients and their first-degree relatives. The amplitude and topography of the P1 component of the visual evoked potential (VEP) are both affected; the latter of which indicates alterations in active brain networks between populations. At least two issues remain unresolved. First, the specificity of this deficit (and suitability as an endophenotype) has yet to be established, with evidence for impaired P1 responses in other clinical populations. Second, it remains unknown whether schizophrenia patients exhibit intact functional modulation of the P1 VEP component; an aspect that may assist in distinguishing effects specific to schizophrenia. We applied electrical neuroimaging analyses to VEPs from chronic schizophrenia patients and healthy controls in response to variation in the parafoveal spatial extent of stimuli. Healthy controls demonstrated robust modulation of the VEP strength and topography as a function of the spatial extent of stimuli during the P1 component. By contrast, no such modulations were evident at early latencies in the responses from patients with schizophrenia. Source estimations localized these deficits to the left precuneus and medial inferior parietal cortex. These findings provide insights on potential underlying low-level impairments in schizophrenia. PMID:21764264

  5. Validation of the baseline severity stratification of objective functional impairment in lumbar degenerative disc disease.

    Science.gov (United States)

    Stienen, Martin N; Smoll, Nicolas R; Joswig, Holger; Corniola, Marco V; Schaller, Karl; Hildebrandt, Gerhard; Gautschi, Oliver P

    2017-05-01

    OBJECTIVE The Timed Up and Go (TUG) test is a simple, objective, and standardized method to measure objective functional impairment (OFI) in patients with lumbar degenerative disc disease (DDD). The objective of the current work was to validate the OFI baseline severity stratification (BSS; with levels of "none," "mild," "moderate," and "severe"). METHODS Data were collected in a prospective IRB-approved 2-center study. Patients were assessed with a comprehensive panel of scales for measuring pain (visual analog scale [VAS] for back and leg pain), functional impairment (Roland-Morris Disability Index [RMDI] and Oswestry Disability Index [ODI]), and health-related quality of life (HRQOL; EQ-5D and SF-12). OFI BSS was determined using age- and sex-adjusted cutoff values. RESULTS A total of 375 consecutive patients scheduled for lumbar spine surgery were included. Each 1-step increase on the OFI BSS corresponded to an increase of 0.53 in the back pain VAS score, 0.69 in the leg pain VAS score, 1.81 points in the RMDI, and 5.93 points in the ODI, as well as to a decrease in HRQOL of -0.073 in the EQ-5D, -1.99 in the SF-12 physical component summary (PCS), and -1.62 in the SF-12 mental component summary (MCS; all p measure of functional impairment for use in daily clinical practice. The presence of OFI indicates the presence of significant functional impairment on subjective outcome measures.

  6. Repeated Sleep Restriction in Adolescent Rats Altered Sleep Patterns and Impaired Spatial Learning/Memory Ability

    Science.gov (United States)

    Yang, Su-Rong; Sun, Hui; Huang, Zhi-Li; Yao, Ming-Hui; Qu, Wei-Min

    2012-01-01

    Study Objectives: To investigate possible differences in the effect of repeated sleep restriction (RSR) during adolescence and adulthood on sleep homeostasis and spatial learning and memory ability. Design: The authors examined electroencephalograms of rats as they were subjected to 4-h daily sleep deprivation that continued for 7 consecutive days and assessed the spatial learning and memory by Morris water maze test (WMT). Participants: Adolescent and adult rats. Measurements and Results: Adolescent rats exhibited a similar amount of rapid eye movement (REM) and nonrapid eye movement (NREM) sleep with higher slow wave activity (SWA, 0.5-4 Hz) and fewer episodes and conversions with prolonged durations, indicating they have better sleep quality than adult rats. After RSR, adult rats showed strong rebound of REM sleep by 31% on sleep deprivation day 1; this value was 37% on sleep deprivation day 7 in adolescents compared with 20-h baseline level. On sleep deprivation day 7, SWA in adult and adolescent rats increased by 47% and 33%, and such elevation lasted for 5 h and 7 h, respectively. Furthermore, the authors investigated the effects of 4-h daily sleep deprivation immediately after the water maze training sessions on spatial cognitive performance. Adolescent rats sleep-restricted for 7 days traveled a longer distance to find the hidden platform during the acquisition training and had fewer numbers of platform crossings in the probe trial than those in the control group, something that did not occur in the sleep-deprived adult rats. Conclusions: Repeated sleep restriction (RSR) altered sleep profiles and mildly impaired spatial learning and memory capability in adolescent rats. Citation: Yang SR; Sun H; Huang ZL; Yao MH; Qu WM. Repeated sleep restriction in adolescent rats altered sleep patterns and impaired spatial learning/memory ability. SLEEP 2012;35(6):849-859. PMID:22654204

  7. Gender dimorphism in aspartame-induced impairment of spatial cognition and insulin sensitivity.

    Science.gov (United States)

    Collison, Kate S; Makhoul, Nadine J; Zaidi, Marya Z; Saleh, Soad M; Andres, Bernard; Inglis, Angela; Al-Rabiah, Rana; Al-Mohanna, Futwan A

    2012-01-01

    Previous studies have linked aspartame consumption to impaired retention of learned behavior in rodents. Prenatal exposure to aspartame has also been shown to impair odor-associative learning in guinea pigs; and recently, aspartame-fed hyperlipidemic zebrafish exhibited weight gain, hyperglycemia and acute swimming defects. We therefore investigated the effects of chronic lifetime exposure to aspartame, commencing in utero, on changes in blood glucose parameters, spatial learning and memory in C57BL/6J mice. Morris Water Maze (MWM) testing was used to assess learning and memory, and a random-fed insulin tolerance test was performed to assess glucose homeostasis. Pearson correlation analysis was used to investigate the associations between body characteristics and MWM performance outcome variables. At 17 weeks of age, male aspartame-fed mice exhibited weight gain, elevated fasting glucose levels and decreased insulin sensitivity compared to controls (Pdifferent from controls. Reference memory during a probe test was affected in both genders, with the aspartame-fed mice spending significantly less time searching for the former location of the platform. Interestingly, the extent of visceral fat deposition correlated positively with non-spatial search strategies such as floating and thigmotaxis, and negatively with time spent in the target quadrant and swimming across the location of the escape platform. These data suggest that lifetime exposure to aspartame, commencing in utero, may affect spatial cognition and glucose homeostasis in C57BL/6J mice, particularly in males.

  8. Deficits of spatial and task-related attentional selection in mild cognitive impairment and Alzheimer's disease.

    Science.gov (United States)

    Redel, P; Bublak, P; Sorg, C; Kurz, A; Förstl, H; Müller, H J; Schneider, W X; Perneczky, R; Finke, K

    2012-01-01

    Visual selective attention was assessed with a partial-report task in patients with probable Alzheimer's disease (AD), amnestic mild cognitive impairment (MCI), and healthy elderly controls. Based on Bundesen's "theory of visual attention" (TVA), two parameters were derived: top-down control of attentional selection, representing task-related attentional weighting for prioritizing relevant visual objects, and spatial distribution of attentional weights across the left and the right hemifield. Compared with controls, MCI patients showed significantly reduced top-down controlled selection, which was further deteriorated in AD subjects. Moreover, attentional weighting was significantly unbalanced across hemifields in MCI and tended to be more lateralized in AD. Across MCI and AD patients, carriers of the apolipoprotein E ε4 allele (ApoE4) displayed a leftward spatial bias, which was the more pronounced the younger the ApoE4-positive patients and the earlier disease onset. These results indicate that impaired top-down control may be linked to early dysfunction of fronto-parietal networks. An early temporo-parietal interhemispheric asymmetry might cause a pathological spatial bias which is associated with ApoE4 genotype and may therefore function as early cognitive marker of upcoming AD. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Frontal and parietal theta burst TMS impairs working memory for visual-spatial conjunctions.

    Science.gov (United States)

    Morgan, Helen M; Jackson, Margaret C; van Koningsbruggen, Martijn G; Shapiro, Kimron L; Linden, David E J

    2013-03-01

    In tasks that selectively probe visual or spatial working memory (WM) frontal and posterior cortical areas show a segregation, with dorsal areas preferentially involved in spatial (e.g. location) WM and ventral areas in visual (e.g. object identity) WM. In a previous fMRI study [1], we showed that right parietal cortex (PC) was more active during WM for orientation, whereas left inferior frontal gyrus (IFG) was more active during colour WM. During WM for colour-orientation conjunctions, activity in these areas was intermediate to the level of activity for the single task preferred and non-preferred information. To examine whether these specialised areas play a critical role in coordinating visual and spatial WM to perform a conjunction task, we used theta burst transcranial magnetic stimulation (TMS) to induce a functional deficit. Compared to sham stimulation, TMS to right PC or left IFG selectively impaired WM for conjunctions but not single features. This is consistent with findings from visual search paradigms, in which frontal and parietal TMS selectively affects search for conjunctions compared to single features, and with combined TMS and functional imaging work suggesting that parietal and frontal regions are functionally coupled in tasks requiring integration of visual and spatial information. Our results thus elucidate mechanisms by which the brain coordinates spatially segregated processing streams and have implications beyond the field of working memory. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Sex-specific impairment of spatial memory in rats following a reminder of predator stress.

    Science.gov (United States)

    Burke, Hanna M; Robinson, Cristina M; Wentz, Bethany; McKay, Jerel; Dexter, Kyle W; Pisansky, Julia M; Talbot, Jeffery N; Zoladz, Phillip R

    2013-07-01

    It has been suggested that cognitive impairments exhibited by people with post-traumatic stress disorder (PTSD) result from intrusive, flashback memories transiently interfering with ongoing cognitive processing. Researchers have further speculated that females are more susceptible to developing PTSD because they form stronger traumatic memories than males, hence females may be more sensitive to the negative effects of intrusive memories on cognition. We have examined how the reminder of a naturalistic stress experience would affect rat spatial memory and if sex was a contributing factor to such effects. Male and female Sprague-Dawley rats were exposed, without contact, to an adult female cat for 30 min. Five weeks later, the rats were trained to locate a hidden platform in the radial-arm water maze and given a single long-term memory test trial 24 h later. Before long-term memory testing, the rats were given a 30-min reminder of the cat exposure experienced 5 weeks earlier. The results indicated that the stress reminder impaired spatial memory in the female rats only. Control manipulations revealed that this effect was not attributable to the original cat exposure adversely impacting learning that occurred 5 weeks later, or to merely exposing rats to a novel environment or predator-related cues immediately before testing. These findings provide evidence that the reminder of a naturalistic stressful experience can impair cognitive processing in rats; moreover, since female rats were more susceptible to the memory-impairing effects of the stress reminder, the findings could lend insight into the existing sex differences in susceptibility to PTSD.

  11. Chronic impairments in spatial learning and memory in rats previously exposed to chlorpyrfos or diisopropylfluorophosphate.

    Science.gov (United States)

    Terry, A V; Beck, W D; Warner, S; Vandenhuerk, L; Callahan, P M

    2012-01-01

    The acute toxicity of organophosphates (OPs) has been studied extensively; however, much less attention has been given to the subject of repeated exposures that are not associated with overt signs of toxicity (i.e., subthreshold exposures). The objective of this study was to determine if the protracted spatial learning impairments we have observed previously after repeated subthreshold exposures to the insecticide chlorpyrifos (CPF) or the alkylphosphate OP, diisopropylfluorophosphate (DFP) persisted for longer periods after exposure. Male Wistar rats (beginning at two months of age) were initially injected subcutaneously with CPF (10.0 or 18.0mg/kg) or DFP (0.25 or 0.75 mg/kg) every other day for 30 days. After an extended OP-free washout period (behavioral testing begun 50 days after the last OP exposure), rats previously exposed to CPF, but not DFP, were impaired in a radial arm maze (RAM) win-shift task as well as a delayed non-match to position procedure. Later experiments (i.e., beginning 140 days after the last OP exposure) revealed impairments in the acquisition of a water maze hidden platform task associated with both OPs. However, only rats previously exposed to DFP were impaired in a second phase of testing when the platform location was changed (indicative of deficits of cognitive flexibility). These results indicate, therefore, that repeated, subthreshold exposures to CPF and DFP may lead to chronic deficits in spatial learning and memory (i.e., long after cholinesterase inhibition has abated) and that insecticide and alkylphosphate-based OPs may have differential effects depending on the cognitive domain evaluated. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Spatial navigation testing discriminates two types of amnestic mild cognitive impairment

    Czech Academy of Sciences Publication Activity Database

    Laczó, J.; Vlček, Kamil; Vyhnálek, M.; Vajnerová, O.; Ort, M.; Holmerová, I.; Tolar, M.; Andel, R.; Bojar, M.; Hort, J.

    2009-01-01

    Roč. 202, č. 2 (2009), s. 252-259 ISSN 0166-4328 R&D Projects: GA MŠk(CZ) 1M0517; GA MŠk(CZ) LC554; GA ČR(CZ) GA309/09/1053; GA ČR(CZ) GA309/09/0286 Institutional research plan: CEZ:AV0Z50110509 Keywords : mild cognitive impairment * spatial navigation * Alzheimer’s disease Subject RIV: FH - Neurology Impact factor: 3.220, year: 2009

  13. Are there gender differences in wellbeing related to work status among persons with severe impairments?

    Science.gov (United States)

    Reine, Ieva; Palmer, Edward; Sonnander, Karin

    2016-12-01

    The aim of this study was to analyse gender differences in wellbeing, as related to work status, among working-age people with severe impairments. This study is based on register and survey data for a sample of 7298 persons, drawn from the entire Swedish population of 15,515 working-age people 16-64 years old who, at the end of 2010, received Sweden's unique personal assistance allowance, an allowance paid from the Swedish Social Insurance Agency (SSIA) to persons with severe impairments, enabling them to pay for assistants to support them in the functions of daily life. Logistic regression models were used to estimate the strength of relations between six measures of wellbeing, work status (not working, irregular work and regular work) and gender, together with key confounders. Of the persons surveyed, 21% responded that they had regular work. Gender differences were found for all confounders, except for age. They were mostly in favour of men, which could reflect the general pattern in the labour market at large. Our results indicated there are substantial differences between non-working, irregularly working and working persons for several wellbeing aspects. This study analyses the contributions to wellbeing of work participation among working-age people with severe impairments, with a focus on gender differences. The analysis shows that work is an important determinant of the six measures of wellbeing examined, where the relationship between work participation and wellbeing is especially strong for peoples' perceived standard of living. This major finding holds for both genders; however, the data show gender imbalance, in that compared with women, there was a larger percentage of men with severe impairments who have regular work. Future research should focus on finer distinctions between the types of work and the value added of personal assistants in the work context. Measures of general health not available for this study are needed to filter out a clearer

  14. Poststroke Hemiparesis Impairs the Rate but not Magnitude of Adaptation of Spatial and Temporal Locomotor Features

    Science.gov (United States)

    Savin, Douglas N.; Tseng, Shih-Chiao; Whitall, Jill; Morton, Susanne M.

    2015-01-01

    Background Persons with stroke and hemiparesis walk with a characteristic pattern of spatial and temporal asymmetry that is resistant to most traditional interventions. It was recently shown in nondisabled persons that the degree of walking symmetry can be readily altered via locomotor adaptation. However, it is unclear whether stroke-related brain damage affects the ability to adapt spatial or temporal gait symmetry. Objective Determine whether locomotor adaptation to a novel swing phase perturbation is impaired in persons with chronic stroke and hemiparesis. Methods Participants with ischemic stroke (14) and nondisabled controls (12) walked on a treadmill before, during, and after adaptation to a unilateral perturbing weight that resisted forward leg movement. Leg kinematics were measured bilaterally, including step length and single-limb support (SLS) time symmetry, limb angle center of oscillation, and interlimb phasing, and magnitude of “initial” and “late” locomotor adaptation rates were determined. Results All participants had similar magnitudes of adaptation and similar initial adaptation rates both spatially and temporally. All 14 participants with stroke and baseline asymmetry temporarily walked with improved SLS time symmetry after adaptation. However, late adaptation rates poststroke were decreased (took more strides to achieve adaptation) compared with controls. Conclusions Mild to moderate hemiparesis does not interfere with the initial acquisition of novel symmetrical gait patterns in both the spatial and temporal domains, though it does disrupt the rate at which “late” adaptive changes are produced. Impairment of the late, slow phase of learning may be an important rehabilitation consideration in this patient population. PMID:22367915

  15. Sociodemographic status of severely disabled and visually impaired elderly people in Turkey.

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    Kıvanç, Sertaç Argun; Akova-Budak, Berna; Olcaysü, Osman Okan; Çevik, Sadık Görkem

    2016-02-01

    To identify the prevalence of ophthalmologic diseases in elderly patients who had been classified as severely disabled and to identify the ophthalmologic conditions leading to visual impairment and blindness. The medical records of 2806 patients who had applied to the Health Board of the Erzurum Region Training and Research Hospital between January 2011 and December 2012 were reviewed. One hundred ninety-nine patients aged >64 years who were classified as severely disabled with disability rates of over 50%, and who were unable to care for themselves or to move and/or communicate without help were included in the study. The most frequently seen disabilities were neurological (47.2%) and those resulting from eye diseases (17.1%). The most common ophthalmologic diseases were cataract, glaucoma, and age-related macular degeneration. The mean right and left eye visual acuities were 1.17 ± 1.10 logMAR and 1.13 ± 1.0 logMAR, respectively. Of the 60 patients with ophthalmologic diseases or conditions, 33 were blind (visual acuity worse than 20/400) and 10 were visually impaired (visual acuity worse than 20/70 but better than 20/400). Cataracts were the main cause of blindness. The mean age of the patients who were still being followed up at the time of application to the disability board was significantly lower than that of the others (p =0.015). Seventy-nine percent of the blind patients were from rural areas, and 88% of these had no regular follow-up. Among the blind and visually impaired, significantly more patients from urban areas had social security insurance (SSI) than those from rural areas (p =0.043). Nearly 64% of the blind patients were women. The follow-up rate was significantly lower in women (p =0.025). According to multinomial logistic regression analysis, the visually impaired and blind patients were more likely to have lower follow-up rates than the other types of severely disabled patients (OR: 0.231, 95% Cl: 0.077-0.688, p=0.009). Blindness gives rise

  16. Sociodemographic status of severely disabled and visually impaired elderly people in Turkey

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    Sertaç Argun Kıvanç

    2016-02-01

    Full Text Available ABSTRACT Purpose: To identify the prevalence of ophthalmologic diseases in elderly patients who had been classified as severely disabled and to identify the ophthalmologic conditions leading to visual impairment and blindness. Methods: The medical records of 2806 patients who had applied to the Health Board of the Erzurum Region Training and Research Hospital between January 2011 and December 2012 were reviewed. One hundred ninety-nine patients aged >64 years who were classified as severely disabled with disability rates of over 50%, and who were unable to care for themselves or to move and/or communicate without help were included in the study. Results: The most frequently seen disabilities were neurological (47.2% and those resulting from eye diseases (17.1%. The most common ophthalmologic diseases were cataract, glaucoma, and age-related macular degeneration. The mean right and left eye visual acuities were 1.17 ± 1.10 logMAR and 1.13 ± 1.0 logMAR, respectively. Of the 60 patients with ophthalmologic diseases or conditions, 33 were blind (visual acuity worse than 20/400 and 10 were visually impaired (visual acuity worse than 20/70 but better than 20/400. Cataracts were the main cause of blindness. The mean age of the patients who were still being followed up at the time of application to the disability board was significantly lower than that of the others (p =0.015. Seventy-nine percent of the blind patients were from rural areas, and 88% of these had no regular follow-up. Among the blind and visually impaired, significantly more patients from urban areas had social security insurance (SSI than those from rural areas (p =0.043. Nearly 64% of the blind patients were women. The follow-up rate was significantly lower in women (p =0.025. According to multinomial logistic regression analysis, the visually impaired and blind patients were more likely to have lower follow-up rates than the other types of severely disabled patients (OR: 0.231, 95

  17. Melatonin administration impairs visuo-spatial performance and inhibits neocortical long-term potentiation in rats.

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    Soto-Moyano, Rubén; Burgos, Héctor; Flores, Francisco; Valladares, Luis; Sierralta, Walter; Fernández, Victor; Pérez, Hernán; Hernández, Paula; Hernández, Alejandro

    2006-10-01

    Melatonin has been shown to inhibit long-term potentiation (LTP) in hippocampal slices of rats. Since LTP may be one of the main mechanisms by which memory traces are encoded and stored in the central nervous system, it is possible that melatonin could modulate cognitive performance by interfering with the cellular and/or molecular mechanisms involved in LTP. We investigated in rats the effects of intraperitoneally-administered melatonin (0.1, 1 and 10 mg/kg), its saline-ethanol solvent, or saline alone, on the acquisition of visuo-spatial memory as well as on the ability of the cerebral cortex to develop LTP in vivo. Visuo-spatial performance was assessed daily in rats, for 10 days, in an 8-arm radial maze, 30 min after they received a single daily dose of melatonin. Visual cortex LTP was determined in sodium pentobarbital anesthetized rats (65 mg/kg i.p.), by potentiating transcallosal evoked responses with a tetanizing train (312 Hz, 500 ms duration) 30 min after administration of a single dose of melatonin. Results showed that melatonin impaired visuo-spatial performance in rats, as revealed by the greater number of errors committed and time spent to solve the task in the radial maze. Melatonin also prevented the induction of neocortical LTP. It is concluded that melatonin, at the doses utilized in this study, could alter some forms of neocortical plasticity involved in short- and long-term visuo-spatial memories in rats.

  18. Acute administration of THC impairs spatial but not associative memory function in zebrafish.

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    Ruhl, Tim; Prinz, Nicole; Oellers, Nadine; Seidel, Nathan Ian; Jonas, Annika; Albayram, Onder; Bilkei-Gorzo, Andras; von der Emde, Gerhard

    2014-10-01

    The present study examined the effect of acute administration of endocannabinoid receptor CB1 ligand ∆-9-tetrahydrocannabinol (THC) on intracellular signalling in the brain and retrieval from two different memory systems in the zebrafish (Danio rerio). First, fish were treated with THC and changes in the phosphorylation level of mitogen-activated protein (MAP) kinases Akt and Erk in the brain were determined 1 h after drug treatment. Next, animals of a second group learned in a two-alternative choice paradigm to discriminate between two colours, whereas a third group solved a spatial cognition task in an open-field maze by use of an ego-allocentric strategy. After memory acquisition and consolidation, animals were pharmacologically treated using the treatment regime as in the first group and then tested again for memory retrieval. We found an enhanced Erk but not Akt phosphorylation suggesting that THC treatment specifically activated Erk signalling in the zebrafish telencephalon. While CB1 agonist THC did not affect behavioural performance of animals in the colour discrimination paradigm, spatial memory was significantly impaired. The effect of THC on spatial learning is probably specific, since neither motor activity nor anxiety-related behaviour was influenced by the drug treatment. That indicates a striking influence of the endocannabinoid system (ECS) on spatial cognition in zebrafish. The results are very coincident with reports on mammals, demonstrating that the ECS is functional highly conserved during vertebrate evolution. We further conclude that the zebrafish provides a promising model organism for ongoing research on the ECS.

  19. Inhibition of hippocampal aromatization impairs spatial memory performance in a male songbird.

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    Bailey, David J; Ma, Chunqi; Soma, Kiran K; Saldanha, Colin J

    2013-12-01

    Recent studies have revealed the presence and regulation of aromatase at the vertebrate synapse, and identified a critical role played by presynaptic estradiol synthesis in the electrophysiological response to auditory and other social cues. However, if and how synaptic aromatization affects behavior remains to be directly tested. We have exploited 3 characteristics of the zebra finch hippocampus (HP) to test the role of synaptocrine estradiol provision on spatial memory function. Although the zebra finch HP contains abundant aromatase transcripts and enzyme activity, immunocytochemical studies reveal widespread pre- and postsynaptic, but sparse to undetectable somal, localization of this enzyme. Further, the superficial location of the avian HP makes possible the more exclusive manipulation of its neurochemical characteristics without perturbation of the neuropil and the resultant induction of astroglial aromatase. Last, as in other vertebrates, the HP is critical for spatial memory performance in this species. Here we report that local inhibition of hippocampal aromatization impairs spatial memory performance in an ecologically valid food-finding task. Local aromatase inhibition also resulted in lower levels of estradiol in the HP, but not in adjacent brain areas, and was achieved without the induction of astroglial aromatase. The observed decrement in acquisition and subsequent memory performance as a consequence of lowered aromatization was similar to that achieved by lesioning this locus. Thus, hippocampal aromatization, much of which is achieved at the synapse in this species, is critical for spatial memory performance.

  20. Spatial Impairment and Memory in Genetic Disorders: Insights from Mouse Models

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    Sang Ah Lee

    2017-02-01

    Full Text Available Research across the cognitive and brain sciences has begun to elucidate some of the processes that guide navigation and spatial memory. Boundary geometry and featural landmarks are two distinct classes of environmental cues that have dissociable neural correlates in spatial representation and follow different patterns of learning. Consequently, spatial navigation depends both on the type of cue available and on the type of learning provided. We investigated this interaction between spatial representation and memory by administering two different tasks (working memory, reference memory using two different environmental cues (rectangular geometry, striped landmark in mouse models of human genetic disorders: Prader-Willi syndrome (PWScrm+/p− mice, n = 12 and Beta-catenin mutation (Thr653Lys-substituted mice, n = 12. This exploratory study provides suggestive evidence that these models exhibit different abilities and impairments in navigating by boundary geometry and featural landmarks, depending on the type of memory task administered. We discuss these data in light of the specific deficits in cognitive and brain function in these human syndromes and their animal model counterparts.

  1. Categorical spatial memory in patients with mild cognitive impairment and Alzheimer dementia: Positional versus object-location recall

    NARCIS (Netherlands)

    Kessels, R.P.C.; Rijken, S.; Joosten-Weyn Banningh, L.W.A.; Schuylenborgh-van Es, N. van; Olde Rikkert, M.G.M.

    2010-01-01

    Memory for object locations, as part of spatial memory function, has rarely been Studied in patients with Alzheimer dementia (AD), while Studies in patients with Mild Cognitive Impairment (MCI) patients are lacking altogether. The present study examined categorical spatial memory function using the

  2. Categorical spatial memory in patients with mild cognitive impairment and Alzheimer dementia: positional versus object-location recall.

    NARCIS (Netherlands)

    Kessels, R.P.C.; Rijken, S.; Joosten-Weyn Banningh, L.W.A.; Schuylenborgh-van Es, N. van; Olde Rikkert, M.G.M.

    2010-01-01

    Memory for object locations, as part of spatial memory function, has rarely been studied in patients with Alzheimer dementia (AD), while studies in patients with Mild Cognitive Impairment (MCI) patients are lacking altogether. The present study examined categorical spatial memory function using the

  3. A comparison of four prompt modes for route finding for community travellers with severe cognitive impairments.

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    Sohlberg, McKay Moore; Fickas, Stephen; Hung, Pei-Fang; Fortier, Andrew

    2007-05-01

    Navigational skills are fundamental to community travel and, hence, personal independence and are often disrupted in people with cognitive impairments. Navigation devices are being developed that can support community navigation by delivering directional information. Selecting an effective mode to provide route-prompts is a critical design issue. This study evaluated the differential effects on pedestrian route finding using different modes of prompting delivered via a handheld electronic device for travellers with severe cognitive impairments. A within-subject comparison study was used to evaluate potential differences in route navigation performance when travellers received directions using four different prompt modes: (1) aerial map image, (2) point of view map image, (3) text based instructions/no image and (4) audio direction/no image. Twenty travellers with severe cognitive impairments due to acquired brain injury walked four equivalent routes using four different prompting modes delivered via a wrist-worn navigation device. Navigation scores were computed that captured accuracy and confidence during navigation. Results of the repeated measures Analysis of Variance suggested that participants performed best when given prompts via speech-based audio directions. The majority of the participants also preferred this prompting mode. Findings are interpreted in the context of cognitive resource allocation theory.

  4. Impaired affective prosody decoding in severe alcohol use disorder and Korsakoff syndrome.

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    Brion, Mélanie; de Timary, Philippe; Mertens de Wilmars, Serge; Maurage, Pierre

    2018-06-01

    Recognizing others' emotions is a fundamental social skill, widely impaired in psychiatric populations. These emotional dysfunctions are involved in the development and maintenance of alcohol-related disorders, but their differential intensity across emotions and their modifications during disease evolution remain underexplored. Affective prosody decoding was assessed through a vocalization task using six emotions, among 17 patients with severe alcohol use disorder, 16 Korsakoff syndrome patients (diagnosed following DSM-V criteria) and 19 controls. Significant disturbances in emotional decoding, particularly for negative emotions, were found in alcohol-related disorders. These impairments, identical for both experimental groups, constitute a core deficit in excessive alcohol use. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Oral Communication Development in Severe to Profound Hearing Impaired Children After Receiving Aural Habilitation

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    Soleimani Farin

    2009-10-01

    Full Text Available Communication, cognition, language, and speech are interrelated and develop together. It should come as no surprise to us that the key to intervention with deaf children is to establish, as early as possible, a functional communication system for the child and the parents. Early intervention programs need to be multidisciplinary, technologically sound and most important, it should take cognizance of the specific context (community, country in which the child and family function. The main aim of this study was to obtain oral communication development regarding current status of the intervention (aural habilitation and speech therapyfor children with severe to profound hearing impairment in Iran. A prospective longitudinal study was undertaken on a consecutive group of children with severe to profound deafness. Nine severe to profound hearing-impaired children out of the primer 42 cases, who were detected below two years old, had been selected in the previous study to receive aural habilitation. The average of their speech intelligibility scores was near 70% at age 6, which was accounted as poor oral communication and only two of them were able to communicate by spoken language. An integrated intervention services continued again for one year and their oral communication skill was assessed by their speech intelligibility. The intelligibility test of children was recorded on audio-tape, when they read 10 questions such as where is your home. This can be answered only in one word. Each tape was presented to10 normal hearing listeners, and their task was to write down, the answers in Persian orthography. At the beginning (at age 6 the average speech intelligibility score of these children was 72% and only two of them had score of 90% and 100%. At age 7, all of the severe groups were over 90%, and only two profound ones achieved the score of 48% and 62%. All of severe groups develop oral communication, but profound ones had a semi-intelligible speech

  6. Rats Fed a Diet Rich in Fats and Sugars Are Impaired in the Use of Spatial Geometry.

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    Tran, Dominic M D; Westbrook, R Frederick

    2015-12-01

    A diet rich in fats and sugars is associated with cognitive deficits in people, and rodent models have shown that such a diet produces deficits on tasks assessing spatial learning and memory. Spatial navigation is guided by two distinct types of information: geometrical, such as distance and direction, and featural, such as luminance and pattern. To clarify the nature of diet-induced spatial impairments, we provided rats with standard chow supplemented with sugar water and a range of energy-rich foods eaten by people, and then we assessed their place- and object-recognition memory. Rats exposed to this diet performed comparably with control rats fed only chow on object recognition but worse on place recognition. This impairment on the place-recognition task was present after only a few days on the diet and persisted across tests. Critically, this spatial impairment was specific to the processing of distance and direction. © The Author(s) 2015.

  7. Tetrahydropalmatine protects against methamphetamine-induced spatial learning and memory impairment in mice

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    Yan-Jiong Chen; Teng Chen; Yan-Ling Liu; Qing Zhong; Yan-Fang Yu; Hong-Liang Su; Haroldo A.Toque; Yong-Hui Dang; Feng Chen; Ming Xu

    2012-01-01

    [Objective] The purpose of this study was to investigate the effect of methamphetamine (MA) on spatial learning and memory and the role of tetrahydropalmatine (THP) in MA-induced changes in these phenomena in mice.[Methods]Male C57BL/6 mice were randomly divided into eight groups,according to different doses of MA,different doses of THP,treatment with both MA and THP,and saline controls.Spatial learning and memory were assessed using the Morris water maze.Western blot was used to detect the expression of extracellular signal-regulated protein kinase (ERK) in the mouse prefrontal cortex (PFC) and hippocampus.[Results] Repeated MA treatment significantly increased the escape latency in the learning phase and decreased the number of platform site crossings in the memory-test phase.ERK1/2 expression was decreased in the PFC but not in the hippocampus of the MA-treated mice.Repeated THP treatment alone did not affect the escape latency,the number of platform site crossings or the total ERK1/2 expression in the brain.Statistically significantly shorter escape latencies and more platform site crossings occurred in MA+THP-trcatcd mice than in MA-treated mice.[Conclusion]Repeated MA administration impairs spatial learning and memory in mice,and its co-administration with THP prevents this impairment,which is probably attributable to changed ERK1/2 expression in the PFC.This study contributes to uncovering the mechanism underlying MA abuse,and to exploring potential therapies.

  8. Severity of explicit memory impairment due to Alzheimer's disease improves effectiveness of implicit learning.

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    Klimkowicz-Mrowiec, Aleksandra; Slowik, Agnieszka; Krzywoszanski, Lukasz; Herzog-Krzywoszanska, Radosława; Szczudlik, Andrzej

    2008-04-01

    Consistent evidence from human and experimental animals studies indicates that memory is organized into two relatively independent systems with different functions and brain mechanisms. The explicit memory system, dependent on the hippocampus and adjacent medial temporal lobe structures, refers to conscious knowledge acquisition and intentional recollection of previous experiences. The implicit memory system, dependent on the striatum, refers to learning of complex information without awareness or intention. The functioning of implicit memory can be observed in progressive, gradual improvement across many trials in performance on implicit learning tasks. The influence of explicit memory on implicit memory has not been precisely identified yet. According to data from some studies, explicit memory seems to exhibit no influence on implicit memory,whereas the other studies indicate that explicit memory may inhibit or facilitate implicit memory. The analysis of performance on implicit learning tasks in patients with different severity of explicit memory impairment due to Alzheimer's disease allows one to identify the potential influence of the explicit memory system on the implicit memory system. 51 patients with explicit memory impairment due to Alzheimer's disease (AD) and 36 healthy controls were tested. Explicit memory was examined by means of a battery of neuropsychological tests. Implicit habit learning was examined on probabilistic classification task (weather prediction task). Patients with moderate explicit memory impairment performed the implicit task significantly better than those with mild AD and controls. Results of our study support the hypothesis of competition between the implicit and explicit memory systems in humans.

  9. Impaired recognition of facial emotions from low-spatial frequencies in Asperger syndrome.

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    Kätsyri, Jari; Saalasti, Satu; Tiippana, Kaisa; von Wendt, Lennart; Sams, Mikko

    2008-01-01

    The theory of 'weak central coherence' [Happe, F., & Frith, U. (2006). The weak coherence account: Detail-focused cognitive style in autism spectrum disorders. Journal of Autism and Developmental Disorders, 36(1), 5-25] implies that persons with autism spectrum disorders (ASDs) have a perceptual bias for local but not for global stimulus features. The recognition of emotional facial expressions representing various different levels of detail has not been studied previously in ASDs. We analyzed the recognition of four basic emotional facial expressions (anger, disgust, fear and happiness) from low-spatial frequencies (overall global shapes without local features) in adults with an ASD. A group of 20 participants with Asperger syndrome (AS) was compared to a group of non-autistic age- and sex-matched controls. Emotion recognition was tested from static and dynamic facial expressions whose spatial frequency contents had been manipulated by low-pass filtering at two levels. The two groups recognized emotions similarly from non-filtered faces and from dynamic vs. static facial expressions. In contrast, the participants with AS were less accurate than controls in recognizing facial emotions from very low-spatial frequencies. The results suggest intact recognition of basic facial emotions and dynamic facial information, but impaired visual processing of global features in ASDs.

  10. Component deficits of visual neglect: "Magnetic" attraction of attention vs. impaired spatial working memory.

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    Toba, Monica N; Rabuffetti, Marco; Duret, Christophe; Pradat-Diehl, Pascale; Gainotti, Guido; Bartolomeo, Paolo

    2018-01-31

    Visual neglect is a disabling consequence of right hemisphere damage, whereby patients fail to detect left-sided objects. Its precise mechanisms are debated, but there is some consensus that distinct component deficits may variously associate and interact in different patients. Here we used a touch-screen based procedure to study two putative component deficits of neglect, rightward "magnetic" attraction of attention and impaired spatial working memory, in a group of 47 right brain-damaged patients, of whom 33 had signs of left neglect. Patients performed a visual search task on three distinct conditions, whereby touched targets could (1) be tagged, (2) disappear or (3) show no change. Magnetic attraction of attention was defined as more left neglect on the tag condition than on the disappear condition, where right-sided disappeared targets could not capture patients' attention. Impaired spatial working memory should instead produce more neglect on the no change condition, where no external cue indicated that a target had already been explored, than on the tag condition. Using a specifically developed analysis algorithm, we identified significant differences of performance between the critical conditions. Neglect patients as a group performed better on the disappear condition than on the no change condition and also better in the tag condition comparing with the no change condition. No difference was found between the tag condition and the disappear condition. Some of our neglect patients had dissociated patterns of performance, with predominant magnetic attraction or impaired spatial working memory. Anatomical results issued from both grey matter analysis and fiber tracking were consistent with the typical patterns of fronto-parietal and occipito-frontal disconnection in neglect, but did not identify lesional patterns specifically associated with one or another deficit, thus suggesting the possible co-localization of attentional and working memory processes in

  11. Illness severity, trait anxiety, cognitive impairment and heart rate variability in bipolar disorder.

    Science.gov (United States)

    Levy, Boaz

    2014-12-30

    Numerous studies have documented a significant association between symptom severity and cognitive functioning in bipolar disorder (BD). These findings advanced speculations about a potential link between the physiological stress associated with illness severity and cognitive dysfunction. To explore this hypothesis, the current study employed heart rate variability (HRV) as a physiological measure that is sensitive to the effects of chronic stress, and a scale of trait anxiety for assessing a psychological condition that is correlated with hyper sympathetic arousal. Analyses indicated that BD patients with High Illness Severity reported more symptoms of trait-anxiety (i.e., State Trait Anxiety Inventory), performed more poorly on a computerized neuropsychological battery (i.e., CNS Vital Signs), and exhibited a more constricted HRV profile (i.e., lower SDNN with elevated LF/HF ratio) than patients with Low Illness Severity. Illness severity was determined by a history of psychosis, illness duration, and number of mood episodes. A third group of healthy controls (n=22) performed better on the neuropsychological battery and exhibited a healthier HRV profile than the BD groups. This study provides preliminary evidence that illness severity and cognitive impairment in BD may be associated with state anxiety and neuro-cardiac alterations that are sensitive to physiological stress. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  12. Intrahippocampal Administration of Amyloid-β1–42 Oligomers Acutely Impairs Spatial Working Memory, Insulin Signaling, and Hippocampal Metabolism

    Science.gov (United States)

    Pearson-Leary, Jiah; McNay, Ewan C.

    2017-01-01

    Increasing evidence suggests that abnormal brain accumulation of amyloid-β1–42 (Aβ1–42) oligomers plays a causal role in Alzheimer’s disease (AD), and in particular may cause the cognitive deficits that are the hallmark of AD. In vitro, Aβ1–42 oligomers impair insulin signaling and suppress neural functioning. We previously showed that endogenous insulin signaling is an obligatory component of normal hippocampal function, and that disrupting this signaling led to a rapid impairment of spatial working memory, while delivery of exogenous insulin to the hippocampus enhanced both memory and metabolism; diet-induced insulin resistance both impaired spatial memory and prevented insulin from increasing metabolism or cognitive function. Hence, we tested the hypothesis that Aβ1–42 oligomers could acutely impair hippocampal metabolic and cognitive processes in vivo in the rat. Our findings support this hypothesis: Aβ1–42 oligomers impaired spontaneous alternation behavior while preventing the task-associated dip in hippocampal ECF glucose observed in control animals. In addition, Aβ1–42 oligomers decreased plasma membrane translocation of the insulin-sensitive glucose transporter 4 (GluT4), and impaired insulin signaling as measured by phosphorylation of Akt. These data show in vivo that Aβ1–42 oligomers can rapidly impair hippocampal cognitive and metabolic processes, and provide support for the hypothesis that elevated Aβ1–42 leads to cognitive impairment via interference with hippocampal insulin signaling. PMID:22430529

  13. Thioredoxin and impaired spatial learning and memory in the rats exposed to intermittent hypoxia

    Institute of Scientific and Technical Information of China (English)

    YANG Xiu-hong; LIU Hui-guo; LIU Xue; CHEN Jun-nan

    2012-01-01

    Background Obstructive sleep apnea (OSA) can cause cognitive dysfunction and may be a reversible cause of cognitive loss in patients with Alzheimer's disease (AD).Chronic exposure to intermittent hypoxia (IH),such as encountered in OSA,is marked by neurodegenerative changes in rat brain.We investigated the change of thioredoxin (Trx),spatial learning and memory in rats exposed to chronic intermittent hypoxia (CIH).Methods Forty healthy male Sprague-Dawley (SD) rats were randomly divided into four groups of ten each:a CIH+normal saline (CIH+NS group),a N-acetylcystein-treated CIH (CIH+NAC) group,a sham CIH group (sham CIH+NS),and a sham NAC-treated sham CIH (CIH+NAC) group.Spatial learning and memory in each group was assessed with the Morris water maze.Real-time PCR and Western blotting were used to examine mRNA and protein expression of Trx in the hippocampus tissue.The terminal deoxynucleotidyl transferase-mediated dUTP-nick end-labeling (TUNEL) method was used to detect the apoptotic cells of the hippocampus CA1 region.Results ClH-rats showed impaired spatial learning and memory in the Morris water maze,including longer mean latencies for the target platform,reduced numbers of passes over the previous target platform and a smaller percentage of time spent in the target quadrant.Trx mRNA and protein levels were significantly decreased in the CIH-hippocampus,meanwhile,an elevated apoptotic index revealed apoptosis of hippocampal neurons of rats exposed to CIH.The rats,which acted better in the Morris water maze,showed higher levels of the Trx mRNA and protein in the hippocampus;apoptotic index of the neurons in the hippocampus of each group was negatively correlated with the Trx mRNA and protein levels.Conclusion The Trx deficit likely plays an important role in the impaired spatial learning and memory in the rats exposed to CIH and may work through the apoptosis of neurons in the hippocampus.

  14. Spatial contrast sensitivity vision loss in children with cortical visual impairment.

    Science.gov (United States)

    Good, William V; Hou, Chuan; Norcia, Anthony M

    2012-11-19

    Although cortical visual impairment (CVI) is the leading cause of bilateral vision impairment in children in Western countries, little is known about the effects of CVI on visual function. The aim of this study was to compare visual evoked potential measures of contrast sensitivity and grating acuity in children with CVI with those of age-matched typically developing controls. The swept parameter visual evoked potential (sVEP) was used to measure contrast sensitivity and grating acuity in 34 children with CVI at 5 months to 5 years of age and in 16 age-matched control children. Contrast thresholds and spatial frequency thresholds (grating acuities) were derived by extrapolating the tuning functions to zero amplitude. These thresholds and maximal suprathreshold response amplitudes were compared between groups. Among 34 children with CVI, 30 had measurable but reduced contrast sensitivity with a median threshold of 10.8% (range 5.0%-30.0% Michelson), and 32 had measurable but reduced grating acuity with median threshold 0.49 logMAR (9.8 c/deg, range 5-14 c/deg). These thresholds were significantly reduced, compared with age-matched control children. In addition, response amplitudes over the entire sweep range for both measures were significantly diminished in children with CVI compared with those of control children. Our results indicate that spatial contrast sensitivity and response amplitudes are strongly affected by CVI. The substantial degree of loss in contrast sensitivity suggests that contrast is a sensitive measure for evaluating vision deficits in patients with CVI.

  15. Managing diabetic patients with moderate or severe renal impairment using DPP-4 inhibitors: focus on vildagliptin

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    Russo E

    2013-04-01

    Full Text Available Eleonora Russo, Giuseppe Penno, Stefano Del Prato Department of Clinical and Experimental Medicine, Section of Diabetes and Metabolic Disease, Azienda Ospedaliero Universitaria di Pisa, and University of Pisa, Pisa, Italy Background: Dipeptidyl peptidase-4 (DPP-4 inhibitors are novel classified oral anti-diabetic drugs for the treatment of type 2 diabetes mellitus (T2DM that provide important reduction in glycated hemoglobin, with a low risk for hypoglycemia and no weight gain. In T2DM patients with reduced renal function, adequate glycemic control is essential to delay the progress of kidney dysfunction, but they are at a greater risk of experiencing hypoglycemic events, especially with longer-acting sulfonylureas and meglitinides. Objective: To evaluate vildagliptin as an option to achieve glycemic control in T2DM patients with moderate or severe chronic kidney disease (CKD. Methods: A comprehensive search in the literature was performed using the term "vildagliptin." Original articles and reviews exploring our topic were carefully selected. Results: Vildagliptin provides effective glycemic control in patients with T2DM and CKD. Dose reductions are required for vildagliptin and other DPP-4 inhibitors, except linagliptin, in T2DM patients with moderate-to-severe CKD. Dose of vildagliptin had to be reduced by half (to 50 mg/day both for moderate (estimated glomerular filtration rate [eGFR] ≥30 to ≤50 mL/min and severe CKD (eGFR < 30 mL/min. Available results support a favorable efficacy, safety, and tolerability profile for vildagliptin in T2DM with moderate or severe renal failure. Preliminary data may suggest additional benefits beyond improvement of glycemic control. Conclusion: Vildagliptin can be safely used in T2DM patients with varying degrees of renal impairment. Dose adjustments for renal impairment are required. Potential long-term renal benefit of vildagliptin needs to be further explored. Keywords: type 2 diabetes mellitus, renal

  16. Increased asymmetric dimethylarginine in severe falciparum malaria: association with impaired nitric oxide bioavailability and fatal outcome.

    Directory of Open Access Journals (Sweden)

    Tsin W Yeo

    2010-04-01

    Full Text Available Asymmetrical dimethylarginine (ADMA, an endogenous inhibitor of nitric oxide synthase (NOS, is a predictor of mortality in critical illness. Severe malaria (SM is associated with decreased NO bioavailability, but the contribution of ADMA to the pathogenesis of impaired NO bioavailability and adverse outcomes in malaria is unknown. In adults with and without falciparum malaria, we tested the hypotheses that plasma ADMA would be: 1 increased in proportion to disease severity, 2 associated with impaired vascular and pulmonary NO bioavailability and 3 independently associated with increased mortality. We assessed plasma dimethylarginines, exhaled NO concentrations and endothelial function in 49 patients with SM, 78 with moderately severe malaria (MSM and 19 healthy controls (HC. Repeat ADMA and endothelial function measurements were performed in patients with SM. Multivariable regression was used to assess the effect of ADMA on mortality and NO bioavailability. Plasma ADMA was increased in SM patients (0.85 microM; 95% CI 0.74-0.96 compared to those with MSM (0.54 microM; 95%CI 0.5-0.56 and HCs (0.64 microM; 95%CI 0.58-0.70; p<0.001. ADMA was an independent predictor of mortality in SM patients with each micromolar elevation increasing the odds of death 18 fold (95% CI 2.0-181; p = 0.01. ADMA was independently associated with decreased exhaled NO (r(s = -0.31 and endothelial function (r(s = -0.32 in all malaria patients, and with reduced exhaled NO (r(s = -0.72 in those with SM. ADMA is increased in SM and associated with decreased vascular and pulmonary NO bioavailability. Inhibition of NOS by ADMA may contribute to increased mortality in severe malaria.

  17. Bacopa monniera Attenuates Scopolamine-Induced Impairment of Spatial Memory in Mice

    Directory of Open Access Journals (Sweden)

    Manish Kumar Saraf

    2011-01-01

    Full Text Available Scopolamine, an anticholinergic, is an attractive amnesic agent for discerning the action of candidate antiamnesic drugs. Bacopa monniera Linn (Syn. Brahmi is one such antiamnesic agent that is frequently used in the ancient Indian medical system. We have earlier reported the reversal of diazepam-induced amnesia with B. monniera. In this study we wanted to test if scopolamine-induced impairment of spatial memory can also be ameliorated by B. monniera using water maze mouse model. The objective of study was to study the effect of B. monniera on scopolamine-induced amnesia. We employed Morris water maze scale to test the amnesic effect of scopolamine and its reversal by B. monniera. Rotarod test was conducted to screen muscle coordination activity of mice. Scopolamine significantly impaired the acquisition and retrieval of memory producing both anterograde and retrograde amnesia. Bacopa monniera extract was able to reverse both anterograde and retrograde amnesia. We propose that B. monniera's effects on cholinergic system may be helpful for developing alternative therapeutic approaches for the treatment of Alzheimer's disease.

  18. Low dose prenatal alcohol exposure does not impair spatial learning and memory in two tests in adult and aged rats.

    Directory of Open Access Journals (Sweden)

    Carlie L Cullen

    Full Text Available Consumption of alcohol during pregnancy can have detrimental impacts on the developing hippocampus, which can lead to deficits in learning and memory function. Although high levels of alcohol exposure can lead to severe deficits, there is a lack of research examining the effects of low levels of exposure. This study used a rat model to determine if prenatal exposure to chronic low dose ethanol would result in deficits in learning and memory performance and if this was associated with morphological changes within the hippocampus. Sprague Dawley rats were fed a liquid diet containing 6% (vol/vol ethanol (EtOH or an isocaloric control diet throughout gestation. Male and Female offspring underwent behavioural testing at 8 (Adult or 15 months (Aged of age. Brains from these animals were collected for stereological analysis of pyramidal neuron number and dendritic morphology within the CA1 and CA3 regions of the dorsal hippocampus. Prenatal ethanol exposed animals did not differ in spatial learning or memory performance in the Morris water maze or Y maze tasks compared to Control offspring. There was no effect of prenatal ethanol exposure on pyramidal cell number or density within the dorsal hippocampus. Overall, this study indicates that chronic low dose prenatal ethanol exposure in this model does not have long term detrimental effects on pyramidal cells within the dorsal hippocampus or impair spatial learning and memory performance.

  19. Safety of high-dose daptomycin in patients with severe renal impairment

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    Tai CH

    2018-03-01

    Full Text Available Chih-Hsun Tai,1 Chi-Hao Shao,2 Chen-You Chen,2 Shu-Wen Lin,1–3 Chien-Chih Wu1,2 1Department of Pharmacy, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan; 2School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan; 3Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan Background: Treatment options are limited for infections due to multidrug-resistant Gram-positive pathogens. Daptomycin is a lipopeptide antibiotic with concentration-dependent killing characteristic and dose-dependent post-antibiotic effect. To achieve optimized pharmacodynamic effect, some experts advocated using a high dose of daptomycin (≥9 mg/kg for severe infections. However, the safety of high-dose therapy in patients with renal impairment remains unknown. This study was aimed to evaluate the safety of daptomycin in patients with severe renal impairment. Methods: This was a retrospective study performed by reviewing electronic medical records. Patients with severe renal impairment who were treated with daptomycin in a tertiary teaching hospital between January 1, 2013, and June 30, 2016, were included for evaluation. The incidence rates of creatine kinase (CK elevation between high-dose (≥9 mg/kg and standard-dose (<9 mg/kg groups were compared. Results: Overall, 164 patients met the inclusion criteria, and 114 (69.5% of them were on renal replacement therapy. Vancomycin-resistant enterococci were the most common pathogens (61.3% of the patients with documented pathogens. The treatment success rate was 51.6% in the 91 patients with bacteremia. The average dose of daptomycin was 8.0±2.3 mg/kg, and 37 (22.6% patients received ≥9 mg/kg. CK levels were followed in 108 (65.9% patients. Significantly higher incidence of CK elevation was found in the high-dose group compared with that in the standard-dose group (10.8% vs 1.6%, P<0.05. Moreover

  20. Impaired spatial processing in a mouse model of fragile X syndrome.

    Science.gov (United States)

    Ghilan, Mohamed; Bettio, Luis E B; Noonan, Athena; Brocardo, Patricia S; Gil-Mohapel, Joana; Christie, Brian R

    2018-05-17

    Fragile X syndrome (FXS) is the most common form of inherited intellectual impairment. The Fmr1 -/y mouse model has been previously shown to have deficits in context discrimination tasks but not in the elevated plus-maze. To further characterize this FXS mouse model and determine whether hippocampal-mediated behaviours are affected in these mice, dentate gyrus (DG)-dependent spatial processing and Cornu ammonis 1 (CA1)-dependent temporal order discrimination tasks were evaluated. In agreement with previous findings of long-term potentiation deficits in the DG of this transgenic model of FXS, the results reported here demonstrate that Fmr1 -/y mice perform poorly in the DG-dependent metric change spatial processing task. However, Fmr1 -/y mice did not present deficits in the CA1-dependent temporal order discrimination task, and were able to remember the order in which objects were presented to them to the same extent as their wild-type littermate controls. These data suggest that the previously reported subregional-specific differences in hippocampal synaptic plasticity observed in the Fmr1 -/y mouse model may manifest as selective behavioural deficits in hippocampal-dependent tasks. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

  1. Spatial short-term memory is impaired in dependent betel quid chewers.

    Science.gov (United States)

    Chiu, Meng-Chun; Shen, Bin; Li, Shuo-Heng; Ho, Ming-Chou

    2016-08-01

    Betel quid is regarded as a human carcinogen by the World Health Organization. It remains unknown whether chewing betel quid has a chronic effect on healthy betel quid chewers' memory. The present study aims to investigate whether chewing betel quid can affect short-term memory (STM). Three groups of participants (24 dependent chewers, 24 non-dependent chewers, and 24 non-chewers) were invited to carry out the matrix span task, the object span task, and the digit span task. All span tasks' results were adopted to assess spatial STM, visual STM, and verbal STM, respectively. Besides, there are three set sizes (small, medium, and large) in each span task. For the matrix span task, results showed that the dependent chewers had worse performances than the non-dependent chewers and the non-chewers at medium and large set sizes. For the object span task and digit span task, there were no differences in between groups. In each group, recognition performances were worse with the increasing set size and showing successful manipulation of memory load. The current study provided the first evidence that dependent betel quid chewing can selectively impair spatial STM rather than visual STM and verbal STM. Theoretical and practical implications of this result are discussed.

  2. Impaired spatial and contextual memory formation in galectin-1 deficient mice

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    Sakaguchi Masanori

    2011-09-01

    Full Text Available Abstract Galectins are a 15 member family of carbohydrate-binding proteins that have been implicated in cancer, immunity, inflammation and development. While galectins are expressed in the central nervous system, little is known about their function in the adult brain. Previously we have shown that galectin-1 (gal-1 is expressed in the adult hippocampus, and, in particular, in putative neural stem cells in the subgranular zone. To evaluate how gal-1 might contribute to hippocampal memory function here we studied galectin-1 null mutant (gal-1-/- mice. Compared to their wildtype littermate controls, gal-1-/- mice exhibited impaired spatial learning in the water maze and contextual fear learning. Interestingly, tone fear conditioning was normal in gal-1-/- mice suggesting that loss of gal-1 might especially impact hippocampal learning and memory. Furthermore, gal-1-/- mice exhibited normal motor function, emotion and sensory processing in a battery of other behavioral tests, suggesting that non-mnemonic performance deficits are unlikely to account for the spatial and contextual learning deficits. Together, these data reveal a role for galectin-carbohydrate signalling in hippocampal memory function.

  3. Angina pectoris severity among coronary heart disease patients is associated with subsequent cognitive impairment.

    Science.gov (United States)

    Weinstein, Galit; Goldbourt, Uri; Tanne, David

    2015-01-01

    The relationship between coronary heart disease (CHD) and cognitive function is not completely elucidated. We examined the association between severity of angina pectoris (AP) in mid-life and subsequent cognitive impairment among CHD patients. Severity of AP according to the Canadian Cardiovascular Society angina classification was assessed in a subgroup of people with chronic CHD, who previously participated in a secondary prevention trial. Cognitive performance was evaluated 15±3 years later, using a validated set of computerized cognitive tests (Neurotrax Computerized Cognitive Battery; computing index scores summarizing performance in each cognitive domain and a global cognitive score). We compared the risk of cognitive deficits in participants with AP class >2 to those with AP≤2, adjusting for vascular risk factors, common carotid-intima media thickness (CC-IMT), and presence of carotid plaques. Among 535 participants (mean age at baseline 57.9±6.6 y; 95% males), AP class >2 was associated with subsequent poorer performance on tests of memory and attention compared to those with AP class ≤2 (β=-4.3±1.8; P=0.016 and β=-3.6±1.7; P=0.029, respectively) and with a higher risk of having impairment in these domains [odds ratio (95% confidence interval)=1.83 (1.11-3.02); P=0.019 and 2.36 (1.34-4.16); P=0.003, for memory and attention, respectively]. These results were similar after controlling for vascular risk factors; however, the association of AP with memory domain attenuated after adjustment for CC-IMT or presence of carotid plaques. In people with preexisting CHD, severity of AP is associated with late-life poorer cognitive performance, independent of other vascular risk factors.

  4. The effect of severe zinc deficiency and zinc supplement on spatial learning and memory.

    Science.gov (United States)

    Tahmasebi Boroujeni, S; Naghdi, N; Shahbazi, M; Farrokhi, A; Bagherzadeh, F; Kazemnejad, A; Javadian, M

    2009-07-01

    Zinc deficiency during pregnancy and during lactation has been shown to impair cognitive function and motor activity in offspring rats. In the present study, the effect of zinc deficiency and zinc supplement on spatial learning and memory in Morris Water Maze (MWM) and motor activity in open field were investigated. Pregnant rats after mating were divided to three groups. Control group fed a standard diet and a zinc deficient (ZnD) group fed a diet deficient in zinc (0.5-1.5 ppm) and a zinc supplement (ZnS) group fed a standard diet and enhanced zinc in the drinking water (10 ppm). All the diets were exposed during the last trisemester of pregnancy and during lactation. Rat's offspring in these groups were tested for spatial learning and memory in MWM at post natal day (PND) 56 and were tested for motor activity in open field at PND 66.The Escape Latency (EL) and Traveled Distance (TD) in the ZnD group were increased but Percentage of Time Spent in the target quadrant (PTS) was decreased compared to the control group. In addition, these were no significant differences in EL and TD, but PTS had significant increase in ZnS compared to the control group. In the open field, Total Distance Moved (TDM) and Time of Motor Activity (TMA) for the ZnD were decreased compared to the control group, but there were no significant differences in TDM and TMA between control and ZnS groups. These findings suggest that zinc deficiency during the last trimester of pregnancy and during lactation impaired spatial learning and memory in their offsprings and has also negative effect on motor activity. In addition, ZnS has a significant effect on spatial learning and memory but no effect on motor activity in their offsprings.

  5. Chronic dietary chlorpyrifos causes long-term spatial memory impairment and thigmotaxic behavior.

    Science.gov (United States)

    López-Granero, Caridad; Ruiz-Muñoz, Ana M; Nieto-Escámez, Francisco A; Colomina, María T; Aschner, Michael; Sánchez-Santed, Fernando

    2016-03-01

    Little is known about the long-term effects of chronic exposure to low-level organophosphate (OP) pesticides, and the role of neurotransmitter systems, other than the cholinergic system, in mediating OP neurotoxicity. In this study, rats were administered 5mg/kg/day of chlorpyrifos (CPF) for 6 months commencing at 3-months-of-age. The animals were examined 7 months later (at 16-months-of-age) for spatial learning and memory in the Morris water maze (MWM) and locomotor activity. In addition, we assessed the chronic effects of CPF on glutamatergic and gamma-aminobutyric acid (GABAergic) function using pharmacological challenges with dizocilpine (MK801) and diazepam. Impaired performance related to altered search patterns, including thigmotaxis and long-term spatial memory was noted in the MWM in animals exposed to CPF, pointing to dietary CPF-induced behavioral disturbances, such as anxiety. Twenty-four hours after the 31st session of repeated acquisition task, 0.1mg/kg MK801, an N-methyl-d-aspartate (NMDA) antagonist was intraperitoneally (i.p.) injected for 4 consecutive days. Decreased latencies in the MWM in the control group were noted after two sessions with MK801 treatment. Once the MWM assessment was completed, animals were administered 0.1 or 0.2mg/kg of MK801 and 1 or 3mg/kg of diazepam i.p., and tested for locomotor activity. Both groups, the CPF dietary and control, displayed analogous performance in motor activity. In conclusion, our data point to a connection between the long-term spatial memory, thigmotaxic response and CPF long after the exposure ended. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. The impairment of MAGMAS function in human is responsible for a severe skeletal dysplasia.

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    Cybel Mehawej

    2014-05-01

    Full Text Available Impairment of the tightly regulated ossification process leads to a wide range of skeletal dysplasias and deciphering their molecular bases has contributed to the understanding of this complex process. Here, we report a homozygous mutation in the mitochondria-associated granulocyte macrophage colony stimulating factor-signaling gene (MAGMAS in a novel and severe spondylodysplastic dysplasia. MAGMAS, also referred to as PAM16 (presequence translocase-associated motor 16, is a mitochondria-associated protein involved in preprotein translocation into the matrix. We show that MAGMAS is specifically expressed in trabecular bone and cartilage at early developmental stages and that the mutation leads to an instability of the protein. We further demonstrate that the mutation described here confers to yeast strains a temperature-sensitive phenotype, impairs the import of mitochondrial matrix pre-proteins and induces cell death. The finding of deleterious MAGMAS mutations in an early lethal skeletal dysplasia supports a key role for this mitochondrial protein in the ossification process.

  7. Subarachnoid Hemorrhage Severely Impairs Brain Parenchymal Cerebrospinal Fluid Circulation in Nonhuman Primate.

    Science.gov (United States)

    Goulay, Romain; Flament, Julien; Gauberti, Maxime; Naveau, Michael; Pasquet, Nolwenn; Gakuba, Clement; Emery, Evelyne; Hantraye, Philippe; Vivien, Denis; Aron-Badin, Romina; Gaberel, Thomas

    2017-08-01

    Subarachnoid hemorrhage (SAH) is a devastating form of stroke with neurological outcomes dependent on the occurrence of delayed cerebral ischemia. It has been shown in rodents that some of the mechanisms leading to delayed cerebral ischemia are related to a decreased circulation of the cerebrospinal fluid (CSF) within the brain parenchyma. Here, we evaluated the cerebral circulation of the CSF in a nonhuman primate in physiological condition and after SAH. We first evaluated in physiological condition the circulation of the brain CSF in Macaca facicularis , using magnetic resonance imaging of the temporal DOTA-Gd distribution after its injection into the CSF. Then, animals were subjected to a minimally invasive SAH before an MRI evaluation of the impact of SAH on the brain parenchymal CSF circulation. We first demonstrate that the CSF actively penetrates the brain parenchyma. Two hours after injection, almost the entire brain is labeled by DOTA-Gd. We also show that our model of SAH in nonhuman primate displays the characteristics of SAH in humans and leads to a dramatic impairment of the brain parenchymal circulation of the CSF. The CSF actively penetrates within the brain parenchyma in the gyrencephalic brain, as described for the glymphatic system in rodent. This parenchymal CSF circulation is severely impaired by SAH. © 2017 American Heart Association, Inc.

  8. Trends in the incidence and causes of severe visual impairment and blindness in children from Israel.

    Science.gov (United States)

    Mezer, Eedy; Chetrit, Angela; Kalter-Leibovici, Ofra; Kinori, Michael; Ben-Zion, Itay; Wygnanski-Jaffe, Tamara

    2015-06-01

    To describe trends in the incidence and causes of legal childhood blindness in Israel, one of the few countries worldwide that maintain a national registry of the blind. We performed a historical cohort study of annual reports of the National Registry of the Blind (NRB) between 1999 and 2013. All data regarding demographic information, year of registration and cause of blindness of children 0-18 years of age registered for blind certification were obtained from the annual reports of the NRB. Causes of legal blindness analyzed were optic atrophy, retinitis pigmentosa, retinopathy of prematurity (ROP), albinism, other retinal disorders, cataract, and glaucoma. The main outcome measure was the incidence of new cases of certified legal blindness. The incidence of newly registered legally blind children in Israel almost halved from 7.7 per 100,000 in 1999 to 3.1 per 100,000 in 2013. The decline was mainly attributable to a decreased incidence of blindness resulting from retinitis pigmentosa and ROP. The incidence of registered cases due to cerebral visual impairment increased. During the past decade the incidence of severe childhood visual impairment and blindness declined in Israel. A continuous decline in consanguineous marriages among the Jewish and Arab populations in Israel may have contributed to the decrease in the rate of vision loss due to retinitis pigmentosa in children. Copyright © 2015 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.

  9. Progressive impairment of directional and spatially precise trajectories by TgF344-AD Rats in the Morris Water Task

    OpenAIRE

    Thompson, Shannon; Harvey, Ryan; Clark, Benjamin; Drake, Emma; Berkowitz, Laura

    2018-01-01

    Spatial navigation is impaired in early stages of Alzheimers disease (AD), and may be a defining behavioral marker of preclinical AD. Nevertheless, limitations of diagnostic criteria for AD and within animal models of AD make characterization of preclinical AD difficult. A new rat model (TgF344-AD) of AD overcomes many of these limitations, though spatial navigation has not been comprehensively assessed. Using the hidden and cued platform variants of the Morris water task, a longitudinal asse...

  10. White Matter Hyperintensities and Cognitive Impairment During Electroconvulsive Therapy in Severely Depressed Elderly Patients

    NARCIS (Netherlands)

    Oudega, M.L.; van Exel, E.; Wattjes, M.P.; Comijs, H.C.; Scheltens, P.; Barkhof, F.; Eikelenboom, P.; Craen, A.J.M.; Beekman, A.T.F.; Stek, M.L.

    2014-01-01

    Objective: Transient cognitive impairment during electroconvulsive therapy (ECT) can be a reason to discontinue ECT in depressed elderly patients. We hypothesized that both white matter hyperintensities and medial temporal lobe atrophy contribute to transient cognitive impairment during ECT.

  11. Impaired hippocampal acetylcholine release parallels spatial memory deficits in Tg2576 mice subjected to basal forebrain cholinergic degeneration

    DEFF Research Database (Denmark)

    Laursen, Bettina; Mørk, Arne; Plath, Niels

    2013-01-01

    (BFCD) in 3 months old male Tg2576 mice to co-express cholinergic degeneration with Aβ overexpression as these characteristics constitutes key hallmarks of AD. At 9 months, SAP lesioned Tg2576 mice were cognitively impaired in two spatial paradigms addressing working memory and mid to long-term memory...

  12. Multimodal MRI reveals structural connectivity differences in 22q11 deletion syndrome related to impaired spatial working memory

    NARCIS (Netherlands)

    O'Hanlon, Erik; Howley, Sarah; Prasad, Sarah; McGrath, Jane; Leemans, Alexander; McDonald, Colm; Garavan, Hugh; Murphy, Kieran C

    2016-01-01

    INTRODUCTION: Impaired spatial working memory is a core cognitive deficit observed in people with 22q11 Deletion syndrome (22q11DS) and has been suggested as a candidate endophenotype for schizophrenia. However, to date, the neuroanatomical mechanisms describing its structural and functional

  13. 7,8-dihydroxyflavone, a TrkB receptor agonist, blocks long-term spatial memory impairment caused by immobilization stress in rats.

    Science.gov (United States)

    Andero, Raül; Daviu, Núria; Escorihuela, Rosa Maria; Nadal, Roser; Armario, Antonio

    2012-03-01

    Post-traumatic stress disorder (PTSD) patients show cognitive deficits, but it is unclear whether these are a consequence of the pathology or a pre-existing factor of vulnerability to PTSD. Animal models may help to demonstrate whether or not exposure to certain stressors can actually induce long-lasting (LL; days) impairment of hippocampus-dependent memory tasks and to characterize neurobiological mechanisms. Adult male rats were exposed to 2-h immobilization on boards (IMO), a severe stressor, and spatial learning in the Morris water maze (MWM) was studied days later. Exposure to IMO did not modify learning or short-term memory in the MWM when learning started 3 or 9 days after IMO, but stressed rats did show impaired long-term memory at both times, in accordance with the severity of the stressor. New treatments to prevent PTSD symptoms are needed. Thus, considering the potential protective role of brain-derived neurotrophic factor (BDNF) on hippocampal function, 7,8-dihydroxyflavone (7,8-DHF), a recently characterized agonist of the BDNF receptor TrkB, was given before or after IMO in additional experiments. Again, exposure to IMO resulted in LL deficit in long-term memory, and such impairment was prevented by the administration of 7,8-DHF either 2 h prior IMO or 8 h after the termination of IMO. The finding that IMO-induced impairment of spatial memory was prevented by pharmacological potentiation of TrkB pathway with 7,8-DHF even when the drug was given 8 h after IMO suggests that IMO-induced impairment is likely to be a LL process that is strongly dependent on the integrity of the BDNF-TrkB system and is susceptible to poststress therapeutic interventions. 7,8-DHF may represent a new therapeutic approach for early treatment of subjects who have suffered traumatic experiences. Copyright © 2010 Wiley Periodicals, Inc.

  14. Spatial learning impairment in prepubertal guinea pigs prenatally exposed to the organophosphorus pesticide chlorpyrifos: Toxicological implications

    Science.gov (United States)

    Mamczarz, Jacek; Pescrille, Joseph D.; Gavrushenko, Lisa; Burke, Richard D.; Fawcett, William P.; DeTolla, Louis J.; Chen, Hegang; Pereira, Edna F.R.; Albuquerque, Edson X.

    2017-01-01

    Exposure of the developing brain to chlorpyrifos (CPF), an organophosphorus (OP) pesticide used extensively in agriculture worldwide, has been associated with increased prevalence of cognitive deficits in children, particularly boys. The present study was designed to test the hypothesis that cognitive deficits induced by prenatal exposure to sub-acute doses of CPF can be reproduced in precocial small species. To address this hypothesis, pregnant guinea pigs were injected daily with CPF (25 mg/kg, s.c.) or vehicle (peanut oil) for 10 days starting on presumed gestation day (GD) 53–55. Offspring were born around GD 65, weaned on postnatal day (PND) 20, and subjected to behavioral tests starting around PND 30. On the day of birth, butyrylcholinesterase (BuChE), an OP bioscavenger used as a biomarker of OP exposures, and acetylcholinesterase (AChE), a major molecular target of OP compounds, were significantly inhibited in the blood of CPF-exposed offspring. In their brains, BuChE, but not AChE, was significantly inhibited. Prenatal CPF exposure had no significant effect on locomotor activity or on locomotor habituation, a form of non-associative memory assessed in open fields. Spatial navigation in the Morris water maze (MWM) was found to be sexually dimorphic among guinea pigs, with males outperforming females. Prenatal CPF exposure impaired spatial learning more significantly among male than female guinea pigs and, consequently, reduced the sexual dimorphism of the task. The results presented here, which strongly support the test hypothesis, reveal that the guinea pig is a valuable animal model for preclinical assessment of the developmental neurotoxicity of OP pesticides. These findings are far reaching as they lay the groundwork for future studies aimed at identifying therapeutic interventions to treat and/or prevent the neurotoxic effects of CPF in the developing brain. PMID:27296654

  15. Disrupting Jagged1-Notch signaling impairs spatial memory formation in adult mice.

    Science.gov (United States)

    Sargin, Derya; Botly, Leigh C P; Higgs, Gemma; Marsolais, Alexander; Frankland, Paul W; Egan, Sean E; Josselyn, Sheena A

    2013-07-01

    It is well-known that Notch signaling plays a critical role in brain development and growing evidence implicates this signaling pathway in adult synaptic plasticity and memory formation. The Notch1 receptor is activated by two subclasses of ligands, Delta-like (including Dll1 and Dll4) and Jagged (including Jag1 and Jag2). Ligand-induced Notch1 receptor signaling is modulated by a family of Fringe proteins, including Lunatic fringe (Lfng). Although Dll1, Jag1 and Lfng are critical regulators of Notch signaling, their relative contribution to memory formation in the adult brain is unknown. To investigate the roles of these important components of Notch signaling in memory formation, we examined spatial and fear memory formation in adult mice with reduced expression of Dll1, Jag1, Lfng and Dll1 plus Lfng. We also examined motor activity, anxiety-like behavior and sensorimotor gating using the acoustic startle response in these mice. Of the lines of mutant mice tested, we found that only mice with reduced Jag1 expression (mice heterozygous for a null mutation in Jag1, Jag1(+/-)) showed a selective impairment in spatial memory formation. Importantly, all other behavior including open field activity, conditioned fear memory (both context and discrete cue), acoustic startle response and prepulse inhibition, was normal in this line of mice. These results provide the first in vivo evidence that Jag1-Notch signaling is critical for memory formation in the adult brain. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

  16. Augmentative And Alternative Communication Systems For Post-Stroke Patients With Severe Communication And Motor Impairment

    Directory of Open Access Journals (Sweden)

    Talieh Zarifian

    2017-02-01

    Full Text Available Background and aims: Adults with acquired neurological disorders (stroke, Traumatic Brain Injury ... develop their verbal communication and literacy capabilities as typical speakers and writers. They use these skills to participate academically, vocationally, recreationally, and socially. Depending upon their neurological condition, they gradually or suddenly lose their speech or language capabilities and are required to rely on Augmentative and Alternative Communication (AAC systems to meet their communication needs. In addition to the loss of their spoken communication, the impact of their neurological condition on their participation patterns is potentially profound with reduced ability to care for themselves, a reduction or loss of employment, and usually a sudden or gradual restriction of their social networks. AAC is an umbrella term that encompasses the communication methods used to supplement or replace speech or writing for those with impairments in the production or comprehension of spoken or written language. During the past five decades, AAC technologies have been developed to compensate for these natural communication losses.      Stroke is one of the main causes of disability in the world. About 20% of stroke patients experience aphasia, with 20-30% of these individuals exhibiting severe communication deficits for at least a portion of their recovery period. Augmentative and Alternative Communication (AAC encompasses the communication methods used to supplement or replace speech or writing for those with impairments in the production of spoken or written language.  Specifically designed Human Computer Interfaces (HCI, as an assistive technology, provides new channels of communication for patients with aphasia, dysarthria, and dyspraxia, when accompanied by movement impairments.       In this workshop after stating a science review of the following types of issues: AAC acceptance (individually, culturally; AAC availability

  17. Plasticity of premotor cortico-muscular coherence in severely impaired stroke patients with hand paralysis.

    Science.gov (United States)

    Belardinelli, Paolo; Laer, Leonard; Ortiz, Erick; Braun, Christoph; Gharabaghi, Alireza

    2017-01-01

    Motor recovery in severely impaired stroke patients is often very limited. To refine therapeutic interventions for regaining motor control in this patient group, the functionally relevant mechanisms of neuronal plasticity need to be detected. Cortico-muscular coherence (CMC) may provide physiological and topographic insights to achieve this goal. Synchronizing limb movements to motor-related brain activation is hypothesized to reestablish cortico-motor control indexed by CMC. In the present study, right-handed, chronic stroke patients with right-hemispheric lesions and left hand paralysis participated in a four-week training for their left upper extremity. A brain-robot interface turned event-related beta-band desynchronization of the lesioned sensorimotor cortex during kinesthetic motor-imagery into the opening of the paralyzed hand by a robotic orthosis. Simultaneous MEG/EMG recordings and individual models from MRIs were used for CMC detection and source reconstruction of cortico-muscular connectivity to the affected finger extensors before and after the training program. The upper extremity-FMA of the patients improved significantly from 16.23 ± 6.79 to 19.52 ± 7.91 (p = 0.0015). All patients showed significantly increased CMC in the beta frequency-band, with a distributed, bi-hemispheric pattern and considerable inter-individual variability. The location of CMC changes was not correlated to the severity of the motor impairment, the motor improvement or the lesion volume. Group analysis of the cortical overlap revealed a common feature in all patients following the intervention: a significantly increased level of ipsilesional premotor CMC that extended from the superior to the middle and inferior frontal gyrus, along with a confined area of increased CMC in the contralesional premotor cortex. In conclusion, functionally relevant modulations of CMC can be detected in patients with long-term, severe motor deficits after a brain-robot assisted

  18. Bariatric surgery in individuals with severe cognitive impairment: report of two cases

    Directory of Open Access Journals (Sweden)

    Everton Cazzo

    2017-04-01

    Full Text Available ABSTRACT CONTEXT: Bariatric surgery has become the gold-standard treatment for refractory morbid obesity. Obesity is frequently associated with certain syndromes that include coexisting cognitive deficits. However, the outcomes from bariatric surgery in this group of individuals remain incompletely determined. CASE REPORT: A 25-year-old male with Prader-Willi syndrome, whose intelligence quotient (IQ was 54, was admitted with a body mass index (BMI of 55 kg/m2, associated with glucose intolerance. He underwent the Scopinaro procedure for biliopancreatic diversion, with uneventful postoperative evolution, and presented a 55% loss of excess weight one year after the surgery, with resolution of glucose intolerance, and without any manifestation of protein-calorie malnutrition. A 28-year-old male with Down syndrome, whose IQ was 68, was admitted with BMI of 41.5 kg/m2, associated with hypertension. He underwent Roux-en-Y gastric bypass, with uneventful postoperative evolution. He presented a 90% loss of excess weight one year after the surgery, with resolution of the hypertension. CONCLUSION: Bariatric surgery among individuals with intellectual impairment is a controversial topic. There is a tendency among these individuals to present significant weight loss and comorbidity control, but less than what is observed in the general obese population. The severity of the intellectual impairment may be taken into consideration in the decision-making process regarding the most appropriate surgical technique. Bariatric surgery is feasible and safe among these individuals, but further research is necessary to deepen these observations.

  19. Using electronic storybooks to support word learning in children with severe language impairments.

    Science.gov (United States)

    Smeets, Daisy J H; van Dijken, Marianne J; Bus, Adriana G

    2014-01-01

    Novel word learning is reported to be problematic for children with severe language impairments (SLI). In this study, we tested electronic storybooks as a tool to support vocabulary acquisition in SLI children. In Experiment 1, 29 kindergarten SLI children heard four e-books each four times: (a) two stories were presented as video books with motion pictures, music, and sounds, and (b) two stories included only static illustrations without music or sounds. Two other stories served as the control condition. Both static and video books were effective in increasing knowledge of unknown words, but static books were most effective. Experiment 2 was designed to examine which elements in video books interfere with word learning: video images or music or sounds. A total of 23 kindergarten SLI children heard 8 storybooks each four times: (a) two static stories without music or sounds, (b) two static stories with music or sounds, (c) two video stories without music or sounds, and (d) two video books with music or sounds. Video images and static illustrations were equally effective, but the presence of music or sounds moderated word learning. In children with severe SLI, background music interfered with learning. Problems with speech perception in noisy conditions may be an underlying factor of SLI and should be considered in selecting teaching aids and learning environments. © Hammill Institute on Disabilities 2012.

  20. Dysphagia and cerebrovascular accident: relationship between severity degree and level of neurological impairment.

    Science.gov (United States)

    Itaquy, Roberta Baldino; Favero, Samara Regina; Ribeiro, Marlise de Castro; Barea, Liselotte Menke; Almeida, Sheila Tamanini de; Mancopes, Renata

    2011-12-01

    The aim of this case study was to verify the occurrence of dysphagia in acute ischemic stroke within 48 hours after the onset of the first symptoms, in order to establish a possible relationship between the level of neurologic impairment and the severity degree of dysphagia. After emergency hospital admission, three patients underwent neurological clinical evaluation (general physical examination, neurological examination, and application of the National Institute of Health Stroke Scale - NIHSS), and clinical assessment of swallowing using the Protocolo Fonoaudiológico de Avaliação do Risco para Disfagia (PARD--Speech-Language Pathology Protocol for Risk Evaluation for Dysphagia). One of the patients presented functional swallowing (NIHSS score 11), while the other two had mild and moderate oropharyngeal dysphagia (NIHSS scores 15 and 19, respectively). The service flow and the delay on the patients' search for medical care determined the small sample. The findings corroborate literature data regarding the severity of the neurological condition and the manifestation of dysphagia.

  1. Severe Malaria Infections Impair Germinal Center Responses by Inhibiting T Follicular Helper Cell Differentiation

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    Victoria Ryg-Cornejo

    2016-01-01

    Full Text Available Naturally acquired immunity to malaria develops only after years of repeated exposure to Plasmodium parasites. Despite the key role antibodies play in protection, the cellular processes underlying the slow acquisition of immunity remain unknown. Using mouse models, we show that severe malaria infection inhibits the establishment of germinal centers (GCs in the spleen. We demonstrate that infection induces high frequencies of T follicular helper (Tfh cell precursors but results in impaired Tfh cell differentiation. Despite high expression of Bcl-6 and IL-21, precursor Tfh cells induced during infection displayed low levels of PD-1 and CXCR5 and co-expressed Th1-associated molecules such as T-bet and CXCR3. Blockade of the inflammatory cytokines TNF and IFN-γ or T-bet deletion restored Tfh cell differentiation and GC responses to infection. Thus, this study demonstrates that the same pro-inflammatory mediators that drive severe malaria pathology have detrimental effects on the induction of protective B cell responses.

  2. Spatial Frequency Selectivity Is Impaired in Dopamine D2 Receptor Knockout Mice

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    Souza, Bruno Oliveira Ferreira; Abou Rjeili, Mira; Quintana, Clémentine; Beaulieu, Jean M.; Casanova, Christian

    2018-01-01

    Dopamine is a neurotransmitter implicated in several brain functions, including vision. In the present study, we investigated the impacts of the lack of D2 dopamine receptors on the structure and function of the primary visual cortex (V1) of D2-KO mice using optical imaging of intrinsic signals. Retinotopic maps were generated in order to measure anatomo-functional parameters such as V1 shape, cortical magnification factor, scatter, and ocular dominance. Contrast sensitivity and spatial frequency selectivity (SF) functions were computed from responses to drifting gratings. When compared to control mice, none of the parameters of the retinotopic maps were affected by D2 receptor loss of function. While the contrast sensitivity function of D2-KO mice did not differ from their wild-type counterparts, SF selectivity function was significantly affected as the optimal SF and the high cut-off frequency (p D2-KO than in WT mice. These findings show that the lack of function of D2 dopamine receptors had no influence on cortical structure whereas it had a significant impact on the spatial frequency selectivity and high cut-off. Taken together, our results suggest that D2 receptors play a specific role on the processing of spatial features in early visual cortex while they do not seem to participate in its development. PMID:29379422

  3. Impairment Severity and Evaluative and Experienced Well-being Among Older Adults: Assessing the Role of Daily Activities.

    Science.gov (United States)

    Freedman, Vicki A; Carr, Deborah; Cornman, Jennifer C; Lucas, Richard E

    2017-03-01

    Physical impairments affect a substantial number of older adults in the United States, with rates increasing with advancing age. Impairment is linked with compromised well-being, although the reasons are not fully understood. We explore the extent to which linkages between impairment severity and well-being are accounted for by older adults' daily activities. We speculate that activities may influence global appraisals of well-being by offering the opportunity to fulfill productive and social roles and may influence daily emotions by shaping the context (places, people) in which life occurs. We examine the effects of impairment severity on life satisfaction and four diary-based experienced well-being measures (happiness, frustration, worry, and sadness). Data are from the Disability and Use of Time supplement to the Panel Study of Income Dynamics ( n = 1,606), a national sample of adults ages 60 years and older in the United States. We estimate nested regression models, taking into account within-person correlations for experienced well-being. Impairment severity is associated with poorer assessments of life satisfaction and all four dimensions of experienced well-being. Activity measures, which encompass eight productive (e.g., household chores) and three leisure (e.g., socializing) activities, account for 10% of the association between impairment and life satisfaction, and virtually none of the association between impairment and experienced well-being. However, psychosocial factors including higher neuroticism, lower self-efficacy, and poorer quality social relationships account for a sizeable share of the associations. Role-fulfilling aspects of activities appear to be more central than contextual aspects of activities to the impairment-well-being relationship. However, potentially modifiable psychosocial factors account for a much greater share of this relationship. Further research is needed on whether interventions targeting these psychosocial factors might

  4. Enhanced odor discrimination and impaired olfactory memory by spatially controlled switch of AMPA receptors.

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    Derya R Shimshek

    2005-11-01

    Full Text Available Genetic perturbations of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPARs are widely used to dissect molecular mechanisms of sensory coding, learning, and memory. In this study, we investigated the role of Ca2+-permeable AMPARs in olfactory behavior. AMPAR modification was obtained by depletion of the GluR-B subunit or expression of unedited GluR-B(Q, both leading to increased Ca2+ permeability of AMPARs. Mice with this functional AMPAR switch, specifically in forebrain, showed enhanced olfactory discrimination and more rapid learning in a go/no-go operant conditioning task. Olfactory memory, however, was dramatically impaired. GluR-B depletion in forebrain was ectopically variable ("mosaic" among individuals and strongly correlated with decreased olfactory memory in hippocampus and cortex. Accordingly, memory was rescued by transgenic GluR-B expression restricted to piriform cortex and hippocampus, while enhanced odor discrimination was independent of both GluR-B variability and transgenic GluR-B expression. Thus, correlated differences in behavior and levels of GluR-B expression allowed a mechanistic and spatial dissection of olfactory learning, discrimination, and memory capabilities.

  5. Enhanced odor discrimination and impaired olfactory memory by spatially controlled switch of AMPA receptors.

    Science.gov (United States)

    Shimshek, Derya R; Bus, Thorsten; Kim, Jinhyun; Mihaljevic, Andre; Mack, Volker; Seeburg, Peter H; Sprengel, Rolf; Schaefer, Andreas T

    2005-11-01

    Genetic perturbations of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPARs) are widely used to dissect molecular mechanisms of sensory coding, learning, and memory. In this study, we investigated the role of Ca2+-permeable AMPARs in olfactory behavior. AMPAR modification was obtained by depletion of the GluR-B subunit or expression of unedited GluR-B(Q), both leading to increased Ca2+ permeability of AMPARs. Mice with this functional AMPAR switch, specifically in forebrain, showed enhanced olfactory discrimination and more rapid learning in a go/no-go operant conditioning task. Olfactory memory, however, was dramatically impaired. GluR-B depletion in forebrain was ectopically variable ("mosaic") among individuals and strongly correlated with decreased olfactory memory in hippocampus and cortex. Accordingly, memory was rescued by transgenic GluR-B expression restricted to piriform cortex and hippocampus, while enhanced odor discrimination was independent of both GluR-B variability and transgenic GluR-B expression. Thus, correlated differences in behavior and levels of GluR-B expression allowed a mechanistic and spatial dissection of olfactory learning, discrimination, and memory capabilities.

  6. Apnea-induced rapid eye movement sleep disruption impairs human spatial navigational memory.

    Science.gov (United States)

    Varga, Andrew W; Kishi, Akifumi; Mantua, Janna; Lim, Jason; Koushyk, Viachaslau; Leibert, David P; Osorio, Ricardo S; Rapoport, David M; Ayappa, Indu

    2014-10-29

    Hippocampal electrophysiology and behavioral evidence support a role for sleep in spatial navigational memory, but the role of particular sleep stages is less clear. Although rodent models suggest the importance of rapid eye movement (REM) sleep in spatial navigational memory, a similar role for REM sleep has never been examined in humans. We recruited subjects with severe obstructive sleep apnea (OSA) who were well treated and adherent with continuous positive airway pressure (CPAP). Restricting CPAP withdrawal to REM through real-time monitoring of the polysomnogram provides a novel way of addressing the role of REM sleep in spatial navigational memory with a physiologically relevant stimulus. Individuals spent two different nights in the laboratory, during which subjects performed timed trials before and after sleep on one of two unique 3D spatial mazes. One night of sleep was normally consolidated with use of therapeutic CPAP throughout, whereas on the other night, CPAP was reduced only in REM sleep, allowing REM OSA to recur. REM disruption via this method caused REM sleep reduction and significantly fragmented any remaining REM sleep without affecting total sleep time, sleep efficiency, or slow-wave sleep. We observed improvements in maze performance after a night of normal sleep that were significantly attenuated after a night of REM disruption without changes in psychomotor vigilance. Furthermore, the improvement in maze completion time significantly positively correlated with the mean REM run duration across both sleep conditions. In conclusion, we demonstrate a novel role for REM sleep in human memory formation and highlight a significant cognitive consequence of OSA. Copyright © 2014 the authors 0270-6474/14/3414571-07$15.00/0.

  7. Discrepancy between severity of lung impairment and seniority on the lung transplantation list.

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    Travaline, J M; Cordova, F C; Furukawa, S; Criner, G J

    2004-12-01

    Organ allocation for lung transplantation, based mainly on accrued time on a waiting list, may not be an equitable system of organ allocation. To provide an objective view of the current practice concerning lung allocation, and timing for transplantation, we examined illness severity and list seniority in patients on a lung transplantation waiting list. Adult patients awaiting lung transplantation underwent testing for mean pulmonary artery pressure (mPpa), maximum oxygen consumption (VO2 max), 6-minute walk distance (6MWD), forced expiratory volume in 1 second, mean partial pressure of carbon dioxide, partial pressure of oxygen/fractional concentration of inspired oxygen, and diffusing capacity of the lung for carbon monoxide. Relationships between physiological variables and waiting list rankings were then determined. Thirty-four patients were tested and there was no correlation between time spent waiting on the list and mPpa (r=0.01; P=.94), VO2 max percentage predicted (r=0.07; P=.71), or 6MWD (r=0.15; P=.42). Many patients with functional impairments as indicated by low maximum VO2 or by short 6MWD are scheduled to receive their transplant after patients with levels that indicate a lower degree of risk. When compared with a hypothetical reranking based on mean Ppa, 24 of the 34 patients (71%) on our current waiting list were found to be 5 positions higher or lower than this new risk-based ranking. Sixteen patients (47%) were 10 or more positions away from their hypothetical severity-based ranking, and 9 (26%) were at least 15 positions out of place. Sixteen of the 34 patients were ranked lower than they would be based on a severity of illness using the pulmonary artery pressure alone, 17 were ranked higher than "should be" based on pulmonary artery mean, and only 1 patient (ranked in position 15) was appropriately positioned based on seniority and severity of disease based on PA mean. Rank order for lung transplantation has no relationship with illness

  8. Interhemispheric Pathways Are Important for Motor Outcome in Individuals with Chronic and Severe Upper Limb Impairment Post Stroke

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    Kathryn S. Hayward

    2017-01-01

    Full Text Available Background. Severity of arm impairment alone does not explain motor outcomes in people with severe impairment post stroke. Objective. Define the contribution of brain biomarkers to upper limb motor outcomes in people with severe arm impairment post stroke. Methods. Paretic arm impairment (Fugl-Meyer upper limb, FM-UL and function (Wolf Motor Function Test rate, WMFT-rate were measured in 15 individuals with severe (FM-UL ≤ 30/66 and 14 with mild–moderate (FM-UL > 40/66 impairment. Transcranial magnetic stimulation and diffusion weight imaging indexed structure and function of the corticospinal tract and corpus callosum. Separate models of the relationship between possible biomarkers and motor outcomes at a single chronic (≥6 months time point post stroke were performed. Results. Age (ΔR20.365, p=0.017 and ipsilesional-transcallosal inhibition (ΔR20.182, p=0.048 explained a 54.7% (p=0.009 variance in paretic WMFT-rate. Prefrontal corpus callous fractional anisotropy (PF-CC FA alone explained 49.3% (p=0.007 variance in FM-UL outcome. The same models did not explain significant variance in mild–moderate stroke. In the severe group, k-means cluster analysis of PF-CC FA distinguished two subgroups, separated by a clinically meaningful and significant difference in motor impairment (p=0.049 and function (p=0.006 outcomes. Conclusion. Corpus callosum function and structure were identified as possible biomarkers of motor outcome in people with chronic and severe arm impairment.

  9. Nephrogenic Systemic Fibrosis Risk After Liver Magnetic Resonance Imaging With Gadoxetate Disodium in Patients With Moderate to Severe Renal Impairment

    Science.gov (United States)

    Lauenstein, Thomas; Ramirez-Garrido, Francisco; Kim, Young Hoon; Rha, Sung Eun; Ricke, Jens; Phongkitkarun, Sith; Boettcher, Joachim; Gupta, Rajan T.; Korpraphong, Pornpim; Tanomkiat, Wiwatana; Furtner, Julia; Liu, Peter S.; Henry, Maren; Endrikat, Jan

    2015-01-01

    Objective The objective of this study was to assess the risk of gadoxetate disodium in liver imaging for the development of nephrogenic systemic fibrosis (NSF) in patients with moderate to severe renal impairment. Materials and Methods We performed a prospective, multicenter, nonrandomized, open-label phase 4 study in 35 centers from May 2009 to July 2013. The study population consisted of patients with moderate to severe renal impairment scheduled for liver imaging with gadoxetate disodium. All patients received a single intravenous bolus injection of 0.025-mmol/kg body weight of liver-specific gadoxetate disodium. The primary target variable was the number of patients who develop NSF within a 2-year follow-up period. Results A total of 357 patients were included, with 85 patients with severe and 193 patients with moderate renal impairment, which were the clinically most relevant groups. The mean time period from diagnosis of renal disease to liver magnetic resonance imaging (MRI) was 1.53 and 5.46 years in the moderate and severe renal impairment cohort, respectively. Overall, 101 patients (28%) underwent additional contrast-enhanced MRI with other gadolinium-based MRI contrast agents within 12 months before the start of the study or in the follow-up. No patient developed symptoms conclusive of NSF within the 2-year follow-up. Conclusions Gadoxetate disodium in patients with moderate to severe renal impairment did not raise any clinically significant safety concern. No NSF cases were observed. PMID:25756684

  10. Spatial Navigation Impairment Is Associated with Alterations in Subcortical Intrinsic Activity in Mild Cognitive Impairment: A Resting-State fMRI Study

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    Zhao Qing

    2017-01-01

    Full Text Available Impairment of spatial navigation (SN skills is one of the features of the Alzheimer’s disease (AD already at the stage of mild cognitive impairment (MCI. We used a computer-based battery of spatial navigation tests to measure the SN performance in 22 MCI patients as well as 21 normal controls (NC. In order to evaluate intrinsic activity in the subcortical regions that may play a role in SN, we measured ALFF, fALFF, and ReHo derived within 14 subcortical regions. We observed reductions of intrinsic activity in MCI patients. We also demonstrated that the MCI versus NC group difference can modulate activity-behavior relationship, that is, the correlation slopes between ReHo and allocentric SN task total errors were significantly different between NC and MCI groups in the right hippocampus (interaction F=4.44, p=0.05, pallidum (F=8.97, p=0.005, and thalamus (F=5.95, p=0.02, which were negative in NC (right hippocampus, r=−0.49; right pallidum, r=−0.50; right thalamus, r=−0.45; all p0.2. These findings may provide a novel insight of the brain mechanism associated with SN impairment in MCI and indicated a stage specificity of brain-behavior correlation in dementia. This trial is registered with ChiCTR-BRC-17011316.

  11. Impairments in Dark Adaptation Are Associated with Age-Related Macular Degeneration Severity and Reticular Pseudodrusen.

    Science.gov (United States)

    Flamendorf, Jason; Agrón, Elvira; Wong, Wai T; Thompson, Darby; Wiley, Henry E; Doss, E Lauren; Al-Holou, Shaza; Ferris, Frederick L; Chew, Emily Y; Cukras, Catherine

    2015-10-01

    We investigate whether ocular and person-based characteristics were associated with dark adaptation (DA). Cross-sectional, single-center, observational study. One hundred sixteen participants older than 50 years of age with a range of age-related macular degeneration (AMD) severity. Participants underwent best-corrected visual acuity (BCVA) testing, ophthalmoscopic examination, and multimodal imaging. Presence of reticular pseudodrusen (RPD) was assessed by masked grading of fundus images and was confirmed with optical coherence tomography. Eyes also were graded for AMD features (drusen, pigmentary changes, late AMD) to generate person-based AMD severity groups. One eye was designated the study eye for DA testing. Nonparametric statistical testing was performed on all comparisons. The primary outcome of this study was the rod intercept time (RIT), which is defined as the time for a participant's visual sensitivity to recover to a stimulus intensity of 5×10(-3) cd/m(2) (a decrease of 3 log units), or until a maximum test duration of 40 minutes was reached. A total of 116 study eyes from 116 participants (mean age, 75.4±9.4 years; 58% female) were analyzed. Increased RIT was associated significantly with increasing AMD severity, increasing age (r = 0.34; P = 0.0002), decreasing BCVA (r = -0.54; P < 0.0001), pseudophakia (P = 0.03), and decreasing subfoveal choroidal thickness (r = -0.27; P = 0.003). Study eyes with RPD (15/116 [13%]) had a significantly greater mean RIT compared with eyes without RPD in any AMD severity group (P < 0.02 for all comparisons), with 80% reaching the DA test ceiling. Impairments in DA increased with age, worse visual acuity, presence of RPD, AMD severity, and decreased subfoveal choroidal thickness. Analysis of covariance found the multivariate model that best fit the data included age, AMD group, and presence of RPD (R(2) = 0.56), with the presence of RPD conferring the largest parameter estimate. Copyright © 2015 American Academy of

  12. Spatial extreme value analysis to project extremes of large-scale indicators for severe weather.

    Science.gov (United States)

    Gilleland, Eric; Brown, Barbara G; Ammann, Caspar M

    2013-09-01

    Concurrently high values of the maximum potential wind speed of updrafts ( W max ) and 0-6 km wind shear (Shear) have been found to represent conducive environments for severe weather, which subsequently provides a way to study severe weather in future climates. Here, we employ a model for the product of these variables (WmSh) from the National Center for Atmospheric Research/United States National Center for Environmental Prediction reanalysis over North America conditioned on their having extreme energy in the spatial field in order to project the predominant spatial patterns of WmSh. The approach is based on the Heffernan and Tawn conditional extreme value model. Results suggest that this technique estimates the spatial behavior of WmSh well, which allows for exploring possible changes in the patterns over time. While the model enables a method for inferring the uncertainty in the patterns, such analysis is difficult with the currently available inference approach. A variation of the method is also explored to investigate how this type of model might be used to qualitatively understand how the spatial patterns of WmSh correspond to extreme river flow events. A case study for river flows from three rivers in northwestern Tennessee is studied, and it is found that advection of WmSh from the Gulf of Mexico prevails while elsewhere, WmSh is generally very low during such extreme events. © 2013 The Authors. Environmetrics published by JohnWiley & Sons, Ltd.

  13. Spatial navigation, episodic memory, episodic future thinking, and theory of mind in children with autism spectrum disorder: evidence for impairments in mental simulation?

    Science.gov (United States)

    Lind, Sophie E; Bowler, Dermot M; Raber, Jacob

    2014-01-01

    This study explored spatial navigation alongside several other cognitive abilities that are thought to share common underlying neurocognitive mechanisms (e.g., the capacity for self-projection, scene construction, or mental simulation), and which we hypothesized may be impaired in autism spectrum disorder (ASD). Twenty intellectually high-functioning children with ASD (with a mean age of ~8 years) were compared to 20 sex, age, IQ, and language ability matched typically developing children on a series of tasks to assess spatial navigation, episodic memory, episodic future thinking (also known as episodic foresight or prospection), theory of mind (ToM), relational memory, and central coherence. This is the first study to explore these abilities concurrently within the same sample. Spatial navigation was assessed using the "memory island" task, which involves finding objects within a realistic, computer simulated, three-dimensional environment. Episodic memory and episodic future thinking were assessed using a past and future event description task. ToM was assessed using the "animations" task, in which children were asked to describe the interactions between two animated triangles. Relational memory was assessed using a recognition task involving memory for items (line drawings), patterned backgrounds, or combinations of items and backgrounds. Central coherence was assessed by exploring differences in performance across segmented and unsegmented versions of block design. Children with ASD were found to show impairments in spatial navigation, episodic memory, episodic future thinking, and central coherence, but not ToM or relational memory. Among children with ASD, spatial navigation was found to be significantly negatively related to the number of repetitive behaviors. In other words, children who showed more repetitive behaviors showed poorer spatial navigation. The theoretical and practical implications of the results are discussed.

  14. Spatial navigation, episodic memory, episodic future thinking, and theory of mind in children with autism spectrum disorder: Evidence for impairments in mental simulation?

    Directory of Open Access Journals (Sweden)

    Sophie Elizabeth Lind

    2014-12-01

    Full Text Available This study explored spatial navigation alongside several other cognitive abilities that are thought to share common underlying neurocognitive mechanisms (e.g., the capacity for self-projection, scene construction, or mental simulation, and which we hypothesised may be impaired in autism spectrum disorder (ASD. Twenty intellectually high-functioning children with ASD (with a mean age of ~8 years were compared to 20 sex, age, IQ, and language ability matched typically developing children on a series of tasks to assess spatial navigation, episodic memory, episodic future thinking (also known as episodic foresight or prospection, theory of mind, relational memory, and central coherence. This is the first study to explore these abilities concurrently within the same sample. Spatial navigation was assessed using the memory island task, which involves finding objects within a realistic, computer simulated, three-dimensional environment. Episodic memory and episodic future thinking were assessed using a past and future event description task. Theory of mind was assessed using the animations task, in which children were asked to describe the interactions between two animated triangles. Relational memory was assessed using a recognition task involving memory for items (line drawings, patterned backgrounds, or combinations of items and backgrounds. Central coherence was assessed by exploring differences in performance across segmented and unsegmented versions of block design. Children with ASD were found to show impairments in spatial navigation, episodic memory, episodic future thinking, and central coherence, but not theory of mind or relational memory. Among children with ASD, spatial navigation was found to be significantly negatively related to number of repetitive behaviours. In other words, children who showed more repetitive behaviours showed poorer spatial navigation. The theoretical and practical implications of the results are discussed.

  15. Spatial navigation, episodic memory, episodic future thinking, and theory of mind in children with autism spectrum disorder: evidence for impairments in mental simulation?

    Science.gov (United States)

    Lind, Sophie E.; Bowler, Dermot M.; Raber, Jacob

    2014-01-01

    This study explored spatial navigation alongside several other cognitive abilities that are thought to share common underlying neurocognitive mechanisms (e.g., the capacity for self-projection, scene construction, or mental simulation), and which we hypothesized may be impaired in autism spectrum disorder (ASD). Twenty intellectually high-functioning children with ASD (with a mean age of ~8 years) were compared to 20 sex, age, IQ, and language ability matched typically developing children on a series of tasks to assess spatial navigation, episodic memory, episodic future thinking (also known as episodic foresight or prospection), theory of mind (ToM), relational memory, and central coherence. This is the first study to explore these abilities concurrently within the same sample. Spatial navigation was assessed using the “memory island” task, which involves finding objects within a realistic, computer simulated, three-dimensional environment. Episodic memory and episodic future thinking were assessed using a past and future event description task. ToM was assessed using the “animations” task, in which children were asked to describe the interactions between two animated triangles. Relational memory was assessed using a recognition task involving memory for items (line drawings), patterned backgrounds, or combinations of items and backgrounds. Central coherence was assessed by exploring differences in performance across segmented and unsegmented versions of block design. Children with ASD were found to show impairments in spatial navigation, episodic memory, episodic future thinking, and central coherence, but not ToM or relational memory. Among children with ASD, spatial navigation was found to be significantly negatively related to the number of repetitive behaviors. In other words, children who showed more repetitive behaviors showed poorer spatial navigation. The theoretical and practical implications of the results are discussed. PMID:25538661

  16. MEMANTINE ATTENUATES THE OKADAIC ACID INDUCED SHORT-TERM SPATIAL MEMORY IMPAIRMENT AND HIPPOCAMPAL CELL LOSS IN RATS.

    Science.gov (United States)

    Dashniani, M; Chighladze, M; Burjanadze, M; Beselia, G; Kruashvili, L

    2016-03-01

    In the present study, the possible beneficial effect of memantine on the Okadaic Acid (OA) induced spatial short-term memory impairment was examined in spatial alternation task, and the neuroprotective potential of memantine on OA-induced structural changes in the hippocampus was evaluated by Nissl staining. OA was dissolved in artificial cerebrospinal fluid (aCSF) and injected intracerebroventriculary (ICV) 200 ng in a volume of 10 μl bilaterally. Vehicle control received aCSF ICV bilaterally. Control and OA injected rats were divided into 2 subgroups injected i.p. with saline or memantine (5 mg/kg). Memantine or saline were given daily for 13 days starting from the day of OA injection. Behavioral study showed that bilateral ICV microinjection of OA induced impairment in spatial short-term memory. Nissl staining in the present study showed that the ICV microinjection of OA significantly decreased the number of surviving pyramidal neurons in the CA1 region of the hippocampus. Chronic administration of memantine effectively attenuated OA induced spatial short-term memory impairment and the OA-induced neuropathological changes in the hippocampus. Therefore, ICV injection of OA can be used as an experimental model to study mechanisms of neurodegeneration and define novel therapeutics targets for AD pathology.

  17. Low Birth Weight Impairs Acquisition of Spatial Memory Task in Pigs

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    Sanne Roelofs

    2018-06-01

    Full Text Available In commercial pig farming, an increasing number of low birth weight (LBW piglets are born, due to selection for large litter sizes. While LBW piglets have a higher risk of pre-weaning mortality, a considerable number of these piglets survive to slaughter age. In humans, LBW is a risk factor for long-term cognitive impairments. In pigs, studies examining the post-weaning effects of LBW on cognition have reported contradictory results. Therefore, the current study aimed to assess the effects of LBW on cognitive development in pigs using an improved study design, by (1 testing a larger sample size than previous studies, (2 assessing acute and chronic stress responses to account for a potential altered stress response in LBW pigs, and (3 testing both female and male pigs to account for potential confounding effects of sex. Learning and memory of 20 LBW pigs and 20 normal birth weight (NBW pigs, both groups consisting of 10 females and 10 males, were compared using a spatial holeboard task. In this task, pigs had to learn and remember the locations of hidden food rewards. After a pig had successfully acquired the task, it was presented with two successive reversal phases during which it was presented with a new configuration of reward locations. The holeboard allows for simultaneous assessment of working and reference memory, as well as measures of motivation, exploration, and behavioral flexibility. Mixed model ANOVAs revealed a transiently impaired reference memory performance of LBW pigs, implying they had more difficulty learning their reward configuration in the holeboard. Also, LBW piglets showed increased pre-weaning hair cortisol concentrations compared to their NBW siblings. No other effects of LBW were found. Sex had no direct or interaction effects on any measures of holeboard performance or stress. It is possible that the enriched housing conditions applied during our study had an ameliorating effect on our pigs' cognitive development

  18. Functional Dissociation of Confident and Not-Confident Errors in the Spatial Delayed Response Task Demonstrates Impairments in Working Memory Encoding and Maintenance in Schizophrenia

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    Jutta S. Mayer

    2018-05-01

    Full Text Available Even though extensively investigated, the nature of working memory (WM deficits in patients with schizophrenia (PSZ is not yet fully understood. In particular, the contribution of different WM sub-processes to the severe WM deficit observed in PSZ is a matter of debate. So far, most research has focused on impaired WM maintenance. By analyzing different types of errors in a spatial delayed response task (DRT, we have recently demonstrated that incorrect yet confident responses (which we labeled as false memory errors rather than incorrect/not-confident responses reflect failures of WM encoding, which was also impaired in PSZ. In the present study, we provide further evidence for a functional dissociation between confident and not-confident errors by manipulating the demands on WM maintenance, i.e., the length over which information has to be maintained in WM. Furthermore, we investigate whether these functionally distinguishable WM processes are impaired in PSZ. Twenty-four PSZ and 24 demographically matched healthy controls (HC performed a spatial DRT in which the length of the delay period was varied between 1, 2, 4, and 6 s. In each trial, participants also rated their level of response confidence. Across both groups, longer delays led to increased rates of incorrect/not-confident responses, while incorrect/confident responses were not affected by delay length. This functional dissociation provides additional support for our proposal that false memory errors (i.e., confident errors reflect problems at the level of WM encoding, while not-confident errors reflect failures of WM maintenance. Schizophrenic patients showed increased numbers of both confident and not-confident errors, suggesting that both sub-processes of WM—encoding and maintenance—are impaired in schizophrenia. Combined with the delay length-dependent functional dissociation, we propose that these impairments in schizophrenic patients are functionally distinguishable.

  19. Severely impaired health-related quality of life in chronic hyperventilation patients: exploratory data.

    Science.gov (United States)

    Chenivesse, Cécile; Similowski, Thomas; Bautin, Nathalie; Fournier, Clément; Robin, Sophie; Wallaert, Benoît; Perez, Thierry

    2014-03-01

    Patients with hyperventilation syndrome (HVS) report severe symptom-related suffering and often complain from insufficient medical attention. However, quality of life data in this context are scarce. We aimed at assessing the health-related quality of life (HRQoL) of HVS patients. Twenty-one HVS patients with extensive cardiorespiratory workup including cardiopulmonary exercise testing (CPET) filled in the generic SF-36 questionnaire and the results were compared to French normal values. Correlations between SF36 dimensions and clinical and functional data were established. All SF-36 scores were markedly decreased in HVS patients compared to healthy subjects: Physical Functioning: 44 ± 24, Social Functioning: 57 ± 27, Role Physical: 21 ± 32, Role Emotional: 48 ± 42, Mental Health: 51 ± 27, Vitality: 34 ± 20, Body Pain: 41 ± 21, General Health: 42 ± 21. These figures were all significantly lower in the HVS patients respective to the normal reference population. They were also lower than corresponding values published in patients with asthma or chronic obstructive pulmonary disease (COPD). "Vitality" and "Physical Functioning" scores were correlated with Nijmegen score (r = -0.594, p = 0.047) and peak respiratory frequency during CPET (r = -0.644, p = 0.019). The SF-36 Social Functioning score was correlated with the ventilatory threshold (r = 0.629, p = 0.034), peak V'E/V'CO2 (ventilation/CO2 production) (r = 0.650, p = 0.016) and peak PaCO2 (r = -0.664, p = 0.027). In conclusion, this study shows that HRQoL can be severely impaired in patients with HVS, which is one more reason to take this condition seriously. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Mixed-severity fire fosters heterogeneous spatial patterns of conifer regeneration in a dry conifer forest

    Science.gov (United States)

    Sparkle L. Malone; Paula J. Fornwalt; Mike A. Battaglia; Marin E. Chambers; Jose M. Iniguez; Carolyn H. Sieg

    2018-01-01

    We examined spatial patterns of post-fire regenerating conifers in a Colorado, USA, dry conifer forest 11-12 years following the reintroduction of mixed-severity fire. We mapped and measured all post-fire regenerating conifers, as well as all other post-fire regenerating trees and all residual (i.e., surviving) trees, in three 4-ha plots following the 2002 Hayman Fire...

  1. Noonan Syndrome: An Underestimated Cause of Severe to Profound Sensorineural Hearing Impairment. Which Clues to Suspect the Diagnosis?

    Science.gov (United States)

    Ziegler, Alban; Loundon, Natalie; Jonard, Laurence; Cavé, Hélène; Baujat, Geneviève; Gherbi, Souad; Couloigner, Vincent; Marlin, Sandrine

    2017-09-01

    To highlight Noonan syndrome as a clinically recognizable cause of severe to profound sensorineural hearing impairment. New clinical cases and review. Patients evaluated for etiological diagnosis by a medical geneticist in a reference center for hearing impairment. Five patients presenting with confirmed Noonan syndrome and profound sensorineural hearing impairment. Diagnostic and review of the literature. Five patients presented with profound sensorineural hearing impairment and molecularly confirmed Noonan syndrome. Sensorineural hearing impairment has been progressive for three patients. Cardiac echography identified pulmonary stenosis in two patients and was normal for the three other patients. Short stature was found in two patients. Mild intellectual disability was found in one patient. Inconspicuous clinical features as facial dysmorphism, cryptorchidism, or easy bruising were of peculiar interest to reach the diagnosis of Noonan syndrome. Profound sensorineural hearing impairment can be the main feature of Noonan syndrome. Associated features are highly variable; thus, detailed medical history and careful physical examination are mandatory to consider the diagnosis in case of a sensorineural hearing impairment.

  2. 20 CFR 404.1521 - What we mean by an impairment(s) that is not severe.

    Science.gov (United States)

    2010-04-01

    ... severe. 404.1521 Section 404.1521 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE... remembering simple instructions; (4) Use of judgment; (5) Responding appropriately to supervision, co-workers and usual work situations; and (6) Dealing with changes in a routine work setting. [50 FR 8728, Mar. 5...

  3. Considering built environment and spatial correlation in modeling pedestrian injury severity.

    Science.gov (United States)

    Prato, Carlo G; Kaplan, Sigal; Patrier, Alexandre; Rasmussen, Thomas K

    2018-01-02

    This study looks at mitigating and aggravating factors that are associated with the injury severity of pedestrians when they have crashes with another road user and overcomes existing limitations in the literature by focusing attention on the built environment and considering spatial correlation across crashes. Reports for 6,539 pedestrian crashes occurred in Denmark between 2006 and 2015 were merged with geographic information system resources containing detailed information about the built environment and exposure at the crash locations. A linearized spatial logit model estimated the probability of pedestrians sustaining a severe or fatal injury conditional on the occurrence of a crash with another road user. This study confirms previous findings about older pedestrians and intoxicated pedestrians being the most vulnerable road users and crashes with heavy vehicles and in roads with higher speed limits being related to the most severe outcomes. This study provides novel perspectives by showing positive spatial correlations of crashes with the same severity outcomes and emphasizing the role of the built environment in the proximity of the crash. This study emphasizes the need for thinking about traffic calming measures, illumination solutions, road maintenance programs, and speed limit reductions. Moreover, this study emphasizes the role of the built environment, because shopping areas, residential areas, and walking traffic density are positively related to a reduction in pedestrian injury severity. Often, these areas have in common a larger pedestrian mass that is more likely to make other road users more aware and attentive, whereas the same does not seem to apply to areas with lower pedestrian density.

  4. Effect of an NCAM mimetic peptide FGL on impairment in spatial learning and memory after neonatal phencyclidine treatment in rats

    DEFF Research Database (Denmark)

    Secher, Thomas; Berezin, Vladimir; Bock, Elisabeth

    2008-01-01

    treatment regimen where FGL was administered throughout development. Rats were tested as adults for spatial reference memory, reversal learning, and working memory in the Morris water maze. The PCP-treated rats demonstrated a robust impairment in working memory and reversal learning. However, the long-term......The FGL peptide is a neural cell adhesion molecule-derived fibroblast growth factor receptor agonist. FGL has both neurotrophic and memory enhancing properties. Neonatal phencyclidine (PCP) treatment on postnatal days 7, 9, and 11 has been shown to result in long-lasting behavioral abnormalities......, including cognitive impairment relevant to schizophrenia. The present study investigated the effect of FGL on spatial learning and memory deficits induced by neonatal PCP treatment. Rat pups were treated with 30mg/kg PCP on postnatal days 7, 9, and 11. Additionally, the rats were subjected to a chronic FGL...

  5. Yes/No Versus Forced-Choice Recognition Memory in Mild Cognitive Impairment and Alzheimer’s Disease: Patterns of Impairment and Associations with Dementia Severity

    Science.gov (United States)

    Clark, Lindsay R.; Stricker, Nikki H.; Libon, David J.; Delano-Wood, Lisa; Salmon, David P.; Delis, Dean C.; Bondi, Mark W.

    2012-01-01

    Memory tests are sensitive to early identification of Alzheimer’s disease (AD) but less useful as the disease advances. However, assessing particular types of recognition memory may better characterize dementia severity in later stages of AD. We sought to examine patterns of recognition memory deficits in individuals with AD and mild cognitive impairment (MCI). Memory performance and global cognition data were collected from participants with AD (n=37), MCI (n=37), and cognitively intact older adults (normal controls, NC; n=35). One-way analyses of variance (ANOVAs) examined differences between groups on yes/no and forced-choice recognition measures. Individuals with amnestic MCI performed worse than NC and nonamnestic MCI participants on yes/no recognition, but were comparable on forced-choice recognition. AD patients were more impaired across yes/no and forced-choice recognition tasks. Individuals with mild AD (≥120 Dementia Rating Scale, DRS) performed better than those with moderate-to-severe AD (recognition, but were equally impaired on yes/no recognition. There were differences in the relationships between learning, recall, and recognition performance across groups. Although yes/no recognition testing may be sensitive to MCI, forced-choice procedures may provide utility in assessing severity of anterograde amnesia in later stages of AD. Implications for assessment of insufficient effort and malingering are also discussed. PMID:23030301

  6. Neuroligin 2 R215H Mutant Mice Manifest Anxiety, Increased Prepulse Inhibition, and Impaired Spatial Learning and Memory

    Directory of Open Access Journals (Sweden)

    Chia-Hsiang Chen

    2017-11-01

    Full Text Available Neuroligin 2 (NLGN2 is a postsynaptic adhesion protein that plays an essential role in synaptogenesis and function of inhibitory neuron. We previously identified a missense mutation R215H of the NLGN2 in a patient with schizophrenia. This missense mutation was shown to be pathogenic in several cell-based assays. The objective of this study was to better understand the behavioral consequences of this mutation in vivo. We generated a line of transgenic mice carrying this mutation using a recombinant-based method. The mice were subjected to a battery of behavioral tests including open field locomotor activity assay, prepulse inhibition (PPI assay, accelerated rotarod test, novel location and novel recognition tests, elevated plus-maze (EPM test, and Morris water maze test. The transgenic animals were viable and fertile, but the Nlgn2 R215H knock-in (KI homozygous mice showed growth retardation, anxiety-like behavior, increased PPI, and impaired spatial learning and memory. There was no significant interaction between sex and genotype in most behavioral tests; however, we observed a significant interaction between sex and genotype in EPM test in this study. Also, we found that the Nlgn2 R215H homozygous KI mice did not express the NLGN2 protein, resembling Nlgn2 knockout mice. Our results demonstrate that Nlgn2 R215H KI homozygous mice manifest several behavioral abnormalities similar to those found in psychiatric patients carrying NLGN2 mutations, indicating that dysfunction of NLGN2 contributes to the pathogenesis of certain psychiatric symptoms commonly present in various mental disorders, not limited to schizophrenia.

  7. Increased lipolysis and energy expenditure in a mouse model with severely impaired glucagon secretion.

    Directory of Open Access Journals (Sweden)

    Phing-How Lou

    Full Text Available BACKGROUND: Secretion of insulin and glucagon is triggered by elevated intracellular calcium levels. Although the precise mechanism by which the calcium signal is coupled to insulin and glucagon granule exocytosis is unclear, synaptotagmin-7 has been shown to be a positive regulator of calcium-dependent insulin and glucagon secretion, and may function as a calcium sensor for insulin and glucagon granule exocytosis. Deletion of synaptotagmin-7 leads to impaired glucose-stimulated insulin secretion and nearly abolished Ca(2+-dependent glucagon secretion in mice. Under non-stressed resting state, however, synaptotagmin-7 KO mice exhibit normal insulin level but severely reduced glucagon level. METHODOLOGY/PRINCIPAL FINDINGS: We studied energy expenditure and metabolism in synaptotagmin-7 KO and control mice using indirect calorimetry and biochemical techniques. Synaptotagmin-7 KO mice had lower body weight and body fat content, and exhibited higher oxygen consumption and basal metabolic rate. Respiratory exchange ratio (RER was lower in synaptotagmin-7 KO mice, suggesting an increased use of lipid in their energy production. Consistent with lower RER, gene expression profiles suggest enhanced lipolysis and increased capacity for fatty acid transport and oxidation in synaptotagmin-7 KO mice. Furthermore, expression of uncoupling protein 3 (UCP3 in skeletal muscle was approximately doubled in the KO mice compared with control mice. CONCLUSIONS: These results show that the lean phenotype in synaptotagmin-7 KO mice was mostly attributed to increased lipolysis and energy expenditure, and suggest that reduced glucagon level may have broad influence on the overall metabolism in the mouse model.

  8. Chronic Stress Impairs Spatial Memory and Motivation for Reward Without Disrupting Motor Ability and Motivation to Explore

    OpenAIRE

    Kleen, Jonathan K.; Sitomer, Matthew T.; Killeen, Peter R.; Conrad, Cheryl D.

    2006-01-01

    This study uses an operant, behavioral model to assess the daily changes in the decay rate of short-term memory, motivation, and motor ability in rats exposed to chronic restraint. Restraint decreased reward-related motivation by 50% without altering memory decay rate or motor ability. Moreover, chronic restraint impaired hippocampal-dependent spatial memory on the Y maze (4-hr delay) and produced CA3 dendritic retraction without altering hippocampal-independent maze navigation (1-min delay) ...

  9. Considering built environment and spatial correlation in modelling pedestrian injury severity

    DEFF Research Database (Denmark)

    Prato, Carlo G.; Kaplan, Sigal; Patrier, Alexandre

    traffic calming measures, illumination solutions, road maintenance programs and speed limit reductions. Moreover, this study emphasises the role of the built environment, as shopping areas, residential areas, and walking traffic density are positively related to a reduction in pedestrian injury severity......This study looks at mitigating and aggravating factors that are associated with the injury severity of pedestrians when they have crashes with another road user and overcomes existing limitations in the literature by posing attention on the built environment and considering spatial correlation...... of pedestrians to sustain a severe or fatal injury conditional on the occurrence of a crash with another road user. This study confirms previous findings about older pedestrians and intoxicated pedestrians being the most vulnerable road users, and crashes with heavy vehicles and in roads with higher speed limits...

  10. Considering built environment and spatial correlation in modelling pedestrian injury severity

    DEFF Research Database (Denmark)

    Prato, Carlo G.; Kaplan, Sigal; Patrier, Alexandre

    2018-01-01

    traffic calming measures, illumination solutions, road maintenance programs and speed limit reductions. Moreover, this study emphasises the role of the built environment, as shopping areas, residential areas, and walking traffic density are positively related to a reduction in pedestrian injury severity......This study looks at mitigating and aggravating factors that are associated with the injury severity of pedestrians when they have crashes with another road user and overcomes existing limitations in the literature by posing attention on the built environment and considering spatial correlation...... of pedestrians to sustain a severe or fatal injury conditional on the occurrence of a crash with another road user. This study confirms previous findings about older pedestrians and intoxicated pedestrians being the most vulnerable road users, and crashes with heavy vehicles and in roads with higher speed limits...

  11. Social Cognition Impairments in Relation to General Cognitive Deficits, Injury Severity, and Prefrontal Lesions in Traumatic Brain Injury Patients

    NARCIS (Netherlands)

    Spikman, Jacoba M.; Timmerman, Marieke E.; Milders, Maarten V.; Veenstra, Wencke S.; van der Naalt, Joukje

    2012-01-01

    Impairments in social behavior are frequently found in moderate to severe traumatic brain injury (TBI) patients and are associated with an unfavorable outcome with regard to return to work and social reintegration. Neuropsychological tests measuring aspects of social cognition are thought to be

  12. Disposition of [G-(3)H]paclitaxel and cremophor EL in a patient with severely impaired renal function

    NARCIS (Netherlands)

    A.J. Gelderblom (Hans); J. Verweij (Jaap); E. Brouwer (Eric); M. Pillay; P. de Bruijn (Peter); K. Nooter (Kees); G. Stoter (Gerrit); A. Sparreboom (Alex)

    1999-01-01

    textabstractIn the present work, we studied the pharmacokinetics and metabolic disposition of [G-(3)H]paclitaxel in a female patient with recurrent ovarian cancer and severe renal impairment (creatinine clearance: approximately 20 ml/min) due to chronic hypertension and

  13. Eye gaze performance for children with severe physical impairments using gaze-based assistive technology-A longitudinal study.

    Science.gov (United States)

    Borgestig, Maria; Sandqvist, Jan; Parsons, Richard; Falkmer, Torbjörn; Hemmingsson, Helena

    2016-01-01

    Gaze-based assistive technology (gaze-based AT) has the potential to provide children affected by severe physical impairments with opportunities for communication and activities. This study aimed to examine changes in eye gaze performance over time (time on task and accuracy) in children with severe physical impairments, without speaking ability, using gaze-based AT. A longitudinal study with a before and after design was conducted on 10 children (aged 1-15 years) with severe physical impairments, who were beginners to gaze-based AT at baseline. Thereafter, all children used the gaze-based AT in daily activities over the course of the study. Compass computer software was used to measure time on task and accuracy with eye selection of targets on screen, and tests were performed with the children at baseline, after 5 months, 9-11 months, and after 15-20 months. Findings showed that the children improved in time on task after 5 months and became more accurate in selecting targets after 15-20 months. This study indicates that these children with severe physical impairments, who were unable to speak, could improve in eye gaze performance. However, the children needed time to practice on a long-term basis to acquire skills needed to develop fast and accurate eye gaze performance.

  14. Spatial Cognition in Autism Spectrum Disorders: Superior, Impaired, or Just Intact?

    Science.gov (United States)

    Edgin, Jamie O.; Pennington, Bruce F.

    2005-01-01

    The profile of spatial ability is of interest across autism spectrum disorders (ASD) because of reported spatial strengths in ASD and due to the recent association of Asperger's syndrome with Nonverbal Learning Disability. Spatial functions were examined in relation to two cognitive theories in autism: the central coherence and executive function…

  15. Rhyme and Syllable Recognition in Severe to Profound Hearing-Impaired Children

    Directory of Open Access Journals (Sweden)

    MohammadReza Keihani

    2003-09-01

    Full Text Available Objective: A research was conducted to assess the phonological awareness in hearing-impaired children in comparison to normal children. In this context, we discussed about the ability of these children in identification of rhyme and word segmentation to syllables. Method and Material: The sample of this study is composed of 320 children, 160 normal & 160 hearing-impaired with a hearing-loss. Of over 70 dB, studying in the 1st t 4th grade of the primary schools in Tehran. They are divided into two groups at each level (20 girls & 20 boys. Results: 1 Hearing-impaired children's scores on test related to rhyme and syllable is lower as compared with normal children. 2 Hearing-impaired children are more potent on test of word segmentation to syllables in comparison to that related to rhyme, while normal children are more successful on test of word segmentation to syllables as compared with that related to rhyme. Discussion: Hearing is an important factor in phonological awareness. Formal education at special schools doesn't compensate for the hearing impairment as to development of the phonological awareness.

  16. Mixed-Severity Fire Fosters Heterogeneous Spatial Patterns of Conifer Regeneration in a Dry Conifer Forest

    Directory of Open Access Journals (Sweden)

    Sparkle L. Malone

    2018-01-01

    Full Text Available We examined spatial patterns of post-fire regenerating conifers in a Colorado, USA, dry conifer forest 11–12 years following the reintroduction of mixed-severity fire. We mapped and measured all post-fire regenerating conifers, as well as all other post-fire regenerating trees and all residual (i.e., surviving trees, in three 4-ha plots following the 2002 Hayman Fire. Residual tree density ranged from 167 to 197 trees ha−1 (TPH, and these trees were clustered at distances up to 30 m. Post-fire regenerating conifers, which ranged in density from 241 to 1036 TPH, were also clustered at distances up to at least 30 m. Moreover, residual tree locations drove post-fire regenerating conifer locations, with the two showing a pattern of repulsion. Topography and post-fire sprouting tree species locations further drove post-fire conifer regeneration locations. These results provide a foundation for anticipating how the reintroduction of mixed-severity fire may affect long-term forest structure, and also yield insights into how historical mixed-severity fire may have regulated the spatially heterogeneous conditions commonly described for pre-settlement dry conifer forests of Colorado and elsewhere.

  17. Impact of spatial kinetics in severe accident analysis for a large HWR

    International Nuclear Information System (INIS)

    Morris, E.E.

    1994-01-01

    The impact on spatial kinetics on the analysis of severe accidents initiated by the unprotected withdrawal of one or more control rods is investigated for a large heavy water reactor. Large inter- and intra-assembly power shifts are observed, and the importance of detailed geometrical modeling of fuel assemblies is demonstrated. Neglect of space-time effects is shown to lead to erroneous estimates of safety margins, and of accident consequences in the event safety margins are exceeded. The results and conclusions are typical of what would be expected for any large, loosely coupled core

  18. Measuring change in activities of daily living in nursing home residents with moderate to severe cognitive impairment

    Directory of Open Access Journals (Sweden)

    Fries Brant E

    2006-04-01

    Full Text Available Abstract Background The objective of this study was to assess the responsiveness of the Minimum Data Set Activities of Daily Living (MDS-ADL Scale to change over time by examining the change in physical function in adults with moderate to severe dementia with no comorbid illness who had been resident in a nursing home for over 90 days. Methods Longitudinal data were collected on nursing home residents with moderate (n = 7001 or severe (n = 4616 dementia in one US state from the US national Minimum Data Set (MDS. Severity of dementia was determined by the MDS Cognitive Performance Scale (CPS. Physical function was assessed by summing the seven items (bed mobility, transfer, locomotion, dressing, eating, toilet use, personal hygiene on the MDS activities of daily living (ADL Long Form scale. Mean change over time of MDS-ADL scores were estimated at three and six months for residents with moderate (CPS score of 3 and severe (CPS score of 4 or 5 dementia. Results Physical function in residents with moderate cognitive impairment deteriorated over six months by an average of 1.78 points on the MDS-ADL Long Form scale, while those with severe cognitive impairment declined by an average of 1.70 points. Approximately one quarter of residents in both groups showed some improvement in physical function over the six month period. Residents with moderate cognitive impairment experienced the greatest deterioration in early-loss and mid-loss ADL items (personal hygiene, dressing, toilet use and residents with severe cognitive impairment showed the greatest deterioration in activities related to eating, a late loss ADL. Conclusion The MDS-ADL Long Form scale detected clinically meaningful change in physical function in a large cohort of long-stay nursing home residents with moderate to severe dementia, supporting its use as a research tool in future studies.

  19. Measuring change in activities of daily living in nursing home residents with moderate to severe cognitive impairment

    Science.gov (United States)

    Carpenter, G Iain; Hastie, Charlotte L; Morris, John N; Fries, Brant E; Ankri, Joel

    2006-01-01

    Background The objective of this study was to assess the responsiveness of the Minimum Data Set Activities of Daily Living (MDS-ADL) Scale to change over time by examining the change in physical function in adults with moderate to severe dementia with no comorbid illness who had been resident in a nursing home for over 90 days. Methods Longitudinal data were collected on nursing home residents with moderate (n = 7001) or severe (n = 4616) dementia in one US state from the US national Minimum Data Set (MDS). Severity of dementia was determined by the MDS Cognitive Performance Scale (CPS). Physical function was assessed by summing the seven items (bed mobility, transfer, locomotion, dressing, eating, toilet use, personal hygiene) on the MDS activities of daily living (ADL) Long Form scale. Mean change over time of MDS-ADL scores were estimated at three and six months for residents with moderate (CPS score of 3) and severe (CPS score of 4 or 5) dementia. Results Physical function in residents with moderate cognitive impairment deteriorated over six months by an average of 1.78 points on the MDS-ADL Long Form scale, while those with severe cognitive impairment declined by an average of 1.70 points. Approximately one quarter of residents in both groups showed some improvement in physical function over the six month period. Residents with moderate cognitive impairment experienced the greatest deterioration in early-loss and mid-loss ADL items (personal hygiene, dressing, toilet use) and residents with severe cognitive impairment showed the greatest deterioration in activities related to eating, a late loss ADL. Conclusion The MDS-ADL Long Form scale detected clinically meaningful change in physical function in a large cohort of long-stay nursing home residents with moderate to severe dementia, supporting its use as a research tool in future studies. PMID:16584565

  20. Hippocampus-dependent spatial memory impairment due to molar tooth loss is ameliorated by an enriched environment.

    Science.gov (United States)

    Kondo, Hiroko; Kurahashi, Minori; Mori, Daisuke; Iinuma, Mitsuo; Tamura, Yasuo; Mizutani, Kenmei; Shimpo, Kan; Sonoda, Shigeru; Azuma, Kagaku; Kubo, Kin-ya

    2016-01-01

    Teeth are crucial, not only for mastication, but for overall nutrition and general health, including cognitive function. Aged mice with chronic stress due to tooth loss exhibit impaired hippocampus-dependent learning and memory. Exposure to an enriched environment restores the reduced hippocampal function. Here, we explored the effects of an enriched environment on learning deficits and hippocampal morphologic changes in aged senescence-accelerated mouse strain P8 (SAMP8) mice with tooth loss. Eight-month-old male aged SAMP8 mice with molar intact or with molars removed were housed in either a standard environment or enriched environment for 3 weeks. The Morris water maze was performed for spatial memory test. The newborn cell proliferation, survival, and differentiation in the hippocampus were analyzed using 5-Bromodeoxyuridine (BrdU) immunohistochemical method. The hippocampal brain-derived neurotrophic factor (BDNF) levels were also measured. Mice with upper molars removed (molarless) exhibited a significant decline in the proliferation and survival of newborn cells in the dentate gyrus (DG) as well as in hippocampal BDNF levels. In addition, neuronal differentiation of newly generated cells was suppressed and hippocampus-dependent spatial memory was impaired. Exposure of molarless mice to an enriched environment attenuated the reductions in the hippocampal BDNF levels and neuronal differentiation, and partially improved the proliferation and survival of newborn cells, as well as the spatial memory ability. These findings indicated that an enriched environment could ameliorate the hippocampus-dependent spatial memory impairment induced by molar tooth loss. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Efficacy of vildagliptin in combination with insulin in patients with type 2 diabetes and severe renal impairment

    Science.gov (United States)

    Lukashevich, Valentina; Schweizer, Anja; Foley, James E; Dickinson, Sheila; Groop, Per-Henrik; Kothny, Wolfgang

    2013-01-01

    Background The purpose of this study was to evaluate the efficacy of vildagliptin 50 mg once daily in patients with severe renal impairment (estimated glomerular filtration rate vildagliptin 50 mg once daily versus placebo in patients with type 2 diabetes and moderate or severe renal impairment. The present data derive from 178 patients with severe renal impairment (baseline estimated glomerular filtration rate approximately 21 mL/min/1.73 m2, 100 randomized to vildagliptin, 78 randomized to placebo), all of whom were receiving insulin therapy (alone or in combination with an oral antidiabetic agent) for longstanding type 2 diabetes (mean approximately 19 years). Results With vildagliptin in combination with insulin, the adjusted mean change (AMΔ) in HbA1c from baseline (7.7% ± 0.1%) was −0.9% ± 0.4% and the between-treatment difference (vildagliptin – placebo) was −0.6% ± 0.2% (P vildagliptin than placebo (45.2% versus 22.8%, P = 0.008). When added to insulin, vildagliptin and placebo had comparable hypoglycemic profiles and did not cause weight gain. Both treatments were similarly well tolerated, with comparable incidences of adverse events, serious adverse events, and deaths. Conclusion When added to insulin therapy in patients with severe renal impairment and longstanding type 2 diabetes, vildagliptin 50 mg once daily was efficacious, eliciting HbA1c reductions consistent with those previously reported for a patient population with much more recent onset of type 2 diabetes and normal renal function, and had a hypoglycemic profile comparable with placebo. Accordingly, vildagliptin is a suitable treatment option for patients with advanced type 2 diabetes and impaired renal function who require insulin therapy and present a serious therapeutic challenge in clinical practice. PMID:23378769

  2. Cobalamin inactivation by nitrous oxide produces severe neurological impairment in fruit bats: protection by methionine and aggravation by folates

    Energy Technology Data Exchange (ETDEWEB)

    van der Westhuyzen, J.; Fernandes-Costa, F.; Metz, J.

    1982-11-01

    Nitrous oxide, which inactivates cobalamin when administered to fruit bats, results in severe neurological impairment leading to ataxia, paralysis and death. This occurs after about 6 weeks in animals depleted of cobalamin by dietary restriction, and after about 10 weeks in cobalamin replete bats. Supplementation of the diet with pteroylglutamic acid caused acceleration of the neurological impairment--the first unequivocal demonstration of aggravation of the neurological lesion in cobalamin deficiency by pteroylglutamic acid. The administration of formyltetrahydropteroylglutamic acid produced similar aggravation of the neurological lesion. Supplementation of the diet with methionine protected the bats from neurological impairment, but failed to prevent death. Methionine supplementation protected against the exacerbating effect of folate, preventing the development of neurological changes. These findings lend support to the hypothesis that the neurological lesion in cobalamin deficiency may be related to a deficiency in the methyl donor S-adenosylmethionine which follows diminished synthesis of methionine.

  3. Severe Affective and Behavioural Dysregulation Is Associated with Significant Psychosocial Adversity and Impairment

    Science.gov (United States)

    Jucksch, Viola; Salbach-Andrae, Harriet; Lenz, Klaus; Goth, Kirstin; Dopfner, Manfred; Poustka, Fritz; Freitag, Christine M.; Lehmkuhl, Gerd; Lehmkuhl, Ulrike; Holtmann, Martin

    2011-01-01

    Background: Recently, a highly heritable behavioral phenotype of simultaneous deviance on the Anxious/Depressed, Attention Problems, and Aggressive Behavior syndrome scales has been identified on the Child Behavior Checklist (CBCL-Dysregulation Profile, CBCL-DP). This study aims to investigate psychosocial adversity and impairment of the CBCL-DP.…

  4. Pharmacokinetics and pharmacodynamics of candesartan cilexetil in patients with normal to severely impaired renal function

    NARCIS (Netherlands)

    Buter, H; Navis, GY; Woittiez, AJJ; de Zeeuw, D; de Jong, PE

    Objective: We studied the pharmacokinetics and pharmacodynamics of single and multiple doses of candesartan cilexetil 8 mg per day in hypertensive patients with different degrees of renal function impairment. Candesartan is an angiotensin II subtype I (AT1) receptor antagonist that is administered

  5. Training of Speechreading for Severely Hearing-Impaired Persons by Human and Computer

    DEFF Research Database (Denmark)

    Bothe, Hans-Heinrich

    2007-01-01

    This paper describes evaluation results for a software programme that is intended to be used as a training-aid for lipreading in German. Tests were carried out in schools for hearing-impaired children in Germany which indicate that the ability to lipread increases significantly already after use...... of the software during a short period of time....

  6. Development of Independent Locomotion in Children with a Severe Visual Impairment

    Science.gov (United States)

    Hallemans, Ann; Ortibus, Els; Truijen, Steven; Meire, Francoise

    2011-01-01

    Locomotion of children and adults with a visual impairment (ages 1-44, n = 28) was compared to that of age-related individuals with normal vision (n = 60). Participants walked barefoot at preferred speed while their gait was recorded by a Vicon[R] system. Walking speed, heading angle, step frequency, stride length, step width, stance phase…

  7. Exposure to swainsonine impairs adult neurogenesis and spatial learning and memory.

    Science.gov (United States)

    Wang, Jiutao; Song, Lingzhen; Zhang, Qi; Zhang, Wei; An, Lei; Zhang, Yamei; Tong, Dewen; Zhao, Baoyu; Chen, Shulin; Zhao, Shanting

    2015-01-05

    Swainsonine (SW) is an indolizidine triol plant alkaloid isolated from the species Astragalus, colloquially termed locoweed. Ingestion induces severe neurological symptoms of livestock and wildlife, including ataxia, trembling, exaggerated fright reactions. Toxicity to the central and peripheral nervous system is caused by inhibition of lysosomal a-mannosidase (AMA) and accumulation of intracellular oligosaccharide. However, the effects of SW on adult neurogenesis and cognition have remained unclear. Therefore, the present study was conducted to examine the effects of SW on adult neurogenesis and learning as well as memory performance in adult mice. SW (10μg/mL in drinking water) was administered orally to mice for 4 weeks. Our results showed that SW reduced proliferation and survival of neural progenitor cells (NPCs) in culture, and in the hippocampus of adult mice. In addition, exposure to SW led to down-regulation of doublecortin (DCX) and synaptophysin (SYP) in the hippocampus. However, caspase 3 and glial fibrillary acidic protein (GFAP) levels were significantly increased in SW-treated mice. Finally, SW-treated mice exhibited deficits in hippocampus-dependent spatial learning and memory. Our findings suggest that SW affects adult neurogenesis and cognitive function. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  8. Triangulated Proxy Reporting: a technique for improving how communication partners come to know people with severe cognitive impairment.

    Science.gov (United States)

    Lyons, Gordon; De Bortoli, Tania; Arthur-Kelly, Michael

    2017-09-01

    This paper explains and demonstrates the pilot application of Triangulated Proxy Reporting (TPR); a practical technique for enhancing communication around people who have severe cognitive impairment (SCI). An introduction explains SCI and how this impacts on communication; and consequently on quality of care and quality of life. This is followed by an explanation of TPR and its origins in triangulation research techniques. An illustrative vignette explicates its utility and value in a group home for a resident with profound multiple disabilities. The Discussion and Conclusion sections propose the wider application of TPR for different cohorts of people with SCIs, their communication partners and service providers. TPR presents as a practical technique for enhancing communication interactions with people who have SCI. The paper demonstrates the potential of the technique for improving engagement amongst those with profound multiple disabilities, severe acquired brain injury and advanced dementia and their partners in and across different care settings. Implications for Rehabilitation Triangulated Proxy Reporting (TPR) shows potential to improve communications between people with severe cognitive impairments and their communication partners. TPR can lead to improved quality of care and quality of life for people with profound multiple disabilities, very advanced dementia and severe acquired brain injury, who otherwise are very difficult to support. TPR is a relatively simple and inexpensive technique that service providers can incorporate into practice to improving communications between clients with severe cognitive impairments, their carers and other support professionals.

  9. A spatial generalized ordered response model to examine highway crash injury severity.

    Science.gov (United States)

    Castro, Marisol; Paleti, Rajesh; Bhat, Chandra R

    2013-03-01

    This paper proposes a flexible econometric structure for injury severity analysis at the level of individual crashes that recognizes the ordinal nature of injury severity categories, allows unobserved heterogeneity in the effects of contributing factors, as well as accommodates spatial dependencies in the injury severity levels experienced in crashes that occur close to one another in space. The modeling framework is applied to analyze the injury severity sustained in crashes occurring on highway road segments in Austin, Texas. The sample is drawn from the Texas Department of Transportation (TxDOT) crash incident files from 2009 and includes a variety of crash characteristics, highway design attributes, driver and vehicle characteristics, and environmental factors. The results from our analysis underscore the value of our proposed model for data fit purposes as well as to accurately estimate variable effects. The most important determinants of injury severity on highways, according to our results, are (1) whether any vehicle occupant is ejected, (2) whether collision type is head-on, (3) whether any vehicle involved in the crash overturned, (4) whether any vehicle occupant is unrestrained by a seat-belt, and (5) whether a commercial truck is involved. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. The shift from plant-plant facilitation to competition under severe water deficit is spatially explicit.

    Science.gov (United States)

    O'Brien, Michael J; Pugnaire, Francisco I; Armas, Cristina; Rodríguez-Echeverría, Susana; Schöb, Christian

    2017-04-01

    The stress-gradient hypothesis predicts a higher frequency of facilitative interactions as resource limitation increases. Under severe resource limitation, it has been suggested that facilitation may revert to competition, and identifying the presence as well as determining the magnitude of this shift is important for predicting the effect of climate change on biodiversity and plant community dynamics. In this study, we perform a meta-analysis to compare temporal differences of species diversity and productivity under a nurse plant ( Retama sphaerocarpa ) with varying annual rainfall quantity to test the effect of water limitation on facilitation. Furthermore, we assess spatial differences in the herbaceous community under nurse plants in situ during a year with below-average rainfall. We found evidence that severe rainfall deficit reduced species diversity and plant productivity under nurse plants relative to open areas. Our results indicate that the switch from facilitation to competition in response to rainfall quantity is nonlinear. The magnitude of this switch depended on the aspect around the nurse plant. Hotter south aspects under nurse plants resulted in negative effects on beneficiary species, while the north aspect still showed facilitation. Combined, these results emphasize the importance of spatial heterogeneity under nurse plants for mediating species loss under reduced precipitation, as predicted by future climate change scenarios. However, the decreased water availability expected under climate change will likely reduce overall facilitation and limit the role of nurse plants as refugia, amplifying biodiversity loss.

  11. Neurocognitive Impairments Are More Severe in the Binge-Eating/Purging Anorexia Nervosa Subtype Than in the Restricting Subtype.

    Science.gov (United States)

    Tamiya, Hiroko; Ouchi, Atushi; Chen, Runshu; Miyazawa, Shiho; Akimoto, Yoritaka; Kaneda, Yasuhiro; Sora, Ichiro

    2018-01-01

    Objective: To evaluate cognitive function impairment in patients with anorexia nervosa (AN) of either the restricting (ANR) or binge-eating/purging (ANBP) subtype. Method: We administered the Japanese version of the MATRICS Consensus Cognitive Battery to 22 patients with ANR, 18 patients with ANBP, and 69 healthy control subjects. Our participants were selected from among the patients at the Kobe University Hospital and community residents. Results: Compared to the healthy controls, the ANR group had significantly lower visual learning and social cognition scores, and the ANBP group had significantly lower processing speed, attention/vigilance, visual learning, reasoning/problem-solving, and social cognition scores. Compared to the ANR group, the ANBP group had significantly lower attention/vigilance scores. Discussion: The AN subtypes differed in cognitive function impairments. Participants with ANBP, which is associated with higher mortality rates than ANR, exhibited greater impairment severities, especially in the attention/vigilance domain, confirming the presence of impairments in continuous concentration. This may relate to the impulsivity, an ANBP characteristic reported in the personality research. Future studies can further clarify the cognitive impairments of each subtype by addressing the subtype cognitive functions and personality characteristics.

  12. Impact of etanercept on work and activity impairment in employed moderate to severe rheumatoid arthritis patients in the United States.

    Science.gov (United States)

    Hone, Devon; Cheng, Annie; Watson, Crystal; Huang, Baisong; Bitman, Bojena; Huang, Xing-Yue; Gandra, Shravanthi R

    2013-10-01

    To quantify the impact of etanercept on work and activity impairment in employed US patients with moderate to severe rheumatoid arthritis (RA). This prospective, observational, longitudinal study recruited RA patients initiating etanercept (50 mg/week) between January 2009 and March 2010. The Work Productivity and Activity Impairment Questionnaire (WPAI) and domestic productivity questionnaire were administered by telephone interviews at baseline and at 1, 2, 3, and 6 months after etanercept initiation. The human capital approach was used to estimate the costs of work impairment. Changes in WPAI measures were analyzed using Wilcoxon's signed rank test. RA patients (n = 204) initiating etanercept were a mean ± SD age of 46.6 ± 10.9 years and 72% were women. After 6 months, 153 patients continued treatment (continuers) and showed significant decreases in overall work impairment (41.9% at baseline versus 25.2% at 6 months; P work hours lost weekly due to RA (3.2 versus 0.8; P = 0.0001). The projected 12-month gain in work productivity for continuers was 284.5 hours per patient, equating to $3,233-22,533 depending on annual income level, which partially or completely offset the annual cost of etanercept ($20,190). Domestic productivity improved from 41.5% at baseline to 69.6% at 6 months (P work and activity impairment; the value of increased work productivity partially or completely offset the cost of treatment. Copyright © 2013 by the American College of Rheumatology.

  13. Spatial frequency domain imaging of burn wounds in a preclinical model of graded burn severity

    Science.gov (United States)

    Nguyen, John Quan; Crouzet, Christian; Mai, Tuan; Riola, Kathleen; Uchitel, Daniel; Liaw, Lih-Huei; Bernal, Nicole; Ponticorvo, Adrien; Choi, Bernard; Durkin, Anthony J.

    2013-06-01

    Frequent monitoring of early-stage burns is necessary for deciding optimal treatment and management. Both superficial and full thickness burns are relatively easy to diagnose based on clinical observation. In between these two extremes are superficial-partial thickness and deep-partial thickness burns. These burns, while visually similar, differ dramatically in terms of clinical treatment and are known to progress in severity over time. The objective of this study was to determine the potential of spatial frequency domain imaging (SFDI) for noninvasively mapping quantitative changes in chromophore and optical properties that may be an indicative of burn wound severity. A controlled protocol of graded burn severity was developed and applied to 17 rats. SFDI data was acquired at multiple near-infrared wavelengths over a course of 3 h. Burn severity was verified using hematoxylin and eosin histology. From this study, we found that changes in water concentration (edema), deoxygenated hemoglobin concentration, and optical scattering (tissue denaturation) to be statistically significant at differentiating superficial partial-thickness burns from deep-partial thickness burns.

  14. Spatial Navigation in Complex and Radial Mazes in APP23 Animals and Neurotrophin Signaling as a Biological Marker of Early Impairment

    Science.gov (United States)

    Hellweg, Rainer; Huber, Roman; Kuhl, Alexander; Riepe, Matthias W.; Lohmann, Peter

    2006-01-01

    Impairment of hippocampal function precedes frontal and parietal cortex impairment in human Alzheimer's disease(AD). Neurotrophins are critical for behavioral performance and neuronal survival in AD. We used complex and radial mazes to assess spatial orientation and learning in wild-type and B6-Tg(ThylAPP)23Sdz (APP23) animals, a transgenic mouse…

  15. Gaze-based assistive technology used in daily life by children with severe physical impairments - parents' experiences.

    Science.gov (United States)

    Borgestig, Maria; Rytterström, Patrik; Hemmingsson, Helena

    2017-07-01

    To describe and explore parents' experiences when their children with severe physical impairments receive gaze-based assistive technology (gaze-based assistive technology (AT)) for use in daily life. Semi-structured interviews were conducted twice, with one year in between, with parents of eight children with cerebral palsy that used gaze-based AT in their daily activities. To understand the parents' experiences, hermeneutical interpretations were used during data analysis. The findings demonstrate that for parents, children's gaze-based AT usage meant that children demonstrated agency, provided them with opportunities to show personality and competencies, and gave children possibilities to develop. Overall, children's gaze-based AT provides hope for a better future for their children with severe physical impairments; a future in which the children can develop and gain influence in life. Gaze-based AT provides children with new opportunities to perform activities and take initiatives to communicate, giving parents hope about the children's future.

  16. Short-term sleep deprivation impairs spatial working memory and modulates expression levels of ionotropic glutamate receptor subunits in hippocampus.

    Science.gov (United States)

    Xie, Meilan; Yan, Jie; He, Chao; Yang, Li; Tan, Gang; Li, Chao; Hu, Zhian; Wang, Jiali

    2015-06-01

    Hippocampus-dependent learning memory is sensitive to sleep deprivation (SD). Although the ionotropic glutamate receptors play a vital role in synaptic plasticity and learning and memory, however, whether the expression of these receptor subunits is modulated by sleep loss remains unclear. In the present study, western blotting was performed by probing with specific antibodies against the ionotropic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits GluA1, GluA2, GluA3, and against the N-methyl-d-aspartate (NMDA) glutamate receptor subunits GluN1, GluN2A, GluN2B. In hippocampus, down regulation of surface GluA1 and GluN2A surface expression were observed in both SD groups. However, surface expression level of GluA2, GluA3, GluN1 and GluN2B was significantly up-regulated in 8h-SD rats when compared to the 4h-SD rats. In parallel with the complex changes in AMPA and NMDA receptor subunit expressions, we found the 8h-SD impaired rat spatial working memory in 30-s-delay T-maze task, whereas no impairment of spatial learning was observed in 4h-SD rats. These results indicate that sleep loss alters the relative expression levels of the AMPA and NMDA receptors, thus affects the synaptic strength and capacity for plasticity and partially contributes to spatial memory impairment. Copyright © 2015. Published by Elsevier B.V.

  17. Spatial learning in the 5-HT1B receptor knockout mouse: selective facilitation/impairment depending on the cognitive demand.

    Science.gov (United States)

    Buhot, Marie-Christine; Wolff, Mathieu; Benhassine, Narimane; Costet, Pierre; Hen, René; Segu, Louis

    2003-01-01

    Age-related memory decline is associated with a combined dysfunction of the cholinergic and serotonergic systems in the hippocampus and frontal cortex, in particular. The 5-HT1B receptor occupies strategic cellular and subcellular locations in these structures, where it plays a role in the modulation of ACh release. In an attempt to characterize the contribution of this receptor to memory functions, 5-HT1B receptor knockout (KO) mice were submitted to various behavioral paradigms carried out in the same experimental context (water maze), which were aimed at exposing mice to various levels of memory demand. 5-HT1BKO mice exhibited a facilitation in the acquisition of a hippocampal-dependent spatial reference memory task in the Morris water maze. This facilitation was selective of task difficulty, showing thus that the genetic inactivation of the 5-HT1B receptor is associated with facilitation when the complexity of the task is increased, and reveals a protective effect on age-related hippocampal-dependent memory decline. Young-adult and aged KO and wild-type (WT) mice were equally able to learn a delayed spatial matching-to-sample working memory task in a radial-arm water maze with short (0 or 5 min) delays. However, 5-HT1BKO mice, only, exhibited a selective memory impairment at intermediate and long (15, 30, and 60 min) delays. Treatment by scopolamine induced the same pattern of performance in wild type as did the mutation for short (5 min, no impairment) and long (60 min, impairment) delays. Taken together, these studies revealed a beneficial effect of the mutation on the acquisition of a spatial reference memory task, but a deleterious effect on a working memory task for long delays. This 5-HT1BKO mouse story highlights the problem of the potential existence of "global memory enhancers."

  18. A jacket for assisting sensorimotor-related impairments and spatial perception

    International Nuclear Information System (INIS)

    Blumenstein, Tobias; Turova, Varvara; Alves-Pinto, Ana; Lampe, Renée

    2017-01-01

    A sensorimotor jacket, which is able to measure distances to nearby objects with ultrasonic sensors and to transmit information about distances via vibrating transducers, has been designed with the aim of improving the spatial awareness of patients with cerebral palsy and to facilitate spatial orientation for blind people. The efficiency was tested for patients diagnosed with cerebral palsy, blind participants and healthy people. A positive impact of the sensorimotor jacket on the performance in a spatial task has been established both in patients with cerebral palsy and blind participants. Moreover, for patients with cerebral palsy, the training effect was visible after only three training exercises. (paper)

  19. Uses of virtual reality in clinical training: developing the spatial skills of children with mobility impairments.

    Science.gov (United States)

    Stanton, D; Foreman, N; Wilson, P N

    1998-01-01

    In this chapter we review some of the ways in which the skills learned in virtual environments (VEs) transfer to real situations, and in particular how information about the spatial layouts of virtual buildings acquired from the exploration of three-dimensional computer-simulations transfers to their real equivalents. Four experiments are briefly described which examined VR use by disabled children. We conclude that spatial information of the kind required for navigation transfers effectively from virtual to real situations. Spatial skills in disabled children showed progressive improvement with repeated exploration of virtual environments. The results are discussed in relation to the potential future benefits of VR in special needs education and training.

  20. Gaze-based assistive technology used in daily life by children with severe physical impairments - parents' experiences

    OpenAIRE

    Borgestig, Maria; Rytterstrom, Patrik; Hemmingsson, Helena

    2017-01-01

    Objective: To describe and explore parents' experiences when their children with severe physical impairments receive gaze-based assistive technology (gaze-based assistive technology (AT)) for use in daily life. Methods: Semi-structured interviews were conducted twice, with one year in between, with parents of eight children with cerebral palsy that used gaze-based AT in their daily activities. To understand the parents' experiences, hermeneutical interpretations were used during data analysis...

  1. Spatial assessment and source identification of heavy metals pollution in surface water using several chemometric techniques.

    Science.gov (United States)

    Ismail, Azimah; Toriman, Mohd Ekhwan; Juahir, Hafizan; Zain, Sharifuddin Md; Habir, Nur Liyana Abdul; Retnam, Ananthy; Kamaruddin, Mohd Khairul Amri; Umar, Roslan; Azid, Azman

    2016-05-15

    This study presents the determination of the spatial variation and source identification of heavy metal pollution in surface water along the Straits of Malacca using several chemometric techniques. Clustering and discrimination of heavy metal compounds in surface water into two groups (northern and southern regions) are observed according to level of concentrations via the application of chemometric techniques. Principal component analysis (PCA) demonstrates that Cu and Cr dominate the source apportionment in northern region with a total variance of 57.62% and is identified with mining and shipping activities. These are the major contamination contributors in the Straits. Land-based pollution originating from vehicular emission with a total variance of 59.43% is attributed to the high level of Pb concentration in the southern region. The results revealed that one state representing each cluster (northern and southern regions) is significant as the main location for investigating heavy metal concentration in the Straits of Malacca which would save monitoring cost and time. The monitoring of spatial variation and source of heavy metals pollution at the northern and southern regions of the Straits of Malacca, Malaysia, using chemometric analysis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. High-functioning autism patients share similar but more severe impairments in verbal theory of mind than schizophrenia patients.

    Science.gov (United States)

    Tin, L N W; Lui, S S Y; Ho, K K Y; Hung, K S Y; Wang, Y; Yeung, H K H; Wong, T Y; Lam, S M; Chan, R C K; Cheung, E F C

    2018-06-01

    Evidence suggests that autism and schizophrenia share similarities in genetic, neuropsychological and behavioural aspects. Although both disorders are associated with theory of mind (ToM) impairments, a few studies have directly compared ToM between autism patients and schizophrenia patients. This study aimed to investigate to what extent high-functioning autism patients and schizophrenia patients share and differ in ToM performance. Thirty high-functioning autism patients, 30 schizophrenia patients and 30 healthy individuals were recruited. Participants were matched in age, gender and estimated intelligence quotient. The verbal-based Faux Pas Task and the visual-based Yoni Task were utilised to examine first- and higher-order, affective and cognitive ToM. The task/item difficulty of two paradigms was examined using mixed model analyses of variance (ANOVAs). Multiple ANOVAs and mixed model ANOVAs were used to examine group differences in ToM. The Faux Pas Task was more difficult than the Yoni Task. High-functioning autism patients showed more severely impaired verbal-based ToM in the Faux Pas Task, but shared similar visual-based ToM impairments in the Yoni Task with schizophrenia patients. The findings that individuals with high-functioning autism shared similar but more severe impairments in verbal ToM than individuals with schizophrenia support the autism-schizophrenia continuum. The finding that verbal-based but not visual-based ToM was more impaired in high-functioning autism patients than schizophrenia patients could be attributable to the varied task/item difficulty between the two paradigms.

  3. Chronic stress impairs spatial memory and motivation for reward without disrupting motor ability and motivation to explore.

    Science.gov (United States)

    Kleen, Jonathan K; Sitomer, Matthew T; Killeen, Peter R; Conrad, Cheryl D

    2006-08-01

    This study uses an operant, behavioral model to assess the daily changes in the decay rate of short-term memory, motivation, and motor ability in rats exposed to chronic restraint. Restraint decreased reward-related motivation by 50% without altering memory decay rate or motor ability. Moreover, chronic restraint impaired hippocampal-dependent spatial memory on the Y maze (4-hr delay) and produced CA3 dendritic retraction without altering hippocampal-independent maze navigation (1-min delay) or locomotion. Thus, mechanisms underlying motivation for food reward differ from those underlying Y maze exploration, and neurobiological substrates of spatial memory, such as the hippocampus, differ from those that underlie short-term memory. Chronic restraint produces functional, neuromorphological, and physiological alterations that parallel symptoms of depression in humans. Copyright 2006 APA, all rights reserved.

  4. Categorical spatial memory in patients with mild cognitive impairment and Alzheimer dementia: positional versus object-location recall.

    Science.gov (United States)

    Kessels, Roy P C; Rijken, Stefan; Joosten-Weyn Banningh, Liesbeth W A; Van Schuylenborgh-VAN Es, Nelleke; Olde Rikkert, Marcel G M

    2010-01-01

    Memory for object locations, as part of spatial memory function, has rarely been studied in patients with Alzheimer dementia (AD), while studies in patients with Mild Cognitive Impairment (MCI) patients are lacking altogether. The present study examined categorical spatial memory function using the Location Learning Test (LLT) in MCI patients (n = 30), AD patients (n = 30), and healthy controls (n = 40). Two scoring methods were compared, aimed at disentangling positional recall (location irrespective of object identity) and object-location binding. The results showed that AD patients performed worse than the MCI patients on the LLT, both on recall of positional information and on recall of the locations of different objects. In addition, both measures could validly discriminate between AD and MCI patients. These findings are in agreement with the notion that visual cued-recall tests may have better diagnostic value than traditional (verbal) free-recall tests in the assessment of patients with suspected MCI or AD.

  5. Vitamin C deficiency in early postnatal life impairs spatial memory and reduces the number of hippocampal neurons in guinea pigs

    DEFF Research Database (Denmark)

    Tveden-Nyborg, Pernille Yde; Johansen, Louise Kruse; Raida, Zindy

    2009-01-01

    C deficiency and neuronal damage in newborn guinea pigs. DESIGN: Thirty 6- to 7-d-old guinea pigs were randomly assigned to 2 groups to receive either a vitamin C-sufficient diet or the same diet containing a low concentration of vitamin C (but adequate to prevent scurvy) for 2 mo. Spatial memory...... was assessed by the Morris Water Maze, and hippocampal neuron numbers were quantified by stereologic techniques. RESULTS: The results showed a reduction in spatial memory (P ... a lower total number of neurons in hippocampal subdivisions (dentate gyrus, cornu ammonis 1, and cornu ammonis 2-3) than did the normal controls (P impaired neuronal development and a functional decrease...

  6. Spatial working memory in aging and mild cognitive impairment: effects of task load and contextual cueing.

    NARCIS (Netherlands)

    Kessels, R.P.C.; Meulenbroek, O.V.; Fernandez, G.S.E.; Olde Rikkert, M.G.M.

    2010-01-01

    Mild Cognitive Impairment (MCI) is characterized by episodic memory deficits, while aspects of working memory may also be implicated, but studies into this latter domain are scarce and results are inconclusive. Using a computerized search paradigm, this study compares 25 young adults, 25 typically

  7. Spatial Working Memory in Aging and Mild Cognitive Impairment: Effects of Task Load and Contextual Cueing

    NARCIS (Netherlands)

    Kessels, R.P.C.; Meulenbroek, O.V.; Fernandez, G.S.E.; Olde Rikkert, M.G.M.

    2010-01-01

    Mild Cognitive Impairment (MCI) is characterized by episodic memory deficits, while aspects of working memory may also be implicated, but studies into this latter domain are scarce and results are inconclusive. Using a computerized search paradigm, this study compares 25 young adults, 25 typically

  8. Allocentric spatial memory testing predicts conversion from mild cognitive impairment to dementia: an initial proof-of-concept study

    Directory of Open Access Journals (Sweden)

    Ruth A Wood

    2016-12-01

    Full Text Available The hippocampus is one of the first regions to exhibit neurodegeneration in Alzheimer’s disease (AD and knowledge of its role in allocentric spatial memory may therefore aid early diagnosis of AD. The 4 Mountains Test (4MT is a short and easily administered test of spatial memory based on the cognitive map theory of hippocampal function as derived from rodent single cell and behavioral studies. The 4MT has been shown in previous cross-sectional studies to be sensitive and specific for mild cognitive impairment due to AD. This report describes the initial results of a longitudinal study testing the hypothesis that allocentric spatial memory is predictive of conversion from mild cognitive impairment to dementia.Fifteen patients with mild cognitive impairment underwent baseline testing on the 4MT in addition to CSF amyloid/tau biomarker studies, volumetric MRI and neuropsychological assessment including the Rey Auditory Verbal Learning Test (RAVLT and Trail Making Test B (TMT-B. At 24 months, 9/15 patients had converted to AD dementia. The 4MT predicted conversion to AD with 93% accuracy (Cohen’s d = 2.52. The predictive accuracies of the comparator measures were as follows: CSF tau/β-amyloid1-42 ratio 92% (d = 1.81, RAVLT 64% (d = 0.41, TMT-B 78% (d = 1.56, and hippocampal volume 77% (d = 0.65. CSF tau levels were strongly negative correlated with 4MT scores (r = -0.71. This proof-of-concept study provides initial support for the hypothesis that allocentric spatial memory testing is a predictive cognitive marker of hippocampal neurodegeneration in pre-dementia AD. The 4MT is a brief, noninvasive, straightforward spatial memory test and is therefore ideally suited for use in routine clinical diagnostic practice. This is of particular importance given the current unmet need for simple accurate diagnostic tests for early AD and the ongoing development of potential disease-modifying therapeutic agents which may be more efficacious when given

  9. Selective Inducible Nitric Oxide Synthase Inhibitor Reversed Zinc Chloride-Induced Spatial Memory Impairment via Increasing Cholinergic Marker Expression.

    Science.gov (United States)

    Tabrizian, Kaveh; Azami, Kian; Belaran, Maryam; Soodi, Maliheh; Abdi, Khosrou; Fanoudi, Sahar; Sanati, Mehdi; Mottaghi Dastjerdi, Negar; Soltany Rezaee-Rad, Mohammad; Sharifzadeh, Mohammad

    2016-10-01

    Zinc, an essential micronutrient and biochemical element of the human body, plays structural, catalytic, and regulatory roles in numerous physiological functions. In the current study, the effects of a pretraining oral administration of zinc chloride (10, 25, and 50 mg/kg) for 14 consecutive days and post-training bilateral intra-hippocampal infusion of 1400W as a selective inducible nitric oxide synthase (iNOS) inhibitor (10, 50, and 100 μM/side), alone and in combination, on the spatial memory retention in Morris water maze (MWM) were investigated. Animals were trained for 4 days and tested 48 h after completion of training. Also, the molecular effects of these compounds on the expression of choline acetyltransferase (ChAT), as a cholinergic marker in the CA1 region of the hippocampus and medial septal area (MSA), were evaluated. Behavioral and molecular findings of this study showed that a 2-week oral administration of zinc chloride (50 mg/kg) impaired spatial memory retention in MWM and decreased ChAT expression. Immunohistochemical analysis of post-training bilateral intra-hippocampal infusion of 1400W revealed a significant increase in ChAT immunoreactivity. Furthermore, post-training bilateral intra-hippocampal infusion of 1400W into the CA1 region of the hippocampus reversed zinc chloride-induced spatial memory impairment in MWM and significantly increased ChAT expression in comparison with zinc chloride-treated animals. Taken together, these results emphasize the role of selective iNOS inhibitors in reversing zinc chloride-induced spatial memory deficits via modulation of cholinergic marker expression.

  10. Adolescent exposure to Bisphenol-A increases anxiety and sucrose preference but impairs spatial memory in rats independent of sex.

    Science.gov (United States)

    Diaz Weinstein, Samantha; Villafane, Joseph J; Juliano, Nicole; Bowman, Rachel E

    2013-09-05

    The endocrine disruptor Bisphenol-A (BPA) has been shown to modulate estrogenic, androgenic, and anti-androgenic effects. The effects of BPA exposure during early organizational periods of development have been well documented. The current study focuses on the effects of short term, low-dose BPA exposure on anxiety, spatial memory and sucrose preference in adolescent rats. Seven week old Sprague Dawley rats (n=18 male, n=18 female) received daily subcutaneous injections (40 µg/kg body weight) of BPA or vehicle for 12 days. Starting on day 6 of injections, subjects were tested on the elevated plus maze which provides a measure of anxiety, the open field test which provides a measure of anxiety and locomotor activity, and object placement, a measure of spatial memory. On the twelfth day of BPA administration, sucrose preference was tested using a standard two-bottle choice (tap versus sucrose solution). All rats gained weight during the study; there was a main effect of sex, but not BPA treatment on body weight. The results indicate that BPA exposure, regardless of sex, increased anxiety on both the elevated plus maze and open field. Spatial memory was impaired on the object recognition task with BPA animals spending significant less time with the object in the novel location than controls. Finally, a significant increase in sucrose consumption for both male and female subjects exposed to BPA was observed. The current data shows that short term BPA exposure, below the current reference safe daily limit of 50 µg/kg day set by the United States Environmental Protection Agency, during adolescent development increases anxiety, impairs spatial memory, and increases sucrose consumption independent of sex. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Exogenous galanin attenuates spatial memory impairment and decreases hippocampal β-amyloid levels in rat model of Alzheimer's disease.

    Science.gov (United States)

    Li, Lei; Yu, Liling; Kong, Qingxia

    2013-11-01

    One of the major pathological characteristics of Alzheimer's disease (AD) is the presence of enhanced deposits of beta-amyloid peptide (Aβ). The neuropeptide galanin (GAL) and its receptors are overexpressed in degenerating brain regions in AD. The functional consequences of galaninergic systems plasticity in AD are unclear. The objective of the present study was to investigate whether exogenous galanin could attenuate spatial memory impairment and hippocampal Aβ aggregation in rat model of AD. The effects of Aβ, galanin, galanin receptor 1 agonist M617 and galanin receptor 2 agonist AR-M1896 on spatial memory were tested by Morris water maze. The effects of Aβ, galanin, M617 and AR-M1896 on hippocampal Aβ protein expression were evaluated by western blot assay. The expression of galanin, galanin receptors 1 and 2 in rats' hippocampus were detected by real time PCR and western blot assay. The results showed that (1) Galanin administration was effective in improving the spatial memory and decreasing hippocampal Aβ levels after intracerebroventricular injection of Aβ; (2) AR-M1896 rather than M617 could imitate these effects of galanin; (3) GAL and GALR2 mRNA and protein levels increased significantly in hippocampus after Aβ administration, while GALR1 mRNA and protein levels did not change; (4) GAL, AR-M1896 and M617 administration did not show significant effect on GAL, GalR1 and GalR2 mRNA and protein levels in hippocampus after Aβ administration. These results implied that galanin receptor 2, but not receptor 1 was involved in the protective effects against spatial memory impairment and hippocampal Aβ aggregation.

  12. Causes of Severe Visual Impairment and Blindness: Comparative Data From Bhutanese and Laotian Schools for the Blind.

    Science.gov (United States)

    Farmer, Lachlan David Mailey; Ng, Soo Khai; Rudkin, Adam; Craig, Jamie; Wangmo, Dechen; Tsang, Hughie; Southisombath, Khamphoua; Griffiths, Andrew; Muecke, James

    2015-01-01

    To determine and compare the major causes of childhood blindness and severe visual impairment in Bhutan and Laos. Independent cross-sectional surveys. This survey consists of 2 cross-sectional observational studies. The Bhutanese component was undertaken at the National Institute for Vision Impairment, the only dedicated school for the blind in Bhutan. The Laotian study was conducted at the National Ophthalmology Centre and Vientiane School for the Blind. Children younger than age 16 were invited to participate. A detailed history and examination were performed consistent with the World Health Organization Prevention of Blindness Eye Examination Record. Of the 53 children examined in both studies, 30 were from Bhutan and 23 were from Laos. Forty percent of Bhutanese and 87.1% of Laotian children assessed were blind, with 26.7% and 4.3%, respectively, being severely visually impaired. Congenital causes of blindness were the most common, representing 45% and 43.5% of the Bhutanese and Laotian children, respectively. Anatomically, the primary site of blinding pathology differed between the cohorts. In Bhutan, the lens comprised 25%, with whole globe at 20% and retina at 15%, but in Laos, whole globe and cornea equally contributed at 30.4%, followed by retina at 17.4%. There was an observable difference in the rates of blindness/severe visual impairment due to measles, with no cases observed in the Bhutanese children but 20.7% of the total pathologies in the Laotian children attributable to congenital measles infection. Consistent with other studies, there is a high rate of blinding disease, which may be prevented, treated, or ameliorated.

  13. Crossed Leg Sign Is Associated With Severity of Unilateral Spatial Neglect After Stroke

    Directory of Open Access Journals (Sweden)

    Gustavo José Luvizutto

    2018-04-01

    Full Text Available BackgroundThe crossed leg sign in patients with right hemisphere stroke is thought to be associated with perceptual disorders, such as unilateral spatial neglect (USN. The aim of this study was to compare the crossed leg sign with the severity of USN during the acute phase of stroke.Experimental proceduresThis was an observational and prospective clinical study of individuals with a diagnosis of right parietal stroke, as confirmed by neuroimaging. The occurrence of the crossed leg sign, the time at which this occurred after the stroke, and a clinical diagnosis of USN were measured and recorded. The patients’ age, sex, and lesion severity, as determined by the National Institutes of Health Stroke Scale and Glasgow coma scale, were included in the analyses as confounding variables. The outcome of interest was the degree of USN, as measured by the cancellation and bisection tests. Binary logistic regression was used to analyze the effect of crossed leg syndrome on the severity of USN. In the adjusted multiple regression model, a p-value of <0.05 was considered statistically significant.ResultsOverall, 60 patients were included in this study. There were no associations between patient demographics and the presence of the crossed leg sign. There was, however, an association between the crossed leg sign and the absolute value of the deviation in the line bisection test (B = −0.234; p = 0.039. The crossed leg sign was not associated with other measures of USN.ConclusionBased on the results of our study, we can conclude that a crossed leg sign in the acute phase of stroke is associated with USN severity, specifically the misinterpretation of the midline.

  14. Impairments of spatial learning and memory following intrahippocampal injection in rats of 3-mercaptopropionic acid-modified CdTe quantum dots and molecular mechanisms.

    Science.gov (United States)

    Wu, Tianshu; He, Keyu; Ang, Shengjun; Ying, Jiali; Zhang, Shihan; Zhang, Ting; Xue, Yuying; Tang, Meng

    2016-01-01

    With the rapid development of nanotechnology, quantum dots (QDs) as advanced nanotechnology products have been widely used in neuroscience, including basic neurological studies and diagnosis or therapy for neurological disorders, due to their superior optical properties. In recent years, there has been intense concern regarding the toxicity of QDs, with a growing number of studies. However, knowledge of neurotoxic consequences of QDs applied in living organisms is lagging behind their development, even if several studies have attempted to evaluate the toxicity of QDs on neural cells. The aim of this study was to evaluate the adverse effects of intrahippocampal injection in rats of 3-mercaptopropionic acid (MPA)-modified CdTe QDs and underlying mechanisms. First of all, we observed impairments in learning efficiency and spatial memory in the MPA-modified CdTe QD-treated rats by using open-field and Y-maze tests, which could be attributed to pathological changes and disruption of ultrastructure of neurons and synapses in the hippocampus. In order to find the mechanisms causing these effects, transcriptome sequencing (RNA-seq), an advanced technology, was used to gain the potentially molecular targets of MPA-modified CdTe QDs. According to ample data from RNA-seq, we chose the signaling pathways of PI3K-Akt and MPAK-ERK to do a thorough investigation, because they play important roles in synaptic plasticity, long-term potentiation, and spatial memory. The data demonstrated that phosphorylated Akt (p-Akt), p-ERK1/2, and c-FOS signal transductions in the hippocampus of rats were involved in the mechanism underlying spatial learning and memory impairments caused by 3.5 nm MPA-modified CdTe QDs.

  15. Streptavidin-conjugated CdSe/ZnS quantum dots impaired synaptic plasticity and spatial memory process

    Energy Technology Data Exchange (ETDEWEB)

    Gao Xiaoyan [Center for Molecular Neurobiology, University Medical Center Hamburg-Eppendorf (Germany); Tang Mingliang [Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences (China); Li Zhifeng; Zha Yingying [University of Science and Technology of China, CAS Key Laboratory of Brain Function and Disease, and School of Life Sciences (China); Cheng Guosheng [Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences (China); Yin Shuting [Center for Molecular Neurobiology, University Medical Center Hamburg-Eppendorf (Germany); Chen Jutao; Ruan Diyun; Chen Lin; Wang Ming, E-mail: wming@ustc.edu.cn [University of Science and Technology of China, CAS Key Laboratory of Brain Function and Disease, and School of Life Sciences (China)

    2013-04-15

    Studies reported that quantum dots (QDs), as a novel probe, demonstrated a promising future for in vivo imaging, but also showed potential toxicity. This study is mainly to investigate in vivo response in the central nervous system (CNS) after exposure to QDs in a rat model of synaptic plasticity and spatial memory. Adult rats were exposed to streptavidin-conjugated CdSe/ZnS QDs (Qdots 525, purchased from Molecular Probes Inc.) by intraperitoneal injection for 7 days, followed by behavioral, electrophysiological, and biochemical examinations. The electrophysiological results show that input/output (I/O) functions were increased, while the peak of paired-pulse reaction and long-term potentiation were decreased after QDs insult, indicating synaptic transmission was enhanced and synaptic plasticity in the hippocampus was impaired. Meanwhile, behavioral experiments provide the evidence that QDs could impair rats' spatial memory process. All the results present evidences of interference of synaptic transmission and plasticity in rat hippocampal dentate gyrus area by QDs insult and suggest potential adverse issues which should be considered in QDs applications.

  16. Streptavidin-conjugated CdSe/ZnS quantum dots impaired synaptic plasticity and spatial memory process

    Science.gov (United States)

    Gao, Xiaoyan; Tang, Mingliang; Li, Zhifeng; Zha, Yingying; Cheng, Guosheng; Yin, Shuting; Chen, Jutao; Ruan, Di-yun; Chen, Lin; Wang, Ming

    2013-04-01

    Studies reported that quantum dots (QDs), as a novel probe, demonstrated a promising future for in vivo imaging, but also showed potential toxicity. This study is mainly to investigate in vivo response in the central nervous system (CNS) after exposure to QDs in a rat model of synaptic plasticity and spatial memory. Adult rats were exposed to streptavidin-conjugated CdSe/ZnS QDs (Qdots 525, purchased from Molecular Probes Inc.) by intraperitoneal injection for 7 days, followed by behavioral, electrophysiological, and biochemical examinations. The electrophysiological results show that input/output ( I/ O) functions were increased, while the peak of paired-pulse reaction and long-term potentiation were decreased after QDs insult, indicating synaptic transmission was enhanced and synaptic plasticity in the hippocampus was impaired. Meanwhile, behavioral experiments provide the evidence that QDs could impair rats' spatial memory process. All the results present evidences of interference of synaptic transmission and plasticity in rat hippocampal dentate gyrus area by QDs insult and suggest potential adverse issues which should be considered in QDs applications.

  17. Streptavidin-conjugated CdSe/ZnS quantum dots impaired synaptic plasticity and spatial memory process

    International Nuclear Information System (INIS)

    Gao Xiaoyan; Tang Mingliang; Li Zhifeng; Zha Yingying; Cheng Guosheng; Yin Shuting; Chen Jutao; Ruan Diyun; Chen Lin; Wang Ming

    2013-01-01

    Studies reported that quantum dots (QDs), as a novel probe, demonstrated a promising future for in vivo imaging, but also showed potential toxicity. This study is mainly to investigate in vivo response in the central nervous system (CNS) after exposure to QDs in a rat model of synaptic plasticity and spatial memory. Adult rats were exposed to streptavidin-conjugated CdSe/ZnS QDs (Qdots 525, purchased from Molecular Probes Inc.) by intraperitoneal injection for 7 days, followed by behavioral, electrophysiological, and biochemical examinations. The electrophysiological results show that input/output (I/O) functions were increased, while the peak of paired-pulse reaction and long-term potentiation were decreased after QDs insult, indicating synaptic transmission was enhanced and synaptic plasticity in the hippocampus was impaired. Meanwhile, behavioral experiments provide the evidence that QDs could impair rats’ spatial memory process. All the results present evidences of interference of synaptic transmission and plasticity in rat hippocampal dentate gyrus area by QDs insult and suggest potential adverse issues which should be considered in QDs applications.

  18. Depression increases in patients with Parkinson?s disease according to the increasing severity of the cognitive impairment

    Directory of Open Access Journals (Sweden)

    Marcos Hortes N. Chagas

    2014-06-01

    Full Text Available Objective : To test the hypothesis that severity of cognitive impairment modifies the association between depression and Parkinson’s disease (PD. Method : One-phase population-based door-to-door surveys. This is a secondary analysis of 1,451 people aged 65 years and older with cognitive impairment living in defined catchment areas. Depression was estimated according to ICD-10, self-reported PD, disability according to WHODAS-II and cognitive status according to the CSI-D. Results : The mean age of the sample was 79.3 years old and most (69% were women. Of the total sample, 16.1% had depression and it was significantly higher among participants with PD. There was an increase on the ORs of the association between depression and PD with decreased scores in the cognitive test (Adjusted OR from 0.98 to 8.04. Conclusion : The association between depression and PD increases with the severity of the cognitive impairment.

  19. Characteristics of highly impaired children with severe chronic pain: a 5-year retrospective study on 2249 pediatric pain patients

    Directory of Open Access Journals (Sweden)

    Zernikow Boris

    2012-05-01

    analgesics and are severely impaired. They are at increased risk for developmental stagnation. Adequate treatment and referral are essential to interrupt progression of the chronic pain process into adulthood.

  20. Exposure to low doses (20 cGy) of Hze results in spatial memory impairment in rats.

    Science.gov (United States)

    Britten, Richard; Johnson, Angela; Davis, Leslie; Green-Mitchell, Shamina; Chabriol, Olivia; Sanford, Larry; Drake, Richard

    INTRODUCTION. Current models predict that the astronauts on a mission to a deep space destination, such as Mars, will be exposed to 25 cGy of Galactic cosmic radiation (GCR). The long-term consequence of exposure to such doses is largely unknown, but given that 1.3 Gy of X-rays has been reported to lead to long-term cognitive deficits (Shore et al, 1976) and that CGR have an RBE of 2-5, it is likely that the predicted 25 cGy of GCR will lead to defects in the cognitive ability of the astronauts during and after the mission. Our studies are designed to help define the GCR dose that will lead to defects in complex working memory, and also to elucidate the mechanisms whereby hadronic radiation diminishes neurocognitive function. The identification of such processes would provide an opportunity for post-mission surveillance, and hopefully will lead to intervention strategies that will ameliorate or attenuate GCR-induced neurocognitive deficits. MATERIALS METHODS. Four-week old male Wistar rats were exposed to either X-rays or 1 GeV 56Fe. At three or six months post exposure the performance of the rats in the Barnes' Maze (Spatial memory) was established. The duration and frequency of REM sleep was also monitored to determine if the neurocognitive deficits arose due to reduced memory consolidation as a result of diminished REM sleep. We used a novel, but maturing technique, called MALDI-MS imaging (or MALDI-MSI), to identify specific regions of the brain where the neuroproteome differs in rats that have developed spatial memory impairments. RESULTS. 11.5 Gy of X-rays led to reduced performance in the Barnes's maze. In contrast, exposure to 20 cGy of Hze (1 GeV 56Fe) resulted in a significant impairment of spatial memory performance as measured in the Barnes' Maze, which was manifested by an increase in relative escape latency REL over a 5 day testing period. Such an increase in REL could arise from the rats becoming less able, or perhaps less willing, to locate the

  1. Long-term heavy ketamine use is associated with spatial memory impairment and altered hippocampal activation

    NARCIS (Netherlands)

    Morgan, C.J.A.; Dodds, C.M.; Furby, H.; Pepper, F.; Johnson, F.; Freeman, T.P.; Hughes, E.; Doeller, C.F.; King, J.; Howes, O.; Stone, J.M.

    2014-01-01

    Ketamine, a non-competitive N-methyl-d-aspartate receptor antagonist, is rising in popularity as a drug of abuse. Preliminary evidence suggests that chronic, heavy ketamine use may have profound effects on spatial memory but the mechanism of these deficits is as yet unclear. This study aimed to

  2. Tau hyperphosphorylation and P-CREB reduction are involved in acrylamide-induced spatial memory impairment: Suppression by curcumin.

    Science.gov (United States)

    Yan, Dandan; Yao, Jianling; Liu, Ying; Zhang, Xing; Wang, Yiqi; Chen, Xiaoyi; Liu, Liegang; Shi, Nian; Yan, Hong

    2018-04-26

    Acrylamide (ACR) is an axonal toxicant that produces peripheral neuropathy in laboratory animals and humans. Epidemiological study found that diet ACR exposure was associated with a mild cognitive decline in men. However, limited information is available as regards its potential and underlying mechanism to cause memory alterations. Curcumin is a polyphenol with neuroprotective and cognitive-enhancing properties. In this study, we aimed to investigate the mechanism of ACR-induced spatial memory impairment and the beneficial effect of curcumin. ACR exposure at 10 mg/kg/d for 7 weeks caused slight gait abnormality and spatial memory deficits, which was associated with an activation of glial cells, a reduction of phosphorylated cAMP response elements binding protein (P-CREB) and an aggregation of hyperphosphorylated tau including p-tau (Ser 262 ), AT8 (p-tau Ser 202 /Thr 205 ) and PHF1 (p-tau Ser 396/404 ) in the hippocampus and cortex. ACR markedly regulate the expression of glycogen synthase kinase-3β (GSK-3β) and cyclin-dependent kinase-5 (cdk5) to accelerate tau hyperphosphorylation. ACR inhibited the protein phosphatase 2A (PP2A) and lysosomal protease cathepsin D to decrease the p-tau dephosphorylation and degradation. The P-CREB and brain derived neurotrophic factor (BDNF) were significantly decreased by ACR. The upstream signalings of P-CREB, extracellular signal-related kinase (ERK) and Akt were markedly inhibited. The protein kinase RNA-like endoplasmic reticulum kinase (PERK) -eukaryotic initiation factor-2α (eIF2α) - activating transcription factor 4 (ATF4) signaling which negatively regulate memory processes by suppressing CREB was activated by ACR. Curcumin alleviated ACR-induced spatial memory impairment through reversing tau abnormalities and P-CREB reduction in the hippocampus. These results offered deeper insight into the mechanisms of and presented a potential new treatment for ACR-induced neurotoxicity. Copyright © 2018 Elsevier Inc. All

  3. Chronic exposure to glufosinate-ammonium induces spatial memory impairments, hippocampal MRI modifications and glutamine synthetase activation in mice.

    Science.gov (United States)

    Calas, André-Guilhem; Richard, Olivier; Même, Sandra; Beloeil, Jean-Claude; Doan, Bich-Thuy; Gefflaut, Thierry; Même, William; Crusio, Wim E; Pichon, Jacques; Montécot, Céline

    2008-07-01

    Glufosinate-ammonium (GLA), the active compound of a worldwide-used herbicide, acts by inhibiting the plant glutamine synthetase (GS) leading to a lethal accumulation of ammonia. GS plays a pivotal role in the mammalian brain where it allows neurotransmitter glutamate recycling within astroglia. Clinical studies report that an acute GLA ingestion induces convulsions and memory impairment in humans. Toxicological studies performed at doses used for herbicidal activity showed that GLA is probably harmless at short or medium range periods. However, effects of low doses of GLA on chronically exposed subjects are not known. In our study, C57BL/6J mice were treated during 10 weeks three times a week with 2.5, 5 and 10mg/kg of GLA. Effects of this chronic treatment were assessed at behavioral, structural and metabolic levels by using tests of spatial memory, locomotor activity and anxiety, hippocampal magnetic resonance imaging (MRI) texture analysis, and hippocampal GS activity assay, respectively. Chronic GLA treatments have effects neither on anxiety nor on locomotor activity of mice but at 5 and 10mg/kg induce (1) mild memory impairments, (2) a modification of hippocampal texture and (3) a significant increase in hippocampal GS activity. It is suggested that these modifications may be causally linked one to another. Since glutamate is the main neurotransmitter in hippocampus where it plays a crucial role in spatial memory, hippocampal MRI texture and spatial memory alterations might be the consequences of hippocampal glutamate homeostasis modification revealed by increased GS activity in hippocampus. The present study provides the first data that show cerebral alterations after chronic exposure to GLA.

  4. Impaired systemic tetrahydrobiopterin bioavailability and increased dihydrobiopterin in adult falciparum malaria: association with disease severity, impaired microvascular function and increased endothelial activation.

    Directory of Open Access Journals (Sweden)

    Tsin W Yeo

    2015-03-01

    Full Text Available Tetrahydrobiopterin (BH₄ is a co-factor required for catalytic activity of nitric oxide synthase (NOS and amino acid-monooxygenases, including phenylalanine hydroxylase. BH4 is unstable: during oxidative stress it is non-enzymatically oxidized to dihydrobiopterin (BH₂, which inhibits NOS. Depending on BH₄ availability, NOS oscillates between NO synthase and NADPH oxidase: as the BH₄/BH₂ ratio decreases, NO production falls and is replaced by superoxide. In African children and Asian adults with severe malaria, NO bioavailability decreases and plasma phenylalanine increases, together suggesting possible BH₄ deficiency. The primary three biopterin metabolites (BH₄, BH₂ and B₀ [biopterin] and their association with disease severity have not been assessed in falciparum malaria. We measured pterin metabolites in urine of adults with severe falciparum malaria (SM; n=12, moderately-severe malaria (MSM, n=17, severe sepsis (SS; n=5 and healthy subjects (HC; n=20 as controls. In SM, urinary BH₄ was decreased (median 0.16 ¼mol/mmol creatinine compared to MSM (median 0.27, SS (median 0.54, and HC (median 0.34]; p<0.001. Conversely, BH₂ was increased in SM (median 0.91 ¼mol/mmol creatinine, compared to MSM (median 0.67, SS (median 0.39, and HC (median 0.52; p<0.001, suggesting increased oxidative stress and insufficient recycling of BH2 back to BH4 in severe malaria. Overall, the median BH₄/BH₂ ratio was lowest in SM [0.18 (IQR: 0.04-0.32] compared to MSM (0.45, IQR 0.27-61, SS (1.03; IQR 0.54-2.38 and controls (0.66; IQR 0.43-1.07; p<0.001. In malaria, a lower BH₄/BH₂ ratio correlated with decreased microvascular reactivity (r=0.41; p=0.03 and increased ICAM-1 (r=-0.52; p=0.005. Decreased BH4 and increased BH₂ in severe malaria (but not in severe sepsis uncouples NOS, leading to impaired NO bioavailability and potentially increased oxidative stress. Adjunctive therapy to regenerate BH4 may have a role in improving NO

  5. Loss of FMRP Impaired Hippocampal Long-Term Plasticity and Spatial Learning in Rats

    Directory of Open Access Journals (Sweden)

    Yonglu Tian

    2017-08-01

    Full Text Available Fragile X syndrome (FXS is a neurodevelopmental disorder caused by mutations in the FMR1 gene that inactivate expression of the gene product, the fragile X mental retardation 1 protein (FMRP. In this study, we used clustered regularly interspaced short palindromic repeats (CRISPR/CRISPR-associated protein 9 (Cas9 technology to generate Fmr1 knockout (KO rats by disruption of the fourth exon of the Fmr1 gene. Western blotting analysis confirmed that the FMRP was absent from the brains of the Fmr1 KO rats (Fmr1exon4-KO. Electrophysiological analysis revealed that the theta-burst stimulation (TBS–induced long-term potentiation (LTP and the low-frequency stimulus (LFS–induced long-term depression (LTD were decreased in the hippocampal Schaffer collateral pathway of the Fmr1exon4-KO rats. Short-term plasticity, measured as the paired-pulse ratio, remained normal in the KO rats. The synaptic strength mediated by the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR was also impaired. Consistent with previous reports, the Fmr1exon4-KO rats demonstrated an enhanced 3,5-dihydroxyphenylglycine (DHPG–induced LTD in the present study, and this enhancement is insensitive to protein translation. In addition, the Fmr1exon4-KO rats showed deficits in the probe trial in the Morris water maze test. These results demonstrate that deletion of the Fmr1 gene in rats specifically impairs long-term synaptic plasticity and hippocampus-dependent learning in a manner resembling the key symptoms of FXS. Furthermore, the Fmr1exon4-KO rats displayed impaired social interaction and macroorchidism, the results consistent with those observed in patients with FXS. Thus, Fmr1exon4-KO rats constitute a novel rat model of FXS that complements existing mouse models.

  6. Prenatal complex rhythmic music sound stimulation facilitates postnatal spatial learning but transiently impairs memory in the domestic chick.

    Science.gov (United States)

    Kauser, H; Roy, S; Pal, A; Sreenivas, V; Mathur, R; Wadhwa, S; Jain, S

    2011-01-01

    Early experience has a profound influence on brain development, and the modulation of prenatal perceptual learning by external environmental stimuli has been shown in birds, rodents and mammals. In the present study, the effect of prenatal complex rhythmic music sound stimulation on postnatal spatial learning, memory and isolation stress was observed. Auditory stimulation with either music or species-specific sounds or no stimulation (control) was provided to separate sets of fertilized eggs from day 10 of incubation. Following hatching, the chicks at age 24, 72 and 120 h were tested on a T-maze for spatial learning and the memory of the learnt task was assessed 24 h after training. In the posthatch chicks at all ages, the plasma corticosterone levels were estimated following 10 min of isolation. The chicks of all ages in the three groups took less (p memory after 24 h of training, only the music-stimulated chicks at posthatch age 24 h took a significantly longer (p music sounds facilitates spatial learning, though the music stimulation transiently impairs postnatal memory. 2011 S. Karger AG, Basel.

  7. Rescue of cAMP response element-binding protein signaling reversed spatial memory retention impairments induced by subanesthetic dose of propofol.

    Science.gov (United States)

    Zhang, Hao; Zhang, Shao-Bo; Zhang, Qing-Qing; Liu, Meng; He, Xing-Ying; Zou, Zui; Sun, Hai-Jing; You, Zhen-Dong; Shi, Xue-Yin

    2013-07-01

    The intravenous anesthetic propofol caused episodic memory impairments in human. We hypothesized propofol caused episodic-like spatial memory retention but not acquisition impairments in rats and rescuing cAMP response element-binding protein (CREB) signaling using selective type IV phosphodiesterase (PDEIV) inhibitor rolipram reversed these effects. Male Sprague-Dawley rats were randomized into four groups: control; propofol (25 mg/kg, intraperitoneal); rolipram; and rolipram + propofol (pretreatment of rolipram 25 min before propofol, 0.3 mg/kg, intraperitoneal). Sedation and motor coordination were evaluated 5, 15, and 25 min after propofol injection. Invisible Morris water maze (MWM) acquisition and probe test (memory retention) were performed 5 min and 24 h after propofol injection. Visible MWM training was simultaneously performed to resist nonspatial effects. Hippocampal CREB signaling was detected 5 min, 50 min, and 24 h after propofol administration. Rolipram did not change propofol-induced anesthetic/sedative states or impair motor skills. No difference was found on the latency to the platform during the visible MWM. Propofol impaired spatial memory retention but not acquisition. Rolipram reversed propofol-induced spatial memory impairments and suppression on cAMP levels, CaMKIIα and CREB phosphorylation, brain-derived neurotropic factor (BDNF) and Arc protein expression. Propofol caused spatial memory retention impairments but not acquisition inability possibly by inhibiting CREB signaling. © 2013 John Wiley & Sons Ltd.

  8. Severe hypoglycemia, impaired awareness of hypoglycemia, and self-monitoring in adults with type 1 diabetes

    DEFF Research Database (Denmark)

    Hendrieckx, Crystal; Jenkins, A; Hagger, Virginia

    2017-01-01

    AIMS: To assess prevalence of severe hypoglycemia, awareness and symptoms of hypoglycemia, and their associations with self-monitoring of blood glucose. METHODS: Diabetes MILES-Australia Study participants completed validated questionnaires and study-specific items. RESULTS: Of 642 adults with ty...... autonomic symptoms, perceived at relatively low glucose levels. Frequent self-monitoring of blood glucose prompted early recognition and treatment of hypoglycemia, suggesting severe hypoglycemia risk can be minimized.......AIMS: To assess prevalence of severe hypoglycemia, awareness and symptoms of hypoglycemia, and their associations with self-monitoring of blood glucose. METHODS: Diabetes MILES-Australia Study participants completed validated questionnaires and study-specific items. RESULTS: Of 642 adults with type...

  9. Deficits in facial emotion recognition indicate behavioral changes and impaired self-awareness after moderate to severe traumatic brain injury.

    Science.gov (United States)

    Spikman, Jacoba M; Milders, Maarten V; Visser-Keizer, Annemarie C; Westerhof-Evers, Herma J; Herben-Dekker, Meike; van der Naalt, Joukje

    2013-01-01

    Traumatic brain injury (TBI) is a leading cause of disability, specifically among younger adults. Behavioral changes are common after moderate to severe TBI and have adverse consequences for social and vocational functioning. It is hypothesized that deficits in social cognition, including facial affect recognition, might underlie these behavioral changes. Measurement of behavioral deficits is complicated, because the rating scales used rely on subjective judgement, often lack specificity and many patients provide unrealistically positive reports of their functioning due to impaired self-awareness. Accordingly, it is important to find performance based tests that allow objective and early identification of these problems. In the present study 51 moderate to severe TBI patients in the sub-acute and chronic stage were assessed with a test for emotion recognition (FEEST) and a questionnaire for behavioral problems (DEX) with a self and proxy rated version. Patients performed worse on the total score and on the negative emotion subscores of the FEEST than a matched group of 31 healthy controls. Patients also exhibited significantly more behavioral problems on both the DEX self and proxy rated version, but proxy ratings revealed more severe problems. No significant correlation was found between FEEST scores and DEX self ratings. However, impaired emotion recognition in the patients, and in particular of Sadness and Anger, was significantly correlated with behavioral problems as rated by proxies and with impaired self-awareness. This is the first study to find these associations, strengthening the proposed recognition of social signals as a condition for adequate social functioning. Hence, deficits in emotion recognition can be conceived as markers for behavioral problems and lack of insight in TBI patients. This finding is also of clinical importance since, unlike behavioral problems, emotion recognition can be objectively measured early after injury, allowing for early

  10. Deficits in facial emotion recognition indicate behavioral changes and impaired self-awareness after moderate to severe traumatic brain injury.

    Directory of Open Access Journals (Sweden)

    Jacoba M Spikman

    Full Text Available Traumatic brain injury (TBI is a leading cause of disability, specifically among younger adults. Behavioral changes are common after moderate to severe TBI and have adverse consequences for social and vocational functioning. It is hypothesized that deficits in social cognition, including facial affect recognition, might underlie these behavioral changes. Measurement of behavioral deficits is complicated, because the rating scales used rely on subjective judgement, often lack specificity and many patients provide unrealistically positive reports of their functioning due to impaired self-awareness. Accordingly, it is important to find performance based tests that allow objective and early identification of these problems. In the present study 51 moderate to severe TBI patients in the sub-acute and chronic stage were assessed with a test for emotion recognition (FEEST and a questionnaire for behavioral problems (DEX with a self and proxy rated version. Patients performed worse on the total score and on the negative emotion subscores of the FEEST than a matched group of 31 healthy controls. Patients also exhibited significantly more behavioral problems on both the DEX self and proxy rated version, but proxy ratings revealed more severe problems. No significant correlation was found between FEEST scores and DEX self ratings. However, impaired emotion recognition in the patients, and in particular of Sadness and Anger, was significantly correlated with behavioral problems as rated by proxies and with impaired self-awareness. This is the first study to find these associations, strengthening the proposed recognition of social signals as a condition for adequate social functioning. Hence, deficits in emotion recognition can be conceived as markers for behavioral problems and lack of insight in TBI patients. This finding is also of clinical importance since, unlike behavioral problems, emotion recognition can be objectively measured early after injury

  11. Physicians' attitudes about artificial feeding in older patients with severe cognitive impairment in Japan: a qualitative study

    Directory of Open Access Journals (Sweden)

    Kai Ichiro

    2007-08-01

    Full Text Available Abstract Background The question of whether to withhold artificial nutrition and hydration (ANH from severely cognitively impaired older adults has remained nearly unexplored in Japan, where provision of ANH is considered standard care. The objective of this study was to identify and analyze factors related to the decision to provide ANH through percutaneous endoscopic gastrostomy (PEG in older Japanese adults with severe cognitive impairment. Methods Retrospective, in-depth interviews with thirty physicians experienced in the care of older, bed-ridden, non-communicative patients with severe cognitive impairment. Interview content included questions about factors influencing the decision to provide or withhold ANH, concerns and dilemmas concerning ANH and the choice of PEG feeding as an ANH method. The process of data collection and analysis followed the Grounded Theory approach. Results Data analysis identified five factors that influence Japanese physicians' decision to provide ANH through PEG tubes: (1 the national health insurance system that allows elderly patients to become long-term hospital in-patients; (2 legal barriers with regard to limiting treatment, including the risk of prosecution; (3 emotional barriers, especially abhorrence of death by 'starvation'; (4 cultural values that promote family-oriented end-of-life decision making; and (5 reimbursement-related factors involved in the choice of PEG. However, a small number of physicians did offer patients' families the option of withholding ANH. These physicians shared certain characteristics, such as a different perception of ANH and repeated communication with families concerning end-of-life care. These qualities were found to reduce some of the effects of the factors that favor provision of ANH. Conclusion The framework of Japan's medical-legal system unintentionally provides many physicians an incentive to routinely offer ANH for this patient group through PEG tubes. It seems

  12. Risk factors for spatial memory impairment in patients with temporal lobe epilepsy

    Czech Academy of Sciences Publication Activity Database

    Amlerová, J.; Laczó, J.; Vlček, Kamil; Javůrková, A.; Andel, R.; Marusič, P.

    2013-01-01

    Roč. 26, č. 1 (2013), s. 57-60 ISSN 1525-5050 R&D Projects: GA ČR(CZ) GA309/09/1053 Grant - others:GA MŠk(CZ) ED1.100/02/0123 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : spatial navigation * temporal lobe epilepsy * Morris water maze Subject RIV: FH - Neurology Impact factor: 2.061, year: 2013

  13. Quality of life and psychiatric work impairment in compulsive buying: increased symptom severity as a function of acquisition behaviors.

    Science.gov (United States)

    Williams, Alishia D

    2012-08-01

    The aims of the current study were to determine if compulsive acquisition behaviors are meaningfully related to quality of life and psychiatric work impairment and to determine if compulsive buyers who engage in 2 forms of acquisition (buying and excessive acquisition of free items) are more impaired than individuals who only engage in 1 form of acquisition. In a community-recruited sample, analysis of covariance conducted between groups identified as noncompulsive buyers (NCB) (n = 30), compulsive buyers who did not acquire free items (CBB) (n = 30), and compulsive buyers who also acquired free items (CBF) (n = 35) revealed that both acquisition groups reported higher levels of depression and stress and lower quality of psychological well-being than the NCB group, despite a comparable number of individuals self-reporting a current mental health disorder in each group. The CBF group reported higher levels of anxiety and general distress as well as greater work inefficiency days compared with the NCB and CBB groups. Furthermore, regression analyses supported the unique contribution of acquisition of free items to the prediction of psychiatric work impairment. Taken together, the findings highlight the serious impact of compulsive buying on work functioning, general quality of life, and psychological well-being and provide avenues for future research to investigate the role of acquisition of free items in symptom severity. Limitations and future directions are discussed. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Vitamin B12 deficiency results in severe oxidative stress, leading to memory retention impairment in Caenorhabditis elegans.

    Science.gov (United States)

    Bito, Tomohiro; Misaki, Taihei; Yabuta, Yukinori; Ishikawa, Takahiro; Kawano, Tsuyoshi; Watanabe, Fumio

    2017-04-01

    Oxidative stress is implicated in various human diseases and conditions, such as a neurodegeneration, which is the major symptom of vitamin B 12 deficiency, although the underlying disease mechanisms associated with vitamin B 12 deficiency are poorly understood. Vitamin B 12 deficiency was found to significantly increase cellular H 2 O 2 and NO content in Caenorhabditis elegans and significantly decrease low molecular antioxidant [reduced glutathione (GSH) and L-ascorbic acid] levels and antioxidant enzyme (superoxide dismutase and catalase) activities, indicating that vitamin B 12 deficiency induces severe oxidative stress leading to oxidative damage of various cellular components in worms. An NaCl chemotaxis associative learning assay indicated that vitamin B 12 deficiency did not affect learning ability but impaired memory retention ability, which decreased to approximately 58% of the control value. When worms were treated with 1mmol/L GSH, L-ascorbic acid, or vitamin E for three generations during vitamin B 12 deficiency, cellular malondialdehyde content as an index of oxidative stress decreased to the control level, but the impairment of memory retention ability was not completely reversed (up to approximately 50%). These results suggest that memory retention impairment formed during vitamin B 12 deficiency is partially attributable to oxidative stress. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  15. Age-dependent impairment of auditory processing under spatially focused and divided attention: an electrophysiological study.

    Science.gov (United States)

    Wild-Wall, Nele; Falkenstein, Michael

    2010-01-01

    By using event-related potentials (ERPs) the present study examines if age-related differences in preparation and processing especially emerge during divided attention. Binaurally presented auditory cues called for focused (valid and invalid) or divided attention to one or both ears. Responses were required to subsequent monaurally presented valid targets (vowels), but had to be suppressed to non-target vowels or invalidly cued vowels. Middle-aged participants were more impaired under divided attention than young ones, likely due to an age-related decline in preparatory attention following cues as was reflected in a decreased CNV. Under divided attention, target processing was increased in the middle-aged, likely reflecting compensatory effort to fulfill task requirements in the difficult condition. Additionally, middle-aged participants processed invalidly cued stimuli more intensely as was reflected by stimulus ERPs. The results suggest an age-related impairment in attentional preparation after auditory cues especially under divided attention and latent difficulties to suppress irrelevant information.

  16. Mutations affecting the SAND domain of DEAF1 cause intellectual disability with severe speech impairment and behavioral problems.

    Science.gov (United States)

    Vulto-van Silfhout, Anneke T; Rajamanickam, Shivakumar; Jensik, Philip J; Vergult, Sarah; de Rocker, Nina; Newhall, Kathryn J; Raghavan, Ramya; Reardon, Sara N; Jarrett, Kelsey; McIntyre, Tara; Bulinski, Joseph; Ownby, Stacy L; Huggenvik, Jodi I; McKnight, G Stanley; Rose, Gregory M; Cai, Xiang; Willaert, Andy; Zweier, Christiane; Endele, Sabine; de Ligt, Joep; van Bon, Bregje W M; Lugtenberg, Dorien; de Vries, Petra F; Veltman, Joris A; van Bokhoven, Hans; Brunner, Han G; Rauch, Anita; de Brouwer, Arjan P M; Carvill, Gemma L; Hoischen, Alexander; Mefford, Heather C; Eichler, Evan E; Vissers, Lisenka E L M; Menten, Björn; Collard, Michael W; de Vries, Bert B A

    2014-05-01

    Recently, we identified in two individuals with intellectual disability (ID) different de novo mutations in DEAF1, which encodes a transcription factor with an important role in embryonic development. To ascertain whether these mutations in DEAF1 are causative for the ID phenotype, we performed targeted resequencing of DEAF1 in an additional cohort of over 2,300 individuals with unexplained ID and identified two additional individuals with de novo mutations in this gene. All four individuals had severe ID with severely affected speech development, and three showed severe behavioral problems. DEAF1 is highly expressed in the CNS, especially during early embryonic development. All four mutations were missense mutations affecting the SAND domain of DEAF1. Altered DEAF1 harboring any of the four amino acid changes showed impaired transcriptional regulation of the DEAF1 promoter. Moreover, behavioral studies in mice with a conditional knockout of Deaf1 in the brain showed memory deficits and increased anxiety-like behavior. Our results demonstrate that mutations in DEAF1 cause ID and behavioral problems, most likely as a result of impaired transcriptional regulation by DEAF1. Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  17. Severely impaired bone material quality in Chihuahua zebrafish resembles classical dominant human osteogenesis imperfecta.

    Science.gov (United States)

    Fiedler, Imke A K; Schmidt, Felix N; Wölfel, Eva M; Plumeyer, Christine; Milovanovic, Petar; Gioia, Roberta; Tonelli, Francesca; Bale, Hrishikesh A; Jähn, Katharina; Besio, Roberta; Forlino, Antonella; Busse, Björn

    2018-04-17

    Excessive skeletal deformations and brittle fractures in the vast majority of patients suffering from osteogenesis imperfecta (OI) are a result of substantially reduced bone quality. Since the mechanical competence of bone is dependent on the tissue characteristics at small length scales, it is of crucial importance to assess how osteogenesis imperfecta manifests at the micro- and nanoscale of bone. In this context, the Chihuahua (Chi/ +) zebrafish, carrying a heterozygous glycine substitution in the α1 chain of collagen type I, has recently been proposed as suitable animal model of classical dominant OI, showing skeletal deformities, altered mineralization patterns and a smaller body size. This study assessed the bone quality properties of Chi/+ at multiple length scales using micro-computed tomography (micro-CT), histomorphometry, quantitative back-scattered electron imaging, Fourier transform infrared spectroscopy, nanoindentation and X-ray microscopy. At the skeletal level, Chi/+ display smaller body size, deformities and fracture calli in the ribs. Morphological changes at the whole bone level showed that the vertebrae in Chi/+ had a smaller size, smaller thickness and distorted shape. At the tissue level, Chi/+ displayed a higher degree of mineralization, lower collagen maturity, lower mineral maturity, altered osteoblast morphology, and lower osteocyte lacunar density compared to WT. The alterations in the cellular, compositional and structural properties of Chi/+ bones bear an explanation for the impaired local mechanical properties, which promote an increase in overall bone fragility in Chi/ +. The quantitative assessment of bone quality in Chi/+ thus further validates this mutant as an important model reflecting osseous characteristics associated with human classical dominant osteogenesis imperfecta. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  18. N-acetylcysteine prevents spatial memory impairment induced by chronic early postnatal glutaric acid and lipopolysaccharide in rat pups.

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    Fernanda S Rodrigues

    Full Text Available BACKGROUND AND AIMS: Glutaric aciduria type I (GA-I is characterized by accumulation of glutaric acid (GA and neurological symptoms, such as cognitive impairment. Although this disease is related to oxidative stress and inflammation, it is not known whether these processes facilitate the memory impairment. Our objective was to investigate the performance of rat pups chronically injected with GA and lipopolysaccharide (LPS in spatial memory test, antioxidant defenses, cytokines levels, Na+, K+-ATPase activity, and hippocampal volume. We also evaluated the effect of N-acetylcysteine (NAC on theses markers. METHODS: Rat pups were injected with GA (5 umol g of body weight-1, subcutaneously; twice per day; from 5th to 28th day of life, and were supplemented with NAC (150 mg/kg/day; intragastric gavage; for the same period. LPS (2 mg/kg; E.coli 055 B5 or vehicle (saline 0.9% was injected intraperitoneally, once per day, from 25th to 28th day of life. Oxidative stress and inflammatory biomarkers as well as hippocampal volume were assessed. RESULTS: GA caused spatial learning deficit in the Barnes maze and LPS potentiated this effect. GA and LPS increased TNF-α and IL-1β levels. The co-administration of these compounds potentiated the increase of IL-1β levels but not TNF-α levels in the hippocampus. GA and LPS increased TBARS (thiobarbituric acid-reactive substance content, reduced antioxidant defenses and inhibited Na+, K+-ATPase activity. GA and LPS co-administration did not have additive effect on oxidative stress markers and Na+, K+ pump. The hippocampal volume did not change after GA or LPS administration. NAC protected against impairment of spatial learning and increase of cytokines levels. NAC Also protected against inhibition of Na+,K+-ATPase activity and oxidative markers. CONCLUSIONS: These results suggest that inflammatory and oxidative markers may underlie at least in part of the neuropathology of GA-I in this model. Thus, NAC could

  19. Pruritus is associated with severely impaired quality of life in patients with primary sclerosing cholangitis.

    Science.gov (United States)

    Gotthardt, Daniel Nils; Rupp, Christian; Bruhin, Miriam; Schellberg, Dieter; Weiss, Karl H; Stefan, Reinhard; Donnerstag, Nadine; Stremmel, Wolfgang; Löwe, Bernd; Juenger, Jana; Sauer, Peter

    2014-12-01

    Quality of life, fundamental to the individual patient, has shown a lack of correlation with severity in research on several diseases. Thus, we aimed to identify factors associated with quality of life in patients with primary sclerosing cholangitis. The Short Form Health Survey and the Patient Health Questionnaire were used to assess quality of life and depression. Complete data sets of 113 patients were analyzed for correlation with sex, age, presence of concomitant inflammatory bowel disease and dominant stenosis, frequency of pruritus, and Mayo Risk Score. Physical functioning decreased with age (P<0.001). Further, women experienced more prominent role limitations because of physical (P<0.03) and emotional (P<0.01) problems. Although patients' quality of life and depression scores were only slightly lower than normal, more frequent pruritus was associated with a considerable reduction in quality of life in terms of physical and social functioning, general and mental health, bodily pain, vitality, and roles (because of physical problems) (P<0.01). It did not differ significantly according to the Mayo Risk Score or the presence of dominant stenoses. Depression scores were only significantly affected in patients with more frequent pruritus. Pruritus severely affects quality of life in patients with primary sclerosing cholangitis and is associated with depression to varying extents, although the most commonly used parameters of disease severity do not correspond to quality of life in these patients. These findings need to be considered with respect to treatment outcomes and indications for liver transplantation.

  20. Plasticity of premotor cortico-muscular coherence in severely impaired stroke patients with hand paralysis

    Directory of Open Access Journals (Sweden)

    Paolo Belardinelli

    2017-01-01

    In conclusion, functionally relevant modulations of CMC can be detected in patients with long-term, severe motor deficits after a brain-robot assisted rehabilitation training. Premotor beta-band CMC may serve as a biomarker and therapeutic target for novel treatment approaches in this patient group.

  1. Decreased Hippocampal 5-HT and DA Levels Following Sub-Chronic Exposure to Noise Stress: Impairment in both Spatial and Recognition Memory in Male Rats.

    Science.gov (United States)

    Haider, Saida; Naqvi, Fizza; Batool, Zehra; Tabassum, Saiqa; Perveen, Tahira; Saleem, Sadia; Haleem, Darakhshan Jabeen

    2012-01-01

    Mankind is exposed to a number of stressors, and among them noise is one which can cause intense stress. High levels of background noise can severely impair one's ability to concentrate. The present study was aimed to investigate the effect of sub-chronic noise stress on cognitive behavior and hippocampal monoamine levels in male rats. The study was performed on 12 male Wistar rats, divided into two groups; the control and noise-exposed. The rats in the test group were subjected to noise stress, 4h daily for 15 days. Cognitive testing was performed by the Elevated Plus Maze test (EPM) and Novel Object Recognition test (NOR). HPLC-EC was used to determine hippocampal monoamine levels and their metabolites. The data obtained revealed a significant decrease in hippocampal serotonin (5-hydroxytryptamine; 5-HT) and dopamine (DA) levels, whereas turnover ratios of 5-HT and DA were significantly increased compared to the controls. Rats exposed to noise exhibited a significant decrement in spatial memory. A significantly decreased recognition index of rats exposed to noise as compared to the control was also observed in the NOR test. Results of the present findings suggest the role of decreased hippocampal 5-HT and DA in the impairment of cognitive function following noise exposure.

  2. Survey of premenstrual symptom severity and impairment in Korean adolescents: premenstrual dysphoric disorder, subthreshold premenstrual dysphoric disorder and premenstrual syndrome.

    Science.gov (United States)

    Yang, Jaewon; Joe, Sook-Haeng; Lee, Moon-Soo; Kim, Seung-Hyun; Jung, In-Kwa

    2014-06-01

    The aims of the study were to examine the prevalence of premenstrual dysphoric disorder (PMDD), subthreshold PMDD and premenstrual syndrome (PMS) among adolescents, and to assess the nature of symptoms and the impact on daily life functions, especially for PMDD and subthreshold PMDD. A cross-sectional survey was conducted among adolescents from an urban area. Participants included 984 girls divided into the following four groups, using a premenstrual symptoms screening tool: PMDD, subthreshold PMDD, moderate/severe PMS and no/mild PMS. An Adolescent Mental Problem Questionnaire, Center for Epidemiological Studies-Depression Scale, revised Children's Manifest Anxiety Scale, and a menstrual information questionnaire were also used. Sixty-three (6.76%) of the subjects met the criteria for PMDD and 58 (6.2%) were subthreshold PMDD. The subthreshold PMDD group included 79.3% who met the symptom criteria for PMDD, but their impairment was moderate, and 21.7% who were falling short by the number of symptoms for PMDD diagnosis, though reporting severe impairment. The symptom intensity and frequency of the subthreshold PMDD subjects were similar to those in subjects with PMDD. In these two groups, 69% had moderate to severe physical symptoms. Psychiatric problems, including depression and anxiety, were higher in the PMDD and subthreshold PMDD groups than in the moderate/severe PMS and no/mild PMS group. In total, 20% of adolescents reported suffering from distressing premenstrual symptoms, and girls with PMDD and subthreshold PMDD were very similar in their symptom severity and characteristics. Prospective daily charting is needed to confirm the accurate diagnosis and management of PMDD. Copyright © 2012 Wiley Publishing Asia Pty Ltd.

  3. Spatial working memory in aging and mild cognitive impairment: effects of task load and contextual cueing.

    Science.gov (United States)

    Kessels, Roy P C; Meulenbroek, Olga; Fernández, Guillén; Olde Rikkert, Marcel G M

    2010-09-01

    Mild Cognitive Impairment (MCI) is characterized by episodic memory deficits, while aspects of working memory may also be implicated, but studies into this latter domain are scarce and results are inconclusive. Using a computerized search paradigm, this study compares 25 young adults, 25 typically aging older adults and 15 amnestic MCI patients as to their working-memory capacities for object-location information and potential differential effects of memory load and additional context cues. An age-related deficit in visuospatial working-memory maintenance was found that became more pronounced with increasing task demands. The MCI group additionally showed reduced maintenance of bound information, i.e., object-location associations, again especially at elevated memory load. No effects of contextual cueing were found. The current findings indicate that working memory should be considered when screening patients for suspected MCI and monitoring its progression.

  4. Ketogenic diet does not impair spatial ability controlled by the hippocampus in male rats.

    Science.gov (United States)

    Fukushima, Atsushi; Ogura, Yuji; Furuta, Miyako; Kakehashi, Chiaki; Funabashi, Toshiya; Akema, Tatsuo

    2015-10-05

    A ketogenic diet was recently shown to reduce glutamate accumulation in synaptic vesicles, decreasing glutamate transmission. We questioned whether a ketogenic diet affects hippocampal function, as glutamate transmission is critically involved in visuospatial ability. In the present study, male Wistar rats were maintained on a ketogenic diet containing 10% protein and 90% fat with complements for 3 weeks to change their energy expenditure from glucose-dependent to fat-dependent. Control rats were fed a diet containing 10% protein, 10% fat, and 80% carbohydrates. The fat-dependent energy expenditure induced by the ketogenic diet led to decreased body weight and increased blood ketone production, though the rats in the two groups consumed the same number of calories. The ketogenic diet did not alter food preferences for the control or high-fat diet containing 10% protein, 45% fat, and 45% carbohydrates. Anxiety in the open field was not altered by ingestion the ketogenic diet. However, rats fed the ketogenic diet performed better in the Y-maze test than rats fed the control diet. No difference was observed between the two groups in the Morris water maze test. Finally, Western blot revealed that the hippocampal expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptor subunit 1 (GluR1) was significantly increased in mice fed a ketogenic diet. These results suggest that hippocampal function is not impaired by a ketogenic diet and we speculate that the fat-dependent energy expenditure does not impair visuospatial ability. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Eyetracking metrics reveal impaired spatial anticipation in behavioural variant frontotemporal dementia.

    Science.gov (United States)

    Primativo, Silvia; Clark, Camilla; Yong, Keir X X; Firth, Nicholas C; Nicholas, Jennifer; Alexander, Daniel; Warren, Jason D; Rohrer, Jonathan D; Crutch, Sebastian J

    2017-11-01

    Eyetracking technology has had limited application in the dementia field to date, with most studies attempting to discriminate syndrome subgroups on the basis of basic oculomotor functions rather than higher-order cognitive abilities. Eyetracking-based tasks may also offer opportunities to reduce or ameliorate problems associated with standard paper-and-pencil cognitive tests such as the complexity and linguistic demands of verbal test instructions, and the problems of tiredness and attention associated with lengthy tasks that generate few data points at a slow rate. In the present paper we adapted the Brixton spatial anticipation test to a computerized instruction-less version where oculomotor metrics, rather than overt verbal responses, were taken into account as indicators of high level cognitive functions. Twelve bvFTD (in whom spatial anticipation deficits were expected), six SD patients (in whom deficits were predicted to be less frequent) and 38 healthy controls were presented with a 10 × 7 matrix of white circles. During each trial (N = 24) a black dot moved across seven positions on the screen, following 12 different patterns. Participants' eye movements were recorded. Frequentist statistical analysis of standard eye movement metrics were complemented by a Bayesian machine learning (ML) approach in which raw eyetracking time series datasets were examined to explore the ability to discriminate diagnostic group performance not only on the overall performance but also on individual trials. The original pen and paper Brixton test identified a spatial anticipation deficit in 7/12 (58%) of bvFTD and in 2/6 (33%) of SD patients. The eyetracking frequentist approach reported the deficit in 11/12 (92%) of bvFTD and in none (0%) of the SD patients. The machine learning approach had the main advantage of identifying significant differences from controls in 24/24 individual trials for bvFTD patients and in only 12/24 for SD patients. Results indicate that the fine

  6. Novelty exposure overcomes foot shock-induced spatial-memory impairment by processes of synaptic-tagging in rats.

    Science.gov (United States)

    Almaguer-Melian, William; Bergado-Rosado, Jorge; Pavón-Fuentes, Nancy; Alberti-Amador, Esteban; Mercerón-Martínez, Daymara; Frey, Julietta U

    2012-01-17

    Novelty processing can transform short-term into long-term memory. We propose that this memory-reinforcing effect of novelty could be explained by mechanisms outlined in the "synaptic tagging hypothesis." Initial short-term memory is sustained by a transient plasticity change at activated synapses and sets synaptic tags. These tags are later able to capture and process the plasticity-related proteins (PRPs), which are required to transform a short-term synaptic change into a long-term one. Novelty is involved in inducing the synthesis of PRPs [Moncada D, et al. (2011) Proc Natl Acad Sci USA 108:12937-12936], which are then captured by the tagged synapses, consolidating memory. In contrast to novelty, stress can impair learning, memory, and synaptic plasticity. Here, we address questions as to whether novelty-induced PRPs are able to prevent the loss of memory caused by stress and if the latter would not interact with the tag-setting process. We used water-maze (WM) training as a spatial learning paradigm to test our hypothesis. Stress was induced by a strong foot shock (FS; 5 × 1 mA, 2 s) applied 5 min after WM training. Our data show that FS reduced long-term but not short-term memory in the WM paradigm. This negative effect on memory consolidation was time- and training-dependent. Interestingly, novelty exposure prevented the stress-induced memory loss of the spatial task and increased BDNF and Arc expression. This rescuing effect was blocked by anisomycin, suggesting that WM-tagged synapses were not reset by FS and were thus able to capture the novelty-induced PRPs, re-establishing FS-impaired long-term memory.

  7. Regional anesthesia as an alternative to general anesthesia for abdominal surgery in patients with severe pulmonary impairment.

    Science.gov (United States)

    Savas, Jeannie F; Litwack, Robert; Davis, Kevin; Miller, Thomas A

    2004-11-01

    It is known that smokers and patients with chronic obstructive pulmonary disease (COPD) experience a higher rate of pulmonary-related complications following abdominal surgery. The impact of anesthetic technique (regional [RA] versus general [GA] versus combination of both) on the complication rate has not been established. This study examined the outcomes of abdominal surgery performed using RA (epidural or continuous spinal) as the sole anesthetic technique in patients with severe pulmonary impairment (SPI). We reviewed a series of 8 general surgery cases performed using RA alone (T4-T6 sensory level) in patients with SPI, as evidenced by an forced expiratory volume in 1 second (FEV(1)) less than 50% predicted and/or home oxygen requirement. One patient also received postoperative epidural analgesia. FEV(1) ranged from 0.3 to 1.84 L; 3 patients required home oxygen therapy, and 5 of the 8 were American Society of Anesthesiology (ASA) class 4. Operations included segmental colectomy (n = 2), open cholecystectomy (n = 1), incisional herniorrhaphy (n = 1), and laparoscopic herniorrhaphy (n = 4). Intraoperative conditions were adequate with RA alone for successful completion of the procedure in all cases. All patients recovered uneventfully except for 1 who developed postoperative pneumonia that resolved with standard therapy. Length of stay was less than 24 hours for 5 of 8 patients. Mortality was 0%. Abdominal surgery can be safely performed using RA alone in selected high-risk patients, making this option an attractive alternative to GA for those with severe pulmonary impairment.

  8. Causes of severe visual impairment and blindness in students in schools for the blind in Northwest Ethiopia.

    Science.gov (United States)

    Asferaw, Mulusew; Woodruff, Geoffrey; Gilbert, Clare

    2017-01-01

    To determine the causes of severe visual impairment and blindness (SVI/BL) among students in schools for the blind in Northwest Ethiopia and to identify preventable and treatable causes. Students attending nine schools for the blind in Northwest Ethiopia were examined and causes assigned using the standard WHO record form for children with blindness and low vision in May and June 2015. 383 students were examined, 357 (93%) of whom were severely visually impaired or blind (blind and four were SVI, total 104. The major anatomical site of visual loss among those 0-15 years was cornea/phthisis (47.1%), usually due to measles and vitamin A deficiency, followed by whole globe (22.1%), lens (9.6%) and uvea (8.7%). Among students aged 16 years and above, corneal/phthisis (76.3%) was the major anatomical cause, followed by lens (6.3%), whole globe (4.7%), uvea (3.6%) and optic nerve (3.2%). The leading underlying aetiology among students aged blindness, mainly as the result of measles and vitamin A deficiency, is still a public health problem in Northwest Ethiopia, and this has not changed as observed in other low-income countries. More than three-fourth of causes of SVI/BL in students in schools for the blind are potentially avoidable, with measles/vitamin A deficiency and cataract being the leading causes.

  9. Gaze-based assistive technology in daily activities in children with severe physical impairments-An intervention study.

    Science.gov (United States)

    Borgestig, Maria; Sandqvist, Jan; Ahlsten, Gunnar; Falkmer, Torbjörn; Hemmingsson, Helena

    2017-04-01

    To establish the impact of a gaze-based assistive technology (AT) intervention on activity repertoire, autonomous use, and goal attainment in children with severe physical impairments, and to examine parents' satisfaction with the gaze-based AT and with services related to the gaze-based AT intervention. Non-experimental multiple case study with before, after, and follow-up design. Ten children with severe physical impairments without speaking ability (aged 1-15 years) participated in gaze-based AT intervention for 9-10 months, during which period the gaze-based AT was implemented in daily activities. Repertoire of computer activities increased for seven children. All children had sustained usage of gaze-based AT in daily activities at follow-up, all had attained goals, and parents' satisfaction with the AT and with services was high. The gaze-based AT intervention was effective in guiding parents and teachers to continue supporting the children to perform activities with the AT after the intervention program.

  10. Cognitive Profiles on the Severe Impairment Battery Are Similar in Alzheimer Disease and Down Syndrome With Dementia.

    Science.gov (United States)

    Dick, Malcolm B; Doran, Eric; Phelan, Michael; Lott, Ira T

    2016-01-01

    Previous research has revealed similarities in the neuropathology, clinical presentation, and risk factors between persons with Alzheimer disease from the general population (GP-AD) and those with Down syndrome (DS-AD). Less is known, however, about the extent of similarities and differences in the cognitive profiles of these 2 populations. Fifty-one moderate to severely demented GP-AD and 59 DS-AD individuals participated in this study which compared the cognitive profiles of these 2 populations on the Severe Impairment Battery (SIB), controlling for sex as well as level of functional ability using a modified version of the Bristol Activities of Daily Living Scale. Overall, the neuropsychological profiles of the higher-functioning individuals within the DS-AD and advanced GP-AD groups, as represented by mean difference scores on the SIB as a whole and across the 9 separate cognitive domains, were very similar to one another after adjusting for sex and functional impairment. To our knowledge, this is the first study to directly compare the cognitive profiles of these 2 populations on the SIB. Findings suggest that the underlying dementia in GP-AD and DS-AD may have corresponding and parallel effects on cognition.

  11. Protein malnutrition impairs the immune response and influences the severity of infection in a hamster model of chronic visceral leishmaniasis.

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    Eugenia Carrillo

    Full Text Available Leishmaniasis remains one of the world's most devastating neglected tropical diseases. It mainly affects developing countries, where it often co-exists with chronic malnutrition, one of the main risk factors for developing the disease. Few studies have been published, however, on the relationship between leishmaniasis progression and malnutrition. The present paper reports the influence of protein malnutrition on the immune response and visceral disease development in adult hamsters infected with Leishmania infantum fed either standard or low protein diets. The low protein diet induced severe malnutrition in these animals, and upon infection with L. infantum 33% had severe visceral leishmaniasis compared to only 8% of animals fed the standard diet. The infected, malnourished animals showed notable leukocyte depletion, mild specific antibody responses, impairment of lymphoproliferation, presence of parasites in blood (16.67% of the hamsters and significant increase of the splenic parasite burden. Animals fed standard diet suffered agranulocytosis and monocytopenia, but showed stronger specific immune responses and had lower parasite loads than their malnourished counterparts. The present results show that protein malnutrition promotes visceral leishmaniasis and provide clues regarding the mechanisms underlying the impairment of the immune system.

  12. The Compression Flow as a Measure to Estimate the Cognitive Impairment Severity in Resting State fMRI and 18FDG-PET Alzheimer's Disease Connectomes

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    Antonio Giuliano Zippo

    2015-12-01

    Full Text Available The human brain appears organized in compartments characterized by seemingly specific functional purposes on many spatial scales. A complementary functional state binds information from specialized districts to return what is called integrated information. This fundamental network dynamics undergoes to severe disarrays in diverse degenerative conditions such as Alzheimer's Diseases (AD. The AD represents a multifarious syndrome characterized by structural, functional and metabolic landmarks. In particular, in the early stages of AD, adaptive functional modifications of the brain networks mislead initial diagnoses because cognitive abilities may result indiscernible from normal subjects. As a matter of facts, current measures of functional integration fail to catch significant differences among normal, mild cognitive impairment (MCI and even AD subjects. The aim of this work is to introduce a new topological feature called Compression Flow (CF to finely estimate the extent of the functional integration in the brain networks. The method uses a Monte Carlo-like estimation of the information integration flows returning the compression ratio between the size of the injected information and the size of the condensed information within the network. We analyzed the resting state connectomes of 75 subjects of the Alzheimer's Disease Neuroimaging Initiative 2 (ADNI repository. Our analyses are focused on the 18FGD-PET and functional MRI (fMRI acquisitions in several clinical screening conditions. Results indicated that CF effectively discriminate MCI, AD and normal subjects by showing a significant decrease of the functional integration in the AD and MCI brain connectomes. This result did not emerge by using a set of common complex network statistics. Furthermore, CF was best correlated with individual clinical scoring scales. In conclusion, we presented a novel measure to quantify the functional integration that resulted efficient to discriminate

  13. Hyperforin prevents beta-amyloid neurotoxicity and spatial memory impairments by disaggregation of Alzheimer's amyloid-beta-deposits.

    Science.gov (United States)

    Dinamarca, M C; Cerpa, W; Garrido, J; Hancke, J L; Inestrosa, N C

    2006-11-01

    The major protein constituent of amyloid deposits in Alzheimer's disease (AD) is the amyloid beta-peptide (Abeta). In the present work, we have determined the effect of hyperforin an acylphloroglucinol compound isolated from Hypericum perforatum (St John's Wort), on Abeta-induced spatial memory impairments and on Abeta neurotoxicity. We report here that hyperforin: (1) decreases amyloid deposit formation in rats injected with amyloid fibrils in the hippocampus; (2) decreases the neuropathological changes and behavioral impairments in a rat model of amyloidosis; (3) prevents Abeta-induced neurotoxicity in hippocampal neurons both from amyloid fibrils and Abeta oligomers, avoiding the increase in reactive oxidative species associated with amyloid toxicity. Both effects could be explained by the capacity of hyperforin to disaggregate amyloid deposits in a dose and time-dependent manner and to decrease Abeta aggregation and amyloid formation. Altogether these evidences suggest that hyperforin may be useful to decrease amyloid burden and toxicity in AD patients, and may be a putative therapeutic agent to fight the disease.

  14. Citalopram Ameliorates Impairments in Spatial Memory and Synaptic Plasticity in Female 3xTgAD Mice

    Directory of Open Access Journals (Sweden)

    Zhang Wei

    2017-01-01

    Full Text Available Alzheimer’s disease (AD is the primary cause of dementia. There is no effective treatment. Amyloid-β peptide (Aβ plays an important role in the pathogenesis and thus strategies suppressing Aβ production and accumulation seem promising. Citalopram is an antidepressant drug and can decrease Aβ production and amyloid plaques in transgenic mice of AD and humans. Whether citalopram can ameliorate memory deficit was not known yet. We tested the effects of citalopram on behavioral performance and synaptic plasticity in female 3xTgAD mice, a well-characterized model of AD. Mice were treated with citalopram or water from 5 months of age for 3 months. Citalopram treatment at approximately 10 mg/kg/day significantly improved spatial memory in the Morris water maze (MWM test, while not affecting anxiety-like and depression-like behavior in 3xTgAD mice. Further, hippocampal long-term potentiation (LTP impairment in 3xTgAD mice was reversed by citalopram treatment. Citalopram treatment also significantly decreased the levels of insoluble Aβ40 in hippocampal and cortical tissues in 3xTgAD mice, accompanied with a reduced amyloid precursor protein (APP. Together, citalopram treatment may be a promising strategy for AD and further clinical trials should be conducted to verify the effect of citalopram on cognition in patients with AD or mild cognitive impairment.

  15. Neurological effects of inorganic arsenic exposure: altered cysteine/glutamate transport, NMDA expression and spatial memory impairment.

    Directory of Open Access Journals (Sweden)

    Lucio A Ramos-Chávez

    2015-02-01

    Full Text Available Inorganic arsenic (iAs is an important natural pollutant. Millions of individuals worldwide drink water with high levels of iAs. Chronic exposure to iAs has been associated with lower IQ and learning disabilities as well as memory impairment. iAs is methylated in tissues such as the brain generating mono and dimethylated species. iAs methylation requires cellular glutathione (GSH, which is the main antioxidant in the central nervous system. In humans, As species cross the placenta and are found in cord blood. A CD1 mouse model was used to investigate effects of gestational iAs exposure which can lead to oxidative damage, disrupted cysteine/glutamate transport and its putative impact in learning and memory. On postnatal days (PNDs 1, 15 and 90, the expression of membrane transporters related to GSH synthesis and glutamate transport and toxicity, such as xCT, EAAC1, GLAST and GLT1, as well as LAT1, were analyzed. Also, the expression of the glutamate receptor N-methyl-D-aspartate (NMDAR subunits NR2A and B as well as the presence of As species in cortex and hippocampus were investigated. On PND 90, an object location task was performed to associate exposure with memory impairment. Gestational exposure to iAs affected the expression of cysteine/glutamate transporters in cortex and hippocampus and induced a negative modulation of NMDAR NR2B subunit in the hippocampus. Behavioral tasks showed significant spatial memory impairment in males while the effect was marginal in females.

  16. Efficacy of vildagliptin in combination with insulin in patients with type 2 diabetes and severe renal impairment

    Directory of Open Access Journals (Sweden)

    Lukashevich V

    2013-01-01

    Full Text Available Valentina Lukashevich,1 Anja Schweizer,2 James E Foley,1 Sheila Dickinson,2 Per-Henrik Groop,3 Wolfgang Kothny11Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 2Novartis Pharma AG, Basel, Switzerland; 3Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Finland, and Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, AustraliaBackground: The purpose of this study was to evaluate the efficacy of vildagliptin 50 mg once daily in patients with severe renal impairment (estimated glomerular filtration rate < 30 mL/min/1.73 m2 and longstanding type 2 diabetes not adequately controlled with insulin therapy, which is a difficult-to-treat population, with limited therapeutic options and a high susceptibility to hypoglycemia.Methods: This was a post hoc subanalysis of data obtained during a previously described randomized, double-blind, parallel-group, 24-week study comparing the efficacy and safety of vildagliptin 50 mg once daily versus placebo in patients with type 2 diabetes and moderate or severe renal impairment. The present data derive from 178 patients with severe renal impairment (baseline estimated glomerular filtration rate approximately 21 mL/min/1.73 m2, 100 randomized to vildagliptin, 78 randomized to placebo, all of whom were receiving insulin therapy (alone or in combination with an oral antidiabetic agent for longstanding type 2 diabetes (mean approximately 19 years.Results: With vildagliptin in combination with insulin, the adjusted mean change (AMΔ in HbA1c from baseline (7.7% ± 0.1% was -0.9% ± 0.4% and the between-treatment difference (vildagliptin – placebo was -0.6% ± 0.2% (P < 0.001. The percentage of patients achieving endpoint HbA1c < 7.0% was significantly higher with vildagliptin than placebo (45.2% versus 22.8%, P = 0.008. When added to insulin, vildagliptin and placebo had

  17. Unilateral lesion of dorsal hippocampus in adult rats impairs contralateral long-term potentiation in vivo and spatial memory in the early postoperative phase.

    Science.gov (United States)

    Li, Hongjie; Wu, Xiaoyan; Bai, Yanrui; Huang, Yan; He, Wenting; Dong, Zhifang

    2012-05-01

    It is well documented that bilateral hippocampal lesions or unilateral hippocampal lesion at birth causes impairment of contralateral LTP and long-term memory. However, effects of unilateral hippocampal lesion in adults on contralateral in vivo LTP and memory are not clear. We here examined the influence of unilateral electrolytic dorsal hippocampal lesion in adult rats on contralateral LTP in vivo and spatial memory during different postoperative phases. We found that acute unilateral hippocampal lesion had no effect on contralateral LTP. However, contralateral LTP was impaired at 1 week after lesion, and was restored to the control level at postoperative week 4. Similarly, spatial memory was also impaired at postoperative week 1, and was restored at postoperative week 4. In addition, the rats at postoperative week 1 showed stronger spatial exploratory behavior in a novel open-field environment. The sham operation had no effects on contralateral LTP, spatial memory and exploration at either postoperative week 1 or week 4. These results suggest that unilateral dorsal hippocampal lesion in adult rats causes transient contralateral LTP impairment and spatial memory deficit. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Acute tubulointerstitial nephritis with severe renal impairment associated with multisystem IgG4-related disease

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    Rafael Coimbra Ferreira Beltrame

    Full Text Available Abstract The IgG4-related disease has a wide clinical spectrum where multiple organs can be affected, and the diagnosis depends on typical histopathological findings and an elevated IgG4 expression in plasma cells in the affected tissue. We describe the clinical presentation and evolution of a patient with acute tubulointerstitial nephritis, severe kidney failure and systemic manifestations such as lymphadenomegaly and chronic pancreatitis. The diagnosis was confirmed by the clinical picture and kidney and lymph node histopathology, in which immunohistochemistry of the lymphoid tissue showed policlonality and increased expression of IgG4, with a IgG4/total IgG ratio > 80%. The patient was treated with prednisone at a dose of 60 mg/day, followed by mycophenolate mofetil, and showed clinical and renal function improvement at 6 months of follow-up. The high index of suspicion of IgG4-related disease with multisystem involvement and the early treatment of this condition are essential to improve the prognosis of affected patients.

  19. Prenatal stress challenge impairs fetal lung development and asthma severity sex-specifically in mice.

    Science.gov (United States)

    Zazara, Dimitra E; Perani, Clara V; Solano, María E; Arck, Petra C

    2018-02-01

    Allergic asthma is an increasing health problem worldwide. Interestingly, prenatal challenges such as stress have been associated with an increased risk for asthma during childhood. The underlying pathogenesis of how prenatal stress increases the risk for asthma still remains unclear. Potential targets could be that the fetal immune ontogeny or fetal lung development are compromised by prenatal challenges. Here, we aimed to identify whether prenatal stress challenge affects fetal lung development in mice. C57BL/6 pregnant mice were challenged with sound stress and fetal lung development was assessed histologically. Whilst prenatal stress challenge did not profoundly affect lung development in male fetuses, it resulted in less extensive terminal sacs, surrounded by thicker mesenchymal tissue in female fetuses. Thus, prenatal stress disrupted fetal lung development sex-specifically. Interestingly, upon prenatal stress challenge, the airway hyperresponsiveness and eosinophilic inflammation- two hallmarks of asthma - were significantly increased in adult female offspring, whilst regulatory CD4+ T cells were reduced. These findings strongly underpin the sex-specific association between s challenged fetal development and a sex-specific altered severity of asthma in adult offspring. Our model now allows to identify maternal markers through which the risk for asthma and possible other diseases is vertically transferred before birth in response to challenges. Such identification then opens avenues for primary disease prevention. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Impaired cardiovascular structure and function in adult survivors of severe acute malnutrition.

    Science.gov (United States)

    Tennant, Ingrid A; Barnett, Alan T; Thompson, Debbie S; Kips, Jan; Boyne, Michael S; Chung, Edward E; Chung, Andrene P; Osmond, Clive; Hanson, Mark A; Gluckman, Peter D; Segers, Patrick; Cruickshank, J Kennedy; Forrester, Terrence E

    2014-09-01

    Malnutrition below 5 years remains a global health issue. Severe acute malnutrition (SAM) presents in childhood as oedematous (kwashiorkor) or nonoedematous (marasmic) forms, with unknown long-term cardiovascular consequences. We hypothesized that cardiovascular structure and function would be poorer in SAM survivors than unexposed controls. We studied 116 adult SAM survivors, 54 after marasmus, 62 kwashiorkor, and 45 age/sex/body mass index-matched community controls who had standardized anthropometry, blood pressure, echocardiography, and arterial tonometry performed. Left ventricular indices and outflow tract diameter, carotid parameters, and pulse wave velocity were measured, with systemic vascular resistance calculated. All were expressed as SD scores. Mean (SD) age was 28.8±7.8 years (55% men). Adjusting for age, sex, height, and weight, SAM survivors had mean (SE) reductions for left ventricular outflow tract diameter of 0.67 (0.16; PMalnutrition survivors are thus likely to develop excess hypertension in later life, especially when exposed to obesity. © 2014 American Heart Association, Inc.

  1. Spatial distributions of dose enhancement around a gold nanoparticle at several depths of proton Bragg peak

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Jihun [Department of Radiation Oncology, Hokkaido University Graduate School of Medicine, Hokkaido University (Japan); Sutherland, Kenneth [Department of Medical Physics, Hokkaido University Graduate School of Medicine, Hokkaido University (Japan); Hashimoto, Takayuki [Department of Radiation Medicine, Hokkaido University Graduate School of Medicine (Japan); Shirato, Hiroki [Department of Radiation Medicine, Hokkaido University Graduate School of Medicine and Global Station for Quantum Medical Science and Engineering, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University (Japan); Date, Hiroyuki, E-mail: date@hs.hokudai.ac.jp [Faculty of Health Sciences, Hokkaido University (Japan)

    2016-10-01

    Gold nanoparticles (GNPs) have been recognized as a promising candidate for a radiation sensitizer. A proton beam incident on a GNP can produce secondary electrons, resulting in an enhancement of the dose around the GNP. However, little is known about the spatial distribution of dose enhancement around the GNP, especially in the direction along the incident proton. The purpose of this study is to determine the spatial distribution of dose enhancement by taking the incident direction into account. Two steps of calculation were conducted using the Geant4 Monte Carlo simulation toolkit. First, the energy spectra of 100 and 195 MeV protons colliding with a GNP were calculated at the Bragg peak and three other depths around the peak in liquid water. Second, the GNP was bombarded by protons with the obtained energy spectra. Radial dose distributions were computed along the incident beam direction. The spatial distributions of the dose enhancement factor (DEF) and subtracted dose (D{sub sub}) were then evaluated. The spatial DEF distributions showed hot spots in the distal radial region from the proton beam axis. The spatial D{sub sub} distribution isotropically spread out around the GNP. Low energy protons caused higher and wider dose enhancement. The macroscopic dose enhancement in clinical applications was also evaluated. The results suggest that the consideration of the spatial distribution of GNPs in treatment planning will maximize the potential of GNPs.

  2. Subcortical vascular cognitive impairment, no dementia : EEG global power independently predicts vascular impairment and brain symmetry index reflects severity of cognitive decline

    NARCIS (Netherlands)

    Sheorajpanday, Rishi V.A.; Mariën, Peter; Nagels, Guy; Weeren, Arie J.T.M.; Saerens, Jos; Van Putten, Michel J.A.M.; de Deyn, Peter P.

    2014-01-01

    Background and Purpose: Vascular cognitive impairment, no dementia (vCIND) is a prevalent and potentially preventable disorder. Clinical presentation of the small-vessel subcortical subtype may be insidious, and differential difficulties can arise with mild cognitive impairment. We investigated EEG

  3. Subcortical Vascular Cognitive Impairment, No Dementia : EEG Global Power Independently Predicts Vascular Impairment and Brain Symmetry Index Reflects Severity of Cognitive Decline

    NARCIS (Netherlands)

    Sheorajpanday, Rishi V. A.; Marien, Peter; Nagels, Guy; Weeren, Arie J. T. M.; Saerens, Jos; van Putten, Michel J. A. M.; De Deyn, Peter P.

    2014-01-01

    Background and Purpose:Vascular cognitive impairment, no dementia (vCIND) is a prevalent and potentially preventable disorder. Clinical presentation of the small-vessel subcortical subtype may be insidious, and differential difficulties can arise with mild cognitive impairment. We investigated EEG

  4. Prenatal Stress Impairs Spatial Learning and Memory Associated with Lower mRNA Level of the CAMKII and CREB in the Adult Female Rat Hippocampus.

    Science.gov (United States)

    Sun, Hongli; Wu, Haibin; Liu, Jianping; Wen, Jun; Zhu, Zhongliang; Li, Hui

    2017-05-01

    Prenatal stress (PS) results in various behavioral and emotional alterations observed in later life. In particular, PS impairs spatial learning and memory processes but the underlying mechanism involved in this pathogenesis still remains unknown. Here, we reported that PS lowered the body weight in offspring rats, particularly in female rats, and impaired spatial learning and memory of female offspring rats in the Morris water maze. Correspondingly, the decreased CaMKII and CREB mRNA in the hippocampus were detected in prenatally stressed female offspring, which partially explained the effect of PS on the spatial learning and memory. Our findings suggested that CaMKII and CREB may be involved in spatial learning and memory processes in the prenatally stressed adult female offspring.

  5. Role of synaptic structural plasticity in impairments of spatial learning and memory induced by developmental lead exposure in Wistar rats.

    Directory of Open Access Journals (Sweden)

    Yongmei Xiao

    Full Text Available Lead (Pb is found to impair cognitive function. Synaptic structural plasticity is considered to be the physiological basis of synaptic functional plasticity and has been recently found to play important roles in learning and memory. To study the effect of Pb on spatial learning and memory at different developmental stages, and its relationship with alterations of synaptic structural plasticity, postnatal rats were randomly divided into three groups: Control; Pre-weaning Pb (Parents were exposed to 2 mM PbCl2 3 weeks before mating until weaning of pups; Post-weaning Pb (Weaned pups were exposed to 2 mM PbCl2 for 9 weeks. The spatial learning and memory of rats was measured by Morris water maze (MWM on PND 85-90. Rat pups in Pre-weaning Pb and Post-weaning Pb groups performed significantly worse than those in Control group (p<0.05. However, there was no significant difference in the performance of MWM between the two Pb-exposure groups. Before MWM (PND 84, the number of neurons and synapses significantly decreased in Pre-weaning Pb group, but not in Post-weaning Pb group. After MWM (PND 91, the number of synapses in Pre-weaning Pb group increased significantly, but it was still less than that of Control group (p<0.05; the number of synapses in Post-weaning Pb group was also less than that of Control group (p<0.05, although the number of synapses has no differences between Post-weaning Pb and Control groups before MWM. In both Pre-weaning Pb and Post-weaning Pb groups, synaptic structural parameters such as thickness of postsynaptic density (PSD, length of synaptic active zone and synaptic curvature increased significantly while width of synaptic cleft decreased significantly compared to Control group (p<0.05. Our data demonstrated that both early and late developmental Pb exposure impaired spatial learning and memory as well as synaptic structural plasticity in Wistar rats.

  6. Allocentric Spatial Memory Testing Predicts Conversion from Mild Cognitive Impairment to Dementia: An Initial Proof-of-Concept Study.

    Science.gov (United States)

    Wood, Ruth A; Moodley, Kuven K; Lever, Colin; Minati, Ludovico; Chan, Dennis

    2016-01-01

    The hippocampus is one of the first regions to exhibit neurodegeneration in Alzheimer's disease (AD), and knowledge of its role in allocentric spatial memory may therefore aid early diagnosis of AD. The 4 Mountains Test (4MT) is a short and easily administered test of spatial memory based on the cognitive map theory of hippocampal function as derived from rodent single cell and behavioral studies. The 4MT has been shown in previous cross-sectional studies to be sensitive and specific for mild cognitive impairment (MCI) due to AD. This report describes the initial results of a longitudinal study testing the hypothesis that allocentric spatial memory is predictive of conversion from MCI to dementia. Fifteen patients with MCI underwent baseline testing on the 4MT in addition to CSF amyloid/tau biomarker studies, volumetric MRI and neuropsychological assessment including the Rey Auditory Verbal Learning Test (RAVLT) and Trail Making Test "B" (TMT-B). At 24 months, 9/15 patients had converted to AD dementia. The 4MT predicted conversion to AD with 93% accuracy (Cohen's d  = 2.52). The predictive accuracies of the comparator measures were as follows: CSF tau/β-amyloid 1-42 ratio 92% ( d  = 1.81), RAVLT 64% ( d  = 0.41), TMT-B 78% ( d  = 1.56), and hippocampal volume 77% ( d  = 0.65). CSF tau levels were strongly negatively correlated with 4MT scores ( r  = -0.71). This proof-of-concept study provides initial support for the hypothesis that allocentric spatial memory testing is a predictive cognitive marker of hippocampal neurodegeneration in pre-dementia AD. The 4MT is a brief, non-invasive, straightforward spatial memory test and is therefore ideally suited for use in routine clinical diagnostic practice. This is of particular importance given the current unmet need for simple accurate diagnostic tests for early AD and the ongoing development of potential disease-modifying therapeutic agents, which may be more efficacious when given earlier in

  7. Chronic Stress Impairs Prefrontal Cortex-Dependent Response Inhibition and Spatial Working Memory

    Science.gov (United States)

    Mika, Agnieszka; Mazur, Gabriel J.; Hoffman, Ann N.; Talboom, Joshua S.; Bimonte-Nelson, Heather A.; Sanabria, Federico; Conrad, Cheryl D.

    2012-01-01

    Chronic stress leads to neurochemical and structural alterations in the prefrontal cortex (PFC) that correspond to deficits in PFC-mediated behaviors. The present study examined the effects of chronic restraint stress on response inhibition (using a response-withholding task, fixed-minimum interval schedule of reinforcement, or FMI), and working memory (using a radial arm water maze, RAWM). Adult male Sprague Dawley rats were first trained on the RAWM and subsequently trained on FMI. Following acquisition of FMI, rats were assigned to a restraint stress (6h/d/28d in wire mesh restrainers) or control condition. Immediately after chronic stress, rats were tested on FMI and subsequently on RAWM. FMI results suggest that chronic stress reduces response inhibition capacity and motivation to initiate the task on selective conditions when food reward was not obtained on the preceding trial. RAWM results suggest that chronic stress produces transient deficits in working memory without altering previously consolidated reference memory. Behavioral measures from FMI failed to correlate with metrics from RAWM except for one in which changes in FMI timing precision negatively correlated with changes in RAWM working memory errors for the controls, a finding that was not observed following chronic stress. Fisher’s r to z transformation revealed no significant differences between control and stress with correlation coefficients. These findings are the first to show that chronic stress impairs both response inhibition and working memory, two behaviors that have never been direct compared within the same animals following chronic stress, using FMI, an appetitive task, and RAWM, a non-appetitive task. PMID:22905921

  8. Insulin protects against Aβ-induced spatial memory impairment, hippocampal apoptosis and MAPKs signaling disruption.

    Science.gov (United States)

    Ghasemi, Rasoul; Zarifkar, Asadollah; Rastegar, Karim; maghsoudi, Nader; Moosavi, Maryam

    2014-10-01

    Alzheimer disease (AD) is a progressive neurodegenerative disease characterized by extracellular deposits of beta amyloid (Aβ) and neuronal loss particularly in the hippocampus. Accumulating evidences have implied that insulin signaling impairment plays a key role in the pathology of AD; as much as it is considered as type 3 Diabetes. MAPKs are a group of signaling molecules which are involved in pathobiology of AD. Therefore this study was designed to investigate if intrahippocampal insulin hinders Aβ-related memory deterioration, hippocampal apoptosis and MAPKs signaling alteration induced by Aβ. Adult male Sprague-Dawely rats weighing 250-300 g were used in this study. The canules were implanted bilaterally into CA1 region. Aβ25-35 was administered during first 4 days after surgery (5 μg/2.5 μL/daily). Insulin treatment (0.5 or 6 mU) was done during days 4-9. The animal's learning and memory capability was assessed on days 10-13 using Morris water maze. After finishing of behavioral studies the hippocampi was isolated and the amount of hippocampal cleaved caspase 3 (the landmark of apoptosis) and the phosphorylated (activated) forms of P38, JNK and ERK was analyzed by western blot. The results showed that insulin in 6 but not 0.5 mU reversed the memory loss induced by Aβ25-35. Western blot analysis revealed that Aβ25-35 induced elevation of caspase-3 and all 3 MAPks subfamily activity, while insulin in 6 mu restored ERK and P38 activation but has no effect on JNK. This study disclosed that intrahippocampal insulin treatment averts not only Aβ-induced memory deterioration but also hippocampal caspase-3, ERK and P38 activation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. The Use of Key Informant Method for Identifying Children with Blindness and Severe Visual Impairment in Developing Countries.

    Science.gov (United States)

    du Toit, Rènée; Courtright, Paul; Lewallen, Susan

    2017-06-01

    An estimated 19 million children are visually impaired; of these, 1.4 million are irreversibly blind. A key challenge is to identify them early in life to benefit maximally from visual rehabilitation, and/or treatment. This aggregative review and structured literature analysis summarizes evidence of what it is about the key informant (KI) approach that works to identify children with blindness or severe visual impairment (B/SVI) in the community (for whom, to what extent, in what circumstances, in what respect, how and why). Peer-reviewed (PubMed, hand search) and grey literature (Google, World Health Organization website, academic theses, direct requests) were included, and methods and criteria used for identification, productivity (number of children referred per KI), accuracy of referrals (positive predictive value, PPV), age of children with B/SVI, KI definition, sex, information about cost and comparisons aggregated. We included 31 documents describing 22 unique KI programs. Mostly KIs identified children with B/SVI in 1-3 weeks, i.e. "campaign mode." In 60%, KIs were community volunteers, others formal health sector workers (FHSW). Around 0.02-1.56 children per KI (median = 0.25) were successfully recruited. PPV ranged from 12 to 66%. In two studies comparing FHSWs and community KIs, the latter were 8 and 10 times more productive. KIs working in campaign mode may provide an effective approach to identifying children with B/SVI in communities. Including identification of ocular problems and/or other impairments has been recommended. Research on factors that influence effectiveness and on whether KIs continue to contribute could inform programs.

  10. Impairment of CDKL5 nuclear localisation as a cause for severe infantile encephalopathy.

    Science.gov (United States)

    Rosas-Vargas, H; Bahi-Buisson, N; Philippe, C; Nectoux, J; Girard, B; N'Guyen Morel, M A; Gitiaux, C; Lazaro, L; Odent, S; Jonveaux, P; Chelly, J; Bienvenu, T

    2008-03-01

    Mutations in the human X-linked cyclin-dependent kinase-like 5 (CDKL5) gene have been shown to cause infantile spasms as well as Rett syndrome-like phenotype. To date, fewer than 20 different mutations have been reported. So far, no clear genotype-phenotype correlation has been established. We screened the entire coding region of CDKL5 in 151 affected girls with a clinically heterogeneous phenotype ranging from encephalopathy with epilepsy to atypical Rett syndrome by denaturing high liquid performance chromatography and direct sequencing, and we identified three novel missense mutations located in catalytic domain (p.Ala40Val, p.Arg65Gln, p.Leu220Pro). Segregation analysis showed that p.Arg65Gln was inherited from the healthy father, which rules out the involvement of CDKL5 in the aetiology of the phenotype in this patient. However, the de novo occurrence was shown for p.Ala40Val and p.Leu220Pro. The p.Ala40Val mutation was observed in two unrelated patients and represented the first recurrent mutation in the CDKL5 gene. For the two de novo mutations, we analysed the cellular localisation of the wild-type and CDKL5 mutants by transfection experiments. We showed that the two CDKL5 mutations cause mislocalisation of the mutant CDKL5 proteins in the cytoplasm. Interestingly these missense mutations that result in a mislocalisation of the CDKL5 protein are associated with severe developmental delay which was apparent within the first months of life characterised by early and generalised hypotonia, and autistic features, and as well as early infantile spasms.

  11. Administration of memantine during withdrawal mitigates overactivity and spatial learning impairments associated with neonatal alcohol exposure in rats.

    Science.gov (United States)

    Idrus, Nirelia M; McGough, Nancy N H; Riley, Edward P; Thomas, Jennifer D

    2014-02-01

    Prenatal alcohol exposure can disrupt central nervous system development, manifesting as behavioral deficits that include motor, emotional, and cognitive dysfunction. Both clinical and animal studies have reported binge drinking during development to be highly correlated with an increased risk of fetal alcohol spectrum disorders (FASD). We hypothesized that binge drinking may be especially damaging because it is associated with episodes of alcohol withdrawal. Specifically, we have been investigating the possibility that NMDA receptor-mediated excitotoxicity occurs during alcohol withdrawal and contributes to developmental alcohol-related neuropathology. Consistent with this hypothesis, administration of the NMDA receptor antagonists MK-801 or eliprodil during withdrawal attenuates behavioral alterations associated with early alcohol exposure. In this study, we investigated the effects of memantine, a clinically used NMDA receptor antagonist, on minimizing ethanol-induced overactivity and spatial learning deficits. Sprague-Dawley pups were exposed to 6.0 g/kg ethanol via intubation on postnatal day (PD) 6, a period of brain development that models late gestation in humans. Controls were intubated with a calorically matched maltose solution. During withdrawal, 24 and 36 hours after ethanol exposure, subjects were injected with a total of either 0, 20, or 30 mg/kg memantine. The subjects' locomotor levels were recorded in open field activity monitors on PDs 18 to 21 and on a serial spatial discrimination reversal learning task on PDs 40 to 43. Alcohol exposure induced overactivity and impaired performance in spatial learning. Memantine administration significantly attenuated the ethanol-associated behavioral alterations in a dose-dependent manner. Thus, memantine may be neuroprotective when administered during ethanol withdrawal. These data have important implications for the treatment of EtOH's neurotoxic effects and provide further support that ethanol withdrawal

  12. Prefrontal cortex and mediodorsal thalamus reduced connectivity is associated with spatial working memory impairment in rats with inflammatory pain.

    Science.gov (United States)

    Cardoso-Cruz, Helder; Sousa, Mafalda; Vieira, Joana B; Lima, Deolinda; Galhardo, Vasco

    2013-11-01

    The medial prefrontal cortex (mPFC) and the mediodorsal thalamus (MD) form interconnected neural circuits that are important for spatial cognition and memory, but it is not known whether the functional connectivity between these areas is affected by the onset of an animal model of inflammatory pain. To address this issue, we implanted 2 multichannel arrays of electrodes in the mPFC and MD of adult rats and recorded local field potential activity during a food-reinforced spatial working memory task. Recordings were performed for 3weeks, before and after the establishment of the pain model. Our results show that inflammatory pain caused an impairment of spatial working memory performance that is associated with changes in the activity of the mPFC-MD circuit; an analysis of partial directed coherence between the areas revealed a global decrease in the connectivity of the circuit. This decrease was observed over a wide frequency range in both the frontothalamic and thalamofrontal directions of the circuit, but was more evident from MD to mPFC. In addition, spectral analysis revealed significant oscillations of power across frequency bands, namely with a strong theta component that oscillated after the onset of the painful condition. Finally, our data revealed that chronic pain induces an increase in theta/gamma phase coherence and a higher level of mPFC-MD coherence, which is partially conserved across frequency bands. The present results demonstrate that functional disturbances in mPFC-MD connectivity are a relevant cause of deficits in pain-related working memory. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  13. Examining Spatial Variation in the Effects of Japanese Red Pine (Pinus densiflora on Burn Severity Using Geographically Weighted Regression

    Directory of Open Access Journals (Sweden)

    Hyun-Joo Lee

    2017-05-01

    Full Text Available Burn severity has profound impacts on the response of post-fire forest ecosystems to fire events. Numerous previous studies have reported that burn severity is determined by variables such as meteorological conditions, pre-fire forest structure, and fuel characteristics. An underlying assumption of these studies was the constant effects of environmental variables on burn severity over space, and these analyses therefore did not consider the spatial dimension. This study examined spatial variation in the effects of Japanese red pine (Pinus densiflora on burn severity. Specifically, this study investigated the presence of spatially varying relationships between Japanese red pine and burn severity due to changes in slope and elevation. We estimated conventional ordinary least squares (OLS and geographically weighted regression (GWR models and compared them using three criteria; the coefficients of determination (R2, Akaike information criterion for small samples (AICc, and Moran’s I-value. The GWR model performed considerably better than the OLS model in explaining variation in burn severity. The results provided strong evidence that the effect of Japanese red pine on burn severity was not constant but varied spatially. Elevation was a significant factor in the variation in the effects of Japanese red pine on burn severity. The influence of red pine on burn severity was considerably higher in low-elevation areas but became less important than the other variables in high-elevation areas. The results of this study can be applied to location-specific strategies for forest managers and can be adopted to improve fire simulation models to more realistically mimic the nature of fire behavior.

  14. Acute tubulointerstitial nephritis with severe renal impairment associated with multisystem IgG4-related disease.

    Science.gov (United States)

    Beltrame, Rafael Coimbra Ferreira; Friderichs, Maurício; Fior, Bárbara Rayanne; Schaefer, Pedro Guilherme; Thomé, Gustavo Gomes; Silva, Dirceu Reis da; Barros, Elvino José Guardão; Seligman, Renato; Veronese, Francisco Veríssimo

    2016-01-01

    The IgG4-related disease has a wide clinical spectrum where multiple organs can be affected, and the diagnosis depends on typical histopathological findings and an elevated IgG4 expression in plasma cells in the affected tissue. We describe the clinical presentation and evolution of a patient with acute tubulointerstitial nephritis, severe kidney failure and systemic manifestations such as lymphadenomegaly and chronic pancreatitis. The diagnosis was confirmed by the clinical picture and kidney and lymph node histopathology, in which immunohistochemistry of the lymphoid tissue showed policlonality and increased expression of IgG4, with a IgG4/total IgG ratio > 80%. The patient was treated with prednisone at a dose of 60 mg/day, followed by mycophenolate mofetil, and showed clinical and renal function improvement at 6 months of follow-up. The high index of suspicion of IgG4-related disease with multisystem involvement and the early treatment of this condition are essential to improve the prognosis of affected patients. Resumo A doença relacionada à IgG4 tem um espectro clínico amplo em que múltiplos órgãos podem ser afetados, e o diagnóstico depende de achados histopatológicos típicos e elevada expressão de IgG4 em plasmócitos no tecido afetado. Descrevemos o quadro clínico e a evolução de um paciente com nefrite túbulo-intersticial aguda, insuficiência renal grave e manifestações sistêmicas como linfoadenomegalias e pancreatite crônica. O diagnóstico foi confirmado pelas características clínicas e pela histopatologia renal e de linfonodo, na qual a imunohistoquímica mostrou tecido linfoide com policlonalidade e expressão aumentada de IgG4, com uma relação IgG4/IgG total > 80%. O paciente foi tratado com prednisona na dose de 60 mg/dia, seguido de micofenolato mofetil, e apresentou melhora clínica e da função renal depois de 6 meses de tratamento. O alto índice de suspeição da doença relacionada ao IgG4 com comprometimento multissist

  15. Spatial patterns of progressive brain volume loss after moderate-severe traumatic brain injury

    Science.gov (United States)

    Jolly, Amy; de Simoni, Sara; Bourke, Niall; Patel, Maneesh C; Scott, Gregory; Sharp, David J

    2018-01-01

    Abstract Traumatic brain injury leads to significant loss of brain volume, which continues into the chronic stage. This can be sensitively measured using volumetric analysis of MRI. Here we: (i) investigated longitudinal patterns of brain atrophy; (ii) tested whether atrophy is greatest in sulcal cortical regions; and (iii) showed how atrophy could be used to power intervention trials aimed at slowing neurodegeneration. In 61 patients with moderate-severe traumatic brain injury (mean age = 41.55 years ± 12.77) and 32 healthy controls (mean age = 34.22 years ± 10.29), cross-sectional and longitudinal (1-year follow-up) brain structure was assessed using voxel-based morphometry on T1-weighted scans. Longitudinal brain volume changes were characterized using a novel neuroimaging analysis pipeline that generates a Jacobian determinant metric, reflecting spatial warping between baseline and follow-up scans. Jacobian determinant values were summarized regionally and compared with clinical and neuropsychological measures. Patients with traumatic brain injury showed lower grey and white matter volume in multiple brain regions compared to controls at baseline. Atrophy over 1 year was pronounced following traumatic brain injury. Patients with traumatic brain injury lost a mean (± standard deviation) of 1.55% ± 2.19 of grey matter volume per year, 1.49% ± 2.20 of white matter volume or 1.51% ± 1.60 of whole brain volume. Healthy controls lost 0.55% ± 1.13 of grey matter volume and gained 0.26% ± 1.11 of white matter volume; equating to a 0.22% ± 0.83 reduction in whole brain volume. Atrophy was greatest in white matter, where the majority (84%) of regions were affected. This effect was independent of and substantially greater than that of ageing. Increased atrophy was also seen in cortical sulci compared to gyri. There was no relationship between atrophy and time since injury or age at baseline. Atrophy rates were related to memory performance at the end of the

  16. The impact of visual impairment on the ability to perform activities of daily living for persons with severe/profound intellectual disability.

    Science.gov (United States)

    Dijkhuizen, Annemarie; Hilgenkamp, Thessa I M; Krijnen, Wim P; van der Schans, Cees P; Waninge, Aly

    2016-01-01

    The ability to perform activities of daily living (ADL) as a component of participation is one of the factors that contribute to quality of life. The ability to perform ADL for persons experiencing severe/profound intellectual disability (ID) may be reduced due to their cognitive and physical capacities. However, until recently, the impact of the significantly prevalent visual impairments on the performance of activities of daily living has not yet been revealed within this group. The purpose of this prospective cross-sectional study was to investigate the impact of visual impairment on the performance of activities of daily living for persons with a severe/profound intellectual disability. The Barthel Index (BI) and Comfortable Walking Speed (CWS) were used to measure the ability of performing activities of daily living (ADL) in 240 persons with severe/profound ID and having Gross Motor Functioning Classification System (GMFCS) levels I, II or III; this included 120 persons with visual impairment. The impact of visual impairment on ADL was analyzed with linear regression. The results of the study demonstrated that visual impairment slightly affects the ability of performing activities of daily living (BI) for persons experiencing a severe/profound intellectual disability. GMFCS Levels II or III, profound ID level, and visual impairment each have the effect of lowering BI scores. GMFCS Levels II or III, and profound ID level each have the effect of increasing CWS scores, which indicates a lower walking speed. A main effect of visual impairment is present on CWS, but our results do show a substantive interaction effect between GMFCS level III and visual impairment on Comfortable Walking Speed in persons with a severe/profound intellectual disability. Visual impairment has a slight effect on ability to perform ADL in persons experiencing severe/profound ID. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Imidacloprid toxicity impairs spatial memory of echolocation bats through neural apoptosis in hippocampal CA1 and medial entorhinal cortex areas.

    Science.gov (United States)

    Hsiao, Chun-Jen; Lin, Ching-Lung; Lin, Tian-Yu; Wang, Sheue-Er; Wu, Chung-Hsin

    2016-04-13

    It has been reported that the decimation of honey bees was because of pesticides of imidacloprid. The imidacloprid is a wildly used neonicotinoid insecticide. However, whether imidacloprid toxicity interferes with the spatial memory of echolocation bats is still unclear. Thus, we compared the spatial memory of Formosan leaf-nosed bats, Hipposideros terasensis, before and after chronic treatment with a low dose of imidacloprid. We observed that stereotyped flight patterns of echolocation bats that received chronic imidacloprid treatment were quite different from their originally learned paths. We further found that neural apoptosis in hippocampal CA1 and medial entorhinal cortex areas of echolocation bats that received imidacloprid treatment was significantly enhanced in comparison with echolocation bats that received sham treatment. Thus, we suggest that imidacloprid toxicity may interfere with the spatial memory of echolocation bats through neural apoptosis in hippocampal CA1 and medial entorhinal cortex areas. The results provide direct evidence that pesticide toxicity causes a spatial memory disorder in echolocation bats. This implies that agricultural pesticides may pose severe threats to the survival of echolocation bats.

  18. Metformin Impairs Spatial Memory and Visual Acuity in Old Male Mice.

    Science.gov (United States)

    Thangthaeng, Nopporn; Rutledge, Margaret; Wong, Jessica M; Vann, Philip H; Forster, Michael J; Sumien, Nathalie

    2017-02-01

    Metformin is an oral anti-diabetic used as first-line therapy for type 2 diabetes. Because benefits of metformin extend beyond diabetes to other age-related pathology, and because its effect on gene expression profiles resembles that of caloric restriction, metformin has a potential as an anti-aging intervention and may soon be assessed as an intervention to extend healthspan. However, beneficial actions of metformin in the central nervous system have not been clearly established. The current study examined the effect of chronic oral metformin treatment on motor and cognitive function when initiated in young, middle-aged, or old male mice. C57BL/6 mice aged 4, 11, or 22 months were randomly assigned to either a metformin group (2 mg/ml in drinking water) or a control group. The mice were monitored weekly for body weight, as well as food and water intake and a battery of behavioral tests for motor, cognitive and visual function was initiated after the first month of treatment. Liver, hippocampus and cortex were collected at the end of the study to assess redox homeostasis. Overall, metformin supplementation in male mice failed to affect blood glucose, body weights and redox homeostasis at any age. It also had no beneficial effect on age-related declines in psychomotor, cognitive or sensory functions. However, metformin treatment had a deleterious effect on spatial memory and visual acuity, and reduced SOD activity in brain regions. These data confirm that metformin treatment may be associated with deleterious effect resulting from the action of metformin on the central nervous system.

  19. Mental Fatigue and Spatial References Impair Soccer Players' Physical and Tactical Performances

    Directory of Open Access Journals (Sweden)

    Diogo Coutinho

    2017-09-01

    Full Text Available This study examined the effects of mental fatigue and additional corridor and pitch sector lines on players' physical and tactical performances during soccer small-sided games. Twelve youth players performed four Gk+6vs6+Gk small-sided games. Prior to the game, one team performed a motor coordination task to induce mental fatigue, while the other one performed a control task. A repeated measures design allowed to compare players' performances across four conditions: (a with mental fatigue against opponents without mental fatigue in a normal pitch (MEN, (b with mental fatigue on a pitch with additional reference lines (#MEN; (c without mental fatigue against mentally fatigued opponents on a normal pitch (CTR; and (d without mental fatigue on a pitch with reference lines (#CTR. Player's physical performance was assessed by the distance covered per minute and the number of accelerations and decelerations (0.5–3.0 m/s2; > −3.0 m/s2. Positional data was used to determine individual (spatial exploration index, time synchronized in longitudinal and lateral directions and team-related variables (length, width, speed of dispersion and contraction. Unclear effects were found for the physical activity measures in most of the conditions. There was a small decrease in time spent laterally synchronized and a moderate decrease in the contraction speed when MEN compared to the CTR. Also, there was a small decrease in the time spent longitudinally synchronized during the #MEN condition compared to MEN. The results showed that mental fatigue affects the ability to use environmental information and players' positioning, while the additional reference lines may have enhanced the use of less relevant information to guide their actions during the #MEN condition. Overall, coaches could manipulate the mental fatigue and reference lines to induce variability and adaptation in young soccer players' behavior.

  20. Prenatal exposure to noise stress: anxiety, impaired spatial memory, and deteriorated hippocampal plasticity in postnatal life.

    Science.gov (United States)

    Barzegar, Marzieh; Sajjadi, Fatemeh Sadat; Talaei, Sayyed Alireza; Hamidi, Gholamali; Salami, Mahmoud

    2015-02-01

    Sound pollution is known as an annoying phenomenon in modern life. Especially, development of organisms during fetal life is more sensitive to environmental tensions. To address a link between the behavioral and electrophysiological aspects of brain function with action of hypothalamus-pituitary-adrenal (HPA) axis in stressed animals, this study was carried out on the male Wistar rats prenatally exposed to sound stress. Groups of pregnant rats were exposed to noise stress for 1, 2, and 4 hour(s). The degree of anxiety and the spatial memory were evaluated by elevated plus maze and Morris water maze, respectively. Basic synaptic activity and long-term potentiation (LTP) induction were assessed in the CA3-CA1 pathway of hippocampus. The serum level of corticosterone was measured in the pregnant mothers and the offspring. The behavioral experiments appeared that the stressed animals performed considerably weaker than the control rats. The prenatal stress negatively affected the basic synaptic responses and led to a lower level of LTP. The pregnant animals showed an increased serum corticosterone in comparison with the nonpregnant females. Also the offspring exposed to the noise stress had a more elevated level of corticosterone than the control rats. Our findings indicate that the corticosterone concentration changes markedly coincides the results of behavioral and electrophysiological experiments. We conclude that, similar to other environmental stresses, the sound stress during fetal life efficiently disturbs both cognitive abilities and synaptic activities. The changes in action of HPA axis may contribute to problems of the brain function in the prenatally stress exposed animals. © 2014 Wiley Periodicals, Inc.

  1. Enriched dairy fat matrix diet prevents early life lipopolysaccharide-induced spatial memory impairment at adulthood.

    Science.gov (United States)

    Dinel, A L; Rey, C; Baudry, C; Fressange-Mazda, C; Le Ruyet, P; Nadjar, A; Pallet, P; Joffre, C; Layé, S

    2016-10-01

    Polyunsaturated fatty acids (PUFAs) are essential fatty acids, which are critical for brain development and later life cognitive functions. The main brain PUFAs are docosahexaenoic acid (DHA) for the n-3 family and arachidonic acid (ARA) for the n-6 family, which are provided to the post-natal brain by breast milk or infant formula. Recently, the use of dairy lipids (DL) in replacement of vegetable lipids (VL) was revealed to potently promote the accretion of DHA in the developing brain. Brain DHA, in addition to be a key component of brain development, display potent anti-inflammatory activities, which protect the brain from adverse inflammatory events. In this work, we evaluated the protective effect of partial replacement of VL by DL, supplemented or not with DHA and ARA, on post-natal inflammation and its consequence on memory. Mice were fed with diets poor in vegetal n-3 PUFA (Def VL), balanced in vegetal n-3/n-6 PUFA (Bal VL), balanced in dairy lipids (Bal DL) or enriched in DHA and ARA (Supp VL; Supp DL) from the first day of gestation until adulthood. At post-natal day 14 (PND14), pups received a single administration of the endotoxin lipopolysaccharide (LPS) and brain cytokine expression, microglia phenotype and neurogenesis were measured. In a second set of experiments, memory and neurogenesis were measured at adulthood. Overall, our data showed that lipid quality of the diet modulates early life LPS effect on microglia phenotype, brain cytokine expression and neurogenesis at PND14 and memory at adulthood. In particular, Bal DL diet protects from the adverse effect of early life LPS exposure on PND14 neurogenesis and adult spatial memory. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Prevalence and causes of severe visual impairment and blindness among children in the lorestan province of iran, using the key informant method.

    Science.gov (United States)

    Razavi, Hessom; Kuper, Hannah; Rezvan, Farhad; Amelie, Khatere; Mahboobi-Pur, Hassan; Oladi, Mohammad Reza; Muhit, Mohammad; Hashemi, Hassan

    2010-03-01

    To estimate the prevalence and causes of severe visual impairment and blindness among children in Lorestan province of Iran, and to assess the feasibility of the Key Informant Method in this setting. Potential cases were identified using the Key Informant Method, in 3 counties of Lorestan province during June through August 2008, and referred for examination. Causes of severe visual impairment/blindness were determined and categorized using standard World Health Organization methods. Of 123 children referred for examination, 27 children were confirmed to have severe visual impairment/blindness or blindness. The median age was11 years (interquartile range 6-13), and 59% were girls. After adjusting for non-attenders, the estimated prevalence of severe visual impairment/blindness was 0.04% (0.03-0.05). The main site of abnormality was retina (44%), followed by disorders of the whole eye (33%). The majority of causes had a hereditary etiology (70%), which was associated with a family history of blindness (P = 0.002). Potentially avoidable causes of severe visual impairment/blindness were found in 14 children (52%). Almost all children with severe visual impairment/blindness had a history of parental consanguinity (93%). Our findings suggest a moderate prevalence of childhood blindness in the Lorestan province of Iran, a high proportion of which may be avoidable, given improved access to ophthalmic and genetic counselling services in rural areas. The Key Informant Method is feasible in Iran; future research is discussed.

  3. A survey of severe visual impairment and blindness in children attending thirteen schools for the blind in sri lanka.

    Science.gov (United States)

    Gao, Zoe; Muecke, James; Edussuriya, Kapila; Dayawansa, Ranasiri; Hammerton, Michael; Kong, Aimee; Sennanayake, Saman; Senaratne, Tissa; Marasinghe, Nirosha; Selva, Dinesh

    2011-02-01

    To identify the causes of blindness and severe visual impairment (BL/SVI) in children attending schools for the blind in Sri Lanka, and to provide optical devices and ophthalmic treatment where indicated. Two hundred and six children under 16 years from 13 schools for the blind in Sri Lanka were examined by a team of ophthalmologists and optometrists. Data were entered in the World Health Organization Prevention of Blindness Eye Examination Record for Childhood Blindness (WHO/PBL ERCB). Of the 206 children, 83.5% were blind (BL = Visual acuity [VA] schools for the blind in Sri Lanka had potentially avoidable causes of BL/SVI. Vision could also be improved in a third of children. The data support the need to develop specialized pediatric ophthalmic services, particularly in the face of advancing neonatal life support in Sri Lanka, and the need for increased provision of optical support.

  4. Long-lasting spatial learning and memory impairments caused by chronic cerebral hypoperfusion associate with a dynamic change of HCN1/HCN2 expression in hippocampal CA1 region.

    Science.gov (United States)

    Luo, Pan; Lu, Yun; Li, Changjun; Zhou, Mei; Chen, Cheng; Lu, Qing; Xu, Xulin; He, Zhi; Guo, Lianjun

    2015-09-01

    Chronic cerebral hypoperfusion (CCH) causes learning and memory impairments and increases the risk of Alzheimer disease (AD) and vascular dementia (VD) through several biologically plausible pathways, yet the mechanisms underlying the disease process remained unclear particularly in a temporal manner. We performed permanent bilateral occlusion of the common carotid arteries (two-vessel occlusion, 2VO) to induce CCH. To determine whether hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are altered at different stages of cognitive impairment caused by CCH, adult male SD rats were randomly distributed into sham-operated 4, 8 and 12weeks group, 2VO 4, 8 and 12weeks group. Learning and memory performance were evaluated with Morris water maze (MWM) and long-term potentiation (LTP) was used to address the underlying synaptic mechanisms. Expression of NeuN, HCN1 and HCN2 in hippocampal CA1, DG and CA3 areas was quantified by immunohistochemistry and western blotting. Our data showed that CCH induced a remarkable spatial learning and memory deficits in rats of 2VO 4, 8, and 12weeks group although neuronal loss only occurred after 4weeks of 2VO surgery in CA1. In addition, a significant reduction of HCN1 surface expression in CA1 was observed in the group that suffered 4weeks ischemia but neither 8 nor 12weeks. However, HCN2 surface expression in CA1 increased throughout the ischemia time-scales (4, 8 and 12w). Our findings indicate spatial learning and memory deficits in the CCH model are associated with disturbed HCN1 and HCN2 surface expression in hippocampal CA1. The altered patterns of both HCN1 and HCN2 surface expression may be implicated in the early stage (4w) of spatial learning and memory impairments; and the stable and long-lasting impairments of spatial learning and memory may partially attribute to the up-regulated HCN2 surface expression. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Early developmental bisphenol-A exposure sex-independently impairs spatial memory by remodeling hippocampal dendritic architecture and synaptic transmission in rats

    Science.gov (United States)

    Liu, Zhi-Hua; Ding, Jin-Jun; Yang, Qian-Qian; Song, Hua-Zeng; Chen, Xiang-Tao; Xu, Yi; Xiao, Gui-Ran; Wang, Hui-Li

    2016-08-01

    Bisphenol-A (BPA, 4, 4‧-isopropylidene-2-diphenol), a synthetic xenoestrogen that widely used in the production of polycarbonate plastics, has been reported to impair hippocampal development and function. Our previous study has shown that BPA exposure impairs Sprague-Dawley (SD) male hippocampal dendritic spine outgrowth. In this study, the sex-effect of chronic BPA exposure on spatial memory in SD male and female rats and the related synaptic mechanism were further investigated. We found that chronic BPA exposure impaired spatial memory in both SD male and female rats, suggesting a dysfunction of hippocampus without gender-specific effect. Further investigation indicated that BPA exposure causes significant impairment of dendrite and spine structure, manifested as decreased dendritic complexity, dendritic spine density and percentage of mushroom shaped spines in hippocampal CA1 and dentate gyrus (DG) neurons. Furthermore, a significant reduction in Arc expression was detected upon BPA exposure. Strikingly, BPA exposure significantly increased the mIPSC amplitude without altering the mEPSC amplitude or frequency, accompanied by increased GABAARβ2/3 on postsynaptic membrane in cultured CA1 neurons. In summary, our study indicated that Arc, together with the increased surface GABAARβ2/3, contributed to BPA induced spatial memory deficits, providing a novel molecular basis for BPA achieved brain impairment.

  6. [Perinatal outcome and cardiac dysfunction in preterm growth-restricted neonates in relation to placental impairment severity].

    Science.gov (United States)

    Candel Pau, Júlia; Castillo Salinas, Félix; Perapoch López, Josep; Carrascosa Lezcano, Antonio; Sánchez García, Olga; Llurba Olivé, Elisa

    2016-10-01

    Intrauterine growth restriction (IUGR) and prematurity have been associated with increased perinatal morbidity and mortality and also with cardiovascular foetal programming. However, there are few studies on the impact of placenta-related IUGR on perinatal outcomes and cardiovascular biomarkers in pre-term infants. To determine differences in neonatal morbidity, mortality and cord blood biomarkers of cardiovascular dysfunction between pre-term placenta-related IUGR and non-IUGR new-borns, and to analyse their relationship with the severity of IUGR according to foetal Doppler evaluation. Prospective cohort study: pre-term infants with placenta-related IUGR and matched pre-term infants without IUGR. A Doppler scan was performed, and placenta-IUGR was classified according to severity. Comparative analysis of perinatal outcomes, neonatal morbidity and mortality, and cord blood levels of biomarkers of cardiovascular dysfunction was performed. IUGR new-borns present lower weight, length, head circumference, and Apgar score at birth, as well as increased neonatal and cardiovascular dysfunction biomarker levels, compared with pre-term new-borns without IUGR. These differences increase with the severity of IUGR determined by prenatal umbilical artery Doppler scan. Placenta-related-IUGR pre-term infants, irrespective of gestational age, present increased neonatal morbidity and mortality that is significantly proportional to the severity of IUGR. Placental impairment and severity also determine levels of cardiovascular dysfunction biomarkers at birth. Copyright © 2015 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  7. [Reliability and validity of the Severe Impairment Battery, short form (SIB-s), in patients with dementia in Spain].

    Science.gov (United States)

    Cruz-Orduña, Isabel; Agüera-Ortiz, Luis F; Montorio-Cerrato, Ignacio; León-Salas, Beatriz; Valle de Juan, M Cristina; Martínez-Martín, Pablo

    2015-01-01

    People with progressive dementia evolve into a state where traditional neuropsychological tests are not effective. Severe Impairment Battery (SIB) and short form (SIB-s) were developed for evaluating the cognitive status in patients with severe dementia. To evaluate the psychometric attributes of the SIB-s in patients with severe dementia. 127 institutionalized patients (female: 86.6%; mean age: 82.6 ± 7.5 years-old) with dementia were assessed with the SIB-s, the Global Deterioration Scale (GDS), Mini-Mental State Examination (MMSE), Severe Mini-Mental State Examination (sMMSE), Barthel Index and FAST. SIB-s acceptability, reliability, validity and precision were analyzed. The mean total score for scale was 19.1 ± 15.34 (range: 0-48). Floor effect was 18.1%, only marginally higher than the desirable 15%. Factor analysis identified a single factor explaining 68% of the total variance of the scale. Cronbach's alpha coefficient was 0.96 and the item-total corrected correlation ranged from 0.27 to 0.83. The item homogeneity value was 0.43. Test-retest and inter-rater reliability for the total score was satisfactory (ICC: 0.96 and 0.95, respectively). The SIB-s showed moderate correlation with functional dependency scales (Barthel Index: 0.48, FAST: -0.74). Standard error of measurement was 3.07 for the total score. The SIB-s is a reliable and valid instrument for evaluating patients with severe dementia in the Spanish population of relatively brief instruments.

  8. Mitochondrial Impairment in Cerebrovascular Endothelial Cells is Involved in the Correlation between Body Temperature and Stroke Severity

    Science.gov (United States)

    Hu, Heng; Doll, Danielle N.; Sun, Jiahong; Lewis, Sara E.; Wimsatt, Jeffrey H.; Kessler, Matthew J.; Simpkins, James W.; Ren, Xuefang

    2016-01-01

    Stroke is the second leading cause of death worldwide. The prognostic influence of body temperature on acute stroke in patients has been recently reported; however, hypothermia has confounded experimental results in animal stroke models. This work aimed to investigate how body temperature could prognose stroke severity as well as reveal a possible mitochondrial mechanism in the association of body temperature and stroke severity. Lipopolysaccharide (LPS) compromises mitochondrial oxidative phosphorylation in cerebrovascular endothelial cells (CVECs) and worsens murine experimental stroke. In this study, we report that LPS (0.1 mg/kg) exacerbates stroke infarction and neurological deficits, in the mean time LPS causes temporary hypothermia in the hyperacute stage during 6 hours post-stroke. Lower body temperature is associated with worse infarction and higher neurological deficit score in the LPS-stroke study. However, warming of the LPS-stroke mice compromises animal survival. Furthermore, a high dose of LPS (2 mg/kg) worsens neurological deficits, but causes persistent severe hypothermia that conceals the LPS exacerbation of stroke infarction. Mitochondrial respiratory chain complex I inhibitor, rotenone, replicates the data profile of the LPS-stroke study. Moreover, we have confirmed that rotenone compromises mitochondrial oxidative phosphorylation in CVECs. Lastly, the pooled data analyses of a large sample size (n=353) demonstrate that stroke mice have lower body temperature compared to sham mice within 6 hours post-surgery; the body temperature is significantly correlated with stroke outcomes; linear regression shows that lower body temperature is significantly associated with higher neurological scores and larger infarct volume. We conclude that post-stroke body temperature predicts stroke severity and mitochondrial impairment in CVECs plays a pivotal role in this hypothermic response. These novel findings suggest that body temperature is prognostic for

  9. Spatial patterns of progressive brain volume loss after moderate-severe traumatic brain injury.

    Science.gov (United States)

    Cole, James H; Jolly, Amy; de Simoni, Sara; Bourke, Niall; Patel, Maneesh C; Scott, Gregory; Sharp, David J

    2018-01-04

    Traumatic brain injury leads to significant loss of brain volume, which continues into the chronic stage. This can be sensitively measured using volumetric analysis of MRI. Here we: (i) investigated longitudinal patterns of brain atrophy; (ii) tested whether atrophy is greatest in sulcal cortical regions; and (iii) showed how atrophy could be used to power intervention trials aimed at slowing neurodegeneration. In 61 patients with moderate-severe traumatic brain injury (mean age = 41.55 years ± 12.77) and 32 healthy controls (mean age = 34.22 years ± 10.29), cross-sectional and longitudinal (1-year follow-up) brain structure was assessed using voxel-based morphometry on T1-weighted scans. Longitudinal brain volume changes were characterized using a novel neuroimaging analysis pipeline that generates a Jacobian determinant metric, reflecting spatial warping between baseline and follow-up scans. Jacobian determinant values were summarized regionally and compared with clinical and neuropsychological measures. Patients with traumatic brain injury showed lower grey and white matter volume in multiple brain regions compared to controls at baseline. Atrophy over 1 year was pronounced following traumatic brain injury. Patients with traumatic brain injury lost a mean (± standard deviation) of 1.55% ± 2.19 of grey matter volume per year, 1.49% ± 2.20 of white matter volume or 1.51% ± 1.60 of whole brain volume. Healthy controls lost 0.55% ± 1.13 of grey matter volume and gained 0.26% ± 1.11 of white matter volume; equating to a 0.22% ± 0.83 reduction in whole brain volume. Atrophy was greatest in white matter, where the majority (84%) of regions were affected. This effect was independent of and substantially greater than that of ageing. Increased atrophy was also seen in cortical sulci compared to gyri. There was no relationship between atrophy and time since injury or age at baseline. Atrophy rates were related to memory performance at the end of the follow

  10. Vestibular Loss in Older Adults Is Associated with Impaired Spatial Navigation: Data from the Triangle Completion Task

    Directory of Open Access Journals (Sweden)

    Yanjun Xie

    2017-04-01

    Full Text Available BackgroundVestibular inputs have been shown to play a critical role in spatial navigation. In this study, we sought to evaluate whether vestibular loss due to aging contributes to impaired spatial navigation as measured by the triangle completion task (TCT.Materials and methodsWe recruited three types of participants: young controls <55 years of age, older controls ≥55 years of age, and older patients from a Neurotology Clinic with evidence of vestibular physiologic impairment but who did not have any known vestibular disorder. We performed the cervical vestibular-evoked myogenic potential to evaluate saccular function and video head impulse testing to quantify horizontal semicircular canal vestibulo-ocular reflex gain. To assess spatial navigation ability, we administered the TCT, in which participants were conveyed along two segments of a pre-drawn triangular path and instructed to complete the final segment independently. We measured the angle (degrees and distance (centimeters of deviation from the correct trajectory. We evaluated the influence of vestibular inputs on TCT performance.ResultsForty-eight adults participated in the study (mean age: 62.0 years; 52.1% females, including 9 young controls, 15 older controls, and 24 clinic patients. Clinic patients had the greatest distance of deviation (67.7 cm, followed by older controls (45.4 cm, then young controls (27.8 cm; p < 0.01. Similarly, clinic patients had greater rotational angles (22.1° compared to older (13.3° and younger controls (12.4°; p < 0.01. Following multivariate linear regression adjusting for demographic variables, loss of otolith function was associated with an 18.2 cm increase in distance of deviation (95% CI: 15.2–47.4 and a 9.2° increase in rotational angle (95% CI: 3.0–15.5. Abnormal semicircular canal function was associated with a 26.0 cm increase in distance of deviation (95% CI: 0.2–51.8 and a 10.8° increase in rotational angle

  11. Loss of EphA4 impairs short-term spatial recognition memory performance and locomotor habituation.

    Science.gov (United States)

    Willi, R; Winter, C; Wieske, F; Kempf, A; Yee, B K; Schwab, M E; Singer, P

    2012-11-01

    EphA4 receptor (EphA4) tyrosine kinase is an important regulator of central nervous system development and synaptic plasticity in the mature brain, but its relevance to the control of normal behavior remains largely unexplored. This study is the first attempt to obtain a behavioral profile of constitutive homozygous and heterozygous EphA4 knockout mice. A deficit in locomotor habituation in the open field, impairment in spatial recognition in the Y-maze and reduced probability of spatial spontaneous alternation in the T-maze were identified in homozygous EphA4(-/-) mice, while heterozygo us EphA4(+/-) mice appeared normal on these tests in comparison with wild-type (WT) controls. The multiple phenotypes observed in EphA4(-/-) mice might stem from an underlying deficit in habituation learning, reflecting an elementary form of nonassociative learning that is in contrast to Pavlovian associative learning, which appeared unaffected by EphA4 disruption. A deficit in motor coordination on the accelerating rotarod was also demonstrated only in EphA4(-/-) mice--a finding in keeping with the presence of abnormal gait in EphA4(-/-) mice--although they were able to improve performance over training. There was no evidence for substantial changes in major neurochemical markers in various brain regions rich in EphA4 as shown by post-mortem analysis. This excludes the possibility of major neurochemical compensation in the brain of EphA4(-/-) mice. In summary, we have demonstrated for the first time the behavioral significance of EphA4 disruption, supporting further investigation of EphA4 as a possible target for behavioral interventions where habituation deficits are prominent. © 2012 The Authors. Genes, Brain and Behavior © 2012 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.

  12. Exogenous hydrogen sulfide eliminates spatial memory retrieval impairment and hippocampal CA1 LTD enhancement caused by acute stress via promoting glutamate uptake.

    Science.gov (United States)

    He, Jin; Guo, Ruixian; Qiu, Pengxin; Su, Xingwen; Yan, Guangmei; Feng, Jianqiang

    2017-05-14

    Acute stress impairs the hippocampus-dependent spatial memory retrieval, and its synaptic mechanisms are associated with hippocampal CA1 long-term depression (LTD) enhancement in the adult rats. Endogenous hydrogen sulfide (H 2 S) is recognized as a novel gasotransmitter and has the neural protective roles. However, very little attention has been paid to understanding the effects of H 2 S on spatial memory retrieval impairment. We observed the protective effects of NaHS (a donor of H 2 S) against spatial memory retrieval impairment caused by acute stress and its synaptic mechanisms. Our results showed that NaHS abolished spatial memory retrieval impairment and hippocampal CA1 LTD enhancement caused by acute stress, but not by glutamate transporter inhibitor l-trans-pyrrolidine-2,4-dicarboxylic (tPDC), indicating that the activation of glutamate transporters is necessary for exogenous H 2 S to exert its roles. Moreover, NaHS restored the decreased glutamate uptake in the hippocampal CA1 synaptosomal fraction caused by acute stress. Dithiothreitol (DTT, a disulfide reducing agent) abolished a decrease in the glutamate uptake caused by acute stress, and NaHS eradicated the decreased glutamate uptake caused by 5,5'-dithio-bis(2-nitrobenzoic)acid (DTNB, a thiol oxidizing agent), collectively, revealing that exogenous H 2 S increases glutamate uptake by reducing disulfide bonds of the glutamate transporters. Additionally, NaHS inhibited the increased expression level of phosphorylated c-Jun-N-terminal kinase (JNK) in the hippocampal CA1 region caused by acute stress. The JNK inhibitor SP600125 eliminated spatial memory retrieval impairment, hippocampal CA1 LTD enhancement and the decreased glutamate uptake caused by acute stress, indicating that exogenous H 2 S exerts these roles by inhibiting the activation of JNK signaling pathway. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  13. Loss of the inducible Hsp70 delays the inflammatory response to skeletal muscle injury and severely impairs muscle regeneration.

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    Sarah M Senf

    Full Text Available Skeletal muscle regeneration following injury is a highly coordinated process that involves transient muscle inflammation, removal of necrotic cellular debris and subsequent replacement of damaged myofibers through secondary myogenesis. However, the molecular mechanisms which coordinate these events are only beginning to be defined. In the current study we demonstrate that Heat shock protein 70 (Hsp70 is increased following muscle injury, and is necessary for the normal sequence of events following severe injury induced by cardiotoxin, and physiological injury induced by modified muscle use. Indeed, Hsp70 ablated mice showed a significantly delayed inflammatory response to muscle injury induced by cardiotoxin, with nearly undetected levels of both neutrophil and macrophage markers 24 hours post-injury. At later time points, Hsp70 ablated mice showed sustained muscle inflammation and necrosis, calcium deposition and impaired fiber regeneration that persisted several weeks post-injury. Through rescue experiments reintroducing Hsp70 intracellular expression plasmids into muscles of Hsp70 ablated mice either prior to injury or post-injury, we confirm that Hsp70 optimally promotes muscle regeneration when expressed during both the inflammatory phase that predominates in the first four days following severe injury and the regenerative phase that predominates thereafter. Additional rescue experiments reintroducing Hsp70 protein into the extracellular microenvironment of injured muscles at the onset of injury provides further evidence that Hsp70 released from damaged muscle may drive the early inflammatory response to injury. Importantly, following induction of physiological injury through muscle reloading following a period of muscle disuse, reduced inflammation in 3-day reloaded muscles of Hsp70 ablated mice was associated with preservation of myofibers, and increased muscle force production at later time points compared to WT. Collectively our

  14. A Simple Method for Estimating the Economic Cost of Productivity Loss Due to Blindness and Moderate to Severe Visual Impairment.

    Science.gov (United States)

    Eckert, Kristen A; Carter, Marissa J; Lansingh, Van C; Wilson, David A; Furtado, João M; Frick, Kevin D; Resnikoff, Serge

    2015-01-01

    To estimate the annual loss of productivity from blindness and moderate to severe visual impairment (MSVI) using simple models (analogous to how a rapid assessment model relates to a comprehensive model) based on minimum wage (MW) and gross national income (GNI) per capita (US$, 2011). Cost of blindness (COB) was calculated for the age group ≥50 years in nine sample countries by assuming the loss of current MW and loss of GNI per capita. It was assumed that all individuals work until 65 years old and that half of visual impairment prevalent in the ≥50 years age group is prevalent in the 50-64 years age group. For cost of MSVI (COMSVI), individual wage and GNI loss of 30% was assumed. Results were compared with the values of the uncorrected refractive error (URE) model of productivity loss. COB (MW method) ranged from $0.1 billion in Honduras to $2.5 billion in the United States, and COMSVI ranged from $0.1 billion in Honduras to $5.3 billion in the US. COB (GNI method) ranged from $0.1 million in Honduras to $7.8 billion in the US, and COMSVI ranged from $0.1 billion in Honduras to $16.5 billion in the US. Most GNI method values were near equivalent to those of the URE model. Although most people with blindness and MSVI live in developing countries, the highest productivity losses are in high income countries. The global economy could improve if eye care were made more accessible and more affordable to all.

  15. [Prevalence of blindness and moderate and severe visual impairment among adults aged 50 years or above in Yangxi County of Guangdong Province: the China Nine-Province Survey].

    Science.gov (United States)

    Ge, Jian; He, Mingguang; Zhao, Jialiang; Fang, Min; Ellwein, Leon B; He, Ning; Yang, Mei; Wang, Yu; Gao, Xuecheng

    2014-03-01

    To investigate the prevalence of blindness and moderate and severe visual impairment among adults aged 50 years or above in Yangxi County of Guangdong Province, China. It was a population-based cross-section study.Geographically defined cluster sampling was used in randomly selecting 5 531 individuals aged 50 years or above in Yangxi County from September 2006 to January 2007. The survey was preceded by a pilot study where operational methods were refined and quality assurance evaluation was carried out. All participants were enumerated using village registers followed by door-to-door visits.Eligible individuals were invited to receive visual acuity measurement and eye examination.Statistical analyses were performed using Stata/SE Statistical Software, release 9.0. Chi-square test was used to investigate the association of age, gender and education with presenting and best corrected visual acuity. Five thousands five hundreds and thirty-one individuals were enumerated and 4 589 persons were examined, the response rate was 82.97%. Based on the criteria of World Health Organization visual impairment classification in 1973, the prevalence of blindness and moderate and severe visual impairment defined as best corrected visual acuity was 2.38% (109/4 589) and 9.44% (433/4 589) respectively. The prevalence of blindness and moderate and severe visual impairment defined as presenting visual acuity was 2.68% (123/4 589) and 18.15% (833/4 589) respectively. The prevalence of blindness and moderate and severe visual impairment was higher in aged (trend χ(2) = 1 239.34, P blindness and visual impairment. The prevalence of blindness and moderate and severe visual impairment is higher among older adults aged 50 years or above in Yangxi County. Cataract remains as the first leading cause of blindness and visual impairment.

  16. Spatial clustering by disease severity among reported Rocky Mountain spotted fever cases in the United States, 2001-2005.

    Science.gov (United States)

    Adjemian, Jennifer Zipser; Krebs, John; Mandel, Eric; McQuiston, Jennifer

    2009-01-01

    Rocky Mountain spotted fever (RMSF) occurs throughout much of the United States, ranging in clinical severity from moderate to fatal infection. Yet, little is known about possible differences among severity levels across geographic locations. To identify significant spatial clusters of severe and non-severe disease, RMSF cases reported to Centers for Disease Control and Prevention (CDC) were geocoded by county and classified by severity level. The statistical software program SaTScan was used to detect significant spatial clusters. Of 4,533 RMSF cases reported, 1,089 hospitalizations (168 with complications) and 23 deaths occurred. Significant clusters of 6 deaths (P = 0.05, RR = 11.4) and 19 hospitalizations with complications (P = 0.02, RR = 3.45) were detected in southwestern Tennessee. Two geographic areas were identified in north-central North Carolina with unusually low rates of severity (P = 0.001, RR = 0.62 and P = 0.001, RR = 0.45, respectively). Of all hospitalizations, 20% were clustered in central Oklahoma (P = 0.02, RR = 1.43). Significant geographic differences in severity were observed, suggesting that biologic and/or anthropogenic factors may be impacting RMSF epidemiology in the United States.

  17. Nano-CuO impairs spatial cognition associated with inhibiting hippocampal long-term potentiation via affecting glutamatergic neurotransmission in rats.

    Science.gov (United States)

    Li, Xiaoliang; Sun, Wei; An, Lei

    2018-06-01

    Manufactured metal nanoparticles and their applications are continuously expanding because of their unique characteristics while their increasing use may predispose to potential health problems. Several studies have reported the adverse effects of copper oxide nanoparticles (nano-CuO) relative to ecotoxicity and cell toxicity, whereas little is known about the neurotoxicity of nano-CuO. The present study aimed to examine its effects on spatial cognition, hippocampal function, and the possible mechanisms. Male Wistar rats were used to establish an animal model, and nano-CuO was administered at a dose of 0.5 mg/kg/day for 2 weeks. The Morris water maze (MWM) test was employed to evaluate learning and memory. The long-term potentiation (LTP) from Schaffer collaterals to the hippocampal CA1 region, and the effects of nano-CuO on synases were recorded in the hippocampal CA1 neurons of rats. MWM test showed that learning and memory abilities were impaired significantly by nano-CuO ( p nano-CuO-treated groups compared with the control group ( p nano-CuO markedly depressed the frequencies of both spontaneous excitatory postsynaptic currents (sEPSCs) and miniature EPSCs (mEPSCs), indicating an effect of nano-CuO on inhibiting the release frequency of glutamate presynapticly ( p nano-CuO-treated animals, which suggested that the effect of nano-CuO modulates postsynaptic receptor kinetics ( p nano-CuO impaired glutamate transmission presynapticly and postsynapticly, which may contribute importantly to diminished LTP and other induced cognitive deficits.

  18. Adult-onset hyperthyroidism impairs spatial learning: possible involvement of mitogen-activated protein kinase signaling pathways.

    Science.gov (United States)

    Bitiktaş, Soner; Kandemir, Başak; Tan, Burak; Kavraal, Şehrazat; Liman, Narin; Dursun, Nurcan; Dönmez-Altuntaş, Hamiyet; Aksan-Kurnaz, Işil; Suer, Cem

    2016-08-03

    Given evidence that mitogen-activated protein kinase (MAPK) activation is part of the nongenomic actions of thyroid hormones, we investigated the possible consequences of hyperthyroidism for the cognitive functioning of adult rats. Young adult rats were treated with L-thyroxine or saline. Twenty rats in each group were exposed to Morris water maze testing, measuring their performance in a hidden-platform spatial task. In a separate set of rats not exposed to Morris water maze testing (untrained rats), the expression and phosphorylated levels of p38-MAPK and of its two downstream effectors, Elk-1 and cAMP response element-binding protein, were evaluated using quantitative reverse transcriptase-PCR and western blotting. Rats with hyperthyroidism showed delayed acquisition of learning compared with their wild-type counterparts, as shown by increased escape latencies and distance moved on the last two trials of daily training in the water maze. The hyperthyroid rats, however, showed no difference during probe trials. Western blot analyses of the hippocampus showed that hyperthyroidism increased phosphorylated p38-MAPK levels in untrained rats. Although our study is correlative in nature and does not exclude the contribution of other molecular targets, our findings suggest that the observed impairments in acquisition during actual learning in rats with hyperthyroidism may result from the increased phosphorylation of p38-MAPK.

  19. Synaptic plasticity and spatial working memory are impaired in the CD mouse model of Williams-Beuren syndrome.

    Science.gov (United States)

    Borralleras, Cristina; Mato, Susana; Amédée, Thierry; Matute, Carlos; Mulle, Christophe; Pérez-Jurado, Luis A; Campuzano, Victoria

    2016-08-02

    Mice heterozygous for a complete deletion (CD) equivalent to the most common deletion found in individuals with Williams-Beuren syndrome (WBS) recapitulate relevant features of the neurocognitive phenotype, such as hypersociability, along with some neuroanatomical alterations in specific brain areas. However, the pathophysiological mechanisms underlying these phenotypes still remain largely unknown. We have studied the synaptic function and cognition in CD mice using hippocampal slices and a behavioral test sensitive to hippocampal function. We have found that long-term potentiation (LTP) elicited by theta burst stimulation (TBS) was significantly impaired in hippocampal field CA1 of CD animals. This deficit might be associated with the observed alterations in spatial working memory. However, we did not detect changes in presynaptic function, LTP induction mechanisms or AMPA and NMDA receptor function. Reduced levels of Brain-derived neurotrophic factor (BDNF) were present in the CA1-CA3 hippocampal region of CD mice, which could account for LTP deficits in these mice. Taken together, these results suggest a defect of CA1 synapses in CD mice to sustain synaptic strength after stimulation. These data represent the first description of synaptic functional deficits in CD mice and further highlights the utility of the CD model to study the mechanisms underlying the WBS neurocognitive profile.

  20. Association between mild cognitive impairment and trajectory-based spatial parameters during timed up and go test using a laser range sensor.

    Science.gov (United States)

    Nishiguchi, Shu; Yorozu, Ayanori; Adachi, Daiki; Takahashi, Masaki; Aoyama, Tomoki

    2017-08-08

    The Timed Up and Go (TUG) test may be a useful tool to detect not only mobility impairment but also possible cognitive impairment. In this cross-sectional study, we used the TUG test to investigate the associations between trajectory-based spatial parameters measured by laser range sensor (LRS) and cognitive impairment in community-dwelling older adults. The participants were 63 community-dwelling older adults (mean age, 73.0 ± 6.3 years). The trajectory-based spatial parameters during the TUG test were measured using an LRS. In each forward and backward phase, we calculated the minimum distance from the marker, the maximum distance from the x-axis (center line), the length of the trajectories, and the area of region surrounded by the trajectory of the center of gravity and the x-axis (center line). We measured mild cognitive impairment using the Mini-Mental State Examination score (26/27 was the cut-off score for defining mild cognitive impairment). Compared with participants with normal cognitive function, those with mild cognitive impairment exhibited the following trajectory-based spatial parameters: short minimum distance from the marker (p = 0.044), narrow area of center of gravity in the forward phase (p = 0.012), and a large forward/whole phase ratio of the area of the center of gravity (p = 0.026) during the TUG test. In multivariate logistic regression analyses, a short minimum distance from the marker (odds ratio [OR]: 0.82, 95% confidence interval [CI]: 0.69-0.98), narrow area of the center of gravity in the forward phase (OR: 0.01, 95% CI: 0.00-0.36), and large forward/whole phase ratio of the area of the center of gravity (OR: 0.94, 95% CI: 0.88-0.99) were independently associated with mild cognitive impairment. In conclusion, our results indicate that some of the trajectory-based spatial parameters measured by LRS during the TUG test were independently associated with cognitive impairment in older adults. In particular, older adults with

  1. Trim9 Deletion Alters the Morphogenesis of Developing and Adult-Born Hippocampal Neurons and Impairs Spatial Learning and Memory.

    Science.gov (United States)

    Winkle, Cortney C; Olsen, Reid H J; Kim, Hyojin; Moy, Sheryl S; Song, Juan; Gupton, Stephanie L

    2016-05-04

    During hippocampal development, newly born neurons migrate to appropriate destinations, extend axons, and ramify dendritic arbors to establish functional circuitry. These developmental stages are recapitulated in the dentate gyrus of the adult hippocampus, where neurons are continuously generated and subsequently incorporate into existing, local circuitry. Here we demonstrate that the E3 ubiquitin ligase TRIM9 regulates these developmental stages in embryonic and adult-born mouse hippocampal neurons in vitro and in vivo Embryonic hippocampal and adult-born dentate granule neurons lacking Trim9 exhibit several morphological defects, including excessive dendritic arborization. Although gross anatomy of the hippocampus was not detectably altered by Trim9 deletion, a significant number of Trim9(-/-) adult-born dentate neurons localized inappropriately. These morphological and localization defects of hippocampal neurons in Trim9(-/-) mice were associated with extreme deficits in spatial learning and memory, suggesting that TRIM9-directed neuronal morphogenesis may be involved in hippocampal-dependent behaviors. Appropriate generation and incorporation of adult-born neurons in the dentate gyrus are critical for spatial learning and memory and other hippocampal functions. Here we identify the brain-enriched E3 ubiquitin ligase TRIM9 as a novel regulator of embryonic and adult hippocampal neuron shape acquisition and hippocampal-dependent behaviors. Genetic deletion of Trim9 elevated dendritic arborization of hippocampal neurons in vitro and in vivo Adult-born dentate granule cells lacking Trim9 similarly exhibited excessive dendritic arborization and mislocalization of cell bodies in vivo These cellular defects were associated with severe deficits in spatial learning and memory. Copyright © 2016 the authors 0270-6474/16/364940-19$15.00/0.

  2. [Prevalence of blindness and moderate and severe visual impairment among adults aged 50 years or above in Shuangcheng City of Heilongjiang Province: the China Nine-Province Survey].

    Science.gov (United States)

    Zhang, Liqiong; Cui, Hao; Zhao, Jialiang; Ellwein, Leon B; Li, Zhijian; Li, Mingsheng; Yu, Nannan; Wang, Yu; Gao, Xuecheng

    2014-03-01

    To investigate the prevalence of blindness and moderate and severe visual impairment among adults aged 50 years or above in Shuangcheng City of Heilongjiang Province, China. It was a population-based cross-section study. Geographically defined cluster sampling was used in randomly selecting 5 841 individuals aged 50 years or above in 28 basic sample units in Shuangcheng City from September to December 2006. The survey was preceded by a pilot study where operational methods were refined and quality assurance evaluation was carried out. All participants were enumerated through village registers followed door-to-door visits.Eligible individuals were invited to receive visual acuity measurement and eye examination. Statistical analyses were performed using Stata/SE Statistical Software, release 9.0. Chi-square test was used to investigate the association of age, gender and education with presenting and best corrected visual acuity. Five thousands four hundreds and eighty-one individuals were enumerated and 5 047 persons were examined, the response rate was 92.08%. Based on the criteria of World Health Organization visual impairment classification in 1973, the prevalence of blindness and moderate and severe visual impairment defined as best corrected visual acuity was 1.72% (87/5 047) and 4.69% (237/5 047) respectively. The prevalence of blindness and moderate and severe visual impairment defined as presenting visual acuity was 1.90% (96/5 047) and 7.23% (365/5 047) respectively. The prevalence of blindness and moderate and severe visual impairment was higher in aged (trend χ(2)=674.44, P blindness and visual impairment. The percentage of the retinal diseases, including age-related macular degeneration, high myopic retinopathy and diabetic retinopathy was 11.31% among the eyes with blindness and moderate and severe visual impairment. Un-corrected refractive error(13.38%) also was the main cause of visual impairment. The prevalence of blindness and moderate and severe

  3. Causes of severe visual impairment and blindness in children in schools for the blind in eastern Africa: changes in the last 14 years.

    Science.gov (United States)

    Njuguna, Margaret; Msukwa, Gerald; Shilio, Bernadeth; Tumwesigye, Cillasy; Courtright, Paul; Lewallen, Susan

    2009-01-01

    To determine the causes of severe visual impairment and blindness in children attending schools for the blind in Kenya, Malawi, Uganda, and Tanzania and to compare the findings with those of a 1994 study. Children attending schools for the blind or annexes in 4 eastern African countries were examined. The major anatomical site of and underlying etiology of severe visual impairment and blindness was recorded using the standardized World Health Organization (WHO) reporting form. A total of 1062 children aged below 16 years were examined of whom 701 (65.2%) had severe visual impairment or blindness. The major anatomical sites of visual loss overall (% and 95% CI) were cornea scar/phthisis bulbi (19%,16.1-21.9), whole globe lesions (15.7%,13.0-18.4), retina (15.4 %, 12.7-18.1), lens related disorders (13.1%, 10.7-15.5), and optic nerve disorders (12.3%, 9.9-14.7). Corneal scar/phthisis was not distributed equally among the countries and was highest in Malawi, similar to findings in 1995. The major etiology of visual loss was childhood factors (29.9%) and an estimated 40% of severe visual impairment and blindness was due to potentially avoidable causes. The major causes of severe visual impairment and blindness overall have not changed appreciably since 1995. There are important differences among countries, however, and using overall estimates for planning may be misleading.

  4. Psychometrics of the Overall Anxiety Severity and Impairment Scale (OASIS) in a sample of women with and without trauma histories.

    Science.gov (United States)

    Norman, Sonya B; Allard, Carolyn B; Trim, Ryan S; Thorp, Steven R; Behrooznia, Michelle; Masino, Tonya T; Stein, Murray B

    2013-04-01

    Many women have unidentified anxiety or trauma histories that can impact their health and medical treatment-seeking behavior. This study examined the sensitivity, specificity, efficiency, and sensitivity to change of the Overall Anxiety Severity and Impairment Scale (OASIS) for identifying an anxiety disorder in a female sample with and without trauma history related to intimate partner violence (IPV). Forty-three women with full or partial PTSD from IPV and 41 women without PTSD completed the OASIS. All participants with trauma history completed the Clinician Administered PTSD Scale. This report is a secondary analysis of a study on the neurobiology of psychological trauma in survivors of IPV recruited from the community. A cut-score of 5 best discriminated those with PTSD from those without, successfully classifying 91% of the sample with 93% sensitivity and 90% specificity. The measure showed strong sensitivity to change in a subsample of 20 participants who completed PTSD treatment and strong convergent and divergent validity in the full sample. This study suggests that the OASIS can identify the presence of an anxiety disorder among a female sample of IPV survivors when PTSD is present.

  5. Cognitive Impairment after Severe Traumatic Brain Injury, Clinical Course and Impact on Outcome: A Swedish-Icelandic Study

    Science.gov (United States)

    Stenberg, Maud; Godbolt, Alison K.; Nygren De Boussard, Catharina; Levi, Richard; Stålnacke, Britt-Marie

    2015-01-01

    Objective. To assess the clinical course of cognitive and emotional impairments in patients with severe TBI (sTBI) from 3 weeks to 1 year after trauma and to study associations with outcomes at 1 year. Methods. Prospective, multicenter, observational study of sTBI in Sweden and Iceland. Patients aged 18–65 years with acute Glasgow Coma Scale 3–8 were assessed with the Barrow Neurological Institute Screen for Higher Cerebral Functions (BNIS) and the Hospital Anxiety and Depression Scale (HADS). Outcome measures were Glasgow Outcome Scale Extended (GOSE) and Rancho Los Amigos Cognitive Scale-Revised (RLAS-R). Results. Cognition was assessed with the BNIS assessed for 42 patients out of 100 at 3 weeks, 75 patients at 3 months, and 78 patients at 1 year. Cognition improved over time, especially from 3 weeks to 3 months. The BNIS subscales “orientation” and “visuospatial and visual problem solving” were associated with the GOSE and RLAS-R at 1 year. Conclusion. Cognition seemed to improve over time after sTBI and appeared to be rather stable from 3 months to 1 year. Since cognitive function was associated with outcomes, these results indicate that early screening of cognitive function could be of importance for rehabilitation planning in a clinical setting. PMID:26783381

  6. Cognitive Impairment after Severe Traumatic Brain Injury, Clinical Course and Impact on Outcome: A Swedish-Icelandic Study

    Directory of Open Access Journals (Sweden)

    Maud Stenberg

    2015-01-01

    Full Text Available Objective. To assess the clinical course of cognitive and emotional impairments in patients with severe TBI (sTBI from 3 weeks to 1 year after trauma and to study associations with outcomes at 1 year. Methods. Prospective, multicenter, observational study of sTBI in Sweden and Iceland. Patients aged 18–65 years with acute Glasgow Coma Scale 3–8 were assessed with the Barrow Neurological Institute Screen for Higher Cerebral Functions (BNIS and the Hospital Anxiety and Depression Scale (HADS. Outcome measures were Glasgow Outcome Scale Extended (GOSE and Rancho Los Amigos Cognitive Scale-Revised (RLAS-R. Results. Cognition was assessed with the BNIS assessed for 42 patients out of 100 at 3 weeks, 75 patients at 3 months, and 78 patients at 1 year. Cognition improved over time, especially from 3 weeks to 3 months. The BNIS subscales “orientation” and “visuospatial and visual problem solving” were associated with the GOSE and RLAS-R at 1 year. Conclusion. Cognition seemed to improve over time after sTBI and appeared to be rather stable from 3 months to 1 year. Since cognitive function was associated with outcomes, these results indicate that early screening of cognitive function could be of importance for rehabilitation planning in a clinical setting.

  7. tDCS combined with optokinetic drift reduces egocentric neglect in severely impaired post-acute patients.

    Science.gov (United States)

    Turgut, Nergiz; Miranda, Marcela; Kastrup, Andreas; Eling, Paul; Hildebrandt, Helmut

    2018-06-01

    Visuospatial neglect is a disabling syndrome resulting in impaired activities of daily living and in longer durations of inpatient rehabilitation. Effective interventions to remediate neglect are still needed. The combination of tDCS and an optokinetic task might qualify as a treatment method. A total of 32 post-acute patients with left (n = 20) or right-sided neglect were allotted to an intervention or a control group (both groups n = 16). The intervention group received eight sessions of 1.5-2.0 mA parietal transcranial direct current stimulation (tDCS) during the performance of an optokinetic task distributed over two weeks. Additionally they received standard therapy for five hours per day. The control group received only the standard therapy. Patients were examined twice before (with 3-4 days between examinations) and twice after treatment (5-6 days between examinations). Compared to the control group and controlling for spontaneous remission, the intervention group improved on spontaneous body orientation and the Clock Drawing Test. Intragroup comparisons showed broad improvements on egocentric but not on allocentric symptoms only for the intervention group. A short additional application of tDCS during an optokinetic task led to improvements of severe neglect compared to a standard neurological early rehabilitation treatment. Improvements seem to concern primarily egocentric rather than allocentric neglect.

  8. Salience Network and Depressive Severities in Parkinson’s Disease with Mild Cognitive Impairment: A Structural Covariance Network Analysis

    Directory of Open Access Journals (Sweden)

    Ya-Ting Chang

    2018-01-01

    Full Text Available Purpose: In Parkinson’s disease with mild cognitive impairment (PD-MCI, we investigated the clinical significance of salience network (SN in depression and cognitive performance.Methods: Seventy seven PD-MCI patients that fulfilled multi-domain and non-amnestic subtype were included. Gray matter structural covariance networks were constructed by 3D T1-magnetic resonance imaging and seed based analysis. The patients were divided into two groups by psychiatric interviews and screening of Geriatric Depression Scale (GDS: PD-MCI with depression (PD-MCI-D or without depression (PD-MCI-ND. The seed or peak cluster volume, or the significant differences in the regression slopes in each seed-peak cluster correlation, were used to evaluate the significance with the neurobehavioral scores.Results: This study is the first to demonstrate that the PD-MCI-ND group presented a larger number of voxels of structural covariance in SN than the PD-MCI-D group. The right fronto-insular seed volumes and the peak cluster of left lingual gyrus showed significant inverse correlation with the Geriatric Depression Scale (GDS; r = -0.231, P = 0.046.Conclusions: This study is the first to validate the clinical significance of the SN in PD-MCI-D. The right insular seed value and the SN correlated with the severity of depression in PD-MCI.

  9. Salience Network and Depressive Severities in Parkinson’s Disease with Mild Cognitive Impairment: A Structural Covariance Network Analysis

    Science.gov (United States)

    Chang, Ya-Ting; Lu, Cheng-Hsien; Wu, Ming-Kung; Hsu, Shih-Wei; Huang, Chi-Wei; Chang, Wen-Neng; Lien, Chia-Yi; Lee, Jun-Jun; Chang, Chiung-Chih

    2018-01-01

    Purpose: In Parkinson’s disease with mild cognitive impairment (PD-MCI), we investigated the clinical significance of salience network (SN) in depression and cognitive performance. Methods: Seventy seven PD-MCI patients that fulfilled multi-domain and non-amnestic subtype were included. Gray matter structural covariance networks were constructed by 3D T1-magnetic resonance imaging and seed based analysis. The patients were divided into two groups by psychiatric interviews and screening of Geriatric Depression Scale (GDS): PD-MCI with depression (PD-MCI-D) or without depression (PD-MCI-ND). The seed or peak cluster volume, or the significant differences in the regression slopes in each seed-peak cluster correlation, were used to evaluate the significance with the neurobehavioral scores. Results: This study is the first to demonstrate that the PD-MCI-ND group presented a larger number of voxels of structural covariance in SN than the PD-MCI-D group. The right fronto-insular seed volumes and the peak cluster of left lingual gyrus showed significant inverse correlation with the Geriatric Depression Scale (GDS; r = -0.231, P = 0.046). Conclusions: This study is the first to validate the clinical significance of the SN in PD-MCI-D. The right insular seed value and the SN correlated with the severity of depression in PD-MCI. PMID:29375361

  10. Salience Network and Depressive Severities in Parkinson's Disease with Mild Cognitive Impairment: A Structural Covariance Network Analysis.

    Science.gov (United States)

    Chang, Ya-Ting; Lu, Cheng-Hsien; Wu, Ming-Kung; Hsu, Shih-Wei; Huang, Chi-Wei; Chang, Wen-Neng; Lien, Chia-Yi; Lee, Jun-Jun; Chang, Chiung-Chih

    2017-01-01

    Purpose: In Parkinson's disease with mild cognitive impairment (PD-MCI), we investigated the clinical significance of salience network (SN) in depression and cognitive performance. Methods: Seventy seven PD-MCI patients that fulfilled multi-domain and non-amnestic subtype were included. Gray matter structural covariance networks were constructed by 3D T1-magnetic resonance imaging and seed based analysis. The patients were divided into two groups by psychiatric interviews and screening of Geriatric Depression Scale (GDS): PD-MCI with depression (PD-MCI-D) or without depression (PD-MCI-ND). The seed or peak cluster volume, or the significant differences in the regression slopes in each seed-peak cluster correlation, were used to evaluate the significance with the neurobehavioral scores. Results: This study is the first to demonstrate that the PD-MCI-ND group presented a larger number of voxels of structural covariance in SN than the PD-MCI-D group. The right fronto-insular seed volumes and the peak cluster of left lingual gyrus showed significant inverse correlation with the Geriatric Depression Scale (GDS; r = -0.231, P = 0.046). Conclusions: This study is the first to validate the clinical significance of the SN in PD-MCI-D. The right insular seed value and the SN correlated with the severity of depression in PD-MCI.

  11. Monitor, a Vibrotactile Aid for Environmental Perception: A Field Evaluation by Four People with Severe Hearing and Vision Impairment

    Directory of Open Access Journals (Sweden)

    Parivash Ranjbar

    2013-01-01

    Full Text Available Monitor is a portable vibrotactile aid to improve the ability of people with severe hearing impairment or deafblindness to detect, identify, and recognize the direction of sound-producing events. It transforms and adapts sounds to the frequency sensitivity range of the skin. The aid was evaluated in the field. Four females (44–54 years with Usher Syndrome I (three with tunnel vision and one with only light perception tested the aid at home and in traffic in three different field studies: without Monitor, with Monitor with an omnidirectional microphone, and with Monitor with a directional microphone. The tests were video-documented, and the two field studies with Monitor were initiated after five weeks of training. The detection scores with omnidirectional and directional microphones were 100% for three participants and above 57% for one, both in their home and traffic environments. In the home environment the identification scores with the omnidirectional microphone were 70%–97% and 58%–95% with the directional microphone. The corresponding values in traffic were 29%–100% and 65%–100%, respectively. Their direction perception was improved to some extent by both microphones. Monitor improved the ability of people with deafblindness to detect, identify, and recognize the direction of events producing sounds.

  12. Monitor, a vibrotactile aid for environmental perception: a field evaluation by four people with severe hearing and vision impairment.

    Science.gov (United States)

    Ranjbar, Parivash; Stenström, Ingeborg

    2013-01-01

    Monitor is a portable vibrotactile aid to improve the ability of people with severe hearing impairment or deafblindness to detect, identify, and recognize the direction of sound-producing events. It transforms and adapts sounds to the frequency sensitivity range of the skin. The aid was evaluated in the field. Four females (44-54 years) with Usher Syndrome I (three with tunnel vision and one with only light perception) tested the aid at home and in traffic in three different field studies: without Monitor, with Monitor with an omnidirectional microphone, and with Monitor with a directional microphone. The tests were video-documented, and the two field studies with Monitor were initiated after five weeks of training. The detection scores with omnidirectional and directional microphones were 100% for three participants and above 57% for one, both in their home and traffic environments. In the home environment the identification scores with the omnidirectional microphone were 70%-97% and 58%-95% with the directional microphone. The corresponding values in traffic were 29%-100% and 65%-100%, respectively. Their direction perception was improved to some extent by both microphones. Monitor improved the ability of people with deafblindness to detect, identify, and recognize the direction of events producing sounds.

  13. Severe Delayed Gastric Emptying Induces Non-acid Reflux up to Proximal Esophagus in Neurologically Impaired Patients.

    Science.gov (United States)

    Ishii, Shinji; Fukahori, Suguru; Asagiri, Kimio; Tanaka, Yoshiaki; Saikusa, Nobuyuki; Hashizume, Naoki; Yoshida, Motomu; Masui, Daisuke; Komatsuzaki, Naoko; Higashidate, Naruki; Sakamoto, Saki; Kurahachi, Tomohiro; Tsuruhisa, Shiori; Nakahara, Hirotomo; Yagi, Minoru

    2017-10-30

    The aim of this study is to investigate the degree of delayed gastric emptying (DGE) and evaluate how the severity of DGE affects gastroesophageal reflux disease (GERD) in neurologically impaired (NI) patients utilizing 24-hour multichannel intraluminal impedance pH measurements (pH/MII) and 13 C-acetate breath test ( 13 C-ABT) analyses. 13 C-ABT and pH/MII were conducted in 26 NI patients who were referred to our institution due to suspected GERD. At first, correlation analyses were performed to investigate the correlation between the 13 C-ABT parameters and the clinical or pH/MII parameters. Thereafter, all patients were divided into 2 groups (DGE and severe DGE [SDGE] group) according to each cut off half emptying time (t 1/2 , 90-170 minutes). Each pH/MII parameter was compared between the 2 groups in each set-up cutoff t 1/2 . The mean t 1/2 of all patients was 215.5 ± 237.2 minutes and the t 1/2 of 24 (92.3%) patients were > 100 minutes. Significant moderate positive correlations were observed between both t 1/2 and lag phase time and the non-acid reflux related parameters. Furthermore, the patients in the SDGE group demonstrated higher non-acid reflux related parameters than those of the DGE groups when the cutoff was t 1/2 ≥ 140 minutes. The present study demonstrated that GE with t 1/2 ≥ 140 minutes was related to an increase of non-acid exposure reaching up to the proximal esophagus in NI patients, and indicating that NI patients with SDGE might have a high risk of non-acid GERD.

  14. A prospective study of severe hypoglycemia and long-term spatial memory in children with type 1 diabetes.

    Science.gov (United States)

    Hershey, Tamara; Lillie, Rema; Sadler, Michelle; White, Neil H

    2004-06-01

    In a previous retrospective study, severe hypoglycemia (SH) was associated with decreased long-term spatial memory in children with type 1 diabetes mellitus (T1DM). In this study, we tested the hypothesis that prospectively ascertained SH would also be associated with decreased spatial long-term memory over time. Children with T1DM (n = 42) and sibling controls (n = 25) performed a spatial delayed response (SDR) task with short and long delays and other neuropsychological tests at baseline and after 15 months of monitoring. Extreme glycemic events and other medical complications were recorded prospectively during follow-up. Fourteen T1DM children experienced at least one episode of SH during the follow-up period (range = 1-5). After controlling for long-delay SDR performance at baseline, age, gender, and age of onset, the presence of SH during the prospective period was statistically associated with decreased long-delay SDR performance at follow-up (semipartial r = -0.38, p = 0.017). This relationship was not seen with short-delay SDR or with verbal or object memory, attention, or motor speed. These results, together with previously reported data, support the hypothesis that SH has specific, negative effects on spatial memory skills in T1DM children.

  15. Chronic prenatal ethanol exposure alters hippocampal GABA(A) receptors and impairs spatial learning in the guinea pig.

    Science.gov (United States)

    Iqbal, U; Dringenberg, H C; Brien, J F; Reynolds, J N

    2004-04-02

    Chronic prenatal ethanol exposure (CPEE) can injure the developing brain, and may lead to the fetal alcohol syndrome (FAS). Previous studies have demonstrated that CPEE upregulates gamma-aminobutyric acid type A (GABA(A)) receptor expression in the cerebral cortex, and decreases functional synaptic plasticity in the hippocampus, in the adult guinea pig. This study tested the hypothesis that CPEE increases GABA(A) receptor expression in the hippocampus of guinea pig offspring that exhibit cognitive deficits in a hippocampal-dependent spatial learning task. Timed, pregnant guinea pigs were treated with ethanol (4 g/kg maternal body weight per day), isocaloric-sucrose/pair-feeding, or water throughout gestation. GABA(A) receptor subunit protein expression in the hippocampus was measured at two development ages: near-term fetus and young adult. In young adult guinea pig offspring, CPEE increased spontaneous locomotor activity in the open-field and impaired task acquisition in the Morris water maze. CPEE did not change GABA(A) receptor subunit protein expression in the near-term fetal hippocampus, but increased expression of the beta2/3-subunit of the GABA(A) receptor in the hippocampus of young adult offspring. CPEE did not change either [(3)H]flunitrazepam binding or GABA potentiation of [(3)H]flunitrazepam binding, but decreased the efficacy of allopregnanolone potentiation of [(3)H]flunitrazepam binding, to hippocampal GABA(A) receptors in adult offspring. Correlational analysis revealed a relationship between increased spontaneous locomotor activity and growth restriction in the hippocampus induced by CPEE. Similarly, an inverse relationship was found between performance in the water maze and the efficacy of allopregnanolone potentiation of [(3)H]flunitrazepam binding in the hippocampus. These data suggest that alterations in hippocampal GABA(A) receptor expression and pharmacological properties contribute to hippocampal-related behavioral and cognitive deficits

  16. Pharmacokinetics and Pharmacodynamics of Luseogliflozin, a Selective SGLT2 Inhibitor, in Japanese Patients With Type 2 Diabetes With Mild to Severe Renal Impairment.

    Science.gov (United States)

    Samukawa, Yoshishige; Haneda, Masakazu; Seino, Yutaka; Sasaki, Takashi; Fukatsu, Atsushi; Kubo, Yusuke; Sato, Yuri; Sakai, Soichi

    2018-04-25

    This open-label, parallel-group, multicenter study aimed to assess the effects of renal impairment on the pharmacokinetics, pharmacodynamics, and safety of luseogliflozin. A single 5-mg dose of luseogliflozin was administered to Japanese patients with type 2 diabetes mellitus in the following groups: G1, normal renal function; G2, mild renal impairment; G3a, mild to moderate impairment; G3b, moderate to severe impairment; G4, severe impairment, based on estimated glomerular filtration rate (eGFR; ≥90, 60-89, 45-59, 30-44, 15-29 mL/min/1.73 m 2 , respectively). While luseogliflozin pharmacokinetics were similar for patients across all renal function groups, the increase in plasma concentration was slightly slower and maximum concentration was slightly reduced in the lower eGFR groups compared with the other groups. However, luseogliflozin pharmacodynamics were affected by the severity of renal impairment. Urinary glucose excretion (UGE) increased in all groups relative to baseline levels, but the degree of UGE increase was smaller in the lower eGFR groups. Moreover, plasma glucose AUC changes from baseline tended to be smaller in the lower eGFR groups. No clear trends were observed between eGFR and incidence, type, or severity of adverse events. Thus, luseogliflozin administration should be carefully considered, as patients with renal impairment may show an insufficient response to treatment. © 2018 The Authors. Clinical Pharmacology in Drug Development Published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.

  17. Spatial patterns of ponderosa pine regeneration in high-severity burn patches

    Science.gov (United States)

    Suzanne M. Owen; Carolyn H. Sieg; Andrew J. Sanchez. Meador; Peter Z. Fule; Jose M. Iniguez; L. Scott. Baggett; Paula J. Fornwalt; Michael A. Battaglia

    2017-01-01

    Contemporary wildfires in southwestern US ponderosa pine forests can leave uncharacteristically large patches of tree mortality, raising concerns about the lack of seed-producing trees, which can prevent or significantly delay ponderosa pine regeneration. We established 4-ha plots in high-severity burn patches in two Arizona wildfires, the 2000 Pumpkin and 2002 Rodeo-...

  18. Comparison of vildagliptin and sitagliptin in patients with type 2 diabetes and severe renal impairment: a randomised clinical trial.

    Science.gov (United States)

    Kothny, Wolfgang; Lukashevich, Valentina; Foley, James E; Rendell, Marc S; Schweizer, Anja

    2015-09-01

    There are limited data comparing dipeptidyl peptidase-4 (DPP-4) inhibitors directly. We compared the safety and efficacy of vildagliptin and sitagliptin in patients with type 2 diabetes and severe renal impairment (RI). This study was a parallel-arm, randomised, multicentre, double-blind, 24 week study conducted in 87 centres across Brazil and the USA. Patients with type 2 diabetes, either drug naive or treated with any glucose-lowering agents, who had inadequate glycaemic control (HbA1c 6.5-10.0% [48-86 mmol/mol]) and an estimated GFR vildagliptin 50 mg once daily or sitagliptin 25 mg once daily. These doses are recommended in this patient population and considered maximally effective. Participants, investigators and the sponsor were blinded to group assignment. Efficacy endpoints included change in HbA1c and fasting plasma glucose (FPG) at all visits and the primary safety endpoint was assessment of treatment-emergent adverse events. In total, 148 patients were randomised, 83 to vildagliptin and 65 to sitagliptin. All patients were analysed. After 24 weeks, the adjusted mean change in HbA1c was -0.54% (5.9 mmol/mol) from a baseline of 7.52% (59 mmol/mol) with vildagliptin and -0.56% (6.1 mmol/mol) from a baseline of 7.80% (62 mmol/mol) with sitagliptin (p = 0.874). FPG decreased by 0.47 ± 0.37 mmol/l with vildagliptin and increased by 0.16 ± 0.43 mmol/l with sitagliptin (p = 0.185). Both treatments were well tolerated with overall similar safety profiles. At their recommended doses for severe RI, vildagliptin (50 mg once daily) compared with sitagliptin (25 mg once daily) demonstrated similar efficacy and both drugs were well tolerated. This study provides further support for the use of DPP-4 inhibitors in patients with severe RI. ClinicalTrials.gov NCT00616811 (completed) This study was planned and conducted by Novartis.

  19. Rhynchophylline suppresses soluble Aβ1-42-induced impairment of spatial cognition function via inhibiting excessive activation of extrasynaptic NR2B-containing NMDA receptors.

    Science.gov (United States)

    Yang, Yang; Ji, Wei-Gang; Zhu, Zhi-Ru; Wu, Yu-Ling; Zhang, Zhi-Yang; Qu, Shao-Chen

    2018-06-01

    Rhynchophylline (RIN) is a significant active component isolated from the Chinese herbal medicine Uncaria rhynchophylla. The overproduction of soluble amyloid β protein (Aβ) oligomers in the hippocampus is closely involved in impairments in cognitive function at the early stage of Alzheimer's disease (AD). Growing evidences show that RIN possesses neuroprotective effects against Aβ-induced neurotoxicity. However, whether RIN can prevent soluble Aβ 1-42 -induced impairments in spatial cognitive function and synaptic plasticity is still unclear. Using the combined methods of behavioral tests, immunofluorescence and electrophysiological recordings, we characterized the key neuroprotective properties of RIN and its possible cellular and molecular mechanisms against soluble Aβ 1-42 -related impairments in rats. Our findings are as follows: (1) RIN efficiently rescued the soluble Aβ 1-42 -induced spatial learning and memory deficits in the Morris water maze test and prevented soluble Aβ 1-42 -induced suppression in long term potentiation (LTP) in the entorhinal cortex (EC)-dentate gyrus (DG) circuit. (2) Excessive activation of extrasynaptic GluN2B-NMDAR and subsequent Ca 2+ overload contributed to the soluble Aβ 1-42 -induced impairments in spatial cognitive function and synaptic plasticity. (3) RIN prevented Aβ 1-42 -induced excessive activation of extrasynaptic NMDARs by reducing extrasynaptic NMDARs -mediated excitatory postsynaptic currents and down regulating GluN2B-NMDAR expression in the DG region, which inhibited Aβ 1-42 -induced Ca 2+ overload mediated by extrasynanptic NMDARs. The results suggest that RIN could be an effective therapeutic candidate for cognitive impairment in AD. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. Spatial and temporal analysis of drought variability at several time scales in Syria during 1961-2012

    Science.gov (United States)

    Mathbout, Shifa; Lopez-Bustins, Joan A.; Martin-Vide, Javier; Bech, Joan; Rodrigo, Fernando S.

    2018-02-01

    This paper analyses the observed spatiotemporal characteristics of drought phenomenon in Syria using the Standardised Precipitation Index (SPI) and the Standardised Precipitation Evapotranspiration Index (SPEI). Temporal variability of drought is calculated for various time scales (3, 6, 9, 12, and 24 months) for 20 weather stations over the 1961-2012 period. The spatial patterns of drought were identified by applying a Principal Component Analysis (PCA) to the SPI and SPEI values at different time scales. The results revealed three heterogeneous and spatially well-defined regions with different temporal evolution of droughts: 1) Northeastern (inland desert); 2) Southern (mountainous landscape); 3) Northwestern (Mediterranean coast). The evolutionary characteristics of drought during 1961-2012 were analysed including spatial and temporal variability of SPI and SPEI, the frequency distribution, and the drought duration. The results of the non-parametric Mann-Kendall test applied to the SPI and SPEI series indicate prevailing significant negative trends (drought) at all stations. Both drought indices have been correlated both on spatial and temporal scales and they are highly comparable, especially, over a 12 and 24 month accumulation period. We concluded that the temporal and spatial characteristics of the SPI and SPEI can be used for developing a drought intensity - areal extent - and frequency curve that assesses the variability of regional droughts in Syria. The analysis of both indices suggests that all three regions had a severe drought in the 1990s, which had never been observed before in the country. Furthermore, the 2007-2010 drought was the driest period in the instrumental record, happening just before the onset of the recent conflict in Syria.

  1. Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: a gradient of severity in cognitive impairments.

    Science.gov (United States)

    Leblond, Claire S; Nava, Caroline; Polge, Anne; Gauthier, Julie; Huguet, Guillaume; Lumbroso, Serge; Giuliano, Fabienne; Stordeur, Coline; Depienne, Christel; Mouzat, Kevin; Pinto, Dalila; Howe, Jennifer; Lemière, Nathalie; Durand, Christelle M; Guibert, Jessica; Ey, Elodie; Toro, Roberto; Peyre, Hugo; Mathieu, Alexandre; Amsellem, Frédérique; Rastam, Maria; Gillberg, I Carina; Rappold, Gudrun A; Holt, Richard; Monaco, Anthony P; Maestrini, Elena; Galan, Pilar; Heron, Delphine; Jacquette, Aurélia; Afenjar, Alexandra; Rastetter, Agnès; Brice, Alexis; Devillard, Françoise; Assouline, Brigitte; Laffargue, Fanny; Lespinasse, James; Chiesa, Jean; Rivier, François; Bonneau, Dominique; Regnault, Beatrice; Zelenika, Diana; Delepine, Marc; Lathrop, Mark; Sanlaville, Damien; Schluth-Bolard, Caroline; Edery, Patrick; Perrin, Laurence; Tabet, Anne Claude; Schmeisser, Michael J; Boeckers, Tobias M; Coleman, Mary; Sato, Daisuke; Szatmari, Peter; Scherer, Stephen W; Rouleau, Guy A; Betancur, Catalina; Leboyer, Marion; Gillberg, Christopher; Delorme, Richard; Bourgeron, Thomas

    2014-09-01

    SHANK genes code for scaffold proteins located at the post-synaptic density of glutamatergic synapses. In neurons, SHANK2 and SHANK3 have a positive effect on the induction and maturation of dendritic spines, whereas SHANK1 induces the enlargement of spine heads. Mutations in SHANK genes have been associated with autism spectrum disorders (ASD), but their prevalence and clinical relevance remain to be determined. Here, we performed a new screen and a meta-analysis of SHANK copy-number and coding-sequence variants in ASD. Copy-number variants were analyzed in 5,657 patients and 19,163 controls, coding-sequence variants were ascertained in 760 to 2,147 patients and 492 to 1,090 controls (depending on the gene), and, individuals carrying de novo or truncating SHANK mutations underwent an extensive clinical investigation. Copy-number variants and truncating mutations in SHANK genes were present in ∼1% of patients with ASD: mutations in SHANK1 were rare (0.04%) and present in males with normal IQ and autism; mutations in SHANK2 were present in 0.17% of patients with ASD and mild intellectual disability; mutations in SHANK3 were present in 0.69% of patients with ASD and up to 2.12% of the cases with moderate to profound intellectual disability. In summary, mutations of the SHANK genes were detected in the whole spectrum of autism with a gradient of severity in cognitive impairment. Given the rare frequency of SHANK1 and SHANK2 deleterious mutations, the clinical relevance of these genes remains to be ascertained. In contrast, the frequency and the penetrance of SHANK3 mutations in individuals with ASD and intellectual disability-more than 1 in 50-warrant its consideration for mutation screening in clinical practice.

  2. Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: a gradient of severity in cognitive impairments.

    Directory of Open Access Journals (Sweden)

    Claire S Leblond

    2014-09-01

    Full Text Available SHANK genes code for scaffold proteins located at the post-synaptic density of glutamatergic synapses. In neurons, SHANK2 and SHANK3 have a positive effect on the induction and maturation of dendritic spines, whereas SHANK1 induces the enlargement of spine heads. Mutations in SHANK genes have been associated with autism spectrum disorders (ASD, but their prevalence and clinical relevance remain to be determined. Here, we performed a new screen and a meta-analysis of SHANK copy-number and coding-sequence variants in ASD. Copy-number variants were analyzed in 5,657 patients and 19,163 controls, coding-sequence variants were ascertained in 760 to 2,147 patients and 492 to 1,090 controls (depending on the gene, and, individuals carrying de novo or truncating SHANK mutations underwent an extensive clinical investigation. Copy-number variants and truncating mutations in SHANK genes were present in ∼1% of patients with ASD: mutations in SHANK1 were rare (0.04% and present in males with normal IQ and autism; mutations in SHANK2 were present in 0.17% of patients with ASD and mild intellectual disability; mutations in SHANK3 were present in 0.69% of patients with ASD and up to 2.12% of the cases with moderate to profound intellectual disability. In summary, mutations of the SHANK genes were detected in the whole spectrum of autism with a gradient of severity in cognitive impairment. Given the rare frequency of SHANK1 and SHANK2 deleterious mutations, the clinical relevance of these genes remains to be ascertained. In contrast, the frequency and the penetrance of SHANK3 mutations in individuals with ASD and intellectual disability-more than 1 in 50-warrant its consideration for mutation screening in clinical practice.

  3. Malnutrition in HIV-Infected Children Is an Indicator of Severe Disease with an Impaired Response to Antiretroviral Therapy

    Science.gov (United States)

    Healy, Michael; Singh, Ravesh; Roider, Julia; Groll, Andreas; Kindra, Chirjeev; Sibaya, Thobekile; Moonsamy, Angeline; McGregor, Callum; Phan, Michelle Q.; Palma, Alejandro; Kloverpris, Henrik; Leslie, Alasdair; Bobat, Raziya; LaRussa, Philip; Ndung'u, Thumbi; Goulder, Philip; Sobieszczyk, Magdalena E.; Archary, Mohendran

    2018-01-01

    Abstract This observational study aimed to describe immunopathogenesis and treatment outcomes in children with and without severe acute malnutrition (SAM) and HIV-infection. We studied markers of microbial translocation (16sDNA), intestinal damage (iFABP), monocyte activation (sCD14), T-cell activation (CD38, HLA-DR) and immune exhaustion (PD1) in 32 HIV-infected children with and 41 HIV-infected children without SAM prior to initiation of antiretroviral therapy (ART) and cross-sectionally compared these children to 15 HIV-uninfected children with and 19 HIV-uninfected children without SAM. We then prospectively measured these markers and correlated them to treatment outcomes in the HIV-infected children at 48 weeks following initiation of ART. Plasma levels of 16sDNA, iFABP and sCD14 were measured by quantitative real time PCR, ELISA and Luminex, respectively. T cell phenotype markers were measured by flow cytometry. Multiple regression analysis was performed using generalized linear models (GLMs) and the least absolute shrinkage and selection operator (LASSO) approach for variable selection. Microbial translocation, T cell activation and exhaustion were increased in HIV-uninfected children with SAM compared to HIV-uninfected children without SAM. In HIV-infected children microbial translocation, immune activation, and exhaustion was strongly increased but did not differ by SAM-status. SAM was associated with increased mortality rates early after ART initiation. Malnutrition, age, microbial translocation, monocyte, and CD8 T cell activation were independently associated with decreased rates of CD4% immune recovery after 48 weeks of ART. SAM is associated with increased microbial translocation, immune activation, and immune exhaustion in HIV-uninfected children and with worse prognosis and impaired immune recovery in HIV-infected children on ART. PMID:28670966

  4. Severe visual impairment and retinal changes in a boy with a deletion of the gene for Nance-Horan syndrome.

    Science.gov (United States)

    Mathys, R; Deconinck, H; Keymolen, K; Jansen, A; Van Esch, H

    2007-01-01

    We present the ophthalmologic findings in a boy with a deletion of Xp22 comprising the gene for Nance-Horan syndrome. Different mechanisms underlying the visual impairment in Nance-Horan syndrome are discussed.

  5. Temporal-spatial characteristics of severe drought events in Southwest China and their relationships to teleconnection indices

    Science.gov (United States)

    Wang, P., III; Wu, C.; Hao, Y.; Xu, K.

    2017-12-01

    In the process of global warming, the frequency and intensity of a series of climate events (such as, precipitation, flood disaster, climate arid) are also being changed. Even in the today of advanced science and technology, the occurrence and severity of drought in China is still devastating impact on social and economic development. We studied the spatial and temporal variability of drought in southwestern China China and its relationships to teleconnection indices. We used the Palmer Drought Severity Index (PDSI) to investigate the variation in drought in southwestern China between 1961 and 2012 using the Mann-Kendall (MK), continuous wavelet transform (CWT) and the rotated empirical orthogonal function (REOF) methods. Additionally, We analyzed the relationships between the time variability of significant patterns and teleconnection indices. The PDSI shows that there is a trend of turning dry in west Tibet; while it is remarkably drying in junction of Yunnan, Guizhou, Sichuan, Chongqing provinces, and the drought in Spring is more severe than in autumn, with a changing oscillation period of 2-7a. It's found the drought strength reducing before rising without a obvious turning point. Also, the drought frequency staggered in spatial distribution, and a larger inter-annual difference. AO and SS are the most important factors among all the drought influence factors, the others differ from the importance.

  6. Cross-sectional and longitudinal relationship between neuroticism and cognitive ability in advanced old age: the moderating role of severe sensory impairment.

    Science.gov (United States)

    Wettstein, Markus; Kuźma, Elżbieta; Wahl, Hans-Werner; Heyl, Vera

    2016-09-01

    Gaining a comprehensive picture of the network of constructs in which cognitive functioning is embedded is crucial across the full lifespan. With respect to personality, previous findings support a relationship between neuroticism and cognitive abilities. However, findings regarding old age are inconsistent. In particular, little is known about potentially moderating variables which might explain some of the inconsistency. Our aim was to examine the moderating effect of severe sensory impairment on cross-sectional and longitudinal associations between neuroticism and cognitive functioning. The study sample consisted of 121 visually impaired (VI), 116 hearing impaired (HI), and 150 sensory unimpaired older adults (UI). Mean age was 82.50 years (SD = 4.71 years). Neuroticism was assessed by the NEO Five Factor Inventory, and multiple established tests were used for the assessment of cognitive performance (e.g., subtests of the revised Wechsler Adult Intelligence Scale). Bivariate correlations and multi-group structural equation models indicated stronger relationships between cognitive abilities and neuroticism in both sensory impaired groups (VI and HI) compared to UI older individuals. This relationship was attenuated but still significant in both sensory impaired groups when controlling for age, education and health (number of chronic conditions). In cross-lagged panel models, higher baseline neuroticism was significantly associated with lower cognitive performance four years later in VI and HI individuals. Our results suggest that sensory impairment moderates both cross-sectional and longitudinal associations between neuroticism and cognitive function in advanced old age.

  7. Long term effect (more than five years) of intrathecal baclofen on impairment, disability, and quality of life in patients with severe spasticity of spinal origin

    NARCIS (Netherlands)

    Zahavi, A; Geertzen, JHB; Middel, B; Staal, M; Rietman, JS

    2004-01-01

    Objectives: To evaluate long term change in impairment, disability, and health related functional status in patients with severe spasticity who received intrathecal baclofen. Methods: A long term ( more than five years) observational longitudinal follow up study assessing 21 patients who received

  8. Efficacy, safety and pharmacokinetics of sugammadex 4 mg kg-1 for reversal of deep neuromuscular blockade in patients with severe renal impairment

    NARCIS (Netherlands)

    Panhuizen, I. F.; Gold, S. J. A.; Buerkle, C.; Snoeck, M. M. J.; Harper, N. J. N.; Kaspers, M. J. G. H.; van den Heuvel, M. W.; Hollmann, M. W.

    2015-01-01

    This study evaluated efficacy and safety of sugammadex 4 mg kg(-1) for deep neuromuscular blockade (NMB) reversal in patients with severe renal impairment (creatinine clearance [CLCR] <30 ml min(-1)) vs those with normal renal function (CLCR ≥80 ml min(-1)). Sugammadex 4 mg kg(-1) was administered

  9. Using Norm-Referenced Tests to Determine Severity of Language Impairment in Children: Disconnect between U.S. Policy Makers and Test Developers

    Science.gov (United States)

    Spaulding, Tammie J.; Szulga, Margaret Swartwout; Figueroa, Cecilia

    2012-01-01

    Purpose: The purpose of this study was to identify various U.S. state education departments' criteria for determining the severity of language impairment in children, with particular focus on the use of norm-referenced tests. A secondary objective was to determine if norm-referenced tests of child language were developed for the purpose of…

  10. 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)

  11. Comparison of Reading Comprehension Skill of Students with Severe to Profound Hearing Impairment from Second up to Fifth Grade of Exceptional Schools with Normal Hearing Students

    Directory of Open Access Journals (Sweden)

    Maryam Jalalipour

    2016-03-01

    Full Text Available Background: Reading is known as one of the most important learning tools. Research results consistently have shown that even a mild hearing impairment could affect the reading skills. Due to the reported differences in reading comprehension skills between hearing impaired students and their normal hearing peers, this research was conducted to compare the differences between the two groups. The other aim was to find any changes in the reading ability of hearing impaired group during elementary school. Methods: This study is a cross-sectional (descriptive–analytic one in which reading comprehension ability of 91 students with severe and profound hearing impairment (33 girls and 58 boys from 2nd up to 5th grade of exceptional schools were compared with 50 2nd grade normal hearing students in Ahvaz, Iran. The first section of Diagnostic Reading Test (Shirazi – Nilipour, 2004 was used in this study. Then the mean reading scores of hearing impaired students in each grade was compared with control group using SPSS 13 with Mann Whitney test. Results: There was a significant difference between average scores of hearing impaired students (boys and girls in 2nd to 5th grade with normal hearing students of 2nd grade (P<0.001. Reading comprehension scores of students with hearing impairment in higher grades had improved slightly, but it was still lower than that of the normal hearing students in the 2nd grade. Conclusion: It appears that reading comprehension skill of students with significant hearing impairment near the end of elementary school years becomes weaker than normal hearing students in the second grade. Therefore, it is essential to find and resolve the underlying reasons of this condition by all professionals who work in the field of education and rehabilitation of these students.

  12. Pre-weaning dietary iron deficiency impairs spatial learning and memory in the cognitive holeboard task in piglets

    Directory of Open Access Journals (Sweden)

    Alexandra eAntonides

    2015-10-01

    Full Text Available Iron deficiency (ID is the most common nutritional deficiency in humans, affecting more than two billion people worldwide. Early-life ID can lead to irreversible deficits in learning and memory. The pig represents a promising model animal for studying such deficits, because of its similarities to humans during early development. We investigated long-term effects of pre-weaning dietary iron deficiency in piglets on growth, blood parameters, cognitive performance and brain histology. Ten male sibling pairs of piglets were removed from the sow 4-6 days after birth. Ten piglets were given an iron dextran injection and were fed a control milk diet for 28 days (100 mg Fe/kg; their ten siblings were given a saline injection and fed an iron deficient milk diet (10 mg Fe/kg. Then, all piglets were fed a balanced commercial pig diet (190-240 mg Fe/kg. From 8 weeks of age, piglets were tested in a spatial cognitive holeboard task. In this task, 4 of 16 holes contain a hidden food reward, allowing measurement of working (short-term memory and reference (long-term memory (RM simultaneously. All piglets received 40-60 acquisition trials, followed by a 16-trial reversal phase. ID piglets showed permanently retarded growth and a strong decrease in blood iron parameters during dietary treatment. After treatment, ID piglets blood iron values restored to normal levels. In the holeboard task, ID piglets showed impaired RM learning during acquisition and reversal. Iron staining at necropsy at 12 weeks of age showed that ID piglets had fewer iron-containing cells in hippocampal regions CA1 and dentate gyrus. The number of iron-containing cells in CA3 correlated positively with acquisition RM performance for all animals. Our results support the hypothesis that early ID leads to lasting cognitive deficits. The piglet as a model animal, tested in the holeboard, can be useful in future research for assessing long-term cognitive effects of early-life diets or diet

  13. Evidence for impairments in using static line drawings of eye gaze cues to orient visual-spatial attention in children with high functioning autism.

    Science.gov (United States)

    Goldberg, Melissa C; Mostow, Allison J; Vecera, Shaun P; Larson, Jennifer C Gidley; Mostofsky, Stewart H; Mahone, E Mark; Denckla, Martha B

    2008-09-01

    We examined the ability to use static line drawings of eye gaze cues to orient visual-spatial attention in children with high functioning autism (HFA) compared to typically developing children (TD). The task was organized such that on valid trials, gaze cues were directed toward the same spatial location as the appearance of an upcoming target, while on invalid trials gaze cues were directed to an opposite location. Unlike TD children, children with HFA showed no advantage in reaction time (RT) on valid trials compared to invalid trials (i.e., no significant validity effect). The two stimulus onset asynchronies (200 ms, 700 ms) did not differentially affect these findings. The results suggest that children with HFA show impairments in utilizing static line drawings of gaze cues to orient visual-spatial attention.

  14. Are we armed with the right data? Pooled individual data review of biomarkers in people with severe upper limb impairment after stroke

    Directory of Open Access Journals (Sweden)

    Kathryn S Hayward, PhD

    2017-01-01

    Full Text Available To build an understanding of the neurobiology underpinning arm recovery in people with severe arm impairment due to stroke, we conducted a pooled individual data systematic review to: 1 characterize brain biomarkers; 2 determine relationship(s between biomarkers and motor outcome; and 3 establish relationship(s between biomarkers and motor recovery. Three electronic databases were searched up to October 2, 2015. Eligible studies included adults with severe arm impairment after stroke. Descriptive statistics were calculated to characterize brain biomarkers, and pooling of individual patient data was performed using mixed-effects linear regression to examine relationships between brain biomarkers and motor outcome and recovery. Thirty-eight articles including individual data from 372 people with severe arm impairment were analysed. The majority of individuals were in the chronic (>6 months phase post stroke (51% and had a subcortical stroke (49%. The presence of a motor evoked potential (indexed by transcranial magnetic stimulation was the only biomarker related to better motor outcome (p = 0.02. There was no relationship between motor outcome and stroke volume (cm3, location (cortical, subcortical, mixed or side (left vs. right, and corticospinal tract asymmetry index (extracted from diffusion weighted imaging. Only one study had longitudinal data, thus no data pooling was possible to address change over time (preventing our third objective. Based on the available evidence, motor evoked potentials at rest were the only biomarker that predicted motor outcome in individuals with severe arm impairment following stroke. Given that few biomarkers emerged, this review highlights the need to move beyond currently known biomarkers and identify new indices with sufficient variability and sensitivity to guide recovery models in individuals with severe motor impairments following stroke. PROSPERO: CRD42015026107.

  15. The comparison of perceived health-related quality of life between Australian children with severe specific language impairment to age and gender-matched peers.

    Science.gov (United States)

    Nicola, Kristy; Watter, Pauline

    2018-02-14

    Children with specific language impairment often present with multiple comorbidities, which may adversely affect both participation in play and academic performance, potentially impacting a child's health-related quality of life. This study 1) explored the suitability of the Pediatric Quality of Life Inventory™ Version 4.0 Generic Core Scales (PedsQL™) for use with a typically developing Australian control group, and 2) compared the health-related quality of life between a control group and Australian children with severe specific language impairment. Health-related quality of life data collected as part of a broader study of 43 children with severe specific language impairment (males = 35, age range 5-16, mean age = 8.79+/- 2.92) enrolled at a special school were used to explore previously unreported findings. Typically developing gender and age matched (+/- 3 months) peers were recruited from local schools. The PedsQL™ child self-report and proxy-report were individually or interviewer-administered to the control group as required, and then compared to the group with specific language impairment. The PedsQL™ was reliable and feasible for use with the control group (N = 43, males = 35, age range = 5-16 years, mean age = 8.74+/- 2.94 years). Control group performance was as expected as per the manual. Parents of the control group scored their children significantly higher than did the children themselves on all scales except the emotional functioning scale. Both the control group children and their parents scored themselves significantly higher on all scales, compared to children with severe specific language impairment and their parents. The PedsQL™ was suitable for use with the control group. Further, the recruitment of a control group provided additional clarity on the extent a severe specific language impairment impacts on an Australian child's perceived health-related quality of life, compared to the manual cut

  16. Perinatal exposure to bisphenol-A impairs spatial memory through upregulation of neurexin1 and neuroligin3 expression in male mouse brain.

    Directory of Open Access Journals (Sweden)

    Dhiraj Kumar

    Full Text Available Bisphenol-A (BPA, a well known endocrine disruptor, impairs learning and memory in rodents. However, the underlying molecular mechanism of BPA induced impairment in learning and memory is not well known. As synaptic plasticity is the cellular basis of memory, the present study investigated the effect of perinatal exposure to BPA on the expression of synaptic proteins neurexin1 (Nrxn1 and neuroligin3 (Nlgn3, dendritic spine density and spatial memory in postnatal male mice. The pregnant mice were orally administered BPA (50 µg/kgbw/d from gestation day (GD 7 to postnatal day (PND 21 and sesame oil was used as a vehicle control. In Morris water maze (MWM test, BPA extended the escape latency time to locate the hidden platform in 8 weeks male mice. RT-PCR and Immunoblotting results showed significant upregulation of Nrxn1 and Nlgn3 expression in both cerebral cortex and hippocampus of 3 and 8 weeks male mice. This was further substantiated by in-situ hybridization and immunofluorescence techniques. BPA also significantly increased the density of dendritic spines in both regions, as analyzed by rapid Golgi staining. Thus our data suggest that perinatal exposure to BPA impairs spatial memory through upregulation of expression of synaptic proteins Nrxn1 and Nlgn3 and increased dendritic spine density in cerebral cortex and hippocampus of postnatal male mice.

  17. Compound danshen tablet ameliorated aβ25-35-induced spatial memory impairment in mice via rescuing imbalance between cytokines and neurotrophins.

    Science.gov (United States)

    Teng, Yan; Zhang, Meng-Qi; Wang, Wen; Liu, Li-Tao; Zhou, Li-Ming; Miao, Shi-Kun; Wan, Li-Hong

    2014-01-14

    Compound Danshen Tablet (CDT), a Traditional Chinese Medicine, has recently been reported to improve spatial cognition in a rat model of Alzheimer's disease. However, in vivo neuroprotective mechanism of the CDT in models of spatial memory impairment is not yet evaluated. The present study is aimed to elucidate the cellular mechanism of CDT on Aβ25-35-induced cognitive impairment in mice. Mice were randomly divided into 5 groups: the control group (sham operated), the Aβ25-35 treated group, the positive drug group, and large and small dosage of the CDT groups, respectively. CDT was administered at a dose of 0.81 g/kg and 0.405 g/kg for 3 weeks. The mice in the positive drug group were treated with 0.4 mg/kg of Huperzine A, whereas the mice of the control and Aβ25-35 treated groups were administrated orally with equivalent saline. After 7 days of preventive treatment, mice were subjected to lateral ventricle injection of Aβ25-35 to establish the mice model of Alzheimer's disease. Spatial memory impairment was evaluated by Morris water maze test. Choline acetyltransferase (ChAT) contents in hippocampus and cortex were quantified by ELISA. The levels of cytokines, receptor of activated protein kinase C1 (RACK1) and brain-derived neurotrophic factor (BDNF) in hippocampus were measured by RT-PCR and ELISA. The results showed that Aβ25-35 caused spatial memory impairment as demonstrated by performance in the Morris water maze test. CDT was able to confer a significant improvement in spatial memory, and protect mice from Aβ25-35-induced neurotoxicity. Additionally, CDT also inhibited the increase of TNF-α and IL-6 level, and increased the expression of choline acetyltransferase (ChAT), receptor of activated protein kinase C1 (RACK1) and brain-derived neurotrophic factor (BDNF) in brain as compared to model mice. These findings strongly implicate that CDT may be a useful treatment against learning and memory deficits in mice by rescuing imbalance between cytokines

  18. Association between anxiety and severe quality-of-life impairment in postmenopausal women: analysis of a multicenter Latin American cross-sectional study.

    Science.gov (United States)

    Núñez-Pizarro, Jorge L; González-Luna, Alejandro; Mezones-Holguín, Edward; Blümel, Juan E; Barón, Germán; Bencosme, Ascanio; Benítez, Zully; Bravo, Luz M; Calle, Andrés; Flores, Daniel; Espinoza, María T; Gómez, Gustavo; Hernández-Bueno, José A; Martino, Mabel; Lima, Selva; Monterrosa, Alvaro; Mostajo, Desiree; Ojeda, Eliana; Onatra, William; Sánchez, Hugo; Tserotas, Konstantinos; Vallejo, María S; Witis, Silvina; Zúñiga, María C; Chedraui, Peter

    2017-06-01

    To evaluate associations between anxiety and severe impairment of quality of life (QoL) in Latin American postmenopausal women. This was a secondary analysis of a multicenter cross-sectional study among postmenopausal women aged 40 to 59 from 11 Latin American countries. We evaluated anxiety (The Goldberg Depression and Anxiety Scale), and QoL (Menopause Rating Scale [MRS]), and included sociodemographic, clinical, lifestyle, and anthropometric variables in the analysis. Poisson family generalized linear models with robust standard errors were used to estimate prevalence ratios (PRs) and 95% CIs. There were two adjusted models: a statistical model that included variables associated with the outcomes in bivariate analyses, and an epidemiologic model that included potentially confounding variables from literature review. Data from 3,503 women were included; 61.9% had anxiety (Goldberg). Severe QoL impairment (total MRS score ≥17) was present in 13.7% of women, as well as severe symptoms (MRS subscales): urogenital (25.5%), psychological (18.5%), and somatic (4.5%). Anxiety was independently associated with severe QoL impairment and severe symptoms in the epidemiological (MRS total score: PR 3.6, 95% CI, 2.6-5.0; somatic: 5.1, 95% CI, 2.6-10.1; psychological: 2.8, 95% CI, 2.2-3.6; and urogenital: 1.4, 95% CI, 1.2-1.6) and the statistical model (MRS total score: PR 3.5, 95% CI, 2.6-4.9; somatic: 5.0, 95% CI, 2.5-9.9; psychological: 2.9, 95% CI, 2.2-3.7; and urogenital: 1.4; 95% CI, 1.2-1.6). In this postmenopausal Latin American sample, anxiety was independently associated with severe QoL impairment. Hence, screening for anxiety in this population is important.

  19. Systemic lipopolysaccharide administration impairs retrieval of context-object discrimination, but not spatial, memory: Evidence for selective disruption of specific hippocampus-dependent memory functions during acute neuroinflammation.

    Science.gov (United States)

    Czerniawski, Jennifer; Miyashita, Teiko; Lewandowski, Gail; Guzowski, John F

    2015-02-01

    Neuroinflammation is implicated in impairments in neuronal function and cognition that arise with aging, trauma, and/or disease. Therefore, understanding the underlying basis of the effect of immune system activation on neural function could lead to therapies for treating cognitive decline. Although neuroinflammation is widely thought to preferentially impair hippocampus-dependent memory, data on the effects of cytokines on cognition are mixed. One possible explanation for these inconsistent results is that cytokines may disrupt specific neural processes underlying some forms of memory but not others. In an earlier study, we tested the effect of systemic administration of bacterial lipopolysaccharide (LPS) on retrieval of hippocampus-dependent context memory and neural circuit function in CA3 and CA1 (Czerniawski and Guzowski, 2014). Paralleling impairment in context discrimination memory, we observed changes in neural circuit function consistent with disrupted pattern separation function. In the current study we tested the hypothesis that acute neuroinflammation selectively disrupts memory retrieval in tasks requiring hippocampal pattern separation processes. Male Sprague-Dawley rats given LPS systemically prior to testing exhibited intact performance in tasks that do not require hippocampal pattern separation processes: novel object recognition and spatial memory in the water maze. By contrast, memory retrieval in a task thought to require hippocampal pattern separation, context-object discrimination, was strongly impaired in LPS-treated rats in the absence of any gross effects on exploratory activity or motivation. These data show that LPS administration does not impair memory retrieval in all hippocampus-dependent tasks, and support the hypothesis that acute neuroinflammation impairs context discrimination memory via disruption of pattern separation processes in hippocampus. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Neuropeptide S ameliorates olfactory spatial memory impairment induced by scopolamine and MK801 through activation of cognate receptor-expressing neurons in the subiculum complex.

    Science.gov (United States)

    Shao, Yu-Feng; Wang, Can; Xie, Jun-Fan; Kong, Xiang-Pan; Xin, Le; Dong, Chao-Yu; Li, Jing; Ren, Wen-Ting; Hou, Yi-Ping

    2016-07-01

    Our previous studies have demonstrated that neuropeptide S (NPS), via selective activation of the neurons bearing NPS receptor (NPSR) in the olfactory cortex, facilitates olfactory function. High level expression of NPSR mRNA in the subiculum complex of hippocampal formation suggests that NPS-NPSR system might be involved in the regulation of olfactory spatial memory. The present study was undertaken to investigate effects of NPS on the scopolamine- or MK801-induced impairment of olfactory spatial memory using computer-assisted 4-hole-board spatial memory test, and by monitoring Fos expression in the subiculum complex in mice. In addition, dual-immunofluorescence microscopy was employed to identify NPS-induced Fos-immunereactive (-ir) neurons that also bear NPSR. Intracerebroventricular administration of NPS (0.5 nmol) significantly increased the number of visits to switched odorants in recall trial in mice suffering from odor-discriminating inability induced by scopolamine, a selective muscarinic cholinergic receptor antagonist, or MK801, a N-methyl-D-aspartate receptor antagonist, after training trials. The improvement of olfactory spatial memory by NPS was abolished by the NPSR antagonist [D-Val(5)]NPS (40 nmol). Ex vivo c-Fos and NPSR immunohistochemistry revealed that, as compared with vehicle-treated mice, NPS markedly enhanced Fos expression in the subiculum complex encompassing the subiculum (S), presubiculum (PrS) and parasubiculum (PaS). The percentages of Fos-ir neurons that also express NPSR were 91.3, 86.5 and 90.0 % in the S, PrS and PaS, respectively. The present findings demonstrate that NPS, via selective activation of the neurons bearing NPSR in the subiculum complex, ameliorates olfactory spatial memory impairment induced by scopolamine and MK801 in mice.

  1. Sex-specific impairment and recovery of spatial learning following the end of chronic unpredictable restraint stress: potential relevance of limbic GAD.

    Science.gov (United States)

    Ortiz, J Bryce; Taylor, Sara B; Hoffman, Ann N; Campbell, Alyssa N; Lucas, Louis R; Conrad, Cheryl D

    2015-04-01

    Chronic restraint stress alters hippocampal-dependent spatial learning and memory in a sex-dependent manner, impairing spatial performance in male rats and leaving intact or facilitating performance in female rats. Moreover, these stress-induced spatial memory deficits improve following post-stress recovery in males. The current study examined whether restraint administered in an unpredictable manner would eliminate these sex differences and impact a post-stress period on spatial ability and limbic glutamic acid decarboxylase (GAD65) expression. Male (n=30) and female (n=30) adult Sprague-Dawley rats were assigned to non-stressed control (Con), chronic stress (Str-Imm), or chronic stress given a post-stress recovery period (Str-Rec). Stressed rats were unpredictably restrained for 21 days using daily non-repeated combinations of physical context, duration, and time of day. Then, all rats were tested on the radial arm water maze (RAWM) for 2 days and given one retention trial on the third day, with brains removed 30min later to assess GAD65 mRNA. In Str-Imm males, deficits occurred on day 1 of RAWM acquisition, an impairment that was not evident in the Str-Rec group. In contrast, females did not show significant outcomes following chronic stress or post-stress recovery. In males, amygdalar GAD65 expression negatively correlated with RAWM performance on day 1. In females, hippocampal CA1 GAD65 positively correlated with RAWM performance on day 1. These results demonstrate that GABAergic function may contribute to the sex differences observed following chronic stress. Furthermore, unpredictable restraint and a recovery period failed to eliminate the sex differences on spatial learning and memory. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Short-term inhibition of 11β-hydroxysteroid dehydrogenase type 1 reversibly improves spatial memory but persistently impairs contextual fear memory in aged mice

    Science.gov (United States)

    Wheelan, Nicola; Webster, Scott P.; Kenyon, Christopher J.; Caughey, Sarah; Walker, Brian R.; Holmes, Megan C.; Seckl, Jonathan R.; Yau, Joyce L.W.

    2015-01-01

    High glucocorticoid levels induced by stress enhance the memory of fearful events and may contribute to the development of anxiety and posttraumatic stress disorder. In contrast, elevated glucocorticoids associated with ageing impair spatial memory. We have previously shown that pharmacological inhibition of the intracellular glucocorticoid-amplifying enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) improves spatial memory in aged mice. However, it is not known whether inhibition of 11β-HSD1 will have any beneficial effects on contextual fear memories in aged mice. Here, we examined the effects of UE2316, a selective 11β-HSD1 inhibitor which accesses the brain, on both spatial and contextual fear memories in aged mice using a vehicle-controlled crossover study design. Short-term UE2316 treatment improved spatial memory in aged mice, an effect which was reversed when UE2316 was substituted with vehicle. In contrast, contextual fear memory induced by foot-shock conditioning was significantly reduced by UE2316 in a non-reversible manner. When the order of treatment was reversed following extinction of the original fear memory, and a second foot-shock conditioning was given in a novel context, UE2316 treated aged mice (previously on vehicle) now showed increased fear memory compared to vehicle-treated aged mice (previously on UE2316). Renewal of the original extinguished fear memory triggered by exposure to a new environmental context may explain these effects. Thus 11β-HSD1 inhibition reverses spatial memory impairments with ageing while reducing the strength and persistence of new contextual fear memories. Potentially this could help prevent anxiety-related disorders in vulnerable elderly individuals. PMID:25497454

  3. Short-term inhibition of 11β-hydroxysteroid dehydrogenase type 1 reversibly improves spatial memory but persistently impairs contextual fear memory in aged mice.

    Science.gov (United States)

    Wheelan, Nicola; Webster, Scott P; Kenyon, Christopher J; Caughey, Sarah; Walker, Brian R; Holmes, Megan C; Seckl, Jonathan R; Yau, Joyce L W

    2015-04-01

    High glucocorticoid levels induced by stress enhance the memory of fearful events and may contribute to the development of anxiety and posttraumatic stress disorder. In contrast, elevated glucocorticoids associated with ageing impair spatial memory. We have previously shown that pharmacological inhibition of the intracellular glucocorticoid-amplifying enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) improves spatial memory in aged mice. However, it is not known whether inhibition of 11β-HSD1 will have any beneficial effects on contextual fear memories in aged mice. Here, we examined the effects of UE2316, a selective 11β-HSD1 inhibitor which accesses the brain, on both spatial and contextual fear memories in aged mice using a vehicle-controlled crossover study design. Short-term UE2316 treatment improved spatial memory in aged mice, an effect which was reversed when UE2316 was substituted with vehicle. In contrast, contextual fear memory induced by foot-shock conditioning was significantly reduced by UE2316 in a non-reversible manner. When the order of treatment was reversed following extinction of the original fear memory, and a second foot-shock conditioning was given in a novel context, UE2316 treated aged mice (previously on vehicle) now showed increased fear memory compared to vehicle-treated aged mice (previously on UE2316). Renewal of the original extinguished fear memory triggered by exposure to a new environmental context may explain these effects. Thus 11β-HSD1 inhibition reverses spatial memory impairments with ageing while reducing the strength and persistence of new contextual fear memories. Potentially this could help prevent anxiety-related disorders in vulnerable elderly individuals. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Single fluoxetine treatment before but not after stress prevents stress-induced hippocampal long-term depression and spatial memory retrieval impairment in rats

    Science.gov (United States)

    Han, Huili; Dai, Chunfang; Dong, Zhifang

    2015-01-01

    A growing body of evidence has shown that chronic treatment with fluoxetine, a widely prescribed medication for treatment of depression, can affect synaptic plasticity in the adult central nervous system. However, it is not well understood whether acute fluoxetine influences synaptic plasticity, especially on hippocampal CA1 long-term depression (LTD), and if so, whether it subsequently impacts hippocampal-dependent spatial memory. Here, we reported that LTD facilitated by elevated-platform stress in hippocampal slices was completely prevented by fluoxetine administration (10 mg/kg, i.p.) 30 min before stress. The LTD was not, however, significantly inhibited by fluoxetine administration immediately after stress. Similarly, fluoxetine incubation (10 μM) during electrophysiological recordings also displayed no influence on the stress-facilitated LTD. In addition, behavioral results showed that a single fluoxetine treatment 30 min before but not after acute stress fully reversed the impairment of spatial memory retrieval in the Morris water maze paradigm. Taken together, these results suggest that acute fluoxetine treatment only before, but not after stress, can prevent hippocampal CA1 LTD and spatial memory retrieval impairment caused by behavioral stress in adult animals. PMID:26218751

  5. Chronic administration of branched-chain amino acids impairs spatial memory and increases brain-derived neurotrophic factor in a rat model.

    Science.gov (United States)

    Scaini, Giselli; Comim, Clarissa M; Oliveira, Giovanna M T; Pasquali, Matheus A B; Quevedo, João; Gelain, Daniel P; Moreira, José Cláudio F; Schuck, Patrícia F; Ferreira, Gustavo C; Bogo, Maurício R; Streck, Emilio L

    2013-09-01

    Maple syrup urine disease (MSUD) is a neurometabolic disorder that leads to the accumulation of branched-chain amino acids (BCAAs) and their α-keto branched-chain by-products. Because the neurotoxic mechanisms of MSUD are poorly understood, this study aimed to evaluate the effects of chronic administration of a BCAA pool (leucine, isoleucine and valine). This study examined the effects of BCAA administration on spatial memory and the levels of brain-derived neurotrophic factor (BNDF). We examined both pro-BDNF and bdnf mRNA expression levels after administration of BCAAs. Furthermore, this study examined whether antioxidant treatment prevented the alterations induced by BCAA administration. Our results demonstrated an increase in BDNF in the hippocampus and cerebral cortex, accompanied by memory impairment in spatial memory tasks. Additionally, chronic administration of BCAAs did not induce a detectable change in pro-BDNF levels. Treatment with N-acetylcysteine and deferoxamine prevented both the memory deficit and the increase in the BDNF levels induced by BCAA administration. In conclusion, these results suggest that when the brain is chronically exposed to high concentrations of BCAA (at millimolar concentrations) an increase in BDNF levels occurs. This increase in BDNF may be related to the impairment of spatial memory. In addition, we demonstrated that antioxidant treatment prevented the negative consequences related to BCAA administration, suggesting that oxidative stress might be involved in the pathophysiological mechanism(s) underlying the brain damage observed in MSUD.

  6. Pattern of cognitive impairment after giving total intravenous anaesthesia vs general anesthesia for electroconvulsive therapy in patients with depressive episode severe

    International Nuclear Information System (INIS)

    Malik, U.E.; Ahmed, N.; Hyder, R.R.

    2017-01-01

    To study the pattern of cognitive impairment after giving total intravenous anesthesia Vs general anesthesia for ECT for patients of Depressive Episode Severe. Study Design: Randomized controlled trial. Place and Duration of Study: Combined Military Hospital Skardu, from 15 Jul 2015 till 15 Jan 2016. Material and Methods: Hundred patients fulfilling the inclusion criteria were included by consecutive sampling technique for this study and divided in to two groups of 50 each. Patients of group A were given TIVA (propofol + succinylcholine). Patients in group B received GA (propofol + succinylcholine + isoflurane). Cognitive functions of patient were assessed by psychiatrist via mini mental state examination (MMSE) test before ECT and two weeks after ECT respectively. Results: Both the groups were assessed for cognitive impairment after TIVA Vs GA. In group A the MMSE showed less cognitive impairment as compared to group B (p<0.05). Conclusion: Cognitive impairment is less in total intravenous anesthesia as compared to general anesthesia for ECT in patients of depressive episode severe. (author)

  7. [Impairment and disability in patients with a severe ischemic cerebral infarction at admission to the rehabilitation center and six months after stroke].

    Science.gov (United States)

    Prevo, A J; Dijkman, M M; Le Fèvre, F A

    1998-03-21

    Evaluation of impairment and disability in stroke patients with a severe cortical infarction at admission as well as six months after the stroke. Prospective and descriptive study. Rehabilitation Centre Heliomare, Wijk aan Zee, the Netherlands. Between 1 January 1987 en 31 May 1992 stroke patients were admitted to the rehabilitation centre with a severe, first ever, cortical infarction without any comorbidity. The patients were dependent in activities of daily living and wheel-chair-bound. Motor and neuropsychological impairment and disability were evaluated at admission to the rehabilitation centre as well as six months after the stroke. Return to home and length of stay were evaluated. 43 patients were included. Recovery of arm and hand function was very poor (there was complete paresis at admission in 33 patients (77%) and six months after the CVA in 25 patients (58%)); recovery of the affected leg was reasonable (complete paresis in 10 (23%) and 0 patients, respectively). Cognitive deficits diminished in severity, but remained noticeable in three-quarters of the patients. Independent walking was achieved by 30 patients (70%), independence in personal activities of daily living by 32 patients (74%) and returning home by 36 patients (84%). The mean hospital stay was 26 weeks (SD: 9.26; range: 11-30). Prognosis of personal independence and returning home after a severe cortical infarction was rather good despite poor recovery of motor and cognitive impairment.

  8. Consequences of severe habitat fragmentation on density, genetics, and spatial capture-recapture analysis of a small bear population.

    Directory of Open Access Journals (Sweden)

    Sean M Murphy

    Full Text Available Loss and fragmentation of natural habitats caused by human land uses have subdivided several formerly contiguous large carnivore populations into multiple small and often isolated subpopulations, which can reduce genetic variation and lead to precipitous population declines. Substantial habitat loss and fragmentation from urban development and agriculture expansion relegated the Highlands-Glades subpopulation (HGS of Florida, USA, black bears (Ursus americanus floridanus to prolonged isolation; increasing human land development is projected to cause ≥ 50% loss of remaining natural habitats occupied by the HGS in coming decades. We conducted a noninvasive genetic spatial capture-recapture study to quantitatively describe the degree of contemporary habitat fragmentation and investigate the consequences of habitat fragmentation on population density and genetics of the HGS. Remaining natural habitats sustaining the HGS were significantly more fragmented and patchier than those supporting Florida's largest black bear subpopulation. Genetic diversity was low (AR = 3.57; HE = 0.49 and effective population size was small (NE = 25 bears, both of which remained unchanged over a period spanning one bear generation despite evidence of some immigration. Subpopulation density (0.054 bear/km2 was among the lowest reported for black bears, was significantly female-biased, and corresponded to a subpopulation size of 98 bears in available habitat. Conserving remaining natural habitats in the area occupied by the small, genetically depauperate HGS, possibly through conservation easements and government land acquisition, is likely the most important immediate step to ensuring continued persistence of bears in this area. Our study also provides evidence that preferentially placing detectors (e.g., hair traps or cameras primarily in quality habitat across fragmented landscapes poses a challenge to estimating density-habitat covariate relationships using spatial

  9. Inactivation of the dorsal hippocampus or the medial prefrontal cortex impairs retrieval but has differential effect on spatial memory reconsolidation.

    Science.gov (United States)

    Rossato, Janine I; Köhler, Cristiano A; Radiske, Andressa; Bevilaqua, Lia R M; Cammarota, Martín

    2015-11-01

    Active memories can incorporate new information through reconsolidation. However, the notion that memory retrieval is necessary for reconsolidation has been recently challenged. Non-reinforced retrieval induces hippocampus and medial prefrontal cortex (mPFC)-dependent reconsolidation of spatial memory in the Morris water maze (MWM). We found that the effect of protein synthesis inhibition on this process is abolished when retrieval of the learned spatial preference is hindered through mPFC inactivation but not when it is blocked by deactivation of dorsal CA1. Our results do not fully agree with the hypothesis that retrieval is unneeded for reconsolidation. Instead, they support the idea that a hierarchic interaction between the hippocampus and the mPFC controls spatial memory in the MWM, and indicate that this cortex is sufficient to retrieve the information essential to reconsolidate the spatial memory trace, even when the hippocampus is inactivated. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Visual Spatial Attention and Speech Segmentation are Both Impaired in Preschoolers at Familial Risk for Developmental Dyslexia

    Science.gov (United States)

    Facoetti, Andrea; Corradi, Nicola; Ruffino, Milena; Gori, Simone; Zorzi, Marco

    2010-01-01

    Phonological skills are foundational of reading acquisition and impaired phonological processing is widely assumed to characterize dyslexic individuals. However, reading by phonological decoding also requires rapid selection of sublexical orthographic units through serial attentional orienting, and recent studies have shown that visual spatial…

  11. The effect of an attachment-based intervention on challenging behaviour: visually and severe intellectually impaired children

    NARCIS (Netherlands)

    Sterkenburg, P.S.; Janssen, C.G.C.; Schuengel, C.

    2008-01-01

    Background A combination of an attachment-based therapy and behaviour modification was investigated for children with persistent challenging behaviour. Method Six clients with visual and severe intellectual disabilities, severe challenging behaviour and with a background of pathogenic care were

  12. Risperidone reverses the spatial object recognition impairment and hippocampal BDNF-TrkB signalling system alterations induced by acute MK-801 treatment

    Science.gov (United States)

    Chen, Guangdong; Lin, Xiaodong; Li, Gongying; Jiang, Diego; Lib, Zhiruo; Jiang, Ronghuan; Zhuo, Chuanjun

    2017-01-01

    The aim of the present study was to investigate the effects of a commonly-used atypical antipsychotic, risperidone, on alterations in spatial learning and in the hippocampal brain-derived neurotrophic factor (BDNF)-tyrosine receptor kinase B (TrkB) signalling system caused by acute dizocilpine maleate (MK-801) treatment. In experiment 1, adult male Sprague-Dawley rats subjected to acute treatment of either low-dose MK801 (0.1 mg/kg) or normal saline (vehicle) were tested for spatial object recognition and hippocampal expression levels of BDNF, TrkB and the phophorylation of TrkB (p-TrkB). We found that compared to the vehicle, MK-801 treatment impaired spatial object recognition of animals and downregulated the expression levels of p-TrkB. In experiment 2, MK-801- or vehicle-treated animals were further injected with risperidone (0.1 mg/kg) or vehicle before behavioural testing and sacrifice. Of note, we found that risperidone successfully reversed the deleterious effects of MK-801 on spatial object recognition and upregulated the hippocampal BDNF-TrkB signalling system. Collectively, the findings suggest that cognitive deficits from acute N-methyl-D-aspartate receptor blockade may be associated with the hypofunction of hippocampal BDNF-TrkB signalling system and that risperidone was able to reverse these alterations. PMID:28451387

  13. Enhanced Long-Term and Impaired Short-Term Spatial Memory in GluA1 AMPA Receptor Subunit Knockout Mice: Evidence for a Dual-Process Memory Model

    Science.gov (United States)

    Sanderson, David J.; Good, Mark A.; Skelton, Kathryn; Sprengel, Rolf; Seeburg, Peter H.; Rawlins, J. Nicholas P.; Bannerman, David M.

    2009-01-01

    The GluA1 AMPA receptor subunit is a key mediator of hippocampal synaptic plasticity and is especially important for a rapidly-induced, short-lasting form of potentiation. GluA1 gene deletion impairs hippocampus-dependent, spatial working memory, but spares hippocampus-dependent spatial reference memory. These findings may reflect the necessity of…

  14. Changes in respiratory function impairment following the treatment of severe pulmonary tuberculosis - limitations for the underlying COPD detection.

    Science.gov (United States)

    Radovic, Milan; Ristic, Lidija; Ciric, Zorica; Dinic-Radovic, Violeta; Stankovic, Ivana; Pejcic, Tatjana; Rancic, Milan; Bogdanovic, Dragan

    2016-01-01

    During the treatment phase of active pulmonary tuberculosis (PTB), respiratory function impairment is usually restrictive. This may become obstructive, as a PTB-associated airflow obstruction (AFO) or as a later manifestation of underlying COPD. The aim of the study was to examine the potential causes and risks for AFO development in PTB by exploring the aspects of spirometry limitations and clinical implications for the underlying COPD detection, taking into account various confounding factors. Prospective, nest case-control study on 40 new cases of PTB with initial restrictive respiratory function impairment, diagnosed and treated according to the directly observed treatment short course (DOTS) strategy. From all observed patients, 37.5% of them developed AFO upon the completion of PTB treatment, with significantly increased average of forced vital capacity (%) (Ppulmonary tuberculosis lesions (OR 1.01-1.05 for 95% CI; P=0.02) and sputum conversion rate on culture (OR 1.02-1.68 for 95% CI; P=0.04) as the most significant predictors for the risk of AFO development. AFO upon PTB treatment is a common manifestation of underlying COPD, which mostly occurs later, during the reparative processes in active PTB, even in the absence of major risk factors, such as cigarette smoking and biomass fuel dust exposure. Initial spirometry testing in patients with active PTB is not a sufficient and accurate approach in the detection of underlying COPD, which may lead to their further potential health deterioration.

  15. Social learning pathways in the relation between parental chronic pain and daily pain severity and functional impairment in adolescents with functional abdominal pain.

    Science.gov (United States)

    Stone, Amanda L; Bruehl, Stephen; Smith, Craig A; Garber, Judy; Walker, Lynn S

    2017-10-06

    Having a parent with chronic pain (CP) may confer greater risk for persistence of CP from childhood into young adulthood. Social learning, such as parental modeling and reinforcement, represents one plausible mechanism for the transmission of risk for CP from parents to offspring. Based on a 7-day pain diary in 154 pediatric patients with functional abdominal CP, we tested a model in which parental CP predicted adolescents' daily average CP severity and functional impairment (distal outcomes) via parental modeling of pain behaviors and parental reinforcement of adolescent's pain behaviors (mediators) and adolescents' cognitive appraisals of pain threat (proximal outcome representing adolescents' encoding of parents' behaviors). Results indicated significant indirect pathways from parental CP status to adolescent average daily pain severity (b = 0.18, SE = 0.08, 95% CI: 0.04, 0.31, p = 0.03) and functional impairment (b = 0.08, SE = 0.04, 95% CI: 0.02, 0.15, p = 0.03) over the 7-day diary period via adolescents' observations of parent pain behaviors and adolescent pain threat appraisal. The indirect pathway through parental reinforcing responses to adolescents' pain did not reach significance for either adolescent pain severity or functional impairment. Identifying mechanisms of increased risk for pain and functional impairment in children of parents with CP ultimately could lead to targeted interventions aimed at improving functioning and quality of life in families with chronic pain. Parental modeling of pain behaviors represents a potentially promising target for family based interventions to ameliorate pediatric chronic pain.

  16. Female Sprague Dawley Rats Show Impaired Spatial Memory in the 8-Arm Radial Maze under Dim Blue and Red Light

    Directory of Open Access Journals (Sweden)

    Michael Pirchl

    2010-01-01

    Full Text Available Light intensity and wavelength strongly influence mood and cognition in humans and rodent animal models. The aim of the present study was to explore if dim white (7.6–17.7 lux , blue (1.3–2.3 lux, and red light (0.8–1.4 lux affect spatial memory of male and female Sprague Dawley rats in the 8-arm radial maze. Our data show that spatial memory significantly improved within 5 daily learning sessions (each 5 trials under dim white light, which was not different between male and female rats. However, dim blue and red light significantly reduced spatial learning of female rats in the 8-arm radial maze in the last training session (session 5. In conclusion, we suggest that female Sprague Dawley rats show reduced learning under blue and red light.

  17. Severe MUPS in a sick-listed population: a cross-sectional study on prevalence, recognition, psychiatric co-morbidity and impairment

    Directory of Open Access Journals (Sweden)

    Koopmans Petra C

    2009-12-01

    Full Text Available Abstract Background Medically unexplained physical symptoms (MUPS have a high prevalence in the general population and are associated with psychiatric morbidity. There are indications that MUPS are an important determinant of frequent and long-term disability. The primary objective was to assess the prevalence of MUPS in sick-listed-employees and its associations with depressive disorders, anxiety disorders, health anxiety, distress and functional impairment. Secondary objectives were to investigate the classification of the occupational health physicians (OHPs, their opinions about the causes as well as the attributions of the employee. Methods In a cross-sectional study of 489 sick-listed employees from 5 OHP group practices, MUPS, depressive disorders, anxiety disorders, health anxiety, distress and functional impairment were assessed with the Patient Health Questionnaire (PHQ, the Whitely Index (WI, the Four- Dimensional Symptom Questionnaire (4DSQ and the Short-Form 36 Health Survey (SF-36. We used a cut off score of 15 on the PHQ for the categorisation of severe MUPS. The opinions of the OHPs were evaluated by means of a separate questionnaire with regard to the presence of employees physical symptoms, and the symptoms attributions, and the diagnoses of the OHPs. Results Severe MUPS had a prevalence of 15.1% in this population of sick-listed employees. These employees had 4-6 times more depressive and anxiety disorders, and were more impaired. Female gender and PHQ-9 scores were determinants of severe MUPS. Most of the time the OHPs diagnosed employees with severe MUPS as having a mental disorder. The employees attributed their physical symptoms in 66% to mental or to both mental and physical causes. Conclusion The prevalence of severe MUPS is higher in long-term sick-listed employees than in the non-sick- listed working population and at least equals the prevalence in the general practice population. Severe MUPS are associated with

  18. Female Sprague Dawley Rats Show Impaired Spatial Memory in the 8-Arm Radial Maze under Dim Blue and Red Light

    OpenAIRE

    Pirchl, Michael; Kemmler, Georg; Humpel, Christian

    2010-01-01

    Light intensity and wavelength strongly influence mood and cognition in humans and rodent animal models. The aim of the present study was to explore if dim white (7.6–17.7 lux) , blue (1.3–2.3 lux), and red light (0.8–1.4 lux) affect spatial memory of male and female Sprague Dawley rats in the 8-arm radial maze. Our data show that spatial memory significantly improved within 5 daily learning sessions (each 5 trials) under dim white light, which was not different between male and female rats. ...

  19. Chronic copper exposure causes spatial memory impairment, selective loss of hippocampal synaptic proteins, and activation of PKR/eIF2α pathway in mice.

    Science.gov (United States)

    Ma, Quan; Ying, Ming; Sui, Xiaojing; Zhang, Huimin; Huang, Haiyan; Yang, Linqing; Huang, Xinfeng; Zhuang, Zhixiong; Liu, Jianjun; Yang, Xifei

    2015-01-01

    Copper is an essential element for human growth and development; however, excessive intake of copper could contribute to neurotoxicity. Here we show that chronic exposure to copper in drinking water impaired spatial memory with simultaneous selective loss of hippocampal pre-synaptic protein synapsin 1, and post-synaptic density protein (PSD)-93/95 in mice. Copper exposure was shown to elevate the levels of nitrotyrosine and 8-hydroxydeoxyguanosine (8-OHdG) in hippocampus, two markers of oxidative stress. Concurrently, we also found that copper exposure activated double stranded RNA-dependent protein kinase (PKR) as evidenced by increased ratio of phosphorylated PKR at Thr451 and total PKR and increased the phosphorylation of its downstream signaling molecule eukaryotic initiation factor 2α (eIF2α) at Ser51 in hippocampus. Consistent with activation of PKR/eIF2α signaling pathway which was shown to mediate synaptic deficit and cognitive impairment, the levels of activating transcription factor 4 (ATF-4), a downstream signaling molecule of eIF2α and a repressor of CREB-mediated gene expression, were significantly increased, while the activity of cAMP response elements binding protein (CREB) was inactivated as suggested by decreased phosphorylation of CREB at Ser133 by copper exposure. In addition, the expression of the pro-apoptotic target molecule C/EBP homology protein (CHOP) of ATF-4 was upregulated and hippocampal neuronal apoptosis was induced by copper exposure. Taken together, we propose that chronic copper exposure might cause spatial memory impairment, selective loss of synaptic proteins, and neuronal apoptosis through the mechanisms involving activation of PKR/eIF2α signaling pathway.

  20. Exendin-4, a glucagon-like peptide 1 receptor agonist, protects against amyloid-β peptide-induced impairment of spatial learning and memory in rats.

    Science.gov (United States)

    Jia, Xiao-Tao; Ye-Tian; Yuan-Li; Zhang, Ge-Juan; Liu, Zhi-Qin; Di, Zheng-Li; Ying, Xiao-Ping; Fang, Yan; Song, Er-Fei; Qi, Jin-Shun; Pan, Yan-Fang

    2016-05-15

    Type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) share specific molecular mechanisms, and agents with proven efficacy in one may be useful against the other. The glucagon-like peptide-1 (GLP-1) receptor agonist exendin-4 has similar properties to GLP-1 and is currently in clinical use for T2DM treatment. Thus, this study was designed to characterize the effects of exendin-4 on the impairment of learning and memory induced by amyloid protein (Aβ) and its probable molecular underlying mechanisms. The results showed that (1) intracerebroventricular (i.c.v.) injection of Aβ1-42 resulted in a significant decline of spatial learning and memory of rats in water maze tests; (2) pretreatment with exendin-4 effectively and dose-dependently protected against the Aβ1-42-induced impairment of spatial learning and memory; (3) exendin-4 treatment significantly decreased the expression of Bax and cleaved caspase-3 and increased the expression of Bcl2 in Aβ1-42-induced Alzheimer's rats. The vision and swimming speed of the rats among all groups in the visible platform tests did not show any difference. These findings indicate that systemic pretreatment with exendin-4 can effectively prevent the behavioral impairment induced by neurotoxic Aβ1-42, and the underlying protective mechanism of exendin-4 may be involved in the Bcl2, Bax and caspase-3 pathways. Thus, the application of exendin-4 or the activation of its signaling pathways may be a promising strategy to ameliorate the degenerative processes observed in AD. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Increased low-frequency oscillation amplitude of sensorimotor cortex associated with the severity of structural impairment in cervical myelopathy.

    Directory of Open Access Journals (Sweden)

    Fuqing Zhou

    Full Text Available Decreases in metabolites and increased motor-related, but decreased sensory-related activation of the sensorimotor cortex (SMC have been observed in patients with cervical myelopathy (CM using advanced MRI techniques. However, the nature of intrinsic neuronal activity in the SMC, and the relationship between cerebral function and structural damage of the spinal cord in patients with CM are not fully understood. The purpose of this study was to assess intrinsic neuronal activity by calculating the regional amplitude of low frequency fluctuations (ALFF using resting-state functional MRI (rs-fMRI, and correlations with clinical and imaging indices. Nineteen patients and 19 age- and sex-matched healthy subjects underwent rs-fMRI scans. ALFF measurements were performed in the SMC, a key brain network likely to impaired or reorganized patients with CM. Compared with healthy subjects, increased amplitude of cortical low-frequency oscillations (LFO was observed in the right precentral gyrus, right postcentral gyrus, and left supplementary motor area. Furthermore, increased z-ALFF values in the right precentral gyrus and right postcentral gyrus correlated with decreased fractional anisotropy values at the C2 level, which indicated increased intrinsic neuronal activity in the SMC corresponding to the structural impairment in the spinal cord of patients with CM. These findings suggest a complex and diverging relationship of cortical functional reorganization and distal spinal anatomical compression in patients with CM and, thus, add important information in understanding how spinal cord integrity may be a factor in the intrinsic covariance of spontaneous low-frequency fluctuations of BOLD signals involved in cortical plasticity.

  2. The impact of severe hypoglycemia and impaired awareness of hypoglycemia on relatives of patients with type 1 diabetes

    DEFF Research Database (Denmark)

    Jørgensen, Hanne V; Pedersen-Bjergaard, Ulrik; Rasmussen, Ase K

    2003-01-01

    .01). CONCLUSIONS: Cohabitants of patients with type 1 diabetes recall significantly more episodes of severe hypoglycemia than the patients. The rate of severe hypoglycemia and state of hypoglycemic awareness are the principal determinants of degree of cohabitants' involvement in their partners' disease....

  3. Selective Spatial Working Memory Impairment in a Group of Children with Mathematics Learning Disabilities and Poor Problem-Solving Skills

    Science.gov (United States)

    Passolunghi, Maria Chiara; Mammarella, Irene Cristina

    2012-01-01

    This study examines visual and spatial working memory skills in 35 third to fifth graders with both mathematics learning disabilities (MLD) and poor problem-solving skills and 35 of their peers with typical development (TD) on tasks involving both low and high attentional control. Results revealed that children with MLD, relative to TD children,…

  4. Daily Access to Sucrose Impairs Aspects of Spatial Memory Tasks Reliant on Pattern Separation and Neural Proliferation in Rats

    Science.gov (United States)

    Reichelt, Amy C.; Morris, Margaret J.; Westbrook, Reginald Frederick

    2016-01-01

    High sugar diets reduce hippocampal neurogenesis, which is required for minimizing interference between memories, a process that involves "pattern separation." We provided rats with 2 h daily access to a sucrose solution for 28 d and assessed their performance on a spatial memory task. Sucrose consuming rats discriminated between objects…

  5. A Case of Severe Hydroxychloroquine-Induced Retinal Toxicity in a Patient with Recent Onset of Renal Impairment: A Review of the Literature on the Use of Hydroxychloroquine in Renal Impairment

    Directory of Open Access Journals (Sweden)

    Rajen Tailor

    2012-01-01

    Full Text Available We present a case of a 67-year-old female who presented with a twelve-month history of progressive blurred vision in both eyes. The patient was on hydroxychloroquine 200 mg twice a day for eight years for the treatment of scarring alopecia. Two years prior to presenting, the patient was found to have chronic kidney disease stage 3 secondary to hypertension. Examination revealed bilateral reduced visual acuities with attenuated arterioles and pigmentary changes on retinal assessment. Goldmann visual fields showed grossly constricted fields in both eyes. The patient was diagnosed with retinal toxicity secondary to hydroxychloroquine probably potentiated by renal impairment. Risk factors for retinal toxicity secondary to hydroxychloroquine can be broadly divided into dose-related and patient-related factors. Our patient developed severe retinal toxicity despite being on the recommended daily dose (400 mg per day. Although retinal toxicity at this dose has been documented, the development of renal impairment without dose adjustment or close monitoring of visual function is likely to have potentiated retinal toxicity. This case highlights the need to monitor renal function in patients on hydroxychloroquine. Should renal impairment develop, either the drug should be stopped or the dose reduced with close monitoring of visual function by an ophthalmologist.

  6. ORBIT II sub-analysis: Impact of impaired renal function following treatment of severely calcified coronary lesions with the Orbital Atherectomy System.

    Science.gov (United States)

    Lee, Michael S; Lee, Arthur C; Shlofmitz, Richard A; Martinsen, Brad J; Hargus, Nick J; Elder, Mahir D; Généreux, Philippe; Chambers, Jeffrey W

    2017-04-01

    To investigate the safety and efficacy of the coronary Orbital Atherectomy System (OAS) to prepare severely calcified lesions for stent deployment in patients grouped by renal function. Percutaneous coronary intervention (PCI) of severely calcified lesions is associated with increased rates of major adverse cardiac events (MACE), including death, myocardial infarction (MI), and target vessel revascularization (TVR) compared with PCI of non-calcified vessels. Patients with chronic kidney disease (CKD) are at increased risk for MACE after PCI. The impact of CKD on coronary orbital atherectomy treatment has not been well characterized. ORBIT II was a prospective, multicenter trial in the U.S., which enrolled 443 patients with severely calcified coronary lesions. The MACE rate was defined as a composite of cardiac death, MI, and target vessel revascularization. Of the 441 patients enrolled with known estimated glomerular filtration rate (eGFR) values at baseline, 333 (75.5%) patients had eGFR renal impairment had a higher MACE rate through one year follow-up due to a higher rate of periprocedural MI. Interestingly, the rates of cardiac death and revascularization through 1-year were similar in patients with eGFR renal impairment and severely calcified coronary lesions. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  7. Relaxin-3 inputs target hippocampal interneurons and deletion of hilar relaxin-3 receptors in "floxed-RXFP3" mice impairs spatial memory.

    Science.gov (United States)

    Haidar, M; Guèvremont, G; Zhang, C; Bathgate, R A D; Timofeeva, E; Smith, C M; Gundlach, A L

    2017-05-01

    Hippocampus is innervated by γ-aminobutyric acid (GABA) "projection" neurons of the nucleus incertus (NI), including a population expressing the neuropeptide, relaxin-3 (RLN3). In studies aimed at gaining an understanding of the role of RLN3 signaling in hippocampus via its G i/o -protein-coupled receptor, RXFP3, we examined the distribution of RLN3-immunoreactive nerve fibres and RXFP3 mRNA-positive neurons in relation to hippocampal GABA neuron populations. RLN3-positive elements were detected in close-apposition with a substantial population of somatostatin (SST)- and GABA-immunoreactive neurons, and a smaller population of parvalbumin- and calretinin-immunoreactive neurons in different hippocampal areas, consistent with the relative distribution patterns of RXFP3 mRNA and these marker transcripts. In light of the functional importance of the dentate gyrus (DG) hilus in learning and memory, and our anatomical data, we examined the possible influence of RLN3/RXFP3 signaling in this region on spatial memory. Using viral-based Cre/LoxP recombination methods and adult mice with a floxed Rxfp3 gene, we deleted Rxfp3 from DG hilar neurons and assessed spatial memory performance and affective behaviors. Following infusions of an AAV (1/2) -Cre-IRES-eGFP vector, Cre expression was observed in DG hilar neurons, including SST-positive cells, and in situ hybridization histochemistry for RXFP3 mRNA confirmed receptor depletion relative to levels in floxed-RXFP3 mice infused with an AAV (1/2) -eGFP (control) vector. RXFP3 depletion within the DG hilus impaired spatial reference memory in an appetitive T-maze task reflected by a reduced percentage of correct choices and increased time to meet criteria, relative to control. In a continuous spontaneous alternation Y-maze task, RXFP3-depleted mice made fewer alternations in the first minute, suggesting impairment of spatial working memory. However, RXFP3-depleted and control mice displayed similar locomotor activity, anxiety

  8. Nogo-A downregulation impairs place avoidance in the Carousel maze but not spatial memory in the Morris water maze

    Czech Academy of Sciences Publication Activity Database

    Petrásek, Tomáš; Prokopová, Iva; Bahník, Štěpán; Schönig, K.; Berger, S.; Valeš, Karel; Tews, B.; Schwab, M. E.; Bartsch, D.; Stuchlík, Aleš

    2014-01-01

    Roč. 107, Jan 2014 (2014), s. 42-49 ISSN 1074-7427 R&D Projects: GA ČR(CZ) GCP303/10/J032; GA ČR(CZ) GBP304/12/G069; GA MZd(CZ) NT13386; GA ČR(CZ) GA14-03627S Grant - others:Rada Programu interní podpory projektů mezinárodní spolupráce AV ČR(CZ) M200111204; Univerzita Karlova(CZ) 365911 Institutional support: RVO:67985823 Keywords : Nogo-A * spatial navigation * cognitive coordination * spatial mazes * transgenic rat model Subject RIV: FH - Neurology Impact factor: 3.652, year: 2014

  9. Spatial trends and impairment assessment of mercury in sport fish in the Sacramento-San Joaquin Delta watershed

    International Nuclear Information System (INIS)

    Melwani, A.R.; Bezalel, S.N.; Hunt, J.A.; Grenier, J.L.; Ichikawa, G.; Heim, W.; Bonnema, A.; Foe, C.; Slotton, D.G.; Davis, J.A.

    2009-01-01

    A three-year study was conducted to examine mercury in sport fish from the Sacramento-San Joaquin Delta. More than 4000 fish from 31 species were collected and analyzed for total mercury in individual muscle filets. Largemouth bass and striped bass were the most contaminated, averaging 0.40 μg/g, while redear sunfish, bluegill and rainbow trout exhibited the lowest (<0.15 μg/g) concentrations. Spatial variation in mercury was evaluated with an analysis of covariance model, which accounted for variability due to fish size and regional hydrology. Significant regional differences in mercury were apparent in size-standardized largemouth bass, with concentrations on the Cosumnes and Mokelumne rivers significantly higher than the central and western Delta. Significant prey-predator mercury correlations were also apparent, which may explain a significant proportion of the spatial variation in the watershed. - Regional differences in sport fish mercury were found in the Sacramento-San Joaquin Delta.

  10. Implantable cardioverter-defibrillators improve survival after coronary artery bypass grafting in patients with severely impaired left ventricular function

    Directory of Open Access Journals (Sweden)

    Pasque Michael K

    2007-01-01

    Full Text Available Abstract Objective Patients with severe left ventricular (LV dysfunction have a poor long term survival despite complete surgical revascularization. Recent data suggests that the use of Implantable Cardioverter-Defibrillator (ICD improves survival in patients with severe LV dysfunction. We compared the survival impact of ICD implantation in patients with severe LV dysfunction who underwent CABG. Methods Between January 1996 and August 2004, 305 patients with LV ejection fraction (EF ≤25% had CABG surgery at our institution. Demographics of patients who had received an ICD (ICD+ in the post -operative period was compared to those without ICD (ICD-. Survival was evaluated by the Kaplan-Meier method. Results Of the entire group, 35 (11.5% patients received an ICD with a median of 2 (+/-2 years after CABG. Indication for ICD implantation was clinical evidence of non sustained ventricular tachycardia (NSVT. There were no differences between the 2 groups with respect to age, gender, NYHA classification, number of bypasses, or other co-morbidities. Survival at 1, 3 and 5 years was 88%, 79%, and 67% for the ICD- group compared to 94%, 89% and 83% for the ICD+ group, respectively (figure, p Conclusion Implantation of ICD after CABG confers improved short and long term survival benefit to patients with severe LV dysfunction. Prophylactic ICD implantation in the setting of severe LV dysfunction and CABG surgery should be considered.

  11. High ethanol and acetaldehyde impair spatial memory in mouse models: opposite effects of aldehyde dehydrogenase 2 and apolipoprotein E on memory.

    Science.gov (United States)

    Jamal, Mostofa; Ameno, Kiyoshi; Miki, Takanori; Tanaka, Naoko; Ono, Junichiro; Shirakami, Gotaro; Sultana, Ruby; Yu, Nakamura; Kinoshita, Hiroshi

    2012-05-01

    Aldehyde dehydrogenase 2 deficiency may directly contribute to excess acetaldehyde (AcH) accumulation after ethanol (EtOH) drinking and AcH mediates some of the behavioral effects of EtOH. Apolipoprotein E has been suggested to be involved in the alteration of attention and memory. We have chosen Aldh2-knockout (Aldh2-KO), ApoE-KO, and their wild-type (WT) control mice to examine the effects of EtOH and AcH on spatial memory and to compare the possible relationship between genetic deficiency and memory using two behavioral assessments. Mice were trained for 4 days, with EtOH (0.5, 1.0, 2.0 g/kg) being given intraperitoneally on day 4. A probe trial was given on day 5 in the non-EtOH state in the Morris water maze (MWM). The results showed that 2.0 g/kg EtOH increased errors, indicating memory impairment on the eight-arm radial maze (RAM) for all the mice studied. One gram per kilogram EtOH impaired the performance of Aldh2-KO and ApoE-KO mice, but not WT mice. We found similar effects of EtOH on the MWM performance, with 2.0 g/kg EtOH increasing the latencies. One gram per kilogram EtOH increased the latencies of Aldh2-KO and WT mice, but not ApoE-KO mice. The 2.0 g/kg EtOH-induced memory impairment in Aldh2-KO mice was greater, suggesting an AcH effect. Furthermore, time spent on the probe trial was shorter in mice that had previously received 2.0 g/kg EtOH. ApoE-KO mice learned more slowly, while Aldh2-KO mice learned more quickly. Both the RAM and MWM results suggest that high EtOH and AcH impair spatial memory in mice, while lower doses do not have consistent memory effects. In addition, we conclude that genetic differences might underlie some of EtOH's effects on memory. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. Broad autism phenotype features of Chinese parents with autistic children and their associations with severity of social impairment in probands.

    Science.gov (United States)

    Shi, Li-Juan; Ou, Jian-Jun; Gong, Jing-Bo; Wang, Su-Hong; Zhou, Yuan-Yue; Zhu, Fu-Rong; Liu, Xu-Dong; Zhao, Jing-Ping; Luo, Xue-Rong

    2015-07-23

    Parents of children with autism have higher rates of broad autism phenotype (BAP) features than parents of typically developing children (TDC) in Western countries. This study was designed to examine the rate of BAP features in parents of children with autism and the relationship between parental BAP and the social impairment of their children in a Chinese sample. A total of 299 families with autistic children and 274 families with TDC participated in this study. Parents were assessed using the Broad Autism Phenotype Questionnaire (BAPQ), which includes self-report, informant-report, and best-estimate versions. Children were assessed using the Chinese version of the Social Responsiveness Scale (SRS). Parents of children with autism were significantly more likely to have BAP features than were parents of TDC; mothers and fathers in families with autistic children had various BAP features. The total scores of the informant and best-estimate BAPQ versions for fathers were significantly associated with their children's SRS total scores in the autism group, whereas the total scores of the three BAPQ versions for mothers were significantly associated with their children's SRS total scores in the TDC group. In the autism group, the total SRS scores of children with "BAP present" parents (informant and best-estimate) were higher than the total SRS scores of children with"BAP absent" parents. In the TDC group, the total SRS scores of children with "BAP present" parents were higher than the total SRS scores of children with"BAP absent" parents (best-estimate). Parents of autistic children were found to have higher rates of BAP than parents of TDC in a sample of Chinese parents. The BAP features of parents are associated with their children's social functioning in both autism families and TDC families, but the patterns of the associations are different.

  13. Deficits in Facial Emotion Recognition Indicate Behavioral Changes and Impaired Self-Awareness after Moderate to Severe Traumatic Brain Injury

    NARCIS (Netherlands)

    Spikman, Jacoba M.; Milders, Maarten V.; Visser-Keizer, Annemarie C.; Westerhof-Evers, Herma J.; Herben-Dekker, Meike; van der Naalt, Joukje

    2013-01-01

    Traumatic brain injury (TBI) is a leading cause of disability, specifically among younger adults. Behavioral changes are common after moderate to severe TBI and have adverse consequences for social and vocational functioning. It is hypothesized that deficits in social cognition, including facial

  14. Stimulus Over-Selectivity and Extinction-Induced Recovery of Performance as a Product of Intellectual Impairment and Autism Severity

    Science.gov (United States)

    Kelly, Michelle P.; Leader, Geraldine; Reed, Phil

    2015-01-01

    The current experiment investigated the extent to which three variables (autism severity, nonverbal intellectual functioning, and verbal intellectual functioning) are associated with over-selective responding in a group of children with Autism Spectrum Disorder. This paper also analyzed the association of these three variables with the recovery of…

  15. Orientation to time as a guide to the presence and severity of cognitive impairment in older hospital patients.

    LENUS (Irish Health Repository)

    O'Keeffe, Emma

    2011-05-01

    Testing of orientation to time is an important part of mental status examination. The validity of errors in different aspects of temporal orientation was examined in older hospital patients as a guide to the presence of dementia or delirium and as a measure of the severity of dementia, as defined by the Global Deterioration Scale.

  16. Improving Comprehension in Adolescents with Severe Receptive Language Impairments: A Randomized Control Trial of Intervention for Coordinating Conjunctions

    Science.gov (United States)

    Ebbels, Susan H.; Maric, Nataša; Murphy, Aoife; Turner, Gail

    2014-01-01

    Background: Little evidence exists for the effectiveness of therapy for children with receptive language difficulties, particularly those whose difficulties are severe and persistent. Aims: To establish the effectiveness of explicit speech and language therapy with visual support for secondary school-aged children with language impairments…

  17. Spatial discrimination deficits as a function of mnemonic interference in aged adults with and without memory impairment.

    Science.gov (United States)

    Reagh, Zachariah M; Roberts, Jared M; Ly, Maria; DiProspero, Natalie; Murray, Elizabeth; Yassa, Michael A

    2014-03-01

    It is well established that aging is associated with declines in episodic memory. In recent years, an emphasis has emerged on the development of behavioral tasks and the identification of biomarkers that are predictive of cognitive decline in healthy as well as pathological aging. Here, we describe a memory task designed to assess the accuracy of discrimination ability for the locations of objects. Object locations were initially encoded incidentally, and appeared in a single space against a 5 × 7 grid. During retrieval, subjects viewed repeated object-location pairings, displacements of 1, 2, 3, or 4 grid spaces, and maximal corner-to-opposite-corner displacements. Subjects were tasked with judging objects in this second viewing as having retained their original location, or having moved. Performance on a task such as this is thought to rely on the capacity of the individual to perform hippocampus-mediated pattern separation. We report a performance deficit associated with a physically healthy aged group compared to young adults specific to trials with low mnemonic interference. Additionally, for aged adults, performance on the task was correlated with performance on the delayed recall portion of the Rey Auditory Verbal Learning Test (RAVLT), a neuropsychological test sensitive to hippocampal dysfunction. In line with prior work, dividing the aged group into unimpaired and impaired subgroups based on RAVLT Delayed Recall scores yielded clearly distinguishable patterns of performance, with the former subgroup performing comparably to young adults, and the latter subgroup showing generally impaired memory performance even with minimal interference. This study builds on existing tasks used in the field, and contributes a novel paradigm for differentiation of healthy from possible pathological aging, and may thus provide an avenue for early detection of age-related cognitive decline. Copyright © 2013 Wiley Periodicals, Inc.

  18. Deficits in Facial Emotion Recognition Indicate Behavioral Changes and Impaired Self-Awareness after Moderate to Severe Traumatic Brain Injury

    OpenAIRE

    Spikman, Jacoba M.; Milders, Maarten V.; Visser-Keizer, Annemarie C.; Westerhof-Evers, Herma J.; Herben-Dekker, Meike; van der Naalt, Joukje

    2013-01-01

    Traumatic brain injury (TBI) is a leading cause of disability, specifically among younger adults. Behavioral changes are common after moderate to severe TBI and have adverse consequences for social and vocational functioning. It is hypothesized that deficits in social cognition, including facial affect recognition, might underlie these behavioral changes. Measurement of behavioral deficits is complicated, because the rating scales used rely on subjective judgement, often lack specificity and ...

  19. Design and technical evaluation of an enhanced location-awareness service enabler for spatial disorientation management of elderly with mild cognitive impairment.

    Science.gov (United States)

    Moreno, Pedro A; Hernando, M Elena; Gómez, Enrique J

    2015-01-01

    The progressive ageing of population has turned the mild cognitive impairment (MCI) into a prevalent disease suffered by elderly. Consequently, the spatial disorientation has become a significant problem for older people and their caregivers. The ambient-assisted living applications are offering location-based services for empowering elderly to go outside and encouraging a greater independence. Therefore, this paper describes the design and technical evaluation of a location-awareness service enabler aimed at supporting and managing probable wandering situations of a person with MCI. Through the presence capabilities of the IP multimedia subsystem (IMS) architecture, the service will alert patient's contacts if a hazardous situation is detected depending on his location. Furthermore, information about the older person's security areas has been included in the user profile managed by IMS. In doing so, the service enabler introduced contribute to "context-awareness" paradigm allowing the adaptation and personalization of services depending on user's context and specific conditions or preferences.

  20. Damage of GABAergic neurons in the medial septum impairs spatial working memory and extinction of active avoidance: effects on proactive interference.

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    Pang, Kevin C H; Jiao, Xilu; Sinha, Swamini; Beck, Kevin D; Servatius, Richard J

    2011-08-01

    The medial septum and diagonal band (MSDB) are important in spatial learning and memory. On the basis of the excitotoxic damage of GABAergic MSDB neurons, we have recently suggested a role for these neurons in controlling proactive interference. Our study sought to test this hypothesis in different behavioral procedures using a new GABAergic immunotoxin. GABA-transporter-saporin (GAT1-SAP) was administered into the MSDB of male Sprague-Dawley rats. Following surgery, rats were trained in a reference memory water maze procedure for 5 days, followed by a working memory (delayed match to position) water maze procedure. Other rats were trained in a lever-press avoidance procedure after intraseptal GAT1-SAP or sham surgery. Intraseptal GAT1-SAP extensively damaged GABAergic neurons while sparing most cholinergic MSDB neurons. Rats treated with GAT1-SAP were not impaired in acquiring a spatial reference memory, learning the location of the escape platform as rapidly as sham rats. In contrast, GAT1-SAP rats were slower than sham rats to learn the platform location in a delayed match to position procedure, in which the platform location was changed every day. Moreover, GAT1-SAP rats returned to previous platform locations more often than sham rats. In the active avoidance procedure, intraseptal GAT1-SAP impaired extinction but not acquisition of the avoidance response. Using a different neurotoxin and behavioral procedures than previous studies, the results of this study paint a similar picture that GABAergic MSDB neurons are important for controlling proactive interference. Copyright © 2010 Wiley-Liss, Inc.

  1. Abnormal social behavior, hyperactivity, impaired remote spatial memory, and increased D1-mediated dopaminergic signaling in neuronal nitric oxide synthase knockout mice

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    Tanda Koichi

    2009-06-01

    Full Text Available Abstract Background Neuronal nitric oxide synthase (nNOS is involved in the regulation of a diverse population of intracellular messenger systems in the brain. In humans, abnormal NOS/nitric oxide metabolism is suggested to contribute to the pathogenesis and pathophysiology of some neuropsychiatric disorders, such as schizophrenia and bipolar disorder. Mice with targeted disruption of the nNOS gene exhibit abnormal behaviors. Here, we subjected nNOS knockout (KO mice to a battery of behavioral tests to further investigate the role of nNOS in neuropsychiatric functions. We also examined the role of nNOS in dopamine/DARPP-32 signaling in striatal slices from nNOS KO mice and the effects of the administration of a dopamine D1 receptor agonist on behavior in nNOS KO mice. Results nNOS KO mice showed hyperlocomotor activity in a novel environment, increased social interaction in their home cage, decreased depression-related behavior, and impaired spatial memory retention. In striatal slices from nNOS KO mice, the effects of a dopamine D1 receptor agonist, SKF81297, on the phosphorylation of DARPP-32 and AMPA receptor subunit GluR1 at protein kinase A sites were enhanced. Consistent with the biochemical results, intraperitoneal injection of a low dose of SKF81297 significantly decreased prepulse inhibition in nNOS KO mice, but not in wild-type mice. Conclusion These findings indicate that nNOS KO upregulates dopamine D1 receptor signaling, and induces abnormal social behavior, hyperactivity and impaired remote spatial memory. nNOS KO mice may serve as a unique animal model of psychiatric disorders.

  2. Modulation of sphingosine 1-phosphate (S1P) attenuates spatial learning and memory impairments in the valproic acid rat model of autism.

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    Wu, Hongmei; Zhang, Quanzhi; Gao, Jingquan; Sun, Caihong; Wang, Jia; Xia, Wei; Cao, Yonggang; Hao, Yanqiu; Wu, Lijie

    2018-03-01

    Autism spectrum disorders (ASD) are a set of pervasive neurodevelopmental disorders that manifest in early childhood, and it is growing up to be a major cause of disability in children. However, the etiology and treatment of ASD are not well understood. In our previous study, we found that serum levels of sphingosine 1-phosphate (S1P) were increased significantly in children with autism, indicating that S1P levels may be involved in ASD. The objective of this study was to identify a link between increased levels of S1P and neurobehavioral changes in autism. We utilized a valproic acid (VPA) -induced rat model of autism to evaluate the levels of S1P and the expression of sphingosine kinase (SphK), a key enzyme for S1P production, in serum and hippocampal tissue. Furthermore, we assessed cognitive functional changes and histopathological and neurochemical alterations in VPA-exposed rats after SphK blockade to explore the possible link between increased levels of S1P and neurobehavioral changes in autism. We found that SphK2 and S1P are upregulated in hippocampal tissue from VPA-exposed rats, while pharmacological inhibition of SphK reduced S1P levels, attenuated spatial learning and memory impairments, increased the expression of phosphorylated CaMKII and CREB and autophagy-related proteins, inhibited cytochrome c release, decreased the expression of apoptosis related proteins, and protected against neuronal loss in the hippocampus. We have demonstrated that an increased level of SphK2/S1P is involved in the spatial learning and memory impairments of autism, and this signaling pathway represents a novel therapeutic target and direction for future studies.

  3. Impaired spatial learning strategies and novel object recognition in mice haploinsufficient for the dual specificity tyrosine-regulated kinase-1A (Dyrk1A.

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    Glòria Arqué

    Full Text Available BACKGROUND: Pathogenic aneuploidies involve the concept of dosage-sensitive genes leading to over- and underexpression phenotypes. Monosomy 21 in human leads to mental retardation and skeletal, immune and respiratory function disturbances. Most of the human condition corresponds to partial monosomies suggesting that critical haploinsufficient genes may be responsible for the phenotypes. The DYRK1A gene is localized on the human chromosome 21q22.2 region, and has been proposed to participate in monosomy 21 phenotypes. It encodes a dual-specificity kinase involved in neuronal development and in adult brain physiology, but its possible role as critical haploinsufficient gene in cognitive function has not been explored. METHODOLOGY/PRINCIPAL FINDINGS: We used mice heterozygous for a Dyrk1A targeted mutation (Dyrk1A+/- to investigate the implication of this gene in the cognitive phenotypes of monosomy 21. Performance of Dyrk1A+/- mice was assayed 1/ in a navigational task using the standard hippocampally related version of the Morris water maze, 2/ in a swimming test designed to reveal potential kinesthetic and stress-related behavioral differences between control and heterozygous mice under two levels of aversiveness (25 degrees C and 17 degrees C and 3/ in a long-term novel object recognition task, sensitive to hippocampal damage. Dyrk1A+/- mice showed impairment in the development of spatial learning strategies in a hippocampally-dependent memory task, they were impaired in their novel object recognition ability and were more sensitive to aversive conditions in the swimming test than euploid control animals. CONCLUSIONS/SIGNIFICANCE: The present results are clear examples where removal of a single gene has a profound effect on phenotype and indicate that haploinsufficiency of DYRK1A might contribute to an impairment of cognitive functions and stress coping behavior in human monosomy 21.

  4. Impact of Moderate to Severe Renal Impairment on Mortality and Appropriate Shocks in Patients with Implantable Cardioverter Defibrillators

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    Venkata M. Alla

    2010-01-01

    Full Text Available Background. Due to underrepresentation of patients with chronic kidney disease (CKD in large Implantable-Cardioverter Defibrillator (ICD clinical trials, the impact of ICD remains uncertain in this population. Methods. Consecutive patients who received ICD at Creighton university medical center between years 2000–2004 were included in a retrospective cohort after excluding those on maintenance dialysis. Based on baseline Glomerular filtration rate (GFR, patients were classified as severe CKD: GFR < 30 mL/min; moderate CKD: GFR: 30–59 mL/min; and mild or no CKD: GFR ≥ 60 mL/min. The impact of GFR on appropriate shocks and survival was assessed using Kaplan-Meier method and Generalized Linear Models (GLM with log-link function. Results. There were 509 patients with a mean follow-up of 3.0 + 1.3 years. Mortality risk was inversely proportional to the estimated GFR: 2 fold higher risk with GFR between 30–59 mL/min and 5 fold higher risk with GFR < 30 mL/min. One hundred and seventy-seven patients received appropriate shock(s; appropriate shock-free survival was lower in patients with severe CKD (GFR < 30 compared to mild or no CKD group (2.8 versus 4.2 yrs. Conclusion. Even moderate renal dysfunction increases all cause mortality in CKD patients with ICD. Severe but not moderate CKD is an independent predictor for time to first appropriate shock.

  5. Malnutrition in HIV-Infected Children Is an Indicator of Severe Disease with an Impaired Response to Antiretroviral Therapy

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    Muenchhoff, Maximilian; Healy, Michael; Singh, Ravesh

    2018-01-01

    This observational study aimed to describe immunopathogenesis and treatment outcomes in children with and without severe acute malnutrition (SAM) and HIV-infection. We studied markers of microbial translocation (16sDNA), intestinal damage (iFABP), monocyte activation (sCD14), T-cell activation (CD...... compared to HIV-uninfected children without SAM. In HIV-infected children microbial translocation, immune activation, and exhaustion was strongly increased but did not differ by SAM-status. SAM was associated with increased mortality rates early after ART initiation. Malnutrition, age, microbial...

  6. Adapted low intensity ergometer aerobic training for early and severely impaired stroke survivors: a pilot randomized controlled trial to explore its feasibility and efficacy.

    Science.gov (United States)

    Wang, Zun; Wang, Lei; Fan, Hongjuan; Jiang, Wenjun; Wang, Sheng; Gu, Zhaohua; Wang, Tong

    2014-09-01

    [Purpose] To evaluate the feasibility and efficacy of adapted low intensity ergometer aerobic training for early and severely impaired stroke survivors. [Subjects] The subjects were forty-eight early stroke survivors. [Methods] Eligible subjects were recruited and randomly assigned to an experimental group and a control group. Both groups participated in comprehensive rehabilitation training. Low intensity aerobic training was only performed by the experimental group. Outcome measures were the Fugl-Meyer motor score, Barthel index, exercise test time, peak heart rate, plasma glucose level and serum lipid profiles. [Results] Patients in the experimental group finished 88.6% of the total aerobic training sessions prescribed. In compliant participants (adherence≥80%), aerobic training significantly improved the Barthel index (from 40.1±21.1 to 79.2±14.2), Fugl-Meyer motor score (from 26.4±19.4 to 45.4±12.7), exercise test time (from 12.2±3.62 min to 13.9±3.6 min), 2-hour glucose level (from 9.22±1.16 mmol/L to 7.21±1.36 mmol/L) and homeostasis model of assessment for insulin resistence index (from 1.72±1.01 to 1.28±0.88). [Conclusion] Preliminary findings suggest that early and severely impaired stroke patients may benefit from low intensity ergometer aerobic training.

  7. Role of the speech-language pathologist: augmentative and alternative communication for acute care patients with severe communication impairments.

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    Vento-Wilson, Margaret T; McGuire, Anthony; Ostergren, Jennifer A

    2015-01-01

    Severe communication deficits occur frequently in acute care. Augmentative and alternative communication (AAC) may improve patient-nurse communication, yet it remains underutilized. The objective of this study was to assess the impact of training student nurses (SNs) in acute and critical care on the use of AAC with regard to confidence levels and likelihood of implementation of AAC by SNs in acute care. Training in AAC techniques was provided to SNs. A pretraining and posttraining assessment was completed along with follow-up surveys conducted after the SNs had an opportunity to use AAC. A 6-fold increase in confidence (P the SNs after AAC training, as was an approximately 3-fold increase in likelihood of use (P The reliable yes/no was the most reported AAC technique (34.7% of the students). Providing SNs with AAC tools accompanied by brief training increases their confidence in the use of AAC and the likelihood that they will use them. Inclusion of AAC education in nursing curricula and nursing orientations could be an important step in risk reduction among patients with severe communication disorders. Further study is needed of the relationship between training student nurses in the use of AAC as a way to change practice and improve communication outcomes.

  8. Ablation of sphingosine 1-phosphate receptor subtype 3 impairs hippocampal neuron excitability in vitro and spatial working memory in vivo

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    Daniela Weth-Malsch

    2016-11-01

    Full Text Available Understanding the role of the bioactive lipid mediator sphingosine 1-phosphate (S1P within the central nervous system has recently gained more and more attention, as it has been connected to major diseases such as multiple sclerosis and Alzheimer's disease. Even though much data about the functions of the five S1P receptors has been collected for other organ systems, we still lack a complete understanding for their specific roles, in particular within the brain. Therefore, it was the aim of this study to further elucidate the role of S1P receptor subtype 3 (S1P3 in vivo and in vitro with a special focus on the hippocampus. Using an S1P3 knock-out mouse model we applied a range of behavioral tests, performed expression studies and whole cell patch clamp recordings in acute hippocampal slices. We were able to show that S1P3 deficient mice display a significant spatial working memory deficit within the T-maze test, but not in anxiety related tests. Furthermore, S1p3 mRNA was expressed throughout the hippocampal formation. Principal neurons in area CA3 lacking S1P3 showed significantly increased interspike intervals and a significantly decreased input resistance. Upon stimulation with S1P CA3 principal neurons from both wildtype and S1P3-/- mice displayed significantly increased evoked EPSC amplitudes and decay times, whereas rise times remained unchanged. These results suggest a specific involvement of S1P3 for the establishment of spatial working memory and neuronal excitability within the hippocampus.

  9. Impaired CD163-mediated hemoglobin-scavenging and severe toxic symptoms in patients treated with gemtuzumab ozogamicin

    DEFF Research Database (Denmark)

    Maniecki, M.B.; Hasle, H.; Friis-Hansen, L.

    2008-01-01

    , and low bilirubin after septicemia-induced intravascular hemolysis indicated abrogated clearance of haptoglobin-hemoglobin complexes. This was further supported by low levels of plasma soluble CD163 and a concordant low number of CD163-expressing monocytes. We show that CD163 positive monocytes...... and macrophages from liver, spleen, and bone marrow coexpress CD33, thus suggesting that the GO-induced cellular cytotoxicity of CD33 positive cells eradicates a significant part of the CD163 positive monocytes and macrophages. The risk of severe toxic symptoms from plasma hemoglobin should be considered after CD......33-targeted chemotherapy when the disease is complicated by a pathologic intravascular hemolysis. Furthermore, the cases provide further circumstantial evidence of a key role of (CD163-expressing) monocytes/macrophages in plasma hemoglobin clearance in vivo Udgivelsesdato: 2008/8/15...

  10. Exposure to activity-based anorexia impairs contextual learning in weight-restored rats without affecting spatial learning, taste, anxiety, or dietary-fat preference.

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    Boersma, Gretha J; Treesukosol, Yada; Cordner, Zachary A; Kastelein, Anneke; Choi, Pique; Moran, Timothy H; Tamashiro, Kellie L

    2016-02-01

    Relapse rates are high amongst cases of anorexia nervosa (AN) suggesting that some alterations induced by AN may remain after weight restoration. To study the consequences of AN without confounds of environmental variability, a rodent model of activity-based anorexia (ABA) can be employed. We hypothesized that exposure to ABA during adolescence may have long-term consequences in taste function, cognition, and anxiety-like behavior after weight restoration. To test this hypothesis, we exposed adolescent female rats to ABA (1.5 h food access, combined with voluntary running wheel access) and compared their behavior to that of control rats after weight restoration was achieved. The rats were tested for learning/memory, anxiety, food preference, and taste in a set of behavioral tests performed during the light period. Our data show that ABA exposure leads to reduced performance during the novel object recognition task, a test for contextual learning, without altering performance in the novel place recognition task or the Barnes maze, both tasks that test spatial learning. Furthermore, we do not observe alterations in unconditioned lick responses to sucrose nor quinine (described by humans as "sweet" and "bitter," respectively). Nor Do we find alterations in anxiety-like behavior during an elevated plus maze or an open field test. Finally, preference for a diet high in fat is not altered. Overall, our data suggest that ABA exposure during adolescence impairs contextual learning in adulthood without altering spatial leaning, taste, anxiety, or fat preference. © 2015 Wiley Periodicals, Inc.

  11. Perinatal exposure to genistein, a soy phytoestrogen, improves spatial learning and memory but impairs passive avoidance learning and memory in offspring.

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    Kohara, Yumi; Kuwahara, Rika; Kawaguchi, Shinichiro; Jojima, Takeshi; Yamashita, Kimihiro

    2014-05-10

    This study investigated the effects of perinatal genistein (GEN) exposure on the central nervous system of rat offspring. Pregnant dams orally received GEN (1 or 10 mg/kg/day) or vehicle (1 ml/kg/day) from gestation day 10 to postnatal day 14. In order to assess the effects of GEN on rat offspring, we used a battery of behavioral tests, including the open-field, elevated plus-maze, MAZE and step-through passive avoidance tests. MAZE test is an appetite-motivation test, and we used this mainly for assessing spatial learning and memory. In the MAZE test, GEN groups exhibited shorter latency from start to goal than the vehicle-treated group in both sexes. On the other hand, performances in the step-through passive avoidance test were non-monotonically inhibited by GEN in both sexes, and a significant difference was observed in low dose of the GEN-treated group compared to the vehicle-treated group in female rats. Furthermore, we found that perinatal exposure to GEN did not significantly alter locomotor activity or emotionality as assessed by the open-field and elevated-plus maze tests. These results suggest that perinatal exposure to GEN improved spatial learning and memory of rat offspring, but impaired their passive avoidance learning and memory. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Prolonged duration of isoflurane anesthesia impairs spatial recognition memory through the activation of JNK1/2 in the hippocampus of mice.

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    Jiang, Shan; Miao, Bei; Chen, Ying

    2017-05-03

    Postoperative cognitive dysfunction is a frequent complication with surgery and anesthesia, and the underlying mechanism is unclear. Our aim was to investigate the effect of different durations of isoflurane anesthesia on spatial recognition memory and activation of JNK1/2 in the hippocampus of mice. In the present study, adult male mice were anesthetized with isoflurane for different durations (1.5% isoflurane for 1, 2, and 4 h). Spatial recognition memory was determined using spontaneous alternation and two-trial recognition memory in Y-maze at 24 h after anesthesia. The activation of JNK1/2 in the hippocampus was tested using western blot. Mice treated with isoflurane for 4 h showed significantly decreased spontaneous alternations and decreased exploration parameters compared with the no anesthesia group, but this was not observed in mice treated with isoflurane for 1 or 2 h. The protein levels of p-JNK1/2 in the hippocampus were significantly increased at 10 min after isoflurane anesthesia for 1, 2, and 4 h compared with no anesthesia. However, only isoflurane anesthesia for 4 h still increased JNK1/2 and p-JNK1/2 levels at 24 h after anesthesia. We concluded that prolonged duration of isoflurane anesthesia maintained the activation of JNK1/2, which led to memory impairment at 24 h after anesthesia.

  13. Impairment of Several Immune Functions and Redox State in Blood Cells of Alzheimer’s Disease Patients. Relevant Role of Neutrophils in Oxidative Stress

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    Carmen Vida

    2018-01-01

    Full Text Available Since aging is considered the most risk factor for sporadic Alzheimer’s Disease (AD, the age-related impairment of the immune system (immunosenescence, based on a chronic oxidative-inflammatory stress situation, could play a key role in the development and progression of AD. Although AD is accompanied by systemic disturbance, reflecting the damage in the brain, the changes in immune response and redox-state in different types of blood cells in AD patients have been scarcely studied. The aim was to analyze the variations in several immune functions and oxidative-inflammatory stress and damage parameters in both isolated peripheral neutrophils and mononuclear blood cells, as well as in whole blood cells, from patients diagnosed with mild (mAD and severe AD, and of age-matched controls (elderly healthy subjects as well as of adult controls. The cognitive decline of all subjects was determined by Mini-Mental State Examination (MMSE test (mAD stage was established at 20 ≤ MMSE ≤ 23 score; AD stage at <18 MMSE; elderly subjects >27 MMSE. The results showed an impairment of the immune functions of human peripheral blood neutrophils and mononuclear cells of mAD and AD patients in relation to healthy elderly subjects, who showed the typical immunosenescence in comparison with the adult individuals. However, several alterations were only observed in severe AD patients (lower chemotaxis, lipopolysaccharide lymphoproliferation, and interleukin (IL-10 release; higher basal proliferation, tumor necrosis factor (TNF-α release, and IL-10/TNF-α ratio, others only in mAD subjects (higher adherence, meanwhile others appeared in both mAD and AD patients (lower phytohemaglutinin lymphoproliferation and higher IL-6 release. This impairment of immune functions could be mediated by: (1 the higher oxidative stress and damage also observed in blood cells from mAD and AD patients and in isolated neutrophils [lower glutathione (GSH levels, high oxidized

  14. Prenatal exposure to maternal very severe obesity is associated with impaired neurodevelopment and executive functioning in children.

    Science.gov (United States)

    Mina, Theresia H; Lahti, Marius; Drake, Amanda J; Denison, Fiona C; Räikkönen, Katri; Norman, Jane E; Reynolds, Rebecca M

    2017-07-01

    BackgroundPrenatal maternal obesity has been associated with an increased risk of neurocognitive problems in childhood, but there are fewer studies on executive functioning.MethodsTests and questionnaires to assess neurodevelopment, executive functioning, and the ability to delay gratification were conducted in 113 children (mean (SD)=4.24 (0.63) years of age) born to mothers with very severe obesity (SO, body mass index (BMI)⩾40 kg/m 2 , n=51) or to lean mothers (BMI⩽25 kg/m 2 , n=62).ResultsPrenatal maternal SO predicted poorer neurodevelopment (unstandardized regression coefficient (B)=-0.42, 95% confidence interval (CI) (-0.82; -0.02)), worse problem-solving (odd ratio (OR)=0.60, 95% CI (1.13; 0.07)), and fine motor skills (OR=4.91, 95% CI (1.27; 19.04)), poorer executive functioning in areas of attention, inhibitory control, and working memory (standardized B=3.75, 95% CI (1.01; 13.93)) but not in self-gratification delay. The effects were independent of maternal concurrent psychological well-being and child's BMI, but not independent of maternal education.ConclusionFuture studies should investigate whether perinatal management of maternal obesity could prevent adverse outcomes in child neurodevelopment.

  15. Nephrotic range proteinuria as a strong risk factor for rapid renal function decline during pre-dialysis phase in type 2 diabetic patients with severely impaired renal function.

    Science.gov (United States)

    Kitai, Yuichiro; Doi, Yohei; Osaki, Keisuke; Sugioka, Sayaka; Koshikawa, Masao; Sugawara, Akira

    2015-12-01

    Proteinuria is an established risk factor for progression of renal disease, including diabetic nephropathy. The predictive power of proteinuria, especially nephrotic range proteinuria, for progressive renal deterioration has been well demonstrated in diabetic patients with normal to relatively preserved renal function. However, little is known about the relationship between severity of proteinuria and renal outcome in pre-dialysis diabetic patients with severely impaired renal function. 125 incident dialysis patients with type 2 diabetes were identified. This study was aimed at retrospectively evaluating the impact of nephrotic range proteinuria (urinary protein-creatinine ratio above 3.5 g/gCr) on renal function decline during the 3 months just prior to dialysis initiation. In total, 103 patients (82.4 %) had nephrotic range proteinuria. The median rate of decline in estimated glomerular filtration rate (eGFR) in this study population was 0.98 (interquartile range 0.51-1.46) ml/min/1.73 m(2) per month. Compared to patients without nephrotic range proteinuria, patients with nephrotic range proteinuria showed significantly faster renal function decline (0.46 [0.24-1.25] versus 1.07 [0.64-1.54] ml/min/1.73 m(2) per month; p = 0.007). After adjusting for gender, age, systolic blood pressure, serum albumin, calcium-phosphorus product, hemoglobin A1c, and use of an angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker, patients with nephrotic range proteinuria showed a 3.89-fold (95 % CI 1.08-14.5) increased risk for rapid renal function decline defined as a decline in eGFR ≥0.5 ml/min/1.73 m(2) per month. Nephrotic range proteinuria is the predominant renal risk factor in type 2 diabetic patients with severely impaired renal function receiving pre-dialysis care.

  16. Brief cognitive assessment of Alzheimer's disease in advanced stages: Proposal for a Brazilian version of the Short Battery for Severe Impairment (SIB-8

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    José Roberto Wajman

    Full Text Available ABSTRACT The measurement of cognitive abilities of patients with severe dementia can serve a wide range of methodological and clinical needs. Objective: To validate a proposed severe impairment battery SIB-8 for a Brazilian population sample as part of the neuropsychological assessment of patients with Alzheimer's disease (AD in advanced stages. Methods: After a systematic process of translation and back-translation, the SIB-8 was applied to 95 patients with AD at different stages; moderate, moderately severe and severe according to FAST subdivisions (5, 6 and 7, with scores on the Mini-Mental State Examination (MMSE of between 5 and 15 and followed by the Division of Behavioral Neurology and the Center for Aging Brain of the Federal University of São Paulo - UNIFESP. Results: Inferential data revealed that the SIB-8 instrument behaved differently at each stage of the disease with a statistical value of sensitivity p<0.001, gradually reflecting the expected course of the dementia, inherent with the decline of cognitive functions. Conclusion: Findings indicated that the SIB-8 is a useful tool for the evaluation and prospective comparison of AD patients in advanced stages, retaining its original characteristics in our population.

  17. Brief cognitive assessment of Alzheimer's disease in advanced stages: Proposal for a Brazilian version of the Short Battery for Severe Impairment (SIB-8).

    Science.gov (United States)

    Wajman, José Roberto; Bertolucci, Paulo Henrique Ferreira

    2013-01-01

    The measurement of cognitive abilities of patients with severe dementia can serve a wide range of methodological and clinical needs. To validate a proposed severe impairment battery SIB-8 for a Brazilian population sample as part of the neuropsychological assessment of patients with Alzheimer's disease (AD) in advanced stages. After a systematic process of translation and back-translation, the SIB-8 was applied to 95 patients with AD at different stages; moderate, moderately severe and severe according to FAST subdivisions (5, 6 and 7), with scores on the Mini-Mental State Examination (MMSE) of between 5 and 15 and followed by the Division of Behavioral Neurology and the Center for Aging Brain of the Federal University of São Paulo - UNIFESP. Inferential data revealed that the SIB-8 instrument behaved differently at each stage of the disease with a statistical value of sensitivity p<0.001, gradually reflecting the expected course of the dementia, inherent with the decline of cognitive functions. Findings indicated that the SIB-8 is a useful tool for the evaluation and prospective comparison of AD patients in advanced stages, retaining its original characteristics in our population.

  18. A survey of severe visual impairment in children attending schools for the blind in a coastal district of Andhra Pradesh in South India.

    Science.gov (United States)

    Krishnaiah, S; Subba Rao, B; Lakshmi Narasamma, K; Amit, G

    2012-08-01

    To identify the major causes of severe childhood visual impairment and blindness among students attending schools for the blind in a coastal district of Andhra Pradesh (AP) in South India. Children ≤ 16 years of age attending six schools for the blind in the study area were interviewed and examined in the year 2009, and causes were classified according to the World Health Organization Program for Prevention of Blindness (WHO/PBL) childhood blindness proforma. A total of 113 children underwent a detailed eye examination by an experienced ophthalmologist. The major causes of blindness were congenital eye anomalies in 46 children (41.4; 95% confidence interval (CI): 32.3-50.6), followed by retinal disorders in 21 children (18.9%; 95% CI: 11.6-26.2), cataract in 9 children (9.7%; 95% CI: 2.9-12.9), and corneal conditions (scar and Staphyloma) in 8 children (7.1%; 95% CI: 2.4-11.8). More than half the children (56.6%) were blind due to conditions that could have been treated or prevented. Congenital anomalies were found to be the most common cause of blindness. The majority of the cases were due to avoidable causes of blindness. Therefore, robust screening measures may help reduce the burden of visual impairment in children.

  19. Efficacy, safety and pharmacokinetics of sugammadex 4 mg kg-1 for reversal of deep neuromuscular blockade in patients with severe renal impairment.

    Science.gov (United States)

    Panhuizen, I F; Gold, S J A; Buerkle, C; Snoeck, M M J; Harper, N J N; Kaspers, M J G H; van den Heuvel, M W; Hollmann, M W

    2015-05-01

    This study evaluated efficacy and safety of sugammadex 4 mg kg(-1) for deep neuromuscular blockade (NMB) reversal in patients with severe renal impairment (creatinine clearance [CLCR] Sugammadex 4 mg kg(-1) was administered at 1-2 post-tetanic counts for reversal of rocuronium NMB. Primary efficacy variable was time from sugammadex to recovery to train-of-four (T4/T1) ratio 0.9. Equivalence between groups was demonstrated if two-sided 95% CI for difference in recovery times was within -1 to +1 min interval. Pharmacokinetics of rocuronium and overall safety were assessed. The intent-to-treat group comprised 67 patients (renal n=35; control n=32). Median (95% CI) time from sugammadex to recovery to T4/T1 ratio 0.9 was 3.1 (2.4-4.6) and 1.9 (1.6-2.8) min for renal patients vs controls. Estimated median (95% CI) difference between groups was 1.3 (0.6-2.4) min; thus equivalence bounds were not met. One control patient experienced acceleromyography-determined NMB recurrence, possibly as a result of premature sugammadex (4 mg kg(-1)) administration, with no clinical evidence of NMB recurrence observed. Rocuronium, encapsulated by Sugammadex, was detectable in plasma at day 7 in 6 patients. Bioanalytical data for sugammadex were collected but could not be used for pharmacokinetics. Sugammadex 4 mg kg(-1) provided rapid reversal of deep rocuronium-induced NMB in renal and control patients. However, considering the prolonged sugammadex-rocuronium complex exposure in patients with severe renal impairment, current safety experience is insufficient to support recommended use of sugammadex in this population. NCT00702715. © The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. The development and psychometric assessment of a questionnaire to assess sleep and daily troubles in parents of children and young adults with severe psychomotor impairment.

    Science.gov (United States)

    Tietze, Anna L; Zernikow, Boris; Otto, Michael; Hirschfeld, Gerrit; Michel, Erik; Koh, Michelle; Blankenburg, Markus

    2014-02-01

    Children with severe psychomotor impairment (SPMI) often experience sleep disturbances that severely distress both the child and his or her parents. Validated questionnaires for the assessment of parents' distress related to their child's sleep disturbances are lacking. We developed and validated a new questionnaire, the HOST (holistic assessment of sleep and daily troubles in parents of children with SPMI) to assess the effect of the sleep disturbances in children with SPMI on their parents. The questionnaire was developed based on published data and expert opinion, and it was refined via direct consultation with affected parents. Its psychometric characteristics were assessed in a sample of parents of 214 children with SPMI. It was retested using a random subsample of the participants. Explorative factor analysis revealed that the HOST was composed of four scales. Fit indices, item analysis, and convergent validity (coherence with preexisting instruments of sleep disturbances and health status) were adequate. Retest analysis (n=62) revealed high stability of the HOST questionnaire and adequate replication validity. Sleep-related difficulties significantly impact the sociomedical characteristics of the parents of children with complex neurologic diseases. Typically, parents are severely affected in various aspects of daily life (i.e., medical health, social life, professional life). The HOST proved to be a valid, reliable and economical assessment tool of sleep-related difficulties in parents and relatives of children with SPMI. The HOST is capable of identifying individuals and specific areas requiring intervention. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Impaired insulin signaling and spatial learning in middle-aged rats: The role of PTP1B.

    Science.gov (United States)

    Kuga, Gabriel Keine; Muñoz, Vitor Rosetto; Gaspar, Rafael Calais; Nakandakari, Susana Castelo Branco Ramos; da Silva, Adelino Sanchez Ramos; Botezelli, José Diego; Leme, José Alexandre Curiacos de Almeida; Gomes, Ricardo José; de Moura, Leandro Pereira; Cintra, Dennys Esper; Ropelle, Eduardo Rochete; Pauli, José Rodrigo

    2018-04-01

    The insulin and Brain-Derived Neurotrophic Factor (BDNF) signaling in the hippocampus promotes synaptic plasticity and memory formation. On the other hand, aging is related to the cognitive decline and is the main risk factor for Alzheimer's Disease (AD). The Protein-Tyrosine Phosphatase 1B (PTP1B) is related to several deleterious processes in neurons and emerges as a promising target for new therapies. In this context, our study aims to investigate the age-related changes in PTP1B content, insulin signaling, β-amyloid content, and Tau phosphorylation in the hippocampus of middle-aged rats. Young (3 months) and middle-aged (17 months) Wistar rats were submitted to Morris-water maze (MWM) test, insulin tolerance test, and molecular analysis in the hippocampus. Aging resulted in increased body weight, and insulin resistance and decreases learning process in MWM. Interestingly, the middle-aged rats have higher levels of PTP-1B, lower phosphorylation of IRS-1, Akt, GSK3β, mTOR, and TrkB. Also, the aging process increased Tau phosphorylation and β-amyloid content in the hippocampus region. In summary, this study provides new evidence that aging-related PTP1B increasing, contributing to insulin resistance and the onset of the AD. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. High-intensity stress elicits robust cortisol increases, and impairs working memory and visuo-spatial declarative memory in Special Forces candidates: A field experiment.

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    Taverniers, John; Van Ruysseveldt, Joris; Smeets, Tom; von Grumbkow, Jasper

    2010-07-01

    While running a selection procedure, 27 male Belgian Special Forces candidates, with a mean age of 27.4 years (SD = 5.1), were randomly assigned to a no-stress control (n = 14) or a high-intensity stress group (n = 13). Participants in the latter group were exposed to an extremely strenuous mock prisoner of war (POW) exercise. Immediately after stress or control treatment, working memory and visuo-spatial declarative memory performances were measured by the digit span (DS) test and the Rey-Osterrieth complex figure (ROCF), respectively. Concurrently, stress levels were assessed by obtaining salivary cortisol measurements and subjectively by the NASA Task Load Index (TLX). As expected, exposure to high-intensity stress led to both robust cortisol increases and significant differences in TLX scores. Stress induction also significantly impaired DS and ROCF performances. Moreover, delta cortisol increases and ROCF performance in the POW stress group showed a significant negative correlation, while DS performances followed the same tendency. Summarizing, the current findings complement and extend previous work on hormonal stress effects, and the subsequent performance deterioration on two memory tests in a unique high-intensity stress environment.

  3. Helicobacter pylori filtrate impairs spatial learning and memory in rats and increases β-amyloid by enhancing expression of presenilin-2

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    Xiu-Lian eWang

    2014-04-01

    Full Text Available Helicobacter pylori (H.pylori infection is related with a high risk of Alzheimer’s Disease (AD, but the intrinsic link between H.pylori infection and AD development is still missing. In the present study, we explored the effect of H.pylori infection on cognitive function and β-amyloid production in rats. We found that intraperitoneal injection of H.pylori filtrate induced spatial learning and memory deficit in rats with a simultaneous retarded dendritic spine maturation in hippocampus. Injection of H.pylori filtrate significantly increased Aβ42 both in the hippocampus and cortex, together with an increased level of presenilin-2 (PS-2, one key component of γ-secretase involved in Aβ production. Incubation of H.pylori filtrate with N2a cells which over-express APP also resulted in increased PS-2 expression and Aβ42 overproduction. Injection of Escherichia coli (E.coli filtrate, another common intestinal bacterium, had no effect on cognitive function in rats and Aβ production in rats and cells. These data suggest a specific effect of H.pylori on cognition and Aβ production. We conclude that soluble surface fractions of H.pylori may promote Aβ42 formation by enhancing the activity of γ-secretase, thus induce cognitive impairment through interrupting the synaptic function.

  4. Mice lacking Ras-GRF1 show contextual fear conditioning but not spatial memory impairments: convergent evidence from two independently generated mouse mutant lines

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    Raffaele ed'Isa

    2011-12-01

    Full Text Available Ras-GRF1 is a neuronal specific guanine exchange factor that, once activated by both ionotropic and metabotropic neurotransmitter receptors, can stimulate Ras proteins, leading to long-term phosphorylation of downstream signaling. The two available reports on the behavior of two independently generated Ras-GRF1 deficient mouse lines provide contrasting evidence on the role of Ras-GRF1 in spatial memory and contextual fear conditioning. These discrepancies may be due to the distinct alterations introduced in the mouse genome by gene targeting in the two lines that could differentially affect expression of nearby genes located in the imprinted region containing the Ras-grf1 locus. In order to determine the real contribution of Ras-GRF1 to spatial memory we compared in Morris Water Maze learning the Brambilla’s mice with a third mouse line (GENA53 in which a nonsense mutation was introduced in the Ras-GRF1 coding region without additional changes in the genome and we found that memory in this task is normal. Also, we measured both contextual and cued fear conditioning, which were previously reported to be affected in the Brambilla’s mice, and we confirmed that contextual learning but not cued conditioning is impaired in both mouse lines. In addition, we also tested both lines for the first time in conditioned place aversion in the Intellicage, an ecological and remotely controlled behavioral test, and we observed normal learning. Finally, based on previous reports of other mutant lines suggesting that Ras-GRF1 may control body weight, we also measured this non-cognitive phenotype and we confirmed that both Ras-GRF1 deficient mutants are smaller than their control littermates. In conclusion, we demonstrate that Ras-GRF1 has no unique role in spatial memory while its function in contextual fear conditioning is likely to be due not only to its involvement in amygdalar functions but possibly to some distinct hippocampal connections specific to

  5. Associations among depression severity, painful physical symptoms, and social and occupational functioning impairment in patients with major depressive disorder: a 3-month, prospective, observational study

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    Harada E

    2017-09-01

    Full Text Available Eiji Harada,1 Yoichi Satoi,2 Atsushi Kuga,1 Hirofumi Tokuoka,1 Toshiaki Kikuchi,3 Koichiro Watanabe,4 Levent Alev,1 Masaru Mimura3 1Biomedicine, Medicines Development Unit Japan, Eli Lilly Japan K.K, Kobe, Japan; 2Statistical Science, Eli Lilly Japan K.K., Kobe, Japan; 3Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan; 4Department of Neuropsychiatry, Kyorin University School of Medicine, Tokyo, Japan Purpose: To investigate associations among depression severity, painful physical symptoms (PPS, and social and occupational functioning impairment in patients with major depressive disorder (MDD who had achieved complete remission (CR or partial remission (PR after acute treatment.Patients and methods: This was a 12-week, multicenter, prospective, observational study. Patients with MDD treated with an antidepressant medication for the previous 12 weeks (±3 weeks who had achieved CR (defined as a 17-item Hamilton Rating Scale for Depression [HAM-D17] score ≤7 or PR (HAM-D17 score ≥8 and ≤8 were enrolled. Depression severity, PPS, and impairment in social and occupational functioning were assessed using the HAM-D17, the Brief Pain Inventory (Short Form (BPI-SF, and the Social and Occupational Functioning Assessment Scale (SOFAS, respectively, at enrollment (Week 12 and after 12 weeks (Week 24.Results: Overall, 323 Japanese patients with MDD were enrolled (CR n=158, PR n=165 and 288 patients completed the study (CR n=139, PR n=149. HAM-D17 and SOFAS scores were strongly and negatively correlated at enrollment (Week 12; P<0.0001 and Week 24 (P<0.0001. A weak negative correlation between the BPI-SF and SOFAS was observed at Week 24 (P=0.0011, but not at enrollment (P=0.164. Remission status at enrollment (CR or PR was associated with achieving normal social and occupational functioning (SOFAS score ≥80 at Week 24 in patients who had not achieved normal social and occupational functioning (SOFAS score <80 at

  6. Enhanced long-term and impaired short-term spatial memory in GluA1 AMPA receptor subunit knockout mice: evidence for a dual-process memory model.

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    Sanderson, David J; Good, Mark A; Skelton, Kathryn; Sprengel, Rolf; Seeburg, Peter H; Rawlins, J Nicholas P; Bannerman, David M

    2009-06-01

    The GluA1 AMPA receptor subunit is a key mediator of hippocampal synaptic plasticity and is especially important for a rapidly-induced, short-lasting form of potentiation. GluA1 gene deletion impairs hippocampus-dependent, spatial working memory, but spares hippocampus-dependent spatial reference memory. These findings may reflect the necessity of GluA1-dependent synaptic plasticity for short-term memory of recently visited places, but not for the ability to form long-term associations between a particular spatial location and an outcome. This hypothesis is in concordance with the theory that short-term and long-term memory depend on dissociable psychological processes. In this study we tested GluA1-/- mice on both short-term and long-term spatial memory using a simple novelty preference task. Mice were given a series of repeated exposures to a particular spatial location (the arm of a Y-maze) before their preference for a novel spatial location (the unvisited arm of the maze) over the familiar spatial location was assessed. GluA1-/- mice were impaired if the interval between the trials was short (1 min), but showed enhanced spatial memory if the interval between the trials was long (24 h). This enhancement was caused by the interval between the exposure trials rather than the interval prior to the test, thus demonstrating enhanced learning and not simply enhanced performance or expression of memory. This seemingly paradoxical enhancement of hippocampus-dependent spatial learning may be caused by GluA1 gene deletion reducing the detrimental effects of short-term memory on subsequent long-term learning. Thus, these results support a dual-process model of memory in which short-term and long-term memory are separate and sometimes competitive processes.

  7. Comprehensive behavioral analysis of the Cdkl5 knockout mice revealed significant enhancement in anxiety- and fear-related behaviors and impairment in both acquisition and long-term retention of spatial reference memory.

    Science.gov (United States)

    Okuda, Kosuke; Takao, Keizo; Watanabe, Aya; Miyakawa, Tsuyoshi; Mizuguchi, Masashi; Tanaka, Teruyuki

    2018-01-01

    Mutations in the Cyclin-dependent kinase-like 5 (CDKL5) gene cause severe neurodevelopmental disorders. Recently we have generated Cdkl5 KO mice by targeting exon 2 on the C57BL/6N background, and demonstrated postsynaptic overaccumulation of GluN2B-containing N-methyl-D-aspartate (NMDA) receptors in the hippocampus. In the current study, we subjected the Cdkl5 KO mice to a battery of comprehensive behavioral tests, aiming to reveal the effects of loss of CDKL5 in a whole perspective of motor, emotional, social, and cognition/memory functions, and to identify its undetermined roles. The neurological screen, rotarod, hot plate, prepulse inhibition, light/dark transition, open field, elevated plus maze, Porsolt forced swim, tail suspension, one-chamber and three-chamber social interaction, 24-h home cage monitoring, contextual and cued fear conditioning, Barnes maze, and T-maze tests were applied on adult Cdkl5 -/Y and +/Y mice. Cdkl5 -/Y mice showed a mild alteration in the gait. Analyses of emotional behaviors revealed significantly enhanced anxiety-like behaviors of Cdkl5 -/Y mice. Depressive-like behaviors and social interaction of Cdkl5 -/Y mice were uniquely altered. The contextual and cued fear conditioning of Cdkl5 -/Y mice were comparable to control mice; however, Cdkl5 -/Y mice showed a significantly increased freezing time and a significantly decreased distance traveled during the pretone period in the altered context. Both acquisition and long-term retention of spatial reference memory were significantly impaired. The morphometric analysis of hippocampal CA1 pyramidal neurons revealed impaired dendritic arborization and immature spine development in Cdkl5 -/Y mice. These results indicate that CDKL5 plays significant roles in regulating emotional behaviors especially on anxiety- and fear-related responses, and in both acquisition and long-term retention of spatial reference memory, which suggests that focus and special attention should be paid to the

  8. Comprehensive behavioral analysis of the Cdkl5 knockout mice revealed significant enhancement in anxiety- and fear-related behaviors and impairment in both acquisition and long-term retention of spatial reference memory.

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    Kosuke Okuda

    Full Text Available Mutations in the Cyclin-dependent kinase-like 5 (CDKL5 gene cause severe neurodevelopmental disorders. Recently we have generated Cdkl5 KO mice by targeting exon 2 on the C57BL/6N background, and demonstrated postsynaptic overaccumulation of GluN2B-containing N-methyl-D-aspartate (NMDA receptors in the hippocampus. In the current study, we subjected the Cdkl5 KO mice to a battery of comprehensive behavioral tests, aiming to reveal the effects of loss of CDKL5 in a whole perspective of motor, emotional, social, and cognition/memory functions, and to identify its undetermined roles. The neurological screen, rotarod, hot plate, prepulse inhibition, light/dark transition, open field, elevated plus maze, Porsolt forced swim, tail suspension, one-chamber and three-chamber social interaction, 24-h home cage monitoring, contextual and cued fear conditioning, Barnes maze, and T-maze tests were applied on adult Cdkl5 -/Y and +/Y mice. Cdkl5 -/Y mice showed a mild alteration in the gait. Analyses of emotional behaviors revealed significantly enhanced anxiety-like behaviors of Cdkl5 -/Y mice. Depressive-like behaviors and social interaction of Cdkl5 -/Y mice were uniquely altered. The contextual and cued fear conditioning of Cdkl5 -/Y mice were comparable to control mice; however, Cdkl5 -/Y mice showed a significantly increased freezing time and a significantly decreased distance traveled during the pretone period in the altered context. Both acquisition and long-term retention of spatial reference memory were significantly impaired. The morphometric analysis of hippocampal CA1 pyramidal neurons revealed impaired dendritic arborization and immature spine development in Cdkl5 -/Y mice. These results indicate that CDKL5 plays significant roles in regulating emotional behaviors especially on anxiety- and fear-related responses, and in both acquisition and long-term retention of spatial reference memory, which suggests that focus and special attention should be

  9. Comprehensive behavioral analysis of the Cdkl5 knockout mice revealed significant enhancement in anxiety- and fear-related behaviors and impairment in both acquisition and long-term retention of spatial reference memory

    Science.gov (United States)

    Okuda, Kosuke; Takao, Keizo; Watanabe, Aya; Miyakawa, Tsuyoshi; Mizuguchi, Masashi

    2018-01-01

    Mutations in the Cyclin-dependent kinase-like 5 (CDKL5) gene cause severe neurodevelopmental disorders. Recently we have generated Cdkl5 KO mice by targeting exon 2 on the C57BL/6N background, and demonstrated postsynaptic overaccumulation of GluN2B-containing N-methyl-D-aspartate (NMDA) receptors in the hippocampus. In the current study, we subjected the Cdkl5 KO mice to a battery of comprehensive behavioral tests, aiming to reveal the effects of loss of CDKL5 in a whole perspective of motor, emotional, social, and cognition/memory functions, and to identify its undetermined roles. The neurological screen, rotarod, hot plate, prepulse inhibition, light/dark transition, open field, elevated plus maze, Porsolt forced swim, tail suspension, one-chamber and three-chamber social interaction, 24-h home cage monitoring, contextual and cued fear conditioning, Barnes maze, and T-maze tests were applied on adult Cdkl5 -/Y and +/Y mice. Cdkl5 -/Y mice showed a mild alteration in the gait. Analyses of emotional behaviors revealed significantly enhanced anxiety-like behaviors of Cdkl5 -/Y mice. Depressive-like behaviors and social interaction of Cdkl5 -/Y mice were uniquely altered. The contextual and cued fear conditioning of Cdkl5 -/Y mice were comparable to control mice; however, Cdkl5 -/Y mice showed a significantly increased freezing time and a significantly decreased distance traveled during the pretone period in the altered context. Both acquisition and long-term retention of spatial reference memory were significantly impaired. The morphometric analysis of hippocampal CA1 pyramidal neurons revealed impaired dendritic arborization and immature spine development in Cdkl5 -/Y mice. These results indicate that CDKL5 plays significant roles in regulating emotional behaviors especially on anxiety- and fear-related responses, and in both acquisition and long-term retention of spatial reference memory, which suggests that focus and special attention should be paid to the

  10. [Prevalence and causes of blindness and moderate and severe visual impairment among adults aged 50 years or above in Yongchuan District of Chongqing City: the China Nine-Province survey].

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    Yin, Zheng-qin; Zhao, Jia-liang; Li, Ping-hua; Ellwein, Leon b; Song, Sheng-fang; Li, Fu-liang; Wang, Ting-gang; Ren, Yi-ming; Yang, Mei; Wang, Yu; Gao, Xue-cheng

    2013-09-01

    To investigate the prevalence and causes of blindness and moderate and severe visual impairment among adults aged 50 years or above in Yongchuan of Chongqing City, China. It was a population-based cross-section study.Geographically defined cluster sampling was used in randomly selecting 5663 individuals aged ≥ 50 years in Yongchuan District. The survey was preceded by a pilot study where operational methods were refined and quality assurance evaluation was carried out. All participants were enumerated through village registers followed door-to-door visits.Eligible individuals were invited to receive visual acuity measurement and eye examination. Prevalence of blindness and moderate and severe visual impairment was calculated according to different age, gender or education. And the reasons of blindness were analyzed.Statistical analyses were performed using Stata/SE Statistical Software, release 9.0. Chi-square test was used to investigate the association of age, gender and education with presenting and best corrected visual acuity. Five thousands six hundreds and sixty-three individuals were enumerated and 5390 persons were examined, the response rate was 95.18%. Based on the criteria of World Health Organization visual impairment classification in 1973, the prevalence of blindness and moderate and severe visual impairment defined as best corrected visual acuity was 2.12% (114/5390) and 5.40% (291/5390) respectively. The prevalence of blindness and moderate and severe visual impairment defined as presenting visual acuity was 2.49% (134/5390) and 10.71% (577/5390) respectively. The prevalence of blindness and moderate and severe visual impairment was higher in aged (trend χ(2) = 951.32, P = 0.000) , female (χ(2) = 33.35, P = 0.000) and illiterate (trend χ(2) equals; 141.32, P = 0.000) persons. Cataract was still the first leading cause of blindness and visual impairment.Un-corrected refractive error also was the main cause of visual impairment. The prevalence

  11. [Prevalence and causes of blindness and moderate and severe visual impairment among adults aged 50 years or above in Changji City of Xinjiang Uygur Autonomous Region: the China Nine-Province survey].

    Science.gov (United States)

    Ma, Xian-zhi; Zhao, Jia-liang; Ellwein, Leon B; Wei, Bin; Chen, Jing; Ye, Ying; Tang, Xiao-dong; Yang, Mei; Wang, Yu; Gao, Xue-cheng

    2013-09-01

    To investigate the prevalence and causes of blindness and moderate and severe visual impairment among adults aged ≥ 50 years in Changji City of Xinjiang Uygur Autonomous Region, China. It was a population-based cross-section study.Geographically defined cluster sampling was used in randomly selecting 5714 individuals aged ≥ 50 years in Changji City. The survey was preceded by a pilot study where operational methods were refined and quality assurance evaluation was carried out. All participants were enumerated through village registers followed door-to-door visits.Eligible individuals were invited to received visual acuity measurement and eye examination. Prevalence of blindness and moderate and severe visual impairment was calculated according to different age, gender or education. And the reasons of blindness were analyzed.Statistical analyses were performed using Stata/SE Statistical Software, release 9.0. Chi-square test was used to investigate the association of age, gender and education with presenting and best corrected visual acuity. Five thousands seven hundreds and fourteen individuals were enumerated and 5250 persons were examined, the response rate was 91.88%. Based on the criteria of World Health Organization visual impairment classification in 1973, the prevalence of blindness and moderate and severe visual impairment defined as best corrected visual acuity was 0.74% (39/5250) and 3.83% (201/5250) respectively. The prevalence of blindness and moderate and severe visual impairment defined as presenting visual acuity was 1.33% (70/5250) and 8.02% (421/5250) respectively. The prevalence of blindness and moderate and severe visual impairment was higher in aged (trend χ(2) = 617.06, P = 0.000) , illiterate (trend χ(2) = 222.35, P = 0.000) persons. Cataract and was the first leading cause of blindness and visual impairment, the retinal diseases, including age-related macular degeneration, high myopic retinopathy, and diabetic retinopathy, were the

  12. The use of Information and Communication Technology (ICT) in the rehabilitation of individuals with severe functional impairments in a municipal care service system.

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    Sandberg, Karl W; Gardelli, Asa; Stubbs, Jonathan

    2005-01-01

    This article explores the development of a scheme to use Information and Communication Technology (ICT) in the training of individuals with severe functional impairments. Computers were used as an integral part of a rehabilitation programme for training, and the authors found that the resource was a useful addition to other treatment methods. This article describes the development and subsequent setting up of computers for training and how the study progressed. The study used a somewhat unique bottom up approach that first trained care-giving staff in computer skills. The caregivers in turn worked with and trained some of those they served. This learning strategy drew upon the concept of learning, empowerment and the motivation of all involved in a system and process. The study found that by using ICT all involved felt a greater sense of empowerment and improvement in the quality of life. That caregivers were involved at all stages was valuable in that they felt an ownership of the process and that they also benefited from being involved because they also learned new skills.

  13. Selective alteration of adult hippocampal neurogenesis and impaired spatial pattern separation performance in the RSK2-deficient mouse model of Coffin-Lowry syndrome.

    Science.gov (United States)

    Castillon, Charlotte; Lunion, Steeve; Desvignes, Nathalie; Hanauer, André; Laroche, Serge; Poirier, Roseline

    2018-07-01

    Adult neurogenesis is involved in certain hippocampus-dependent cognitive functions and is linked to psychiatric diseases including intellectual disabilities. The Coffin-Lowry syndrome (CLS) is a developmental disorder caused by mutations in the Rsk2 gene and characterized by intellectual disabilities associated with growth retardation. How RSK2-deficiency leads to cognitive dysfunctions in CLS is however poorly understood. Here, using Rsk2 Knock-Out mice, we characterized the impact of RSK2 deficiency on adult hippocampal neurogenesis in vivo. We report that the absence of RSK2 does not affect basal proliferation, differentiation and survival of dentate gyrus adult-born neurons but alters the maturation progression of young immature newborn neurons. Moreover, when RSK2-deficient mice were submitted to spatial learning, in contrast to wild-type mice, proliferation of adult generated neurons was decreased and no pro-survival effect of learning was observed. Thus, learning failed to recruit a selective population of young newborn neurons in association with deficient long-term memory recall. Given the proposed role of the dentate gyrus and of adult-generated newborn neurons in hippocampal-dependent pattern separation function, we explored this function in a delayed non-matching to place task and in an object-place pattern separation task and report severe deficits in spatial pattern separation in Rsk2-KO mice. Together, this study reveals a previously unknown role for RSK2 in the early stages of maturation and learning-dependent involvement of adult-born dentate gyrus neurons. These alterations associated with a deficit in the ability of RSK2-deficient mice to finely discriminate relatively similar spatial configurations, may contribute to cognitive dysfunction in CLS. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. Palmoplantar psoriasis is associated with greater impairment of health-related quality of life compared to moderate-to-severe plaque psoriasis

    Science.gov (United States)

    Chung, Jina; Duffin, Kristina Callis; Takeshita, Junko; Shin, Daniel B.; Krueger, Gerald G.; Robertson, Andrew D.; Troxel, Andrea B.; Van Voorhees, Abby S.; Edson-Heredia, Emily; Gelfand, Joel M.

    2014-01-01

    Background The impact of palmoplantar psoriasis on health-related quality of life (QoL) is largely unknown. Objective To compare clinical characteristics and patient-reported outcomes between patients with palmoplantar psoriasis and moderate-to-severe plaque psoriasis. Methods We conducted a cross-sectional study of patients with plaque psoriasis (N=1,153) and palmoplantar psoriasis (N=66) currently receiving systemic or light treatment for psoriasis. Results Patients with palmoplantar psoriasis were more likely to report Dermatology Life Quality Index scores that correspond to at least a moderate impact on QoL (odds ratio [OR] 2.08; 95% confidence interval [CI], 1.20-3.61); problems with mobility (OR 1.98; 95% CI, 1.10-3.58), self-care (OR 3.12; 95% CI, 1.24-7.86), and usual activities (OR 2.47; 95% CI, 1.44-4.22) on the European Quality of Life-5 Dimensions questionnaire; and heavy topical prescription use of at least twice daily in the preceding week (OR 2.81; 95% CI, 1.63-4.85) than those with plaque psoriasis. Limitations Our assessment tools may not account for all dimensions of health-related QoL affected by palmoplantar disease, and these results may not be generalizable to patients with milder forms of psoriasis. Conclusion Patients with palmoplantar psoriasis suffer from greater health-related QoL impairment and are more likely to report heavy use of topical prescriptions than those with moderate-to-severe plaque psoriasis. PMID:24894455

  15. Multi-modal MRI analysis with disease-specific spatial filtering: initial testing to predict mild cognitive impairment patients who convert to Alzheimer’s disease

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    Kenichi eOishi

    2011-08-01

    Full Text Available Background: Alterations of the gray and white matter have been identified in Alzheimer’s disease (AD by structural MRI and diffusion tensor imaging (DTI. However, whether the combination of these modalities could increase the diagnostic performance is unknown.Methods: Participants included 19 AD patients, 22 amnestic mild cognitive impairment (aMCI patients, and 22 cognitively normal elderly (NC. The aMCI group was further divided into an aMCI-converter group (converted to AD dementia within three years, and an aMCI-stable group who did not convert in this time period. A T1-weighted image, a T2 map, and a DTI of each participant were normalized, and voxel-based comparisons between AD and NC groups were performed. Regions-of-interest, which defined the areas with significant differences between AD and NC, were created for each modality and named disease-specific spatial filters (DSF. Linear discriminant analysis was used to optimize the combination of multiple MRI measurements extracted by DSF to effectively differentiate AD from NC. The resultant DSF and the discriminant function were applied to the aMCI group to investigate the power to differentiate the aMCI-converters from the aMCI-stable patients. Results: The multi-modal approach with AD-specific filters led to a predictive model with an area under the receiver operating characteristic curve (AUC of 0.93, in differentiating aMCI-converters from aMCI-stable patients. This AUC was better than that of a single-contrast-based approach, such as T1-based morphometry or diffusion anisotropy analysis. Conclusion: The multi-modal approach has the potential to increase the value of MRI in predicting conversion from aMCI to AD.

  16. Postoperative pain impairs subsequent performance on a spatial memory task via effects on N-methyl-D-aspartate receptor in aged rats.

    Science.gov (United States)

    Chi, Haidong; Kawano, Takashi; Tamura, Takahiko; Iwata, Hideki; Takahashi, Yasuhiro; Eguchi, Satoru; Yamazaki, Fumimoto; Kumagai, Naoko; Yokoyama, Masataka

    2013-12-18

    Pain may be associated with postoperative cognitive dysfunction (POCD); however, this relationship remains under investigated. Therefore, we examined the impact of postoperative pain on cognitive functions in aged animals. Rats were allocated to the following groups: control (C), 1.2 % isoflurane for 2 hours alone (I), I with laparotomy (IL), IL with analgesia using local ropivacaine (IL+R), and IL with analgesia using systemic morphine (IL+M). Pain was assessed by rat grimace scale (RGS). Spatial memory was evaluated using a radial maze from postoperative days (POD) 3 to 14. NMDA receptor (NR) 2 subunits in hippocampus were measured by ELISA. Finally, effects of memantine, a low-affinity uncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, on postoperative cognitive performance were tested. Postoperative RGS was increased in Group IL, but not in other groups. The number of memory errors in Group I were comparable to that in Group C, whereas errors in Group IL were increased. Importantly, in Group IL+R and IL+M, cognitive impairment was not found. The memory errors were positively correlated with the levels of NMDA receptor 2 subunits in hippocampus. Prophylactic treatment with memantine could prevent the development of memory deficits observed in Group IL without an analgesic effect. Postoperative pain contributes to the development of memory deficits after anesthesia and surgery via up-regulation of hippocampal NMDA receptors. Our findings suggest that postoperative pain management may be important for the prevention of POCD in elderly patients. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Danshen-Chuanxiong-Honghua Ameliorates Cerebral Impairment and Improves Spatial Cognitive Deficits after Transient Focal Ischemia and Identification of Active Compounds

    Directory of Open Access Journals (Sweden)

    Xianhua Zhang

    2017-07-01

    Full Text Available Previously, we only apply a traditional Chinese medicine (TCM Danshen-Chuanxiong-Honghua (DCH for cardioprotection via anti-inflammation in rats of acute myocardial infarction by occluding coronary artery. Presently, we select not only DCH but also its main absorbed compound ferulic acid (FA for cerebra protection via similar action of mechanism above in animals of the transient middle cerebral artery occlusion (tMCAO. We investigated whether oral administration of DCH and FA could ameliorate MCAO-induced brain lesions in animals. By using liquid chromatography-tandem mass spectrometry (LC-MS/MS, we analyzed four compounds, including tanshinol, salvianolic acid B, hydroxysafflor yellow A and especially FA as the putative active components of DCH extract in the plasma, cerebrospinal fluid and injured hippocampus of rats with MCAO. In our study, it was assumed that FA played a similar neuroprotective role to DCH. We found that oral pretreatment with DCH (10 or 20 g/kg and FA (100 mg/kg improved neurological function and alleviated the infarct volume as well as brain edema in a dose-dependent manner. These changes were accompanied by improved ischemia-induced apoptosis and decreased the inflammatory response. Additionally, chronic treatment with DCH reversed MCAO-induced spatial cognitive deficits in a manner associated with enhanced neurogenesis and increased the expression of brain-derived neurotrophic factor in lesions of the hippocampus. These findings suggest that DCH has the ability to recover cognitive impairment and offer neuroprotection against cerebral ischemic injury via inhibiting microenvironmental inflammation and triggering of neurogenesis in the hippocampus. FA could be one of the potential active compounds.

  18. [Prevalence and causes of blindness and moderate and severe visual impairment among adults aged 50 years or above in Longyao County of Hebei Province:the China Nine-Province survey].

    Science.gov (United States)

    Lü, Jian-hua; Zhao, Jia-liang; Ellwein, Leon B; Li, Shan-yu; Han, Dong; Yan, Zhong-yang; Zhang, Hong-bin; Yang, Mei; Wang, Yu; Gao, Xue-cheng

    2013-09-01

    To investigate the prevalence and causes of blindness and moderate and severe visual impairment among adults aged ≥ 50 years in Longyao County, Hebei Province, China. It was a population-based cross-section study.Geographically defined cluster sampling was used in randomly selecting 5527 individuals aged ≥ 50 years in Longyao County. The survey was preceded by a pilot study where operational methods were refined and quality assurance evaluation was carried out. All participants were enumerated through village registers followed door-to-door visits.Eligible individuals were invited to receive visual acuity measurement and eye examination. Prevalence of blindness and moderate and severe visual impairment was calculated according to different age, gender or education. And the reasons of blindness were analyzed.Statistical analyses were performed using Stata/SE Statistical Software, release 9.0. Chi-square test was used to investigate the association of age, gender and education with presenting and best corrected visual acuity. Five thousands five hundreds and twenty-seven individuals were enumerated and 5051 persons were examined, the response rate was 91.39%. Based on the criteria of World Health Organization visual impairment classification in 1973, the prevalence of blindness and moderate and severe visual impairment defined as best corrected visual acuity was 1.05% (53/5051) and 3.46% (175/5051) respectively. The prevalence of blindness and moderate and severe visual impairment defined as presenting visual acuity was 1.48% (75/5051) and 7.94% (401/5051) respectively. The prevalence of blindness and moderate and severe visual impairment was higher in aged (trend χ(2) = 897.27, P = 0.000) , female (χ(2) = 30.32, P = 0.000), illiterate (trend χ(2) = 83.20, P = 0.000) persons. Cataract was still the first leading cause of blindness. Un-corrected refractive error also was the main cause of visual impairment. The prevalence of blindness and moderate and severe

  19. [Prevalence and causes of blindness and moderate and severe visual impairment among adults aged 50 years or above in Luxi County of Yunnan Province: the China Nine-Province survey].

    Science.gov (United States)

    Cai, Ning; Yuan, Yuan-sheng; Zhao, Jia-liang; Zhong, Hua; Ellwein, Leon B; Chen, Miao-miao; Dan, Ai-hua; Sun, Peng; Luo, Ting-hao; Wang, Yu; Gao, Xue-cheng

    2013-09-01

    To investigate the prevalence and causes of blindness and moderate and severe visual impairment among adults aged ≥ 50 years in Luxi County of Yunnan Province, China. It was a population-based cross-section study. Geographically defined cluster sampling was used in randomly selecting 5575 individuals aged ≥ 50 years in Luxi County. The survey was preceded by a pilot study where operational methods were refined and quality assurance evaluation was carried out. All participants were enumerated through village registers followed door-to-door visits.Eligible individuals were invited to receive visual acuity measurement and eye examination. Prevalence of blindness and moderate and severe visual impairment was calculated according to different age, gender or education. And the reasons of blindness were analyzed.Statistical analyses were performed using Stata/SE Statistical Software, release 9.0. Chi-square test was used to investigate the association of age, gender and education with presenting and best corrected visual acuity. Five thousands five hundreds and seventy-five individuals were enumerated and 5151 persons were examined, the response rate was 92.39%. Based on the criteria of World Health Organization visual impairment classification in 1973, the prevalence of blindness and moderate and severe visual impairment defined as best corrected visual acuity was 4.95% (255/5151) and 9.51% (490/5151) , respectively. The prevalence of blindness and moderate and severe visual impairment defined as presenting visual acuity was 5.40% (278/5151) and 15.84% (816/5151) , respectively. The prevalence of blindness and moderate and severe visual impairment was higher in aged (χ(2) = 1349.21, P = 0.000) , illiterate (χ(2) = 203.55, P = 0.000) persons. Cataract was still the first leading cause of blindness and visual impairment. The prevalence of blindness and moderate and severe visual impairment is highest in China Nine-Province Survey among older adults aged ≥ 50 years

  20. 20 CFR 220.184 - If the annuitant becomes disabled by another impairment(s).

    Science.gov (United States)

    2010-04-01

    ... impairment(s). 220.184 Section 220.184 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE... Activity or Medical Improvement § 220.184 If the annuitant becomes disabled by another impairment(s). If a new severe impairment(s) begins in or before the month in which the last impairment(s) ends, the Board...

  1. Retinopathy of prematurity as a major cause of severe visual impairment and blindness in children in schools for the blind in Guadalajara city, Mexico.

    Science.gov (United States)

    Zepeda-Romero, L C; Barrera-de-Leon, J C; Camacho-Choza, C; Gonzalez Bernal, C; Camarena-Garcia, E; Diaz-Alatorre, C; Gutierrez-Padilla, J A; Gilbert, C

    2011-11-01

    To determine the causes of blindness in students attending schools for the blind in Guadalajara city, Mexico and to assess the availability of screening for retinopathy of prematurity (ROP) in local neonatal intensive care units. Information on causes of blindness was obtained by interview with parents and teachers, review of records and examination. Causes of visual loss in children with a distance visual acuity of blind) were determined and classified according to the WHO's classification system for children. Of 153 children in the two participating schools, 144 were severely visual impaired or blind. Their ages ranged from 4 months to 15 years and 58% were female. ROP was the most common cause of visual loss (34.7%), followed by optic nerve lesions (17.4%) and glaucoma (14.6%). 25/59 (42.3%) children aged 0-4 years were blind from ROP compared with 6/32 (18.8%) children aged 10-15 years. 78% of children blind from ROP had psychomotor delay and less than half (46%) had not received treatment for ROP. All five privately funded neonatal intensive care units in the city regularly screen for ROP compared with only four of the 12 units in the public sector. ROP is the leading cause of blindness in children in Mexico despite national guidelines being in place. Health policies promoting primary prevention through improved neonatal care need to be implemented. Advocacy is required so that the time ophthalmologists spend screening and treating ROP is included in their job description and hence salaried.

  2. Detection of systemic inflammation in severely impaired chronic pain patients, and effects of a CBT-ACT-based multi-modal pain rehabilitation program.

    Science.gov (United States)

    Hysing, E-B; Smith, L; Thulin, M; Karlsten, R; Gordh, T

    2017-12-29

    Aims A few previous studies indicate an ongoing of low-grade systemic inflammation in chronic pain patients (CPP) [1, 2]. In the present study we investigated the plasma inflammatory profile in severely impaired chronic pain patients. In addition we studied if there were any alterations in inflammation patterns at one-year follow up, after the patients had taken part in a CBT-ACT based 4 weeks in-hospital pain rehabilitation program (PRP). Methods Blood samples were collected from 52 well characterized chronic pain patients. Plasma from matched healthy blood donors were used as controls. At one year after the treatment program, 28 of the patients were available for follow up. Instead of only analyzing single inflammation-related substances, we used a new multiplex panel enabling the simultaneous analysis of 92 inflammation-related proteins, mainly cytokines and chemokines (Proseek Inflammation, Olink, Uppsala, Sweden). Multivariate statistics were used for analysis. Results Clear signs of increased inflammatory activity were detected in the pain patients. Accepting a false discovery rate (FDR) of 5%, there were significant differences in 43 of the 92 inflammatory biomarkers. The expression of 8 biomarkers were 4 times higher in patients compared to controls. Three biomarkers, CXCL5, SIRT2, AXIN1 were more than 8 times higher. The conventional marker for inflammation, CRP, did not differ. Of the 28 patients available for follow up one year after the intervention, all showed lower levels of the inflammatory biomarker initially raised. Conclusions The results indicate that CPP suffer from a low grade of chronic systemic inflammation, not detectable by CRP analysis. This may have implications for the general pain hypersensitivity, and other symptoms, often described in this group of patients. We conclude that inflammatory plasma proteins may be measureable molecular markers to distinguishes CPP from pain free controls, and that a CBT-ACT pain rehab program seem to

  3. Impairment-oriented training or Bobath therapy for severe arm paresis after stroke: a single-blind, multicentre randomized controlled trial.

    Science.gov (United States)

    Platz, T; Eickhof, C; van Kaick, S; Engel, U; Pinkowski, C; Kalok, S; Pause, M

    2005-10-01

    To study the effects of augmented exercise therapy time for arm rehabilitation as either Bobath therapy or the impairment-oriented training (Arm BASIS training) in stroke patients with arm severe paresis. Single blind, multicentre randomized control trial. Three inpatient neurorehabilitation centres. Sixty-two anterior circulation ischaemic stroke patients. Random assignment to three group: (A) no augmented exercise therapy time, (B) augmented exercise therapy time as Bobath therapy and (C) augmented exercise therapy time as Arm BASIS training. Fugl-Meyer arm motor score. Secondary measure: Action Research Arm Test (ARA). Ancillary measures: Fugl-Meyer arm sensation and joint motion/pain scores and the Ashworth Scale (elbow flexors). An overall effect of augmented exercise therapy time on Fugl-Meyer scores after four weeks was not corroborated (mean and 95% confidence interval (CI) of change scores: no augmented exercise therapy time (n=20) 8.8, 5.2-12.3; augmented exercise therapy time (n=40) 9.9, 6.8-13.9; p = 0.2657). The group who received the augmented exercise therapy time as Arm BASIS training (n=20) had, however, higher gains than the group receiving the augmented exercise therapy time as Bobath therapy (n=20) (mean and 95% CI of change scores: Bobath 7.2, 2.6-11.8; BASIS 12.6, 8.4-16.8; p = 0.0432). Passive joint motion/pain deteriorated less in the group who received BASIS training (mean and 95% CI of change scores: Bobath -3.2, -5.2 to -1.1; BASIS 0.1, -1.8-2.0; p = 0.0090). ARA, Fugl-Meyer arm sensation, and Ashworth Scale scores were not differentially affected. The augmented exercise therapy time as Arm BASIS training enhanced selective motor control. Type of training was more relevant for recovery of motor control than therapeutic time spent.

  4. A Spatial Analysis of Land Use and Network Effects on Frequency and Severity of Cyclist-Motorist Crashes in the Copenhagen Region

    DEFF Research Database (Denmark)

    Kaplan, Sigal; Prato, Carlo Giacomo

    2015-01-01

    Objective: Urban and transport planners worldwide have recently designed and implemented policies for increasing the number of cyclists. Although cycling is on the rise even in car-oriented cities and regions, the fear of being involved in a crash is still the main obstacle to further increases...... in cycling market shares. The current study proposes the first joint model of frequency and severity of cyclist-motorist collisions with the aim of unraveling the factors contributing to both the probability of being involved in a crash and, conditional on the crash occurrence, experiencing a severe injury......, controlled for traffic exposure of nonmotorized and motorized transport modes, evaluated the effect of infrastructure and land use, and accounted for heterogeneity and spatial correlation across links.Results: Results confirmed the existence of the phenomenon of safety in numbers and added to the narrative...

  5. Fus1 KO mouse as a model of oxidative stress-mediated sporadic Alzheimer’s disease: circadian disruption and long-term spatial and olfactory memory impairments.

    Directory of Open Access Journals (Sweden)

    Guillermo Coronas-Samano

    2016-11-01

    Full Text Available Insufficient advances in the development of effective therapeutic treatments of sporadic Alzheimer's Disease (sAD to date are largely due to the lack of sAD-relevant animal models. While the vast majority of models do recapitulate AD's hallmarks of plaques and tangles by virtue of tau and/or beta amyloid overexpression, these models do not reflect the fact that in sAD (unlike familial AD these genes are not risk factors per se and that other mechanisms like oxidative stress, metabolic dysregulation and inflammation play key roles in AD etiology. Here we characterize and propose the Fus1 KO mice that lack a mitochondrial protein Fus1/Tusc2 as a new sAD model. To establish sAD relevance, we assessed sAD related deficits in Fus1 KO and WT adult mice of 4-5 months old, the equivalent human age when the earliest cognitive and olfactory sAD symptoms arise. Fus1 KO mice showed oxidative stress (increased levels of ROS, decreased levels of PRDX1, disruption of metabolic homeostasis (decreased levels of ACC2, increased phosphorylation of AMPK, autophagy (decreased levels of LC3-II, PKC (decreased levels of RACK1 and calcium signaling (decreased levels of Calb2 in the olfactory bulb and/or hippocampus. Mice were behaviorally tested using objective and accurate video tracking (Noldus, in which Fus1 KO mice showed clear deficits in olfactory memory (decreased habituation/cross-habituation in the short and long term, olfactory guided navigation memory (inability to reduce their latency to find the hidden cookie, spatial memory (learning impairments on finding the platform in the Morris water maze and showed more sleep time during the diurnal cycle. Fus1 KO mice did not show clear deficits in olfactory perception (cross-habituation, association memory (passive avoidance or in species-typical behavior (nest building and no increased anxiety (open field, light-dark box or depression/anhedonia (sucrose preference at this relatively young age. These

  6. Fus1 KO Mouse As a Model of Oxidative Stress-Mediated Sporadic Alzheimer's Disease: Circadian Disruption and Long-Term Spatial and Olfactory Memory Impairments.

    Science.gov (United States)

    Coronas-Samano, Guillermo; Baker, Keeley L; Tan, Winston J T; Ivanova, Alla V; Verhagen, Justus V

    2016-01-01

    Insufficient advances in the development of effective therapeutic treatments of sporadic Alzheimer's Disease (sAD) to date are largely due to the lack of sAD-relevant animal models. While the vast majority of models do recapitulate AD's hallmarks of plaques and tangles by virtue of tau and/or beta amyloid overexpression, these models do not reflect the fact that in sAD (unlike familial AD) these genes are not risk factors per se and that other mechanisms like oxidative stress, metabolic dysregulation and inflammation play key roles in AD etiology. Here we characterize and propose the Fus1 KO mice that lack a mitochondrial protein Fus1/Tusc2 as a new sAD model. To establish sAD relevance, we assessed sAD related deficits in Fus1 KO and WT adult mice of 4-5 months old, the equivalent human age when the earliest cognitive and olfactory sAD symptoms arise. Fus1 KO mice showed oxidative stress (increased levels of ROS, decreased levels of PRDX1), disruption of metabolic homeostasis (decreased levels of ACC2, increased phosphorylation of AMPK), autophagy (decreased levels of LC3-II), PKC (decreased levels of RACK1) and calcium signaling (decreased levels of Calb2) in the olfactory bulb and/or hippocampus. Mice were behaviorally tested using objective and accurate video tracking (Noldus), in which Fus1 KO mice showed clear deficits in olfactory memory (decreased habituation/cross-habituation in the short and long term), olfactory guided navigation memory (inability to reduce their latency to find the hidden cookie), spatial memory (learning impairments on finding the platform in the Morris water maze) and showed more sleep time during the diurnal cycle. Fus1 KO mice did not show clear deficits in olfactory perception (cross-habituation), association memory (passive avoidance) or in species-typical behavior (nest building) and no increased anxiety (open field, light-dark box) or depression/anhedonia (sucrose preference) at this relatively young age. These neurobehavioral

  7. Lumbar spine and total-body dual-energy X-ray absorptiometry in children with severe neurological impairment and intellectual disability: a pilot study of artefacts and disrupting factors

    NARCIS (Netherlands)

    Mergler, S.; Rieken, R.; Tibboel, D.; Evenhuis, H. M.; van Rijn, R. R.; Penning, C.

    2012-01-01

    Children with severe neurological impairment and intellectual disability (ID) are susceptible for developing low bone mineral density (BMD) and fractures. BMD is generally measured with dual-energy X-ray absorptiometry (DXA). To describe the occurrence of factors that may influence the feasibility

  8. The Association of Health-Related Quality of Life with Severity of Visual Impairment among People Aged 40–64 Years: Findings from the 2006–2010 Behavioral Risk Factor Surveillance System

    Science.gov (United States)

    Crews, John E.; Chou, Chiu-Fang; Zack, Matthew M.; Zhang, Xinzhi; Bullard, Kai McKeever; Morse, Alan R.; Saaddine, Jinan B.

    2016-01-01

    Purpose To examine the association of health-related quality of life (HRQoL) with severity of visual impairment among people aged 40–64 years. Methods We used cross-sectional data from the 2006–2010 Behavioral Risk Factor Surveillance System to examine six measures of HRQoL: self-reported health, physically unhealthy days, mentally unhealthy days, activity limitation days, life satisfaction, and disability. Visual impairment was categorized as no, a little, or moderate/severe. We examined the association between visual impairment and HRQoL using logistic regression accounting for the survey’s complex design. Results Overall, 23.0% of the participants reported a little difficult seeing, while 16.8% reported moderate/severe difficulty seeing. People aged 40–64 years with moderate/severe visual impairment had more frequent (≥14) physically unhealthy days, mentally unhealthy days, and activity limitation days in the last 30 days, as well as greater life dissatisfaction, greater disability, and poorer health compared to people reporting no or a little visual impairment. After controlling for covariates (age, sex, marital status, race/ethnicity, education, income, state, year, health insurance, heart disease, stroke, heart attack, body mass index, leisure-time activity, smoking, and medical care costs), and compared to people with no visual impairment, those with moderate/severe visual impairment were more likely to have fair/poor health (odds ratio, OR, 2.01, 95% confidence interval, CI, 1.82–2.23), life dissatisfaction (OR 2.06, 95% CI 1.80–2.35), disability (OR 1.95, 95% CI 1.80–2.13), and frequent physically unhealthy days (OR 1.69, 95% CI 1.52–1.88), mentally unhealthy days (OR 1.84, 95% CI 1.66–2.05), and activity limitation days (OR 1.94, 95% CI 1.71–2.20; all p visual impairment among people aged 40–64 years. PMID:27159347

  9. Malnutrition According to Mini Nutritional Assessment Is Associated With Severe Functional Impairment in Geriatric Patients Before and up to 6 Months After Hip Fracture.

    Science.gov (United States)

    Goisser, Sabine; Schrader, Eva; Singler, Katrin; Bertsch, Thomas; Gefeller, Olaf; Biber, Roland; Bail, Hermann Josef; Sieber, Cornel C; Volkert, Dorothee

    2015-08-01

    Hip fractures (HFs) in old age frequently cause severe functional impairment and deteriorating autonomy in everyday life. Many older patients with HFs are malnourished or at risk of malnutrition. In this study, we examined the relationship between nutritional status of geriatric patients before HF and their functional and clinical course up to 6 months after hospital discharge. Observational study with follow-up after 6 months. Four wards of the department of trauma and orthopedic surgery of a large urban maximum care hospital (Klinikum Nürnberg, Nuremberg, Germany). Geriatric patients aged ≥75 years with surgically repaired proximal femoral fracture. Prefracture nutritional status was determined by Mini Nutritional Assessment (MNA). Comorbidities and complications during hospital stay were obtained from medical documentation. Functional status before HF, postoperatively, at hospital discharge, and 6 months later was assessed by Barthel Index for activities of daily living (ADL) and patients' mobility level and related to MNA categories. Associations were evaluated using χ(2), Fisher exact, Kruskal-Wallis, Mann-Whitney-U, Jonckheere-Terpstra, and Cochrane-Armitage tests as appropriate, as well as analysis of covariance with repeated measures. Of 97 included patients, 17% were malnourished and 38% at risk of malnutrition before HF. Participants with (risk of) malnutrition were equally mobile but more dependent in ADL prior to HF than well-nourished patients (P patients more often suffered from remaining losses in ADL ≥25% of initial Barthel Index points (P = .033) and less often had regained their prefracture mobility level (P = .020) than well-nourished patients. Clinical course did not differ significantly between the groups with different nutritional status. In this study with geriatric HF patients from all functional and cognitive levels, worse prefracture nutritional status was associated with worse functional status and more frequent remaining

  10. Individuals with severely impaired vision can learn useful orientation and mobility skills in virtual streets and can use them to improve real street safety.

    Science.gov (United States)

    Bowman, Ellen Lambert; Liu, Lei

    2017-01-01

    -based orientation and mobility training could be as efficient as real street training in improving street safety in individuals with severely impaired vision.

  11. A combination of two truncating mutations in USH2A causes more severe and progressive hearing impairment in Usher syndrome type IIa.

    Science.gov (United States)

    Hartel, Bas P; Löfgren, Maria; Huygen, Patrick L M; Guchelaar, Iris; Lo-A-Njoe Kort, Nicole; Sadeghi, Andre M; van Wijk, Erwin; Tranebjærg, Lisbeth; Kremer, Hannie; Kimberling, William J; Cremers, Cor W R J; Möller, Claes; Pennings, Ronald J E

    2016-09-01

    Usher syndrome is an inherited disorder that is characterized by hearing impairment (HI), retinitis pigmentosa, and in some cases vestibular dysfunction. Usher syndrome type IIa is caused by mutations in USH2A. HI in these patients is highly heterogeneous and the present study evaluates the effects of different types of USH2A mutations on the audiometric phenotype. Data from two large centres of expertise on Usher Syndrome in the Netherlands and Sweden were combined in order to create a large combined sample of patients to identify possible genotype-phenotype correlations. A retrospective study on HI in 110 patients (65 Dutch and 45 Swedish) genetically diagnosed with Usher syndrome type IIa. We used methods especially designed for characterizing and testing differences in audiological phenotype between patient subgroups. These methods included Age Related Typical Audiograms (ARTA) and a method to evaluate the difference in the degree of HI developed throughout life between subgroups. Cross-sectional linear regression analysis of last-visit audiograms for the best hearing ear demonstrated a gradual decline of hearing over decades. The congenital level of HI was in the range of 16-33 dB at 0.25-0.5 kHz, and in the range of 51-60 dB at 1-8 kHz. The annual threshold deterioration was in the range of 0.4-0.5 dB/year at 0.25-2 kHz and in the range of 0.7-0.8 dB/year at 4-8 kHz. Patients with two truncating mutations, including homozygotes for the common c.2299delG mutation, developed significantly more severe HI throughout life than patients with one truncating mutation combined with one nontruncating mutation, and patients with two nontruncating mutations. The results have direct implications for patient counselling in terms of prognosis of hearing and may serve as baseline measures for future (genetic) therapeutic interventions. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. γ-aminobutyric acidA (GABAA) receptor regulates ERK1/2 phosphorylation in rat hippocampus in high doses of Methyl Tert-Butyl Ether (MTBE)-induced impairment of spatial memory

    International Nuclear Information System (INIS)

    Zheng Gang; Zhang Wenbin; Zhang Yun; Chen Yaoming; Liu Mingchao; Yao Ting; Yang Yanxia; Zhao Fang; Li Jingxia; Huang Chuanshu; Luo Wenjing; Chen Jingyuan

    2009-01-01

    Experimental and occupational exposure to Methyl Tert-Butyl Ether (MTBE) has been reported to induce neurotoxicological and neurobehavioral effects, such as headache, nausea, dizziness, and disorientation, etc. However, the molecular mechanisms involved in MTBE-induced neurotoxicity are still not well understood. In the present study, we investigated the effects of MTBE on spatial memory and the expression and function of GABA A receptor in the hippocampus. Our results demonstrated that intraventricular injection of MTBE impaired the performance of the rats in a Morris water maze task, and significantly increased the expression of GABA A receptor α1 subunit in the hippocampus. The phosphorylation of ERK1/2 decreased after the MTBE injection. Furthermore, the decreased ability of learning and the reduction of phosphorylated ERK1/2 level of the MTBE-treated rats was partly reversed by bicuculline injected 30 min before the training. These results suggested that MTBE exposure could result in impaired spatial memory. GABA A receptor may play an important role in the MTBE-induced impairment of learning and memory by regulating the phosphorylation of ERK in the hippocampus.

  13. Magnitude and Causes of Low Vision Disability (Moderate and Severe Visual Impairment) among Students of Al-Noor Institute for the Blind in Al-Hassa, Saudi Arabia: A case series.

    Science.gov (United States)

    Al-Wadani, Fahad; Khandekar, Rajiv; Al-Hussain, Muneera A; Alkhawaja, Ahmed A; Khan, Mohammed Sarfaraz; Alsulaiman, Ramzy A

    2012-02-01

    This study aimed to estimate the magnitude and causes of low vision disability (severe visual impairment [SVI] and moderate visual impairment [MVI]) among students at Al-Noor Institute for the Blind (NIB) in Al-Hassa, Saudi Arabia in 2006. An optometrist conducted refraction of 122 eyes of the 61 students (27 boys and 34 girls) with MVI (vision visual acuity was ≥6/18 and in 28 (23%) eyes, it was visual impairment in 16 (13.1%) and 9 (7.4%) eyes. These students were prescribed optical and non-optical low vision aids. Retinal disease was the main cause of SVI and MVI in our series. Some students at Al-Noor Institute for the Blind have curable low vision conditions. Rehabilitation of low vision disability should be different from that offered to the absolutely blind.

  14. Slow information processing after very severe closed head injury : impaired access to declarative knowledge and intact application and acquisition of procedural knowledge

    NARCIS (Netherlands)

    Timmerman, ME; Brouwer, WH

    As an explanation of the pattern of slow information processing after closed head injury (CHI), hypotheses of impaired access to declarative memory and intact application and acquisition of procedural memory after CHI are presented. These two hypotheses were tested by means of four cognitive

  15. A combination of two truncating mutations in USH2A causes more severe and progressive hearing impairment in Usher syndrome type IIa

    NARCIS (Netherlands)

    Hartel, B.P.; Lofgren, M.; Huygen, P.L.; Guchelaar, I.; Lo, A.N.K.N.; Sadeghi, A.M.; van Wijk, E.; Tranebjaerg, L.; Kremer, H.; Kimberling, W.J.; Cremers, C.W.R.J.; Moller, C.; Pennings, R.J.

    2016-01-01

    OBJECTIVES: Usher syndrome is an inherited disorder that is characterized by hearing impairment (HI), retinitis pigmentosa, and in some cases vestibular dysfunction. Usher syndrome type IIa is caused by mutations in USH2A. HI in these patients is highly heterogeneous and the present study evaluates

  16. Monkey Management: Using Spatial Ecology to Understand the Extent and Severity of Human-Baboon Conflict in the Cape Peninsula, South Africa

    Directory of Open Access Journals (Sweden)

    Tali S. Hoffman

    2012-09-01

    Full Text Available Conflict with humans poses one of the greatest threats to the persistence and survival of all wildlife. In the Cape Peninsula, South Africa, human-baboon conflict levels remain high despite substantial investment by conservation authorities in a variety of mitigation measures. Here we explore how spatial ecology can inform wildlife managers on the extent and severity of both current and projected human-baboon conflict. We apply conservative and generous densities - 2.3 and 5.9 baboons/km2 - to hypothetical landscape management scenarios to estimate whether the chacma baboon (Papio ursinus population in the Cape Peninsula is currently overabundant. We correlate conflict indices with spatial variables to explain intertroop differences in conflict levels. We investigate how an understanding of key elements of baboon ecology, including sleeping-site characteristics and intertroop territoriality, can direct management efforts and mitigate conflict. Our findings suggest that the current population of 475 baboons i