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Sample records for activity impairment questionnaire

  1. The Dutch patients' perspective on oculopharyngeal muscular dystrophy: A questionnaire study on fatigue, pain and impairments.

    PubMed

    van der Sluijs, Barbara M; Knoop, Hans; Bleijenberg, Gijs; van Engelen, Baziel G M; Voermans, Nicol C

    2016-03-01

    Research on oculopharyngeal muscular dystrophy focuses mainly on genetic and pathophysiological aspects. Clinically, oculopharyngeal muscular dystrophy is often considered as a disease with a relatively mild initial disease course with no or only mild functional disabilities. However the occurrence of fatigue, pain and functional impairments other than dysphagia has never been studied systematically. The aim of this study is therefore to assess the prevalence of fatigue, pain, and functional limitations, and the social participation and psychological well-being of oculopharyngeal muscular dystrophy patients. We performed a questionnaire study on fatigue, pain, functional impairments, social participation and psychological distress in 35 genetically confirmed oculopharyngeal muscular dystrophy patients with an average disease duration of 11.6 years. We showed that 19 (54%) of the patients experienced severe fatigue and also 19 (54%) experienced pain. Limitations in daily life activities and social participation were detected in 33 (94%) of the patients. Many patients reported pelvic girdle weakness and limitations in ambulation. Fatigue severity was related to functional impairments, while pain and disease duration were not. Psychological distress was not different from healthy adults. In conclusion, fatigue and pain are present among approximately half of the patients, and almost all patients are impaired in daily life activities, social participation and ambulation. These data should be taken into account in symptomatic management of oculopharyngeal muscular dystrophy.

  2. Validation of the Walking Impairment Questionnaire for Spanish patients.

    PubMed

    Lozano, Francisco S; March, José R; González-Porras, José R; Carrasco, Eduardo; Lobos, José M; Areitio-Aurtena, Alix

    2013-09-01

    Hintergrund: Der Walking Impairment Questionaire (WIQ) ist ein kurzer, einfach auszufüllender, krankheitsspezifischer Fragebogen zur Beurteilung des intermittierenden Hinkens. Eine spanische Version des WIQ wurde kürzlich in Texas für spanisch sprechende Amerikaner validiert, aber es sollte auch eine Validierung für spanisch sprechende Europäer geben. Patienten und Methoden: Nach der kulturellen Anpassung des WIQ füllten 920 Patienten mit Claudicatio intermittens(ankle brachial index < 0.9) zwei Fragenbögen aus (spanische Version des WIQ und European Quality of Life 5 Dimenions [EQ-5D]). Die Validierung wurde bestimmt durch den Vergleich des WIQ mit dem EQ-5D. Die Reliabilität und interne Übereinstimmung wurden mit dem Intra-class Korrelationskoeffizienten (ICC) und Cronbach‘s alpha gemessen. Ergebnisse: Die drei Domänen des WIQ korrelierten sehr stark mit dem EQ-5D Gesundheitsergebnis (p < 0.001). Test-Retest-Reliabilität (ICC = 096) und interne Konsistenz (Cronbach‘s alpha = 0.92) waren hervorragend. Schlussfolgerungen: Die spanische Version des WIQ für spanisch sprechende Europäer war valide und reproduzierbar. Sie kann für spanisch sprechende Europäer mit Claudicatio intermittens benutzt werden.

  3. AD8 Informant Questionnaire for Cognitive Impairment: Pragmatic Diagnostic Test Accuracy Study.

    PubMed

    Larner, A J

    2015-09-01

    The diagnostic accuracy of the AD8 informant questionnaire for cognitive impairment was assessed in patients referred to a dedicated memory clinic. This pragmatic prospective study of consecutive referrals attending with an informant who completed AD8 (n = 212) lasted 12 months. Diagnosis used standard clinical diagnostic criteria for dementia and mild cognitive impairment as reference standard (prevalence of cognitive impairment = 0.62). The AD8 proved acceptable to informants, was quick, and easy to use. Using the cutoff of ≥2/8, AD8 was highly sensitive (0.97) for diagnosis of cognitive impairment but specificity was poor (0.17). Combining AD8 with either the Mini-Mental State Examination or the Six-Item Cognitive Impairment Test showed little additional diagnostic benefit. In conclusion, AD8 is very sensitive for cognitive impairment in a memory clinic but specificity may be inadequate.

  4. Development of the multiple sclerosis (MS) early mobility impairment questionnaire (EMIQ).

    PubMed

    Ziemssen, Tjalf; Phillips, Glenn; Shah, Ruchit; Mathias, Adam; Foley, Catherine; Coon, Cheryl; Sen, Rohini; Lee, Andrew; Agarwal, Sonalee

    2016-10-01

    The Early Mobility Impairment Questionnaire (EMIQ) was developed to facilitate early identification of mobility impairments in multiple sclerosis (MS) patients. We describe the initial development of the EMIQ with a focus on the psychometric evaluation of the questionnaire using classical and item response theory methods. The initial 20-item EMIQ was constructed by clinical specialists and qualitatively tested among people with MS and physicians via cognitive interviews. Data from an observational study was used to make additional updates to the instrument based on exploratory factor analysis (EFA) and item response theory (IRT) analysis, and psychometric analyses were performed to evaluate the reliability and validity of the final instrument's scores and screening properties (i.e., sensitivity and specificity). Based on qualitative interview analyses, a revised 15-item EMIQ was included in the observational study. EFA, IRT and item-to-item correlation analyses revealed redundant items which were removed leading to the final nine-item EMIQ. The nine-item EMIQ performed well with respect to: test-retest reliability (ICC = 0.858); internal consistency (α = 0.893); convergent validity; and known-groups methods for construct validity. A cut-point of 41 on the 0-to-100 scale resulted in sufficient sensitivity and specificity statistics for viably identifying patients with mobility impairment. The EMIQ is a content valid and psychometrically sound instrument for capturing MS patients' experience with mobility impairments in a clinical practice setting. Additional research is suggested to further confirm the EMIQ's screening properties over time.

  5. Preliminary reliability of the five item physical activity questionnaire

    PubMed Central

    Cho, Min-Haeng

    2016-01-01

    [Purpose] The purpose of this study was to design a physical activity questionnaire reflecting on the basic principles and recommendations of exercise and to examine its reliability. [Subjects and Methods] 342 males and 374 females from the community centers (senior center, residential culture center, sport center, and YWCA center) participated in this study. [Results] The test-retest reliability of the physical activity questionnaire, measured with an interval of three months, being between 0.61 and 0.91 signifies that the questionnaire was useful instrument for assessing physical activity levels. [Conclusion] This study found that the simple physical activity questionnaire containing the frequency, duration, intensity, overall length, and type of activities that the person performed during their leisure time was reliable. PMID:28174459

  6. Preliminary reliability of the five item physical activity questionnaire.

    PubMed

    Cho, Min-Haeng

    2016-12-01

    [Purpose] The purpose of this study was to design a physical activity questionnaire reflecting on the basic principles and recommendations of exercise and to examine its reliability. [Subjects and Methods] 342 males and 374 females from the community centers (senior center, residential culture center, sport center, and YWCA center) participated in this study. [Results] The test-retest reliability of the physical activity questionnaire, measured with an interval of three months, being between 0.61 and 0.91 signifies that the questionnaire was useful instrument for assessing physical activity levels. [Conclusion] This study found that the simple physical activity questionnaire containing the frequency, duration, intensity, overall length, and type of activities that the person performed during their leisure time was reliable.

  7. Development and Initial Testing of the Penn Parkinson's Daily Activities Questionnaire

    PubMed Central

    Brennan, Laura; Siderowf, Andrew; Rubright, Jonathan D.; Rick, Jacqueline; Dahodwala, Nabila; Duda, John E.; Hurtig, Howard; Stern, Matthew; Xie, Sharon X.; Rennert, Lior; Karlawish, Jason; Shea, Judy A.; Trojanowski, John Q.; Weintraub, Daniel

    2015-01-01

    Objective The aim of this work was to describe the development and psychometric analysis of the Penn Parkinson's Daily Activities Questionnaire. The questionnaire is an item response theory-based tool for rating cognitive instrumental activities of daily living in PD. Methods Candidate items for the Penn Parkinson's Daily Activities Questionnaire were developed through literature review and focus groups of patients and knowledgeable informants. Item selection and calibration of item-response theory parameters were performed using responses from a cohort of PD patients and knowledgeable informants (n = 388). In independent cohorts of PD patients and knowledgeable informants, assessments of test-retest reliability (n = 50), and construct validity (n = 68) of the questionnaire were subsequently performed. Construct validity was assessed by correlating questionnaire scores with measures of motor function, cognition, an existing activities of daily living measure, and directly observed daily function. Results Fifty items were retained in the final questionnaire item bank. Items were excluded owing to redundancy, difficult reading level, and when item-response theory parameters could not be calculated. Test-retest reliability was high (intraclass correlation coefficient = 0.97; P < 0.001). The questionnaire correlated strongly with cognition (r = 0.68; P < 0.001) and directly observed daily function (r = 0.87; P < 0.001), but not with motor impairment (r = 0.08; P = 0.53). The questionnaire score accurately discriminated between PD patients with and without dementia (receiver operating characteristic curve = 0.91; 95% confidence interval: 0.85–0.97). Conclusions The Penn Parkinson's Daily Activities Questionnaire shows strong evidence of reliability and validity. Item response theory-based psychometric analysis suggests that this questionnaire can discriminate across a range of daily functions. PMID:26249849

  8. Adaptation and validation of the Spanish version of the Clinical Impairment Assessment Questionnaire.

    PubMed

    Martín, Josune; Padierna, Angel; Unzurrunzaga, Anette; González, Nerea; Berjano, Belén; Quintana, José M

    2015-08-01

    The Clinical Impairment Assessment (CIA) assesses psychosocial impairment secondary to an eating disorder. The aim of this study was to create and validate a Spanish-language version of the CIA. Using a forward-backward translation methodology, we translated the CIA into Spanish and evaluated its psychometric characteristics in a clinical sample of 178 ED patients. Cronbach's alpha values, confirmatory factor analysis (CFA), and correlations between the CIA and the Eating Attitudes Test-12 and the Health-Related Quality of Life in ED-short form questionnaires evaluated the reliability, construct validity, and convergent validity, respectively. Known-groups validity was also studied comparing the CIA according to different groups; responsiveness was assessed by means of effect sizes. Data revealed a three-factor structure similar to that of the original CIA. Cronbach alpha coefficient of 0.91 for the total CIA score supported its internal consistency and correlations with other instruments demonstrated convergent validity. The total CIA score and factor scores also significantly discriminated between employment status, evidencing known-groups validity. Responsiveness parameters showed moderate changes for patients with restrictive eating disorders. These findings suggest that the CIA can be reliably and validly used in Spain in a number of different clinical contexts, by researchers and clinicians alike.

  9. Translation and validation of a Chinese version of the Mandibular Function Impairment Questionnaire.

    PubMed

    Xu, L; Cai, B; Fang, Z

    2016-08-01

    To adapt the English version of the Mandibular Function Impairment Questionnaire (MFIQ) for Chinese-speaking patients with temporomandibular disorder (TMD) and to evaluate its validity and reliability. In total, 352 patients diagnosed with TMD according to the research diagnostic criteria for TMD (RDC/TMD) Axis I were included in this study. The psychometric evaluation included reliability, which was evaluated by internal consistency (Cronbach's alpha coefficient), and test-retest reliability and validity, which were tested by content and construct validity. Because the content validity of item 11 (kissing) was low (0·12), this item was excluded in subsequent analyses. For exploratory factor analysis, three factors were extracted, accounting for 63·6% of the variance. All items had factor loadings above 0·4. Two models were tested by confirmatory factor analysis, and the two-factor model was adopted (χ(2) /df = 2·279, root mean square error of approximation (RMSEA) = 0·086, comparative fit index (CFI) = 0·910). Internal reliability (coefficient alpha values of 0·925 and 0·720 for each factor) and test-retest reliability (ICCfactor1 = 0·895, 95% CIfactor1 = 0·869-0·918, ICCfactor2 = 0·720, 95% CIfactor2 = 0·645-0·783) of the Chinese MFIQ were excellent. A reliable and valid Chinese version of the MFIQ was constructed for the evaluation of Chinese patients with TMD after some modification of the English version of the MFIQ.

  10. An enhanced functional ability questionnaire (faVIQ) to measure the impact of rehabilitation services on the visually impaired

    PubMed Central

    Wolffsohn, James Stuart; Jackson, Jonathan; Hunt, Olivia Anne; Cottriall, Charles; Lindsay, Jennifer; Gilmour, Richard; Sinclair, Anne; Harper, Robert

    2014-01-01

    AIM To develop a short, enhanced functional ability Quality of Vision (faVIQ) instrument based on previous questionnaires employing comprehensive modern statistical techniques to ensure the use of an appropriate response scale, items and scoring of the visual related difficulties experienced by patients with visual impairment. METHODS Items in current quality-of-life questionnaires for the visually impaired were refined by a multi-professional group and visually impaired focus groups. The resulting 76 items were completed by 293 visually impaired patients with stable vision on two occasions separated by a month. The faVIQ scores of 75 patients with no ocular pathology were compared to 75 age and gender matched patients with visual impairment. RESULTS Rasch analysis reduced the faVIQ items to 27. Correlation to standard visual metrics was moderate (r=0.32-0.46) and to the NEI-VFQ was 0.48. The faVIQ was able to clearly discriminate between age and gender matched populations with no ocular pathology and visual impairment with an index of 0.983 and 95% sensitivity and 95% specificity using a cut off of 29. CONCLUSION The faVIQ allows sensitive assessment of quality-of-life in the visually impaired and should support studies which evaluate the effectiveness of low vision rehabilitation services. PMID:24634868

  11. Validity and Reliability of the School Physical Activity Environment Questionnaire

    ERIC Educational Resources Information Center

    Martin, Jeffrey J.; McCaughtry, Nate; Flory, Sara; Murphy, Anne; Wisdom, Kimberlydawn

    2011-01-01

    The goal of the current study was to establish the factor validity of the Questionnaire Assessing School Physical Activity Environment (Robertson-Wilson, Levesque, & Holden, 2007) using confirmatory factor analysis procedures. Another goal was to establish internal reliability and test-retest reliability. The confirmatory factor analysis…

  12. Validation of a questionnaire for assessing fecal impaction in the elderly: impact of cognitive impairment, and using a proxy

    PubMed Central

    2013-01-01

    Background Studies on the epidemiology of fecal impaction are limited by the absence of a valid and reliable instrument to identify the condition in the elderly. Our aim is to validate a questionnaire for identifying fecal impaction in the elderly and to assess the impact of cognitive impairment and the aid of a proxy on its reliability. Methods We developed a 5 questions’ questionnaire. The questionnaire was presented to twenty doctors to test its face validity. Feasibility was pre-tested with ten non institutionalized subjects who completed the questionnaire twice, once alone or with the help of a proxy, and another along with the researcher. For the validation of the questionnaire all residents in a single nursing-home were invited to participate, allowing the self-decision of using a proxy. Medical records of all subjects were abstracted without knowledge of subjects’ answers and agreement between fecal impaction according to self-reported and medical records analyzed. Physical impairment was measured with the Barthel’s test and cognitive impairment with the mini-mental test. Results In the face validity only minor changes in wording were suggested. In the feasibility pre-test all subjects were able to understand and complete the questionnaire and all questions were considered appropriate and easily understandable. One-hundred and ninety-nine of the 244 residents participated in the study (mean age 86,1 ± 6,6). One hundred and forty two subjects understood all questions; not understanding them was inversely associated with cognitive impairment score (aOR: 0.86; 95% CI: 0.82-0.91). One hundred and sixty decided to use a proxy; the use of a proxy was inversely associated with educative level (0.13 (0.02-0.72), minimental’s score (0.85; 0.76-0.95) and Barthel’s score (0.96; 0.94-0.99). Agreement between medical records and self-completed questionnaire was 85.9% (kappa 0.72 (0,62- 0,82). Disagreement was unrelated to education and cognitive

  13. Marine Science Activities for Visually Impaired.

    ERIC Educational Resources Information Center

    Schatz, Dennis; And Others

    These marine education materials are based on the approach that students learn best when given a multisensory experience. The activities are intended to develop such experiences for the visually impaired child. Activities are intended to supplement an upper-elementary science curriculum or be the basis of a unit on marine biology. The guide is…

  14. Generic ABILHAND Questionnaire Can Measure Manual Ability across a Variety of Motor Impairments

    ERIC Educational Resources Information Center

    Simone, Anna; Rota, Viviana; Tesio, Luigi; Perucca, Laura

    2011-01-01

    ABILHAND is, in its original version, a 46-item, 4-level questionnaire. It measures the difficulty perceived by patients with rheumatoid arthritis as they do various daily manual tasks. ABILHAND was originally built through Rasch analysis. In a later study, it was simplified to a generic 23-item, three-level questionnaire, showing both…

  15. The use of research questionnaires with hearing impaired adults: online vs. paper-and-pencil administration

    PubMed Central

    2012-01-01

    Background When evaluating hearing rehabilitation, it is reasonable to use self-report questionnaires as outcome measure. Questionnaires used in audiological research are developed and validated for the paper-and-pencil format. As computer and Internet use is increasing, standardized questionnaires used in the audiological context should be evaluated to determine the viability of the online administration format. The aim of this study was to compare administration of questionnaires online versus paper- and pencil of four standardised questionnaires used in hearing research and clinic. We included the Hearing Handicap Inventory for the Elderly (HHIE), the International Outcome Inventory for Hearing Aids (IOI-HA), Satisfaction with Amplification in Daily Life (SADL), and the Hospital Anxiety and Depression Scale (HADS). Methods A cross-over design was used by randomly letting the participants complete the questionnaires either online or on paper. After 3 weeks the participants filled out the same questionnaires again but in the other format. A total of 65 hearing-aid users were recruited from a hearing clinic to participate on a voluntary basis and of these 53 completed both versions of the questionnaires. Results A significant main effect of format was found on the HHIE (p < 0.001), with participants reporting higher scores on the online format than in the paper format. There was no interaction effect. For the other questionnaires were no significant main or interaction effects of format. Significant correlations between the two ways of presenting the measures was found for all questionnaires (p<0.05). The results from reliability tests showed Cronbachs α’s above .70 for all four questionnaires and differences in Cronbachs α between administration formats were negligible. Conclusions For three of the four included questionnaires the participants’ scores remained consistent across administrations and formats. For the fourth included questionnaire (HHIE) a

  16. 78 FR 38098 - Proposed Information Collection (Knee and Lower Leg Disability Benefits Questionnaire) Activity...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-25

    ... AFFAIRS Proposed Information Collection (Knee and Lower Leg Disability Benefits Questionnaire) Activity... Disability Benefits Questionnaire)'' in any correspondence. During the comment period, comments may be viewed.... SUPPLEMENTARY INFORMATION: Title: Knee and Lower Leg Conditions Disability Benefits Questionnaire, VA Form...

  17. 78 FR 34708 - Proposed Information Collection (Ankle Conditions Disability Benefits Questionnaire) Activity...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-10

    ... AFFAIRS Proposed Information Collection (Ankle Conditions Disability Benefits Questionnaire) Activity... Control No. 2900--NEW (Ankle Conditions Disability Benefits Questionnaire)'' in any correspondence. During... Conditions Disability Benefits Questionnaire, VA Form 21-0960M-2. OMB Control Number: 2900--NEW...

  18. Comparing the validity of 2 physical activity questionnaire formats in African-American and Hispanic women

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The purpose of this study was to compare the validity of 2 physical activity questionnaire formats—one that lists activities (Checklist questionnaire) and one that assesses overall activities (Global questionnaire) by domain. Two questionnaire formats were validated among 260 African-American and Hi...

  19. Validation of the Oxford Participation and Activities Questionnaire

    PubMed Central

    Morley, David; Dummett, Sarah; Kelly, Laura; Dawson, Jill; Fitzpatrick, Ray; Jenkinson, Crispin

    2016-01-01

    Purpose There is growing interest in the management of long-term conditions and in keeping people active and participating in the community. Testing the effectiveness of interventions that aim to affect activities and participation can be challenging without a well-developed, valid, and reliable instrument. This study therefore aims to develop a patient-reported outcome measure, the Oxford Participation and Activities Questionnaire (Ox-PAQ), which is theoretically grounded in the World Health Organization’s International Classification of Functioning, Disability, and Health (ICF) and fully compliant with current best practice guidelines. Methods Questionnaire items generated from patient interviews and based on the nine chapters of the ICF were administered by postal survey to 386 people with three neurological conditions: motor neuron disease, multiple sclerosis, and Parkinson’s disease. Participants also completed the Medical Outcomes Study (MOS) 36-Item Short Form Health Survey (SF-36) and EQ-5D-5L. Results Thus, 334 participants completed the survey, a response rate of 86.5%. Factor analysis techniques identified three Ox-PAQ domains, consisting of 23 items, accounting for 72.8% of variance. Internal reliability for the three domains was high (Cronbach’s α: 0.81–0.96), as was test–retest reliability (intraclass correlation: 0.83–0.92). Concurrent validity was demonstrated through highly significant relationships with relevant domains of the MOS SF-36 and the EQ- 5D-5L. Assessment of known-groups validity identified significant differences in Ox-PAQ scores among the three conditions included in the survey. Conclusion Results suggest that the Ox-PAQ is a valid and reliable measure of participation and activity. The measure will now be validated in a range of further conditions, and additional properties, such as responsiveness, will also be assessed in the next phase of the instrument’s development. PMID:27366108

  20. Psychometric properties of the Brazilian version of Pfeffer's Functional Activities Questionnaire

    PubMed Central

    Assis, Luciana de Oliveira; de Paula, Jonas J.; Assis, Marcella G.; de Moraes, Edgar N.; Malloy-Diniz, Leandro F.

    2014-01-01

    Pfeffer's Functional Activities Questionnaire (FAQ) is one of the most commonly employed tools in studies on pathological cognitive aging. Despite the different versions of the questionnaire translated for use in clinical practice, few studies have analyzed the psychometric properties of the Brazilian version of the FAQ (P-FAQ). Thus, the aim of the present study was to analyze the P-FAQ with regard to internal consistency, factorial structure and associations with demographic factors (age, sex, and schooling), depressive symptoms, cognitive measures and other measures of functionality. One hundred sixty-one older adults were divided into four groups (91 with dementia, 46 with mild cognitive impairment, 11 with psychiatric disorders and 13 healthy controls). All participants were evaluated by cognitive, behavioral and functional tests and scales. Their caregivers answered the P-FAQ. The questionnaire showed high internal consistency (α = 0.91). Factor analysis revealed a two-factor structure, which, accounted for 66% of the total variance. The P-FAQ was not correlated with demographic factors, was weakly correlated with depressive symptoms (ϱ = 0.271, p < 0.01, R2 = 7%) and strongly correlated with cognitive measures (Matttis Dementia Rating Scale total score: ϱ = −0.574, p < 0.01, R2 = 33%) as well as complex instrumental activities of daily living (ϱ = −0.845, p < 0.01, R2 = 71%). Cognitive performance and depression status were independent predictors of P-FAQ scores in regression models. The present findings indicate that the P-FAQ has satisfactory reliability, internal consistency, construct validity and ecological validity. Therefore, this questionnaire can be used in clinical practice and research involving the Brazilian population of older adults. PMID:25309432

  1. The Oxford Participation and Activities Questionnaire: study protocol

    PubMed Central

    Morley, David; Dummett, Sarah; Kelly, Laura; Dawson, Jill; Fitzpatrick, Ray; Jenkinson, Crispin

    2014-01-01

    Background With an ageing population and increasing demands on health and social care services, there is growing importance attached to the management of long-term conditions, including maximizing the cost-effectiveness of treatments. In line with this, there is increasing emphasis on the need to keep people both active and participating in daily life. Consequently, it is essential that well developed and validated instruments that can meaningfully assess levels of participation and activity are widely available. Current measures, however, are largely focused on disability and rehabilitation, and there is no measure of activity or participation for generic use that fully meets the standards set by regulatory bodies such as the US Food and Drug Administration. Here we detail a protocol for the development and validation of a new patient-reported outcome measure (PROM) for assessment of participation and activity in people experiencing a variety of health conditions, ie, the Oxford Participation and Activities Questionnaire (Ox-PAQ). The stages incorporated in its development are entirely in line with current regulations and represent best practice in the development of PROMs. Methods Development of the Ox-PAQ is theoretically grounded in the World Health Organization International Classification of Functioning, Disability, and Health. The project incorporates a new strategy of engaging with stakeholders from the outset in an attempt to identify those characteristics of PROMs considered most important to a range of potential users. Items will be generated through interviews with patients from a range of conditions. Pretesting of the instrument will be via cognitive interviews and focus groups. A postal survey will be conducted, with data subject to factor and Rasch analysis in order to identify appropriate dimensions and redundant items. Reliability will be assessed by Cronbach’s alpha and item-total correlations. A second, large-scale postal survey will follow

  2. The 'Technology - Activities of Daily Living Questionnaire': a version with a technology-related subscale

    PubMed Central

    Muñoz-Neira, Carlos; López, Oscar L.; Riveros, Rodrigo; Nuñez-Huasaf, Javier; Flores, Patricia; Slachevsky, Andrea

    2016-01-01

    Background Information and communication technology (ICT) has become an increasingly important part of daily life. The ability to use technology is becoming essential for autonomous functioning in society. Current functional scales for patients with cognitive impairment do not evaluate the use of technology. The objective of this study was to develop and validate a new version of the Activities of Daily Living Questionnaire (ADLQ) that incorporates an ICT subscale. Method A new technology-based subscale was incorporated into the Spanish Version of the ADLQ (SV-ADLQ), entitled The Technology Version of the ADLQ (T-ADLQ). The T-ADLQ was administered to 63 caregivers of dementia patients, 21 proxies of mild cognitive impairment patients and 44 proxies of normal elderly subjects (mean age of the sample ± SD: 73.5 ± 8.30). We analysed the convergent validity, internal consistency, reliability cut-off point, sensitivity and specificity of the T-ADLQ. The results of the T-ADLQ were compared to the SV-ADLQ. Results The T-ADLQ showed significant correlations with the Mini-mental Test (MMSE), the Frontal Assesment Battery (FAB) as well as other measures of functional impairment and dementia severity (MMSE: r = −0.70; FAB: r = −0.65; Functional Assessment Questionnaire: r = 0.77; Instrumental Activities of Daily Living Scale: r = −0.75; Clinical Dementia Rating Scale: r = 0.72; p<0.001). The T-ADLQ showed a good reliability with a relatively high Cronbach’s alpha coefficient (Cronbach’s alpha = 0.861). When considering a functional impairment cut-off point greater than 29.25%, the sensitivity and specificity of the T-ADLQ were 82% and 90%, respectively. The area under the ROC curve (AUC) was 0.937 for the T-ADLQ and 0.932 for the original version of the test. Conclusions The T-ADLQ revealed adequate indicators of validity and reliability for the functional assessment of activities of daily living in dementia patients. However, the inclusion of technology items in

  3. Reliability and Validity of the PAQ-C Questionnaire to Assess Physical Activity in Children

    ERIC Educational Resources Information Center

    Benítez-Porres, Javier; López-Fernández, Iván; Raya, Juan Francisco; Álvarez Carnero, Sabrina; Alvero-Cruz, José Ramón; Álvarez Carnero, Elvis

    2016-01-01

    Background: Physical activity (PA) assessment by questionnaire is a cornerstone in the field of sport epidemiology studies. The Physical Activity Questionnaire for Children (PAQ-C) has been used widely to assess PA in healthy school populations. The aim of this study was to evaluate the reliability and validity of the PAQ-C questionnaire in…

  4. 78 FR 34174 - Proposed Information Collection (Pension Claim Questionnaire for Farm Income) Activity: Comment...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-06

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF VETERANS AFFAIRS Proposed Information Collection (Pension Claim Questionnaire for Farm Income) Activity: Comment... techniques or the use of other forms of information technology. Title: Pension Claim Questionnaire for...

  5. 78 FR 57925 - Agency Information Collection (Pension Claim Questionnaire for Farm Income) Activity Under OMB...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-20

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF VETERANS AFFAIRS Agency Information Collection (Pension Claim Questionnaire for Farm Income) Activity Under OMB... ``OMB Control No. 2900-0095.'' SUPPLEMENTARY INFORMATION: Title: Pension Claim Questionnaire for...

  6. 75 FR 62636 - Proposed Information Collection (Status of Dependents Questionnaire) Activity: Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-12

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF VETERANS AFFAIRS Proposed Information Collection (Status of Dependents Questionnaire) Activity: Comment Request... techniques or the use of other forms of information technology. Title: Status of Dependents Questionnaire,...

  7. 78 FR 46422 - Proposed Information Collection (Status of Dependents Questionnaire) Activity: Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-31

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF VETERANS AFFAIRS Proposed Information Collection (Status of Dependents Questionnaire) Activity: Comment Request... of Dependents Questionnaire, VA Form 21-0538. OMB Control Number: 2900-0500. Type of...

  8. Assessing adult leisure activities: an extension of a self-report activity questionnaire.

    PubMed

    Jopp, Daniela S; Hertzog, Christopher

    2010-03-01

    Everyday leisure activities in adulthood and old age have been investigated with respect to constructs such as successful aging, an engaged lifestyle, and prevention of age-related cognitive decline. They also relate to mental health and have clinical value, as they can inform diagnosis and interventions. In the present study, the authors enhanced the content validity of the Victoria Longitudinal Study activity questionnaire by adding items on physical and social activities and validated a shortened version of the questionnaire. The proposed leisure activity model included 11 activity categories: 3 types of social activities (i.e., activities with close social partners, group-centered public activity, religious activities), physical activities, developmental activities, experiential activities, crafts, game playing, TV watching, travel, and technology use. Confirmatory factor analyses validated the proposed factor structure in 2 independent samples. A higher order model with a general activity factor fitted the activity factor correlations with relatively little loss of fit. Convergent and discriminant validity for the activity scales were supported by patterns of their correlations with education, health, depression, cognition, and personality. In sum, the scores derived from of the augmented Victoria Longitudinal Study activity questionnaire demonstrate good reliability, and validity evidence supports their use as measures of leisure activities in young, middle-aged, and older individuals.

  9. Assessing Adult Leisure Activities: An Extension of a Self-Report Activity Questionnaire

    PubMed Central

    Jopp, Daniela; Hertzog, Christopher

    2009-01-01

    Everyday leisure activities in adulthood and old age have been investigated with respect to constructs such as successful aging, an engaged lifestyle, and prevention of age-related cognitive decline. They also relate to mental health and have clinical value as they can inform diagnosis and interventions. In the present study, we enhanced the content validity of the Victoria Longitudinal Study activity questionnaire by adding items on physical and social activities, and validated a shortened version of the questionnaire. Our proposed leisure activity model included 11 activity categories: three types of social activities (i.e., activities with close social partners, group-centered public activity, religious activities), physical, developmental, and experiential activities, crafts, game playing, TV watching, travel, and technology use. Confirmatory factor analyses validated the proposed factor structure in two independent samples. A higher-order model with a general activity factor fitted the activity factor correlations with relatively little loss of fit. Convergent and discriminant validity for the activity scales were supported by patterns of their correlations with education, health, depression, cognition, and personality. In sum, the scores derived from of the augmented VLS activity questionnaire demonstrate good reliability, and validity evidence supports their use as measure of leisure activities in young, middle-aged, and older individuals. PMID:20230157

  10. Qualitative attributes and measurement properties of physical activity questionnaires: a checklist.

    PubMed

    Terwee, Caroline B; Mokkink, Lidwine B; van Poppel, Mireille N M; Chinapaw, Mai J M; van Mechelen, Willem; de Vet, Henrica C W

    2010-07-01

    The large number of available physical activity (PA) questionnaires makes it difficult to select the most appropriate questionnaire for a certain purpose. This choice is further hampered by incomplete reporting and unsatisfactory evaluation of the content and measurement properties of the questionnaires. We provide a checklist for appraising the qualitative attributes and measurement properties of PA questionnaires, as a tool for selecting the most appropriate PA questionnaire for a certain target population and purpose. The checklist is called the Quality Assessment of Physical Activity Questionnaire (QAPAQ). This review is one of a group of four reviews in this issue of Sports Medicine on the content and measurement properties of physical activity questionnaires. Part 1 of the checklist can be used to appraise the qualitative attributes of PA questionnaires, i.e. the construct to be measured by the questionnaire, the purpose and target population for which it was developed, the format, interpretability and ease of use. Part 2 of the checklist can be used to appraise the measurement properties of a PA questionnaire, i.e. reliability (parameters of measurement error and reliability coefficients), validity (face and content validity, criterion validity and construct validity) and responsiveness. The QAPAQ can be used to select the most appropriate PA questionnaire for a certain purpose, but it can also be used to design or report a study on measurement properties of PA questionnaires. Using such a checklist will contribute to improving the assessment, reporting and appraisal of the content and measurement properties of PA questionnaires.

  11. 78 FR 36643 - Proposed Information Collection (Wrist Conditions Disability Benefits Questionnaire) Activity...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-18

    ... AFFAIRS Proposed Information Collection (Wrist Conditions Disability Benefits Questionnaire) Activity... . Please refer to ``OMB Control No. 2900--NEW (Wrist Conditions Disability Benefits Questionnaire)'' in any... Conditions Disability Benefits Questionnaire, VA Form 21-0960M-16. OMB Control Number: 2900-NEW...

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    2013-06-17

    ... AFFAIRS Proposed Information Collection (Wrist Conditions Disability Benefits Questionnaire) Activity... . Please refer to ``OMB Control No. 2900-NEW (Wrist Conditions Disability Benefits Questionnaire)'' in any... Conditions Disability Benefits Questionnaire, VA Form 21-0960M-16. OMB Control Number: 2900-NEW...

  13. 78 FR 35098 - Proposed Information Collection (Hand and Finger Disability Benefits Questionnaire) Activity...

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    2013-06-11

    ... AFFAIRS Proposed Information Collection (Hand and Finger Disability Benefits Questionnaire) Activity... . Please refer to ``OMB Control No. 2900-NEW (Hand or Finger Disability Benefits Questionnaire)'' in any.... Title: Hand and Finger Disability Benefits Questionnaire, VA Form 21-0960M-7. OMB Control Number:...

  14. Physical Education Lessons and Activity Status of Visually Impaired and Sighted Adolescents.

    PubMed

    Demirturk, Funda; Kaya, Mustafa

    2015-11-15

    BACKGROUND This study investigated participation in physical education and sports lessons of visually impaired adolescents and their sighted peers and compared their physical activity levels. MATERIAL AND METHODS A total of 22 visually impaired children of mean age 13.59±1.14 years and 31 sighted children aged 13.61±0.50 years participated in the study. A questionnaire prepared for this study was used to investigate participation of visually impaired adolescents and their sighted peers in physical education and sports lessons at school and the problems they encounter while doing sports. The Turkish version of the International Physical Activity Questionnaire - short-form (IPAQ-SF) was used to evaluate the physical activity level of the subjects. RESULTS The results of our study suggest that physical activity levels of visually impaired children and their sighted children were similar (p>0.05). Totally blind children had lower IPAQ scores than those with low vision (p<0.05), and girls were less active physically than boys (p<0.05). There were few differences in physical education lessons of the groups, in taking part in sports-related organizations, and future plans. CONCLUSIONS Children in secondary school, especially visually impaired children, need to be more motivated and more encouraged to take part in various sports or physical activities.

  15. Active-Q: Validation of the Web-Based Physical Activity Questionnaire Using Doubly Labeled Water

    PubMed Central

    Trolle Lagerros, Ylva; Christensen, Sara Elisabeth; Möller, Elisabeth; Wright, Antony; Sjölander, Arvid; Bälter, Katarina

    2012-01-01

    Background Increased use of the Internet provides new opportunities for collecting data in large studies. The aim of our new Web-based questionnaire, Active-Q, is to assess total physical activity and inactivity in adults. Active-Q assesses habitual activity during the past year via questions in four different domains: (1) daily occupation, (2) transportation to and from daily occupation, (3) leisure time activities, and (4) sporting activities. Objective The objective of our study is to validate Active-Q’s energy expenditure estimates using the doubly labeled water (DLW) method, and to assess the reproducibility of Active-Q by comparing the results of the questionnaire completed by the same group on two occasions. Methods The validity and reproducibility of Active-Q were assessed in a group of 37 individuals, aged 20 to 65 years. Active-Q was distributed via email to the participants. The total energy expenditure of the participants was assessed using DLW for 11 consecutive days. Results The median time to complete Active-Q was 6.1 minutes. The majority of participants (27/37, 73%) reported that the questionnaire was “easy” or “very easy” to answer. On average, Active-Q overestimated the total daily energy expenditure by 440 kJ compared with the DLW. The Spearman correlation between the two methods was r = 0.52 (P < .001). The intraclass correlation coefficient for total energy expenditure between the results of Active-Q completed on two occasions was 0.83 (95% CI 0.73-0.93). Conclusions Active-Q is a valid and reproducible method of assessing total energy expenditure. It is also a user-friendly method and suitable for Web-based data collection in large epidemiological studies. PMID:22356755

  16. Development of a Scottish physical activity questionnaire: a tool for use in physical activity interventions

    PubMed Central

    Lowther, M.; Mutrie, N.; Loughlan, C.; McFarlane, C.

    1999-01-01

    OBJECTIVES: Three studies were undertaken to establish the reliability and validity of the Scottish physical activity questionnaire (SPAQ), developed to aid seven day recall of leisure and occupational physical activity. METHODS: To establish reliability, SPAQs (n = 34) were completed on a Monday and the following Wednesday. Thus each questionnaire measured four identical days. To establish concurrent validity, 94 participants completed a SPAQ and an adapted stage of exercise behaviour change questionnaire. Responses to SPAQ were then analysed by stage of exercise behaviour change. In a further study of criterion validity, 30 volunteers wore a Caltrac motion sensor for four consecutive days, after which they completed a SPAQ. RESULTS: In the first study, total physical activity had a coefficient of repeatability (R) of 53 minutes. Occupational physical activity showed a similar variance (R = 54.6 minutes) but leisure physical activity was more reliable (R = 29.3 minutes). The main variation in occupational physical activity was found to be walking (R = 39.8 minutes). In study 2, a one way analysis of variance showed the expected relation between physical activity and stage of exercise behaviour change, confirming the concurrent validity of SPAQ with the stage of exercise behaviour change model. In study 3, several erroneous recordings affected both SPAQ and the Caltrac results (kcal). After relevant corrections had been made, the correlation between the two measurement devices was 0.52 (p < 0.05). CONCLUSIONS: SPAQ has been shown to be reliable and to hold strong concurrent validity and limited criterion validity. The main limitation in SPAQ appears to be the measurement of occupational walking. It is therefore recommended that further work be conducted to refine the measurement of this physical activity component. It is evident nonetheless that SPAQ can be used with confidence to measure outcomes in physical activity interventions when account is taken of its

  17. Comparison of IPAQ-SF and Two Other Physical Activity Questionnaires with Accelerometer in Adolescent Boys

    PubMed Central

    Mäestu, Jarek; Lätt, Evelin; Jürimäe, Jaak; Vainik, Uku

    2017-01-01

    Self-report measures of physical activity (PA) are easy to use and popular but their reliability is often questioned. Therefore, the general aim of the present study was to investigate the association of PA questionnaires with accelerometer derived PA, in a sample of adolescent boys. In total, 191 pubertal boys (mean age 14.0 years) completed three self-report questionnaires and wore an accelerometer (ActiGraph GT1M) for 7 consecutive days. The PA questionnaires were: International Physical Activity Questionnaire-Short Form (IPAQ-SF), Tartu Physical Activity Questionnaire (TPAQ), and the Inactivity subscale from Domain-Specific Impulsivity (DSI) scale. All three questionnaires were significantly correlated with accelerometer derived MVPA: the correlations were 0.31 for the IPAQ-SF MVPA, 0.34 for the TPAQ MVPA and -0.29 for the DSI Inactivity scale. Nevertheless, none of the questionnaires can be used as a reliable individual-level estimate of MVPA in male adolescents. The boys underreported their MVPA in IPAQ-SF as compared to accelerometer-derived MVPA (respective averages 43 and 56 minutes); underreporting was more marked in active boys with average daily MVPA at least 60 minutes, and was not significant in less active boys. Conversely, MVPA index from TPAQ overestimated the MVPA in less active boys but underestimated it in more active boys. The sedentary time reported in IPAQ-SF was an underestimate as compared to accelerometer-derived sedentary time (averages 519 and 545 minutes, respectively). PMID:28056080

  18. 78 FR 44625 - Proposed Information Collection (Wrist Conditions Disability Benefits Questionnaire) Activity...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-24

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF VETERANS AFFAIRS Proposed Information Collection (Wrist Conditions Disability Benefits Questionnaire) Activity... ``Wrist Conditions Disability Benefits Questionnaire, VA Form 21-0960M-16.'' On June 18, 2013 (78 FR...

  19. 76 FR 44087 - Agency Information Collection (Employment Questionnaire) Activity Under OMB Review

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    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF VETERANS AFFAIRS Agency Information Collection (Employment Questionnaire) Activity Under OMB Review AGENCY... INFORMATION: Title: Employment Questionnaire, VA Forms 21-4140 and 21-4140-1. OMB Control Number:...

  20. 76 FR 27386 - Proposed Information Collection (Employment Questionnaire) Activity; Comment Request

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    2011-05-11

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF VETERANS AFFAIRS Proposed Information Collection (Employment Questionnaire) Activity; Comment Request AGENCY...: Employment Questionnaire, VA Forms 21-4140 and 21-4140-1. OMB Control Number: 2900-0079. Type of...

  1. 75 FR 10027 - Proposed Information Collection (Marital Status Questionnaire) Activity: Comment Request

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    2010-03-04

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF VETERANS AFFAIRS Proposed Information Collection (Marital Status Questionnaire) Activity: Comment Request AGENCY.... Title: Marital Status Questionnaire, VA Form 21-0537. OMB Control Number: 2900-0495. Type of...

  2. 75 FR 80114 - Agency Information Collection (Status of Dependents Questionnaire) Activity Under OMB Review

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    2010-12-21

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF VETERANS AFFAIRS Agency Information Collection (Status of Dependents Questionnaire) Activity Under OMB Review... INFORMATION: Title: Status of Dependents Questionnaire, VA Form 21-0538. OMB Control Number: 2900-0500....

  3. 75 FR 26346 - Agency Information Collection (Marital Status Questionnaire) Activity Under OMB Review

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    2010-05-11

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF VETERANS AFFAIRS Agency Information Collection (Marital Status Questionnaire) Activity Under OMB Review AGENCY...: Marital Status Questionnaire, VA Form 21-0537. OMB Control Number: 2900-0495. Type of Review: Extension...

  4. 78 FR 48941 - Agency Information Collection (Marital Status Questionnaire) Activity Under OMB Review

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    2013-08-12

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF VETERANS AFFAIRS Agency Information Collection (Marital Status Questionnaire) Activity Under OMB Review AGENCY... Questionnaire, VA Form 21-0537. OMB Control Number: 2900-0495. Type of Review: Extension of a currently...

  5. The Impact of Vision Impairment (IVI) Questionnaire; Validation of the Thai-Version and the Implementation on Vision-Related Quality of Life in Thai Rural Community.

    PubMed

    Ratanasukon, Mansing; Tongsomboon, Jongjit; Bhurayanontachai, Patama; Jirarattanasopa, Pichai

    2016-01-01

    The objective of this study is to validate the Thai-version of the impact of vision impairment (IVI) questionnaire and to evaluate its impact on vision-related quality of life (VRQoL) in southern Thailand. The IVI questionnaire was translated into Thai according to WHO translation guidelines. In addition to the routine ophthalmological examinations, a Thai version of the IVI questionnaire was administered to all participants. A total of 120 patients with visual impairment who presented at Songklanagarind hospital, Songkhla province, were enrolled in the study; 30 had age-related macular degeneration (AMD), 30 had cataract, 30 had diabetic retinopathy, 30 had glaucoma, and 30 non-visually impaired individuals comprised the control group. Statistical analysis demonstrated the Thai-version IVI questionnaire is valid and reliable to evaluate the VRQoL of the Thai patients through three subscales: (i) mobility and independence, (ii) reading and accessing information, and (iii) emotional well-being. The results demonstrated high consistency in all subscales with Cronbach's alpha ranging from 0.787 to 0.849. Rasch analysis revealed the validity of the Thai-version IVI to assess VRQoL through all three subscales. Test-retest reliability was also high (intraclass correlation coefficient = 0.96). The composite score of the IVI was significantly higher in participants with visual impairment compared with healthy participants. Moreover, the subscale scores of reading and accessing information, and emotional well-being were highest in participants with AMD. While the subscale scores of mobility and independence were highest among those with either cataracts or diabetic retinopathy. The symptoms of the common vision impairment diseases are associated with an adverse impact on VRQoL in a clinic-based population as demonstrated in this study.

  6. The Impact of Vision Impairment (IVI) Questionnaire; Validation of the Thai-Version and the Implementation on Vision-Related Quality of Life in Thai Rural Community

    PubMed Central

    Ratanasukon, Mansing; Tongsomboon, Jongjit; Bhurayanontachai, Patama; Jirarattanasopa, Pichai

    2016-01-01

    The objective of this study is to validate the Thai-version of the impact of vision impairment (IVI) questionnaire and to evaluate its impact on vision-related quality of life (VRQoL) in southern Thailand. The IVI questionnaire was translated into Thai according to WHO translation guidelines. In addition to the routine ophthalmological examinations, a Thai version of the IVI questionnaire was administered to all participants. A total of 120 patients with visual impairment who presented at Songklanagarind hospital, Songkhla province, were enrolled in the study; 30 had age-related macular degeneration (AMD), 30 had cataract, 30 had diabetic retinopathy, 30 had glaucoma, and 30 non-visually impaired individuals comprised the control group. Statistical analysis demonstrated the Thai-version IVI questionnaire is valid and reliable to evaluate the VRQoL of the Thai patients through three subscales: (i) mobility and independence, (ii) reading and accessing information, and (iii) emotional well-being. The results demonstrated high consistency in all subscales with Cronbach’s alpha ranging from 0.787 to 0.849. Rasch analysis revealed the validity of the Thai-version IVI to assess VRQoL through all three subscales. Test-retest reliability was also high (intraclass correlation coefficient = 0.96). The composite score of the IVI was significantly higher in participants with visual impairment compared with healthy participants. Moreover, the subscale scores of reading and accessing information, and emotional well-being were highest in participants with AMD. While the subscale scores of mobility and independence were highest among those with either cataracts or diabetic retinopathy. The symptoms of the common vision impairment diseases are associated with an adverse impact on VRQoL in a clinic-based population as demonstrated in this study. PMID:27191960

  7. Science Activities for the Physically Impaired.

    ERIC Educational Resources Information Center

    James, Melodee L.

    1987-01-01

    Describes the nine modules of the SAVI/SELPH program, a hands-on, multisensory science program developed for grade 4-7 visually impaired, orthopedically disabled, learning disabled, deaf, and multihandicapped students. Modules consist of measurement, structures of life, scientific reasoning, communication, magnetism and electricity, mixtures and…

  8. Motivation and Physical Activity in Adolescents with Visual Impairments

    ERIC Educational Resources Information Center

    Kozub, Francis M.

    2006-01-01

    It is found that individuals with visual impairments have levels of intrinsic and extrinsic motivation and amotivation that influence their use of free time and lead to adaptive or maladaptive outcomes. As such, inactive individuals with visual impairments, lacking motivation to engage in physical activity, become dependent members of society who…

  9. Validation in London of a physical activity questionnaire for use in a study of postmenopausal osteopaenia.

    PubMed Central

    Suleiman, S; Nelson, M

    1997-01-01

    STUDY OBJECTIVE: To determine the validity of a self administered physical activity questionnaire to be used as part of a screening device for postmenopausal osteopaenia (with additional questions on medical history and calcium intake). DESIGN: A questionnaire was posted to 86 perimenopausal women to enquire about weekly hours spent in non-sedentary activity at work, in the household, and during leisure hours. Subjects who returned the questionnaire were visited at home and asked to complete a four day activity diary and subsequently to undertake a submaximal estimate of VO2 MAX, carried out using a treadmill ergometer. They were interviewed to clarify questionnaire and diary entries. Questionnaire validity was assessed in comparison with the diary estimates of hours of activity and with VO2 MAX. PARTICIPANTS: A total of 86 perimenopausal women aged 43-54 years were randomly selected from a GP list in Hammersmith, London. Thirty five women (41%) returned the questionnaire. They were visited at home, given the diary to complete, and invited to attend the physiology laboratory for VO2 MAX measurements. Twenty six of the 35 (74%) completed the study and were included in the final analysis. MAIN RESULTS: Women spent an average of 51 hours per week in non-sedentary activities. Questionnaire and diary yielded similar results (51.05 versus 51.30 h/wk), and there was a good correlation between diary and questionnaire estimates of total weekly hours of non-sedentary activity (r = 0.45, p < 0.05). Other significant correlations were for standing (r = 0.69, p < 0.01), leisure activities (r = 0.66, p < 0.01), and for light household activities (r = 0.42, p < 0.05). Correlations were better for employed than non-employed subjects. In relation to the diary, the questionnaire correctly classified 60% into the top or bottom half of the distribution activity. Sensitivity and specificity of the questionnaire were both equal to 61.5%. CONCLUSIONS: The questionnaire is useful for

  10. Validation of the Regicor Short Physical Activity Questionnaire for the Adult Population

    PubMed Central

    Molina, Luis; Sarmiento, Manuel; Peñafiel, Judith; Donaire, David; Garcia-Aymerich, Judith; Gomez, Miquel; Ble, Mireia; Ruiz, Sonia; Frances, Albert; Schröder, Helmut; Marrugat, Jaume; Elosua, Roberto

    2017-01-01

    Objective To develop and validate a short questionnaire to estimate physical activity (PA) practice and sedentary behavior for the adult population. Methods The short questionnaire was developed using data from a cross-sectional population-based survey (n = 6352) that included the Minnesota leisure-time PA questionnaire. Activities that explained a significant proportion of the variability of population PA practice were identified. Validation of the short questionnaire included a cross-sectional component to assess validity with respect to the data collected by accelerometers and a longitudinal component to assess reliability and sensitivity to detect changes (n = 114, aged 35 to 74 years). Results Six types of activities that accounted for 87% of population variability in PA estimated with the Minnesota questionnaire were selected. The short questionnaire estimates energy expenditure in total PA and by intensity (light, moderate, vigorous), and includes 2 questions about sedentary behavior and a question about occupational PA. The short questionnaire showed high reliability, with intraclass correlation coefficients ranging between 0.79 to 0.95. The Spearman correlation coefficients between estimated energy expenditure obtained with the questionnaire and the number of steps detected by the accelerometer were as follows: 0.36 for total PA, 0.40 for moderate intensity, and 0.26 for vigorous intensity. The questionnaire was sensitive to detect changes in moderate and vigorous PA (correlation coefficients ranging from 0.26 to 0.34). Conclusion The REGICOR short questionnaire is reliable, valid, and sensitive to detect changes in moderate and vigorous PA. This questionnaire could be used in daily clinical practice and epidemiological studies. PMID:28085886

  11. A measurement error model for physical activity level as measured by a questionnaire with application to the 1999-2006 NHANES questionnaire.

    PubMed

    Tooze, Janet A; Troiano, Richard P; Carroll, Raymond J; Moshfegh, Alanna J; Freedman, Laurence S

    2013-06-01

    Systematic investigations into the structure of measurement error of physical activity questionnaires are lacking. We propose a measurement error model for a physical activity questionnaire that uses physical activity level (the ratio of total energy expenditure to basal energy expenditure) to relate questionnaire-based reports of physical activity level to true physical activity levels. The 1999-2006 National Health and Nutrition Examination Survey physical activity questionnaire was administered to 433 participants aged 40-69 years in the Observing Protein and Energy Nutrition (OPEN) Study (Maryland, 1999-2000). Valid estimates of participants' total energy expenditure were also available from doubly labeled water, and basal energy expenditure was estimated from an equation; the ratio of those measures estimated true physical activity level ("truth"). We present a measurement error model that accommodates the mixture of errors that arise from assuming a classical measurement error model for doubly labeled water and a Berkson error model for the equation used to estimate basal energy expenditure. The method was then applied to the OPEN Study. Correlations between the questionnaire-based physical activity level and truth were modest (r = 0.32-0.41); attenuation factors (0.43-0.73) indicate that the use of questionnaire-based physical activity level would lead to attenuated estimates of effect size. Results suggest that sample sizes for estimating relationships between physical activity level and disease should be inflated, and that regression calibration can be used to provide measurement error-adjusted estimates of relationships between physical activity and disease.

  12. Active Mobility and Environment: A Pilot Qualitative Study for the Design of a New Questionnaire.

    PubMed

    Hess, Franck; Salze, Paul; Weber, Christiane; Feuillet, Thierry; Charreire, Hélène; Menai, Mehdi; Perchoux, Camille; Nazare, Julie-Anne; Simon, Chantal; Oppert, Jean-Michel; Enaux, Christophe

    2017-01-01

    It is generally accepted that active mobility, mainly walking and cycling, contributes to people's physical and mental health. One of the current challenges is to improve our understanding of this type of behaviour. This study aims to identify factors from the daily-life environment that may be related to active mobility behaviours, in order to design a new questionnaire for a quantitative study of a large adult population. The new questionnaire obtained through this pilot study combines information from interviews with existing questionnaires materials in order to introduce new factors while retaining the factors already assessed. This approach comprises three stages. The first was a content analysis (Reinert method) of interviews with a sample of participants about daily living activities as well as mobility. This stage led to a typology of factors suggested by interviews. The second was a scoping review of the literature in order to identify the active mobility questionnaires currently used in international literature. The last stage was a cross-tabulation of the factors resulting from the written interviews and the questionnaires. A table of the inter-relationships between the interview-based typology and the questionnaires shows discrepancies between factors considered by the existing questionnaires, and factors coming from individual interviews. Independent factors which were ignored in or absent from the questionnaires are the housing situation within the urban structure, overall consideration of the activity space beyond the limits of the residential neighbourhood, the perception of all the transportation modes, and the time scheduling impacting the modes actually used. Our new questionnaire integrates both the usual factors and the new factors that may be related to active mobility behaviours.

  13. Active Mobility and Environment: A Pilot Qualitative Study for the Design of a New Questionnaire

    PubMed Central

    Salze, Paul; Weber, Christiane; Feuillet, Thierry; Charreire, Hélène; Menai, Mehdi; Perchoux, Camille; Nazare, Julie-Anne; Simon, Chantal; Oppert, Jean-Michel

    2017-01-01

    It is generally accepted that active mobility, mainly walking and cycling, contributes to people’s physical and mental health. One of the current challenges is to improve our understanding of this type of behaviour. This study aims to identify factors from the daily-life environment that may be related to active mobility behaviours, in order to design a new questionnaire for a quantitative study of a large adult population. The new questionnaire obtained through this pilot study combines information from interviews with existing questionnaires materials in order to introduce new factors while retaining the factors already assessed. This approach comprises three stages. The first was a content analysis (Reinert method) of interviews with a sample of participants about daily living activities as well as mobility. This stage led to a typology of factors suggested by interviews. The second was a scoping review of the literature in order to identify the active mobility questionnaires currently used in international literature. The last stage was a cross-tabulation of the factors resulting from the written interviews and the questionnaires. A table of the inter-relationships between the interview-based typology and the questionnaires shows discrepancies between factors considered by the existing questionnaires, and factors coming from individual interviews. Independent factors which were ignored in or absent from the questionnaires are the housing situation within the urban structure, overall consideration of the activity space beyond the limits of the residential neighbourhood, the perception of all the transportation modes, and the time scheduling impacting the modes actually used. Our new questionnaire integrates both the usual factors and the new factors that may be related to active mobility behaviours. PMID:28052086

  14. Impact of after school programming on physical activity among adolescents with visual impairments.

    PubMed

    Cervantes, Carlos M; Porretta, David L

    2013-04-01

    The purpose of this study was to examine the impact of an after school physical activity intervention on adolescents with visual impairments within the context of Social Cognitive Theory. Four adolescents with visual impairments (1 female, 3 males) between 14 and 19 years of age from a residential school for the blind served as participants. We used a range-bound changing criterion single-subject design. Physical activity was measured using ActiGraph accelerometers. Questionnaires were used to obtain information on selected social cognitive theory constructs. Results show that the intervention exerted functional control over the target behaviors (e.g., leisure-time physical activity) during intervention phases. Similarly, changes in scores for selected social cognitive constructs, in particular for outcome expectancy value, suggest a positive relationship between those constructs and physical activity behavior. No maintenance effects were observed.

  15. Assessment of quality of life in patients with visual impairments using a new visual function questionnaire: the VFQ-J11

    PubMed Central

    Nakano, Tadashi; Kawashima, Motoko; Hiratsuka, Yoshimune; Tamura, Hiroshi; Ono, Koichi; Murakami, Akira; Tsubota, Kazuo; Yamada, Masakazu

    2016-01-01

    Background The purpose of the present study was to assess the vision-related quality of life (QOL) of visually impaired patients using the Japanese 11-item National Eye Institute Visual Function Questionnaire (VFQ-J11). Comparisons with the 25-item version (VFQ-25) and the EuroQoL Index using a large group of patients with various degrees of impairments and various causative diseases were performed. Methods A total of 232 visually impaired Japanese patients were recruited from six ophthalmology departments in Japan. Information on ophthalmic findings and patient backgrounds was collected, and information on QOL and utility assessments was collected from the patients by means of survey questionnaires. Results The average age of patients was 69.6±14.3 years. Both the vision-related QOL scores (VFQ-25 composite and VFQ-J11) were significantly associated with better and worse visual acuity (VA) in visually impaired subjects (all P<0.01). VFQ-J11 was comparable to VFQ-25 regardless of causative diseases. VFQ-25 composite and the VFQ-J11 scores were concurrently associated with a range of systemic medical disorders. EuroQoL Index had a significant association with better eye VA (P<0.01), but not with worse eye VA, or any systemic disorders. Conclusion VFQ-J11 provides valid data on vision-related QOL and is less of a burden for patients with vision problems. PMID:27784982

  16. The Turkish version of the pregnancy physical activity questionnaire: cross-cultural adaptation, reliability, and validity

    PubMed Central

    Tosun, Ozge Celiker; Solmaz, Ulas; Ekin, Atalay; Tosun, Gokhan; Mutlu, Ebru Kaya; Okyay, Emre; Adiyeke, Mehmet; Gezer, Cenk; Mat, Emre; Malkoc, Mehtap

    2015-01-01

    [Purpose] The aim of this study was to translate the Pregnancy Physical Activity Questionnaire, adapt it for use with Turkish subjects and determine its reliability and validity. [Subjects and Methods] The Pregnancy Physical Activity Questionnaire was translated into Turkish and administered twice at 7–14-day intervals to pregnant women to assess the test-retest reliability. Cronbach’s α was used for internal consistency, and the inter-rater correlation coefficient was used to calculate the test-retest reliability. The Turkish Short Form 36 Health Survey (SF-36) and the International Physical Activity Questionnaire were used to estimate validity. [Results] The internal consistency during the first and third trimesters of pregnancy was excellent, with Cronbach’s α values of 0.93 and 0.95, respectively. The mean interval between the two assessments was 11.1 ± 2.1 days. The correlation coefficient between the total activity measured by the Turkish version of the Pregnancy Physical Activity Questionnaire and the International Physical Activity Questionnaire estimates of the total metabolic equivalent were fair to poor during the first, second, and third trimesters of pregnancy (r = 0.17, r = 0.17, r = 0.21, respectively). The Turkish version of the Pregnancy Physical Activity Questionnaire showed fair correlations with the Short Form 36 Health Survey physical component score (r = −0.30) and mental component score (r = −0.37) for the first trimester of pregnancy. [Conclusion] The Turkish version of the Pregnancy Physical Activity Questionnaire was found to be reliable and valid for assessing a pregnant woman’s physical activity. PMID:26644678

  17. Pregnancy physical activity questionnaire (PPAQ): reliability and validity of Turkish version

    PubMed Central

    Çırak, Yasemin; Yılmaz, Gül Deniz; Demir, Yasemin Parlak; Dalkılınç, Murat; Yaman, Selen

    2015-01-01

    [Purpose] The aim of this study was to translate the Pregnancy Physical Activity Questionnaire into Turkish and test its reliability and validity among Turkish pregnant women. [Subjects and Methods] The subjects were 204 healthy, single pregnant women between the ages 18 and 40 who volunteered to participate in this study. Reliability was evaluated by measuring the one-week test-retest reliability with the intraclass correlation coefficient and Pearson’s correlation analysis. Concurrent validity was examined by comparing the Pregnancy Physical Activity Questionnaire with the long form of the International Physical Activity Questionnaire and step counts with pedometer. [Results] The mean age of the participants was 28.23±4.94 years, and the mean for BMI was 26.09±4.40. For test-retest reliability, r values were respectively 0.961, 0.934, 0.957 and 0.981 for self-reported sedentary, light, moderate, and vigorous activity, respectively. Intraclass correlation coefficient scores ranged from 0.924 to 0.993. For validity, the Pearson’s correlation coefficients between the Pregnancy Physical Activity Questionnaire and long form of the International Physical Activity Questionnaire ranged from moderate (r = 0.329) to high (r = 0.672). The correlation value between the total score of the Pregnancy Physical Activity Questionnaire and the step counts was 0.70. [Conclusion] The Turkish version of the Pregnancy Physical Activity Questionnaire is a valid and reliable tool for measurement of the physical activity level of pregnant women. PMID:26834336

  18. Comparison of the Physical Activity and Sedentary Behaviour Assessment Questionnaire and the Short-Form International Physical Activity Questionnaire: An Analysis of Health Survey for England Data

    PubMed Central

    Scholes, Shaun; Bridges, Sally; Ng Fat, Linda; Mindell, Jennifer S.

    2016-01-01

    Background The Physical Activity and Sedentary Behaviour Assessment Questionnaire (PASBAQ), used within the Health Survey for England (HSE) at 5-yearly intervals, is not included annually due to funding and interview-length constraints. Policy-makers and data-users are keen to consider shorter instruments such as the Short-form International Physical Activity Questionnaire (IPAQ) for the annual survey. Both questionnaires were administered in HSE 2012, enabling comparative assessment in a random sample of 1252 adults. Methods Relative agreement using prevalence-adjusted bias-adjusted Kappa (PABAK) statistics was estimated for: sufficient aerobic activity (moderate-to-vigorous physical activity [MVPA] ≥150minutes/week); inactivity (MVPA<30minutes/week); and excessive sitting (≥540minutes/weekday). Cross-sectional associations with health outcomes were compared across tertiles of MVPA and tertiles of sitting time using logistic regression with tests for linear trend. Results Compared with PASBAQ data, IPAQ-assessed estimates of sufficient aerobic activity and inactivity were higher and lower, respectively; estimates of excessive sitting were higher. Demographic patterns in prevalence were similar. Agreement using PABAK statistics was fair-to-moderate for sufficient aerobic activity (0.32–0.49), moderate-to-substantial for inactivity (0.42–0.74), and moderate-to-substantial for excessive sitting (0.49–0.75). As with the PASBAQ, IPAQ-assessed MVPA and sitting each showed graded associations with mental well-being (women: P for trend = 0.003 and 0.004, respectively) and obesity (women: P for trend = 0.007 and 0.014, respectively). Conclusions Capturing habitual physical activity and sedentary behaviour through brief questionnaires is complex. Differences in prevalence estimates can reflect differences in questionnaire structure and content rather than differences in reported behaviour. Treating all IPAQ-assessed walking as moderate-intensity contributed to the

  19. Non-Exercise Estimation of VO[subscript 2]max Using the International Physical Activity Questionnaire

    ERIC Educational Resources Information Center

    Schembre, Susan M.; Riebe, Deborah A.

    2011-01-01

    Non-exercise equations developed from self-reported physical activity can estimate maximal oxygen uptake (VO[subscript 2]max) as well as sub-maximal exercise testing. The International Physical Activity Questionnaire is the most widely used and validated self-report measure of physical activity. This study aimed to develop and test a VO[subscript…

  20. Validity and Reliability of the Persian Version of Baecke Habitual Physical Activity Questionnaire in Healthy Subjects

    PubMed Central

    Sadeghisani, Meissam; Dehghan Manshadi, Farideh; Azimi, Hadi; Montazeri, Ali

    2016-01-01

    Background Baecke Habitual Physical Activity Questionnaire (BHPAQ) has widely been employed in clinical and laboratorial studies as a tool for measuring subjects' physical activities. But, the reliability and validity of this questionnaire have not been investigated among Persian speakers. Objectives Therefore, the aim of the current study was examining the reliability and validity of the Persian version of the BHPAQ in healthy Persian adults. Materials and Methods After following the process of forward-backward translation, 32 subjects were invited to fill out the Persian version of the questionnaire in two independent sessions (3 - 7 days after the first session) in order to determine the reliability index. Also, the validity of the questionnaire was assessed through concurrent validity by 126 subjects (66 males and 60 females) answering both the Baecke and the International Physical Activity Questionnaire (IPAQ). Results An acceptable level of intraclass correlation coefficient (ICC of work score = 0.95, sport score = 0.93, and leisure score = 0.77) was achieved for the Persian Baecke questionnaire. Correlations between Persian Baecke and IPAQ with and without the score for sitting position were found to be 0.19 and 0.36, respectively. Conclusions The Persian version of the BHPAQ is a reliable and valid instrument that can be used to measure the level of habitual functional activities in Persian-speaking subjects. PMID:27826396

  1. Psychometric Properties of the Modified RESIDE Physical Activity Questionnaire among Low-Income Overweight Women

    PubMed Central

    Jones, Sydney A.; Evenson, Kelly R.; Johnston, Larry F.; Trost, Stewart G.; Samuel-Hodge, Carmen; Jewell, David A.; Kraschnewski, Jennifer L.; Keyserling, Thomas C.

    2014-01-01

    Objective This study explored the criterion-related validity and test-retest reliability of the modified RESIDential Enviroment (RESIDE) physical activity questionnaire and whether the instrument’s validity varied by body mass index (BMI), education, race/ethnicity, or employment status. Design Validation study using baseline data collected for randomized trial of a weight loss intervention. Method Participants recruited from health departments wore an ActiGraph accelerometer and self-reported non-occupational walking, moderate and vigorous physical activity on the modified RESIDE questionnaire. We assessed validity (n=152) using Spearman correlation coefficients (SCC), and reliability (n=57) using intraclass correlation coefficients (ICC). Results When compared to steps, moderate physical activity, and bouts of moderate/vigorous physical activity measured by accelerometer, these questionnaire measures showed fair evidence for validity: recreational walking (SCC 0.23–0.36), total walking (SCC 0.24–0.37), and total moderate physical activity (SCC 0.18–0.36). Correlations for self-reported walking and moderate physical activity were higher among unemployed participants and women with lower BMIs. Generally no other variability in the validity of the instrument was found. Evidence for reliability of RESIDE measures of recreational walking, total walking, and total moderate physical activity was substantial (ICC 0.56–0.68). Conclusions Evidence for questionnaire validity and reliability varied by activity domain and was strongest for walking measures. The questionnaire may capture physical activity less accurately among women with higher BMIs and employed participants. Capturing occupational activity, specifically walking at work, may improve questionnaire validity. PMID:24462117

  2. Assessment of physical activity in older people with and without cognitive impairment.

    PubMed

    Hauer, Klaus; Lord, Stephen R; Lindemann, Ulrich; Lamb, Sarah E; Aminian, Kamiar; Schwenk, Michael

    2011-10-01

    The purpose of this study was to validate a new interview-administered physical activity questionnaire (Assessment of Physical Activity in Frail Older People; APAFOP) in older people with and without cognitive impairment. The authors assessed feasibility, validity, and test-retest reliability in 168 people (n = 78 with, n = 88 without cognitive impairment). Concurrent validity was assessed against an inertia-based motion sensor and an established questionnaire. Sensitivity to change was tested in an ongoing study in patients with mild to moderate dementia (n = 81). Assessment of physical activity by the APAFOP and the motion sensor correlated well in the total sample (TS; p = .705), as well as in the subsamples with cognitive impairment (CI; p = .585) and without CI (p = .787). Excellent feasibility with an acceptance rate of 100%, test-retest reliability (intraclass correlation coefficients ranging from .973 (TS) to .975 (CI) to .966 (no CI), and sensitivity to change (effect sizes: 0.35-1.47) were found in both subsamples.

  3. Validation of the Physical Activity Questionnaire for Older Children (PAQ-C) among Chinese children

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study initially validates the Chinese version of the Physical Activity Questionnaire for Older Children (PAQ-C), which has been identified as a potentially valid instrument to assess moderate-to-vigorous physical activity (MVPA) in children among diverse racial groups. The psychometric properti...

  4. Validity of a Questionnaire to Assess the Physical Activity Level in Coronary Artery Disease Patients

    ERIC Educational Resources Information Center

    Guiraud, Thibaut; Granger, Richard; Bousquet, Marc; Gremeaux, Vincent

    2012-01-01

    The aim of the study is to compare, in coronary artery disease patients, physical activity (PA) assessed with the Dijon Physical Activity Questionnaire (DPAQ) and the true PA objectively measured using an accelerometer. Seventy patients wore an accelerometer (MyWellness Key actimeter) throughout 1 week after a cardiac rehabilitation program that…

  5. Validation Evidence for the Netherlands Physical Activity Questionnaire for Young Children: The Iowa Bone Development Study

    ERIC Educational Resources Information Center

    Janz, Kathleen F.; Broffitt, Barbara; Levy, Steven M.

    2005-01-01

    In this paper, the authors present reliability and validity information for the Netherlands (Health Education Project) Physical Activity Questionnaire (NPAQ), a global proxy report of children's everyday activity preferences (Montoye, Kemper, Saris, & Washburn, 1996). In this study, the authors examined the measurement properties of a global…

  6. Reliability and Validity of the Flemish Physical Activity Computerized Questionnaire in Adults

    ERIC Educational Resources Information Center

    Matton, Lynn; Wijndaele, Katrien; Duvigneaud, Nathalie; Duquet, William; Philippaerts, Renaat; Thomis, Martine; Lefevre, Johan

    2007-01-01

    The purpose of this study was to investigate the test-retest reliability and concurrent validity of the Flemish Physical Activity Computerized Questionnaire (FPACQ) in employed/unemployed and retired people. The FPACQ was developed to assess detailed information on several dimensions of physical activity and sedentary behavior over a usual week. A…

  7. Looking at the Social Activity for Adolescents with Orthopedic Impairments

    ERIC Educational Resources Information Center

    Biastro, Leslie; Frank, Heather; Larwin, Karen H.

    2015-01-01

    Adolescents with identified orthopedic impairments are often less likely to participate in social activities outside of the school setting. However, the adolescents who are able to participate in activities have higher social skills, more academic successes, and show more satisfaction in their roles as family member or friend. The aim of this…

  8. Physical Activity and Adiposity Markers at Older Ages: Accelerometer Vs Questionnaire Data

    PubMed Central

    Sabia, Séverine; Cogranne, Pol; van Hees, Vincent T.; Bell, Joshua A.; Elbaz, Alexis; Kivimaki, Mika; Singh-Manoux, Archana

    2015-01-01

    Objective Physical activity is critically important for successful aging, but its effect on adiposity markers at older ages is unclear as much of the evidence comes from self-reported data on physical activity. We assessed the associations of questionnaire-assessed and accelerometer-assessed physical activity with adiposity markers in older adults. Design/Setting/Participants This was a cross-sectional study on 3940 participants (age range 60-83 years) of the Whitehall II study who completed a 20-item physical activity questionnaire and wore a wrist-mounted accelerometer for 9 days in 2012 and 2013. Measurements Total physical activity was estimated using metabolic equivalent hours/week for the questionnaire and mean acceleration for the accelerometer. Time spent in moderate-and-vigorous physical activity (MVPA) was also assessed by questionnaire and accelerometer. Adiposity assessment included body mass index, waist circumference, and fat mass index. Fat mass index was calculated as fat mass/height² (kg/m²), with fat mass estimated using bioimpedance. Results Greater total physical activity was associated with lower adiposity for all adiposity markers in a dose-response manner. In men, the strength of this association was 2.4 to 2.8 times stronger with the accelerometer than with questionnaire data. In women, it was 1.9 to 2.3 times stronger. For MVPA, questionnaire data in men suggested no further benefit for adiposity markers past 1 hour/week of activity. This was not the case for accelerometer-assessed MVPA where, for example, compared with men undertaking <1 hour/week of accelerometer-assessed MVPA, waist circumference was 3.06 (95% confidence interval 2.06–4.06) cm lower in those performing MVPA 1–2.5 hours/week, 4.69 (3.47–5.91) cm lower in those undertaking 2.5–4 hours/week, and 7.11 (5.93–8.29) cm lower in those performing ≥4 hours/week. Conclusions The association of physical activity with adiposity markers in older adults was

  9. Validation of Self-Report Measures of Physical Activity: A Case Study Using the New Zealand Physical Activity Questionnaire

    ERIC Educational Resources Information Center

    Mackay, Lisa M.; Schofield, Grant M.; Schluter, Philip J.

    2007-01-01

    Accurate measurement of physical activity is fundamentally important in epidemiological research of physical activity behavior. A widely used telephone-based physical activity questionnaire was compared with other methods of administration and objective measures (pedometers and accelerometers) among 80 adults (43 women). The telephone…

  10. Differential Item Functioning Analysis of the 2003-04 NHANES Physical Activity Questionnaire

    ERIC Educational Resources Information Center

    Gao, Yong; Zhu, Weimo

    2011-01-01

    Using differential item functioning (DIF) analyses, this study examined whether there were any DIF items in the National Health and Nutrition Examination Survey (NHANES) physical activity (PA) questionnaire. A subset of adult data from the 2003-04 NHANES study (n = 3,083) was used. PA items related to respondents' occupational, transportation,…

  11. Effect of memory impairment on training outcomes in ACTIVE

    PubMed Central

    UNVERZAGT, FREDERICK W.; KASTEN, LINDA; JOHNSON, KATHY E.; REBOK, GEORGE W.; MARSISKE, MICHAEL; KOEPKE, KATHY MANN; ELIAS, JEFFREY W.; MORRIS, JOHN N.; WILLIS, SHERRY L.; BALL, KARLENE; REXROTH, DANIEL F.; SMITH, DAVID M.; WOLINSKY, FREDRIC D.; TENNSTEDT, SHARON L.

    2009-01-01

    Cognitive training improves mental abilities in older adults, but the trainability of persons with memory impairment is unclear. We conducted a subgroup analysis of subjects in the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) trial to examine this issue. ACTIVE enrolled 2802 non-demented, community-dwelling adults aged 65 years and older and randomly assigned them to one of four groups: Memory training, reasoning training, speed-of-processing training, or no-contact control. For this study, participants were defined as memory-impaired if baseline Rey Auditory Verbal Learning Test (AVLT) sum recall score was 1.5 SD or more below predicted AVLT sum recall score from a regression-derived formula using age, education, ethnicity, and vocabulary from all subjects at baseline. Assessments were taken at baseline (BL), post-test, first annual (A1), and second annual (A2) follow-up. One hundred and ninety-three subjects were defined as memory-impaired and 2580 were memory-normal. Training gain as a function memory status (impaired vs. normal) was compared in a mixed effects model. Results indicated that memory-impaired participants failed to benefit from Memory training but did show normal training gains after reasoning and speed training. Memory function appears to mediate response to structured cognitive interventions in older adults. PMID:17942013

  12. Physical Activity Characteristics across GOLD Quadrants Depend on the Questionnaire Used

    PubMed Central

    Demeyer, Heleen; Gimeno-Santos, Elena; Rabinovich, Roberto A.; Hornikx, Miek; Louvaris, Zafeiris; de Boer, Willem I.; Karlsson, Niklas; de Jong, Corina; Van der Molen, Thys; Vogiatzis, Ioannis; Janssens, Wim; Garcia-Aymerich, Judith; Troosters, Thierry; Polkey, Michael I.

    2016-01-01

    Background The GOLD multidimensional classification of COPD severity combines the exacerbation risk with the symptom experience, for which 3 different questionnaires are permitted. This study investigated differences in physical activity (PA) in the different GOLD quadrants and patient’s distribution in relation to the questionnaire used. Methods 136 COPD patients (58±21% FEV1 predicted, 34F/102M) completed COPD assessment test (CAT), clinical COPD questionnaire (CCQ) and modified Medical Research Council (mMRC) questionnaire. Exacerbation history, spirometry and 6MWD were collected. PA was objectively measured for 2 periods of 1 week, 6 months apart, in 5 European centres; to minimise seasonal and clinical variation the average of these two periods was used for analysis. Results GOLD quadrants C+D had reduced PA compared with A+B (3824 [2976] vs. 5508 [4671] steps.d-1, p<0.0001). The choice of questionnaire yielded different patient distributions (agreement mMRC-CAT κ = 0.57; CCQ-mMRC κ = 0.71; CCQ-CAT κ = 0.72) with different clinical characteristics. PA was notably lower in patients with an mMRC score ≥2 (3430 [2537] vs. 5443 [3776] steps.d-1, p <0.001) in both the low and high risk quadrants. Conclusions Using different questionnaires changes the patient distribution and results in different clinical characteristics. Therefore, standardization of the questionnaire used for classification is critical to allow comparison of different studies using this as an entry criterion. Clinical Trial Registration ClinicalTrials.gov NCT01388218 PMID:26974332

  13. Familiar Sports and Activities Adapted for Multiply Impaired Persons.

    ERIC Educational Resources Information Center

    Schilling, Mary Lou, Ed.

    1984-01-01

    Means of adapting some familiar and popular physical activities for multiply impaired persons are described. Games reviewed are dice baseball, one base baseball, in-house bowling, wheelchair bowling, ramp bowling, swing-ball bowling, table tennis, shuffleboard, beanbag bingo and tic-tac-toe, balloon basketball, circle football, and wheelchair…

  14. Physical Activities for Children with Severe Multiple Impairments.

    ERIC Educational Resources Information Center

    Grosse, Susan J.

    1981-01-01

    Intended for teachers of students with severe multiple impairments, the booklet examines the role of physical activities in the education of this population and suggests approaches to exhancing their motor development. Suggestions are offered for stimulating movement in preschool, elementary, and secondary immobile children, including tactile…

  15. Active and Passive Perceptual Learning in the Visually Impaired.

    ERIC Educational Resources Information Center

    Conrod, Beverley E.; And Others

    1986-01-01

    Active and passive perceptual training methods were tested with 30 macular degeneration patients to improve their residual vision. The main conclusion was that perceptual training may contribute to successful visual adjustment and that the effect of training is not limited to a particular level of visual impairment. (Author/CL)

  16. Active Reading Experience Questionnaire: Development and Validation of an Instrument for Studying Active Reading Activities

    ERIC Educational Resources Information Center

    Palilonis, Jennifer; Butler, Darrell

    2015-01-01

    The increasing adoption of mobile platforms and digital textbooks in university classrooms continues to have a profound impact on higher education. Advocates believe that providing students digital textbooks with built-in annotation features and interactive study tools will improve learning by facilitating active reading, a task essential to…

  17. Physical activity among dental health professionals in Hyderabad City: A questionnaire survey

    PubMed Central

    Srilatha, Adepu; Doshi, Dolar; Reddy, M. Padma; Kulkarni, Suhas; Reddy, B. Srikanth; Reddy, Sahithi

    2016-01-01

    Background: To assess and compare physical activity based on age, gender, marital status, education, and employment among dental health professionals in Hyderabad City, India. Materials and Methods: A cross-sectional questionnaire study was conducted among dentists and they were personally interviewed by a single trained interviewer. The frequency (in days) and time (in minutes) spent in doing vigorous- and moderate-intensity activity in a typical week in three domains and sedentary behavior were assessed using 16-item Global Physical Activity Questionnaire. Metabolic equivalents (METs) were used to express the intensity of physical activities. Results: Overall, 60.7% of the 313 respondents were physically active, with activity at work and commuting activity were the main contributors of physical activity. With increasing age, there was a decrease in physical activity with more sedentary behavior, professionals in age group of 21–30 years, who were single, those with Bachelor's Degree and those in teaching field performed activity at work, commuting, and recreational activity for more minutes with overall high MET minutes per week and least sedentary behavior. Conclusion: The prevalence of physical activity was high among dental health professionals. PMID:28182058

  18. Physical activity and mild cognitive impairment and Alzheimer's disease.

    PubMed

    Lautenschlager, Nicola T; Cox, Kay; Kurz, Alexander F

    2010-09-01

    Regular physical activity undoubtedly has many health benefits for all age groups. In the past decade, researchers and clinicians have begun to focus their attention on whether physical activity also can improve health outcomes of older adults who experience mild cognitive impairment (MCI) or dementia. This ongoing question is gaining relevance in light of the aging of the world population and with it the rise of age-related conditions, such as cognitive impairment. Not surprisingly, physical activity is among the potential protective lifestyle factors mentioned when strategies to delay or prevent dementia are discussed. The first large-scale multidomain intervention trials are under way to put this to the test. This review aims to give an overview of recent trials of physical activity in patients with MCI or dementia.

  19. Reliability and validity of an internet-based questionnaire measuring lifetime physical activity.

    PubMed

    De Vera, Mary A; Ratzlaff, Charles; Doerfling, Paul; Kopec, Jacek

    2010-11-15

    Lifetime exposure to physical activity is an important construct for evaluating associations between physical activity and disease outcomes, given the long induction periods in many chronic diseases. The authors' objective in this study was to evaluate the measurement properties of the Lifetime Physical Activity Questionnaire (L-PAQ), a novel Internet-based, self-administered instrument measuring lifetime physical activity, among Canadian men and women in 2005-2006. Reliability was examined using a test-retest study. Validity was examined in a 2-part study consisting of 1) comparisons with previously validated instruments measuring similar constructs, the Lifetime Total Physical Activity Questionnaire (LT-PAQ) and the Chasan-Taber Physical Activity Questionnaire (CT-PAQ), and 2) a priori hypothesis tests of constructs measured by the L-PAQ. The L-PAQ demonstrated good reliability, with intraclass correlation coefficients ranging from 0.67 (household activity) to 0.89 (sports/recreation). Comparison between the L-PAQ and the LT-PAQ resulted in Spearman correlation coefficients ranging from 0.41 (total activity) to 0.71 (household activity); comparison between the L-PAQ and the CT-PAQ yielded coefficients of 0.58 (sports/recreation), 0.56 (household activity), and 0.50 (total activity). L-PAQ validity was further supported by observed relations between the L-PAQ and sociodemographic variables, consistent with a priori hypotheses. Overall, the L-PAQ is a useful instrument for assessing multiple domains of lifetime physical activity with acceptable reliability and validity.

  20. The Work and Home Activities Questionnaire: Energy Expenditure Estimates and Association With Percent Body Fat

    PubMed Central

    Block, Gladys; Jensen, Christopher D.; Block, Torin J.; Norris, Jean; Dalvi, Tapashi B.; Fung, Ellen B.

    2015-01-01

    Background Understanding and increasing physical activity requires assessment of occupational, home, leisure and sedentary activities. Methods A physical activity questionnaire was developed using data from a large representative U.S. sample; includes occupational, leisure and home-based domains; and produces estimates of energy expenditure, percent body fat, minutes in various domains, and meeting recommendations. It was tested in 396 persons, mean age 44 years. Estimates were evaluated in relation to percent body fat measured by dual-energy x-ray absorptiometry. Results Median energy expenditure was 2,365 kcal (women) and 2.960 kcal (men). Women spent 35.1 minutes/day in moderate household activities, 13.0 minutes in moderate leisure and 4.0 minutes in vigorous activities. Men spent 18.0, 22.5 and 15.6 minutes/day in those activities, respectively. Men and women spent 276.4 and 257.0 minutes/day in sedentary activities. Respondents who met recommendations through vigorous activities had significantly lower percent body fat than those who did not, while meeting recommendations only through moderate activities was not associated with percent body fat. Predicted and observed percent body fat correlated at r = .73 and r = .82 for men and women respectively, P < .0001. Conclusions This questionnaire may be useful for understanding health effects of different components of activity, and for interventions to increase activity levels. PMID:19998851

  1. Candesartan Ameliorates Impaired Fear Extinction Induced by Innate Immune Activation

    PubMed Central

    Quiñones, María M.; Maldonado, Lizette; Velazquez, Bethzaly; Porter, James T.

    2015-01-01

    Patients with post-traumatic stress disorder (PTSD) tend to show signs of a relatively increased inflammatory state suggesting that activation of the immune system may contribute to the development of PTSD. In the present study, we tested whether activation of the innate immune system can disrupt acquisition or recall of auditory fear extinction using an animal model of PTSD. Male adolescent rats received auditory fear conditioning in context A. The next day, an intraperitoneal injection of lipopolysaccharide (LPS; 100 μg/kg) prior to auditory fear extinction in context B impaired acquisition and recall of extinction. LPS (100 μg/kg) given after extinction training did not impair extinction recall suggesting that LPS did not affect consolidation of extinction. In contrast to cued fear extinction, contextual fear extinction was not affected by prior injection of LPS (100 μg/kg). Although LPS also reduced locomotion, we could dissociate the effects of LPS on extinction and locomotion by using a lower dose of LPS (50 μg/kg) which impaired locomotion without affecting extinction. In addition, 15 hrs after an injection of 250 μg/kg LPS in adult rats, extinction learning and recall were impaired without affecting locomotion. A sub-chronic treatment with candesartan, an angiotensin II type 1 receptor blocker, prevented the LPS-induced impairment of extinction in adult rats. Our results demonstrate that activation of the innate immune system can disrupt auditory fear extinction in adolescent and adult animals. These findings also provide direction for clinical studies of novel treatments that modulate the innate immune system for stress-related disorders like PTSD. PMID:26520214

  2. Candesartan ameliorates impaired fear extinction induced by innate immune activation.

    PubMed

    Quiñones, María M; Maldonado, Lizette; Velazquez, Bethzaly; Porter, James T

    2016-02-01

    Patients with post-traumatic stress disorder (PTSD) tend to show signs of a relatively increased inflammatory state suggesting that activation of the immune system may contribute to the development of PTSD. In the present study, we tested whether activation of the innate immune system can disrupt acquisition or recall of auditory fear extinction using an animal model of PTSD. Male adolescent rats received auditory fear conditioning in context A. The next day, an intraperitoneal injection of lipopolysaccharide (LPS; 100 μg/kg) prior to auditory fear extinction in context B impaired acquisition and recall of extinction. LPS (100 μg/kg) given after extinction training did not impair extinction recall suggesting that LPS did not affect consolidation of extinction. In contrast to cued fear extinction, contextual fear extinction was not affected by prior injection of LPS (100 μg/kg). Although LPS also reduced locomotion, we could dissociate the effects of LPS on extinction and locomotion by using a lower dose of LPS (50 μg/kg) which impaired locomotion without affecting extinction. In addition, 15 h after an injection of 250 μg/kg LPS in adult rats, extinction learning and recall were impaired without affecting locomotion. A sub-chronic treatment with candesartan, an angiotensin II type 1 receptor blocker, prevented the LPS-induced impairment of extinction in adult rats. Our results demonstrate that activation of the innate immune system can disrupt auditory fear extinction in adolescent and adult animals. These findings also provide direction for clinical studies of novel treatments that modulate the innate immune system for stress-related disorders like PTSD.

  3. Prefrontal activity and impaired memory encoding strategies in schizophrenia.

    PubMed

    Guimond, Synthia; Hawco, Colin; Lepage, Martin

    2017-03-08

    Schizophrenia patients have significant memory difficulties that have far-reaching implications in their daily life. These impairments are partly attributed to an inability to self-initiate effective memory encoding strategies, but its core neurobiological correlates remain unknown. The current study addresses this critical gap in our knowledge of episodic memory impairments in schizophrenia. Schizophrenia patients (n = 35) and healthy controls (n = 23) underwent a Semantic Encoding Memory Task (SEMT) during an fMRI scan. Brain activity was examined for conditions where participants were a) prompted to use semantic encoding strategies, or b) not prompted but required to self-initiate such strategies. When prompted to use semantic encoding strategies, schizophrenia patients exhibited similar recognition performance and brain activity as healthy controls. However, when required to self-initiate these strategies, patients had significant reduced recognition performance and brain activity in the left dorsolateral prefrontal cortex, as well as in the left temporal gyrus, left superior parietal lobule, and cerebellum. When patients were divided based on performance on the SEMT, the subgroup with more severe deficits in self-initiation also showed greater reduction in left dorsolateral prefrontal activity. These results suggest that impaired self-initiation of elaborative encoding strategies is a driving feature of memory deficits in schizophrenia. We also identified the neural correlates of impaired self-initiation of semantic encoding strategies, in which a failure to activate the left dorsolateral prefrontal cortex plays a key role. These findings provide important new targets in the development of novel treatments aiming to improve memory and ultimately patients' outcome.

  4. Validity and Reliability of International Physical Activity Questionnaire-Short Form in Chinese Youth

    ERIC Educational Resources Information Center

    Wang, Chao; Chen, Peijie; Zhuang, Jie

    2013-01-01

    Purpose: The psychometric profiles of the widely used International Physical Activity Questionnaire-Short Form (IPAQ-SF) in Chinese youth have not been reported. The purpose of this study was to examine the validity and reliability of the IPAQ-SF using a sample of Chinese youth. Method: One thousand and twenty-one youth (M[subscript age] = 14.26 ±…

  5. Reliability and validity of the Flemish Physical Activity Computerized Questionnaire in adults.

    PubMed

    Matton, Lynn; Wijndaele, Katrien; Duvigneaud, Nathalie; Duquet, William; Philippaerts, Renaat; Thomis, Martine; Lefevre, Johan

    2007-09-01

    The purpose of this study was to investigate the test-retest reliability and concurrent validity of the Flemish Physical Activity Computerized Questionnaire (FPACQ) in employed/unemployed and retired people. The FPACQ was developed to assess detailed information on several dimensions of physical activity and sedentary behavior over a usual week. A triaxial accelerometer, the RT3 Triaxial Research Tracker (RT3), in combination with a written 7-day activity record, was used as the objective criterion measure. In employed/unemployed people, 2-week test-retest reliability for several activity variables calculated from the FPACQ was good to excellent with intraclass correlations (ICCs) ranging from .67 to .99. In retired people ICCs were lower but, except for time spent eating, still fair to excellent, ranging from .57 to .96. Except for time spent in leisure time activities for men and the average energy expenditure related to sports participation in women, correlations between the RT3 and the FPACQ generally supported the relative validity of the FPACQ for employed/unemployed people (r ranging from .37 to .88). Values for retired people were somewhat lower (r ranging from .15 to .85), but most variables still reached at least moderate correlations. Concerning absolute validity, the FPACQ generally overestimated physical activity and underestimated sedentary behavior compared to the RT3. From this study, it can be concluded that the FPACQ is a reliable and reasonably valid questionnaire for assessing different dimensions of physical activity and sedentary behavior.

  6. Impaired Brain Creatine Kinase Activity in Huntington's Disease

    PubMed Central

    Zhang, S.F.; Hennessey, T.; Yang, L.; Starkova, N.N.; Beal, M.F.; Starkov, A.A.

    2011-01-01

    Background Huntington's disease (HD) is associated with impaired energy metabolism in the brain. Creatine kinase (CK) catalyzes ATP-dependent phosphorylation of creatine (Cr) into phosphocreatine (PCr), thereby serving as readily available high-capacity spatial and temporal ATP buffering. Objective: Substantial evidence supports a specific role of the Cr/PCr system in neurodegenerative diseases. In the brain, the Cr/PCr ATP-buffering system is established by a concerted operation of the brain-specific cytosolic enzyme BB-CK and ubiquitous mitochondrial uMt-CK. It is not yet established whether the activity of these CK isoenzymes is impaired in HD. Methods We measured PCr, Cr, ATP and ADP in brain extracts of 3 mouse models of HD – R6/2 mice, N171-82Q and HdhQ111 mice – and the activity of CK in cytosolic and mitochondrial brain fractions from the same mice. Results The PCr was significantly increased in mouse HD brain extracts as compared to nontransgenic littermates. We also found an approximately 27% decrease in CK activity in both cytosolic and mitochondrial fractions of R6/2 and N171-82Q mice, and an approximately 25% decrease in the mitochondria from HdhQ111 mice. Moreover, uMt-CK and BB-CK activities were approximately 63% lower in HD human brain samples as compared to nondiseased controls. Conclusion Our findings lend strong support to the role of impaired energy metabolism in HD, and point out the potential importance of impairment of the CK-catalyzed ATP-buffering system in the etiology of HD. PMID:21124007

  7. Hypoxia induced cognitive impairment modulating activity of Cyperus rotundus.

    PubMed

    Kandikattu, Hemanth Kumar; Deep, Satya Narayan; Razack, Sakina; Amruta, Narayanappa; Prasad, Dipti; Khanum, Farhath

    2017-03-27

    Hypobaric hypoxia leads to decrease in cellular oxygen content which subsequently damages the hippocampus with an increase in brain oxidative stress and impairs the memory of the individual. In the present study, we have evaluated the cognitive impairment modulating activity of total oligomeric flavonoids fraction of Cyperus rotundus (TOF) in Sprague Dawley rats. The rats were trained for memory activity for a period of 7days followed by 7days exposure to 25,000ft. altitude and the spatial reference memory was evaluated. Behavioral analysis of the rats by Morris water maze experiment showed that TOF supplementation enhanced the spatial reference memory activity of the rats exposed to hypobaric hypoxia. The decrease in antioxidant status of the animals exposed to hypoxia was restored with TOF supplementation. The increase in ROS, lipid peroxidation products and protein carbonyls of the hippocampus was significantly decreased in animals with TOF administration. The histological assessment of the pyramidal cells of the hippocampus of hypoxia-exposed animals showed nuclear damage and TOF supplementation prevented nuclear damage. TOF administration suppressed hypoxia-induced increase in serotonin, dopamine, and norepinephrine. GABA and Ach levels were decreased by hypoxia which was prevented by TOF supplementation. The increase in GFAP, HIF-1α and VEGF expression in CA3 region of the hippocampus in hypoxia-exposed rats was decreased in TOF administered rats. Taken together, TOF extract ameliorates hypobaric hypoxia induced memory impairment and neurodegeneration in hippocampus through its anti-stress effects.

  8. Development of the Oxford Participation and Activities Questionnaire: constructing an item pool

    PubMed Central

    Kelly, Laura; Jenkinson, Crispin; Dummett, Sarah; Dawson, Jill; Fitzpatrick, Ray; Morley, David

    2015-01-01

    Purpose The Oxford Participation and Activities Questionnaire is a patient-reported outcome measure in development that is grounded on the World Health Organization International Classification of Functioning, Disability, and Health (ICF). The study reported here aimed to inform and generate an item pool for the new measure, which is specifically designed for the assessment of participation and activity in patients experiencing a range of health conditions. Methods Items were informed through in-depth interviews conducted with 37 participants spanning a range of conditions. Interviews aimed to identify how their condition impacted their ability to participate in meaningful activities. Conditions included arthritis, cancer, chronic back pain, diabetes, motor neuron disease, multiple sclerosis, Parkinson’s disease, and spinal cord injury. Transcripts were analyzed using the framework method. Statements relating to ICF themes were recast as questionnaire items and shown for review to an expert panel. Cognitive debrief interviews (n=13) were used to assess items for face and content validity. Results ICF themes relevant to activities and participation in everyday life were explored, and a total of 222 items formed the initial item pool. This item pool was refined by the research team and 28 generic items were mapped onto all nine chapters of the ICF construct, detailing activity and participation. Cognitive interviewing confirmed the questionnaire instructions, items, and response options were acceptable to participants. Conclusion Using a clear conceptual basis to inform item generation, 28 items have been identified as suitable to undergo further psychometric testing. A large-scale postal survey will follow in order to refine the instrument further and to assess its psychometric properties. The final instrument is intended for use in clinical trials and interventions targeted at maintaining or improving activity and participation. PMID:26056503

  9. Assessing Metacognitive Activities: The In-Depth Comparison of a Task-Specific Questionnaire with Think-Aloud Protocols

    ERIC Educational Resources Information Center

    Schellings, Gonny L.; van Hout-Wolters, Bernadette H. A .M.; Veenman, Marcel V. J.; Meijer, Joost

    2013-01-01

    Teaching and assessing metacognitive activities are important educational objectives, and teachers are calling for efficient instruments. The advantages of questionnaires in measuring metacognitive activities are obvious, but serious validity issues appear. For example, correlations of questionnaire data with think-aloud measures are generally…

  10. A self-efficacy questionnaire regarding leisure time physical activity: Psychometric properties among Iranian male adolescents

    PubMed Central

    Abasi, Mohammad Hadi; Eslami, Ahmad Ali; Rakhshani, Fatemeh; Shiri, Mansoor

    2016-01-01

    Background: Attention to different aspects of self-efficacy leads to actual evaluation of self-efficacy about physical activity. This study was carried out in order to design and determine psychometric characteristics of a questionnaire for evaluation of self-efficacy about leisure time physical activity (SELPA) among Iranian adolescent boys, with an emphasis on regulatory self-efficacy. Materials and Methods: This descriptive–analytic study was conducted in 734 male adolescents aged 15–19 years in Isfahan. After item generation and item selection based on review of literature and other questionnaires, content validity index (CVI) and content validity ratio (CVR) were determined and items were modified employing the opinions of expert panel (N = 10). Comprehensibility of the questionnaire was determined by members of target group (N = 35). Exploratory factors analysis (EFA) was operated on sample 1 (N1 = 325) and confirmatory factors analysis (CFA) on sample 2 (N2 = 347). Reliability of SELPA was estimated via internal consistency method. Results: According to EFA, barrier self-efficacy and scheduling self-efficacy are the two main aspects of SELPA with the total variance of 65%. The suggested model was confirmed by CFA and all fitness indices of the corrected model were good. Cronbach's alpha was totally estimated as 0.89 and for barrier and scheduling self-efficacy, it was 0.86 and 0.81, respectively. Conclusions: The results provide some evidence for acceptable validity and reliability of SELPA in Iranian adolescent boys. However, further investigations, especially for evaluation of predictive power of the questionnaire, are necessary. PMID:26985219

  11. Development and evaluation of the physical activity questionnaire for elderly Japanese: the Nakanojo study.

    PubMed

    Yasunaga, Akitomo; Park, Hyuntae; Watanabe, Eiji; Togo, Fumiharu; Park, Sungjin; Shephard, Roy J; Aoyagi, Yukitoshi

    2007-10-01

    The Physical Activity Questionnaire for Elderly Japanese (PAQ-EJ) is a self-administered physical activity questionnaire for elderly Japanese; the authors report here on its repeatability and direct and indirect validity. Reliability was assessed by repeat administration after 1 month. Direct validation was based on accelerometer data collected every 4 s for 1 month in 147 individuals age 65-85 years. Indirect validation against a 10-item Barthel index (activities of daily living [ADL]) was completed in 3,084 individuals age 65-99 years. The test-retest coefficient was high (r = .64-.71). Total and subtotal scores for lower (transportation, housework, and labor) and higher intensity activities (exercise/sports) were significantly correlated with step counts and durations of physical activity <3 and >or=3 METs (r = .41, .28, .53), respectively. Controlling for age and ADL, scores for transportation, exercise/sports, and labor were greater in men, but women performed more housework. Sex- and ADL- or age-adjusted PAQ-EJ scores were significantly lower in older and dependent people. PAQ-EJ repeatability and validity seem comparable to those of instruments used in Western epidemiological studies.

  12. 76 FR 8846 - Proposed Information Collection (Disability Benefits Questionnaires-Group 1) Activity: Comment...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-15

    .... Titles: a. Hematologic and Lymphatic Conditions, Including Leukemia Disability Benefits Questionnaire, VA... Cancer and Leukemias) Disability Benefits Questionnaire, VA Form 21-0960O-1. l. Eating...

  13. Promoting Leisure-Time Physical Activity for Students with Visual Impairments Using Generalization Tactics

    ERIC Educational Resources Information Center

    Haegele, Justin A.

    2015-01-01

    Important and favorable health effects of physical activity have been well documented. Unfortunately, school-aged individuals who are visually impaired tend to be less physically active than their peers without visual impairments. Although students with visual impairments learn skills to participate in physical activities during their PE classes,…

  14. The Self-Presentation Motives for Physical Activity Questionnaire: Instrument Development and Preliminary Construct Validity Evidence.

    PubMed

    Howle, Timothy C; Dimmock, James A; Whipp, Peter R; Jackson, Ben

    2015-06-01

    With the aim of advancing the literature on impression management in physical activity settings, we developed a theoretically derived 2 by 2 instrument that was designed to measure different types of context-specific self-presentation motives. Following item generation and expert review (Study 1), the instrument was completed by 206 group exercise class attendees (Study 2) and 463 high school physical education students (Study 3). Our analyses supported the intended factor structure (i.e., reflecting acquisitive-agentic, acquisitive-communal, protective-agentic, and protective-communal motives). We found some support for construct validity, and the self-presentation motives were associated with variables of theoretical and applied interest (e.g., impression motivation and construction, social anxiety, social and achievement goals, efficacy beliefs, engagement). Taken together, the results indicate that the Self-presentation Motives for Physical Activity Questionnaire (SMPAQ) may be useful for measuring various types of self-presentation motives in physical activity settings.

  15. Measuring and validating physical activity and sedentary behavior comparing a parental questionnaire to accelerometer data and diaries.

    PubMed

    Bringolf-Isler, Bettina; Mäder, Urs; Ruch, Nicole; Kriemler, Susi; Grize, Leticia; Braun-Fahrländer, Charlotte

    2012-05-01

    Accurately measuring children's physical activity and their sedentary behavior is challenging. The present study compared 189 parental responses to a questionnaire surveying physical activity and sedentary behavior of children aged 6-14 years, to accelerometer outputs and time activity diaries for the same group. Responses were analyzed taking age, sex and maternal education into account. Correlation coefficients between questionnaire reports and accelerometer-based physical activity across all age groups were acceptable (up to r = .55). Yet, adjustment for age markedly attenuated these associations, suggesting concomitant influences of biological and behavioral processes linked to age. The comparisons of general time indications in the questionnaire with 24h-diary records suggested that parents tended to under- and over-report single activities, possibly due to social desirability. We conclude that physical activity questionnaires need to be designed for specific age groups and be administered in combination with objective measurements.

  16. Physical activity for elderly persons with neurological impairment: a review.

    PubMed

    Eldar, R; Marincek, C

    2000-09-01

    The paper reviews studies conducted on physical activities and exercise in elderly persons with neurological impairment due to stroke, Guillain-Barre syndrome, Parkinson's disease, multiple sclerosis or post-polio syndrome. The paper concludes: (i) it is not possible at present to draw conclusions regarding persons with Guillain-Barre syndrome and Parkinson's disease; (ii) individuals with multiple sclerosis and post-polio syndrome benefit from physical activity, but all studies have so far been conducted on those under 65 years of age, and its effect on elderly persons with these diseases is not known; (iii) exercise and customary activities (walking and swimming) should be encouraged and promoted in elderly persons after stroke.

  17. 76 FR 33417 - Agency Information Collection (Disability Benefits Questionnaires-Group 2) Activity Under OMB Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-08

    ... Questionnaire, VA Form 21-0960A-4. d. Diabetic Peripheral Neuropathy (Diabetic Sensory-Motor Peripheral.... Flatfoot (PES PLANUS) Disability Benefits Questionnaire, VA Form 21-0960M-5. l. Foot Miscellaneous...

  18. Endothelial RIG-I activation impairs endothelial function

    SciTech Connect

    Asdonk, Tobias; Nickenig, Georg; Zimmer, Sebastian

    2012-03-30

    Highlights: Black-Right-Pointing-Pointer RIG-I activation impairs endothelial function in vivo. Black-Right-Pointing-Pointer RIG-I activation alters HCAEC biology in vitro. Black-Right-Pointing-Pointer EPC function is affected by RIG-I stimulation in vitro. -- Abstract: Background: Endothelial dysfunction is a crucial part of the chronic inflammatory atherosclerotic process and is mediated by innate and acquired immune mechanisms. Recent studies suggest that pattern recognition receptors (PRR) specialized in immunorecognition of nucleic acids may play an important role in endothelial biology in a proatherogenic manner. Here, we analyzed the impact of endothelial retinoic acid inducible gene I (RIG-I) activation upon vascular endothelial biology. Methods and results: Wild type mice were injected intravenously with 32.5 {mu}g of the RIG-ligand 3pRNA (RNA with triphosphate at the 5 Prime end) or polyA control every other day for 7 days. In 3pRNA-treated mice, endothelium-depended vasodilation was significantly impaired, vascular oxidative stress significantly increased and circulating endothelial microparticle (EMP) numbers significantly elevated compared to controls. To gain further insight in RIG-I dependent endothelial biology, cultured human coronary endothelial cells (HCAEC) and endothelial progenitor cells (EPC) were stimulated in vitro with 3pRNA. Both cells types express RIG-I and react with receptor upregulation upon stimulation. Reactive oxygen species (ROS) formation is enhanced in both cell types, whereas apoptosis and proliferation is not significantly affected in HCAEC. Importantly, HCAEC release significant amounts of proinflammatory cytokines in response to RIG-I stimulation. Conclusion: This study shows that activation of the cytoplasmatic nucleic acid receptor RIG-I leads to endothelial dysfunction. RIG-I induced endothelial damage could therefore be an important pathway in atherogenesis.

  19. Self-reported visual impairment and impact on vision-related activities in an elderly Nigerian population: report from the Ibadan Study of Ageing

    PubMed Central

    Bekibele, CO; Gureje, Oye

    2010-01-01

    Background Studies have shown an association between visual impairment and poor overall function. Studies from Africa and developing countries show high prevalence of visual impairment. More information is needed on the community prevalence and impact of visual impairment among elderly Africans. Methods A multi-stage stratified sampling of households was implemented to select persons aged 65 years and over in the south-western and north-central parts of Nigeria. Impairments of distant and near vision were based on subjective self-reports obtained with the use of items derived from the World Health Organization multi-country World Health Survey questionnaire. Impairment was defined as reporting much difficulty to questions on distant and near vision. Disabilities in activities of daily living (ADL) and instrumental activities of daily living (IADL) were evaluated by interview, using standardized scales. Results A total of 2054 subjects 957 (46.6%) males and 1097 (53.4) females responded to the questions on vision. 22% (n=453) of the respondents reported distant vision impairment, and 18% (n=377) reported near vision impairment (not mutually exclusive). 15% (n= 312) however reported impairment for both far and near vision. Impairment of distant vision increased progressively with age (P < 0.01). Persons with self reported near vision impairment had elevated risk of functional disability in several IADLs and ADLs than those with out. Distant vision impairment was less associated with role limitations in both ADLs and IADLs. Conclusion The prevalence of self reported distant visual impairment was high but that for near visual impairment was less than expected in this elderly African population. Impairment of near vision was found to carry with it a higher burden of functional disability than that of distant vision. PMID:18780258

  20. Physical activity parenting: A systematic review of questionnaires and their associations with child activity levels

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Insufficient physical activity (PA) is considered a critical contributor to childhood overweight. Parents are a key in influencing their child's PA through various mechanisms of PA parenting, including support, restriction of PA, and facilitation of enrollment in PA classes or activities. However, s...

  1. Psychometric properties of the 7-Day Physical Activity Recall questionnaire in individuals with severe mental illness.

    PubMed

    Soundy, Andy; Taylor, Adrian; Faulkner, Guy; Rowlands, Ann

    2007-12-01

    Few self-report measures of physical activity have been validated in individuals with severe mental illness. The purpose of this study was to examine the validity and reliability of a 7-day recall measure (7DR: [Blair, S. N. (1984). How to assess exercise habits and physical fitness. In J. D. Matarazzo, N. E. Miller, & S. M. Weiss, (Eds.), Behavioural health: A handbook of health enhancement and disease prevention (pp. 424-447). New York: Wiley.]) through comparison with RT3 triaxial accelerometry data. Fourteen individuals took part in the study. Validity was considered by Kendall's tau correlation and (Bland, J. M., & Altman, D. G. (1986). Statistical-methods for assessing agreement between 2 methods of clinical measurement. Lancet, 1(8476), 307-310) limits of agreement and test-retest reliability was measured by ICC. The only significant correlation between measures was total energy expenditure (tau = 0.43). The 7-DR over reported moderate physical activity by 16.9 +/- 52.3 min/day, but under reported vigorous physical activity by -10.4 +/- 24.3 min/day. Test retest ICC was significant for all outcome measures. Overall, the 7-DR was reliable but exhibited questionable validity. The use of self-report questionnaires such as the 7-DR may inaccurately estimate the levels of physical activity in this population, and may not be sensitive to monitoring intervention-related changes in physical activity.

  2. Test-retest reliability of a questionnaire to assess physical environmental factors pertaining to physical activity

    PubMed Central

    Evenson, Kelly R; McGinn, Aileen P

    2005-01-01

    Background Despite the documented benefits of physical activity, many adults do not obtain the recommended amounts. Barriers to physical activity occur at multiple levels, including at the individual, interpersonal, and environmental levels. Only until more recently has there been a concerted focus on how the physical environment might affect physical activity behavior. With this new area of study, self-report measures should be psychometrically tested before use in research studies. Therefore the objective of this study was to document the test-retest reliability of a questionnaire designed to assess physical environmental factors that might be associated with physical activity in a diverse adult population. Methods Test and retest surveys were conducted over the telephone with 106 African American and White women and men living in either Forsyth County, North Carolina or Jackson, Mississippi. Reliability of self-reported environmental factors across four domains (e.g., access to facilities and destinations, functionality and safety, aesthetics, natural environment) was determined using intraclass correlation coefficients (ICC) overall and separately by gender and race. Results Generally items displayed moderate and sometimes substantial reliability (ICC between 0.4 to 0.8), with a few differences by gender or race, across each of the domains. Conclusion This study provides some psychometric evidence for the use of many of these questions in studies examining the effect of self-reported physical environmental measures on physical activity behaviors, among African American and White women and men. PMID:15958168

  3. Ionizing Radiation Impairs T Cell Activation by Affecting Metabolic Reprogramming.

    PubMed

    Li, Heng-Hong; Wang, Yi-Wen; Chen, Renxiang; Zhou, Bin; Ashwell, Jonathan D; Fornace, Albert J

    2015-01-01

    Ionizing radiation has a variety of acute and long-lasting adverse effects on the immune system. Whereas measureable effects of radiation on immune cell cytotoxicity and population change have been well studied in human and animal models, little is known about the functional alterations of the surviving immune cells after ionizing radiation. The objective of this study was to delineate the effects of radiation on T cell function by studying the alterations of T cell receptor activation and metabolic changes in activated T cells isolated from previously irradiated animals. Using a global metabolomics profiling approach, for the first time we demonstrate that ionizing radiation impairs metabolic reprogramming of T cell activation, which leads to substantial decreases in the efficiency of key metabolic processes required for activation, such as glucose uptake, glycolysis, and energy metabolism. In-depth understanding of how radiation impacts T cell function highlighting modulation of metabolism during activation is not only a novel approach to investigate the pivotal processes in the shift of T cell homeostasis after radiation, it also may lead to new targets for therapeutic manipulation in the combination of radiotherapy and immune therapy. Given that appreciable effects were observed with as low as 10 cGy, our results also have implications for low dose environmental exposures.

  4. Validation of the SQUASH Physical Activity Questionnaire in a Multi-Ethnic Population: The HELIUS Study

    PubMed Central

    Gademan, M. G. J.; Snijder, M. B.; Engelbert, R. H. H.; Dijkshoorn, H.; Terwee, C. B.; Stronks, K.

    2016-01-01

    Purpose To investigate the reliability and validity of the SQUASH physical activity (PA) questionnaire in a multi-ethnic population living in the Netherlands. Methods We included participants from the HELIUS study, a population-based cohort study. In this study we included Dutch (n = 114), Turkish (n = 88), Moroccan (n = 74), South-Asian Surinamese (n = 98) and African Surinamese (n = 91) adults, aged 18–70 years. The SQUASH was self-administered twice to assess test-re-test reliability (mean interval 6–7 weeks) and participants wore an accelerometer and heart rate monitor (Actiheart) to enable assessment of construct validity. Results We observed low test-re-test reliability; Intra class correlation coefficients ranged from low (0.05 for moderate/high intensity PA in African Surinamese women) to acceptable (0.78 for light intensity PA in Moroccan women). The discrepancy between self-reported and measured PA differed on the basis of the intensity of activity: self-reported light intensity PA was lower than measured but self-reported moderate/high intensity PA was higher than measured, with wide limits of agreement. The discrepancy between questionnaire and Actiheart measures of moderate intensity PA did not differ between ethnic minority and Dutch participants with correction for relevant confounders. Additionally, the SQUASH overestimated the number of participants meeting the Dutch PA norm; Cohen’s kappas for the agreement were poor, the highest being 0.30 in Dutch women. Conclusion We found considerable variation in the test-re-test reliability and validity of self-reported PA with no consistency based on ethnic origin. Our findings imply that the SQUASH does not provide a valid basis for comparison of PA between ethnic groups. PMID:27575490

  5. Assessing Adult Leisure Activities: An Extension of a Self-Report Activity Questionnaire

    ERIC Educational Resources Information Center

    Jopp, Daniela S.; Hertzog, Christopher

    2010-01-01

    Everyday leisure activities in adulthood and old age have been investigated with respect to constructs such as successful aging, an engaged lifestyle, and prevention of age-related cognitive decline. They also relate to mental health and have clinical value, as they can inform diagnosis and interventions. In the present study, the authors enhanced…

  6. Does physical activity influence semantic memory activation in amnestic mild cognitive impairment?

    PubMed

    Smith, J Carson; Nielson, Kristy A; Woodard, John L; Seidenberg, Michael; Verber, Matthew D; Durgerian, Sally; Antuono, Piero; Butts, Alissa M; Hantke, Nathan C; Lancaster, Melissa A; Rao, Stephen M

    2011-07-30

    The effect of physical activity (PA) on functional brain activation for semantic memory in amnestic mild cognitive impairment (aMCI) was examined using event-related functional magnetic resonance imaging during fame discrimination. Significantly greater semantic memory activation occurred in the left caudate of High- versus Low-PA patients, (P=0.03), suggesting PA may enhance memory-related caudate activation in aMCI.

  7. NOX Activity Is Increased in Mild Cognitive Impairment

    PubMed Central

    Gupta, Sunita; Parrino, Taryn E.; Knight, Alecia G.; Ebenezer, Philip J.; Weidner, Adam M.; LeVine, Harry; Keller, Jeffrey N.; Markesbery, William R.

    2010-01-01

    Abstract This study was undertaken to investigate the profile of NADPH oxidase (NOX) in the clinical progression of Alzheimer's disease (AD). Specifically, NOX activity and expression of the regulatory subunit p47phox and the catalytic subunit gp91phox was evaluated in affected (superior and middle temporal gyri) and unaffected (cerebellum) brain regions from a longitudinally followed group of patients. This group included both control and late-stage AD subjects, and also subjects with preclinical AD and with amnestic mild cognitive impairment (MCI) to evaluate the profile of NOX in the earliest stages of dementia. Data show significant elevations in NOX activity and expression in the temporal gyri of MCI patients as compared with controls, but not in preclinical or late-stage AD samples, and not in the cerebellum. Immunohistochemical evaluations of NOX expression indicate that whereas microglia express high levels of gp91phox, moderate levels of gp91phox also are expressed in neurons. Finally, in vitro experiments showed that NOX inhibition blunted the ability of oligomeric amyloid beta peptides to injure cultured neurons. Collectively, these data show that NOX expression and activity are upregulated specifically in a vulnerable brain region of MCI patients, and suggest that increases in NOX-associated redox pathways in neurons might participate in the early pathogenesis of AD. Antioxid. Redox Signal. 12, 1371–1382. PMID:19929442

  8. Activation of the TGFβ pathway impairs endothelial to haematopoietic transition.

    PubMed

    Vargel, Özge; Zhang, Yang; Kosim, Kinga; Ganter, Kerstin; Foehr, Sophia; Mardenborough, Yannicka; Shvartsman, Maya; Enright, Anton J; Krijgsveld, Jeroen; Lancrin, Christophe

    2016-02-19

    The endothelial to haematopoietic transition (EHT) is a key developmental process where a drastic change of endothelial cell morphology leads to the formation of blood stem and progenitor cells during embryogenesis. As TGFβ signalling triggers a similar event during embryonic development called epithelial to mesenchymal transition (EMT), we hypothesised that TGFβ activity could play a similar role in EHT as well. We used the mouse embryonic stem cell differentiation system for in vitro recapitulation of EHT and performed gain and loss of function analyses of the TGFβ pathway. Quantitative proteomics analysis showed that TGFβ treatment during EHT increased the secretion of several proteins linked to the vascular lineage. Live cell imaging showed that TGFβ blocked the formation of round blood cells. Using gene expression profiling we demonstrated that the TGFβ signalling activation decreased haematopoietic genes expression and increased the transcription of endothelial and extracellular matrix genes as well as EMT markers. Finally we found that the expression of the transcription factor Sox17 was up-regulated upon TGFβ signalling activation and showed that its overexpression was enough to block blood cell formation. In conclusion we showed that triggering the TGFβ pathway does not enhance EHT as we hypothesised but instead impairs it.

  9. 76 FR 61149 - Agency Information Collection (Disability Benefits Questionnaires-Group 4) Activity Under OMB Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-03

    ... Form 21- 0960-I-5. Urinary Tract (including Bladder & Urethra) Conditions (excluding Male Reproductive System) Disability Benefits Questionnaire, VA Form 21- 0960-J-4. Respiratory Conditions (other...

  10. Accelerometer-Determined Physical Activity and Its Comparison with the International Physical Activity Questionnaire in a Sample of Nigerian Adults

    PubMed Central

    Oyeyemi, Adewale L.; Umar, Maimuna; Oguche, Friday; Aliyu, Salamatu U.; Oyeyemi, Adetoyeje Y.

    2014-01-01

    Introduction Accurate assessment of physical activity to identify current levels and changes within the population is dependent on the precision of the measurement tools. The aim of this study was to compare components of physical activity measured with an adapted version of the International Physical Activity Questionnaire (Hausa IPAQ-SF) and the accelerometer in a sample of Nigeria adults. Methods One hundred and forty-four participants (Mean age = 32.6±9.9 years, 40.3% women) in a cross-sectional study wore an accelerometer for seven consecutive days and completed the Hausa IPAQ-SF questionnaire on the eighth day. Total physical activity, time spent in moderate-to-vigorous activity (MVPA) and sedentary time assessed by Hausa IPAQ-SF and accelerometer were compared. The absolute and criterion- related validity of the Hausa IPAQ-SF was assessed by Bland-Altman analysis and Spearman Correlation Coefficients, respectively. Specificity and sensitivity were calculated to classify individuals according to the global standard guideline for sufficient physical activity. Results Compared with the accelerometer, higher time in MVPA and total physical activity were reported on the Hausa IPAQ-SF (p<0.001), while low to moderate correlations (Rs = 0.03–0.38) were found between the two methods. The 95% limits of agreement were wide between methods for total physical activity (−23019 to 20375 METmin.d−1) and sedentary time (−510 to 150 min.d−1). The sensitivity (76.2%) of Hausa IPAQ-SF to identify insufficiently active people was good, but its specificity (33.3%) to correctly classify sufficiently active people was low. Conclusions The Hausa IPAQ-SF overestimated components of physical activity among Nigerian adults, and demonstrated poor to moderate evidence of absolute and criterion validity. Further evaluation of IPAQ and other self-report physical activity instruments in other Africa populations could enhance accurate evaluation of physical activity data

  11. Measuring physical activity-related environmental factors: reliability and predictive validity of the European environmental questionnaire ALPHA

    PubMed Central

    2010-01-01

    Background A questionnaire to assess physical activity related environmental factors in the European population (a 49-item and an 11-item version) was created as part of the framework of the EU-funded project "Instruments for Assessing Levels of PHysical Activity and fitness (ALPHA)". This paper reports on the development and assessment of the questionnaire's test-retest stability, predictive validity, and applicability to European adults. Methods The first pilot test was conducted in Belgium, France and the UK. In total 190 adults completed both forms of the ALPHA questionnaire twice with a one-week interval. Physical activity was concurrently measured (i) by administration of the long version of the International Physical Activity Questionnaire (IPAQ) by interview and (ii) by accelerometry (Actigraph™ device). After adaptations, the second field test took place in Belgium, the UK and Austria; 166 adults completed the adapted questionnaire at two time points, with minimum one-week interval. In both field studies intraclass correlation coefficients (ICC) and proportion of agreement were computed to assess the stability of the two test scores. Predictive validity was examined in the first field test by correlating the results of the questionnaires with physical activity data from accelerometry and long IPAQ-last 7 days. Results The reliability scores of the ALPHA questionnaire were moderate-to good in the first field testing (ICC range 0.66 - 0.86) and good in the second field testing (ICC range 0.71 - 0.87). The proportion of agreement for the ALPHA short increased significantly from the first (range 50 - 83%) to the second field testing (range 85 - 95%). Environmental scales from both versions of the ALPHA questionnaire were significantly associated with self-reported minutes of transport-related walking, and objectively measured low intensity physical activity levels, particularly in women. Both versions were easily administered with an average completion time

  12. Reliability of questionnaires to assess the healthy eating and activity environment of a child's home and school.

    PubMed

    Wilson, Annabelle; Magarey, Anthea; Mastersson, Nadia

    2013-01-01

    Childhood overweight and obesity are a growing concern globally, and environments, including the home and school, can contribute to this epidemic. This paper assesses the reliability of two questionnaires (parent and teacher) used in the evaluation of a community-based childhood obesity prevention intervention, the eat well be active (ewba) Community Programs. Parents and teachers were recruited from two primary schools and they completed the same questionnaire twice in 2008 and 2009. Data from both questionnaires were classified into outcomes relevant to healthy eating and activity, and target outcomes, based on the goals of the ewba Community Programs, were identified. Fourteen and 12 outcomes were developed from the parent and teacher questionnaires, respectively. Sixty parents and 28 teachers participated in the reliability study. Intraclass correlation coefficients for outcomes ranged from 0.37 to 0.92 (parent) (P < 0.05) and from 0.42 to 0.86 (teacher) (P < 0.05). Internal consistency, measured by Cronbach's alpha, of teacher scores ranged from 0.11 to 0.91 and 0.13 to 0.78 for scores from the parent questionnaire. The parent and teacher questionnaires are moderately reliable tools for simultaneously assessing child intakes, environments, attitudes, and knowledge associated with healthy eating and physical activity in the home and school and may be useful for evaluation of similar programs.

  13. Impaired release of corticosterone from adrenals contributes to impairment of circadian rhythms of activity in hyperammonemic rats.

    PubMed

    Llansola, Marta; Ahabrach, Hanan; Errami, Mohammed; Cabrera-Pastor, Andrea; Addaoudi, Kaoutar; Felipo, Vicente

    2013-08-15

    Patients with liver cirrhosis may present impaired sleep-wake and circadian rhythms, relative adrenal insufficiency and altered hypothalamus-pituitary-adrenal gland (HPA) axis. The underlying mechanisms remain unclear. Circadian rhythms are modulated by corticosteroids which secretion is regulated by HPA axis. Hyperammonemia alters circadian rhythms of activity and corticosterone in rats. The aims were: (1) assessing whether corticosterone alterations are responsible for altered circadian rhythm in hyperammonemia: (2) to shed light on the mechanism by which corticosterone circadian rhythm is altered in hyperammonemia. The effects of daily corticosterone injection at ZT10 on circadian rhythms of activity, plasma corticosterone, adreno-corticotropic hormone (ACTH) and hypothalamic corticotropic releasing hormone (CRH) were assessed in control and hyperammonemic rats. ACTH-induced corticosterone release was analyzed in cultured adrenal cells. Corticosterone injection restores the corticosterone peak in hyperammonemic rats and their activity and circadian rhythm. Plasma ACTH and CRH in hypothalamus are increased in hyperammonemic rats. Corticosterone injection normalizes ACTH. Chronic hyperammonemia impairs adrenal function, reduces corticosterone content and ACTH-induced corticosterone release in adrenals, leading to reduced feedback modulation of HPA axis by corticosterone which contributes to impair circadian rhythms of activity. Impaired circadian rhythms and motor activity may be corrected in hyperammonemia and hepatic encephalopathy by corticosterone treatment.

  14. 78 FR 35661 - Proposed Information Collection (Disability Benefits Questionnaires) Activity: Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-13

    .... Hairy Cell and Other B-Cell Leukemias Disability Benefits Questionnaire, VA Form 21-0960b-1. c... exposure: Hairy Cell and ] Other Chronic B-cell Leukemias, Parkinson's and Ischemic Heart diseases.... Hairy Cell and Other B-Cell Leukemias Disability Benefits Questionnaire, VA Form 21-0960b-1-500....

  15. 75 FR 60170 - Proposed Information Collection (Disability Benefits Questionnaires) Activity: Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-29

    ...-0960a-1. b. Hairy Cell and Other B-Cell Leukemias Disability Benefits Questionnaire, VA Form 21-0960b-1... on herbicide exposure: Hairy Cell and Other Chronic B-cell Leukemias, Parkinson's and Ischemic Heart...,750. b. Hairy Cell and Other B-Cell Leukemias Disability Benefits Questionnaire, VA Form...

  16. 75 FR 76081 - Agency Information Collection (Disability Benefits Questionnaires) Activity Under OMB Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-07

    .... Hairy Cell and Other B-Cell Leukemias Disability Benefits Questionnaire, VA Form 21-0960b-1. c... exposure: Hairy Cell and Other Chronic B-cell Leukemias, Parkinson's and Ischemic Heart diseases. Veterans... Form 21-0960a-1--13,750. b. Hairy Cell and Other B-Cell Leukemias Disability Benefits Questionnaire,...

  17. Development of the parents' perception of their involvement in their child's tennis activity questionnaire (Q-PPICTA).

    PubMed

    Hurtel, V; Lacassagne, M-F

    2013-08-01

    The purpose of this study was to develop and validate a questionnaire for assessing parents' perception of their involvement in their children's tennis activity (Q-PPICTA). The validation required four successive studies. In study 1, a preliminary version of the questionnaire was formulated after selecting and adapting items taken from existing questionnaires and interviews conducted with the parents of 36 young tennis players. Three factors for measuring parental involvement in sport were identified and retained: emotional, logistic, and informational supports. In study 2, exploratory factor analyses were performed on data collected from 214 parents of tennis players. Results attested the questionnaire's three-factor structure and ascertained its internal consistency. In study 3, a confirmatory factor analysis as well as tests on convergent and discriminant validity were carried out on data gathered from a different sample of 220 parents of tennis players. Statistics confirmed the questionnaire's three-factor structure and reliability. In study 4, the questionnaire's external construct validity was compared with another sample consisting of 192 parents and their children. Overall, results underlined satisfactory psychometric properties for the Q-PPICTA. Nevertheless, further studies are required to confirm the questionnaire's accuracy, reliability, and temporal validity.

  18. Assessing Activity Limitations in Patients with Neuromuscular Diseases: Is the ACTIVLIM Questionnaire Linked to ICF and ICF-CY?

    ERIC Educational Resources Information Center

    Raggi, Alberto; Leonardi, Matilde

    2009-01-01

    The objective of this study was to explore to what extent the ACTIVLIM questionnaire, designed to evaluate limitations in activities involving upper and lower limbs in adults and children with neuromuscular diseases, is linked to the domains of the Activities and Participation of the International Classification of Functioning, Disability and…

  19. Lower Cortisol Activity is Associated with First-Time Driving while Impaired

    PubMed Central

    Couture, Sophie; Ouimet, Marie Claude; Gianoulakis, Christina; Tremblay, Jacques; Ng Ying Kin, NMK; Brochu, Serge; Pruessner, Jens; Dedovic, Katarina; Brown, Thomas G

    2015-01-01

    Driving while impaired (DWI) is a grave and persistent high-risk behavior. Previous work demonstrated that DWI recidivists had attenuated cortisol reactivity compared to non-DWI drivers. This suggests that cortisol is a neurobiological marker of high-risk driving. The present study tested the hypothesis that this initial finding would extend to first-time DWI (fDWI) offenders compared to non-DWI drivers. Male fDWI offenders (n = 139) and non-DWI drivers (n = 31) were exposed to a stress task, and their salivary cortisol activity (total output and reactivity) was measured. Participants also completed questionnaires on sensation seeking, impulsivity, substance use, and engagement in risky and criminal behaviors. As hypothesized, fDWI offenders, compared to non-DWI drivers, had lower cortisol reactivity; fDWI offenders also showed lower total output. In addition, cortisol activity was the most important predictor of group membership, after accounting for alcohol misuse patterns and consequences and other personality and problem behavior characteristics. The findings indicate that attenuated cortisol activity is an independent factor associated with DWI offending risk at an earlier stage in the DWI trajectory than previously detected. PMID:25922575

  20. A systematic review of reliability and objective criterion-related validity of physical activity questionnaires

    PubMed Central

    2012-01-01

    Physical inactivity is one of the four leading risk factors for global mortality. Accurate measurement of physical activity (PA) and in particular by physical activity questionnaires (PAQs) remains a challenge. The aim of this paper is to provide an updated systematic review of the reliability and validity characteristics of existing and more recently developed PAQs and to quantitatively compare the performance between existing and newly developed PAQs. A literature search of electronic databases was performed for studies assessing reliability and validity data of PAQs using an objective criterion measurement of PA between January 1997 and December 2011. Articles meeting the inclusion criteria were screened and data were extracted to provide a systematic overview of measurement properties. Due to differences in reported outcomes and criterion methods a quantitative meta-analysis was not possible. In total, 31 studies testing 34 newly developed PAQs, and 65 studies examining 96 existing PAQs were included. Very few PAQs showed good results on both reliability and validity. Median reliability correlation coefficients were 0.62–0.71 for existing, and 0.74–0.76 for new PAQs. Median validity coefficients ranged from 0.30–0.39 for existing, and from 0.25–0.41 for new PAQs. Although the majority of PAQs appear to have acceptable reliability, the validity is moderate at best. Newly developed PAQs do not appear to perform substantially better than existing PAQs in terms of reliability and validity. Future PAQ studies should include measures of absolute validity and the error structure of the instrument. PMID:22938557

  1. Cost Template for Meaningful Activity Intervention for Mild Cognitive Impairment

    PubMed Central

    Yueh-Feng Lu, Yvonne; Bakas, Tamilyn; Haase, Joan E.

    2013-01-01

    Purpose To describe and compare cost estimates for a pilot study of the Daily Enhancement of Meaningful Activity (DEMA) intervention for persons with mild cognitive impairment (PwMCI)-caregiver dyads. Background The increasing complexity of the health care system and rising health care costs, have forced nurse scientists to find ways to effectively improve health care quality and control cost, but no studies have examined costs for new programs that target PwMCI-caregiver dyads. Description of the project Pilot study data were used to develop a cost template and calculate the cost of implementing the DEMA. Outcomes Mean cost per dyad was estimated to be $1,327.97 in the clinical setting, compared with $1,069.06 if a telephone delivery mode had been used for four of the six face-to-face sessions. This difference was largely due to transportation-related expenses and staff cost. Implications DEMA should be evaluated further with larger and more diverse samples as a technology-delivered health promotion program that could reduce costs. PMID:23392066

  2. Facilitation of quadriceps activation is impaired following eccentric exercise.

    PubMed

    Hedayatpour, N; Arendt-Nielsen, L; Falla, D

    2014-04-01

    Contracting the knee flexor muscles immediately before a maximum voluntary contraction (MVC) of knee extension increases the maximal force that the extensor muscles can exert. It is hypothesized that this phenomenon can be impaired by muscle fiber damage following eccentric exercise [delayed onset muscle soreness (DOMS)]. This study investigates the effect of eccentric exercise and DOMS on knee extension MVC immediately following a reciprocal-resisted knee flexion contraction. Electromyography (EMG) was recorded from the knee extensors and flexors of 12 healthy men during knee extension MVCs performed in a reciprocal (maximal knee extension preceded by resisted knee flexion), and nonreciprocal condition (preceded by relaxation of the knee flexors). At baseline, knee extension MVC force was greater during the reciprocal condition (P < 0.001), whereas immediately after, 24 and 48 h after eccentric exercise, the MVC force was not different between conditions. Similarly, at baseline, the EMG amplitude of the quadriceps during the MVC was larger for the reciprocal condition (P < 0.001). However, immediately after, 24 and 48 h postexercise the EMG amplitude was similar between conditions. In conclusion, eccentric exercise abolished the facilitation of force production for the knee extensors, which normally occurs when maximum knee extension is preceded by activation of the knee flexors.

  3. Increasing SK2 channel activity impairs associative learning

    PubMed Central

    McKay, Bridget M.; Oh, M. Matthew; Galvez, Roberto; Burgdorf, Jeffrey; Kroes, Roger A.; Weiss, Craig; Adelman, John P.; Moskal, Joseph R.

    2012-01-01

    Enhanced intrinsic neuronal excitability of hippocampal pyramidal neurons via reductions in the postburst afterhyperpolarization (AHP) has been hypothesized to be a biomarker of successful learning. This is supported by considerable evidence that pharmacologic enhancement of neuronal excitability facilitates learning. However, it has yet to be demonstrated that pharmacologic reduction of neuronal excitability restricted to the hippocampus can retard acquisition of a hippocampus-dependent task. Thus, the present study was designed to address this latter point using a small conductance potassium (SK) channel activator NS309 focally applied to the dorsal hippocampus. SK channels are important contributors to intrinsic excitability, as measured by the medium postburst AHP. NS309 increased the medium AHP and reduced excitatory postsynaptic potential width of CA1 neurons in vitro. In vivo, NS309 reduced the spontaneous firing rate of CA1 pyramidal neurons and impaired trace eyeblink conditioning in rats. Conversely, trace eyeblink conditioning reduced levels of SK2 channel mRNA and protein in the hippocampus. Therefore, the present findings indicate that modulation of SK channels is an important cellular mechanism for associative learning and further support postburst AHP reductions in hippocampal pyramidal neurons as a biomarker of successful learning. PMID:22552186

  4. 76 FR 16478 - Proposed Information Collection (Disability Benefits Questionnaires-Group 2) Activity: Comment...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-23

    ... Form 21-0960A-4. d. Diabetic Peripheral Neuropathy (Diabetic Sensory-Motor Peripheral Neuropathy.... Flatfoot (PES PLANUS) Disability Benefits Questionnaire, VA Form 21-0960M-5. l. Foot Miscellaneous...

  5. 76 FR 35950 - Agency Information Collection (Disability Benefits Questionnaires-Group 3) Activity Under OMB Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-20

    .... Breast Conditions and Disorders Disability Benefits Questionnaire, VA Form 21-0960K-1. m. Gynecological.... Osteomyelitis Disability Benefits Questionnaire, VA Form 21- 0960M-11. q. Ear Conditions (Including Vestibular.... n. VA Form 21-0960L-2--1,250. o. VA Form 21-0960M-3--25,000. p. VA Form 21-0960M-11--10,000. q....

  6. Validity of the Physical Activity Questionnaires IPAQ-SF and GPAQ for Cancer Survivors: Insights from a Spanish Cohort.

    PubMed

    Ruiz-Casado, A; Alejo, L B; Santos-Lozano, A; Soria, A; Ortega, M J; Pagola, I; Fiuza-Luces, C; Palomo, I; Garatachea, N; Cebolla, H; Lucia, A

    2016-11-01

    Regular physical activity (PA) decreases mortality risk in survivors of breast and colorectal cancer. Such impacts of exercise have prompted initiatives designed both to promote and adequately monitor PA in cancer survivors. This study examines the validity of 2 widely used self-report methods for PA determination, the International Physical Activity Questionnaire short version (IPAQ-SF) and Global Physical Activity Questionnaire (GPAQ). Both instruments were compared with the triaxial accelerometry (Actigraph) method as an objective reference standard. Study participants were 204 cancer survivors (both sexes, aged 18-79 years). Compared with accelerometry, both questionnaires significantly overestimated PA levels (across all intensities) and underestimated physical inactivity levels. No differences were detected between the 2 questionnaires except for a shorter inactivity time estimated by GPAQ (p=0.001). The Bland and Altman method confirmed that both questionnaires overestimated all PA levels. Receiver operating characteristic (ROC) analysis classified IPAQ and GPAQ as fair and poor predictors, respectively, of the proportions of survivors fulfilling international PA recommendations (≥150 min·week(-1) of moderate-vigorous PA). IPAQ-SF showed a higher sensitivity but lower specificity than GPAQ. Our data do not support the use of IPAQ-SF or GPAQ to determine PA or inactivity levels in cancer survivors.

  7. Cognitive Correlates of Functional Abilities in Individuals with Mild Cognitive Impairment: Comparison of Questionnaire, Direct Observation and Performance-based Measures

    PubMed Central

    Schmitter-Edgecombe, Maureen; Parsey, Carolyn M.

    2014-01-01

    The relationship between and the cognitive correlates of several proxy measures of functional status were studied in a population with mild cognitive impairment (MCI). Participants were 51 individuals diagnosed with MCI and 51 cognitively healthy older adults (OA). Participants completed performance-based functional status tests, standardized neuropsychological tests, and performed eight activities of daily living (e.g., watered plants, filled medication dispenser) while under direct observation in a campus apartment. An informant interview about everyday functioning was also conducted. Compared to the OA control group, the MCI group performed more poorly on all proxy measures of everyday functioning. The informant-report of instrumental activities of daily living (IADL) did not correlate with the two performance-based measures; however, both the informant-report IADL and the performance-based everyday problem-solving test correlated with the direct observation measure. After controlling for age and education, cognitive predictors did not explain a significant amount of variance in the performance-based measures; however, performance on a delayed memory task was a unique predictor for the informant-report IADL, and processing speed predicted unique variance for the direct observation score. These findings indicate that differing methods for evaluating functional status are not assessing completely overlapping aspects of everyday functioning in the MCI population. PMID:24766574

  8. Parents' Perceptions of Physical Activity for Their Children with Visual Impairments

    ERIC Educational Resources Information Center

    Perkins, Kara; Columna, Luis; Lieberman, Lauren; Bailey, JoEllen

    2013-01-01

    Introduction: Ongoing communication with parents and the acknowledgment of their preferences and expectations are crucial to promote the participation of physical activity by children with visual impairments. Purpose: The study presented here explored parents' perceptions of physical activity for their children with visual impairments and explored…

  9. Introducing an Outcome Expectation Questionnaire and Its Psychometric Properties Regarding Leisure Time Physical Activity for Iranian Male Adolescent

    PubMed Central

    Abasi, Mohammad Hadi; Eslami, Ahmad Ali; Rakhshani, Fatemeh

    2015-01-01

    Background: Outcome expectation (OE) is known as a psychosocial determinant of leisure time physical activity (LTPA). Despite importance of this construct evaluation, there is no evidence of special questionnaire for measuring OE in Persian speaking Iranian male adolescents. Objectives: This article reports development and psychometric evaluation process of a specific questionnaire that evaluates OE about LTPA among Iranian male adolescents. Materials and Methods: Literature review and group discussions were used to select 26 items of this questionnaire based on 3 dimensions of OE (self-evaluation, social expectancy, and physical expectancy). All Participants (n = 720) were divided into two groups randomly after evaluating comprehensibility, face and content validity, and items analysis. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were separately operated on one of these groups for evaluation of the construct validity of questionnaire. The reliability of the questionnaire was estimated by the Cronbach α. Results: EFA extracted 3 main factors explained 45.80%, 10.31%, and 7.51% of OE variance, respectively. Almost all fit indexes in CFA were acceptable (CMIN = 107.39, CMIN/DF = 2.619, CFI = 0.938, PCFI = 0.699, RMSEA = 0.067, PCLOSE = 0.034). Finally 11 items remained in the questionnaire, which showed excellent reliability on main study (α = 0.85). Conclusions: This study provided evidence regarding the reliability and validity of the Iranian male adolescent outcome expectation about leisure time physical activity (IMAO-PAC) and illustrated that this new questionnaire can be used to measure the perceived exercise benefits among target group in observational and interventional studies. PMID:26082851

  10. Nutrition and Physical Activity Knowledge Assessment: Development of Questionnaires and Evaluation of Reliability in African American and Latino Children

    ERIC Educational Resources Information Center

    Roberts, Lindsay S.; Sharma, Sushma; Hudes, Mark L.; Fleming, Sharon E.

    2012-01-01

    Background: African-American and Latino children living in neighborhoods with a low-socioeconomic index are more at risk of obesity-associated metabolic disease than their higher socioeconomic index and/or white peers. Currently, consistent and reliable questionnaires to evaluate nutrition and physical activity knowledge in these children are…

  11. Construct Validation of Physical Activity Surveys in Culturally Diverse Older Adults: A Comparison of Four Commonly Used Questionnaires

    ERIC Educational Resources Information Center

    Moore, Delilah S.; Ellis, Rebecca; Allen, Priscilla D.; Cherry, Katie E.; Monroe, Pamela A.; O'Neil, Carol E.; Wood, Robert H.

    2008-01-01

    The purpose of this study was to establish validity evidence of four physical activity (PA) questionnaires in culturally diverse older adults by comparing self-report PA with performance-based physical function. Participants were 54 older adults who completed the Continuous Scale Physical Functional Performance 10-item Test (CS-PFP10), Physical…

  12. Impaired voluntary neuromuscular activation limits muscle power in mobility-limited older adults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background. Age-related alterations of neuromuscular activation may contribute to deficits in muscle power and mobility function. This study assesses whether impaired activation of the agonist quadriceps and antagonist hamstrings, including amplitude- and velocity-dependent characteristics of activa...

  13. The patient-specific functional scale is more responsive than the Roland Morris disability questionnaire when activity limitation is low.

    PubMed

    Hall, Amanda M; Maher, Chris G; Latimer, Jane; Ferreira, Manuela L; Costa, Leonardo O P

    2011-01-01

    The primary objective of this study was to determine which questionnaire, the Roland Morris disability questionnaire (RMDQ) or the patient-specific functional scale (PSFS), was better at detecting change in activity limitation in a large cohort of patients with low back pain undergoing rehabilitation. A secondary aim was to determine if the responsiveness of the questionnaires was influenced by the patient's level of activity limitation at baseline. Responsiveness statistics, including effect size statistics, Pearson's r correlations and receiver operative characteristic (ROC) curve analysis were used to determine ability to detect change in activity limitation on 831 patients with low back pain. Data were analysed at two time points; directly after treatment (termed short-term) and several weeks post-treatment (termed mid-term). The data were subsequently re-analysed on sub-sets of the full cohort according to the level of activity limitation from RMDQ baseline scores. In the total cohort we found that the PSFS was more responsive than the RMDQ; however, in the subgroup with high activity limitation this pattern was not observed. This is true for time points up to 6 months post-treatment. In conclusion, the RMDQ and PSFS both demonstrate good responsiveness according to the definitions given in previous guidelines. The PSFS is more responsive than the RMDQ for patients with low levels of activity limitation but not for patients with high levels of activity limitation.

  14. Physical activity practice, body image and visual impairment: a comparison between Brazilian and Italian children and adolescents.

    PubMed

    Greguol, Márcia; Gobbi, Erica; Carraro, Attilio

    2014-01-01

    The aim of this study was to analyze the physical activity and body image of children and adolescents with visual impairment (VI) in Brazil and Italy. For this, 41 children and adolescents with VI (19 Brazilian and 22 Italian) aged 10.22 ± 2.19 years old (18 girls and 23 boys) answered the Physical Activity Questionnaire for Children (PAQ-C), the Offer Self-Image Questionnaire (OSIQ), and an instrument with information about the disability, body weight and height. We analyzed the relationship between data from PAQ-C and OSIQ, as well as the gender, level of disability (blindness or low vision) and country using independent Mann-Whitney test. Body mass index (BMI) values were higher for Brazilian youths, with more than half of them classified as overweight and obese. Italian youths exhibited values of body image that were more positive and only 27% presented overweight or obesity. Blind children and adolescents were less active than those with low vision, but no differences were found between countries or genders. In Brazil, we detected significant correlations (p>0.05) between physical activity, body image and BMI, which more active youths presenting lower values of BMI and a better perception of body image. Physical activity seems to have a positive influence on body image and BMI for children and adolescents with VI, thus it should be encouraged especially for those with higher disability degrees.

  15. 76 FR 80965 - Agency Information Collection Activities; Proposed collection: Applicant Questionnaire: Race...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-27

    ... Questionnaire: Race, National Origin, Gender, and Disability Demographics; Revision of a Currently Approved...: Race, National Origin, Gender and Disability Demographics (3) The agency form number, if any, and the... information on race, national origin, gender and disability of an applicant/or employee in accordance with...

  16. Physical Activity, Body Composition, and Perceived Quality of Life of Adults with Visual Impairments

    ERIC Educational Resources Information Center

    Holbrook, Elizabeth A.; Caputo, Jennifer L.; Perry, Tara L.; Fuller, Dana K.; Morgan, Don W.

    2009-01-01

    Relatively little is known about the health and fitness of adults with visual impairments. This article documents the physical activity levels and body-composition profiles of young and middle-aged adults with visual impairments and addresses the concomitant effects of these factors on perceived quality of life. (Contains 2 tables.)

  17. AccesSports: A Model for Adapting Mainstream Sports Activities for Individuals with Visual Impairments.

    ERIC Educational Resources Information Center

    Ponchilla, Paul E.

    1995-01-01

    The AccesSports Model allows professionals with basic knowledge of visual impairments and mainstream sports to analyze any sports activity and design adaptations needed for targets or goals, boundaries, and rules to enable individuals with visual impairments to participate. Suggestions for modifying baseball, table tennis, swim racing, wrestling,…

  18. Insulin-Dependent Activation of MCH Neurons Impairs Locomotor Activity and Insulin Sensitivity in Obesity.

    PubMed

    Hausen, A Christine; Ruud, Johan; Jiang, Hong; Hess, Simon; Varbanov, Hristo; Kloppenburg, Peter; Brüning, Jens C

    2016-12-06

    Melanin-concentrating-hormone (MCH)-expressing neurons (MCH neurons) in the lateral hypothalamus (LH) are critical regulators of energy and glucose homeostasis. Here, we demonstrate that insulin increases the excitability of these neurons in control mice. In vivo, insulin promotes phosphatidylinositol 3-kinase (PI3K) signaling in MCH neurons, and cell-type-specific deletion of the insulin receptor (IR) abrogates this response. While lean mice lacking the IR in MCH neurons (IR(ΔMCH)) exhibit no detectable metabolic phenotype under normal diet feeding, they present with improved locomotor activity and insulin sensitivity under high-fat-diet-fed, obese conditions. Similarly, obesity promotes PI3 kinase signaling in these neurons, and this response is abrogated in IR(ΔMCH) mice. In turn, acute chemogenetic activation of MCH neurons impairs locomotor activity but not insulin sensitivity. Collectively, our experiments reveal an insulin-dependent activation of MCH neurons in obesity, which contributes via distinct mechanisms to the manifestation of impaired locomotor activity and insulin resistance.

  19. Impaired enzymatic defensive activity, mitochondrial dysfunction and proteasome activation are involved in RTT cell oxidative damage.

    PubMed

    Cervellati, Carlo; Sticozzi, Claudia; Romani, Arianna; Belmonte, Giuseppe; De Rasmo, Domenico; Signorile, Anna; Cervellati, Franco; Milanese, Chiara; Mastroberardino, Pier Giorgio; Pecorelli, Alessandra; Savelli, Vinno; Forman, Henry J; Hayek, Joussef; Valacchi, Giuseppe

    2015-10-01

    A strong correlation between oxidative stress (OS) and Rett syndrome (RTT), a rare neurodevelopmental disorder affecting females in the 95% of the cases, has been well documented although the source of OS and the effect of a redox imbalance in this pathology has not been yet investigated. Using freshly isolated skin fibroblasts from RTT patients and healthy subjects, we have demonstrated in RTT cells high levels of H2O2 and HNE protein adducts. These findings correlated with the constitutive activation of NADPH-oxidase (NOX) and that was prevented by a NOX inhibitor and iron chelator pre-treatment, showing its direct involvement. In parallel, we demonstrated an increase in mitochondrial oxidant production, altered mitochondrial biogenesis and impaired proteasome activity in RTT samples. Further, we found that the key cellular defensive enzymes: glutathione peroxidase, superoxide dismutase and thioredoxin reductases activities were also significantly lower in RTT. Taken all together, our findings suggest that the systemic OS levels in RTT can be a consequence of both: increased endogenous oxidants as well as altered mitochondrial biogenesis with a decreased activity of defensive enzymes that leads to posttranslational oxidant protein modification and a proteasome activity impairment.

  20. Selective Impairment of Living Things and Musical Instruments on a Verbal "Semantic Knowledge Questionnaire" in a Case of Apperceptive Visual Agnosia

    ERIC Educational Resources Information Center

    Masullo, Carlo; Piccininni, Chiara; Quaranta, Davide; Vita, Maria Gabriella; Gaudino, Simona; Gainotti, Guido

    2012-01-01

    Semantic memory was investigated in a patient (MR) affected by a severe apperceptive visual agnosia, due to an ischemic cerebral lesion, bilaterally affecting the infero-mesial parts of the temporo-occipital cortices. The study was made by means of a Semantic Knowledge Questionnaire (Laiacona, Barbarotto, Trivelli, & Capitani, 1993), which takes…

  1. Assessment of Diet and Physical Activity of Brazilian Schoolchildren: Usability Testing of a Web-Based Questionnaire

    PubMed Central

    2013-01-01

    Background Information and communication technology (ICT) has been used with increasing frequency for the assessment of diet and physical activity in health surveys. A number of Web-based questionnaires have been developed for children and adolescents. However, their usability characteristics have scarcely been reported, despite their potential importance for improving the feasibility and validity of ICT-based methods. Objective The objective of this study was to describe the usability evaluation of the Consumo Alimentar e Atividade Física de Escolares (CAAFE) questionnaire (Food Consumption and Physical Activity Questionnaire for schoolchildren), a new Web-based survey tool for the self-assessment of diet and physical activity by schoolchildren. Methods A total of 114 schoolchildren aged 6 to 12 years took part in questionnaire usability testing carried out in computer classrooms at five elementary schools in the city of Florianopolis, Brazil. Schoolchildren used a personal computer (PC) equipped with software for recording what is on the computer screen and the children’s speech during usability testing. Quantitative and qualitative analyses took into account objective usability metrics such as error counts and time to complete a task. Data on the main difficulties in accomplishing the task and the level of satisfaction expressed by the children were assessed by the observers using a standardized form and interviews with the children. Descriptive statistics and content analysis were used to summarize both the quantitative and the qualitative aspects of the data obtained. Results The mean time for completing the questionnaire was 13.7 minutes (SD 3.68). Compared to the children in 2nd or 3rd grades, those in 4th or 5th grades spent less time completing the questionnaire (median 12.4 vs 13.3 minutes, P=.022), asked for help less frequently (median 0 vs 1.0 count, P=.005), had a lower error count (median 2.0 vs 8.0 count, P<.001), and obtained a higher overall

  2. Prediction of VO[subscript 2]max in Children and Adolescents Using Exercise Testing and Physical Activity Questionnaire Data

    ERIC Educational Resources Information Center

    Black, Nate E.; Vehrs, Pat R.; Fellingham, Gilbert W.; George, James D.; Hager, Ron

    2016-01-01

    Purpose: The purpose of this study was to evaluate the use of a treadmill walk-jog-run exercise test previously validated in adults and physical activity questionnaire data to estimate maximum oxygen consumption (VO[subscript 2]max) in boys (n = 62) and girls (n = 66) aged 12 to 17 years old. Methods: Data were collected from Physical Activity…

  3. Sexual health in women with pelvic floor disorders: measuring the sexual activity and function with questionnaires--a summary.

    PubMed

    Espuña Pons, Montserrat

    2009-05-01

    The integration of sexual health into the health care services is important. In women attending urogynecological clinics, the urinary function, anorectal function, and anatomical defects are more often evaluated than those related to sexual activity and function. A group of experts in urogynecology, sexuality, and patient reported outcome development, met in a roundtable with the final objective of reviewing what is currently available and what is needed to accurately evaluate sexual function in women with pelvic floor dysfunction. An article was prepared for each of the issued presented during the roundtable and combined into this supplement. This article is a summary of all articles included in this supplement. The pathophysiology of sexual dysfunction as related to pelvic floor disorders has not been well established. Sexuality questionnaires and scales play an integral role in the diagnosis and treatment of female sexual dysfunction. The Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ) is the only validated female sexual function questionnaire specifically developed to assess sexual function in women with urinary incontinence and/or pelvic organ prolapse; however, the PISQ does not screen for sexual activity. The effects of treatments for pelvic floor problems on sexual function have received little attention. There is a need for a validated sexual function measure that evaluates not only the impact of pelvic floor dysfunction on sexual function but also the impact on sexual activity.

  4. Development of a Questionnaire Designed To Evaluate the Employee Development Activities at Paradise Valley Community College Center: Politics, Law, and Economics of Higher Education.

    ERIC Educational Resources Information Center

    Cristiano, Marilyn J.; Nellis, Deo E.

    This paper describes the development of a questionnaire for evaluating the activities of the Employee Development Program (EDP) at Paradise Valley Community College Center (PVCCC) in Phoenix (Arizona). Four major goals of the evaluation of the activities of the EDP, and a means for ensuring the content validity of the questionnaire are described.…

  5. The Development of the Lunchtime Enjoyment of Activity and Play Questionnaire

    ERIC Educational Resources Information Center

    Hyndman, Brendon; Telford, Amanda; Finch, Caroline; Ullah, Shahid; Benson, Amanda C.

    2013-01-01

    Background: Enjoyment of physical activity is as an important determinant of children's participation in physical activity. Despite this, there is an absence of reliable measures for assessing children's enjoyment of play activities during school lunchtime. The purpose of this study was to develop and assess the reliability of the Lunchtime…

  6. The Effect of Gender and Level of Vision on the Physical Activity Level of Children and Adolescents with Visual Impairment

    ERIC Educational Resources Information Center

    Aslan, Ummuhan Bas; Calik, Bilge Basakci; Kitis, Ali

    2012-01-01

    This study was planned in order to determine physical activity levels of visually impaired children and adolescents and to investigate the effect of gender and level of vision on physical activity level in visually impaired children and adolescents. A total of 30 visually impaired children and adolescents (16 low vision and 14 blind) aged between…

  7. Development and psychometric properties of a belief-based Physical Activity Questionnaire for Diabetic Patients (PAQ-DP)

    PubMed Central

    2010-01-01

    Background This study carried out to develop a scale for assessing diabetic patients' perceptions about physical activity and to test its psychometric properties (The Physical Activity Questionnaire for Diabetic Patients-PAQ-DP). Methods An item pool extracted from the Theory of Planned Behavior literature was generated. Then an expert panel evaluated the items by assessing content validity index and content validity ratio. Consequently exploratory factor analysis (EFA) was performed to indicate the scale constructs. In addition reliability analyses including internal consistency and test-retest analysis were carried out. Results In all a sample of 127 women with diabetes participated in the study. Twenty-two items were initially extracted from the literature. A six-factor solution (containing 19 items) emerged as a result of an exploratory factor analysis namely: instrumental attitude, subjective norm, perceived behavioral control, affective attitude, self-identity, and intention explaining 60.30% of the variance observed. Additional analyses indicated satisfactory results for internal consistency (Cronbach's alpha ranging from 0.54 to 0.8) and intraclass correlation coefficients (ranging from 0.40 to 0.92). Conclusions The Physical Activity Questionnaire for Diabetic Patients (PAQ-DP) is the first instrument that applies the Theory of Planned Behavior in its constructs. The findings indicated that the PAQ-DP is a reliable and valid measure for assessing physical activity perceptions and now is available and can be used in future studies. PMID:21062466

  8. Validation of Veterans Specific Activity Questionnaire to assess exercise tolerance of Chinese elderly with coronary heart disease

    PubMed Central

    Wang, Yan; Shi, Jing-Jing; Wang, Bo-Zhong

    2016-01-01

    Objective The Veterans Specific Activity Questionnaire (VSAQ) has been used to assess exercise tolerance. Nevertheless, there is no validated Chinese version. The aim of this study is to determine whether a questionnaire-based method using the Chinese version of VSAQ (the modified VSAQ) is a practical tool to assess exercise tolerance of Chinese elderly with coronary heart disease. Methods One hundred thirty consecutive elderly patients who were diagnosed with coronary heart disease (CHD) (mean age 68.9 ± 6.0 years) referred for treadmill exercise testing (TET) for clinical reasons were included in the study. They were asked to complete a questionnaire for clinical characteristics information on age, sex, history, exercise habits, medications, the original VSAQ and the modified VSAQ. We investigated the relationship between exercise tolerance in metabolic equivalents (METs) estimated by VSAQ and that obtained by TET. Results The METs by the original VSAQ and the modified VSAQ did not difference significantly (P = 0.528). The modified VSAQ scores were significantly correlated with the METs obtained by TET (r = 0.819, 95% CI: 0.753–0.873, P < 0.01), and the scores of original VSAQ also correlated with the METs by TET (r = 0.804, 95% CI: 0.745–0.854, P < 0.01). The Bland-Altman graph analysis showed few values outside the limits of agreement, suggesting good precision between the METs estimated by questionnaire and the METs obtained by TET. Conclusions The Chinese version of the VSAQ confirmed its validity and equivalence to the original version, especially when evaluating individuals with coronary heart disease and older adults. The results showed that the VSAQ is a valuable tool to assess the exercise tolerance. PMID:28321240

  9. Activating Autophagy in Hippocampal Cells Alleviates the Morphine-Induced Memory Impairment.

    PubMed

    Pan, Jingrui; He, Lei; Li, Xiangpen; Li, Mei; Zhang, Xiaoni; Venesky, Jacob; Li, Yi; Peng, Ying

    2017-04-01

    Morphine abuse in treating severe and chronic pain has become a worldwide problem. But, chronic morphine exposure can cause memory impairment with its mechanisms not fully elucidated by past research sstudies which all focused on the harmful effects of morphine. Autophagy is an important pathway for cells to maintain survival. Here we showed that repeated morphine injection into C57BL/6 mice at a dose of 15 mg/kg per day for 7 days activated autophagic flux mainly in the hippocampi, especially in neurons of hippocampal CA1 region and microglia, with spatial memory impairment confirmed by Morris water maze test. Autophagy inhibition by 3-methyladenine obviously aggravates this morphine-induced memory impairment, accompanied with increased cell deaths in stratum pyramidale of hippocampal CA1, CA3, and DG regions and the activation of microglia to induce inflammation in hippocampus, such as upregulated expression of TNF-α, IL-1β, IL-6, and iNOS, as well as NF-κB' s activation, while morphine alone promoted microglial immunosuppression in hippocampus with autophagy activation which was also confirmed in primary microglia. Taken together, our data indicates that autophagy activating in hippocampal cells can alleviate the memory impairment caused by morphine, by decreasing neuronal deaths in hippocampus and suppressing inflammation in hippocampal microglia, implying that modulating the activation of autophagy might be a promising method to prevent or treat the memory impairment caused by morphine.

  10. Evidence for the validity of the Children's Attraction to Physical Activity questionnaire (CAPA) with young children.

    PubMed

    Rose, Elizabeth; Larkin, Dawne; Hands, Beth; Howard, Barbara; Parker, Helen

    2009-09-01

    Attraction to physical activity is important to an individual's intrinsic motivation to engage in play, games and sports. While there are instruments designed to measure attraction to physical activity in middle childhood years, the lack of authentic measures in young children has impeded research in this area. In this study we sought to address the validity of a scale to tap young children's attraction to physical activity. Evidence for validity was based on internal consistency, content analysis, and factor structure. Australian school children (180 boys and 154 girls) from school year two, aged 6-8 years, were individually administered a modified version of the Children's Attraction to Physical Activity Scale (CAPA) [Brustad RJ. Who will go out to play? Parental and psychological influences on children's attraction to physical activity. Pediatr Exerc Sci 1993;5:210-23; Brustad RJ. Attraction to physical activity in urban school children: parental socialization and gender influences. Res Q Exerc Sport 1996;67:316-23]. The results indicated that internal consistency was acceptable for most of the subscales when negative statements were excluded from the analyses. Factor analysis revealed that the liking of games and sports, liking of physical exertion and exercise, and the importance of exercise subscales were more robust. Second order factor analysis indicated that the overall construct of attraction to physical activity was viable in this age group. With some modifications, the scale appears to provide a valid approach to the measurement of attraction to physical activity in young children.

  11. “How hard could it be?” A descriptive analysis of errors made on a validated lifetime physical activity questionnaire

    PubMed Central

    Anderton, Natalie; Newhouse, Megan E.; Ainsworth, Barbara E.; Nygaard, Ingrid E.; Egger, Marlene J.; Shaw, Janet M.

    2015-01-01

    Background Measuring historical physical activity in epidemiologic research depends on self-report. We aimed to describe data reporting errors women made in completing two validated questionnaires – Lifetime Physical Activity Questionnaire (LPAQ) and Occupational Questionnaire (OQ). Methods Participants, 229 women aged 38 – 65 years, completed questionnaires on paper (n=160) or by web interface (n=69). One research assistant collected questionnaire data, identified potential errors and contacted participants to trouble-shoot errors. Results Women made mean 9.7 (SD 11.2) errors on paper and 7.1 (SD 6.2) errors on electronic versions of the LPAQ and 2.6 (SD 3.8) and 1.1 (SD 1.4) errors on paper and electronic versions of the OQ, respectively. Fewer mistakes were made on electronic versions of both questionnaires combined (8.5±6.1) when compared to the paper versions (12.7±13.1). Only ~2% of the sample completed all questionnaires without detectable errors. The most common errors were reporting activities or frequencies inconsistently between past year survey and the current age epoch, reporting more years than allowed by age epoch and missing information. Conclusions Despite the implications of “self-report” questionnaires, we recommend researchers provide participants with additional instructions, either verbally or as written tip sheet or both, and follow-up after questionnaire completion to correct mistakes as needed. PMID:24809450

  12. Sexual Dysfunction in Breast Cancer Survivors: Cross-Cultural Adaptation of the Sexual Activity Questionnaire for Use in Portugal.

    PubMed

    da Costa, Filipa Alves; Ribeiro, Manuel Castro; Braga, Sofia; Carvalho, Elisabete; Francisco, Fátima; Miranda, Ana Costa; Moreira, António; Fallowfield, Lesley

    2016-09-01

    Introdução: A crescente população de sobreviventes de cancro da mama tem redireccionado o interesse investigacional e prático para o impacto da doença e do seu tratamento nas várias áreas da qualidade de vida. A falta de questionários para avaliar de forma objectiva a disfunção sexual conduziu à necessidade de adaptar e validar culturalmente o Sexual Activity Questionnaire para utilização em Portugal. Material e Métodos: O Sexual Activity Questionnaire foi traduzido e retrovertido, sua versão de consenso refinada após teste de compreensão, e subsequentemente auto-administrado a uma amostra alargada de sobreviventes de cancro da mama em dois momentos, espaçados 15 dias, para julgar a sua validade e fiabilidade. Resultados: Após alterações minor à versão de consenso, o Sexual Activity Questionnaire foi aplicado a 134 doentes. Obteve-se uma estrutura de três factores (75,5% da variância), compreendendo as escalas do Prazer, Hábito e Desconforto, todas com boa consistência interna (α de Cronbach > 0,70), boa validade concorrente com o FACt-An e a checklist BCPT (r de Spearman > 0,65; p-value < 0,001) e estabilidade temporal aceitável (k de Cohen > 0,44). Foi identificada inactividade sexual em 23,9% das mulheres, devido a falta de interesse ou ao facto de não ter parceiro. Discussão: Os dados reportados pelos doentes conduziram a alterações nos cuidados prestados, que passaram a contemplar a oncosexologia. Estudos futuros deverão focar-se na aplicabilidade deste questionário a amostras com diferentes características e mesmo à população global, para se poderem generalizar os resultados. Conclusão: A versão obtida do Sexual Activity Questionnaire é válida para avaliar a função sexual em sobreviventes de cancro da mama em Portugal.

  13. Physical Activities for Impaired, Disabled, and Handicapped Individuals.

    ERIC Educational Resources Information Center

    American Alliance for Health, Physical Education, and Recreation, Washington, DC.

    The first in a series of seven booklets on physical education and recreation for the handicapped provides information on activities and teaching methods. Teaching techniques concerning motivation, program planning, and group organization are considered. A bibliography lists approximately 50 references on teaching such activities as archery,…

  14. Breaking-up sedentary time is associated with impairment in activities of daily living.

    PubMed

    Sardinha, Luis B; Ekelund, Ulf; dos Santos, Leandro; Cyrino, Edilson S; Silva, Analiza M; Santos, Diana A

    2015-12-01

    Identifying modifiable behaviors associated with prevention of activities of daily living (ADL) impairments is vital to implement preventive strategies for independent living in elderly. We aimed to examine the associations between objectively measured breaks in sedentary time with ADL impairments and physical independence. Cross-sectional assessments were carried out in 371 participants (131 male) aged 65-103 years from the Portuguese surveillance system of physical activity. Physical activity (PA) and sedentary time (ST) were assessed with accelerometry, and ADL impairments and physical independence with the self-reported 12-item composite physical function scale. Using ROC analyses a cut-off of 7 hourly breaks in sedentary time was identified which maximized the sensitivity and specificity in diagnosing physical dependence. Logistic regression analysis demonstrated that, independently of moderate-to-vigorous PA (MVPA), participants performing ≤ 7 hourly breaks in sedentary time had 2 to 7 fold increased odds for impairment in 10 of the 12 ADL. When stratifying ADL into basic, instrumental and advanced ADL we verified that less than 7 hourly breaks in sedentary time was associated with a 2 to 5 fold increased odds for impairments and physical dependence, independent of MVPA. No associations were observed between meeting PA guidelines and basic, instrumental, and advanced ADL impairment although time in MVPA was lower in participants showing impairments. In conclusion, the frequency of breaks in sedentary time in older ages is independently associated with lower risk for ADL impairments and physical dependence. Our findings support interventions to encourage older adults to increase overall PA by interrupting sedentary time.

  15. Leisure-time physical activity and neuropsychiatric symptoms of community-dwelling persons with cognitive impairment.

    PubMed

    Chiu, Yi-Chen; Kolanowski, Ann M; Huang, Chien-Ying; Lin, Li-Jung; Chang, Ting-Huan; Hsu, Kuang-Hung; Hu, Chaur-Jong; Chen, Ying-Jen

    2014-01-01

    Physical activities are recommended to reduce neuropsychiatric symptoms of nursing home residents with mild dementia. However, relevant information is not available for community-dwelling persons with cognitive impairment. Therefore, this cross-sectional study examined the effects of leisure-time physical activities on cognitively impaired persons' neuropsychiatric symptoms and their family caregivers' distress. Activities were described in terms of their frequency, duration, number of different types, and energy expenditure. Participants were 58 dyads of persons with cognitive impairment and their family caregivers. Data on leisure-time physical activities and neuropsychiatric symptoms were collected using a 7-Day Physical Activity Recall and Chinese Neuropsychiatric Inventory, respectively. The most frequently reported activity was strolling (70.7%). The mean weekly activity frequency, duration, and energy expenditure were 4.52 (SD=4.27) times, 3.7 (SD=4.38) h, and 771.47 (SD=886.38) kcal, respectively. The number of different activity types negatively and significantly predicted cognitively impaired persons' mood and psychosis as well as family caregivers' distress.

  16. Assessing face validity of a physical activity questionnaire for Spanish-speaking women in California

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: A review of the literature produced no rigorously tested and validated Spanish-language physical activity survey or evaluation tools for use by USDA’s food assistance and education programs. The purpose of the current study was to develop and evaluate the face validity of a visually enha...

  17. Reliability and Validity of the International Physical Activity Questionnaire for Assessing Walking

    ERIC Educational Resources Information Center

    van der Ploeg, Hidde P.; Tudor-Locke, Catrine; Marshall, Alison L.; Craig, Cora; Hagstromer, Maria; Sjostrom, Michael; Bauman, Adrian

    2010-01-01

    The single most commonly reported physical activity in public health surveys is walking. As evidence accumulates that walking is important for preventing weight gain and reducing the risk of diabetes, there is increased need to capture this behavior in a valid and reliable manner. Although the disadvantages of a self-report methodology are well…

  18. The experience of choice in physical activity contexts for adults with mobility impairments.

    PubMed

    Morphy, Lorraine Y; Goodwin, Donna

    2012-04-01

    This exploratory study described the experiences of choice in physical activity contexts for adults with mobility impairments. The experiences of 3 female and 2 males with mobility impairments between 18 and 23 years of age were described using the interpretive phenomenological methods of individual interviews, written stories, and field notes. Thematic analysis revealed three themes: (a) interpreting the setting described participants' interpretation of the environment, person, and task when making movement choices; (b) alternative selection described how participants actively engaged in analyzing alternatives and choosing among them; and (c) implications of choices made described participants' evaluations of good and bad choices and what was learned. Evidence of effective choice making among adults with physical impairments suggests the potential efficacy of ecological task analysis as a pedagogical tool in physical activity contexts.

  19. Cholinergic Enhancement of Frontal Lobe Activity in Mild Cognitive Impairment

    ERIC Educational Resources Information Center

    Saykin, Andrew J.; Wishart, Heather A.; Rabin, Laura A.; Flashman, Laura A.; McHugh, Tara L.; Mamourian, Alexander C.; Santulli, Robert B.

    2004-01-01

    Cholinesterase inhibitors positively affect cognition in Alzheimer's disease (AD) and other conditions, but no controlled functional MRI studies have examined where their effects occur in the brain. We examined the effects of donepezil hydrochloride (Aricept[Registered sign]) on cognition and brain activity in patients with amnestic mild cognitive…

  20. Interleukin-19 impairment in active Crohn's disease patients.

    PubMed

    Cantó, Elisabet; Garcia Planella, Esther; Zamora-Atenza, Carlos; Nieto, Juan Camilo; Gordillo, Jordi; Ortiz, Ma Angels; Metón, Isidoro; Serrano, Elena; Vegas, Esteban; García-Bosch, Orlando; Juárez, Cándido; Vidal, Sílvia

    2014-01-01

    The exact function of interleukin-19 (IL-19) on immune response is poorly understood. In mice, IL-19 up-regulates TNFα and IL-6 expression and its deficiency increases susceptibility to DSS-induced colitis. In humans, IL-19 favors a Th2 response and is elevated in several diseases. We here investigate the expression and effects of IL-19 on cells from active Crohn's disease (CD) patient. Twenty-three active CD patients and 20 healthy controls (HC) were included. mRNA and protein IL-19 levels were analyzed in monocytes. IL-19 effects were determined in vitro on the T cell phenotype and in the production of cytokines by immune cells. We observed that unstimulated and TLR-activated monocytes expressed significantly lower IL-19 mRNA in active CD patients than in HC (logFC = -1.97 unstimulated; -1.88 with Pam3CSK4; and -1.91 with FSL-1; p<0.001). These results were confirmed at protein level. Exogenous IL-19 had an anti-inflammatory effect on HC but not on CD patients. IL-19 decreased TNFα production in PBMC (850.7 ± 75.29 pg/ml vs 2626.0 ± 350 pg/ml; p<0.01) and increased CTLA4 expression (22.04 ± 1.55% vs 13.98 ± 2.05%; p<0.05) and IL-4 production (32.5 ± 8.9 pg/ml vs 13.5 ± 2.9 pg/ml; p<0.05) in T cells from HC. IL-10 regulated IL-19 production in both active CD patients and HC. We observed that three of the miRNAs that can modulate IL-19 mRNA expression, were up-regulated in monocytes from active CD patients. These results suggested that IL-19 had an anti-inflammatory role in this study. Defects in IL-19 expression and the lack of response to this cytokine could contribute to inflammatory mechanisms in active CD patients.

  1. Novel FOXC2 Mutation in Hereditary Distichiasis Impairs DNA-Binding Activity and Transcriptional Activation

    PubMed Central

    Zhang, Leilei; He, Jie; Han, Bing; Lu, Linna; Fan, Jiayan; Zhang, He; Ge, Shengfang; Zhou, Yixiong; Jia, Renbing; Fan, Xianqun

    2016-01-01

    Distichiasis presents as double rows of eyelashes arising from aberrant differentiation of the meibomian glands of the eyelids, and it may be sporadic or hereditary. FOXC2 gene mutations in hereditary distichiasis are rarely reported. Here, we examined two generations of a Chinese family with hereditary distichiasis but without lymphedema or other features of LD syndrome. The FOXC2 gene was amplified and sequenced in all family members. Subcellular localization and luciferase assays were performed to assess the activity of the mutant FOXC2 protein. Clinical examinations showed distichiasis, lower eyelid ectropion, congenital ptosis and photophobia in all affected individuals. Sequence analysis revealed a novel frameshift mutation, c.964_965insG, in the coding region of the FOXC2 gene. This mutation caused protein truncation due to the presence of a premature stop codon. A fluorescence assay showed that this mutation did not change the nuclear localization of the protein. However, it impaired DNA-binding activity and decreased transcriptional activation. This is the first report of a FOXC2 mutation in hereditary distichiasis in the Chinese population. The findings of our study expand the FOXC2 mutation spectrum and contribute to the understanding of the genotype-phenotype correlation of this disease. PMID:27570485

  2. Impaired suppressor activity in children affected by coeliac disease.

    PubMed Central

    Pignata, C; Troncone, R; Monaco, G; Ciriaco, M; Farris, E; Carminati, G; Auricchio, S

    1985-01-01

    Immunoregulatory cells were enumerated in 19 coeliac disease children on a gluten free diet by means of monoclonal antibodies that define total T lymphocytes (T3), helper/inducer T cells (T4), suppressor/cytotoxic T cells (T8) and monocytes (M1), as well as by means of surface receptors for Fc fragments of IgM and IgG (T mu and T gamma, respectively). In addition, suppressor cell function was assessed in 17 coeliac disease patients by examining the ability of concanavalin-A (Con-A)-activated suppressor cells to inhibit autologous cell response to mitogenic stimulus as compared with age-matched controls. No statistically significant differences were found in the percentages of subsets defined by monoclonal antibodies between coeliac disease patients and age-matched controls, whereas coeliac disease patients had a significant decrease of the subpopulation bearing membrane receptor for Fc fragment of IgG. Mean value was 8.5% in coeliac patients versus 13.4% in age-matched controls. In the functional assay, mononuclear cells from 10 out of 17 coeliac disease patients either totally or partially failed to suppress responder cells after Con-A-activation. This defect is not related to HLA-DR status, because no difference was found between patients-HLA-matched and unmatched normal individuals. In this assay, mononuclear cells of three coeliac disease patients with low suppressor activity were able to inhibit responder cells to the same extent as controls, when indomethacin was used to block prostaglandin production in the induction phase of Con-A-activated suppressor cells. Our results suggest that an abnormality in immunoregulation may play a role in the pathogenesis of coeliac disease. PMID:3156076

  3. Identification of mild cognitive impairment in ACTIVE: algorithmic classification and stability.

    PubMed

    Cook, Sarah E; Marsiske, Michael; Thomas, Kelsey R; Unverzagt, Frederick W; Wadley, Virginia G; Langbaum, Jessica B S; Crowe, Michael

    2013-01-01

    Rates of mild cognitive impairment (MCI) have varied substantially, depending on the criteria used and the samples surveyed. The present investigation used a psychometric algorithm for identifying MCI and its stability to determine if low cognitive functioning was related to poorer longitudinal outcomes. The Advanced Cognitive Training of Independent and Vital Elders (ACTIVE) study is a multi-site longitudinal investigation of long-term effects of cognitive training with older adults. ACTIVE exclusion criteria eliminated participants at highest risk for dementia (i.e., Mini-Mental State Examination < 23). Using composite normative for sample- and training-corrected psychometric data, 8.07% of the sample had amnestic impairment, while 25.09% had a non-amnestic impairment at baseline. Poorer baseline functional scores were observed in those with impairment at the first visit, including a higher rate of attrition, depressive symptoms, and self-reported physical functioning. Participants were then classified based upon the stability of their classification. Those who were stably impaired over the 5-year interval had the worst functional outcomes (e.g., Instrumental Activities of Daily Living performance), and inconsistency in classification over time also appeared to be associated increased risk. These findings suggest that there is prognostic value in assessing and tracking cognition to assist in identifying the critical baseline features associated with poorer outcomes.

  4. COPD symptom burden: impact on health care resource utilization, and work and activity impairment

    PubMed Central

    Ding, Bo; Small, Mark; Bergström, Gina; Holmgren, Ulf

    2017-01-01

    Background Chronic obstructive pulmonary disease (COPD) can greatly impact the quality of life by limiting patients’ activities. However, data on impact of symptomatic burden on the health care resource utilization (HCRU) and employment in COPD are lacking. We examined the association between COPD Assessment Test (CAT) score and direct/indirect costs associated with HCRU and work productivity. Methods Data from >2,100 patients with COPD consulting for routine care were derived from respiratory disease-specific programs in Europe, the USA and China. Questionnaires, including CAT and Work Productivity and Activity Impairment (WPAI), were used to collect the past and current disease status data and HCRU characteristics from physicians (general practitioners/specialists) and patients. A regression approach was used to quantify the association of CAT with HCRU and WPAI variables. CAT score was modeled as a continuous independent variable (range: 0–40). Results Ninety percent of patients with COPD had a CAT score ≥10. Short-acting therapy and maintenance bronchodilator monotherapy, respectively, were currently prescribed to patients with CAT scores of 10–19 (5.8% and 27.6%), 20–29 (5.1% and 13.1%) and 30–40 (2.8% and 6.6%). Prescribing of maintenance bronchodilator dual therapy was low across the CAT score groups (0–9, 7.8%; 10–19, 6.4%; 20–29, 5.9%; 30–40, 4.4%), whereas maintenance triple combination therapy was prescribed more commonly in patients with higher CAT scores (0–9, 16.1%; 10–19, 23.2%; 20–29, 25.9%; 30–40, 35.5%). Increasing CAT scores were significantly associated with a higher frequency of primary care physician visits (P<0.001), pulmonologist visits (P=0.007), exacerbations requiring hospitalization (P<0.001) and WPAI scores (P<0.001). Conclusion Most patients with COPD presented with high symptom levels, despite being treated for COPD. Increasing symptom burden was associated with increasing HCRU and had a detrimental impact

  5. Measuring the Environment for Friendliness Toward Physical Activity: A Comparison of the Reliability of 3 Questionnaires

    PubMed Central

    Brownson, Ross C.; Chang, Jen Jen; Eyler, Amy A.; Ainsworth, Barbara E.; Kirtland, Karen A.; Saelens, Brian E.; Sallis, James F.

    2004-01-01

    Objectives. We tested the reliability of 3 instruments that assessed social and physical environments. Methods. We conducted a test–retest study among US adults (n = 289). We used telephone survey methods to measure suitableness of the perceived (vs objective) environment for recreational physical activity and nonmotorized transportation. Results. Most questions in our surveys that attempted to measure specific characteristics of the built environment showed moderate to high reliability. Questions about the social environment showed lower reliability than those that assessed the physical environment. Certain blocks of questions appeared to be selectively more reliable for urban or rural respondents. Conclusions. Despite differences in content and in response formats, all 3 surveys showed evidence of reliability, and most items are now ready for use in research and in public health surveillance. PMID:14998817

  6. Inhibition of Rac1 Activity in the Hippocampus Impairs the Forgetting of Contextual Fear Memory.

    PubMed

    Jiang, Lizhu; Mao, Rongrong; Zhou, Qixin; Yang, Yuexiong; Cao, Jun; Ding, Yuqiang; Yang, Yuan; Zhang, Xia; Li, Lingjiang; Xu, Lin

    2016-03-01

    Fear is crucial for survival, whereas hypermnesia of fear can be detrimental. Inhibition of the Rac GTPase is recently reported to impair the forgetting of initially acquired memory in Drosophila. Here, we investigated whether inhibition of Rac1 activity in rat hippocampus could contribute to the hypermnesia of contextual fear. We found that spaced but not massed training of contextual fear conditioning caused inhibition of Rac1 activity in the hippocampus and heightened contextual fear. Furthermore, intrahippocampal injection of the Rac1 inhibitor NSC23766 heightened contextual fear in massed training, while Rac1 activator CN04-A weakened contextual fear in spaced training rats. Our study firstly demonstrates that contextual fear memory in rats is actively regulated by Rac1 activity in the hippocampus, which suggests that the forgetting impairment of traumatic events in posttraumatic stress disorder may be contributed to the pathological inhibition of Rac1 activity in the hippocampus.

  7. Selective impairment of living things and musical instruments on a verbal 'Semantic Knowledge Questionnaire' in a case of apperceptive visual agnosia.

    PubMed

    Masullo, Carlo; Piccininni, Chiara; Quaranta, Davide; Vita, Maria Gabriella; Gaudino, Simona; Gainotti, Guido

    2012-10-01

    Semantic memory was investigated in a patient (MR) affected by a severe apperceptive visual agnosia, due to an ischemic cerebral lesion, bilaterally affecting the infero-mesial parts of the temporo-occipital cortices. The study was made by means of a Semantic Knowledge Questionnaire (Laiacona, Barbarotto, Trivelli, & Capitani, 1993), which takes separately into account four categories of living beings (animals, fruits, vegetables and body parts) and of artefacts (furniture, tools, vehicles and musical instruments), does not require a visual analysis and allows to distinguish errors concerning super-ordinate categorization, perceptual features and functional/encyclopedic knowledge. When the total number of errors obtained on all the categories of living and non-living beings was considered, a non-significant trend toward a higher number of errors in living stimuli was observed. This difference, however, became significant when body parts and musical instruments were excluded from the analysis. Furthermore, the number of errors obtained on the musical instruments was similar to that obtained on the living categories of animals, fruits and vegetables and significantly higher of that obtained in the other artefact categories. This difference was still significant when familiarity, frequency of use and prototypicality of each stimulus entered into a logistic regression analysis. On the other hand, a separate analysis of errors obtained on questions exploring super-ordinate categorization, perceptual features and functional/encyclopedic attributes showed that the differences between living and non-living stimuli and between musical instruments and other artefact categories were mainly due to errors obtained on questions exploring perceptual features. All these data are at variance with the 'domains of knowledge' hypothesis', which assumes that the breakdown of different categories of living and non-living things respects the distinction between biological entities and

  8. Impaired synaptic development in a maternal immune activation mouse model of neurodevelopmental disorders.

    PubMed

    Coiro, Pierluca; Padmashri, Ragunathan; Suresh, Anand; Spartz, Elizabeth; Pendyala, Gurudutt; Chou, Shinnyi; Jung, Yoosun; Meays, Brittney; Roy, Shreya; Gautam, Nagsen; Alnouti, Yazen; Li, Ming; Dunaevsky, Anna

    2015-11-01

    Both genetic and environmental factors are thought to contribute to neurodevelopmental and neuropsychiatric disorders with maternal immune activation (MIA) being a risk factor for both autism spectrum disorders and schizophrenia. Although MIA mouse offspring exhibit behavioral impairments, the synaptic alterations in vivo that mediate these behaviors are not known. Here we employed in vivo multiphoton imaging to determine that in the cortex of young MIA offspring there is a reduction in number and turnover rates of dendritic spines, sites of majority of excitatory synaptic inputs. Significantly, spine impairments persisted into adulthood and correlated with increased repetitive behavior, an ASD relevant behavioral phenotype. Structural analysis of synaptic inputs revealed a reorganization of presynaptic inputs with a larger proportion of spines being contacted by both excitatory and inhibitory presynaptic terminals. These structural impairments were accompanied by altered excitatory and inhibitory synaptic transmission. Finally, we report that a postnatal treatment of MIA offspring with the anti-inflammatory drug ibudilast, prevented both synaptic and behavioral impairments. Our results suggest that a possible altered inflammatory state associated with maternal immune activation results in impaired synaptic development that persists into adulthood but which can be prevented with early anti-inflammatory treatment.

  9. Impairments, activity limitations, and participation restrictions of the international classification of functioning, disability, and health model in children with ambulatory cerebral palsy

    PubMed Central

    Mutlu, Akmer; Büğüsan, Sema; Kara, Özgün K.

    2017-01-01

    Objectives: To examine the impairments, activity limitations, and participation restrictions in children with spastic unilateral and bilateral cerebral palsy (CP). We investigated the relationship between these factors according to the international classification of functioning, disability, and health (ICF) model. Methods: This prospective cross sectional study included 60 children aged between 4-18 years with spastic CP (30 unilateral, 30 bilateral involvement) classified as Levels I and II on the gross motor function classification system. Children had been referred to the Pediatric Rehabilitation Unit in the Department of Physiotherapy and Rehabilitation, Hacettepe University, Ankara, Turkey between March 2014 and March 2015. The Physician Rating scale was used to assess body functions and structures. The Gillette Functional Assessment Questionnaire 22-item skill set, Pediatric Functional Independence Measure, and Pediatric Outcomes Data Collection Instrument were used to assess activity and participation levels. Results: There was a significant positive correlation between impairments and activity limitations (r=0.558; p=0.000), as well as between activity limitations and participation restrictions (r=0.354, p=0.005). Conclusion: These results show that activity limitations in children with unilateral and bilateral ambulatory CP may be related to their impairments and participation restrictions, although the sample size of our study is not large enough for generalizations. Overall, our study highlights the need for up-to-date, practical evaluation methods according to the ICF model. PMID:28133691

  10. Pridopidine activates neuroprotective pathways impaired in Huntington Disease

    PubMed Central

    Geva, Michal; Kusko, Rebecca; Soares, Holly; Fowler, Kevin D.; Birnberg, Tal; Barash, Steve; -Wagner, Avia Merenlender; Fine, Tania; Lysaght, Andrew; Weiner, Brian; Cha, Yoonjeong; Kolitz, Sarah; Towfic, Fadi; Orbach, Aric; Laufer, Ralph; Zeskind, Ben; Grossman, Iris; Hayden, Michael R.

    2016-01-01

    Pridopidine has demonstrated improvement in Huntington Disease (HD) motor symptoms as measured by secondary endpoints in clinical trials. Originally described as a dopamine stabilizer, this mechanism is insufficient to explain the clinical and preclinical effects of pridopidine. This study therefore explored pridopidine’s potential mechanisms of action. The effect of pridopidine versus sham treatment on genome-wide expression profiling in the rat striatum was analysed and compared to the pathological expression profile in Q175 knock-in (Q175 KI) vs Q25 WT mouse models. A broad, unbiased pathway analysis was conducted, followed by testing the enrichment of relevant pathways. Pridopidine upregulated the BDNF pathway (P = 1.73E-10), and its effect on BDNF secretion was sigma 1 receptor (S1R) dependent. Many of the same genes were independently found to be downregulated in Q175 KI mice compared to WT (5.2e-7 < P < 0.04). In addition, pridopidine treatment upregulated the glucocorticoid receptor (GR) response, D1R-associated genes and the AKT/PI3K pathway (P = 1E-10, P = 0.001, P = 0.004, respectively). Pridopidine upregulates expression of BDNF, D1R, GR and AKT/PI3K pathways, known to promote neuronal plasticity and survival, as well as reported to demonstrate therapeutic benefit in HD animal models. Activation of S1R, necessary for its effect on the BDNF pathway, represents a core component of the mode of action of pridopidine. Since the newly identified pathways are downregulated in neurodegenerative diseases, including HD, these findings suggest that pridopidine may exert neuroprotective effects beyond its role in alleviating some symptoms of HD. PMID:27466197

  11. The Development, Dissemination, and Evaluation of Science Activities for Hearing-Impaired Children. Final Report.

    ERIC Educational Resources Information Center

    Barman, Charles R.; Shedd, Jill D.

    The main focus of this project was to prepare a handbook of science activities and to disseminate this handbook to K-8 teachers of the hearing-impaired in the State of Indiana. The handbook, titled "Doing Science Using the Learning Cycle," was developed by a select group of teachers and several consultants with expertise in curriculum…

  12. Adaptation and reliability of neighborhood environment walkability scale (NEWS) for Iran: A questionnaire for assessing environmental correlates of physical activity

    PubMed Central

    Hakimian, Pantea; Lak, Azadeh

    2016-01-01

    Background: In spite of the increased range of inactivity and obesity among Iranian adults, insufficient research has been done on environmental factors influencing physical activity. As a result adapting a subjective (self-report) measurement tool for assessment of physical environment in Iran is critical. Accordingly, in this study Neighborhood Environment Walkability Scale (NEWS) was adapted for Iran and also its reliability was evaluated. Methods: This study was conducted using a systematic adaptation method consisting of 3 steps: translate-back translation procedures, revision by a multidisciplinary panel of local experts and a cognitive study. Then NEWS-Iran was completed among adults aged 18 to 65 years (N=19) with an interval of 15 days. Intra-Class Coefficient (ICC) was used to evaluate the reliability of the adapted questionnaire. Results: NEWS-Iran is an adapted version of NEWS-A (abbreviated) and in the adaptation process five items were added from other versions of NEWS, two subscales were significantly modified for a shorter and more effective questionnaire, and five new items were added about climate factors and site-specific uses. NEWS-Iran showed almost perfect reliability (ICCs: more than 0.8) for all subscales, with items having moderate to almost perfect reliability scores (ICCs: 0.56-0.96). Conclusion: This study introduced NEWS-Iran, which is a reliable version of NEWS for measuring environmental perceptions related to physical activity behavior adapted for Iran. It is the first adapted version of NEWS which demonstrates a systematic adaptation process used by earlier studies. It can be used for other developing countries with similar environmental, social and cultural context. PMID:28210592

  13. Adaptation and reliability of neighborhood environment walkability scale (NEWS) for Iran: A questionnaire for assessing environmental correlates of physical activity.

    PubMed

    Hakimian, Pantea; Lak, Azadeh

    2016-01-01

    Background: In spite of the increased range of inactivity and obesity among Iranian adults, insufficient research has been done on environmental factors influencing physical activity. As a result adapting a subjective (self-report) measurement tool for assessment of physical environment in Iran is critical. Accordingly, in this study Neighborhood Environment Walkability Scale (NEWS) was adapted for Iran and also its reliability was evaluated. Methods: This study was conducted using a systematic adaptation method consisting of 3 steps: translate-back translation procedures, revision by a multidisciplinary panel of local experts and a cognitive study. Then NEWS-Iran was completed among adults aged 18 to 65 years (N=19) with an interval of 15 days. Intra-Class Coefficient (ICC) was used to evaluate the reliability of the adapted questionnaire. Results: NEWS-Iran is an adapted version of NEWS-A (abbreviated) and in the adaptation process five items were added from other versions of NEWS, two subscales were significantly modified for a shorter and more effective questionnaire, and five new items were added about climate factors and site-specific uses. NEWS-Iran showed almost perfect reliability (ICCs: more than 0.8) for all subscales, with items having moderate to almost perfect reliability scores (ICCs: 0.56-0.96). Conclusion: This study introduced NEWS-Iran, which is a reliable version of NEWS for measuring environmental perceptions related to physical activity behavior adapted for Iran. It is the first adapted version of NEWS which demonstrates a systematic adaptation process used by earlier studies. It can be used for other developing countries with similar environmental, social and cultural context.

  14. Assessing practice-based influences on adolescent psychosocial development in sport: the activity context in youth sport questionnaire.

    PubMed

    García Bengoechea, Enrique; Sabiston, Catherine M; Wilson, Philip M

    2017-01-01

    The aim of this study was to provide initial evidence of validity and reliability of scores derived from the Activity Context in Youth Sport Questionnaire (ACYSQ), an instrument designed to offer a comprehensive assessment of the activities adolescents take part in during sport practices. Two studies were designed for the purposes of item development and selection, and to provide evidence of structural and criterion validity of ACYSQ scores, respectively (N = 334; M age = 14.93, SD = 1.76 years). Confirmatory factor analysis (CFA) supported the adequacy of a 20-item ACYSQ measurement model, which was invariant across gender, and comprised the following dimensions: (1) stimulation; (2) usefulness-value; (3) authenticity; (4) repetition-boredom; and (5) ineffectiveness. Internal consistency reliability estimates and composite reliability estimates for ACYSQ subscale scores ranged from 0.72 to 0.91. In regression analyses, stimulation predicted enjoyment and perceived competence, ineffectiveness was significantly associated with perceived competence and authenticity emerged as a predictor of commitment in sport. These findings indicate that the ACYSQ displays adequate psychometric properties and the use of the instrument may be useful for studying selected activity-based features of the practice environment and their motivational consequences in youth sport.

  15. The reliability and validity of the English version of the Evaluation of Daily Activity Questionnaire for people with rheumatoid arthritis

    PubMed Central

    Tennant, Alan; Tyson, Sarah F.; Nordenskiöld, Ulla; Hawkins, Ruth; Prior, Yeliz

    2015-01-01

    Objectives. The Evaluation of Daily Activity Questionnaire (EDAQ) includes 138 items in 14 domains identified as important by people with RA. The aim of this study was to test the validity and reliability of the English EDAQ. Methods. A total of 502 participants completed two questionnaires 3 weeks apart. The first consisted of the EDAQ, HAQ, RA Quality of Life (RAQoL) and the Medical Outcomes Scale (MOS) 36-item Short-Form Health Survey (SF-36v2), and the second consisted of the EDAQ only. The 14 EDAQ domains were tested for: unidimensionality—using confirmatory factor analysis; fit, response dependency, invariance across groups (differential item functioning)—using Rasch analysis; internal consistency [Person Separation Index (PSI)]; concurrent validity—by correlations with the HAQ, SF-36v2 and RAQoL; and test–retest reliability (Spearman’s correlations). Results. Confirmatory factor analysis of the 14 EDAQ domains indicated unidimensionality, after adjustment for local dependency in each domain. All domains achieved a root mean square error of approximation <0.10 and satisfied Rasch model expectations for local dependency. DIF by age, gender and employment status was largely absent. The PSI was consistent with individual use (PSI = 0.94 for all 14 domains). For all domains, except Caring, concurrent validity was good: HAQ (rs = 0.72–0.91), RAQoL (rs = 0.67–0.82) and SF36v2 Physical Function scale (rs = −0.60 to −0.84) and test–retest reliability was good (rs = 0.70–0.89). Conclusion. Analysis supported a 14-domain, two-component structure (Self care and Mobility) of the EDAQ, where each domain, and both components, satisfied Rasch model requirements, and have robust reliability and validity. PMID:25863045

  16. Performance of the international physical activity questionnaire (short form) in subgroups of the Hong Kong chinese population

    PubMed Central

    2011-01-01

    Background The International Physical Activity Questionnaire (IPAQ-SF) has been validated and recommended as an efficient method to assess physical activity, but its validity has not been investigated in different population subgroups. We examined variations in IPAQ validity in the Hong Kong Chinese population by six factors: sex, age, job status, educational level, body mass index (BMI), and visceral fat level (VFL). Methods A total of 1,270 adults (aged 42.9 ± SD 14.4 years, 46.1% male) completed the Chinese version of IPAQ (IPAQ-C) and wore an accelerometer (ActiGraph) for four days afterwards. The IPAQ-C and the ActiGraph were compared in terms of estimated Metabolic Equivalent Task minutes per week (MET-min/wk), minutes spent in activity of moderate or vigorous intensity (MVPA), and agreement in the classification of physical activity. Results The overall Spearman correlation (ρ) of between the IPAQ-C and ActiGraph was low (0.11 ± 0.03; range in subgroups 0.06-0.24) and was the highest among high VFL participants (0.24 ± 0.05). Difference between self-reported and ActiGraph-derived MET-min/wk (overall 2966 ± 140) was the smallest among participants with tertiary education (1804 ± 208). When physical activity was categorized into over or under 150 min/wk, overall agreement between self-report and accelerometer was 81.3% (± 1.1%; subgroup range: 77.2%-91.4%); agreement was the highest among those who were employed full-time in physically demanding jobs (91.4% ± 2.7%). Conclusions Sex, age, job status, educational level, and obesity were found to influence the criterion validity of IPAQ-C, yet none of the subgroups showed good validity (ρ = 0.06 to 0.24). IPAQ-SF validity is questionable in our Chinese population. PMID:21801461

  17. Visfatin Impairs Endothelium-Dependent Relaxation in Rat and Human Mesenteric Microvessels through Nicotinamide Phosphoribosyltransferase Activity

    PubMed Central

    Angulo, Javier; Villalobos, Laura A.; Cercas, Elena; Leivas, Alejandra; Bermejo, Elena; Carraro, Raffaele; Sánchez-Ferrer, Carlos F.; Peiró, Concepción

    2011-01-01

    Visfatin, also known as extracellular pre–B-cell colony–enhancing factor (PBEF) and nicotinamide phosphoribosyltransferase (Nampt), is an adipocytokine whose circulating levels are enhanced in metabolic disorders, such as type 2 diabetes mellitus and obesity. Circulating visfatin levels have been positively associated with vascular damage and endothelial dysfunction. Here, we investigated the ability of visfatin to directly impair vascular reactivity in mesenteric microvessels from both male Sprague-Dawley rats and patients undergoing non-urgent, non-septic abdominal surgery. The pre-incubation of rat microvessels with visfatin (50 and 100 ng/mL) did not modify the contractile response to noradrenaline (1 pmol/L to 30 µmol/L), as determined using a small vessel myograph. However, visfatin (10 to 100 ng/mL) concentration-dependently impaired the relaxation to acetylcholine (ACh; 100 pmol/L to 3 µmol/L), without interfering with the endothelium-independent relaxation to sodium nitroprusside (1 nmol/L to 3 µmol/L). In both cultured human umbilical vein endothelial cells and rat microvascular preparations, visfatin (50 ng/mL) stimulated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, as determined by lucigenin-derived chemiluminiscence. The relaxation to ACh impaired by visfatin was restored by the NADPH oxidase inhibitor apocynin (10 µmol/L). Additionally, the Nampt inhibitor APO866 (10 mmol/L to 10 µmol/L), but not an insulin receptor-blocking antibody, also prevented the stimulation of NADPH oxidase and the relaxation impairment elicited by visfatin. Accordingly, the product of Nampt activity nicotinamide mononucleotide (100 nmol/L to 1 mmol/L) stimulated endothelial NADPH oxidase activity and concentration-dependently impaired ACh-induced vasorelaxation. In human mesenteric microvessels pre-contracted with 35 mmol/L potassium chloride, the endothelium-dependent vasodilation to bradykinin (1 nmol/L to 3 µmol/L) was equally impaired by

  18. Impaired anterior insular activation during risky decision making in young adults with internet gaming disorder.

    PubMed

    Lee, Deokjong; Lee, Junghan; Yoon, Kang Joon; Kee, Namkoong; Jung, Young-Chul

    2016-05-25

    Internet gaming disorder is defined as excessive and compulsive use of the internet to engage in games that leads to clinically significant psychosocial impairment. We tested the hypothesis that individuals with internet gaming disorder would be less sensitive to high-risk situations and show aberrant brain activation related to risk prediction processing. Young adults with internet gaming disorder underwent functional MRI while performing a risky decision-making task. The healthy control group showed stronger activations within the dorsal attention network and the anterior insular cortex, which were not found in the internet gaming disorder group. Our findings imply that young adults with internet gaming disorder show impaired anterior insular activation during risky decision making, which might make them vulnerable when they need to adapt new behavioral strategies in high-risk situations.

  19. Physical activity correlates with neurological impairment and disability in multiple sclerosis.

    PubMed

    Motl, Robert W; Snook, Erin M; Wynn, Daniel R; Vollmer, Timothy

    2008-06-01

    This study examined the correlation of physical activity with neurological impairment and disability in persons with multiple sclerosis (MS). Eighty individuals with MS wore an accelerometer for 7 days and completed the Symptom Inventory (SI), Performance Scales (PS), and Expanded Disability Status Scale. There were large negative correlations between the accelerometer and SI (r = -0.56; rho = -0.58) and Expanded Disability Status Scale (r = -0.60; rho = -0.69) and a moderate negative correlation between the accelerometer and PS (r = -0.39; rho = -0.48) indicating that physical activity was associated with reduced neurological impairment and disability. Such findings provide a preliminary basis for using an accelerometer and the SI and PS as outcome measures in large-scale prospective and experimental examinations of the effect of physical activity behavior on disability and dependence in MS.

  20. Impairment variables predicting activity limitation in individuals with lower limb amputation.

    PubMed

    Raya, Michele A; Gailey, Robert S; Fiebert, Ira M; Roach, Kathyrn E

    2010-03-01

    The purpose of this study was to determine whether measures of impairment (i.e., muscle strength, balance), personal factors (i.e., comorbidities, demographic information) and amputation specific variables (i.e., time since amputation, cause of amputation, level of amputation) were able to predict performance on the six-minute walk test, a measure of activity limitation, in individuals with lower limb amputation. A total of 72 individuals with lower limb amputation ranging in age from 21-83 were tested for balance, limb muscle strength and function. Medical comorbidities were recorded and activity limitation was measured using the six-minute walk test. Data were analyzed and multivariate relationships were examined using multiple linear regression. Impairment variables of strength, balance, subject demographics, time since amputation, cause of amputation and level of amputation were all significant predictors and explained 72% of the variance in the outcome variable. Strength of the hip extensors was the strongest predictor, accounting for 30.9% of the total variance. Multiple factors impact six minute walk scores in individuals with lower limb amputation. Impairments in hip strength and balance appear to be the two most significant. The findings of this study support the use of the six-minute walk test to underscore impairments of the musculoskeletal system that can affect ambulation ability in the amputee.

  1. Tim-3 pathway affects NK cell impairment in patients with active tuberculosis.

    PubMed

    Wang, Feng; Hou, Hongyan; Wu, Shiji; Tang, Qing; Huang, Min; Yin, Botao; Huang, Jing; Liu, Weiyong; Mao, Lie; Lu, Yanfang; Sun, Ziyong

    2015-12-01

    Active tuberculosis (TB) patients show impaired NK cell function, and the underlying mechanism remains largely unknown. In this study, we confirmed the decrease in activation, cytokine secretion, and degranulation potential of NK cells in active TB patients. We further investigated whether coinhibitory receptor Tim-3 was involved with impairment of NK cells. Our results revealed that the expression of Tim-3 on NK cells was increased in active TB patients. Tim-3 expression was inversely correlated with IL-12-stimualted IFN-γ production. Moreover, blocking the Tim-3 pathway restored IFN-γ secretion and degranulation of NK cells. Blocking this pathway also increased NK cell cytotoxicity against K562 target cells, and improved the ability of NK cells to control Mtb growth in monocyte-derived macrophages. The Tim-3 expression on NK cells was also observed to be significantly decreased in TB patients post-treatment. In this study, we have identified that Tim-3 is involved with NK cell impairment in TB patients.

  2. Development and Validation of a Short Form of the Valued Life Activities Disability Questionnaire for Rheumatoid Arthritis

    PubMed Central

    Katz, Patricia P.; Radvanski, Diane C.; Allen, Diane; Buyske, Steven; Schiff, Samuel; Nadkarni, Anagha; Rosenblatt, Lisa; Maclean, Ross; Hassett, Afton L.

    2011-01-01

    Objective Develop and validate a shortened version of the Valued Life Activities disability and accommodations scale (VLA) for individuals with rheumatoid arthritis (RA). Methods To shorten the existing VLA measure, item response theory analyses were conducted using data from 449 patients with RA. Next, the resulting 14-item shortened version of the VLA scale (S-VLA) was evaluated by structured interviews among 20 RA patients. Lastly, the S-VLA was administered to 150 RA patients along with other measures including the Health Assessment Questionnaire (HAQ) and SF-36. A random sample of 50 patients completed the S-VLA two weeks later to assess reliability. Item statistics were calculated to evaluate correlations between individual items and S-VLA total score. Correlations between the S-VLA and other measures were used to evaluate validity. Results Test–retest reliability was 0.91, while Cronbach’s alpha for the S-VLA was 0.95. None of the 14 items were associated with improved alpha coefficients when omitted. All items were strongly correlated with the S-VLA total score. S-VLA scores were highly positively correlated with HAQ (r=0.81; p≤0.001), patient-reported disease activity (r=0.71; p≤0.001), satisfaction with abilities (r=0.82; p≤0.001), and number of days with activity limitations (r=0.65; p≤0.001). In addition, as hypothesized, the S-VLA was inversely correlated with SF-36 Physical Component Summary score (r=−0.78; p≤0.001) and subscales: Physical Functioning (r=−0.80; p≤0.001), Role Physical (r=−0.67; p≤0.001) and Social Functioning (r=−0.72; p≤0.001). Conclusions The S-VLA is a short, valid, and reliable instrument that may prove useful for monitoring disability among individuals with RA. PMID:21905253

  3. HIV Glycoprotein Gp120 Impairs Fast Axonal Transport by Activating Tak1 Signaling Pathways

    PubMed Central

    Berth, Sarah H.; Mesnard-Hoaglin, Nichole; Wang, Bin; Kim, Hajwa; Song, Yuyu; Sapar, Maria; Morfini, Gerardo

    2016-01-01

    Sensory neuropathies are the most common neurological complication of HIV. Of these, distal sensory polyneuropathy (DSP) is directly caused by HIV infection and characterized by length-dependent axonal degeneration of dorsal root ganglion (DRG) neurons. Mechanisms for axonal degeneration in DSP remain unclear, but recent experiments revealed that the HIV glycoprotein gp120 is internalized and localized within axons of DRG neurons. Based on these findings, we investigated whether intra-axonal gp120 might impair fast axonal transport (FAT), a cellular process critical for appropriate maintenance of the axonal compartment. Significantly, we found that gp120 severely impaired both anterograde and retrograde FAT. Providing a mechanistic basis for these effects, pharmacological experiments revealed an involvement of various phosphotransferases in this toxic effect, including members of mitogen-activated protein kinase pathways (Tak-1, p38, and c-Jun N-terminal Kinase (JNK)), inhibitor of kappa-B-kinase 2 (IKK2), and PP1. Biochemical experiments and axonal outgrowth assays in cell lines and primary cultures extended these findings. Impairments in neurite outgrowth in DRG neurons by gp120 were rescued using a Tak-1 inhibitor, implicating a Tak-1 mitogen-activated protein kinase pathway in gp120 neurotoxicity. Taken together, these observations indicate that kinase-based impairments in FAT represent a novel mechanism underlying gp120 neurotoxicity consistent with the dying-back degeneration seen in DSP. Targeting gp120-based impairments in FAT with specific kinase inhibitors might provide a novel therapeutic strategy to prevent axonal degeneration in DSP. PMID:27872270

  4. Is a single question of the Global Physical Activity Questionnaire (GPAQ) valid for measuring sedentary behaviour in the Chilean population?

    PubMed

    Aguilar-Farias, Nicolas; Leppe Zamora, Jaime

    2016-09-08

    A study was conducted to assess the validity of the Global Physical Activity Questionnaire (GPAQ) for measuring sedentary behaviour (SB) in the Chilean adult population. About 217 adults (93/124 male/female, 43.8 ± 15.75 years) who were randomly selected during National Health Survey 2009-2010 completed the protocol. The participants wore an ActiGraph GT3X (AG) for 7 consecutive days and then completed the GPAQ (single-item question for measuring time spent sitting in a usual day). Validity was examined using Spearman's correlation, mean bias and limits of agreement (LoA), with AG (vertical axis <100 counts · min(-1)) as the reference standard for estimates of SB in bouts of 1 (AG1), 5 (AG5) and 10 (AG10) min. Agreement between the GPAQ and AG for classifying data into quartiles and tertiles was assessed with kappa method. The GPAQ showed fair correlation with AG1, AG5 and AG10 (range = 0.23-0.26), with large mean biases (range = -293.9, -76.12 min · day(-1)). Agreement between the GPAQ and AG1, AG5 and AG10 was poor for categorising time spent in SB into tertiles and quartiles. The single question from the GPAQ has shown fair validity for measuring SB and poor ability for correctly classifying individuals into tertiles or quartiles of SB in a Chilean population.

  5. Psychometric properties of the Social Cognitive Theory questionnaire for physical activity in a sample of Iranian adolescent girl students.

    PubMed

    Ardestani, M S; Niknami, S; Hidarnia, A; Hajizadeh, E

    2016-08-18

    This research examined the validity and reliability of a researcher-developed questionnaire based on Social Cognitive Theory (SCT) to assess the physical activity behaviour of Iranian adolescent girls (SCT-PAIAGS). Psychometric properties of the SCT-PAIAGS were assessed by determining its face validity, content and construct validity as well as its reliability. In order to evaluate factor structure, cross-sectional research was conducted on 400 high-school girls in Tehran. Content validity index, content validity ratio and impact score for the SCT-PAIAGS varied between 0.97-1, 0.91-1 and 4.6-4.9 respectively. Confirmatory factor analysis approved a six-factor structure comprising self-efficacy, self-regulation, family support, friend support, outcome expectancy and self-efficacy to overcoming impediments. Factor loadings, t-values and fit indices showed that the SCT model was fitted to the data. Cronbach's α-coefficient ranged from 0.78 to 0.85 and intraclass correlation coefficient from 0.73 to 0.90.

  6. Antiamnesic activity of Syzygium cumini against scopolamine induced spatial memory impairments in rats.

    PubMed

    Alikatte, Kanaka Latha; Akondi, Butchi Raju; Yerragunta, Venu Gopal; Veerareddy, Prabhakar Reddy; Palle, Suresh

    2012-11-01

    We evaluated the Antiamnesic effects of methanolic extract of Syzygium cumini (MESC) on spatial memory impairments induced by scopolamine (1 mg/kg, i.p.), a muscarinic antagonist, using the Radial arm maze, Morris water maze, learned helpless ness tests. Effect of MESC was evaluated and compared to standard drug, piracetam (200 mg/kg, i.p.). The MESC significantly (p<0.05) improved the impairment of short term or working memory induced by scopolamine in the Radial arm maze test, and significantly (p<0.05) reversed cognitive impairments in rats as measured by the learned helplessness test. In addition, MESC decreased escape latencies in the Morris water maze test. The activity of acetylcholinesterase in the brain was inhibited significantly (p<0.05) by treatment with MESC to a level similar to that observed in rats treated with piracetam. Moreover treatment with MESC (200 and 400 mg/kg, p.o.) to scopolamine induced rats significantly (p<0.05) decreased TBARS levels which was accompanied by an increase in the activities of SOD and Catalase. MESC has dose dependent effect and 400 mg/kg dose shown more prominent results when compared to 200 mg/kg dose of MESC. These results indicate that MESC may exert anti-amnesic activity via inhibition of acetylcholinesterase and antioxidant mechanisms in the brain.

  7. Aldosterone impairs vascular reactivity by decreasing glucose-6-phosphate dehydrogenase activity

    PubMed Central

    Leopold, Jane A.; Dam, Aamir; Maron, Bradley A.; Scribner, Anne W.; Liao, Ronglih; Handy, Diane E.; Stanton, Robert C.; Pitt, Bertram; Loscalzo, Joseph

    2013-01-01

    Hyperaldosteronism is associated with impaired vascular reactivity; however, the mechanism by which aldosterone promotes endothelial dysfunction remains unknown. Glucose-6-phosphate dehydrogenase (G6pd), the principal source of Nadph, modulates vascular function by limiting oxidant stress to preserve bioavailable nitric oxide (NO•). In these studies, we show that aldosterone (10−9-10−7 mol/l) decreases endothelial G6pd expression and activity in vitro resulting in increased oxidant stress and decreased cGMP levels similar to what is observed in G6pd-deficient cells. Aldosterone decreases G6pd expression by protein kinase A activation to increase expression of Crem, which interferes with Creb binding to the G6pd promoter. In vivo, infusion of aldosterone decreases vascular G6pd expression and impairs vascular reactivity. These effects are abrogated by spironolactone or vascular gene transfer of G6pd. These studies demonstrate that aldosterone induces a G6pd-deficient phenotype to impair endothelial function; aldosterone antagonism or gene transfer of G6pd improves vascular reactivity by restoring G6pd activity. PMID:17273168

  8. Sustained inflammasome activity in macrophages impairs wound healing in type 2 diabetic humans and mice.

    PubMed

    Mirza, Rita E; Fang, Milie M; Weinheimer-Haus, Eileen M; Ennis, William J; Koh, Timothy J

    2014-03-01

    The hypothesis of this study was that sustained activity of the Nod-like receptor protein (NLRP)-3 inflammasome in wounds of diabetic humans and mice contributes to the persistent inflammatory response and impaired healing characteristic of these wounds. Macrophages (Mp) isolated from wounds on diabetic humans and db/db mice exhibited sustained inflammasome activity associated with low level of expression of endogenous inflammasome inhibitors. Soluble factors in the biochemical milieu of these wounds are sufficient to activate the inflammasome, as wound-conditioned medium activates caspase-1 and induces release of interleukin (IL)-1β and IL-18 in cultured Mp via a reactive oxygen species-mediated pathway. Importantly, inhibiting inflammasome activity in wounds of db/db mice using topical application of pharmacological inhibitors improved healing of these wounds, induced a switch from proinflammatory to healing-associated Mp phenotypes, and increased levels of prohealing growth factors. Furthermore, data generated from bone marrow-transfer experiments from NLRP-3 or caspase-1 knockout to db/db mice indicated that blocking inflammasome activity in bone marrow cells is sufficient to improve healing. Our findings indicate that sustained inflammasome activity in wound Mp contributes to impaired early healing responses of diabetic wounds and that the inflammasome may represent a new therapeutic target for improving healing in diabetic individuals.

  9. Impaired translocation and activation of mitochondrial Akt1 mitigated mitochondrial oxidative phosphorylation Complex V activity in diabetic myocardium.

    PubMed

    Yang, Jia-Ying; Deng, Wu; Chen, Yumay; Fan, Weiwei; Baldwin, Kenneth M; Jope, Richard S; Wallace, Douglas C; Wang, Ping H

    2013-06-01

    Insulin can translocate Akt to mitochondria in cardiac muscle. The goals of this study were to define sub-mitochondrial localization of the translocated Akt, to dissect the effects of insulin on Akt isoform translocation, and to determine the direct effect of mitochondrial Akt activation on Complex V activity in normal and diabetic myocardium. The translocated Akt sequentially localized to the mitochondrial intermembrane space, inner membrane, and matrix. To confirm Akt translocation, in vitro import assay showed rapid entry of Akt into mitochondria. Akt isoforms were differentially regulated by insulin stimulation, only Akt1 translocated into mitochondria. In the insulin-resistant Type 2 diabetes model, Akt1 translocation was blunted. Mitochondrial activation of Akt1 increased Complex V activity by 24% in normal myocardium in vivo and restored Complex V activity in diabetic myocardium. Basal mitochondrial Complex V activity was lower by 22% in the Akt1(-/-) myocardium. Insulin-stimulated Complex V activity was not impaired in the Akt1(-/-) myocardium, due to compensatory translocation of Akt2 to mitochondria. Akt1 is the primary isoform that relayed insulin signaling to mitochondria and modulated mitochondrial Complex V activity. Activation of mitochondrial Akt1 enhanced ATP production and increased phosphocreatine in cardiac muscle cells. Dysregulation of this signal pathway might impair mitochondrial bioenergetics in diabetic myocardium.

  10. Mutation in E1, the ubiquitin activating enzyme, reduces Drosophila lifespan and results in motor impairment.

    PubMed

    Liu, Hsiu-Yu; Pfleger, Cathie M

    2013-01-01

    Neurodegenerative diseases cause tremendous suffering for those afflicted and their families. Many of these diseases involve accumulation of mis-folded or aggregated proteins thought to play a causal role in disease pathology. Ubiquitinated proteins are often found in these protein aggregates, and the aggregates themselves have been shown to inhibit the activity of the proteasome. These and other alterations in the Ubiquitin Pathway observed in neurodegenerative diseases have led to the question of whether impairment of the Ubiquitin Pathway on its own can increase mortality or if ongoing neurodegeneration alters Ubiquitin Pathway function as a side-effect. To address the role of the Ubiquitin Pathway in vivo, we studied loss-of-function mutations in the Drosophila Ubiquitin Activating Enzyme, Uba1 or E1, the most upstream enzyme in the Ubiquitin Pathway. Loss of only one functional copy of E1 caused a significant reduction in adult lifespan. Rare homozygous hypomorphic E1 mutants reached adulthood. These mutants exhibited further reduced lifespan and showed inappropriate Ras activation in the brain. Removing just one functional copy of Ras restored the lifespan of heterozygous E1 mutants to that of wild-type flies and increased the survival of homozygous E1 mutants. E1 homozygous mutants also showed severe motor impairment. Our findings suggest that processes that impair the Ubiquitin Pathway are sufficient to cause early mortality. Reduced lifespan and motor impairment are seen in the human disease X-linked Infantile Spinal Muscular Atrophy, which is associated with mutation in human E1 warranting further analysis of these mutants as a potential animal model for study of this disease.

  11. Impairments in prehension produced by early postnatal sensory motor cortex activity blockade.

    PubMed

    Martin, J H; Donarummo, L; Hacking, A

    2000-02-01

    This study examined the effects of blocking neural activity in sensory motor cortex during early postnatal development on prehension. We infused muscimol, either unilaterally or bilaterally, into the sensory motor cortex of cats to block activity continuously between postnatal weeks 3-7. After stopping infusion, we trained animals to reach and grasp a cube of meat and tested behavior thereafter. Animals that had not received muscimol infusion (unilateral saline infusion; age-matched) reached for the meat accurately with small end-point errors. They grasped the meat using coordinated digit flexion followed by forearm supination on 82.7% of trials. Performance using either limb did not differ significantly. In animals receiving unilateral muscimol infusion, reaching and grasping using the limb ipsilateral to the infusion were similar to controls. The limb contralateral to infusion showed significant increases in systematic and variable reaching end-point errors, often requiring subsequent corrective movements to contact the meat. Grasping occurred on only 14.8% of trials, replaced on most trials by raking without distal movements. Compensatory adjustments in reach length and angle, to maintain end-point accuracy as movements were started from a more lateral position, were less effective using the contralateral limb than ipsilateral limb. With bilateral inactivations, the form of reaching and grasping impairments was identical to that produced by unilateral inactivation, but the magnitude of the reaching impairments was less. We discuss these results in terms of the differential effects of unilateral and bilateral inactivation on corticospinal tract development. We also investigated the degree to which these prehension impairments after unilateral blockade reflect control by each hemisphere. In animals that had received unilateral blockade between postnatal weeks (PWs) 3 and 7, we silenced on-going activity (after PW 11) during task performance using continuous

  12. Minocycline improves postoperative cognitive impairment in aged mice by inhibiting astrocytic activation.

    PubMed

    Jin, Wen-Jie; Feng, Shan-Wu; Feng, Zhou; Lu, Shun-Mei; Qi, Tao; Qian, Yan-Ning

    2014-01-08

    Astrocytes are proving to be critical for the development of cognitive functions. In addition, astrocytic activation contributes to cognitive impairment induced by chronic cerebral hypoperfusion. Minocycline has been shown to exhibit long-term neuroprotective effects in vascular cognitive impairment rat models through the inhibition of astrogliosis, and has demonstrated potential for the prevention and treatment of postoperative cognitive decline in elderly patients. This study aimed to examine the effect of minocycline on hippocampal astrocytes and long-term postoperative cognitive dysfunction in aged mice. Mice were intraperitoneally injected with 45 mg/kg minocycline once a day for 30 days after 70% hepatectomy. Hippocampus-dependent spatial memory ability was evaluated using the Morris water maze test. The expression levels of hippocampal glial fibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule-1 were evaluated by western blotting, and the hippocampal mRNA relative expression levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6 were tested using real-time PCR. The Morris water maze test showed that escape latency and swim distance were significantly prolonged by the surgery, but the extent of impairment was mitigated by minocycline treatment. Hippocampal GFAP levels and mRNA levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6 showed corresponding changes that were consistent with the variations in spatial memory. Minocycline was able to alleviate hepatectomy-related long-term spatial memory impairment in aged mice, and was associated with reduced levels of hippocampal GFAP and proinflammatory cytokines resulting from astrocytic activation.

  13. Impaired dual tasking in Parkinson's disease is associated with reduced focusing of cortico-striatal activity.

    PubMed

    Nieuwhof, Freek; Bloem, Bastiaan R; Reelick, Miriam F; Aarts, Esther; Maidan, Inbal; Mirelman, Anat; Hausdorff, Jeffrey M; Toni, Ivan; Helmich, Rick C

    2017-03-17

    Impaired dual tasking, namely the inability to concurrently perform a cognitive and a motor task (e.g. 'stops walking while talking'), is a largely unexplained and frequent symptom of Parkinson's disease. Here we consider two circuit-level accounts of how striatal dopamine depletion might lead to impaired dual tasking in patients with Parkinson's disease. First, the loss of segregation between striatal territories induced by dopamine depletion may lead to dysfunctional overlaps between the motor and cognitive processes usually implemented in parallel cortico-striatal circuits. Second, the known dorso-posterior to ventro-anterior gradient of dopamine depletion in patients with Parkinson's disease may cause a funnelling of motor and cognitive processes into the relatively spared ventro-anterior putamen, causing a neural bottleneck. Using functional magnetic resonance imaging, we measured brain activity in 19 patients with Parkinson's disease and 26 control subjects during performance of a motor task (auditory-cued ankle movements), a cognitive task (implementing a switch-stay rule), and both tasks simultaneously (dual task). The distribution of task-related activity respected the known segregation between motor and cognitive territories of the putamen in both groups, with motor-related responses in the dorso-posterior putamen and task switch-related responses in the ventro-anterior putamen. During dual task performance, patients made more motor and cognitive errors than control subjects. They recruited a striatal territory (ventro-posterior putamen) not engaged during either the cognitive or the motor task, nor used by controls. Relatively higher ventro-posterior putamen activity in controls was associated with worse dual task performance. These observations suggest that dual task impairments in Parkinson's disease are related to reduced spatial focusing of striatal activity. This pattern of striatal activity may be explained by a loss of functional segregation

  14. Insect cell-expressed p180erbB3 possesses an impaired tyrosine kinase activity.

    PubMed Central

    Guy, P M; Platko, J V; Cantley, L C; Cerione, R A; Carraway, K L

    1994-01-01

    Protein kinases share a number of highly conserved or invariant amino acid residues in their catalytic domains, suggesting that these residues are necessary for kinase activity. In p180erbB3, a receptor tyrosine kinase belonging to the epidermal growth factor (EGF) receptor subfamily, three of these residues are altered, suggesting that this protein might have an impaired protein tyrosine kinase activity. To test this hypothesis, we have expressed human EGF receptor and bovine p180erbB3 in insect cells via baculovirus infection and have compared their autophosphorylation and substrate phosphorylation activities. We have found that, while the EGF receptor readily undergoes EGF-stimulated autophosphorylation and catalyzes the incorporation of phosphate into the model substrates (E4Y1)n (random 4:1 copolymer of glutamic acid and tyrosine) and GST-p85 (glutathione S-transferase fusion protein with the 85-kDa subunit of phosphatidylinositol 3-kinase), p180erbB3 autophosphorylation and substrate phosphorylation are at least 2 orders of magnitude less efficient. However, p180erbB3 is capable of binding the ATP analog 5'-p-fluorosulfonylbenzoyladenosine, indicating that the lack of observed kinase activity is probably not due to nonfunctional or denatured receptors expressed by the insect cells. On the basis of these results, we propose that p180erbB3 possesses an impaired intrinsic tyrosine kinase activity. Images PMID:8058768

  15. Impaired dendritic inhibition leads to epileptic activity in a computer model of CA3.

    PubMed

    Sanjay, M; Neymotin, Samuel A; Krothapalli, Srinivasa B

    2015-11-01

    Temporal lobe epilepsy (TLE) is a common type of epilepsy with hippocampus as the usual site of origin. The CA3 subfield of hippocampus is reported to have a low epileptic threshold and hence initiates the disorder in patients with TLE. This study computationally investigates how impaired dendritic inhibition of pyramidal cells in the vulnerable CA3 subfield leads to generation of epileptic activity. A model of CA3 subfield consisting of 800 pyramidal cells, 200 basket cells (BC) and 200 Oriens-Lacunosum Moleculare (O-LM) interneurons was used. The dendritic inhibition provided by O-LM interneurons is reported to be selectively impaired in some TLEs. A step-wise approach is taken to investigate how alterations in network connectivity lead to generation of epileptic patterns. Initially, dendritic inhibition alone was reduced, followed by an increase in the external inputs received at the distal dendrites of pyramidal cells, and finally additional changes were made at the synapses between all neurons in the network. In the first case, when the dendritic inhibition of pyramidal cells alone was reduced, the local field potential activity changed from a theta-modulated gamma pattern to a prominently gamma frequency pattern. In the second case, in addition to this reduction of dendritic inhibition, with a simultaneous large increase in the external excitatory inputs received by pyramidal cells, the basket cells entered a state of depolarization block, causing the network to generate a typical ictal activity pattern. In the third case, when the dendritic inhibition onto the pyramidal cells was reduced and changes were simultaneously made in synaptic connectivity between all neurons in the network, the basket cells were again observed to enter depolarization block. In the third case, impairment of dendritic inhibition required to generate an ictal activity pattern was lesser than the two previous cases. Moreover, the ictal like activity began earlier in the third case

  16. Microglia activation and phagocytosis: relationship with aging and cognitive impairment in the rhesus monkey.

    PubMed

    Shobin, Eli; Bowley, Michael P; Estrada, Larissa I; Heyworth, Nadine C; Orczykowski, Mary E; Eldridge, Sherri A; Calderazzo, Samantha M; Mortazavi, Farzad; Moore, Tara L; Rosene, Douglas L

    2017-02-25

    While cognitive decline is observed in the normal aging monkey, neurons are not lost with age. Instead, frontal white matter is lost as myelin degenerates and both correlate with age-related cognitive decline. As age-related myelin damage increases, there should be an increase in clearance of damaged myelin by microglial phagocytosis. In this study, brains of behaviorally tested rhesus monkeys were assessed using unbiased stereology to quantify the density of activated microglia (LN3 antibody positive) and phagocytic microglia (galectin-3 (Gal-3) antibody positive) in three white matter regions: the corpus callosum, cingulum bundle (CGB), and frontal white matter (FWM). LN3 cell density was significantly increased in the CGB, whereas Gal-3 cell density was significantly increased in all regions. Increases in Gal-3 cell density in the FWM were associated with cognitive impairment. In the FWM of old animals, Gal-3-positive microglia were classified by morphological subtype as ramified, hypertrophic, or amoeboid. The densities of hypertrophic and amoeboid microglia significantly correlated with cognitive impairment. Finally, microglia were double-labeled with LN3 and Gal-3 showing that 91% of Gal-3 cells were also LN3 positive, thus expressing an "activated" phenotype. Furthermore, 15% of all double-labeled cells formed phagocytic cups. Overall, these results suggest that microglia become activated in white matter with age where the majority express a phagocytic phenotype. We hypothesize that age-related phagocytic activation of microglia is a response to accumulating myelin pathology. The association of Gal-3 in the FWM with cognitive impairment may reflect regional differences in damage or dysfunction of normal clearance mechanisms.

  17. Impaired autophagy activity is linked to elevated ER-stress and inflammation in aging adipose tissue

    PubMed Central

    Ghosh, Amiya Kumar; Mau, Theresa; O'Brien, Martin; Garg, Sanjay; Yung, Raymond

    2016-01-01

    Adipose tissue dysfunction in aging is associated with inflammation, metabolic syndrome and other diseases. We propose that impaired protein homeostasis due to compromised lysosomal degradation (micro-autophagy) might promote aberrant ER stress response and inflammation in aging adipose tissue. Using C57BL/6 mouse model, we demonstrate that adipose tissue-derived stromal vascular fraction (SVF) cells from old (18-20 months) mice have reduced expression of autophagy markers as compared to the younger (4-6 months) cohort. Elevated expressions of ER-stress marker CHOP and autophagy substrate SQSTM1/p62 are observed in old SVFs compared to young, when treated with either vehicle or with thapsigargin (Tg), an ER stress inducer. Treatment with bafilomycin A1 (Baf), a vacuolar-type H (+)-ATPase, or Tg elevated expressions of CHOP, and SQSTM1/p62 and LC-3-II, in 3T3-L1-preadipocytes. We also demonstrate impaired autophagy activity in old SVFs by analyzing increased accumulation of autophagy substrates LC3-II and p62. Compromised autophagy activity in old SVFs is correlated with enhanced release of pro-inflammatory cytokines IL-6 and MCP-1. Finally, SVFs from calorie restricted old mice (CR-O) have shown enhanced autophagy activity compared to ad libitum fed old mice (AL-O). Our results support the notion that diminished autophagy activity with aging contributes to increased adipose tissue ER stress and inflammation. PMID:27777379

  18. Long-Term Heavy Ketamine Use is Associated with Spatial Memory Impairment and Altered Hippocampal Activation

    PubMed Central

    Morgan, Celia J. A.; Dodds, Chris M.; Furby, Hannah; Pepper, Fiona; Fam, Johnson; Freeman, Tom P.; Hughes, Emer; Doeller, Christian; King, John; Howes, Oliver; Stone, James 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 examine the neural mechanism by which heavy ketamine use impairs spatial memory processing. In a sample of 11 frequent ketamine users and 15 poly-drug controls, matched for IQ, age, years in education. We used fMRI utilizing 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. PMID:25538631

  19. Defective histone supply causes condensin-dependent chromatin alterations, SAC activation and chromosome decatenation impairment

    PubMed Central

    Murillo-Pineda, Marina; Cabello-Lobato, María J.; Clemente-Ruiz, Marta; Monje-Casas, Fernando; Prado, Félix

    2014-01-01

    The structural organization of chromosomes is essential for their correct function and dynamics during the cell cycle. The assembly of DNA into chromatin provides the substrate for topoisomerases and condensins, which introduce the different levels of superhelical torsion required for DNA metabolism. In particular, Top2 and condensin are directly involved in both the resolution of precatenanes that form during replication and the formation of the intramolecular loop that detects tension at the centromeric chromatin during chromosome biorientation. Here we show that histone depletion activates the spindle assembly checkpoint (SAC) and impairs sister chromatid decatenation, leading to chromosome mis-segregation and lethality in the absence of the SAC. We demonstrate that histone depletion impairs chromosome biorientation and activates the Aurora-dependent pathway, which detects tension problems at the kinetochore. Interestingly, SAC activation is suppressed by the absence of Top2 and Smc2, an essential component of condensin. Indeed, smc2-8 suppresses catenanes accumulation, mitotic arrest and growth defects induced by histone depletion at semi-permissive temperature. Remarkably, SAC activation by histone depletion is associated with condensin-mediated alterations of the centromeric chromatin. Therefore, our results reveal the importance of a precise interplay between histone supply and condensin/Top2 for pericentric chromatin structure, precatenanes resolution and centromere biorientation. PMID:25300489

  20. Neuroblastoma Arginase Activity Creates an Immunosuppressive Microenvironment That Impairs Autologous and Engineered Immunity.

    PubMed

    Mussai, Francis; Egan, Sharon; Hunter, Stuart; Webber, Hannah; Fisher, Jonathan; Wheat, Rachel; McConville, Carmel; Sbirkov, Yordan; Wheeler, Kate; Bendle, Gavin; Petrie, Kevin; Anderson, John; Chesler, Louis; De Santo, Carmela

    2015-08-01

    Neuroblastoma is the most common extracranial solid tumor of childhood, and survival remains poor for patients with advanced disease. Novel immune therapies are currently in development, but clinical outcomes have not matched preclinical results. Here, we describe key mechanisms in which neuroblastoma inhibits the immune response. We show that murine and human neuroblastoma tumor cells suppress T-cell proliferation through increased arginase activity. Arginase II is the predominant isoform expressed and creates an arginine-deplete local and systemic microenvironment. Neuroblastoma arginase activity results in inhibition of myeloid cell activation and suppression of bone marrow CD34(+) progenitor proliferation. Finally, we demonstrate that the arginase activity of neuroblastoma impairs NY-ESO-1-specific T-cell receptor and GD2-specific chimeric antigen receptor-engineered T-cell proliferation and cytotoxicity. High arginase II expression correlates with poor survival for patients with neuroblastoma. The results support the hypothesis that neuroblastoma creates an arginase-dependent immunosuppressive microenvironment in both the tumor and blood that leads to impaired immunosurveillance and suboptimal efficacy of immunotherapeutic approaches.

  1. The Effects of Intellectual, Physical, and Social Activity on Further Prognosis in Mild Cognitive Impairment

    PubMed Central

    Bidzan, Leszek; Bidzan, Mariola; Pąchalska, Maria

    2016-01-01

    Background Our goal was to specify the relationship between the level of activity (intellectual, physical, and social) in persons diagnosed with mild cognitive impairment (MCI) and the further progression of cognitive dysfunction. Material/Methods We examined 193 patients diagnosed with MCI (according to the criteria of the Working Group on Mild Cognitive Impairment) and under treatment at our Mental Disorders Clinic. It was assumed that these persons would remain under systematic psychiatric observation until dementia was diagnosed. The present study results from a seven-year observation period. The mini–mental state examination (MMSE), the Activity Scale (with the intellectual, physical, and social subscales), and the Instrumental Activities of Daily Living (IADL) scale were used to evaluate the participants’ status at baseline. The MMSE was re-administered after one year and again at the end of the observation (either upon diagnosis of dementia or after seven years). At each meeting with the participant, the clinical diagnosis was verified to determine if the patient had dementia or not. Of the 193 people initially qualified for the study, 75 were available for the final analysis. Results It was found that there was no statistically significant difference in the baseline MMSE scores between the persons with stable MCI and the persons who had progressed to dementia. However, statistically significant differences in the level of activity at baseline on both the global IADL scale and the Activity Scale between those with stable MCI and those who had progressed to dementia were found. These differences were manifested in the IADL subscales for telephone use, shopping, transportation, and personal finances, and in the physical activity subscale. Conclusions An evaluation of intellectual, physical, and social activity can be useful in determining the prognosis for the future course of MCI. PMID:27434501

  2. The Effects of Intellectual, Physical, and Social Activity on Further Prognosis in Mild Cognitive Impairment.

    PubMed

    Bidzan, Leszek; Bidzan, Mariola; Pąchalska, Maria

    2016-07-19

    BACKGROUND Our goal was to specify the relationship between the level of activity (intellectual, physical, and social) in persons diagnosed with mild cognitive impairment (MCI) and the further progression of cognitive dysfunction. MATERIAL AND METHODS We examined 193 patients diagnosed with MCI (according to the criteria of the Working Group on Mild Cognitive Impairment) and under treatment at our Mental Disorders Clinic. It was assumed that these persons would remain under systematic psychiatric observation until dementia was diagnosed. The present study results from a seven-year observation period. The mini-mental state examination (MMSE), the Activity Scale (with the intellectual, physical, and social subscales), and the Instrumental Activities of Daily Living (IADL) scale were used to evaluate the participants' status at baseline. The MMSE was re-administered after one year and again at the end of the observation (either upon diagnosis of dementia or after seven years). At each meeting with the participant, the clinical diagnosis was verified to determine if the patient had dementia or not. Of the 193 people initially qualified for the study, 75 were available for the final analysis. RESULTS It was found that there was no statistically significant difference in the baseline MMSE scores between the persons with stable MCI and the persons who had progressed to dementia. However, statistically significant differences in the level of activity at baseline on both the global IADL scale and the Activity Scale between those with stable MCI and those who had progressed to dementia were found. These differences were manifested in the IADL subscales for telephone use, shopping, transportation, and personal finances, and in the physical activity subscale. CONCLUSIONS An evaluation of intellectual, physical, and social activity can be useful in determining the prognosis for the future course of MCI.

  3. MicroRNA-424 impairs ubiquitination to activate STAT3 and promote prostate tumor progression

    PubMed Central

    Dallavalle, Cecilia; Civenni, Gianluca; Merulla, Jessica; Ostano, Paola; Mello-Grand, Maurizia; Rossi, Simona; Losa, Marco; D’Ambrosio, Gioacchino; Sessa, Fausto; Thalmann, George N.; Zitella, Andrea; Chiorino, Giovanna; Catapano, Carlo V.

    2016-01-01

    Mutations and deletions in components of ubiquitin ligase complexes that lead to alterations in protein turnover are important mechanisms in driving tumorigenesis. Here we describe an alternative mechanism involving upregulation of the microRNA miR-424 that leads to impaired ubiquitination and degradation of oncogenic transcription factors in prostate cancers. We found that miR-424 targets the E3 ubiquitin ligase COP1 and identified STAT3 as a key substrate of COP1 in promoting tumorigenic and cancer stem-like properties in prostate epithelial cells. Altered protein turnover due to impaired COP1 function led to accumulation and enhanced basal and cytokine-induced activity of STAT3. We further determined that loss of the ETS factor ESE3/EHF is the initial event that triggers the deregulation of the miR-424/COP1/STAT3 axis. COP1 silencing and STAT3 activation were effectively reverted by blocking of miR-424, suggesting a possible strategy to attack this key node of tumorigenesis in ESE3/EHF–deficient tumors. These results establish miR-424 as an oncogenic effector linked to noncanonical activation of STAT3 and as a potential therapeutic target. PMID:27820701

  4. Impairing autophagy in retinal pigment epithelium leads to inflammasome activation and enhanced macrophage-mediated angiogenesis

    PubMed Central

    Liu, Jian; Copland, David A.; Theodoropoulou, Sofia; Chiu, Hsi An Amy; Barba, Miriam Durazo; Mak, Ka Wang; Mack, Matthias; Nicholson, Lindsay B.; Dick, Andrew D.

    2016-01-01

    Age-related decreases in autophagy contribute to the progression of age-related macular degeneration (AMD). We have now studied the interaction between autophagy impaired in retinal pigment epithelium (RPE) and the responses of macrophages. We find that dying RPE cells can activate the macrophage inflammasome and promote angiogenesis. In vitro, inhibiting rotenone-induced autophagy in RPE cells elicits caspase-3 mediated cell death. Co-culture of damaged RPE with macrophages leads to the secretion of IL-1β, IL-6 and nitrite oxide. Exogenous IL-6 protects the dysfunctional RPE but IL-1β causes enhanced cell death. Furthermore, IL-1β toxicity is more pronounced in dysfunctional RPE cells showing reduced IRAK3 gene expression. Co-culture of macrophages with damaged RPE also elicits elevated levels of pro-angiogenic proteins that promote ex vivo choroidal vessel sprouting. In vivo, impaired autophagy in the eye promotes photoreceptor and RPE degeneration and recruitment of inflammasome-activated macrophages. The degenerative tissue environment drives an enhanced pro-angiogenic response, demonstrated by increased size of laser-induced choroidal neovascularization (CNV) lesions. The contribution of macrophages was confirmed by depletion of CCR2+ monocytes, which attenuates CNV in the presence of RPE degeneration. Our results suggest that the interplay between perturbed RPE homeostasis and activated macrophages influences key features of AMD development. PMID:26847702

  5. Neuroprotective Effects of AMP-Activated Protein Kinase on Scopolamine Induced Memory Impairment

    PubMed Central

    Kim, Soo-Jeong; Lee, Jun-Ho; Chung, Hwan-Suck; Song, Joo-Hyun; Ha, Joohun

    2013-01-01

    AMP-activated protein kinase (AMPK), an important regulator of energy metabolism, is activated in response to cellular stress when intracellular levels of AMP increase. We investigated the neuroprotective effects of AMPK against scopolamine-induced memory impairment in vivo and glutamate-induced cytotoxicity in vitro. An adenovirus expressing AMPK wild type alpha subunit (WT) or a dominant negative form (DN) was injected into the hippocampus of rats using a stereotaxic apparatus. The AMPK WT-injected rats showed significant reversal of the scopolamine induced cognitive deficit as evaluated by escape latency in the Morris water maze. In addition, they showed enhanced acetylcholinesterase (AChE)-reactive neurons in the hippocampus, implying increased cholinergic activity in response to AMPK. We also studied the cellular mechanism by which AMPK protects against glutamate-induced cell death in primary cultured rat hippocampal neurons. We further demonstrated that AMPK WT-infected cells increased cell viability and reduced Annexin V positive hippocampal neurons. Western blot analysis indicated that AMPK WT-infected cells reduced the expression of Bax and had no effects on Bcl-2, which resulted in a decreased Bax/Bcl-2 ratio. These data suggest that AMPK is a useful cognitive impairment treatment target, and that its beneficial effects are mediated via the protective capacity of hippocampal neurons. PMID:23946693

  6. Impaired ALDH2 activity decreases the mitochondrial respiration in H9C2 cardiomyocytes.

    PubMed

    Mali, Vishal R; Deshpande, Mandar; Pan, Guodong; Thandavarayan, Rajarajan A; Palaniyandi, Suresh S

    2016-02-01

    Reactive oxygen species (ROS)-mediated reactive aldehydes induce cellular stress. In cardiovascular diseases such as ischemia-reperfusion injury, lipid-peroxidation derived reactive aldehydes such as 4-hydroxy-2-nonenal (4HNE) are known to contribute to the pathogenesis. 4HNE is involved in ROS formation, abnormal calcium handling and more importantly defective mitochondrial respiration. Aldehyde dehydrogenase (ALDH) superfamily contains NAD(P)(+)-dependent isozymes which can detoxify endogenous and exogenous aldehydes into non-toxic carboxylic acids. Therefore we hypothesize that 4HNE afflicts mitochondrial respiration and leads to cell death by impairing ALDH2 activity in cultured H9C2 cardiomyocyte cell lines. H9C2 cardiomyocytes were treated with 25, 50 and 75 μM 4HNE and its vehicle, ethanol as well as 25, 50 and 75 μM disulfiram (DSF), an inhibitor of ALDH2 and its vehicle (DMSO) for 4 h. 4HNE significantly decreased ALDH2 activity, ALDH2 protein levels, mitochondrial respiration and mitochondrial respiratory reserve capacity, and increased 4HNE adduct formation and cell death in cultured H9C2 cardiomyocytes. ALDH2 inhibition by DSF and ALDH2 siRNA attenuated ALDH2 activity besides reducing ALDH2 levels, mitochondrial respiration and mitochondrial respiratory reserve capacity and increased cell death. Our results indicate that ALDH2 impairment can lead to poor mitochondrial respiration and increased cell death in cultured H9C2 cardiomyocytes.

  7. Development of a novel questionnaire evaluating disability in activities of daily living in the upper extremities of patients undergoing maintenance hemodialysis.

    PubMed

    Kutsuna, Toshiki; Matsunaga, Atsuhiko; Takagi, Yutaka; Motohashi, Sachiko; Yamamoto, Kazuya; Matsumoto, Takuya; Ishii, Akira; Takahira, Naonobu; Yoshida, Atsushi; Masuda, Takashi

    2011-04-01

    The aim of the present study was to develop a novel questionnaire evaluating disability in the activities of daily living in the upper extremities of hemodialysis (HD) patients (QDUE-HD). We recruited 83 patients (40 males and 43 females) aged 66 ± 8 years, and measured their muscle strength and range of motion in the upper extremities. Moreover, 14 patients performed a six-week exercise training regimen (the exercise group) and were compared with 15 patients not performing such training (the control group). In an initial questionnaire consisting of 37 items, 30 were taken from the Disabilities of the Arm, Shoulder and Hand questionnaire and the Activities of Daily Living Test, and the remaining seven were selected from activities that HD patients perceived as impossible or extremely difficult to perform. The principal factor analysis focused on 11 items, as 26 showing floor and ceiling effects were excluded. These 11 items were divided into two categories consisting of six items termed "light work" and five termed "holding activities". The scores for light work and holding activities correlated significantly and positively with both muscle strength and range of motion in the upper extremities. These scores increased significantly after the six-week exercise training as compared with those before training in the exercise group. We conclude that the QDUE-HD is clinically useful for evaluating disability in activities of daily living in the upper extremities of HD patients because of its high reliability, validity and responsiveness.

  8. Cognitively-Related Basic Activities of Daily Living Impairment Greatly Increases the Risk of Death in Alzheimers Disease

    PubMed Central

    Liang, Fu-Wen; Chan, Wenyaw; Chen, Ping-Jen; Zimmerman, Carissa; Waring, Stephen; Doody, Rachelle

    2016-01-01

    Introduction Some Alzheimer’s disease (AD) patients die without ever developing cognitively impaired basic activities of daily living (basic ADL), which may reflect slower disease progression or better compensatory mechanisms. Although impaired basic ADL is related to disease severity, it may exert an independent risk for death. This study examined the association between impaired basic ADL and survival of AD patients, and proposed a multistate approach for modeling the time to death for patients who demonstrate different patterns of progression of AD that do or do not include basic ADL impairment. Methods 1029 patients with probable AD at the Baylor College of Medicine Alzheimer’s Disease and Memory Disorders Center met the criteria for this study. Two complementary definitions were used to define development of basic ADL impairment using the Physical Self-Maintenance Scale score. A weighted Cox regression model, including a time-dependent covariate (development of basic ADL impairment), and a multistate survival model were applied to examine the effect of basic ADL impairment on survival. Results As expected decreased ability to perform basic ADL at baseline, age at initial visit, years of education, and sex were all associated with significantly higher mortality risk. In those unimpaired at baseline, the development of basic ADL impairment was also associated with a much greater risk of death (hazard ratios 1.77–4.06) over and above the risk conferred by loss of MMSE points. A multi-state Cox model, controlling for those other variables quantified the substantive increase in hazard ratios for death conferred by the development of basic ADL impairment by two definitions and can be applied to calculate the short term risk of mortality in individual patients. Conclusions The current study demonstrates that the presence of basic ADL impairment or the development of such impairments are important predictors of death in AD patients, regardless of severity. PMID

  9. A screening questionnaire for voice problems after treatment of early glottic cancer

    SciTech Connect

    Gogh, Christine D.L. van . E-mail: cdl.vangogh@vumc.nl; Verdonck-de Leeuw, Irma M.; Boon-Kamma, Brigitte A.; Langendijk, Johannes A.; Kuik, Dirk J.; Mahieu, Hans F.

    2005-07-01

    Purpose: After treatment for early glottic cancer, a considerable number of patients end up with voice problems interfering with daily life activities. A 5-item screening questionnaire was designed for detection of voice impairment. The purpose of this study is to assess psychometric properties of this questionnaire in clinical practice. Methods and Materials: The questionnaire was completed by 110 controls without voice complaints and 177 patients after radiotherapy or laser surgery for early glottic cancer. Results: Based on normative data of the controls, a score of 5 or less on at least 1 of the 5 questions was considered to state overall voice impairment. Reliability of the questionnaire proved to be good. Voice impairment was reported in 44% of the patients treated with radiotherapy vs. 29% of the patients treated with endoscopic laser surgery. Conclusions: The questionnaire proved to be a reliable, valid, and feasible method to detect voice impairment in daily life. The questionnaire is easy to fill in, and interpretation is straightforward. It is useful for both radiation oncologists and otorhinolaryngologists in their follow-up of patients treated for early glottic cancer.

  10. Functional impairment of natural killer cells in active ulcerative colitis: reversion of the defective natural killer activity by interleukin 2.

    PubMed Central

    Manzano, L; Alvarez-Mon, M; Abreu, L; Antonio Vargas, J; de la Morena, E; Corugedo, F; Duràntez, A

    1992-01-01

    We have studied the functional characteristics and clinical importance of the natural killer (NK) cytotoxicity of peripheral blood mononuclear cells (PBMNC) from patients with ulcerative colitis. Normal NK activity was observed in PBMNC from patients with inactive disease, but a pronounced decrease was found in those with active disease. Clinical change from active to inactive disease was associated with enhancement of the depressed NK activity. The impairment of NK cytotoxicity found in patients with active disese could not be ascribed to a deficient number of NK cells as the amounts of HNK-1+, CD16+ (Leu 11), and CD11b (OKM1) cells in PBMNC were within normal ranges. This defective cytotoxic PBMNC activity was normalised by short term (18 hour) incubation with recombinant interleukin 2 (rIL-2). Moreover, long term (5 day) incubation of these effector cells with rIL-2 induced strong cytotoxic activity against NK resistant and NK sensitive target cells in patients with active and inactive disease. We also found that both precursors and effectors of cytotoxic activity promoted by short term and long term incubation with rIL-2 of PBMNC from the patients showed the phenotype of NK cells (CD16+, CD3-). Taken together, these results show that active ulcerative colitis is associated with a defective function of NK cells that is found to be normal in the inactive stage of the disease. The possible pathogenic and therapeutic implications of these findings are discussed. PMID:1541421

  11. The Sedentary Time and Activity Reporting Questionnaire (STAR-Q): reliability and validity against doubly labeled water and 7-day activity diaries.

    PubMed

    Csizmadi, Ilona; Neilson, Heather K; Kopciuk, Karen A; Khandwala, Farah; Liu, Andrew; Friedenreich, Christine M; Yasui, Yutaka; Rabasa-Lhoret, Rémi; Bryant, Heather E; Lau, David C W; Robson, Paula J

    2014-08-15

    We determined measurement properties of the Sedentary Time and Activity Reporting Questionnaire (STAR-Q), which was designed to estimate past-month activity energy expenditure (AEE). STAR-Q validity and reliability were assessed in 102 adults in Alberta, Canada (2009-2011), who completed 14-day doubly labeled water (DLW) protocols, 7-day activity diaries on day 15, and the STAR-Q on day 14 and again at 3 and 6 months. Three-month reliability was substantial for total energy expenditure (TEE) and AEE (intraclass correlation coefficients of 0.84 and 0.73, respectively), while 6-month reliability was moderate. STAR-Q-derived TEE and AEE were moderately correlated with DLW estimates (Spearman's ρs of 0.53 and 0.40, respectively; P < 0.001), and on average, the STAR-Q overestimated TEE and AEE (median differences were 367 kcal/day and 293 kcal/day, respectively). Body mass index-, age-, sex-, and season-adjusted concordance correlation coefficients (CCCs) were 0.24 (95% confidence interval (CI): 0.07, 0.36) and 0.21 (95% CI: 0.11, 0.32) for STAR-Q-derived versus DLW-derived TEE and AEE, respectively. Agreement between the diaries and STAR-Q (metabolic equivalent-hours/day) was strongest for occupational sedentary time (adjusted CCC = 0.76, 95% CI: 0.64, 0.85) and overall strenuous activity (adjusted CCC = 0.64, 95% CI: 0.49, 0.76). The STAR-Q demonstrated substantial validity for estimating occupational sedentary time and strenuous activity and fair validity for ranking individuals by AEE.

  12. Glucocorticoids impair oocyte developmental potential by triggering apoptosis of ovarian cells via activating the Fas system

    PubMed Central

    Yuan, Hong-Jie; Han, Xiao; He, Nan; Wang, Guo-Liang; Gong, Shuai; Lin, Juan; Gao, Min; Tan, Jing-He

    2016-01-01

    Previous studies indicate that stress damages oocytes with increased secretion of glucorticoids. However, although injection of female mice with cortisol decreased oocyte competence, exposure of mouse oocytes directly to physiological or stress-induced concentrations of glucorticoids did not affect oocyte maturation and embryo development. This study has explored the mechanisms by which glucocorticoids impair oocyte competence. Female mice were injected with cortisol and the effects of cortisol-injection on oocyte competence, ovarian cell apoptosis and Fas/FasL activation were observed. The results showed that cortisol-injection decreased (a) oocyte developmental potential, (b) the E2/P4 ratio in serum and ovaries, and (c) expression of insulin-like growth factor 1, brain-derived neurotrophic factor and glucocorticoid receptor in mural granulosa cells (MGCs), while increasing levels of (a) cortisol in serum and ovaries, (b) apoptosis in MGCs and cumulus cells (CCs), (c) FasL secretion in ovaries and during oocyte maturation in vitro, and (d) Fas in MGCs, CCs and oocytes. The detrimental effects of cortisol-injection on oocyte competence and apoptosis of MGCs and CCs were significantly relieved when the gld (generalized lymphoproliferative disorder) mice harboring FasL mutations were observed. Together, the results suggested that glucocorticoids impair oocyte competence by triggering apoptosis of ovarian cells via activating the Fas system. PMID:27040909

  13. Activity-Dependent p25 Generation Regulates Synaptic Plasticity and Aβ-Induced Cognitive Impairment

    PubMed Central

    Seo, Jinsoo; Giusti-Rodríguez, Paola; Zhou, Ying; Rudenko, Andrii; Cho, Sukhee; Ota, Kristie T.; Park, Christine; Patzke, Holger; Madabhushi, Ram; Pan, Ling; Mungenast, Alison E.; Guan, Ji-Song; Delalle, Ivana; Tsai, Li-Huei

    2015-01-01

    SUMMARY Cyclin-dependent kinase 5 regulates numerous neuronal functions with its activator, p35. Under neurotoxic conditions, p35 undergoes proteolytic cleavage to liberate p25, which has been implicated in various neurodegenerative diseases. Here, we show that p25 is generated following neuronal activity under physiological conditions in a GluN2B- and CaMKIIα-dependent manner. Moreover, we developed a knockin mouse model in which endogenous p35 is replaced with a calpain-resistant mutant p35 (Δp35KI) to prevent p25 generation. The Δp35KI mice exhibit impaired long-term depression and defective memory extinction, likely mediated through persistent GluA1 phosphorylation at Ser845. Finally, crossing the Δp35KI mice with the 5XFAD mouse model of Alzheimer's disease (AD) resulted in an amelioration of β-amyloid (Aβ)-induced synaptic depression and cognitive impairment. Together, these results reveal a physiological role of p25 production in synaptic plasticity and memory and provide new insights into the function of p25 in Aβ-associated neurotoxicity and AD-like pathology. PMID:24725413

  14. Hyperhomocysteinaemia in rats is associated with erectile dysfunction by impairing endothelial nitric oxide synthase activity

    PubMed Central

    Jiang, Weijun; Xiong, Lei; Bin Yang; Li, Weiwei; Zhang, Jing; Zhou, Qing; Wu, Qiuyue; Li, Tianfu; Zhang, Cui; Zhang, Mingchao; Xia, Xinyi

    2016-01-01

    To investigate the effect of hyperhomocysteinaemia (HHCy) on penile erectile function in a rat model, a methionine-rich diet was used in which erectile function, the reproductive system, and nitric oxide synthase were characterized. The intracavernous pressure, apomorphine experiments, measurement of oxidative stress, hematoxylin and eosin staining, immunohistochemistry analysis, reverse transcription-polymerase chain reactions and measurement of endothelial nitric oxide synthase activity were utilized. Our results showed that erections in the middle-dose, high-dose, and interference (INF) groups were significantly lower than the control (P < 0.05). INF group, being fed with vitamins B and folic acid, demonstrated markedly improved penile erections compared with the middle-dose group (P < 0.05). HHCy-induced eNOS and phospho-eNOS protein expression was reduced and the antioxidant effect was markedly impaired. The data of the present data provide evidence that HHCy is a vascular risk factor for erectile dysfunction by impairing cavernosa endothelial nitric oxide synthase activity. Intake of vitamins B can alleviate this abnormality. PMID:27221552

  15. Glucocorticoids impair oocyte developmental potential by triggering apoptosis of ovarian cells via activating the Fas system.

    PubMed

    Yuan, Hong-Jie; Han, Xiao; He, Nan; Wang, Guo-Liang; Gong, Shuai; Lin, Juan; Gao, Min; Tan, Jing-He

    2016-04-04

    Previous studies indicate that stress damages oocytes with increased secretion of glucorticoids. However, although injection of female mice with cortisol decreased oocyte competence, exposure of mouse oocytes directly to physiological or stress-induced concentrations of glucorticoids did not affect oocyte maturation and embryo development. This study has explored the mechanisms by which glucocorticoids impair oocyte competence. Female mice were injected with cortisol and the effects of cortisol-injection on oocyte competence, ovarian cell apoptosis and Fas/FasL activation were observed. The results showed that cortisol-injection decreased (a) oocyte developmental potential, (b) the E2/P4 ratio in serum and ovaries, and (c) expression of insulin-like growth factor 1, brain-derived neurotrophic factor and glucocorticoid receptor in mural granulosa cells (MGCs), while increasing levels of (a) cortisol in serum and ovaries, (b) apoptosis in MGCs and cumulus cells (CCs), (c) FasL secretion in ovaries and during oocyte maturation in vitro, and (d) Fas in MGCs, CCs and oocytes. The detrimental effects of cortisol-injection on oocyte competence and apoptosis of MGCs and CCs were significantly relieved when the gld (generalized lymphoproliferative disorder) mice harboring FasL mutations were observed. Together, the results suggested that glucocorticoids impair oocyte competence by triggering apoptosis of ovarian cells via activating the Fas system.

  16. Conditional expression of constitutively active estrogen receptor {alpha} in chondrocytes impairs longitudinal bone growth in mice

    SciTech Connect

    Ikeda, Kazuhiro; Tsukui, Tohru; Imazawa, Yukiko; Horie-Inoue, Kuniko; Inoue, Satoshi

    2012-09-07

    Highlights: Black-Right-Pointing-Pointer Conditional transgenic mice expressing constitutively active estrogen receptor {alpha} (caER{alpha}) in chondrocytes were developed. Black-Right-Pointing-Pointer Expression of caER{alpha} in chondrocytes impaired longitudinal bone growth in mice. Black-Right-Pointing-Pointer caER{alpha} affects chondrocyte proliferation and differentiation. Black-Right-Pointing-Pointer This mouse model is useful for understanding the physiological role of ER{alpha}in vivo. -- Abstract: Estrogen plays important roles in the regulation of chondrocyte proliferation and differentiation, which are essential steps for longitudinal bone growth; however, the mechanisms of estrogen action on chondrocytes have not been fully elucidated. In the present study, we generated conditional transgenic mice, designated as caER{alpha}{sup ColII}, expressing constitutively active mutant estrogen receptor (ER) {alpha} in chondrocytes, using the chondrocyte-specific type II collagen promoter-driven Cre transgenic mice. caER{alpha}{sup ColII} mice showed retardation in longitudinal growth, with short bone lengths. BrdU labeling showed reduced proliferation of hypertrophic chondrocytes in the proliferating layer of the growth plate of tibia in caER{alpha}{sup ColII} mice. In situ hybridization analysis of type X collagen revealed that the maturation of hypertrophic chondrocytes was impaired in caER{alpha}{sup ColII} mice. These results suggest that ER{alpha} is a critical regulator of chondrocyte proliferation and maturation during skeletal development, mediating longitudinal bone growth in vivo.

  17. Subclinical zinc deficiency impairs pancreatic digestive enzyme activity and digestive capacity of weaned piglets.

    PubMed

    Brugger, Daniel; Windisch, Wilhelm M

    2016-08-01

    This study investigated the effects of short-term subclinical Zn deficiency on exocrine pancreatic activity and changes in digestive capacity. A total of forty-eight weaned piglets were fed ad libitum a basal diet (maize and soyabean meal) with adequate Zn supply (88 mg Zn/kg diet) during a 2-week acclimatisation phase. Animals were then assigned to eight dietary treatment groups (n 6) according to a complete randomised block design considering litter, live weight and sex. All pigs were fed restrictively (450 g diet/d) the basal diet but with varying ZnSO4.7H2O additions, resulting in 28·1, 33·6, 38·8, 42·7, 47·5, 58·2, 67·8 and 88·0 mg Zn/kg diet for a total experimental period of 8 d. Pancreatic Zn concentrations and pancreatic activities of trypsin, chymotrypsin, carboxypeptidase A and B, elastase and α-amylase exhibited a broken-line response to stepwise reduction in dietary Zn by declining beneath thresholds of 39·0, 58·0, 58·0, 41·2, 47·5, 57·7 and 58·0 mg Zn/kg diet, respectively. Furthermore, carboxypeptidase B and α-amylase activities were significantly lower in samples with reduced pancreatic Zn contents. Coefficients of faecal digestibility of DM, crude protein, total lipids and crude ash responded similarly to pancreatic enzyme activities by declining below dietary thresholds of 54·7, 45·0, 46·9 and 58·2 mg Zn/kg diet, respectively. In conclusion, (1) subclinical Zn deficiency impaired pancreatic exocrine enzymes, (2) this response was connected to pancreatic Zn metabolism and (3) the decline in catalytic activity impaired faecal digestibility already after 1 week of insufficient alimentary Zn supply and very early before clinical deficiency symptoms arise.

  18. Cognitive Stimulation Modulates Platelet Total Phospholipases A2 Activity in Subjects with Mild Cognitive Impairment

    PubMed Central

    Balietti, Marta; Giuli, Cinzia; Fattoretti, Patrizia; Fabbietti, Paolo; Postacchini, Demetrio; Conti, Fiorenzo

    2016-01-01

    We evaluated the effect of cognitive stimulation (CS) on platelet total phospholipases A2 activity (tPLA2A) in patients with mild cognitive impairment (MCI_P). At baseline, tPLA2A negatively correlated with Mini-Mental State Examination score (MMSE_s): patients with MMSE_s <26 (Subgroup 1) had significantly higher activity than those with MMSE_s ≥26 (Subgroup 2), who had values similar to the healthy elderly. Regarding CS effect, Subgroup 1 had a significant tPLA2A reduction, whereas Subgroup 2 did not significantly changes after training. Our results showed for the first time that tPLA2A correlates with the cognitive conditions of MCI_P, and that CS acts selectively on subjects with a dysregulated tPLA2A. PMID:26836161

  19. Cognitive Stimulation Modulates Platelet Total Phospholipases A2 Activity in Subjects with Mild Cognitive Impairment.

    PubMed

    Balietti, Marta; Giuli, Cinzia; Fattoretti, Patrizia; Fabbietti, Paolo; Postacchini, Demetrio; Conti, Fiorenzo

    2016-01-01

    We evaluated the effect of cognitive stimulation (CS) on platelet total phospholipases A2 activity (tPLA2A) in patients with mild cognitive impairment (MCI_P). At baseline, tPLA2A negatively correlated with Mini-Mental State Examination score (MMSE_s): patients with MMSE_s <26 (Subgroup 1) had significantly higher activity than those with MMSE_s ≥26 (Subgroup 2), who had values similar to the healthy elderly. Regarding CS effect, Subgroup 1 had a significant tPLA2A reduction, whereas Subgroup 2 did not significantly changes after training. Our results showed for the first time that tPLA2A correlates with the cognitive conditions of MCI_P, and that CS acts selectively on subjects with a dysregulated tPLA2A.

  20. Impaired antigen presentation and potent phagocytic activity identifying tumor-tolerant human monocytes.

    PubMed

    Soares-Schanoski, Alessandra; Jurado, Teresa; Córdoba, Raúl; Siliceo, María; Fresno, Carlos Del; Gómez-Piña, Vanesa; Toledano, Victor; Vallejo-Cremades, Maria T; Alfonso-Iñiguez, Sergio; Carballo-Palos, Arkaitz; Fernández-Ruiz, Irene; Cubillas-Zapata, Carolina; Biswas, Subhra K; Arnalich, Francisco; García-Río, Francisco; López-Collazo, Eduardo

    2012-06-29

    Monocyte exposure to tumor cells induces a transient state in which these cells are refractory to further exposure to cancer. This phenomenon, termed "tumor tolerance", is characterized by a decreased production of proinflammatory cytokines in response to tumors. In the past, we found that this effect comprises IRAK-M up regulation and TLR4 and CD44 activation. Herein we have established a human model of tumor tolerance and have observed a marked down-regulation of MHCII molecules as well as the MHCII master regulator, CIITA, in monocytes/macrophages. These cells combine an impaired capability for antigen presentation with potent phagocytic activity and exhibit an M2-like phenotype. In addition circulating monocytes isolated from Chronic Lymphocytic Leukemia patients exhibited the same profile as tumor tolerant cells after tumor ex vivo exposition.

  1. Decreased histone deacetylase 2 impairs Nrf2 activation by oxidative stress

    SciTech Connect

    Mercado, Nicolas; Thimmulappa, Rajesh; Thomas, Catherine M.R.; Fenwick, Peter S.; Chana, Kirandeep K.; Donnelly, Louise E.; Biswal, Shyam; Ito, Kazuhiro; Barnes, Peter J.

    2011-03-11

    Research highlights: {yields} Nrf2 anti-oxidant function is impaired when HDAC activity is inhibited. {yields} HDAC inhibition decreases Nrf2 protein stability. {yields} HDAC2 is involved in reduced Nrf2 stability and both correlate in COPD samples. {yields} HDAC inhibition increases Nrf2 acetylation. -- Abstract: Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a crucial role in cellular defence against oxidative stress by inducing the expression of multiple anti-oxidant genes. However, where high levels of oxidative stress are observed, such as chronic obstructive pulmonary disease (COPD), Nrf2 activity is reduced, although the molecular mechanism for this defect is uncertain. Here, we show that down-regulation of histone deacetylase (HDAC) 2 causes Nrf2 instability, resulting in reduced anti-oxidant gene expression and increase sensitivity to oxidative stress. Although Nrf2 protein was clearly stabilized after hydrogen peroxide (H{sub 2}O{sub 2}) stimulation in a bronchial epithelial cell line (BEAS2B), Nrf2 stability was decreased and Nrf2 acetylation increased in the presence of an HDAC inhibitor, trichostatin A (TSA). TSA also reduced Nrf2-regulated heme-oxygenase-1 (HO-1) expression in these cells, and this was confirmed in acute cigarette-smoke exposed mice in vivo. HDAC2 knock-down by RNA interference resulted in reduced H{sub 2}O{sub 2}-induced Nrf2 protein stability and activity in BEAS2B cells, whereas HDAC1 knockdown had no effect. Furthermore, monocyte-derived macrophages obtained from healthy volunteers (non-smokers and smokers) and COPD patients showed a significant correlation between HDAC2 expression and Nrf2 expression (r = 0.92, p < 0.0001). Thus, reduced HDAC2 activity in COPD may account for increased Nrf2 acetylation, reduced Nrf2 stability and impaired anti oxidant defences.

  2. Impairments in Background and Event-Related Alpha-Band Oscillatory Activity in Patients with Schizophrenia

    PubMed Central

    Abeles, Ilana Y.; Gomez-Ramirez, Manuel

    2014-01-01

    Studies show that patients with schizophrenia exhibit impaired responses to sensory stimuli, especially at the early stages of neural processing. In particular, patients’ alpha-band (8–14 Hz) event-related desynchronization (ERD) and visual P1 event-related potential (ERP) component tend to be significantly reduced, with P1 ERP deficits greater for visual stimuli biased towards the magnocellular system. In healthy controls, studies show that pre-stimulus alpha (background alpha) plays a pivotal role in sensory processing and behavior, largely by shaping the neural responses to incoming stimuli. Here, we address whether patients’ ERD and P1 deficits stem from impairments in pre-stimulus alpha mechanisms. To address this question we recorded electrophysiological activity in patients with schizophrenia and healthy controls while they engaged in a visual discrimination task with low, medium, and high contrast stimuli. The results revealed a significant decrease in patients’ ERDs, which was largely driven by reductions in pre-stimulus alpha. These reductions were most prominent in right-hemispheric areas. We also observed a systematic relationship between pre-stimulus alpha and the P1 component across different contrast levels. However, this relationship was only observed in healthy controls. Taken together, these findings highlight a substantial anomaly in patients’ amplitude-based alpha background activity over visual areas. The results provide further support that pre-stimulus alpha activity plays an active role in perception by modulating the neural responses to incoming sensory inputs, a mechanism that seems to be compromised in schizophrenia. PMID:24646909

  3. Fractal Dimension of EEG Activity Senses Neuronal Impairment in Acute Stroke

    PubMed Central

    Zappasodi, Filippo; Olejarczyk, Elzbieta; Marzetti, Laura; Assenza, Giovanni; Pizzella, Vittorio; Tecchio, Franca

    2014-01-01

    The brain is a self-organizing system which displays self-similarities at different spatial and temporal scales. Thus, the complexity of its dynamics, associated to efficient processing and functional advantages, is expected to be captured by a measure of its scale-free (fractal) properties. Under the hypothesis that the fractal dimension (FD) of the electroencephalographic signal (EEG) is optimally sensitive to the neuronal dysfunction secondary to a brain lesion, we tested the FD’s ability in assessing two key processes in acute stroke: the clinical impairment and the recovery prognosis. Resting EEG was collected in 36 patients 4–10 days after a unilateral ischemic stroke in the middle cerebral artery territory and 19 healthy controls. National Health Institute Stroke Scale (NIHss) was collected at T0 and 6 months later. Highuchi FD, its inter-hemispheric asymmetry (FDasy) and spectral band powers were calculated for EEG signals. FD was smaller in patients than in controls (1.447±0.092 vs 1.525±0.105) and its reduction was paired to a worse acute clinical status. FD decrease was associated to alpha increase and beta decrease of oscillatory activity power. Larger FDasy in acute phase was paired to a worse clinical recovery at six months. FD in our patients captured the loss of complexity reflecting the global system dysfunction resulting from the structural damage. This decrease seems to reveal the intimate nature of structure-function unity, where the regional neural multi-scale self-similar activity is impaired by the anatomical lesion. This picture is coherent with neuronal activity complexity decrease paired to a reduced repertoire of functional abilities. FDasy result highlights the functional relevance of the balance between homologous brain structures’ activities in stroke recovery. PMID:24967904

  4. Stress affects theta activity in limbic networks and impairs novelty-induced exploration and familiarization

    PubMed Central

    Jacinto, Luis R.; Reis, Joana S.; Dias, Nuno S.; Cerqueira, João J.; Correia, José H.; Sousa, Nuno

    2013-01-01

    Exposure to a novel environment triggers the response of several brain areas that regulate emotional behaviors. Here, we studied theta oscillations within the hippocampus (HPC)-amygdala (AMY)-medial prefrontal cortex (mPFC) network in exploration of a novel environment and subsequent familiarization through repeated exposures to that same environment; in addition, we assessed how concomitant stress exposure could disrupt this activity and impair both behavioral processes. Local field potentials (LFP) were simultaneously recorded from dorsal and ventral hippocampus (dHPC and vHPC, respectively), basolateral amygdala (BLA) and mPFC in freely behaving rats while they were exposed to a novel environment, then repeatedly re-exposed over the course of 3 weeks to that same environment and, finally, on re-exposure to a novel unfamiliar environment. A longitudinal analysis of theta activity within this circuit revealed a reduction of vHPC and BLA theta power and vHPC-BLA theta coherence through familiarization which was correlated with a return to normal exploratory behavior in control rats. In contrast, a persistent over-activation of the same brain regions was observed in stressed rats that displayed impairments in novel exploration and familiarization processes. Importantly, we show that stress also affected intra-hippocampal synchrony and heightened the coherence between vHPC and BLA. In summary, we demonstrate that modulatory theta activity in the aforementioned circuit, namely in the vHPC and BLA, is correlated with the expression of anxiety in novelty-induced exploration and familiarization in both normal and pathological conditions. PMID:24137113

  5. Fractal dimension of EEG activity senses neuronal impairment in acute stroke.

    PubMed

    Zappasodi, Filippo; Olejarczyk, Elzbieta; Marzetti, Laura; Assenza, Giovanni; Pizzella, Vittorio; Tecchio, Franca

    2014-01-01

    The brain is a self-organizing system which displays self-similarities at different spatial and temporal scales. Thus, the complexity of its dynamics, associated to efficient processing and functional advantages, is expected to be captured by a measure of its scale-free (fractal) properties. Under the hypothesis that the fractal dimension (FD) of the electroencephalographic signal (EEG) is optimally sensitive to the neuronal dysfunction secondary to a brain lesion, we tested the FD's ability in assessing two key processes in acute stroke: the clinical impairment and the recovery prognosis. Resting EEG was collected in 36 patients 4-10 days after a unilateral ischemic stroke in the middle cerebral artery territory and 19 healthy controls. National Health Institute Stroke Scale (NIHss) was collected at T0 and 6 months later. Highuchi FD, its inter-hemispheric asymmetry (FDasy) and spectral band powers were calculated for EEG signals. FD was smaller in patients than in controls (1.447±0.092 vs 1.525±0.105) and its reduction was paired to a worse acute clinical status. FD decrease was associated to alpha increase and beta decrease of oscillatory activity power. Larger FDasy in acute phase was paired to a worse clinical recovery at six months. FD in our patients captured the loss of complexity reflecting the global system dysfunction resulting from the structural damage. This decrease seems to reveal the intimate nature of structure-function unity, where the regional neural multi-scale self-similar activity is impaired by the anatomical lesion. This picture is coherent with neuronal activity complexity decrease paired to a reduced repertoire of functional abilities. FDasy result highlights the functional relevance of the balance between homologous brain structures' activities in stroke recovery.

  6. Plasminogen Activator Inhibitor-1 Is Involved in Impaired Bone Repair Associated with Diabetes in Female Mice

    PubMed Central

    Mao, Li; Kawao, Naoyuki; Tamura, Yukinori; Okumoto, Katsumi; Okada, Kiyotaka; Yano, Masato; Matsuo, Osamu; Kaji, Hiroshi

    2014-01-01

    Previous studies suggest that fracture healing is impaired in diabetes; however, the underlying mechanism remains unclear. Here, we investigated the roles of plasminogen activator inhibitor-1 (PAI-1) in the impaired bone repair process by using streptozotocin (STZ)-induced diabetic female wild-type (PAI-1+/+) and PAI-1-deficient (PAI-1−/−) mice. Bone repair and the number of alkaline phosphatase (ALP)-positive cells at the site of a femoral bone damage were comparable in PAI-1+/+ and PAI-1−/− mice without STZ treatment. Although the bone repair process was delayed by STZ treatment in PAI-1+/+ mice, this delayed bone repair was blunted in PAI-1−/− mice. The reduction in the number of ALP-positive cells at the site of bone damage induced by STZ treatment was attenuated in PAI-1−/− mice compared to PAI-1+/+ mice. On the other hand, PAI-1 deficiency increased the levels of ALP and type I collagen mRNA in female mice with or without STZ treatment, and the levels of Osterix and osteocalcin mRNA, suppressed by diabetic state in PAI-1+/+ mice, were partially protected in PAI-1−/− mice. PAI-1 deficiency did not affect formation of the cartilage matrix and the levels of types II and X collagen and aggrecan mRNA suppressed by STZ treatment, although PAI-1 deficiency increased the expression of chondrogenic markers in mice without STZ treatment. The present study indicates that PAI-1 is involved in the impaired bone repair process induced by the diabetic state in part through a decrease in the number of ALP-positive cells. PMID:24651693

  7. Plasminogen activator inhibitor-1 is involved in impaired bone repair associated with diabetes in female mice.

    PubMed

    Mao, Li; Kawao, Naoyuki; Tamura, Yukinori; Okumoto, Katsumi; Okada, Kiyotaka; Yano, Masato; Matsuo, Osamu; Kaji, Hiroshi

    2014-01-01

    Previous studies suggest that fracture healing is impaired in diabetes; however, the underlying mechanism remains unclear. Here, we investigated the roles of plasminogen activator inhibitor-1 (PAI-1) in the impaired bone repair process by using streptozotocin (STZ)-induced diabetic female wild-type (PAI-1+/+) and PAI-1-deficient (PAI-1-/-) mice. Bone repair and the number of alkaline phosphatase (ALP)-positive cells at the site of a femoral bone damage were comparable in PAI-1+/+ and PAI-1-/- mice without STZ treatment. Although the bone repair process was delayed by STZ treatment in PAI-1+/+ mice, this delayed bone repair was blunted in PAI-1-/- mice. The reduction in the number of ALP-positive cells at the site of bone damage induced by STZ treatment was attenuated in PAI-1-/- mice compared to PAI-1+/+ mice. On the other hand, PAI-1 deficiency increased the levels of ALP and type I collagen mRNA in female mice with or without STZ treatment, and the levels of Osterix and osteocalcin mRNA, suppressed by diabetic state in PAI-1+/+ mice, were partially protected in PAI-1-/- mice. PAI-1 deficiency did not affect formation of the cartilage matrix and the levels of types II and X collagen and aggrecan mRNA suppressed by STZ treatment, although PAI-1 deficiency increased the expression of chondrogenic markers in mice without STZ treatment. The present study indicates that PAI-1 is involved in the impaired bone repair process induced by the diabetic state in part through a decrease in the number of ALP-positive cells.

  8. Neuroanatomic substrates of semantic memory impairment in Alzheimer’s disease: Patterns of functional MRI activation

    PubMed Central

    SAYKIN, ANDREW J.; FLASHMAN, LAURA A.; FRUTIGER, SALLY A.; JOHNSON, STERLING C.; MAMOURIAN, ALEXANDER C.; MORITZ, CHAD H.; O’JILE, JUDITH R.; RIORDAN, HENRY J.; SANTULLI, ROBERT B.; SMITH, CYNTHIA A.; WEAVER, JOHN B.

    2015-01-01

    Impairment in semantic processing occurs early in Alzheimer’s disease (AD) and differential impact on subtypes of semantic relations have been reported, yet there is little data on the neuroanatomic basis of these deficits. Patients with mild AD and healthy controls underwent 3 functional MRI auditory stimulation tasks requiring semantic or phonological decisions (match–mismatch) about word pairs (category–exemplar, category–function, pseudoword). Patients showed a significant performance deficit only on the exemplar task. On voxel-based fMRI activation analyses, controls showed a clear activation focus in the left superior temporal gyrus for the phonological task; patients showed additional foci in the left dorsolateral prefrontal and bilateral cingulate areas. On the semantic tasks, predominant activation foci were seen in the inferior and middle frontal gyrus (left greater than right) in both groups but patients showed additional activation suggesting compensatory recruitment of locally expanded foci and remote regions, for example, right frontal activation during the exemplar task. Covariance analyses indicated that exemplar task performance was strongly related to signal increase in bilateral medial prefrontal cortex. The authors conclude that fMRI can reveal similarities and differences in functional neuroanatomical processing of semantic and phonological information in mild AD compared to healthy elderly, and can help to bridge cognitive and neural investigations of the integrity of semantic networks in AD. PMID:10439584

  9. Visually Impaired Older Adults and Home-Based Leisure Activities: The Effects of Person-Environment Congruence

    ERIC Educational Resources Information Center

    Stevens-Ratchford, Regina; Krause, Airi

    2004-01-01

    This qualitative study explored the effect of person-environment congruence on participation in homebased leisure activities by two legally blind older adults who lived independently in the community. The results indicated that visual impairment increased the time spent in home-based leisure activities and that the participants used various…

  10. Associative learning over trials activates the hippocampus in healthy elderly but not mild cognitive impairment.

    PubMed

    Johnson, Sterling C; Schmitz, Taylor W; Asthana, Sanjay; Gluck, Mark A; Myers, Catherine

    2008-03-01

    The ability to form associations between choice alternatives and their contingent outcomes is an important aspect of learning that may be sensitive to hippocampal dysfunction in memory disorders of aging such as amnestic mild cognitive impairment (MCIa), or early Alzheimer disease. In this preliminary study we examined brain activation using functional magnetic resonance imaging (fMRI) in 12 healthy elderly participants and nine patients with MCIa during an associative learning task. Using a high-field 3.0-Tesla MRI scanner, we examined the dynamic neural response during associative learning over trials. The slope of signal attenuation associated with learning was analyzed for differences between groups within an a priori defined hippocampal region. Results indicated dynamic signal attenuation associated with learning in the healthy elderly sample, but not in MCIa. The absence of an associative learning effect in the MCIa sample reaffirms an important link between the learning difficulties that are commonly encountered in MCIa and the mesial temporal region.

  11. Brain Network Activation (BNA) reveals scopolamine-induced impairment of visual working memory.

    PubMed

    Reches, Amit; Levy-Cooperman, Naama; Laufer, Ilan; Shani-Hershkovitch, Revital; Ziv, Keren; Kerem, Dani; Gal, Noga; Stern, Yaki; Cukierman, Guy; Romach, Myroslava K; Sellers, Edward M; Geva, Amir B

    2014-09-01

    The overarching goal of this event-related potential (ERP) study was to examine the effects of scopolamine on the dynamics of brain network activation using a novel ERP network analysis method known as Brain Network Activation (BNA). BNA was used for extracting group-common stimulus-activated network patterns elicited to matching probe stimuli in the context of a delayed matching-to-sample task following placebo and scopolamine treatments administered to healthy participants. The BNA extracted networks revealed the existence of two pathophysiological mechanisms following scopolamine, disconnection, and compensation. Specifically, weaker frontal theta and parietal alpha coupling was accompanied with enhanced fronto-centro-parietal theta activation relative to placebo. In addition, using the characteristic BNA network of each treatment as well as corresponding literature-guided selective subnetworks as combined biomarkers managed to differentiate between individual responses to each of the treatments. Behavioral effects associated with scopolamine included delayed response time and impaired response accuracy. These results indicate that the BNA method is sensitive to the effects of scopolamine on working memory and that it may potentially enable diagnosis and treatment assessment of dysfunctions associated with cholinergic deficiency.

  12. Impaired fMRI activation in patients with primary brain tumors.

    PubMed

    Jiang, Zhen; Krainik, Alexandre; David, Olivier; Salon, Caroline; Troprès, Irène; Hoffmann, Dominique; Pannetier, Nicolas; Barbier, Emmanuel L; Bombìn, Eduardo Ramos; Warnking, Jan; Pasteris, Caroline; Chabardes, Stefan; Berger, François; Grand, Sylvie; Segebarth, Christoph; Gay, Emmanuel; Le Bas, Jean-François

    2010-08-15

    To characterize peritumoral BOLD contrast disorders, 25 patients referred for resection of primary frontal or parietal neoplasms (low-grade glioma (LGG) (n=8); high-grade glioma (HGG) (n=7); meningioma (n=10)) without macroscopic tumoral infiltration of the primary sensorimotor cortex (SM1) were examined preoperatively using BOLD fMRI during simple motor tasks. Overall cerebral BOLD signal was estimated using vasoreactivity to carbogen inhalation. Using bolus of gadolinium, cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) were estimated. In a 1cm(3) region-of-interest centered on maximal T-value in SM1 contralateral to movements, interhemispheric asymmetry was evaluated using interhemispheric ratios for BOLD and perfusion parameters. During motor tasks contralateral to the tumor, ipsitumoral sensorimotor activations were decreased in HGG and meningiomas, correlated to the distance between the tumor and SM1. Whereas CBV was decreased in ipsitumoral SM1 for HGG, it remained normal in meningiomas. Changes in basal perfusion could not explain motor activation impairment in SM1. Decreased interhemispheric ratio of the BOLD response to carbogen was the best predictor to model the asymmetry of motor activation (R=0.51). Moreover, 94.9+/-4.9% of all motor activations overlapped significant BOLD response to carbogen inhalation.

  13. Modeled changes of cerebellar activity in mutant mice are predictive of their learning impairments

    PubMed Central

    Badura, Aleksandra; Clopath, Claudia; Schonewille, Martijn; De Zeeuw, Chris I.

    2016-01-01

    Translating neuronal activity to measurable behavioral changes has been a long-standing goal of systems neuroscience. Recently, we have developed a model of phase-reversal learning of the vestibulo-ocular reflex, a well-established, cerebellar-dependent task. The model, comprising both the cerebellar cortex and vestibular nuclei, reproduces behavioral data and accounts for the changes in neural activity during learning in wild type mice. Here, we used our model to predict Purkinje cell spiking as well as behavior before and after learning of five different lines of mutant mice with distinct cell-specific alterations of the cerebellar cortical circuitry. We tested these predictions by obtaining electrophysiological data depicting changes in neuronal spiking. We show that our data is largely consistent with the model predictions for simple spike modulation of Purkinje cells and concomitant behavioral learning in four of the mutants. In addition, our model accurately predicts a shift in simple spike activity in a mutant mouse with a brainstem specific mutation. This combination of electrophysiological and computational techniques opens a possibility of predicting behavioral impairments from neural activity. PMID:27805050

  14. Modeled changes of cerebellar activity in mutant mice are predictive of their learning impairments

    NASA Astrophysics Data System (ADS)

    Badura, Aleksandra; Clopath, Claudia; Schonewille, Martijn; de Zeeuw, Chris I.

    2016-11-01

    Translating neuronal activity to measurable behavioral changes has been a long-standing goal of systems neuroscience. Recently, we have developed a model of phase-reversal learning of the vestibulo-ocular reflex, a well-established, cerebellar-dependent task. The model, comprising both the cerebellar cortex and vestibular nuclei, reproduces behavioral data and accounts for the changes in neural activity during learning in wild type mice. Here, we used our model to predict Purkinje cell spiking as well as behavior before and after learning of five different lines of mutant mice with distinct cell-specific alterations of the cerebellar cortical circuitry. We tested these predictions by obtaining electrophysiological data depicting changes in neuronal spiking. We show that our data is largely consistent with the model predictions for simple spike modulation of Purkinje cells and concomitant behavioral learning in four of the mutants. In addition, our model accurately predicts a shift in simple spike activity in a mutant mouse with a brainstem specific mutation. This combination of electrophysiological and computational techniques opens a possibility of predicting behavioral impairments from neural activity.

  15. Inhibition of ecto-ATPase activities impairs HIV-1 infection of macrophages.

    PubMed

    Schachter, Julieta; Delgado, Kelly Valcárcel; Barreto-de-Souza, Victor; Bou-Habib, Dumith Chequer; Persechini, Pedro Muanis; Meyer-Fernandes, José Roberto

    2015-05-01

    Nucleotides and nucleosides are secreted into extracellular media at different concentrations as a consequence of different physiologic and pathological conditions. Ecto-nucleotidases, enzymes present on the surface of most cells, hydrolyze these extracellular nucleotides and reduce the concentration of them, thus affecting the activation of different nucleotide and nucleoside receptors. Also, ecto-nucleotidases are present in a number of microorganisms and play important roles in host-pathogen interactions. Here, we characterized the ecto-ATPase activities present on the surface of HIV-1 particle and human macrophages as well. We found that the kinetic properties of HIV-1 and macrophage ecto-ATPases are similar, suggesting that the enzyme is the same. This ecto-ATPase activity was increased in macrophages infected in vitro with HIV-1. Using three different non-related ecto-ATPase inhibitors-POM-1, ARL67156 and BG0-we showed that the inhibition of these macrophage and viral ecto-ATPase activities impairs HIV-1 infection. In addition, we also found that elevated extracellular concentrations of ATP inhibit HIV-1 production by infected macrophages.

  16. CALHM1 deficiency impairs cerebral neuron activity and memory flexibility in mice

    PubMed Central

    Vingtdeux, Valérie; Chang, Eric H.; Frattini, Stephen A.; Zhao, Haitian; Chandakkar, Pallavi; Adrien, Leslie; Strohl, Joshua J.; Gibson, Elizabeth L.; Ohmoto, Makoto; Matsumoto, Ichiro; Huerta, Patricio T.; Marambaud, Philippe

    2016-01-01

    CALHM1 is a cell surface calcium channel expressed in cerebral neurons. CALHM1 function in the brain remains unknown, but recent results showed that neuronal CALHM1 controls intracellular calcium signaling and cell excitability, two mechanisms required for synaptic function. Here, we describe the generation of Calhm1 knockout (Calhm1−/−) mice and investigate CALHM1 role in neuronal and cognitive functions. Structural analysis revealed that Calhm1−/− brains had normal regional and cellular architecture, and showed no evidence of neuronal or synaptic loss, indicating that CALHM1 deficiency does not affect brain development or brain integrity in adulthood. However, Calhm1−/− mice showed a severe impairment in memory flexibility, assessed in the Morris water maze, and a significant disruption of long-term potentiation without alteration of long-term depression, measured in ex vivo hippocampal slices. Importantly, in primary neurons and hippocampal slices, CALHM1 activation facilitated the phosphorylation of NMDA and AMPA receptors by protein kinase A. Furthermore, neuronal CALHM1 activation potentiated the effect of glutamate on the expression of c-Fos and C/EBPβ, two immediate-early gene markers of neuronal activity. Thus, CALHM1 controls synaptic activity in cerebral neurons and is required for the flexible processing of memory in mice. These results shed light on CALHM1 physiology in the mammalian brain. PMID:27066908

  17. Functional measures developed for clinical populations identified impairment among active workers with upper extremity disorders

    PubMed Central

    Gardner, Bethany T.; Dale, Ann Marie; Buckner-Petty, Skye; Rachford, Robert; Strickland, Jaime; Kaskutas, Vicki; Evanoff, Bradley

    2017-01-01

    Purpose Few studies have explored measures of function across a range of health outcomes in a general working population. Using four upper extremity (UE) case definitions from the scientific literature, we described the performance of functional measures of work, activities of daily living, and overall health. Methods A sample of 573 workers completed several functional measures: modified recall versions of the QuickDASH, Levine Functional Status Scale (FSS), DASH Work module (DASH-W), and standard SF-8 physical component score. We determined case status based on four UE case definitions: 1) UE symptoms, 2) UE musculoskeletal disorders (MSD), 3) carpal tunnel syndrome (CTS), and 4) work limitations due to UE symptoms. We calculated effect sizes for each case definition to show the magnitude of the differences that were detected between cases and non-cases for each case definition on each functional measure. Sensitivity and specificity analyses showed how well each measure identified functional impairments across the UE case definitions. Results All measures discriminated between cases and non-cases for each case definition with the largest effect sizes for CTS and work limitations, particularly for the modified FSS and DASH-W measures. Specificity was high and sensitivity was low for outcomes of UE symptoms and UE MSD in all measures. Sensitivity was high for CTS and work limitations. Conclusions Functional measures developed specifically for use in clinical, treatment-seeking populations may identify mild levels of impairment in relatively healthy, active working populations, but measures performed better among workers with CTS or those reporting limitations at work. PMID:26091980

  18. Coordination between proteasome impairment and caspase activation leading to TAU pathology: neuroprotection by cAMP

    PubMed Central

    Metcalfe, M J; Huang, Q; Figueiredo-Pereira, M E

    2012-01-01

    Neurofibrillary tangles (NFTs) are hallmarks of Alzheimer's disease (AD). The main component of NFTs is TAU, a highly soluble microtubule-associated protein. However, when TAU is cleaved at Asp421 by caspases it becomes prone to aggregation leading to NFTs. What triggers caspase activation resulting in TAU cleavage remains unclear. We investigated in rat cortical neurons a potential coordination between proteasome impairment and caspase activation. We demonstrate that upon proteasome inhibition, the early accumulation of detergent-soluble ubiquitinated (SUb) proteins paves the way to caspase activation and TAU pathology. This occurs with two drugs that inhibit the proteasome by different means: the product of inflammation prostaglandin J2 (PGJ2) and epoxomicin. Our results pinpoint a critical early event, that is, the buildup of SUb proteins that contributes to caspase activation, TAU cleavage, TAU/Ub-protein aggregation and neuronal death. Furthermore, to our knowledge, we are the first to demonstrate that elevating cAMP in neurons with dibutyryl-cAMP (db-cAMP) or the lipophilic peptide PACAP27 prevents/diminishes caspase activation, TAU cleavage and neuronal death induced by PGJ2, as long as these PGJ2-induced changes are moderate. db-cAMP also stimulated proteasomes, and mitigated proteasome inhibition induced by PGJ2. We propose that targeting cAMP/PKA to boost proteasome activity in a sustainable manner could offer an effective approach to avoid early accumulation of SUb proteins and later caspase activation, and TAU cleavage, possibly preventing/delaying AD neurodegeneration. PMID:22717581

  19. Impaired NADPH oxidase activity in peripheral blood lymphocytes of galactosemia patients.

    PubMed

    Al-Essa, Mazen; Dhaunsi, Gursev S; Al-Qabandi, Wafa'a; Khan, Islam

    2013-07-01

    Galactosemia is an autosomal recessive disorder with a wide range of clinical abnormalities. Cellular oxidative stress is considered as one of the pathogenic mechanisms of galactosemia. In this study, we examined the activity of NADPH oxidase (NOX), a major superoxide-generating enzyme system, in peripheral blood lymphocytes (PBL) from galactosemia patients. PBL were isolated from galactosemia patients and healthy control subjects and used for cell culture studies and biochemical assays. PBL were cultured in the presence or absence of galactose or galactose-1-phosphate (Gal-1-P), and enzyme activities and/or gene expression of NOX, catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPx) were measured in the cell homogenates. PBL isolated from galactosemia patients showed significantly reduced (P < 0.01) activities of catalase and GPx; however SOD activity remained unaltered. Galactosemia patients were found to have significantly (P < 0.01) increased levels of malondialdehyde (MDA) in blood lymphocytes. Enzymatic activity of NOX was significantly (P < 0.001) reduced in galactosemia patients; however, Western blotting revealed that NOX-1 protein was not significantly altered. Interestingly, levels of NOX activity in lymphocytes isolated from galactosemia patients significantly increased but remained subnormal when cultured in galactose-deficient medium for two weeks, indicating a galactose-mediated inhibition of NOX. Lymphocytes isolated from control subjects were found to have significantly (P < 0.01) reduced NOX activity when cultured in the presence of galactose or Gal-1-P for two weeks. These results show that galactose-induced cellular oxidative stress is not NOX mediated. However, impairment of the NOX system might be responsible for some of the clinical complications in galactosemia patients.

  20. Validation of a new questionnaire to assess the impact of Whiplash Associated Disorders: The Whiplash Activity and participation List (WAL).

    PubMed

    Stenneberg, Martijn S; Schmitt, Maarten A; van Trijffel, Emiel; Schröder, Carin D; Lindeboom, Robert

    2015-02-01

    Valid questionnaires for measuring functional limitations in patients with Whiplash Associated Disorders (WAD) are lacking, since existing measures are not suitable for addressing the specific limitations of these patients and because of cross contamination between theoretical constructs. The objective of this study was to evaluate dimensionality, test-retest reliability, measurement error, construct validity, and responsiveness of a new condition-specific questionnaire for WAD as well as to estimate the minimally important change score. Patients with WAD grade I or II were recruited from physical therapy practices and rehabilitation centers. Dimensionality was examined by internal consistency analysis (Cronbach's alpha) and factor analysis. Test-retest reliability was estimated by intraclass correlations and measurement error was calculated by the minimal detectable change (MDC) scores. Construct validity was investigated by testing predefined hypotheses on correlations of the WAL scores with generic health measures and by using the known group method. Responsiveness was expressed as the minimal clinically important change (MCIC) score. 73 patients (53 women) were included. Cronbach's alpha was high (0.95) and unidimensionality was plausible because factor analysis showed 40.3% variance explained by one dominant factor, which was more than 4.5 times larger than the second largest factor. Test-retest reliability was excellent (0.92, 95% CI 0.87-0.95). Construct validity was supported by 14 out of 15 confirmed hypotheses and the WAL showed statistically significant differences between known groups. MDC was 16 points while the MCIC was 18 points. In conclusion, the present study suggests that the WAL has adequate measurement properties, but additional research is needed.

  1. Zopiclone Increases the Arousal Threshold without Impairing Genioglossus Activity in Obstructive Sleep Apnea

    PubMed Central

    Carter, Sophie G.; Berger, Michael S.; Carberry, Jayne C.; Bilston, Lynne E.; Butler, Jane E.; Tong, Benjamin K.Y.; Martins, Rodrigo T.; Fisher, Lauren P.; McKenzie, David K.; Grunstein, Ronald R.; Eckert, Danny J.

    2016-01-01

    Study Objectives: To determine the effects of the nonbenzodiazepine sedative zopiclone on the threshold to arousal with increasing respiratory effort and genioglossus muscle activity and to examine potential physiological factors mediating disparate effects of zopiclone on obstructive sleep apnea (OSA) severity between patients. Methods: Twelve patients with OSA (apnea-hypopnea index = 41 ± 8 events/h) were studied during 2 single night sleep studies conducted approximately 1 w apart after receiving 7.5 mg of zopiclone or placebo according to a double-blind, placebo-controlled, randomized, crossover design. The respiratory arousal threshold (epiglottic pressure immediately prior to arousal during naturally occurring respiratory events), genioglossus activity and its responsiveness to pharyngeal pressure during respiratory events, and markers of OSA severity were compared between conditions. Genioglossus movement patterns and upper airway anatomy were also assessed via magnetic resonance imaging in a subset of participants (n = 7) during wakefulness. Results: Zopiclone increased the respiratory arousal threshold versus placebo (−31.8 ± 5.6 versus −26.4 ± 4.6 cmH2O, P = 0.02) without impairing genioglossus muscle activity or its responsiveness to negative pharyngeal pressure during respiratory events (−0.56 ± 0.2 versus −0.44 ± 0.1 %max/-cmH2O, P = 0.48). There was substantial interindividual variability in the changes in OSA severity with zopiclone explained, at least in part, by differences in pathophysiological characteristics including body mass index, arousal threshold, and genioglossus movement patterns. Conclusions: In a group of patients with predominantly severe OSA, zopiclone increased the arousal threshold without reducing genioglossus muscle activity or its responsiveness to negative pharyngeal pressure. These properties may be beneficial in some patients with OSA with certain pathophysiological characteristics but may worsen hypoxemia in

  2. Acute caffeine administration effect on brain activation patterns in mild cognitive impairment.

    PubMed

    Haller, Sven; Montandon, Marie-Louise; Rodriguez, Cristelle; Moser, Dominik; Toma, Simona; Hofmeister, Jeremy; Sinanaj, Indrit; Lovblad, Karl-Olof; Giannakopoulos, Panteleimon

    2014-01-01

    Previous studies showed that acute caffeine administration enhances task-related brain activation in elderly individuals with preserved cognition. To explore the effects of this widely used agent on cognition and brain activation in early phases of cognitive decline, we performed a double-blinded, placebo-controlled functional magnetic resonance imaging (fMRI) study during an n-back working memory task in 17 individuals with mild cognitive impairment (MCI) compared to 17 age-matched healthy controls (HC). All individuals were regular caffeine consumers with an overnight abstinence and given 200 mg caffeine versus placebo tablets 30 minutes before testing. Analyses included assessment of task-related activation (general linear model), functional connectivity (tensorial-independent component analysis, TICA), baseline perfusion (arterial spin labeling, ASL), grey matter density (voxel-based morphometry, VBM), and white matter microstructure (tract-based spatial statistics, TBSS). Acute caffeine administration induced a focal activation of the prefrontal areas in HC with a more diffuse and posteromedial activation pattern in MCI individuals. In MCI, TICA documented a significant caffeine-related enhancement in the prefrontal cortex, supplementary motor area, ventral premotor and parietal cortex as well as the basal ganglia and cerebellum. The absence of significant group differences in baseline ASL perfusion patterns supports a neuronal rather than a purely vascular origin of these differences. The VBM and TBSS analyses excluded potentially confounding differences in grey matter density and white matter microstructure between MCI and HC. The present findings suggest a posterior displacement of working memory-related brain activation patterns after caffeine administration in MCI that may represent a compensatory mechanism to counterbalance a frontal lobe dysfunction.

  3. CFTR impairment upregulates c-Src activity through IL-1β autocrine signaling.

    PubMed

    Massip-Copiz, María Macarena; Clauzure, Mariángeles; Valdivieso, Ángel Gabriel; Santa-Coloma, Tomás Antonio

    2017-02-15

    Cystic Fibrosis (CF) is a disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Previously, we found several genes showing a differential expression in CFDE cells (epithelial cells derived from a CF patient). One corresponded to c-Src; its expression and activity was found increased in CFDE cells, acting as a signaling molecule between the CFTR activity and MUC1 overexpression. Here we report that bronchial IB3-1 cells (CF cells) also showed increased c-Src activity compared to 'CFTR-corrected' S9 cells. In addition, three different Caco-2 cell lines, each stably transfected with a different CFTR-specific shRNAs, displayed increased c-Src activity. The IL-1β receptor antagonist IL1RN reduced the c-Src activity of Caco-2/pRS26 cells (expressing a CFTR-specific shRNA). In addition, increased mitochondrial and cellular ROS levels were detected in Caco-2/pRS26 cells. ROS levels were partially reduced by incubation with PP2 (c-Src inhibitor) or IL1RN, and further reduced by using the NOX1/4 inhibitor GKT137831. Thus, IL-1β→c-Src and IL-1β→NOX signaling pathways appear to be responsible for the production of cellular and mitochondrial ROS in CFTR-KD cells. In conclusion, IL-1β constitutes a new step in the CFTR signaling pathway, located upstream of c-Src, which is stimulated in cells with impaired CFTR activity.

  4. Mitochondrial ATP synthase activity is impaired by suppressed O-GlcNAcylation in Alzheimer's disease

    PubMed Central

    Cha, Moon-Yong; Cho, Hyun Jin; Kim, Chaeyoung; Jung, Yang Ouk; Kang, Min Jueng; Murray, Melissa E.; Hong, Hyun Seok; Choi, Young-Joo; Choi, Heesun; Kim, Dong Kyu; Choi, Hyunjung; Kim, Jisoo; Dickson, Dennis W.; Song, Hyun Kyu; Cho, Jin Won; Yi, Eugene C.; Kim, Jungsu; Jin, Seok Min; Mook-Jung, Inhee

    2015-01-01

    Glycosylation with O-linked β-N-acetylglucosamine (O-GlcNAc) is one of the protein glycosylations affecting various intracellular events. However, the role of O-GlcNAcylation in neurodegenerative diseases such as Alzheimer's disease (AD) is poorly understood. Mitochondrial adenosine 5′-triphosphate (ATP) synthase is a multiprotein complex that synthesizes ATP from ADP and Pi. Here, we found that ATP synthase subunit α (ATP5A) was O-GlcNAcylated at Thr432 and ATP5A O-GlcNAcylation was decreased in the brains of AD patients and transgenic mouse model, as well as Aβ-treated cells. Indeed, Aβ bound to ATP synthase directly and reduced the O-GlcNAcylation of ATP5A by inhibition of direct interaction between ATP5A and mitochondrial O-GlcNAc transferase, resulting in decreased ATP production and ATPase activity. Furthermore, treatment of O-GlcNAcase inhibitor rescued the Aβ-induced impairment in ATP production and ATPase activity. These results indicate that Aβ-mediated reduction of ATP synthase activity in AD pathology results from direct binding between Aβ and ATP synthase and inhibition of O-GlcNAcylation of Thr432 residue on ATP5A. PMID:26358770

  5. Developmental Alcohol Exposure Impairs Activity-Dependent S-Nitrosylation of NDEL1 for Neuronal Maturation.

    PubMed

    Saito, Atsushi; Taniguchi, Yu; Kim, Sun-Hong; Selvakumar, Balakrishnan; Perez, Gabriel; Ballinger, Michael D; Zhu, Xiaolei; Sabra, James; Jallow, Mariama; Yan, Priscilla; Ito, Koki; Rajendran, Shreenath; Hirotsune, Shinji; Wynshaw-Boris, Anthony; Snyder, Solomon H; Sawa, Akira; Kamiya, Atsushi

    2016-07-01

    Neuronal nitric oxide synthase is involved in diverse signaling cascades that regulate neuronal development and functions via S-Nitrosylation-mediated mechanism or the soluble guanylate cyclase (sGC)/cyclic guanosine monophosphate (cGMP) pathway activated by nitric oxide. Although it has been studied extensively in vitro and in invertebrate animals, effects on mammalian brain development and underlying mechanisms remain poorly understood. Here we report that genetic deletion of "Nos1" disrupts dendritic development, whereas pharmacological inhibition of the sGC/cGMP pathway does not alter dendritic growth during cerebral cortex development. Instead, nuclear distribution element-like (NDEL1), a protein that regulates dendritic development, is specifically S-nitrosylated at cysteine 203, thereby accelerating dendritic arborization. This post-translational modification is enhanced by N-methyl-D-aspartate receptor-mediated neuronal activity, the main regulator of dendritic formation. Notably, we found that disruption of S-Nitrosylation of NDEL1 mediates impaired dendritic maturation caused by developmental alcohol exposure, a model of developmental brain abnormalities resulting from maternal alcohol use. These results highlight S-Nitrosylation as a key activity-dependent mechanism underlying neonatal brain maturation and suggest that reduction of S-Nitrosylation of NDEL1 acts as a pathological factor mediating neurodevelopmental abnormalities caused by maternal alcohol exposure.

  6. Reduced Sensory Oscillatory Activity during Rapid Auditory Processing as a Correlate of Language-Learning Impairment

    PubMed Central

    Heim, Sabine; Friedman, Jennifer Thomas; Keil, Andreas; Benasich, April A.

    2010-01-01

    Successful language acquisition has been hypothesized to involve the ability to integrate rapidly presented, brief acoustic cues in sensory cortex. A body of work has suggested that this ability is compromised in language-learning impairment (LLI). The present research aimed to examine sensory integration during rapid auditory processing by means of electrophysiological measures of oscillatory brain activity using data from a larger longitudinal study. Twenty-nine children with LLI and control participants with typical language development (n=18) listened to tone doublets presented at a temporal interval that is essential for accurate speech processing (70-ms interstimulus interval). The children performed a deviant (pitch change of second tone) detection task, or listened passively. The electroencephalogram was recorded from 64 electrodes. Data were source-projected to the auditory cortices and submitted to wavelet analysis, resulting in time-frequency representations of electrocortical activity. Results show significantly reduced amplitude and phase-locking of early (45–75 ms) oscillations in the gamma-band range (29–52 Hz), specifically in the LLI group, for the second stimulus of the tone doublet. This suggests altered temporal organization of sensory oscillatory activity in LLI when processing rapid sequences. PMID:21822356

  7. Activation of NO-cGMP Signaling Rescues Age-Related Memory Impairment in Crickets

    PubMed Central

    Matsumoto, Yukihisa; Matsumoto, Chihiro S.; Takahashi, Toshihumi; Mizunami, Makoto

    2016-01-01

    Age-related memory impairment (AMI) is a common feature and a debilitating phenotype of brain aging in many animals. However, the molecular mechanisms underlying AMI are still largely unknown. The cricket Gryllus bimaculatus is a useful experimental animal for studying age-related changes in learning and memory capability; because the cricket has relatively short life-cycle and a high capability of olfactory learning and memory. Moreover, the molecular mechanisms underlying memory formation in crickets have been examined in detail. In the present study, we trained male crickets of different ages by multiple-trial olfactory conditioning to determine whether AMI occurs in crickets. Crickets 3 weeks after the final molt (3-week-old crickets) exhibited levels of retention similar to those of 1-week-old crickets at 30 min or 2 h after training; however they showed significantly decreased levels of 1-day retention, indicating AMI in long-term memory (LTM) but not in anesthesia-resistant memory (ARM) in olfactory learning of crickets. Furthermore, 3-week-old crickets injected with a nitric oxide (NO) donor, a cyclic GMP (cGMP) analog or a cyclic AMP (cAMP) analog into the hemolymph before conditioning exhibited a normal level of LTM, the same level as that in 1-week-old crickets. The rescue effect by NO donor or cGMP analog injection was absent when the crickets were injected after the conditioning. For the first time, an NO donor and a cGMP analog were found to antagonize the age-related impairment of LTM formation, suggesting that deterioration of NO synthase (NOS) or molecules upstream of NOS activation is involved in brain-aging processes. PMID:27616985

  8. Spermidine Suppresses Age-Associated Memory Impairment by Preventing Adverse Increase of Presynaptic Active Zone Size and Release

    PubMed Central

    Gupta, Varun K.; Pech, Ulrike; Fulterer, Andreas; Ender, Anatoli; Mauermann, Stephan F.; Andlauer, Till F. M.; Beuschel, Christine; Thriene, Kerstin; Quentin, Christine; Schwärzel, Martin; Mielke, Thorsten; Madeo, Frank; Dengjel, Joern; Fiala, André; Sigrist, Stephan J.

    2016-01-01

    Memories are assumed to be formed by sets of synapses changing their structural or functional performance. The efficacy of forming new memories declines with advancing age, but the synaptic changes underlying age-induced memory impairment remain poorly understood. Recently, we found spermidine feeding to specifically suppress age-dependent impairments in forming olfactory memories, providing a mean to search for synaptic changes involved in age-dependent memory impairment. Here, we show that a specific synaptic compartment, the presynaptic active zone (AZ), increases the size of its ultrastructural elaboration and releases significantly more synaptic vesicles with advancing age. These age-induced AZ changes, however, were fully suppressed by spermidine feeding. A genetically enforced enlargement of AZ scaffolds (four gene-copies of BRP) impaired memory formation in young animals. Thus, in the Drosophila nervous system, aging AZs seem to steer towards the upper limit of their operational range, limiting synaptic plasticity and contributing to impairment of memory formation. Spermidine feeding suppresses age-dependent memory impairment by counteracting these age-dependent changes directly at the synapse. PMID:27684064

  9. Impaired endothelial progenitor cell activity is associated with reduced arterial elasticity in patients with essential hypertension.

    PubMed

    Yang, Zhen; Chen, Long; Su, Chen; Xia, Wen-Hao; Wang, Yan; Wang, Jie-Mei; Chen, Fei; Zhang, Yuan-Yuan; Wu, Fang; Xu, Shi-Yue; Zhang, Xiao-Lin; Tao, Jun

    2010-01-01

    Endothelial dysfunction is related to reduced arterial elasticity in patients with essential hypertension. Circulating endothelial progenitor cells (EPCs), an important endogenous repair approach for endothelial injury, is altered in hypertensive patients. However, the association between alteration in circulating EPCs and hypertension-related reduced arterial elasticity has not been reported. The purpose of this study is to investigate the association between alteration in circulating EPCs and hypertension-related reduced arterial elasticity. We measured the artery elasticity profiles including brachial-ankle PWV (baPWV) and C1 large and C2 small artery elasticity indices in patients with essential hypertension (n = 20) and age-matched normotensive subjects (n = 21). The number and activity of circulating EPCs isolated from peripheral blood were determined. Compared to normotensive subjects, the patients with hypertension exhibited decreased C1 large and C2 small artery elasticity indices, as well as increased baPWV. The number of circulating EPCs did not differ between the two groups. The migratory and proliferative activities of circulating EPCs in hypertensive patients were lower than those in normotensive subjects. Both proliferatory and migratory activities of circulating EPCs closely correlated with arterial elasticity profiles, including baPWV and C1 large and C2 small artery elasticity indices. Multivariate analysis identified both proliferative and migratory activities of circulating EPCs as independent predictors of the artery elasticity profiles. The present study demonstrates for the first time that impaired activity of circulating EPCs is associated with reduced arterial elasticity in patients with hypertension. The fall in endogenous repair capacity of vascular endothelium may be involved in the pathogenesis of hypertension-related vascular injury.

  10. Retinitis Pigmentosa Mutations in Bad Response to Refrigeration 2 (Brr2) Impair ATPase and Helicase Activity.

    PubMed

    Ledoux, Sarah; Guthrie, Christine

    2016-06-03

    Brr2 is an RNA-dependent ATPase required to unwind the U4/U6 snRNA duplex during spliceosome assembly. Mutations within the ratchet helix of the Brr2 RNA binding channel result in a form of degenerative human blindness known as retinitis pigmentosa (RP). The biochemical consequences of these mutations on Brr2's RNA binding, helicase, and ATPase activity have not yet been characterized. Therefore, we identified the largest construct of Brr2 that is soluble in vitro, which truncates the first 247 amino acids of the N terminus (Δ247-Brr2), to characterize the effects of the RP mutations on Brr2 activity. The Δ247-Brr2 RP mutants exhibit a gradient of severity of weakened RNA binding, reduced helicase activity, and reduced ATPase activity compared with wild type Δ247-Brr2. The globular C-terminal Jab1/Mpn1-like domain of Prp8 increases the ability of Δ247-Brr2 to bind the U4/U6 snRNA duplex at high pH and increases Δ247-Brr2's RNA-dependent ATPase activity and the extent of RNA unwinding. However, this domain of Prp8 does not differentially affect the Δ247-Brr2 RP mutants compared with the wild type Δ247-Brr2. When stimulated by Prp8, wild type Δ247-Brr2 is able to unwind long stable duplexes in vitro, and even the RP mutants capable of binding RNA with tight affinity are incapable of fully unwinding short duplex RNAs. Our data suggest that the RP mutations within the ratchet helix impair Brr2 translocation through RNA helices.

  11. The Survey Questionnaire

    ERIC Educational Resources Information Center

    Ritter, Lois A. Ed.; Sue, Valerie M., Ed.

    2007-01-01

    Internet-based surveys are still relatively new, and researchers are just beginning to articulate best practices for questionnaire design. Online questionnaire design has generally been guided by the principles applying to other self-administered instruments, such as paper-based questionnaires. Web-based questionnaires, however, have the potential…

  12. Cigarette smoking impairs Na+-K+-ATPase activity in the human coronary microcirculation.

    PubMed

    Miura, Hiroto; Toyama, Kazuyoshi; Pratt, Phillip F; Gutterman, David D

    2011-01-01

    The extracellular K(+) concentration ([K(+)](o)) has been proposed to link cardiac metabolism with coronary perfusion and arrhythmogenesis, particularly during ischemia. Several animal studies have also supported K(+) as an EDHF that activates Na(+)-K(+)-ATPase and/or inwardly rectifying K(+) (K(ir)) channels. Therefore, we examined the vascular reactivity of human coronary arterioles (HCAs) to small elevations in [K(+)](o), the influence of risk factors for coronary disease, and the role of K(+) as an EDHF. Changes in the internal diameter of HCAs were recorded with videomicroscopy. Most vessels dilated to increases in [K(+)](o) with a maximal dilation of 55 ± 6% primarily at 12.5-20.0 mM KCl (n = 38, average: 16 ± 1 mM). Ouabain, a Na(+)-K(+)-ATPase inhibitor, alone reduced the dilation, and the addition of Ba(2+), a K(ir) channel blocker, abolished the remaining dilation, whereas neither endothelial denudation nor Ba(2+) alone reduced the dilation. Multivariate analysis revealed that cigarette smoking was the only risk factor associated with impaired dilation to K(+). Ouabain significantly reduced the vasodilation in HCAs from subjects without cigarette smoking but not in those with smoking. Cigarette smoking downregulated the expression of the Na(+)-K(+)-ATPase catalytic α(1)-subunit but not Kir2.1 in the vessels. Ouabain abolished the dilation in endothelium-denuded vessels to a same extent to that with the combination of ouabain and Ba(2+) in endothelium-intact vessels, whereas neither ouabain nor ouabain plus Ba(2+) reduced EDHF-mediated dilations to bradykinin and ADP. A rise in [K(+)](o) dilates HCAs primarily via the activation of Na(+)-K(+)-ATPase in vascular smooth muscle cells with a considerable contribution of K(ir) channels in the endothelium, indicating that [K(+)](o) may modify coronary microvascular resistance in humans. Na(+)-K(+)-ATPase activity is impaired in subjects who smoke, possibly contributing to dysregulation of the coronary

  13. Database of Standardized Questionnaires About Walking & Bicycling

    Cancer.gov

    This database contains questionnaire items and a list of validation studies for standardized items related to walking and biking. The items come from multiple national and international physical activity questionnaires.

  14. Focal hyperemia followed by spreading oligemia and impaired activation of rCBF in classic migraine

    SciTech Connect

    Olesen, J.; Larsen, B.; Lauritzen, M.

    1981-04-01

    Regional cerebral blood flow (rCBF) was measured in 254 areas of a hemisphere with the xenon 133 intraarterial injection method. Six cases of classic migraine were followed from the normal state into the prodromal phase, and in 3 cases further into the headache phase. One patient with common migraine was similarly followed during his only classic attack. The attacks were initiated by focal hyperemia in 3 patients. During prodromes all patients displayed occipitoparietal rCBF reduction (oligemia), but in only 1 case did the reduction approach critical values. Oligemia gradually spread anteriorly in the course of 15 to 45 minutes. In 4 patients a global oligemia was observed. In 4 patients severe headache was present concomitantly with oligemia and with no sign of hyperemia or nonhomogeneous brain perfusion. The normal rCBF increase during cortical activity (hand movement, speech, and similar activities) was impaired in 6 patients. The results indicate that the vasospastic model of the migraine attack is too simplistic.

  15. Naturalistic Assessment of Everyday Activities and Prompting Technologies in Mild Cognitive Impairment

    PubMed Central

    Seelye, Adriana M.; Schmitter-Edgecombe, Maureen; Cook, Diane J.; Crandall, Aaron

    2014-01-01

    Older adults with mild cognitive impairment (MCI) often have difficulty performing complex instrumental activities of daily living (IADLs), which are critical to independent living. In this study, amnestic multi-domain MCI (N = 29), amnestic single-domain MCI (N = 18), and healthy older participants (N = 47) completed eight scripted IADLs (e.g., cook oatmeal on the stove) in a smart apartment testbed. We developed and experimented with a graded hierarchy of technology-based prompts to investigate both the amount of prompting and type of prompts required to assist individuals with MCI in completing the activities. When task errors occurred, progressive levels of assistance were provided, starting with the lowest level needed to adjust performance. Results showed that the multi-domain MCI group made more errors and required more prompts than the single-domain MCI and healthy older adult groups. Similar to the other two groups, the multi-domain MCI group responded well to the indirect prompts and did not need a higher level of prompting to get back on track successfully with the tasks. Need for prompting assistance was best predicted by verbal memory abilities in multi-domain amnestic MCI. Participants across groups indicated that they perceived the prompting technology to be very helpful. PMID:23351284

  16. Mnemonic strategy training partially restores hippocampal activity in patients with mild cognitive impairment

    PubMed Central

    Hampstead, Benjamin M.; Stringer, Anthony Y.; Stilla, Randall F.; Giddens, Michelle; Sathian, K.

    2012-01-01

    Learning and memory deficits typify patients with mild cognitive impairment (MCI) and are generally attributed to medial temporal lobe dysfunction. Although the hippocampus is perhaps the most commonly studied neuroanatomical structure in these patients, there have been few attempts to identify rehabilitative interventions that facilitate its functioning. Here, we present results from a randomized, controlled, single-blind study in which patients with MCI and healthy elderly controls (HEC) were randomized to either 3 sessions of mnemonic strategy training (MS) or a matched-exposure control group (XP). All participants underwent pre- and post-training fMRI scanning as they encoded and retrieved object-location associations. For the current report, fMRI analyses were restricted to the hippocampus, as defined anatomically. Before training, MCI patients showed reduced hippocampal activity during both encoding and retrieval, relative to HEC. Following training, the MCI MS group demonstrated increased activity during both encoding and retrieval. There were significant differences between the MCI MS and MCI XP groups during retrieval, especially within the right hippocampus. Thus, MS facilitated hippocampal functioning in a partially restorative manner. We conclude that cognitive rehabilitation techniques may help mitigate hippocampal dysfunction in MCI patients. PMID:22368035

  17. Out of control: Diminished prefrontal activity coincides with impaired motor performance due to choking under pressure

    PubMed Central

    Lee, Taraz G.; Grafton, Scott T.

    2014-01-01

    There are three non-exclusive theoretical explanations for the paradoxical collapse of performance due to large financial incentives. It has been proposed that “choking under pressure” is either due to distraction, interference via an increase in top-down control and performance monitoring, or excessive levels of arousal in the face of large losses. Given the known neural architecture involved in executive control and reward, we used fMRI of human participants during incentivized motor performance to provide evidence to support and/or reconcile these competing models in a visuomotor task. We show that the execution of a pre-trained motor task during neuroimaging is impaired by high rewards. BOLD activity occurring prior to movement onset is increased in dorsolateral prefrontal cortex and functional connectivity between this region and motor cortex is likewise increased just prior to choking. However, the extent of this increase in functional connectivity is inversely related to a participant's propensity to choke, suggesting that a failure in exerting top-down influence on motor control underlies choking under pressure due to large incentives. These results are consistent with a distraction account of choking and suggest that frontal influences on motor activity are necessary to protect performance from vulnerability under pressure. PMID:25449744

  18. High glucose impairs insulin signaling via activation of PKR pathway in L6 muscle cells.

    PubMed

    Udumula, Mary Priyanka; Babu, Mangali Suresh; Bhat, Audesh; Dhar, Indu; Sriram, Dharmarajan; Dhar, Arti

    2017-05-06

    Double stranded RNA (dsRNA) activated protein kinase R (PKR), a ubiquitously expressed serine/threonine kinase is a key inducer of inflammation, insulin resistance and glucose homeostasis in obesity. Recent studies have demonstrated that PKR can respond to metabolic stress in mice as well as in humans. However the underlying molecular mechanism is not fully understood. The aim of the present study was to examine the effect of high glucose on cultured rat L6 muscle cells and to investigate whether inhibition of PKR could prevent any deleterious effects of high glucose in these cells. PKR expression was determined by immunofluorescence and immunoblotting. The expression of different insulin signaling gene markers were measured by RT-PCR. Oxidative stress and apoptosis were determined by flow cytometry. High glucose treated L6 muscle cells developed a significant increase in PKR expression. Impaired insulin signaling as well as reduced insulin stimulated glucose uptake was observed in high glucose treated L6 muscle cells. A significant increase in reactive oxygen species generation and apoptosis formation was also observed in high glucose treated cultured L6 muscle cells. All these effects of high glucose were attenuated by a selective PKR inhibitor imoxin. Our study demonstrates PKR may have an additive role against the deleterious effects of high glucose in diabetes. Prevention of PKR activation, by safer and specific inhibitors is a therapeutic option in metabolic disorders that needs to be explored further.

  19. Impaired tropomyosin-troponin interactions reduce activation of the actin thin filament.

    PubMed

    Robaszkiewicz, Katarzyna; Ostrowska, Zofia; Cyranka-Czaja, Anna; Moraczewska, Joanna

    2015-05-01

    Tropomyosin and troponin are bound to the actin filament to control the contraction of striated muscle in the Ca-dependent manner. The interactions between both regulatory proteins important for the regulation process are not fully understood. To gain more insight into the mechanisms of the thin filament regulation by skeletal α-tropomyosin and troponin, we analyzed effects of seven myopathy-related substitutions: Leu99Met, Ala155Thr, Arg167Gly, Arg167Cys, Arg167His, Lys168Glu, and Arg244Gly. All substitutions reduced Ca-dependent activation of the actomyosin ATPase. The effects of mutations in Arg167 and Lys168 were the most severe. The amino acid substitutions did not significantly affect troponin binding to the whole filament, but reduced 1.2-2.8 fold the affinity of troponin to tropomyosin alone. The excimer fluorescence of N-(1-pyrene)iodoacetamide, a probe attached to the central Cys190, demonstrated that substitutions located near the troponin core domain-binding region strongly affected conformational changes accompanying the tropomyosin-troponin interactions. The thermal stability of all tropomyosin mutants was lower than the stability of the wild type tropomyosin, with TM reduced by 5.3-8.5°C. Together the analyses demonstrated that the myopathy-causing mutations affected tropomyosin structure and led to changes in interactions between tropomyosin and troponin, which impaired the transition of the thin filament from the inactive off to the active on state.

  20. Aryl hydrocarbon receptor activation impairs extracellular matrix remodeling during zebra fish fin regeneration.

    PubMed

    Andreasen, Eric A; Mathew, Lijoy K; Löhr, Christiane V; Hasson, Rachelle; Tanguay, Robert L

    2007-01-01

    Adult zebra fish completely regenerate their caudal (tail) fin following partial amputation. Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) inhibits this regenerative process. Proper regulation of transcription, innervation, vascularization, and extracellular matrix (ECM) composition is essential for complete fin regeneration. Previous microarray studies suggest that genes involved in ECM regulation are misexpressed following activation of the aryl hydrocarbon receptor. To investigate whether TCDD blocks regeneration by impairing ECM remodeling, male zebra fish were i.p. injected with 50 ng/g TCDD or vehicle, and caudal fins were amputated. By 3 days postamputation (dpa), the vascular network in the regenerating fin of TCDD-exposed fish was disorganized compared to vehicle-exposed animals. Furthermore, immunohistochemical staining revealed that axonal outgrowth was impacted by TCDD as early as 3 dpa. Histological analysis demonstrated that TCDD exposure leads to an accumulation of collagen at the end of the fin ray just distal to the amputation site by 3 dpa. Mature lepidotrichial-forming cells (fin ray-forming cells) were not observed in the fins of TCDD-treated fish. The capacity to metabolize ECM was also altered by TCDD exposure. Quantitative real-time PCR studies revealed that the aryl hydrocarbon pathway is active and that matrix-remodeling genes are expressed in the regenerate following TCDD exposure.

  1. Activation of the arousal response and impairment of performance increase with anxiety and stressor intensity.

    PubMed

    Noteboom, J T; Barnholt, K R; Enoka, R M

    2001-11-01

    The purpose of this study was to determine the effect of trait anxiety and stressor intensity on arousal and motor performance during a pinch task. We examined the steadiness of a precision task in the presence and absence of an imposed stressor on subjects with moderate and low trait anxiety. Subjects with the 26 highest and 14 lowest anxiety scores were assigned to one of three groups: a control group (5 women, 5 men), a moderate-anxiety group (8 women, 8 men), or a low-anxiety group (7 women, 7 men). Subjects in the anxiety groups received electric shocks and experienced significant increases in cognitive and physiological arousal compared with baseline and control subjects, especially subjects in the moderate-anxiety group. Heart rate, systolic blood pressure, and electrodermal activity were elevated during the stressor, whereas diastolic blood pressure was unchanged. Cognitive and physiological arousal tended to increase with stressor intensity and was accompanied by changes in steadiness. Although steadiness was markedly reduced with the highest intensity of shock, the average electromyogram activity was unaffected by the stressor. These findings indicate that the increase in arousal and the impairment of steadiness increased with trait anxiety and with the intensity of the noxious stimulus.

  2. Out of control: diminished prefrontal activity coincides with impaired motor performance due to choking under pressure.

    PubMed

    Lee, Taraz G; Grafton, Scott T

    2015-01-15

    There are three non-exclusive theoretical explanations for the paradoxical collapse of performance due to large financial incentives. It has been proposed that "choking under pressure" is either due to distraction, interference via an increase in top-down control and performance monitoring, or excessive levels of arousal in the face of large losses. Given the known neural architecture involved in executive control and reward, we used fMRI of human participants during incentivized motor performance to provide evidence to support and/or reconcile these competing models in a visuomotor task. We show that the execution of a pre-trained motor task during neuroimaging is impaired by high rewards. BOLD activity occurring prior to movement onset is increased in dorsolateral prefrontal cortex and functional connectivity between this region and motor cortex is likewise increased just prior to choking. However, the extent of this increase in functional connectivity is inversely related to a participant's propensity to choke, suggesting that a failure in exerting top-down influence on motor control underlies choking under pressure due to large incentives. These results are consistent with a distraction account of choking and suggest that frontal influences on motor activity are necessary to protect performance from vulnerability under pressure.

  3. Impaired activity-dependent neural circuit assembly and refinement in autism spectrum disorder genetic models

    PubMed Central

    Doll, Caleb A.; Broadie, Kendal

    2014-01-01

    Early-use activity during circuit-specific critical periods refines brain circuitry by the coupled processes of eliminating inappropriate synapses and strengthening maintained synapses. We theorize these activity-dependent (A-D) developmental processes are specifically impaired in autism spectrum disorders (ASDs). ASD genetic models in both mouse and Drosophila have pioneered our insights into normal A-D neural circuit assembly and consolidation, and how these developmental mechanisms go awry in specific genetic conditions. The monogenic fragile X syndrome (FXS), a common cause of heritable ASD and intellectual disability, has been particularly well linked to defects in A-D critical period processes. The fragile X mental retardation protein (FMRP) is positively activity-regulated in expression and function, in turn regulates excitability and activity in a negative feedback loop, and appears to be required for the A-D remodeling of synaptic connectivity during early-use critical periods. The Drosophila FXS model has been shown to functionally conserve the roles of human FMRP in synaptogenesis, and has been centrally important in generating our current mechanistic understanding of the FXS disease state. Recent advances in Drosophila optogenetics, transgenic calcium reporters, highly-targeted transgenic drivers for individually-identified neurons, and a vastly improved connectome of the brain are now being combined to provide unparalleled opportunities to both manipulate and monitor A-D processes during critical period brain development in defined neural circuits. The field is now poised to exploit this new Drosophila transgenic toolbox for the systematic dissection of A-D mechanisms in normal versus ASD brain development, particularly utilizing the well-established Drosophila FXS disease model. PMID:24570656

  4. Isoniazid suppresses antioxidant response element activities and impairs adipogenesis in mouse and human preadipocytes

    SciTech Connect

    Chen, Yanyan; Xue, Peng; Hou, Yongyong; Zhang, Hao; Zheng, Hongzhi; Zhou, Tong; Qu, Weidong; Teng, Weiping; Zhang, Qiang; Andersen, Melvin E.; Pi, Jingbo

    2013-12-15

    Transcriptional signaling through the antioxidant response element (ARE), orchestrated by the Nuclear factor E2-related factor 2 (Nrf2), is a major cellular defense mechanism against oxidative or electrophilic stress. Here, we reported that isoniazid (INH), a widely used antitubercular drug, displays a substantial inhibitory property against ARE activities in diverse mouse and human cells. In 3T3-L1 preadipocytes, INH concentration-dependently suppressed the ARE-luciferase reporter activity and mRNA expression of various ARE-dependent antioxidant genes under basal and oxidative stressed conditions. In keeping with our previous findings that Nrf2-ARE plays a critical role in adipogenesis by regulating expression of CCAAT/enhancer-binding protein β (C/EBPβ) and peroxisome proliferator-activated receptor γ (PPARγ), suppression of ARE signaling by INH hampered adipogenic differentiation of 3T3-L1 cells and human adipose-derived stem cells (ADSCs). Following adipogenesis induced by hormonal cocktails, INH-treated 3T3-L1 cells and ADSCs displayed significantly reduced levels of lipid accumulation and attenuated expression of C/EBPα and PPARγ. Time-course studies in 3T3-L1 cells revealed that inhibition of adipogenesis by INH occurred in the early stage of terminal adipogenic differentiation, where reduced expression of C/EBPβ and C/EBPδ was observed. To our knowledge, the present study is the first to demonstrate that INH suppresses ARE signaling and interrupts with the transcriptional network of adipogenesis, leading to impaired adipogenic differentiation. The inhibition of ARE signaling may be a potential underlying mechanism by which INH attenuates cellular antioxidant response contributing to various complications. - Highlights: • Isoniazid suppresses ARE-mediated transcriptional activity. • Isoniazid inhibits adipogenesis in preadipocytes. • Isoniazid suppresses adipogenic gene expression during adipogenesis.

  5. [Plasma antioxidant activity--a test for impaired biological functions of endoecology, exotrophy, and inflammation reactions].

    PubMed

    Titov, V N; Krylin, V V; Dmitriev, V A; Iashin, Ia I

    2010-07-01

    The authors discuss the diagnostic value of a test for total serum antioxidant activity determined by an electrochemistry method on a liquid chromatograph (without a column), by using an amperometric detector, as well as the composition of the endogenously synthesized hydrophilic and hydrophobic acceptors of reactive oxygen species (ROS). Uric acid is a major hydrophilic acceptor of ROS; monoenic oleic fatty acid acts as its major lipophilic acceptor. The constant determined by the authors for of 03 oleic acid oxidation during automatic titration in the organic medium is an order of magnitude higher than that for alpha-tocopherol, beta-carotene and linoleic fatty acid; its concentration is also an order of magnitude higher. In oxidative stress, the adrenal steroid hormone dehydroepiandrosterone initiates oleic acid synthesis via expression of palmitoyl elongase and steatoryl desaturase. In early steps of phylogenesis in primates, spontaneous mutation resulted in ascorbic acid synthesis gene knockout; phylogenetically, further other mutation knocked out the gene encoding the synthesis of uricase and the conversion of uric acid to alantoin. In primates, uric acid became not only a catabolite of purine bases in vivo, but also the major endogenous hydrophilic acceptor of ROS. This philogenetic order makes it clear why the epithelium in the proximal nephron tubule entirely reabsorbs uric acid (a catabolite?) from primary urine and then secretes it again to urine depending on the impairment of biological functions of endoecology (the intercellular medium being contaminated with biological rubbish), the activation of a biological inflammatory reaction, the cellular production of ROS, and the reduction in serum total antioxidant activity. With each biological reaction, there was an increase in the blood content of uric acid as a hydrophilic acceptor of ROS, by actively lowering its secretion into urine. Uric acid is a diagnostic test of inflammation, or rather compensatory

  6. Activated pancreatic stellate cells can impair pancreatic islet function in mice

    PubMed Central

    Zang, Guangxiang; Sandberg, Monica; Carlsson, Per-Ola; Welsh, Nils; Jansson, Leif

    2015-01-01

    Background Pancreatic or islet fibrosis is often associated with activated pancreatic stellate cells (PSCs). PSCs are considered not only to promote fibrosis, but also to be associated with glucose intolerance in some diseases. We therefore evaluated morphological and functional relationships between islets and PSCs in the normal mouse pancreas and transplanted islets. Methods Immunohistochemistry was used to map the presence of PSCs in the normal mouse pancreas and islets implanted under the renal capsule. We isolated and cultured mouse PSCs and characterized them morphologically by immunofluorescence staining. Furthermore, we measured their cytokine production and determined their effects on insulin release from simultaneously cultured islets. Results PSCs were scattered throughout the pancreas, with occasional cells within the islets, particularly in the islet capsule. In islet transplants they were found mainly in the graft periphery. Cultured PSCs became functionally activated and produced several cytokines. Throughout the culture period they linearly increased their production of interleukin-6 and mammalian keratinocyte-derived chemokine. PSC cytokine production was not affected by acute hyperglycemia. Syngeneic islets co-cultured with PSCs for 24–48 h increased their insulin release and lowered their insulin content. However, short-term insulin release in batch-type incubations was unaffected after 48 h of co-culture. Increased islet cell caspase-3 activation and a decreased islet cell replication were consistently observed after co-culture for 2 or 7 days. Conclusion Activated PSCs may contribute to impaired islet endocrine function seen in exocrine pancreatitis and in islet fibrosis associated with some cases of type 2 diabetes. PMID:25854824

  7. Skeletal muscle regeneration is delayed by reduction in Xin expression: consequence of impaired satellite cell activation?

    PubMed

    Nissar, Aliyah A; Zemanek, Bart; Labatia, Rita; Atkinson, Daniel J; van der Ven, Peter F M; Fürst, Dieter O; Hawke, Thomas J

    2012-01-01

    Xin is a striated muscle-specific actin-binding protein whose mRNA expression has been observed in damaged skeletal muscle. Here we demonstrate increased Xin protein expression early postinjury (≤ 12 h) and localization primarily to the periphery of damaged myofibers. At 1 day postinjury, Xin is colocalized with MyoD, confirming expression in activated satellite cells (SCs). By 5 days postinjury, Xin is evident in newly regenerated myofibers, with a return to preinjury levels by 14 days of regeneration. To determine whether the increased Xin expression is functionally relevant, tibialis anterior muscles of wild-type mice were infected with Xin-short hairpin RNA (shRNA) adenovirus, whereas the contralateral tibialis anterior received control adenovirus (Control). Four days postinfection, muscles were harvested or injured with cardiotoxin and collected at 3, 5, or 14 days thereafter. When compared with Control, Xin-shRNA infection attenuated muscle regeneration as demonstrated by Myh3 expression and fiber areas. Given the colocalization of Xin and MyoD, we isolated single myofibers from infected muscles to investigate the effect of silencing Xin on SC function. Relative to Control, SC activation, but not proliferation, was significantly impaired in Xin-shRNA-infected muscles. To determine whether Xin affects the G0-G1 transition, cell cycle reentry was assessed on infected C2C12 myoblasts using a methylcellulose assay. No difference in reentry was noted between groups, suggesting that Xin contributes to SC activation by means other than affecting G0-G1 transition. Together these data demonstrate a critical role for Xin in SC activation and reduction in Xin expression results in attenuated skeletal muscle repair.

  8. The role of physical activity in the management of impaired glucose tolerance: a systematic review

    PubMed Central

    Khunti, K.; Bull, F.; Gorely, T.; Davies, M. J.

    2007-01-01

    Although physical activity is widely reported to reduce the risk of type 2 diabetes in individuals with prediabetes, few studies have examined this issue independently of other lifestyle modifications. The aim of this review is to conduct a systematic review of controlled trials to determine the independent effect of exercise on glucose levels and risk of type 2 diabetes in people with prediabetes (IGT and/or IFG). A detailed search of MEDLINE (1966–2006) and EMBASE (1980–2006) found 279 potentially relevant studies, eight of which met the inclusion criteria for this review. All eight studies were controlled trials in individuals with impaired glucose tolerance. Seven studies used a multi-component lifestyle intervention that included exercise, diet and weight loss goals and one used a structured exercise training intervention. Four studies used the incidence of diabetes over the course of the study as an outcome variable and four relied on 2-h plasma glucose as an outcome measure. In the four studies that measured the incidence of diabetes as an outcome, the risk of diabetes was reduced by approximately 50% (range 42–63%); as these studies reported only small changes in physical activity levels, the reduced risk of diabetes is likely to be attributable to factors other than physical activity. In the remaining four studies, only one reported significant improvements in 2-h plasma glucose even though all but one reported small to moderate increases in maximal oxygen uptake. These results indicate that the contribution of physical activity independent of dietary or weight loss changes to the prevention of type 2 diabetes in people with prediabetes is equivocal. PMID:17415549

  9. Criterion-Related Validity of the Short Form of the International Physical Activity Questionnaire in Adults Who Are Blind

    ERIC Educational Resources Information Center

    Marmeleira, Jose; Laranjo, Luis; Marques, Olga; Batalha, Nuno

    2013-01-01

    This article describes the results of a recommendation from the World Health Organization (2004) that it was important to examine whether high-risk groups meet the current general recommendation of at least 30 minutes of moderate or greater physical activity per day. Doing so required an accurate measurement of physical activity for supporting the…

  10. Development of new physical activity and sedentary behavior change self-efficacy questionnaires using item response modeling

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Theoretically, increased levels of physical activity self-efficacy (PASE) should lead to increased physical activity, but few studies have reported this effect among youth. This failure may be at least partially attributable to measurement limitations. In this study, Item Response Modeling (IRM) was...

  11. M-CSF receptor mutations in hereditary diffuse leukoencephalopathy with spheroids impair not only kinase activity but also surface expression

    SciTech Connect

    Hiyoshi, Masateru; Hashimoto, Michihiro; Yukihara, Mamiko; Bhuyan, Farzana; Suzu, Shinya

    2013-11-01

    Highlights: •Many mutations were identified in Fms as a putative genetic cause of HDLS. •All of the mutations tested severely impair the kinase activity. •Most of the mutations also impair the trafficking to the cell surface. •These defects further suggest that HDLS is caused by a loss of Fms function. -- Abstract: The tyrosine kinase Fms, the cell surface receptor for M-CSF and IL-34, is critical for microglial proliferation and differentiation in the brain. Recently, a number of mutations have been identified in Fms as a putative genetic cause of hereditary diffuse leukoencephalopathy with spheroids (HDLS), implying an important role of microglial dysfunction in HDLS pathogenesis. In this study, we initially confirmed that 11 mutations, which reside within the ATP-binding or major tyrosine kinase domain, caused a severe impairment of ligand-induced Fms auto-phosphorylation. Intriguingly, we found that 10 of the 11 mutants also showed a weak cell surface expression, which was associated with a concomitant increase in the low molecular weight hypo-N-glycosylated immature gp130Fms-like species. Indeed, the mutant proteins heavily accumulated to the Golgi-like perinuclear regions. These results indicate that all of the Fms mutations tested severely impair the kinase activity and most of the mutations also impair the trafficking to the cell surface, further suggesting that HDLS is caused by the loss of Fms function.

  12. Liking and wanting of drug and nondrug rewards in active cocaine users: the STRAP-R questionnaire

    SciTech Connect

    Goldstein, R.Z.; Goldstein, R.Z.; Woicik, P.A..; Moeller, S.J.; Telang, F.; Jayne, M.; Wong, C.; Wang, G-J.; Fowler, J.S.; Volkow, N.D.

    2008-10-01

    Few studies have examined the subjective value attributed to drug rewards specifically as it compares with the value attributed to primary non-drug rewards in addicted individuals. The objective of this study is to assess liking and wanting of expected drug rewards as compared to food and sex while respondents report about three different situations (current, and hypothetical in general, and under drug influence). In all, 20 cocaine-addicted individuals (mean abstinence = 2 days) and 20 healthy control subjects were administered the STRAP-R (Sensitivity To Reinforcement of Addictive and other Primary Rewards) questionnaire after receiving an oral dose of the dopamine agonist methylphenidate (20 mg) or placebo. The reinforcers relative value changed within the addicted sample when reporting about the under drug influence situation (drug > food; otherwise, drug < food). This change was highest in the addicted individuals with the youngest age of cocaine use onset. Moreover, drug wanting exceeded drug liking in the addicted subjects when reporting about this situation during methylphenidate. Thus, cocaine-addicted individuals assign the highest subjective valence to drug rewards but only when recalling cue-related situations. When recalling this situation, they also report higher drug wanting than hedonic liking, a motivational shift that was only significant during methylphenidate. Together, these valence shifts may underlie compulsive stimulant abuse upon pharmacological or behavioural cue exposure in addicted individuals. Additional studies are required to assess the reliability of the STRAP-R in larger samples and to examine its validity in measuring the subjective value attributed to experienced reinforcers or in predicting behaviour.

  13. Sexual Activity of Young Adults Who Are Visually Impaired and the Need for Effective Sex Education

    ERIC Educational Resources Information Center

    Kelly, Stacy M.; Kapperman, Gaylen

    2012-01-01

    Introduction: Little research has been reported on all aspects of sexuality as it pertains to individuals with visual impairments. This article analyzes data on the sexual experiences of young adults who are visually impaired and young adults without disabilities. Methods: The authors conducted a secondary analysis of the National Longitudinal…

  14. HIV-1 Nef Impairs Key Functional Activities in Human Macrophages through CD36 Downregulation

    PubMed Central

    Olivetta, Eleonora; Tirelli, Valentina; Chiozzini, Chiara; Scazzocchio, Beatrice; Romano, Ignazio; Arenaccio, Claudia; Sanchez, Massimo

    2014-01-01

    Monocytes and macrophages utilize the class A and B scavenger receptors to recognize and perform phagocytosis of invading microbes before a pathogen-specific immune response is generated. HIV-1 Nef protein affects the innate immune system impairing oxidative burst response and phagocytic capacity of macrophages. Our data show that exogenous recombinant myristoylated Nef protein induces a marked CD36 downregulation in monocytes from Peripheral Blood Mononuclear Cells, in Monocyte-Derived Macrophages (MDMs) differentiated by cytokines and in MDMs contained in a mixed culture obtained expanding PBMCs under Human Erythroid Massive Amplification condition. Under the latter culture condition we identify three main populations after 6 days of expansion: lymphocytes (37.8±14.7%), erythroblasts (46.7±6.1%) and MDMs (15.7±7.5%). The Nef addition to the cell culture significantly downregulates CD36 expression in MDMs, but not in erythroid cells. Furthermore, CD36 inhibition is highly specific since it does not modify the expression levels of other MDM markers such as CD14, CD11c, CD86, CD68, CD206, Toll-like Receptor 2 and Toll-like Receptor 4. Similar results were obtained in MDMs infected with VSV-G pseudotyped HIV-1-expressing Nef. The reduced CD36 membrane expression is associated with decrease of correspondent CD36 mRNA transcript. Furthermore, Nef-induced CD36 downregulation is linked to both impaired scavenger activity with reduced capability to take up oxidized lipoproteins and to significant decreased phagocytosis of fluorescent beads and GFP-expressing Salmonella tiphymurium. In addition we observed that Nef induces TNF-α release in MDMs. Although these data suggest a possible involvement of TNF-α in mediating Nef activity, our results exclude a possible relationship between Nef-induced TNF-α release and Nef-mediated CD36 downregulation. The present work shows that HIV-1 Nef protein may have a role in the strategies elaborated by HIV-1 to alter pathogen

  15. Parental Influence and the Attraction to Physical Activity for Youths Who Are Visually Impaired at a Residential-Day School

    ERIC Educational Resources Information Center

    Ward, Stefan; Farnsworth, Charles; Babkes-Stellino, Megan; Perrett, Jamis

    2011-01-01

    The study reported here investigated social influences on the attraction to physical activity and perceptions of physical competence among youths with visual impairments. The study was a qualitative case study of a residential-day school in a western state. Eight youths (5 boys and 3 girls) aged 10-18 were interviewed. The participants were chosen…

  16. Interest of active posturography to detect age-related and early Parkinson's disease-related impairments in mediolateral postural control.

    PubMed

    Bonnet, Cédrick T; Delval, Arnaud; Defebvre, Luc

    2014-11-15

    Patients with Parkinson's disease display impairments of postural control most particularly in active, challenging conditions. The objective of the present study was to analyze early signs of disease-related and also age-related impairments in mediolateral body extension and postural control. Fifty-five participants (18 Hoehn and Yahr stage 2 patients in the off-drug condition, 18 healthy elderly control subjects, and 19 young adults) were included in the study. The participants performed a quiet stance task and two active tasks that analyzed the performance in mediolateral body motion: a limit of stability and a rhythmic weight shift task. As expected, the patients displayed significantly lower and slower body displacement (head, neck, lower back, center of pressure) than elderly control subjects when performing the two body excursion tasks. However, the behavioral variability in both tasks was similar between the groups. Under these active conditions, the patients showed significantly lower contribution of the hip postural control mechanisms compared with the elderly control subjects. Overall, the patients seemed to lower their performance in order to prevent a mediolateral postural instability. However, these patients, at an early stage of their disease, were not unstable in quiet stance. Complementarily, elderly control subjects displayed slower body performance than young adults, which therefore showed an additional age-related impairment in mediolateral postural control. Overall, the study illustrated markers of age-related and Parkinson's disease impairments in mediolateral postural control that may constrain everyday activities in elderly adults and even more in patients with Parkinson's disease.

  17. The Prevalence of Binge Eating Disorder and Its Relationship to Work and Classroom Productivity and Activity Impairment

    ERIC Educational Resources Information Center

    Filipova, Anna A.; Stoffel, Cheri L.

    2016-01-01

    Objective: The study aimed to determine the prevalence of binge eating disorder on university campus, its associations with health risk factors, and its associations with work and classroom productivity and activity impairment, adjusted for health risk factors. Participants: The study was conducted at a public midwestern university in the United…

  18. Nootropic activity of Crataeva nurvala Buch-Ham against scopolamine induced cognitive impairment

    PubMed Central

    Bhattacharjee, Atanu; Shashidhara, Shastry Chakrakodi; Saha, Santanu

    2015-01-01

    Loss of cognition is one of the age related mental problems and a characteristic symptom of neurodegenerative disorders like Alzheimer’s. Crataeva nurvala Buch-Ham, a well explored traditional Indian medicinal plant of Westernghats, is routinely used as folkloric medicine to treat various ailments in particular urolithiasis and neurological disorders associated with cognitive dysfunction. The objective of the study was to evaluate the nootropic activity of Crataeva nurvala Buch-Ham stem bark in different learning and memory paradigm viz. Elevated plus maze and Y-maze against scopolamine induced cognitive impairment. Moreover, to elucidate possible mechanism, we studied the influence of Crataeva nurvala ethanolic extract on central cholinergic activity via estimating the whole brain acetyl cholinesterase enzyme. Ethanolic extracts of Crataeva nurvala (100, 200 and 400 mg/kg body weight) were administered to adult Wistar rats for successive seven days and the acquisition, retention and retrieval of spatial recognition memory was determined against scopolamine (1 mg/kg, i.p.) induced amnesia through exteroceptive behavioral models viz. Elevated plus maze and Y-maze models. Further, whole brain acetyl cholinesterase enzyme was estimated through Ellman’s method. Pretreatment with Crataeva nurvala ethanolic extract significantly improved spatial learning and memory against scopolamine induced amnesia. Moreover, Crataeva nurvala extract decreased rat brain acetyl cholinesterase activity in a dose dependent manner and comparable to the standard drug Piracetam. The results indicate that ethanolic extract of Crataeva nurvala might be a useful as nootropic agent to delay the onset and reduce the severity of symptoms associated with dementia and Alzheimer’s disease. The underlying mechanism of action of its nootropic potentiality might be attributed to its anticholinesterase property. PMID:27065767

  19. The Diabetes Self-Management Questionnaire (DSMQ): development and evaluation of an instrument to assess diabetes self-care activities associated with glycaemic control

    PubMed Central

    2013-01-01

    Background Though several questionnaires on self-care and regimen adherence have been introduced, the evaluations do not always report consistent and substantial correlations with measures of glycaemic control. Small ability to explain variance in HbA1c constitutes a significant limitation of an instrument’s use for scientific purposes as well as clinical practice. In order to assess self-care activities which can predict glycaemic control, the Diabetes Self-Management Questionnaire (DSMQ) was designed. Methods A 16 item questionnaire to assess self-care activities associated with glycaemic control was developed, based on theoretical considerations and a process of empirical improvements. Four subscales, ‘Glucose Management’ (GM), ‘Dietary Control’ (DC), ‘Physical Activity’ (PA), and ‘Health-Care Use’ (HU), as well as a ‘Sum Scale’ (SS) as a global measure of self-care were derived. To evaluate its psychometric quality, 261 patients with type 1 or 2 diabetes were assessed with the DSMQ and an established analogous scale, the Summary of Diabetes Self-Care Activities Measure (SDSCA). The DSMQ’s item and scale characteristics as well as factorial and convergent validity were analysed, and its convergence with HbA1c was compared to the SDSCA. Results The items showed appropriate characteristics (mean item-total-correlation: 0.46 ± 0.12; mean correlation with HbA1c: -0.23 ± 0.09). Overall internal consistency (Cronbach’s alpha) was good (0.84), consistencies of the subscales were acceptable (GM: 0.77; DC: 0.77; PA: 0.76; HU: 0.60). Principal component analysis indicated a four factor structure and confirmed the designed scale structure. Confirmatory factor analysis indicated appropriate fit of the four factor model. The DSMQ scales showed significant convergent correlations with their parallel SDSCA scales (GM: 0.57; DC: 0.52; PA: 0.58; HU: n/a; SS: 0.57) and HbA1c (GM: -0.39; DC: -0.30; PA: -0.15; HU: -0.22; SS: -0.40). All correlations with

  20. The Manchester Respiratory Activities of Daily Living questionnaire for use in COPD patients: translation into Portuguese and cross-cultural adaptation for use in Brazil

    PubMed Central

    Junkes-Cunha, Maíra; Mayer, Anamaria Fleig; Reis, Cardine; Yohannes, Abebaw M.; Maurici, Rosemeri

    2016-01-01

    Objective : To translate The Manchester Respiratory Activities of Daily Living (MRADL) questionnaire into Portuguese and to create a version of the MRADL that is cross-culturally adapted for use in Brazil. Methods : The English-language version of the MRADL was translated into Portuguese by two health care researchers who were fluent in English. A consensus version was obtained by other two researchers and a pulmonologist. That version was back-translated into English by another translator who was a native speaker of English and fluent in Portuguese. The cognitive debriefing process consisted in having 10 COPD patients complete the translated questionnaire in order to test its understandability, clarity, and acceptability in the target population. On the basis of the results, the final Portuguese-language version of the MRADL was produced and approved by the committee and one of the authors of the original questionnaire. Results : The author of the MRADL questioned only a few items in the translated version, and some changes were made to the mobility and personal hygiene domains. Cultural differences regarding the domestic activities domain were found, in particular regarding the item "Do you have the ability to do a full clothes wash and hang them out to dry?", due to socioeconomic and climatic issues. The item "Do you take care of your garden?" was questioned by the participants who lived in apartments, being modified to "Do you take care of your garden or plants in your apartment?" Conclusions : The final Portuguese-language version of the MRADL adapted for use in Brazil was found to be easy to understand and easily applied. PMID:26982036

  1. Retinal Structures and Visual Cortex Activity are Impaired Prior to Clinical Vision Loss in Glaucoma

    PubMed Central

    Murphy, Matthew C.; Conner, Ian P.; Teng, Cindy Y.; Lawrence, Jesse D.; Safiullah, Zaid; Wang, Bo; Bilonick, Richard A.; Kim, Seong-Gi; Wollstein, Gadi; Schuman, Joel S.; Chan, Kevin C.

    2016-01-01

    Glaucoma is the second leading cause of blindness worldwide and its pathogenesis remains unclear. In this study, we measured the structure, metabolism and function of the visual system by optical coherence tomography and multi-modal magnetic resonance imaging in healthy subjects and glaucoma patients with different degrees of vision loss. We found that inner retinal layer thinning, optic nerve cupping and reduced visual cortex activity occurred before patients showed visual field impairment. The primary visual cortex also exhibited more severe functional deficits than higher-order visual brain areas in glaucoma. Within the visual cortex, choline metabolism was perturbed along with increasing disease severity in the eye, optic radiation and visual field. In summary, this study showed evidence that glaucoma deterioration is already present in the eye and the brain before substantial vision loss can be detected clinically using current testing methods. In addition, cortical cholinergic abnormalities are involved during trans-neuronal degeneration and can be detected non-invasively in glaucoma. The current results can be of impact for identifying early glaucoma mechanisms, detecting and monitoring pathophysiological events and eye-brain-behavior relationships, and guiding vision preservation strategies in the visual system, which may help reduce the burden of this irreversible but preventable neurodegenerative disease. PMID:27510406

  2. Disrupting pre-SMA activity impairs facial happiness recognition: an event-related TMS study.

    PubMed

    Rochas, Vincent; Gelmini, Lauriane; Krolak-Salmon, Pierre; Poulet, Emmanuel; Saoud, Mohamed; Brunelin, Jerome; Bediou, Benoit

    2013-07-01

    It has been suggested that the left pre-supplementary motor area (pre-SMA) could be implicated in facial emotion expression and recognition, especially for laughter/happiness. To test this hypothesis, in a single-blind, randomized crossover study, we investigated the impact of transcranial magnetic stimulation (TMS) on performances of 18 healthy participants during a facial emotion recognition task. Using a neuronavigation system based on T1-weighted magnetic resonance imaging of each participant, TMS (5 pulses, 10 Hz) was delivered over the pre-SMA or the vertex (control condition) in an event-related fashion after the presentation of happy, fear, and angry faces. Compared with performances during vertex stimulation, we observed that TMS applied over the left pre-SMA specifically disrupted facial happiness recognition (FHR). No difference was observed between the 2 conditions neither for fear and anger recognition nor for reaction times (RT). Thus, interfering with pre-SMA activity with event-related TMS after stimulus presentation produced a selective impairment in the recognition of happy faces. These findings provide new insights into the functional implication of the pre-SMA in FHR, which may rely on the mirror properties of pre-SMA neurons.

  3. Effects of Exercise Interventions and Physical Activity Behavior on Cancer Related Cognitive Impairments: A Systematic Review

    PubMed Central

    Zimmer, Philipp; Baumann, Freerk T.; Oberste, Max; Wright, Peter; Garthe, Alexander; Schenk, Alexander; Elter, Thomas; Galvao, Daniel A.; Bloch, Wilhelm; Hübner, Sven T.; Wolf, Florian

    2016-01-01

    This systematic review analyzes current data on effects of exercise interventions and physical activity behavior on objective and subjective cancer related cognitive impairments (CRCI). Out of the 19 studies which met all inclusion criteria, five RCTs investigated rodents, whereas the other 14 trials explored humans and these included six RCTs, one controlled trial, two prospective noncontrolled trials, one case series, one observational study, and three cross-sectional studies. The results from animal models revealed positive effects of exercise during and after chemotherapy or radiation on structural alterations of the central nervous system, physiological as well as neuropsychological outcomes. The overall study quality in patient studies was poor. The current data on intervention studies showed preliminary positive effects of Asian-influenced movement programs (e.g., Yoga) with benefits on self-perceived cognitive functions as well as a reduction of chronic inflammation for breast cancer patients in the aftercare. Exercise potentially contributes to the prevention and rehabilitation of CRCI. Additional RCTs with standardized neuropsychological assessments and controlling for potential confounders are needed to confirm and expand preliminary findings. PMID:27144158

  4. Validity and reliability of questionnaires measuring physical activity self-efficacy, enjoyment, social support among Hong Kong Chinese children

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Physical activity (PA) correlates have not been extensively studied in Hong Kong children. The aim of this study is to assess the validity and reliability of translated scales to measure PA related self-efficacy, enjoyment and social support in Hong Kong Chinese children. Sample 1 (n=273, aged 8–12 ...

  5. Age-related decline of autocrine pituitary adenylate cyclase-activating polypeptide impairs angiogenic capacity of rat cerebromicrovascular endothelial cells.

    PubMed

    Banki, Eszter; Sosnowska, Danuta; Tucsek, Zsuzsanna; Gautam, Tripti; Toth, Peter; Tarantini, Stefano; Tamas, Andrea; Helyes, Zsuzsanna; Reglodi, Dora; Sonntag, William E; Csiszar, Anna; Ungvari, Zoltan

    2015-06-01

    Aging impairs angiogenic capacity of cerebromicrovascular endothelial cells (CMVECs) promoting microvascular rarefaction, but the underlying mechanisms remain elusive. PACAP is an evolutionarily conserved neuropeptide secreted by endothelial cells and neurons, which confers important antiaging effects. To test the hypothesis that age-related changes in autocrine PACAP signaling contributes to dysregulation of endothelial angiogenic capacity, primary CMVECs were isolated from 3-month-old (young) and 24-month-old (aged) Fischer 344 x Brown Norway rats. In aged CMVECs, expression of PACAP was decreased, which was associated with impaired capacity to form capillary-like structures, impaired adhesiveness to collagen (assessed using electric cell-substrate impedance sensing [ECIS] technology), and increased apoptosis (caspase3 activity) when compared with young cells. Overexpression of PACAP in aged CMVECs resulted in increased formation of capillary-like structures, whereas it did not affect cell adhesion. Treatment with recombinant PACAP also significantly increased endothelial tube formation and inhibited apoptosis in aged CMVECs. In young CMVECs shRNA knockdown of autocrine PACAP expression significantly impaired tube formation capacity, mimicking the aging phenotype. Cellular and mitochondrial reactive oxygen species production (dihydroethidium and MitoSox fluorescence, respectively) were increased in aged CMVECs and were unaffected by PACAP. Collectively, PACAP exerts proangiogenic effects and age-related dysregulation of autocrine PACAP signaling may contribute to impaired angiogenic capacity of CMVECs in aging.

  6. Age-Related Decline of Autocrine Pituitary Adenylate Cyclase-Activating Polypeptide Impairs Angiogenic Capacity of Rat Cerebromicrovascular Endothelial Cells

    PubMed Central

    Banki, Eszter; Sosnowska, Danuta; Tucsek, Zsuzsanna; Gautam, Tripti; Toth, Peter; Tarantini, Stefano; Tamas, Andrea; Helyes, Zsuzsanna; Reglodi, Dora; Sonntag, William E.; Csiszar, Anna

    2015-01-01

    Aging impairs angiogenic capacity of cerebromicrovascular endothelial cells (CMVECs) promoting microvascular rarefaction, but the underlying mechanisms remain elusive. PACAP is an evolutionarily conserved neuropeptide secreted by endothelial cells and neurons, which confers important antiaging effects. To test the hypothesis that age-related changes in autocrine PACAP signaling contributes to dysregulation of endothelial angiogenic capacity, primary CMVECs were isolated from 3-month-old (young) and 24-month-old (aged) Fischer 344 x Brown Norway rats. In aged CMVECs, expression of PACAP was decreased, which was associated with impaired capacity to form capillary-like structures, impaired adhesiveness to collagen (assessed using electric cell-substrate impedance sensing [ECIS] technology), and increased apoptosis (caspase3 activity) when compared with young cells. Overexpression of PACAP in aged CMVECs resulted in increased formation of capillary-like structures, whereas it did not affect cell adhesion. Treatment with recombinant PACAP also significantly increased endothelial tube formation and inhibited apoptosis in aged CMVECs. In young CMVECs shRNA knockdown of autocrine PACAP expression significantly impaired tube formation capacity, mimicking the aging phenotype. Cellular and mitochondrial reactive oxygen species production (dihydroethidium and MitoSox fluorescence, respectively) were increased in aged CMVECs and were unaffected by PACAP. Collectively, PACAP exerts proangiogenic effects and age-related dysregulation of autocrine PACAP signaling may contribute to impaired angiogenic capacity of CMVECs in aging. PMID:25136000

  7. Is there a role for physical activity in preventing cognitive decline in people with mild cognitive impairment?

    PubMed

    Barber, Sally E; Clegg, Andrew P; Young, John B

    2012-01-01

    Mild cognitive impairment (MCI) is a common clinical syndrome that identifies people at high risk of developing dementia. Although treatments for MCI are currently unavailable, preliminary evidence has identified potential neuro-protective effects of physical activity, which may lead to improved outcomes. However, there is uncertainty regarding the effectiveness, feasibility and acceptability of this treatment strategy. These uncertainties require further investigation before physical activity interventions can be recommended for routine care.

  8. Impaired NK Cell Activation and Chemotaxis toward Dendritic Cells Exposed to Complement-Opsonized HIV-1.

    PubMed

    Ellegård, Rada; Crisci, Elisa; Andersson, Jonas; Shankar, Esaki M; Nyström, Sofia; Hinkula, Jorma; Larsson, Marie

    2015-08-15

    Mucosa resident dendritic cells (DCs) may represent one of the first immune cells that HIV-1 encounters during sexual transmission. The virions in body fluids can be opsonized with complement factors because of HIV-mediated triggering of the complement cascade, and this appears to influence numerous aspects of the immune defense targeting the virus. One key attribute of host defense is the ability to attract immune cells to the site of infection. In this study, we investigated whether the opsonization of HIV with complement (C-HIV) or a mixture of complement and Abs (CI-HIV) affected the cytokine and chemokine responses generated by DCs, as well as their ability to attract other immune cells. We found that the expression levels of CXCL8, CXCL10, CCL3, and CCL17 were lowered after exposure to either C-HIV or CI-HIV relative to free HIV (F-HIV). DCs exposed to F-HIV induced higher cell migration, consisting mainly of NK cells, compared with opsonized virus, and the chemotaxis of NK cells was dependent on CCL3 and CXCL10. NK cell exposure to supernatants derived from HIV-exposed DCs showed that F-HIV induced phenotypic activation (e.g., increased levels of TIM3, CD69, and CD25) and effector function (e.g., production of IFNγ and killing of target cells) in NK cells, whereas C-HIV and CI-HIV did not. The impairment of NK cell recruitment by DCs exposed to complement-opsonized HIV and the lack of NK activation may contribute to the failure of innate immune responses to control HIV at the site of initial mucosa infection.

  9. Targeted STIM deletion impairs calcium homeostasis, NFAT activation, and growth of smooth muscle

    PubMed Central

    Mancarella, Salvatore; Potireddy, Santhi; Wang, Youjun; Gao, Hui; Gandhirajan, Rajesh Kumar; Autieri, Michael; Scalia, Rosario; Cheng, Zhongjian; Wang, Hong; Madesh, Muniswamy; Houser, Steven R.; Gill, Donald L.

    2013-01-01

    The Ca2+-sensing stromal interaction molecule (STIM) proteins are crucial Ca2+ signal coordinators. Cre-lox technology was used to generate smooth muscle (sm)-targeted STIM1-, STIM2-, and double STIM1/STIM2-knockout (KO) mouse models, which reveal the essential role of STIM proteins in Ca2+ homeostasis and their crucial role in controlling function, growth, and development of smooth muscle cells (SMCs). Compared to Cre+/− littermates, sm-STIM1-KO mice showed high mortality (50% by 30 d) and reduced bodyweight. While sm-STIM2-KO was without detectable phenotype, the STIM1/STIM double-KO was perinatally lethal, revealing an essential role of STIM1 partially rescued by STIM2. Vascular and intestinal smooth muscle tissues from sm-STIM1-KO mice developed abnormally with distended, thinned morphology. While depolarization-induced aortic contraction was unchanged in sm-STIM1-KO mice, α1-adrenergic-mediated contraction was 26% reduced, and store-dependent contraction almost eliminated. Neointimal formation induced by carotid artery ligation was suppressed by 54%, and in vitro PDGF-induced proliferation was greatly reduced (79%) in sm-STIM1-KO. Notably, the Ca2+ store-refilling rate in STIM1-KO SMCs was substantially reduced, and sustained PDGF-induced Ca2+ entry was abolished. This defective Ca2+ homeostasis prevents PDGF-induced NFAT activation in both contractile and proliferating SMCs. We conclude that STIM1-regulated Ca2+ homeostasis is crucial for NFAT-mediated transcriptional control required for induction of SMC proliferation, development, and growth responses to injury.—Mancarella, S., Potireddy, S., Wang, Y., Gao, H., Gandhirajan, K., Autieri, M., Scalia, R., Cheng, Z., Wang, H., Madesh, M., Houser, S. R., Gill, D. L. Targeted STIM deletion impairs calcium homeostasis, NFAT activation, and growth of smooth muscle. PMID:23159931

  10. Validity of dietary eicosapentaenoic acid and docosahexaenoic acid intakes determined by interviewer-administrated food frequency questionnaire among older adults with mild-to-moderate cognitive impairment or dementia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Epidemiological research is increasingly focused on elderly populations, many of whom exhibit mild to moderate cognitive impairments. This presents a challenge for collection and interpretation of self-reported dietary data. There are few reports on the impact of cognitive function and dementia o...

  11. Behavioral Assessment: Questionnaires.

    ERIC Educational Resources Information Center

    Wilson, C. Chrisman

    1980-01-01

    This is a general discussion of the validity, reliability, function, and format of questionnaires designed to measure problem behavior, noncompliance, anxiety, social interaction, hyperactivity, drug use, and sexual behavior. Commonly used questionnaires are cited. (CP)

  12. Memory Impairment in Korsakoff's Psychosis: A Correlation with Brain Noradrenergic Activity.

    ERIC Educational Resources Information Center

    McEntee, William J.; Mair, Robert G.

    1978-01-01

    The concentration of the primary brain metabolite of norepinephrine is diminished in the lumbar spinal fluid of patients with Korsakoff's syndrome. The extent of its reduction is correlated with measures of memory impairment. (BB)

  13. Conversion of Questionnaire Data

    SciTech Connect

    Powell, Danny H; Elwood Jr, Robert H

    2011-01-01

    During the survey, respondents are asked to provide qualitative answers (well, adequate, needs improvement) on how well material control and accountability (MC&A) functions are being performed. These responses can be used to develop failure probabilities for basic events performed during routine operation of the MC&A systems. The failure frequencies for individual events may be used to estimate total system effectiveness using a fault tree in a probabilistic risk analysis (PRA). Numeric risk values are required for the PRA fault tree calculations that are performed to evaluate system effectiveness. So, the performance ratings in the questionnaire must be converted to relative risk values for all of the basic MC&A tasks performed in the facility. If a specific material protection, control, and accountability (MPC&A) task is being performed at the 'perfect' level, the task is considered to have a near zero risk of failure. If the task is performed at a less than perfect level, the deficiency in performance represents some risk of failure for the event. As the degree of deficiency in performance increases, the risk of failure increases. If a task that should be performed is not being performed, that task is in a state of failure. The failure probabilities of all basic events contribute to the total system risk. Conversion of questionnaire MPC&A system performance data to numeric values is a separate function from the process of completing the questionnaire. When specific questions in the questionnaire are answered, the focus is on correctly assessing and reporting, in an adjectival manner, the actual performance of the related MC&A function. Prior to conversion, consideration should not be given to the numeric value that will be assigned during the conversion process. In the conversion process, adjectival responses to questions on system performance are quantified based on a log normal scale typically used in human error analysis (see A.D. Swain and H.E. Guttmann

  14. Autophagy ameliorates cognitive impairment through activation of PVT1 and apoptosis in diabetes mice.

    PubMed

    Li, Zhigui; Hao, Shuang; Yin, Hongqiang; Gao, Jing; Yang, Zhuo

    2016-05-15

    The underlying mechanisms of cognitive impairment in diabetes remain incompletely characterized. Here we show that the autophagic inhibition by 3-methyladenine (3-MA) aggravates cognitive impairment in streptozotocin-induced diabetic mice, including exacerbation of anxiety-like behaviors and aggravation in spatial learning and memory, especially the spatial reversal memory. Further neuronal function identification confirmed that both long term potentiation (LTP) and depotentiation (DPT) were exacerbated by autophagic inhibition in diabetic mice, which indicating impairment of synaptic plasticity. However, no significant change of pair-pulse facilitation (PPF) was recorded in diabetic mice with autophagic suppression compared with the diabetic mice, which indicated that presynaptic function was not affected by autophagic inhibition in diabetes. Subsequent hippocampal neuronal cell death analysis showed that the apoptotic cell death, but not the regulated necrosis, significantly increased in autophagic suppression of diabetic mice. Finally, molecular mechanism that may lead to cell death was identified. The long non-coding RNA PVT1 (plasmacytoma variant translocation 1) expression was analyzed, and data revealed that PVT1 was decreased significantly by 3-MA in diabetes. These findings show that PVT1-mediated autophagy may protect hippocampal neurons from impairment of synaptic plasticity and apoptosis, and then ameliorates cognitive impairment in diabetes. These intriguing findings will help pave the way for exciting functional studies of autophagy in cognitive impairment and diabetes that may alter the existing paradigms.

  15. Questionnaire Construction Manual

    DTIC Science & Technology

    1976-07-01

    Questionnaire Results A. Overview 8. Social De ■* ability and Acquiescence Response Sets C. Other Response Sets or Errors D. Effects of General Pretest...Attitudes of Respondents E. Effects of Demographic Characteristics of Responses XIII. Evaluating Questionnaire Results A. Overview B. Scoring...34questionnaire" refers to an ordered arrangement of items (questions, in effect ) intended to elicit the evaluations, judgments, comparisons, attitudes

  16. Decreasing nicotinic receptor activity and the spatial learning impairment caused by the NMDA glutamate antagonist dizocilpine in rats

    PubMed Central

    Burke, Dennis A.; Heshmati, Pooneh; Kholdebarin, Ehsan; Levin, Edward D.

    2014-01-01

    Nicotinic systems have been shown by a variety of studies to be involved in cognitive function. Nicotinic receptors have an inherent property to become desensitized after activation. The relative role of nicotinic receptor activation vs. net receptor inactivation by desensitization in the cognitive effects of nicotinic drugs remains to be fully understood. In these studies, we tested the effects of the α7 nicotinic receptor antagonist methyllycaconitine (MLA), the α4β2 nicotinic receptor antagonist dihydro-β-erythroidine (DHβE), the nonspecific nicotinic channel blocker mecamylamine and the α4β2 nicotinic receptor desensitizing agent sazetidine-A on learning in a repeated acquisition test. Adult female Sprague-Dawley rats were trained on a repeated acquisition learning procedure in an 8-arm radial maze. MLA (1–4 mg/kg), DHβE (1–4 mg/kg), mecamylamine (0.125–0.5 mg/kg) or sazetidine-A (1 and 3 mg/kg) were administered in four different studies either alone or together with the NMDA glutamate antagonist dizocilpine (0.05 and 0.10 mg/kg). MLA significantly counteracted the learning impairment caused by dizocilpine. The overall choice accuracy impairment caused by dizocilpine was significantly attenuated by co-administration of DHβE. Low doses of the non-specific nicotinic antagonist mecamylamine also reduced dizocilpine-induced repeated acquisition impairment. Sazetidine-A reversed the accuracy impairment caused by dizocilpine. These studies provide evidence that a net decrease in nicotinic receptor activity can improve learning by attenuating learning impairment induced by NMDA glutamate blockade. This adds to evidence in cognitive tests that nicotinic antagonists can improve cognitive function. Further research characterizing the efficacy and mechanisms underlying nicotinic antagonist and desensitization induced cognitive improvement is warranted. PMID:25064338

  17. HIV Tat Impairs Neurogenesis through Functioning As a Notch Ligand and Activation of Notch Signaling Pathway.

    PubMed

    Fan, Yan; Gao, Xiang; Chen, Jinhui; Liu, Ying; He, Johnny J

    2016-11-02

    Alterations in adult neurogenesis have been noted in the brain of HIV-infected individuals and are likely linked to HIV-associated neurocognitive deficits, including those in learning and memory. But the underlying molecular mechanisms are not fully understood. In the study, we took advantage of doxycycline-inducible and astrocyte-specific HIV-1 Tat transgenic mice (iTat) and determined the relationship between Tat expression and neurogenesis. Tat expression in astrocytes was associated with fewer neuron progenitor cells (NPCs), fewer immature neurons, and fewer mature neurons in the dentate gyrus of the hippocampus of the mouse brain. In vitro NPC-derived neurosphere assays showed that Tat-containing conditioned media from astrocytes or recombinant Tat protein inhibited NPC proliferation and migration and altered NPC differentiation, while immunodepletion of Tat from Tat-containing conditioned media or heat inactivation of recombinant Tat abrogated those effects. Notch signaling downstream gene Hes1 promoter-driven luciferase reporter gene assay and Western blotting showed that recombinant Tat or Tat-containing conditioned media activated Hes1 transcription and protein expression, which were abrogated by Tat heat inactivation, immunodepletion, and cysteine mutation at position 30. Last, Notch signaling inhibitor N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT) significantly rescued Tat-impaired NPC differentiation in vitro and neurogenesis in vivo Together, these results show that Tat adversely affects NPCs and neurogenesis through Notch signaling and point to the potential of developing Notch signaling inhibitors as HIV/neuroAIDS therapeutics.

  18. Lexical Activation during Sentence Comprehension in Adolescents with History of Specific Language Impairment

    PubMed Central

    Borovsky, Arielle; Burns, Erin; Elman, Jeffrey L.; Evans, Julia L.

    2015-01-01

    One remarkable characteristic of speech comprehension in typically developing (TD) children and adults is the speed with which the listener can integrate information across multiple lexical items to anticipate upcoming referents. Although children with Specific Language Impairment (SLI) show lexical deficits (Sheng & McGregor, 2010) and slower speed of processing (Leonard et al., 2007), relatively little is known about how these deficits manifest in real-time sentence comprehension. In this study, we examine lexical activation in the comprehension of simple transitive sentences in adolescents with a history of SLI and age-matched, TD peers. Participants listened to sentences that consisted of the form, Article-Agent-Action-Article-Theme, (e.g., The pirate chases the ship) while viewing pictures of four objects that varied in their relationship to the Agent and Action of the sentence (e.g., Target, Agent-Related, Action-Related, and Unrelated). Adolescents with SLI were as fast as their TD peers to fixate on the sentence’s final item (the Target) but differed in their post-action onset visual fixations to the Action-Related item. Additional exploratory analyses of the spatial distribution of their visual fixations revealed that the SLI group had a qualitatively different pattern of fixations to object images than did the control group. The findings indicate that adolescents with SLI integrate lexical information across words to anticipate likely or expected meanings with the same relative fluency and speed as do their TD peers. However, the failure of the SLI group to show increased fixations to Action-Related items after the onset of the action suggests lexical integration deficits that result in failure to consider alternate sentence interpretations. PMID:24099807

  19. Association of ADAM33 gene polymorphism and arginase activity with susceptibility to ventilatory impairment in wood dust-exposed workers.

    PubMed

    Saad-Hussein, A; Thabet, E H; Taha, M M; Shahy, E M; Mahdy-Abdallah, H

    2016-09-01

    ADAM33 represents an important gene of susceptibility for lung function impairment. This work aimed to evaluate the association between genetic polymorphism of ADAM33 at four single nucleotide polymorphisms (T1, T2, S1, and Q1) and arginase activity with respiratory functions impairment in wood workers. The study was done to compare ventilatory functions and arginase activity of 82 wood workers and 81 controls. Genotyping was determined by using the polymerase chain restriction fragment length polymorphism method. Forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), and peak expiratory flow rate (PEF) of the workers were significantly reduced compared with the controls. T1 single nucleotide polymorphism (SNP) was associated with obvious decline in the FEV1, FVC, and PEF in wood workers, while T2 SNP was associated with decline in FEV1 and PEF. A significant increase in arginase activity was found in T2 and S1 SNPs of the exposed workers. Increase in duration of exposure was correlated with the decline in ventilatory functions. This inverse correlation was significant for pulmonary function indices in AA and GG genotypes of T1 and T2, respectively. Moreover, significance was detected for FVC and FEV1 in AA and GA genotypes of S1 and Q1. A positive correlation between arginase activity and duration of exposure was found to be significant in GG genotype of S1 SNP. An association between ADAM33 gene polymorphism and impaired lung functions was detected in wood dust-exposed workers. Arginase activity may play an associated important role in increasing this impairment in wood workers.

  20. Pterostilbene attenuates lipopolysaccharide-induced learning and memory impairment possibly via inhibiting microglia activation and protecting neuronal injury in mice.

    PubMed

    Hou, Yue; Xie, Guanbo; Miao, Fengrong; Ding, Lingling; Mou, Yanhua; Wang, Lihui; Su, Guangyue; Chen, Guoliang; Yang, Jingyu; Wu, Chunfu

    2014-10-03

    The present study aims to evaluate the effects of pterostilbene on lipopolysaccharide (LPS)-induced learning and memory impairment as well as the possible changes of microglia and neurons. Firstly, learning and memory function was investigated by behavioral tests. Pterostilbene attenuated LPS-induced learning and memory impairment tested by Y-maze and Morris water maze. Secondly, immunohistochemical method was used to study the changes of microglia and neurons. The results showed that pterostilbene produced a significant decrease in the number of Iba-1 and Doublecortin (DCX) positive cells and a significant increase in neuronal nuclear antigen (NeuN)-stained area of neurons in mouse hippocampal compared to the LPS group. Finally, an in vitro study was performed to further confirm the inhibitory effect on microglia activation and protective effect on neurons exerted by pterostilbene. The results demonstrated that pterostilbene significantly inhibited microglia activation, showing the obvious decrease of LPS-induced production of NO, TNF-α and IL-6 in N9 microglial cells. In addition, the viability of SH-SY5Y cells decreased by conditioned media of LPS-activated N9 microglial cells was remarkably recovered by pterostilbene. In summary, the present study demonstrated for the first time that pterostilbene attenuated LPS-induced learning and memory impairment, which may be associated with its inhibitory effect on microglia activation and protective effect on neuronal injury.

  1. Sulforaphane Ameliorates Okadaic Acid-Induced Memory Impairment in Rats by Activating the Nrf2/HO-1 Antioxidant Pathway.

    PubMed

    Dwivedi, Subhash; Rajasekar, N; Hanif, Kashif; Nath, Chandishwar; Shukla, Rakesh

    2016-10-01

    Okadaic acid (OKA) causes memory impairment and attenuates nuclear factor erythroid 2-related factor 2 (Nrf2) along with oxidative stress and neuroinflammation in rats. Sulforaphane (dietary isothiocyanate compound), an activator of Nrf2 signaling, exhibits neuroprotective effects. However, the protective effect of sulforaphane in OKA-induced neurotoxicity remains uninvestigated. Therefore, in the present study, the role of sulforaphane in OKA-induced memory impairment in rats was explored. A significant increased Nrf2 expression in the hippocampus and cerebral cortex was observed in trained (Morris water maze) rats, and a significant decreased Nrf2 expression in memory-impaired (OKA, 200 ng icv) rats indicated its involvement in memory function. Sulforaphane administration (5 and 10 mg/kg, ip, days 1 and 2) ameliorates OKA-induced memory impairment in rats. The treatment also restored Nrf2 and its downstream antioxidant protein expression (GCLC, HO-1) and attenuated oxidative stress (ROS, nitrite, GSH), neuroinflammation (NF-κB, TNF-α, IL-10), and neuronal apoptosis in the cerebral cortex and hippocampus of OKA-treated rats. Further, to determine whether modulation of Nrf2 signaling is responsible for the protective effect of sulforaphane, in vitro, Nrf2 siRNA and its downstream HO-1 inhibition studies were carried out in a rat astrocytoma cell line (C6). The protective effects of sulforaphane were abolished with Nrf2 siRNA and HO-1 inhibition in astrocytes. The results suggest that Nrf2-dependent activation of cellular antioxidant machinery results in sulforaphane-mediated protection against OKA-induced memory impairment in rats. Graphical Abstract ᅟ.

  2. Increased Muscle Sympathetic Nerve Activity and Impaired Executive Performance Capacity in Obstructive Sleep Apnea

    PubMed Central

    Goya, Thiago T.; Silva, Rosyvaldo F.; Guerra, Renan S.; Lima, Marta F.; Barbosa, Eline R.F.; Cunha, Paulo Jannuzzi; Lobo, Denise M.L.; Buchpiguel, Carlos A.; Busatto-Filho, Geraldo; Negrão, Carlos E.; Lorenzi-Filho, Geraldo; Ueno-Pardi, Linda M.

    2016-01-01

    Study Objectives: To investigate muscle sympathetic nerve activity (MSNA) response and executive performance during mental stress in obstructive sleep apnea (OSA). Methods: Individuals with no other comorbidities (age = 52 ± 1 y, body mass index = 29 ± 0.4, kg/m2) were divided into two groups: (1) control (n = 15) and (2) untreated OSA (n = 20) defined by polysomnography. Mini-Mental State of Examination (MMSE) and Inteligence quocient (IQ) were assessed. Heart rate (HR), blood pressure (BP), and MSNA (microneurography) were measured at baseline and during 3 min of the Stroop Color Word Test (SCWT). Sustained attention and inhibitory control were assessed by the number of correct answers and errors during SCWT. Results: Control and OSA groups (apnea-hypopnea index, AHI = 8 ± 1 and 47 ± 1 events/h, respectively) were similar in age, MMSE, and IQ. Baseline HR and BP were similar and increased similarly during SCWT in control and OSA groups. In contrast, baseline MSNA was higher in OSA compared to controls. Moreover, MSNA significantly increased in the third minute of SCWT in OSA, but remained unchanged in controls (P < 0.05). The number of correct answers was lower and the number of errors was significantly higher during the second and third minutes of SCWT in the OSA group (P < 0.05). There was a significant correlation (P < 0.01) between the number of errors in the third minute of SCWT with AHI (r = 0.59), arousal index (r = 0.55), and minimum O2 saturation (r = −0.57). Conclusions: As compared to controls, MSNA is increased in patients with OSA at rest, and further significant MSNA increments and worse executive performance are seen during mental stress. Clinical Trial Registration: URL: http://www.clinicaltrials.gov, registration number: NCT002289625. Citation: Goya TT, Silva RF, Guerra RS, Lima MF, Barbosa ER, Cunha PJ, Lobo DM, Buchpiguel CA, Busatto-Filho G, Negrão CE, Lorenzi-Filho G, Ueno-Pardi LM. Increased muscle sympathetic nerve activity and

  3. Selective impairment of T lymphocyte activation through the T cell receptor/CD3 complex after cytomegalovirus infection.

    PubMed Central

    Timón, M; Arnaiz-Villena, A; Ruiz-Contreras, J; Ramos-Amador, J T; Pacheco, A; Regueiro, J R

    1993-01-01

    Cytomegalovirus (CMV) infection is reported to cause transient immunosuppression in man. In this study we have analysed the effect of CMV on T lymphocyte function in 29 children diagnosed for acute CMV infection. Peripheral blood mononuclear cells (PBMC) obtained from the patients showed a significant specific impairment in their proliferative response to enterotoxins A and C1, to concanavalin A and to the anti-CD3 MoAb OKT3. The impaired responses were corrected with exogenous IL-2. In contrast, stimulation using phytohaemagglutinin, as well as activation signals delivered through the surface molecules CD26 or CD28, elicited normal proliferative responses in CMV PBMC. The results indicate that the T cell anergy associated with CMV infection is restricted to the T cell receptor/CD3 activation pathway. PMID:8403514

  4. Validation of Taiwan Performance-Based Instrumental Activities of Daily Living (TPIADL), a Performance- Based Measurement of Instrumental Activities of Daily Living for Patients with Vascular Cognitive Impairment

    PubMed Central

    Chen, Hui-Mei; Lin, Hsiu-Fen; Huang, Mei-Feng; Chang, Chun-Wei; Yeh, Yi-Chun; Lo, Yi-Ching; Yen, Cheng-Fang; Chen, Cheng-Sheng

    2016-01-01

    Objective Patients with cerebrovascular diseases often presented both cognitive and physical impairment. Disability in everyday functioning involving cognitive impairment among patients may be hard to completely rely on informants’ reports, as their reports may be confounded with physical impairment. The aim of this study was to validate a performance-based measure of functional assessment, the Taiwan Performance-Based Instrumental Activities of Daily Living (TPIADL), for vascular cognitive impairment (VCI) by examining its psychometric properties and diagnostic accuracy. Methods Ninety-seven patients with cerebrovascular diseases, including 30 with vascular dementia (VaD), 28 with mild cognitive impairment and 39 with no cognitive impairment, and 49 healthy control adults were recruited during study period. The TPIADL, as well as the Mini Mental State Examination (MMSE), Lawton-IADL and Barthel Index (BI), were performed. The internal consistency, convergent and criteria validity of the TPIADL were examined. Results Cronbach’s alpha of the TPIADL test was 0.84. The TPIADL scores were significantly correlated with the Lawton IADL (r = –0.587, p <0.01). Notably, the TPIADL had a higher correlation coefficient with the cognitive domain of Lawton IADL (r = –0.663) than with physical domain of Lawton IADL (r = –0.541). The area under the relative operating characteristic curve was 0.888 (95% CI = 0.812–0.965) to differentiate VaD from other groups. The optimal cut-off point of the TPIADL for detecting VaD was 6/7, which gives a sensitivity of 73.3% and a specificity of 84.5%. Conclusion The TPIADL is a brief and sensitive tool for the detection of IADL impairment in patients with VaD. PMID:27851810

  5. Reliability and validity of the modified child and adolescent physical activity and nutrition survey (CAPANS-C) questionnaire examining potential correlates of physical activity participation among Chinese-Australian youth

    PubMed Central

    2014-01-01

    Background To date, few questionnaires examining psychosocial influences of physical activity (PA) participation have been psychometrically tested among Culturally and Linguistically Diverse (CALD) youth. An understanding of these influences may help explain the observed differences in PA among CALD youth. Therefore, this study examined the reliability and predictive validity of a brief self-report questionnaire examining potential psychological and social correlates of physical activity among a sample of Chinese-Australian youth. Methods Two Chinese-weekend cultural schools from eastern metropolitan Melbourne consented to participate in this study. In total, 505 students aged 11 to 16 years were eligible for inclusion in the present study, and of these, 106 students agreed to participate (21% response rate). Participants completed at 37-item self-report questionnaire examining perceived psychological and social influences on physical activity participation twice, with a test–retest interval of 7 days. Predictive validity, internal consistency and test–retest reliability were evaluated using exploratory factor analyses, Cronbach’s α coefficient, and the intraclass correlation coefficient (ICC) respectively. Predictive validity was assessed by correlating responses against duration spent in self-reported moderate-to-vigorous physical activity (MVPA). Results The exploratory factor analysis revealed a nine factor structure, with the majority of factors exhibiting high internal consistency (α ≥ 0.6). In addition, four of the nine factors had an ICC ≥ 0.6. Spearman rank-order correlations coefficients between the nine factors and self-reported minutes spent in MVPA ranged from -0.5 to 0.3 for all participants. Conclusion This is the first study to examine the psychometric properties of a potential psychological and social correlates questionnaire among Chinese-Australian youth. The questionnaire was found to provide reliable estimates on a range

  6. Technical Aids for the Speech-Impaired - Proposal for Research and Development Activities.

    ERIC Educational Resources Information Center

    Lundman, Margita; And Others

    The report gives an account of the needs of the speech impaired for technical aids, and presents a draft of a proposed research and development program coordinated by the Swedish Institute for the Handicapped in collaboration with the International Commission on Technical Aids, Housing and Transportation. The development of communication skills is…

  7. Abnormal Functional Lateralization and Activity of Language Brain Areas in Typical Specific Language Impairment (Developmental Dysphasia)

    ERIC Educational Resources Information Center

    de Guibert, Clement; Maumet, Camille; Jannin, Pierre; Ferre, Jean-Christophe; Treguier, Catherine; Barillot, Christian; Le Rumeur, Elisabeth; Allaire, Catherine; Biraben, Arnaud

    2011-01-01

    Atypical functional lateralization and specialization for language have been proposed to account for developmental language disorders, yet results from functional neuroimaging studies are sparse and inconsistent. This functional magnetic resonance imaging study compared children with a specific subtype of specific language impairment affecting…

  8. D1 Receptor Activation in the Mushroom Bodies Rescues Sleep Loss Induced Learning Impairments in Drosophila

    PubMed Central

    Seugnet, Laurent; Suzuki, Yasuko; Vine, Lucy; Gottschalk, Laura; Shaw, Paul J

    2008-01-01

    Background Extended wakefulness disrupts acquisition of short term memories in mammals. However, the underlying molecular mechanisms triggered by extended waking and restored by sleep are unknown. Moreover, the neuronal circuits that depend on sleep for optimal learning remain unidentified. Results Learning was evaluated using Aversive Phototaxic Suppression (APS). In this task, flies learn to avoid light that is paired with an aversive stimulus (quinine /humidity). We demonstrate extensive homology in sleep deprivation induced learning impairment between flies and humans. Both 6 h and 12 h of sleep deprivation are sufficient to impair learning in Canton-S (Cs) flies. Moreover, learning is impaired at the end of the normal waking-day in direct correlation with time spent awake. Mechanistic studies indicate that this task requires intact mushroom bodies (MBs) and requires the Dopamine D1-like receptor (dDA1). Importantly, sleep deprivation induced learning impairments could be rescued by targeted gene expression of the dDA1 receptor to the MBs. Conclusion These data provide direct evidence that extended wakefulness disrupts learning in Drosophila. These results demonstrate that it is possible to prevent the effects of sleep deprivation by targeting a single neuronal structure and identify cellular and molecular targets adversely affected by extended waking in a genetically tractable model organism. PMID:18674913

  9. Activity-Based Intervention for Multiple-Disabled Visually Impaired People

    ERIC Educational Resources Information Center

    Tellevik, Jon Magne; Elmerskog, Bengt

    2009-01-01

    The article describes assessment, planning and training for people with multiple disabilities and visual impairment (MDVI). The ImPAct MDVI project, an EU Comenius programme, addressed concerns expressed by teachers of children and young people with MDVI as to how they are expected to integrate the diverse curriculum elements and particular skills…

  10. Promotion Considerations for Exercise and Physical Activity in Mentally Impaired, Diseased, and Disabled Older Adults.

    ERIC Educational Resources Information Center

    Frizzell, Linda Bane

    This paper reports evidence indicating that adapted exercise has a preventive effect on the incidence and progression of chronic diseases which are often related to the aging process. Exercise is known to preserve many physiological responses in the healthy elderly, yet those with physical impairments are often discouraged from exercising because…

  11. Individual Literacy Activities with Hearing-Impaired Children in the Preschool Period

    ERIC Educational Resources Information Center

    Karasu, H. Pelin

    2014-01-01

    The ability to recognize sight words, phonological awareness, syntax, semantics, and pragmatic skills begins to develop during the preschool period, and is important for formal reading education. The purpose of this study was to define individualized studies that support the development of literacy skills among hearing-impaired preschool children.…

  12. Physical Activity and Social Engagement Patterns during Physical Education of Youth with Visual Impairments

    ERIC Educational Resources Information Center

    Oh, Hyun-Kyoung; Ozturk, Mehmet A.; Kozub, Francis M.

    2004-01-01

    Individuals with visual impairments have a greater need to be physically fit because in comparison to sighted peers they have increased demands for energy to carry out everyday tasks (Lieberman & McHugh, 2001). Further, their level of vision influences many critical areas such as motor learning, ability to interact in games, and understanding of…

  13. Atomoxetine reverses locomotor hyperactivity, impaired novel object recognition, and prepulse inhibition impairment in mice lacking pituitary adenylate cyclase-activating polypeptide.

    PubMed

    Shibasaki, Y; Hayata-Takano, A; Hazama, K; Nakazawa, T; Shintani, N; Kasai, A; Nagayasu, K; Hashimoto, R; Tanida, M; Katayama, T; Matsuzaki, S; Yamada, K; Taniike, M; Onaka, Y; Ago, Y; Waschek, J A; Köves, K; Reglődi, D; Tamas, A; Matsuda, T; Baba, A; Hashimoto, H

    2015-06-25

    Attention-deficit/hyperactivity disorder (ADHD) is a complex neurobehavioral disorder that is characterized by attention difficulties, impulsivity, and hyperactivity. A non-stimulant drug, atomoxetine (ATX), which is a selective noradrenaline reuptake inhibitor, is widely used for ADHD because it exhibits fewer adverse effects compared to conventional psychostimulants. However, little is known about the therapeutic mechanisms of ATX. ATX treatment significantly alleviated hyperactivity of pituitary adenylate cyclase-activating polypeptide (PACAP)-deficient (PACAP(-/-)) mice with C57BL/6J and 129S6/SvEvTac hybrid background. ATX also improved impaired novel object recognition memory and prepulse inhibition in PACAP(-/-) mice with CD1 background. The ATX-induced increases in extracellular noradrenaline and dopamine levels were significantly higher in the prefrontal cortex of PACAP(-/-) mice compared to wild-type mice with C57BL/6J and 129S6/SvEvTac hybrid background. These results suggest that ATX treatment-induced increases in central monoamine metabolism may be involved in the rescue of ADHD-related abnormalities in PACAP(-/-) mice. Our current study suggests that PACAP(-/-) mice are an ideal rodent model with predictive validity for the study of ADHD etiology and drug development. Additionally, the potential effects of differences in genetic background of PACAP(-/-) mice on behaviors are discussed.

  14. Operational Definition of Active and Healthy Aging (AHA): The European Innovation Partnership (EIP) on AHA Reference Site Questionnaire: Montpellier October 20-21, 2014, Lisbon July 2, 2015.

    PubMed

    Bousquet, Jean; Malva, Joao; Nogues, Michel; Mañas, Leocadio Rodriguez; Vellas, Bruno; Farrell, John

    2015-12-01

    A core operational definition of active and healthy aging (AHA) is needed to conduct comparisons. A conceptual AHA framework proposed by the European Innovation Partnership on Active and Healthy Ageing Reference Site Network includes several items such as functioning (individual capability and underlying body systems), well-being, activities and participation, and diseases (including noncommunicable diseases, frailty, mental and oral health disorders). The instruments proposed to assess the conceptual framework of AHA have common applicability and availability attributes. The approach includes core and optional domains/instruments depending on the needs and the questions. A major common domain is function, as measured by the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0). WHODAS 2.0 can be used across all diseases and healthy individuals. It covers many of the AHA dimensions proposed by the Reference Site network. However, WHODAS 2.0 does not include all dimensions proposed for AHA assessment. The second common domain is health-related quality of life (HRQoL). A report of the AHA questionnaire in the form of a spider net has been proposed to facilitate usual comparisons across individuals and groups of interest.

  15. Asp120Asn mutation impairs the catalytic activity of NDM-1 metallo-β-lactamase: experimental and computational study.

    PubMed

    Chen, Jiao; Chen, Hui; Zhu, Tong; Zhou, Dandan; Zhang, Fang; Lao, Xingzhen; Zheng, Heng

    2014-04-14

    New Delhi metallo-β-lactamase-1 (NDM-1) has attracted extensive attention in recent years for its high activity for hydrolyzing almost all β-lactam antibiotics. Like other metallo-β-lactamases (MβLs), NDM-1 features an invariant Asp120 that ligates the zinc ion (ZN2) in the active site. Previous studies showed that substitutions of Asp120 with residues such as Ala, Ser, Asn and Glu dramatically impaired the MβL (BcII, IMP-1, L1) activity, but no consensus about the exact role of Asp120 has reached. Here we constructed D120N mutant of NDM-1 by site-directed mutagenesis. The replacement of Asp120 with Asn, which has much weaker metal ligating capabilities than Asp, severely impaired the lactamase activity without abolishing the ZN2 site. Molecular dynamics simulations suggested that the ZN1-ZN2 distance increased because of mutation, leading to a rearrangement of the active site, including the bridging OH(-). Thereby, the Mulliken charges of ZN1 and ZN2 redistributed, especially for ZN2, which might be the major cause of the impaired activity. Reducing the point charges of Asp120 carboxyl oxygens weakened the ionic interactions between Asp120 and ZN2, and the positions of the zinc ions were also changed as a result. It is proposed that Asp120 acts as a strong ZN2 ligand, positioning ZN2 for catalytically important interactions with the substrate, stabilizing the negatively charged amide nitrogen of the hydrolyzed intermediate, and more importantly, orienting the ZN-bound OH(-) for nucleophilic attacks and protonation. These functions are of general importance for catalyzing β-lactam antibiotics by NDM-1 as well as other MβLs.

  16. Piracetam prevents scopolamine-induced memory impairment and decrease of NTPDase, 5'-nucleotidase and adenosine deaminase activities.

    PubMed

    Marisco, Patricia C; Carvalho, Fabiano B; Rosa, Michelle M; Girardi, Bruna A; Gutierres, Jessié M; Jaques, Jeandre A S; Salla, Ana P S; Pimentel, Víctor C; Schetinger, Maria Rosa C; Leal, Daniela B R; Mello, Carlos F; Rubin, Maribel A

    2013-08-01

    Piracetam improves cognitive function in animals and in human beings, but its mechanism of action is still not completely known. In the present study, we investigated whether enzymes involved in extracellular adenine nucleotide metabolism, adenosine triphosphate diphosphohydrolase (NTPDase), 5'-nucleotidase and adenosine deaminase (ADA) are affected by piracetam in the hippocampus and cerebral cortex of animals subjected to scopolamine-induced memory impairment. Piracetam (0.02 μmol/5 μL, intracerebroventricular, 60 min pre-training) prevented memory impairment induced by scopolamine (1 mg/kg, intraperitoneal, immediately post-training) in the inhibitory avoidance learning and in the object recognition task. Scopolamine reduced the activity of NTPDase in hippocampus (53 % for ATP and 53 % for ADP hydrolysis) and cerebral cortex (28 % for ATP hydrolysis). Scopolamine also decreased the activity of 5'-nucleotidase (43 %) and ADA (91 %) in hippocampus. The same effect was observed in the cerebral cortex for 5'-nucleotidase (38 %) and ADA (68 %) activities. Piracetam fully prevented scopolamine-induced memory impairment and decrease of NTPDase, 5'-nucleotidase and adenosine deaminase activities in synaptosomes from cerebral cortex and hippocampus. In vitro experiments show that piracetam and scopolamine did not alter enzymatic activity in cerebral cortex synaptosomes. Moreover, piracetam prevented scopolamine-induced increase of TBARS levels in hippocampus and cerebral cortex. These results suggest that piracetam-induced improvement of memory is associated with protection against oxidative stress and maintenance of NTPDase, 5'-nucleotidase and ADA activities, and suggest the purinergic system as a putative target of piracetam.

  17. Comparison of psychometric properties between usual-week and past-week self-reported physical activity questionnaires: a systematic review.

    PubMed

    Doma, Kenji; Speyer, Renée; Leicht, Anthony S; Cordier, Reinie

    2017-01-31

    The aim was to critically appraise the methodological quality of studies and determine the psychometric qualities of Past-week and Usual-week Physical Activity Questionnaires (PAQs). Data sources were obtained from Pubmed and Embase. The eligibility criteria for selecting studies included: 1) at least one psychometric property of PAQs was examined in adults; 2) the PAQs either had a recall period of usual 7-days (Usual-week PAQs) within the past 12 months or during the past 7-days (Past-week PAQs); and 3) PAQs were self-administered. Study quality was evaluated using the COSMIN taxonomy and the overall psychometric qualities evaluated using pre-established psychometric criteria. Overall, 45 studies were reviewed to assess the psychometric properties of 21 PAQs with the methodological quality of most studies showing good to excellent ratings. When the relationship between PAQs and other instruments (i.e., convergent validity) were compared between recall methods, Past-week PAQs appeared to have stronger correlations than Usual-week PAQs. For the overall psychometric quality, the Incidental and Planned Exercise Questionnaire for the Usual-week (IPEQ-WA) and for the Past-week (IPEQ-W) had the greatest number of positive ratings. For all included PAQs, very few psychometric properties were assessed with poor ratings for the majority of the overall qualities of psychometric properties indicating the limitation of current PAQs. More research that covers a greater spectrum of psychometric properties is required to gain a better understanding of the qualities of current PAQs.

  18. Osteopontin That Is Elevated in the Airways during COPD Impairs the Antibacterial Activity of Common Innate Antibiotics.

    PubMed

    Gela, Anele; Bhongir, Ravi K V; Mori, Michiko; Keenan, Paul; Mörgelin, Matthias; Erjefält, Jonas S; Herwald, Heiko; Egesten, Arne; Kasetty, Gopinath

    2016-01-01

    Bacterial infections of the respiratory tract contribute to exacerbations and disease progression in chronic obstructive pulmonary disease (COPD). There is also an increased risk of invasive pneumococcal disease in COPD. The underlying mechanisms are not fully understood but include impaired mucociliary clearance and structural remodeling of the airways. In addition, antimicrobial proteins that are constitutively expressed or induced during inflammatory conditions are an important part of the airway innate host defense. In the present study, we show that osteopontin (OPN), a multifunctional glycoprotein that is highly upregulated in the airways of COPD patients co-localizes with several antimicrobial proteins expressed in the airways. In vitro, OPN bound lactoferrin, secretory leukocyte peptidase inhibitor (SLPI), midkine, human beta defensin-3 (hBD-3), and thymic stromal lymphopoietin (TSLP) but showed low or no affinity for lysozyme and LL-37. Binding of OPN impaired the antibacterial activity against the important bacterial pathogens Streptococcus pneumoniae and Pseudomonas aeruginosa. Interestingly, OPN reduced lysozyme-induced killing of S. pneumoniae, a finding that could be explained by binding of OPN to the bacterial surface, thereby shielding the bacteria. A fragment of OPN generated by elastase of P. aeruginosa retained some inhibitory effect. Some antimicrobial proteins have additional functions. However, the muramidase-activity of lysozyme and the protease inhibitory function of SLPI were not affected by OPN. Taken together, OPN can contribute to the impairment of innate host defense by interfering with the function of antimicrobial proteins, thus increasing the vulnerability to acquire infections during COPD.

  19. Osteopontin That Is Elevated in the Airways during COPD Impairs the Antibacterial Activity of Common Innate Antibiotics

    PubMed Central

    Mori, Michiko; Keenan, Paul; Mörgelin, Matthias; Erjefält, Jonas S.; Herwald, Heiko; Egesten, Arne; Kasetty, Gopinath

    2016-01-01

    Bacterial infections of the respiratory tract contribute to exacerbations and disease progression in chronic obstructive pulmonary disease (COPD). There is also an increased risk of invasive pneumococcal disease in COPD. The underlying mechanisms are not fully understood but include impaired mucociliary clearance and structural remodeling of the airways. In addition, antimicrobial proteins that are constitutively expressed or induced during inflammatory conditions are an important part of the airway innate host defense. In the present study, we show that osteopontin (OPN), a multifunctional glycoprotein that is highly upregulated in the airways of COPD patients co-localizes with several antimicrobial proteins expressed in the airways. In vitro, OPN bound lactoferrin, secretory leukocyte peptidase inhibitor (SLPI), midkine, human beta defensin-3 (hBD-3), and thymic stromal lymphopoietin (TSLP) but showed low or no affinity for lysozyme and LL-37. Binding of OPN impaired the antibacterial activity against the important bacterial pathogens Streptococcus pneumoniae and Pseudomonas aeruginosa. Interestingly, OPN reduced lysozyme-induced killing of S. pneumoniae, a finding that could be explained by binding of OPN to the bacterial surface, thereby shielding the bacteria. A fragment of OPN generated by elastase of P. aeruginosa retained some inhibitory effect. Some antimicrobial proteins have additional functions. However, the muramidase-activity of lysozyme and the protease inhibitory function of SLPI were not affected by OPN. Taken together, OPN can contribute to the impairment of innate host defense by interfering with the function of antimicrobial proteins, thus increasing the vulnerability to acquire infections during COPD. PMID:26731746

  20. Activity-dependent BDNF release and TRPC signaling is impaired in hippocampal neurons of Mecp2 mutant mice.

    PubMed

    Li, Wei; Calfa, Gaston; Larimore, Jennifer; Pozzo-Miller, Lucas

    2012-10-16

    Dysfunction of the neurotrophin brain-derived neurotrophic factor (BDNF) is implicated in Rett syndrome (RTT), but the state of its releasable pool and downstream signaling in mice lacking methyl-CpG-binding protein-2 (Mecp2) is unknown. Here, we show that membrane currents and dendritic Ca(2+) signals evoked by recombinant BDNF or an activator of diacylglycerol (DAG)-sensitive transient receptor potential canonical (TRPC) channels are impaired in CA3 pyramidal neurons of symptomatic Mecp2 mutant mice. TRPC3 and TRPC6 mRNA and protein levels are lower in Mecp2 mutant hippocampus, and chromatin immunoprecipitation (ChIP) identified Trpc3 as a target of MeCP2 transcriptional regulation. BDNF mRNA and protein levels are also lower in Mecp2 mutant hippocampus and dentate gyrus granule cells, which is reflected in impaired activity-dependent release of endogenous BDNF estimated from TRPC currents and dendritic Ca(2+) signals in CA3 pyramidal neurons. These results identify the gene encoding TRPC3 channels as a MeCP2 target and suggest a potential therapeutic strategy to boost impaired BDNF signaling in RTT.

  1. Physician Enabling Skills Questionnaire

    PubMed Central

    Hudon, Catherine; Lambert, Mireille; Almirall, José

    2015-01-01

    Abstract Objective To evaluate the reliability and validity of the newly developed Physician Enabling Skills Questionnaire (PESQ) by assessing its internal consistency, test-retest reliability, concurrent validity with patient-centred care, and predictive validity with patient activation and patient enablement. Design Validation study. Setting Saguenay, Que. Participants One hundred patients with at least 1 chronic disease who presented in a waiting room of a regional health centre family medicine unit. Main outcome measures Family physicians’ enabling skills, measured with the PESQ at 2 points in time (ie, while in the waiting room at the family medicine unit and 2 weeks later through a mail survey); patient-centred care, assessed with the Patient Perception of Patient-Centredness instrument; patient activation, assessed with the Patient Activation Measure; and patient enablement, assessed with the Patient Enablement Instrument. Results The internal consistency of the 6 subscales of the PESQ was adequate (Cronbach α = .69 to .92). The test-retest reliability was very good (r = 0.90; 95% CI 0.84 to 0.93). Concurrent validity with the Patient Perception of Patient-Centredness instrument was good (r = −0.67; 95% CI −0.78 to −0.53; P < .001). The PESQ accounts for 11% of the total variance with the Patient Activation Measure (r2 = 0.11; P = .002) and 19% of the variance with the Patient Enablement Instrument (r2 = 0.19; P < .001). Conclusion The newly developed PESQ presents good psychometric properties, allowing for its use in practice and research. PMID:26889507

  2. PPARγ as a molecular target of EPA anti-inflammatory activity during TNF-α-impaired skeletal muscle cell differentiation.

    PubMed

    Magee, Peter; Pearson, Stephen; Whittingham-Dowd, Jayde; Allen, Jeremy

    2012-11-01

    Activated skeletal muscle satellite cells facilitate muscle repair or growth through proliferation, differentiation and fusion into new or existing myotubes. Elevated levels of the proinflammatory cytokine tumor necrosis factor-α (TNF-α) impair this process and are documented to have significant roles in muscle pathology. Recent evidence shows that the ω-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) can block TNF-mediated suppression of progenitor cell differentiation, but the nature of this activity and its significance for local regulation of inflammation are not known. In the current study, we examined differentiation of the C2C12 myoblast line during treatment with TNF-α and EPA and measured the expression, activation and inhibition of peroxisome proliferator-activated receptor-γ (PPARγ), as several studies have shown its involvement in mediating EPA activity and the inhibition of nuclear factor (NF)-κB inflammatory gene activation. We found that TNF-α treatment increased NF-κB activity and reduced expression and activation of PPARγ, resulting in impaired myotube formation. EPA treatment attenuated these effects of TNF-α and was associated with up-regulation of PPARγ. Furthermore, EPA inhibited TNF-α-mediated transcription and secretion of interleukin (IL)-6, a key target gene of TNF-mediated NF-κB transcriptional activity. Pretreatment with a PPARγ selective antagonist inhibited some of the actions of EPA but was only partially effective in reversing inhibition of IL-6 production. These results show that EPA activity was associated with altered expression and activation of PPARγ, but exerted through both PPARγ-dependent and PPARγ-independent pathways leading to suppression of the proinflammatory cellular microenvironment.

  3. [Effects of physical activity and physical training on the psychological status of older persons with and without cognitive impairment].

    PubMed

    Gogulla, S; Lemke, N; Hauer, K

    2012-06-01

    Fear of falling and depression in the elderly and among cognitively impaired people lead to restrictions in quality of life. Being more active is associated with improved mental health as documented in cross-sectional and longitudinal studies. This is especially true for depression. Such epidemiologic evidence is lacking in fear of falling. This review summarizes current evidence from epidemiological and randomized controlled trials (RCTs) and gives an outlook for future research perspectives. The majority of studies included in this review document a significant reduction of depression and fear of falling in older persons by physical training with less evidence in persons with cognitive impairment. With respect to intensity, duration, and amount of exercise, evidence-based recommendations were limited by the small number of high-quality comparative RCTs. High-intensity strength or endurance training was the most effective for reducing depression, while participation in Tai-Chi or multifactorial training programs was most effective to reduce fear of falling.

  4. Significant bone microarchitecture impairment in premenopausal women with active celiac disease.

    PubMed

    Zanchetta, María Belén; Costa, Florencia; Longobardi, Vanesa; Longarini, Gabriela; Mazure, Roberto Martín; Moreno, María Laura; Vázquez, Horacio; Silveira, Fernando; Niveloni, Sonia; Smecuol, Edgardo; Temprano, María de la Paz; Hwang, Hui Jer; González, Andrea; Mauriño, Eduardo César; Bogado, Cesar; Zanchetta, Jose R; Bai, Julio César

    2015-07-01

    Patients with active celiac disease (CD) are more likely to have osteoporosis and increased risk of fractures. High-resolution peripheral quantitative computed tomography (HR-pQCT) permits three-dimensional exploration of bone microarchitectural characteristics measuring separately cortical and trabecular compartments, and giving a more profound insight into bone disease pathophysiology and fracture. We aimed to determine the volumetric and microarchitectural characteristics of peripheral bones-distal radius and tibia-in an adult premenopausal cohort with active CD assessed at diagnosis. We prospectively enrolled 31 consecutive premenopausal women with newly diagnosed CD (median age 29 years, range: 18-49) and 22 healthy women of similar age (median age 30 years, range 21-41) and body mass index. Compared with controls, peripheral bones of CD patients were significantly lower in terms of total volumetric density mg/cm(3) (mean ± SD: 274.7 ± 51.7 vs. 324.7 ± 45.8, p 0.0006 at the radius; 264.4 ± 48.7 vs. 307 ± 40.7, p 0.002 at the tibia), trabecular density mg/cm(3) (118.6 ± 31.5 vs. 161.9 ± 33.6, p<0.0001 at the radius; 127.9 ± 28.7 vs. 157.6 ± 15.6, p < 0.0001 at the tibia); bone volume/trabecular volume ratio % (9.9 ± 2.6 vs. 13.5 ± 2.8, p<0.0001 at the radius; 10.6 ± 2.4 vs. 13.1 ± 1.3, p < 0.0001 at the tibia); number of trabeculae 1/mm (1.69 ± 0.27 vs. 1.89 ± 0.26, p 0.009 at the radius; 1.53 ± 0.32 vs. 1.80 ± 0.26, p 0.002 at the tibia); and trabecular thickness mm (0.058 ± 0.010 vs. 0.071 ± 0.008, p < 0.0001 at the radius with no significant difference at the tibia). Cortical density was significantly lower in both regions (D comp mg/cm(3) 860 ± 57.2 vs. 893.9 ± 43, p 0.02; 902.7 ± 48.7 vs. 932.6 ± 32.6, p 0.01 in radius and tibia respectively). Although cortical thickness was lower in CD patients, it failed to show any significant inter-group difference (a-8% decay with p 0.11 in both bones). Patients with symptomatic CD (n = 22) had

  5. Utah Drug Use Questionnaire.

    ERIC Educational Resources Information Center

    Governor's Citizen Advisory Committee on Drugs, Salt Lake City, UT.

    This questionnaire assesses drug use practices in junior and senior high school students. The 21 multiple choice items pertain to drug use practices, use history, available of drugs, main reason for drug use, and demographic data. The questionnaire is untimed, group administered, and may be given by the classroom teacher in about 10 minutes. Item…

  6. Write Your Own Questionnaire

    ERIC Educational Resources Information Center

    Cook, David I.

    1975-01-01

    Contends that student evaluative questionnaires should be designed by instructors themselves to help improve their classroom performance and therefore should contain only questions that students are capable of answering objectively and not, for instance, questions about the relevancy of the course. Contains a sample questionnaire. (GH)

  7. Wesleyan University Student Questionnaire.

    ERIC Educational Resources Information Center

    Haagen, C. Hess

    This questionnaire assesses marijuana use practices in college students. The 30 items (multiple choice or free response) are concerned with personal and demographic data, marijuana smoking practices, use history, effects from smoking marijuana, present attitude toward the substance, and use of other drugs. The Questionnaire is untimed and…

  8. Impaired NK-mediated regulation of T-cell activity in multiple sclerosis is reconstituted by IL-2 receptor modulation.

    PubMed

    Gross, Catharina C; Schulte-Mecklenbeck, Andreas; Rünzi, Anna; Kuhlmann, Tanja; Posevitz-Fejfár, Anita; Schwab, Nicholas; Schneider-Hohendorf, Tilman; Herich, Sebastian; Held, Kathrin; Konjević, Matea; Hartwig, Marvin; Dornmair, Klaus; Hohlfeld, Reinhard; Ziemssen, Tjalf; Klotz, Luisa; Meuth, Sven G; Wiendl, Heinz

    2016-05-24

    Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS) resulting from a breakdown in peripheral immune tolerance. Although a beneficial role of natural killer (NK)-cell immune-regulatory function has been proposed, it still needs to be elucidated whether NK cells are functionally impaired as part of the disease. We observed NK cells in active MS lesions in close proximity to T cells. In accordance with a higher migratory capacity across the blood-brain barrier, CD56(bright) NK cells represent the major intrathecal NK-cell subset in both MS patients and healthy individuals. Investigating the peripheral blood and cerebrospinal fluid of MS patients treated with natalizumab revealed that transmigration of this subset depends on the α4β1 integrin very late antigen (VLA)-4. Although no MS-related changes in the migratory capacity of NK cells were observed, NK cells derived from patients with MS exhibit a reduced cytolytic activity in response to antigen-activated CD4(+) T cells. Defective NK-mediated immune regulation in MS is mainly attributable to a CD4(+) T-cell evasion caused by an impaired DNAX accessory molecule (DNAM)-1/CD155 interaction. Both the expression of the activating NK-cell receptor DNAM-1, a genetic alteration consistently found in MS-association studies, and up-regulation of the receptor's ligand CD155 on CD4(+) T cells are reduced in MS. Therapeutic immune modulation of IL-2 receptor restores impaired immune regulation in MS by increasing the proportion of CD155-expressing CD4(+) T cells and the cytolytic activity of NK cells.

  9. Inhibition of Glutamate Carboxypeptidase II (GCPII) activity as a treatment for cognitive impairment in multiple sclerosis

    PubMed Central

    Rahn, Kristen A.; Watkins, Crystal C.; Alt, Jesse; Rais, Rana; Stathis, Marigo; Grishkan, Inna; Crainiceau, Ciprian M.; Pomper, Martin G.; Rojas, Camilo; Pletnikov, Mikhail V.; Calabresi, Peter A.; Brandt, Jason; Barker, Peter B.; Slusher, Barbara S.; Kaplin, Adam I.

    2012-01-01

    Half of all patients with multiple sclerosis (MS) experience cognitive impairment, for which there is no pharmacological treatment. Using magnetic resonance spectroscopy (MRS), we examined metabolic changes in the hippocampi of MS patients, compared the findings to performance on a neurocognitive test battery, and found that N-acetylaspartylglutamate (NAAG) concentration correlated with cognitive functioning. Specifically, MS patients with cognitive impairment had low hippocampal NAAG levels, whereas those with normal cognition demonstrated higher levels. We then evaluated glutamate carboxypeptidase II (GCPII) inhibitors, known to increase brain NAAG levels, on cognition in the experimental autoimmune encephalomyelitis (EAE) model of MS. Whereas GCPII inhibitor administration did not affect physical disabilities, it increased brain NAAG levels and dramatically improved learning and memory test performance compared with vehicle-treated EAE mice. These data suggest that NAAG is a unique biomarker for cognitive function in MS and that inhibition of GCPII might be a unique therapeutic strategy for recovery of cognitive function. PMID:23169655

  10. Abnormal functional lateralization and activity of language brain areas in typical specific language impairment (developmental dysphasia).

    PubMed

    de Guibert, Clément; Maumet, Camille; Jannin, Pierre; Ferré, Jean-Christophe; Tréguier, Catherine; Barillot, Christian; Le Rumeur, Elisabeth; Allaire, Catherine; Biraben, Arnaud

    2011-10-01

    Atypical functional lateralization and specialization for language have been proposed to account for developmental language disorders, yet results from functional neuroimaging studies are sparse and inconsistent. This functional magnetic resonance imaging study compared children with a specific subtype of specific language impairment affecting structural language (n = 21), to a matched group of typically developing children using a panel of four language tasks neither requiring reading nor metalinguistic skills, including two auditory lexico-semantic tasks (category fluency and responsive naming) and two visual phonological tasks based on picture naming. Data processing involved normalizing the data with respect to a matched pairs paediatric template, groups and between-groups analysis, and laterality indices assessment within regions of interest using single and combined task analysis. Children with specific language impairment exhibited a significant lack of left lateralization in all core language regions (inferior frontal gyrus-opercularis, inferior frontal gyrus-triangularis, supramarginal gyrus and superior temporal gyrus), across single or combined task analysis, but no difference of lateralization for the rest of the brain. Between-group comparisons revealed a left hypoactivation of Wernicke's area at the posterior superior temporal/supramarginal junction during the responsive naming task, and a right hyperactivation encompassing the anterior insula with adjacent inferior frontal gyrus and the head of the caudate nucleus during the first phonological task. This study thus provides evidence that this subtype of specific language impairment is associated with atypical lateralization and functioning of core language areas.

  11. Abnormal functional lateralization and activity of language brain areas in typical specific language impairment (developmental dysphasia)

    PubMed Central

    De Guibert, Clément; Maumet, Camille; Jannin, Pierre; Ferré, Jean-Christophe; Tréguier, Catherine; Barillot, Christian; Le Rumeur, Elisabeth; Allaire, Catherine; Biraben, Arnaud

    2011-01-01

    Atypical functional lateralization and specialization for language have been proposed to account for developmental language disorders, yet results from functional neuroimaging studies are sparse and inconsistent. This functional magnetic resonance imaging study compared children with a specific subtype of specific language impairment affecting structural language (n=21), to a matched group of typically-developing children using a panel of four language tasks neither requiring reading nor metalinguistic skills, including two auditory lexico-semantic tasks (category fluency and responsive naming) and two visual phonological tasks based on picture naming. Data processing involved normalizing the data with respect to a matched pairs pediatric template, groups and between-groups analysis, and laterality indexes assessment within regions of interest using single and combined task analysis. Children with specific language impairment exhibited a significant lack of left lateralization in all core language regions (inferior frontal gyrus-opercularis, inferior frontal gyrus-triangularis, supramarginal gyrus, superior temporal gyrus), across single or combined task analysis, but no difference of lateralization for the rest of the brain. Between-group comparisons revealed a left hypoactivation of Wernicke’s area at the posterior superior temporal/supramarginal junction during the responsive naming task, and a right hyperactivation encompassing the anterior insula with adjacent inferior frontal gyrus and the head of the caudate nucleus during the first phonological task. This study thus provides evidence that this specific subtype of specific language impairment is associated with atypical lateralization and functioning of core language areas. PMID:21719430

  12. Visual Impairment

    MedlinePlus

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Visual Impairment KidsHealth > For Teens > Visual Impairment Print A ... with the brain, making vision impossible. What Is Visual Impairment? Many people have some type of visual ...

  13. Venom of Parasitoid Pteromalus puparum Impairs Host Humoral Antimicrobial Activity by Decreasing Host Cecropin and Lysozyme Gene Expression

    PubMed Central

    Fang, Qi; Wang, Bei-Bei; Ye, Xin-Hai; Wang, Fei; Ye, Gong-Yin

    2016-01-01

    Insect host/parasitoid interactions are co-evolved systems in which host defenses are balanced by parasitoid mechanisms to disable or hide from host immune effectors. Here, we report that Pteromalus puparum venom impairs the antimicrobial activity of its host Pieris rapae. Inhibition zone results showed that bead injection induced the antimicrobial activity of the host hemolymph but that venom inhibited it. The cDNAs encoding cecropin and lysozyme were screened. Relative quantitative PCR results indicated that all of the microorganisms and bead injections up-regulated the transcript levels of the two genes but that venom down-regulated them. At 8 h post bead challenge, there was a peak in the transcript level of the cecropin gene, whereas the peak of lysozyme gene occurred at 24 h. The transcripts levels of the two genes were higher in the granulocytes and fat body than in other tissues. RNA interference decreased the transcript levels of the two genes and the antimicrobial activity of the pupal hemolymph. Venom injections similarly silenced the expression of the two genes during the first 8 h post-treatment in time- and dose-dependent manners, after which the silence effects abated. Additionally, recombinant cecropin and lysozyme had no significant effect on the emergence rate of pupae that were parasitized by P. puparum females. These findings suggest one mechanism of impairing host antimicrobial activity by parasitoid venom. PMID:26907346

  14. Amyloid-beta leads to impaired cellular respiration, energy production and mitochondrial electron chain complex activities in human neuroblastoma cells.

    PubMed

    Rhein, V; Baysang, G; Rao, S; Meier, F; Bonert, A; Müller-Spahn, F; Eckert, A

    2009-09-01

    Evidence suggests that amyloid-beta (Abeta) protein is a key factor in the pathogenesis of Alzheimer's disease (AD) and it has been recently proposed that mitochondria are involved in the biochemical pathway by which Abeta can lead to neuronal dysfunction. Here we investigated the specific effects of Abeta on mitochondrial function under physiological conditions. Mitochondrial respiratory functions and energy metabolism were analyzed in control and in human wild-type amyloid precursor protein (APP) stably transfected human neuroblastoma cells (SH-SY5Y). Mitochondrial respiratory capacity of mitochondrial electron transport chain (ETC) in vital cells was measured with a high-resolution respirometry system (Oxygraph-2k). In addition, we determined the individual activities of mitochondrial complexes I-IV that compose ETC and ATP cellular levels. While the activities of complexes I and II did not change between cell types, complex IV activity was significantly reduced in APP cells. In contrast, activity of complex III was significantly enhanced in APP cells, as compensatory response in order to balance the defect of complex IV. However, this compensatory mechanism could not prevent the strong impairment of total respiration in vital APP cells. As a result, the respiratory control ratio (state3/state4) together with ATP production decreased in the APP cells in comparison with the control cells. Chronic exposure to soluble Abeta protein may result in an impairment of energy homeostasis due to a decreased respiratory capacity of mitochondrial electron transport chain which, in turn, may accelerate neurons demise.

  15. Ginsenoside Rg3 Alleviates Lipopolysaccharide-Induced Learning and Memory Impairments by Anti-Inflammatory Activity in Rats

    PubMed Central

    Lee, Bombi; Sur, Bongjun; Park, Jinhee; Kim, Sung-Hun; Kwon, Sunoh; Yeom, Mijung; Shim, Insop; Lee, Hyejung; Hahm, Dae-Hyun

    2013-01-01

    The purpose of this study was to examine whether ginsenoside Rg3 (GRg3) could improve learning and memory impairments and inflammatory reactions induced by injecting lipopolysaccharide (LPS) into the brains of rats. The effects of GRg3 on proinflammatory mediators in the hippocampus and the underlying mechanisms of these effects were also investigated. Injection of LPS into the lateral ventricle caused chronic inflammation and produced deficits in learning in a memory-impairment animal model. Daily administration of GRg3 (10, 20, and 50 mg/kg, i.p.) for 21 consecutive days markedly improved the LPS-induced learning and memory disabilities demonstrated on the step-through passive avoidance test and Morris water maze test. GRg3 administration significantly decreased expression of pro-inflammatory mediators such as tumor necrosis factor-α, interleukin-1β, and cyclooxygenase-2 in the hippocampus, as assessed by reverse transcription-polymerase chain reaction analysis and immunohistochemistry. Together, these findings suggest that GRg3 significantly attenuated LPS-induced cognitive impairment by inhibiting the expression of pro-inflammatory mediators in the rat brain. These results suggest that GRg3 may be effective for preventing or slowing the development of neurological disorders, including Alzheimer’s disease, by improving cognitive and memory functions due to its anti-inflammatory activity in the brain. PMID:24244826

  16. Functional impairment in mild cognitive impairment evidenced using performance-based measurement.

    PubMed

    Puente, Antonio Nicolas; Terry, Douglas P; Faraco, Carlos C; Brown, Courtney L; Miller, L Stephen

    2014-12-01

    Older adults (OAs) with mild cognitive impairment (MCI) are traditionally thought to have preservation of activities of daily living (ADLs). However, recent evidence suggests OAs with MCI may have difficulty completing ADLs and specifically instrumental ADLs (IADLs). The ADLs are frequently evaluated through self- or collateral report questionnaires, while performance-based measures are infrequently utilized, despite the decreased bias and increased accuracy and sensitivity associated with these instruments. This investigation compared ADLs between community-dwelling OAs with (n = 20) and without MCI (n = 30) using a self-report questionnaire (Older American Resources and Services Activities of Daily Living Scale; OARS), a collateral report questionnaire (OARS), and a performance-based measure (the Direct Assessment of Functional Status-Revised). Consistent with our hypothesis, OAs with MCI had decreased ADLs and IADLs on the performance-based measure compared to cognitively intact OAs, while there were no differences in ADLs or IADLs on self-report questionnaires or collateral report questionnaires. Our results suggest OAs with MCI have decreased ability to complete IADLs. However, this investigation suggests these deficits may not be detected by questionnaires and are more likely to be found with performance-based testing.

  17. High-intensity physical activity modulates diet effects on cerebrospinal amyloid-β levels in normal aging and mild cognitive impairment.

    PubMed

    Baker, Laura D; Bayer-Carter, Jennifer L; Skinner, Jeannine; Montine, Thomas J; Cholerton, Brenna A; Callaghan, Maureen; Leverenz, James B; Walter, Brooke K; Tsai, Elaine; Postupna, Nadia; Lampe, Johanna; Craft, Suzanne

    2012-01-01

    We previously showed that amyloid-β 1-42 (Aβ(42)) levels in cerebrospinal fluid (CSF) were markedly altered in response to a 4-week dietary intervention in normal aging and mild cognitive impairment (MCI). Here, we re-examined the data to assess whether diet-induced effects on CSF Aβ(42) were modulated by high intensity physical activity (hi-PA). Normal older adults (n = 18, mean age = 68.6 ± 7.4 y) and adults with amnestic MCI (n = 23, mean age = 68.0 ± 6.5 y) received a low saturated fat/low glycemic index (LOW) diet or a high saturated fat/high glycemic index (HIGH) diet, and CSF levels of Aβ(42), tau, and IL-8 were measured at baseline and week 4. Pre-study activity levels were assessed using a 7-d questionnaire, and weekly duration of hi-PA was quantified. At baseline, increased hi-PA in normals predicted lower CSF levels of tau (r = -0.54, p = 0.020) and IL-8 (r = -0.70, p = 0.025). Diet-induced effects on CSF Aβ(42) during the intervention study were modulated by hi-PA, and the nature of this effect differed for normals and MCI (ANOVA, p = 0.039). That is, for normal adults, increased hi-PA attenuated the effects of the HIGH diet on CSF Aβ(42) whereas in MCI, increased hi-PA potentiated the effects of the LOW diet. Our results suggest that normal adults who engage in hi-PA are less vulnerable to the pathological effects of an unhealthy diet, while in MCI, the benefit of a healthy diet on Aβ modulation is greatest when paired with hi-PA. Exercise may thus interact with diet to alter pathological processes that ultimately modify risk of Alzheimer's disease.

  18. Guarana (Paullinia cupana) ameliorates memory impairment and modulates acetylcholinesterase activity in Poloxamer-407-induced hyperlipidemia in rat brain.

    PubMed

    Ruchel, Jader B; Braun, Josiane B S; Adefegha, Stephen A; Guedes Manzoni, Alessandra; Abdalla, Fátima H; de Oliveira, Juliana S; Trelles, Kelly; Signor, Cristiane; Lopes, Sônia T A; da Silva, Cássia B; Castilhos, Lívia G; Rubin, Maribel A; Leal, Daniela B R

    2017-01-01

    Hyperlipidemia is a risk factor for the development of cognitive dysfunction and atherosclerosis. Natural compounds have recently received special attention in relation to the treatment of disease due to their low cost and wide margin of safety. Thus, the aim of this study was to determine the possible preventive effect of guarana powder (Paullinia cupana) on memory impairment and acetylcholinesterase (AChE) activity in the brain structures of rats with Poloxamer-407-induced hyperlipidemia. Adult male Wistar rats were pretreated with guarana (12.5, 25 and 50mg/kg/day) and caffeine (0.2mg/kg/day) by gavage for a period of 30days. Simvastatin (0.04mg/kg) was administered as a comparative standard. Acute hyperlipidemia was induced with intraperitoneal injections of 500mg/kg of Poloxamer-407. Memory tests and evaluations of anxiety were performed. The cortex, cerebellum, hippocampus, hypothalamus and striatum were separated to assess acetylcholinesterase activity. Our results revealed that guarana powder was able to reduce the levels of TC and LDL-C in a manner similar to simvastatin. Guarana powder also partially reduced the liver damage caused by hyperlipidemia. Guarana was able to prevent changes in the activity of AChE and improve memory impairment due to hyperlipidemia. Guarana powder may therefore be a source of promising phytochemicals that can be used as adjuvant therapy in the management of hyperlipidemia and cognitive disorders.

  19. Phenotypic dysregulation of microglial activation in young offspring rats with maternal sleep deprivation-induced cognitive impairment

    PubMed Central

    Zhao, Qiuying; Xie, Xiaofang; Fan, Yonghua; Zhang, Jinqiang; Jiang, Wei; Wu, Xiaohui; Yan, Shuo; Chen, Yubo; Peng, Cheng; You, Zili

    2015-01-01

    Despite the potential adverse effects of maternal sleep deprivation (MSD) on physiological and behavioral aspects of offspring, the mechanisms remain poorly understood. The present study was intended to investigate the roles of microglia on neurodevelopment and cognition in young offspring rats with prenatal sleep deprivation. Pregnant Wistar rats received 72 h sleep deprivation in the last trimester of gestation, and their prepuberty male offspring were given the intraperitoneal injection with or without minocycline. The results showed the number of Iba1+ microglia increased, that of hippocampal neurogenesis decreased, and the hippocampus-dependent spatial learning and memory were impaired in MSD offspring. The classical microglial activation markers (M1 phenotype) IL-1β, IL-6, TNF-α, CD68 and iNOS were increased, while the alternative microglial activation markers (M2 phenotype) Arg1, Ym1, IL-4, IL-10 and CD206 were reduced in hippocampus of MSD offspring. After minocycline administration, the MSD offspring showed improvement in MWM behaviors and increase in BrdU+/DCX+ cells. Minocycline reduced Iba1+ cells, suppressed the production of pro-inflammatory molecules, and reversed the reduction of M2 microglial markers in the MSD prepuberty offspring. These results indicate that dysregulation in microglial pro- and anti-inflammatory activation is involved in MSD-induced inhibition of neurogenesis and impairment of spatial learning and memory. PMID:25830666

  20. Impaired bactericidal but not fungicidal activity of polymorphonuclear neutrophils in patients with chronic lymphocytic leukemia.

    PubMed

    Kontoyiannis, Dimitrios P; Georgiadou, Sarah P; Wierda, William G; Wright, Susan; Albert, Nathaniel D; Ferrajoli, Alessandra; Keating, Michael; Lewis, Russell E

    2013-08-01

    We examined the qualitative polymorphonuclear neutrophil (PMN)-associated immune impairment in patients with chronic lymphocytic leukemia (CLL) by characterizing phagocytic killing of key non-opsonized bacterial (Staphylococcus aureus and Pseudomonas aeruginosa) and fungal (Candida albicans and Aspergillus fumigatus) pathogens. Neutrophils were collected from 47 non-neutropenic patients with CLL (PMN count > 1000/mm(3)) and age-matched and young healthy controls (five each). A subset of patients (13%) had prior or subsequent infections. We found that the patients with CLL had diminished PMN microbicidal response against bacteria but not against fungi compared with the controls. Compared to patients with effective PMN responses, we did not identify differences of basal PMN pathogen-associated molecular pattern receptor gene expression, soluble pathogen-associated molecular pattern gene expression or inflammatory cytokine signatures in patients with impaired PMN responses when PMNs were analyzed in multiplex real-time polymerase chain reaction assays. However, differences in PMN microbicidal response against A. fumigatus in patients with CLL were associated with the degree of hypogammaglobulinemia.

  1. Impaired bactericidal but not fungicidal activity of polymorphonuclear neutrophils in patients with chronic lymphocytic leukemia

    PubMed Central

    Kontoyiannis, Dimitrios P.; Georgiadou, Sarah P.; Wierda, William G.; Wright, Susan; Albert, Nathaniel D.; Ferrajoli, Alessandra; Keating, Michael; Lewis, Russell E.

    2013-01-01

    We examined the qualitative polymorphonuclear neutrophil (PMN)-associated immune impairment in patients with chronic lymphocytic leukemia (CLL) by characterizing phagocytic killing of key nonopsonized bacterial (Staphylococcus aureus and Pseudomonas aeruginosa) and fungal (Candida albicans and Aspergillus fumigatus) pathogens. Neutrophils were collected from 47 nonneutropenic CLL patients (PMN count > 1000/mm3), and age-matched and young healthy controls (five each). A subset of patients (13%) had prior or subsequent infections. We found that the CLL patients had diminished PMN microbicidal response against bacteria but not against fungi than did the controls. Compared to patients with effective PMN responses, we did not identify differences of basal PMN pathogen-associated molecular pattern receptor gene expression, soluble pathogen-associated molecular pattern gene expression, or inflammatory cytokine signatures in patients with impaired PMN responses when PMNs were analyzed in multiplex real-time polymerase chain reaction assays. However, differences in PMN microbicidal response against A. fumigatus in CLL patients were associated with the degree of hypogammaglobulinemia. PMID:23163595

  2. Glucocorticoid receptor activation impairs hippocampal plasticity by suppressing BDNF expression in obese mice

    PubMed Central

    Wosiski-Kuhn, Marlena; Erion, Joanna R.; Gomez-Sanchez, Elise P.; Gomez-Sanchez, Celso E.; Stranahan, Alexis M.

    2015-01-01

    Diabetes and obesity are associated with perturbation of adrenal steroid hormones and impairment of hippocampal plasticity, but the question of whether these conditions recruit glucocorticoid-mediated molecular cascades that are comparable to other stressors has yet to be fully addressed. We have used a genetic mouse model of obesity and diabetes with chronically elevated glucocorticoids to determine the mechanism for glucocorticoid-induced deficits in hippocampal synaptic function. Pharmacological inhibition of adrenal steroidogenesis attenuates structural and functional impairments by regulating plasticity among dendritic spines in the hippocampus of leptin receptor deficient (db/db) mice. Synaptic deficits evoked by exposure to elevated corticosterone levels in db/db mice are attributable to glucocorticoid receptor-mediated transrepression of AP-1 actions at BDNF promoters I and IV. db/db mice exhibit corticosterone-mediated reductions in brain-derived neurotrophic factor (BDNF), and a change in the ratio of TrkB to P75NTR that silences the functional response to BDNF stimulation. Lentiviral suppression of glucocorticoid receptor expression rescues behavioral and synaptic function in db/db mice, and also reinstates BDNF expression, underscoring the relevance of molecular mechanisms previously demonstrated after psychological stress to the functional alterations observed in obesity and diabetes. PMID:24636513

  3. Exercise-Induced Noradrenergic Activation Enhances Memory Consolidation in Both Normal Aging and Patients with Amnestic Mild Cognitive Impairment

    PubMed Central

    Segal, Sabrina K.; Cotman, Carl W.; Cahill, Lawrence F.

    2013-01-01

    Post-trial pharmacological activation of the noradrenergic system can facilitate memory consolidation. Because exercise activates the locus coeruleus and increases brain norepinephrine release, we hypothesized that post-trial exercise could function as a natural stimulus to enhance memory consolidation. We investigated this in amnestic mild cognitive impairment (aMCI) and cognitively normal elderly individuals by examining the effects of an acute bout of post-learning, aerobic exercise (6 minutes at 70% VO2 max on a stationary bicycle) on memory for some emotional images. Exercise significantly elevated endogenous norepinephrine (measured via the biomarker, salivary alpha-amylase) in both aMCI patients and controls. Additionally, exercise retrogradely enhanced memory in both aMCI patients and controls. Acute exercise that activates the noradrenergic system may serve as a beneficial, natural, and practical therapeutic intervention for cognitive decline in the aging population. PMID:22914593

  4. Exercise-induced noradrenergic activation enhances memory consolidation in both normal aging and patients with amnestic mild cognitive impairment.

    PubMed

    Segal, Sabrina K; Cotman, Carl W; Cahill, Lawrence F

    2012-01-01

    Post-trial pharmacological activation of the noradrenergic system can facilitate memory consolidation. Because exercise activates the locus coeruleus and increases brain norepinephrine release, we hypothesized that post-trial exercise could function as a natural stimulus to enhance memory consolidation. We investigated this in amnestic mild cognitive impairment (aMCI) and cognitively normal elderly individuals by examining the effects of an acute bout of post-learning, aerobic exercise (6 minutes at 70% VO2 max on a stationary bicycle) on memory for some emotional images. Exercise significantly elevated endogenous norepinephrine (measured via the biomarker, salivary alpha-amylase) in both aMCI patients and controls. Additionally, exercise retrogradely enhanced memory in both aMCI patients and controls. Acute exercise that activates the noradrenergic system may serve as a beneficial, natural, and practical therapeutic intervention for cognitive decline in the aging population.

  5. Psychometric Properties of the Physical Activity Questionnaire for Older Children in Italy: Testing the Validity among a General and Clinical Pediatric Population

    PubMed Central

    Gobbi, Erica; Elliot, Catherine; Varnier, Maurizio; Carraro, Attilio

    2016-01-01

    The purpose of this research was to assess an Italian version of the Physical Activity Questionnaire for Older Children (PAQ-C-It). Three separate studies were conducted, whereby testing general psychometric properties, construct validity, concurrent validity and the factor structure of the PAQ-C-It among general and clinical pediatric population. Study 1 (n = 1170) examined the psychometric properties, internal consistency, factor structure (exploratory factor analysis, EFA) and construct validity with enjoyment perception during physical activity. Study 2 (n = 59) reported on reliability, construct validity with enjoyment and BMI, and on cross-sectional concurrent validity with objectively measured MVPA (tri-axial accelerometry) over the span of seven consecutive days. Study 3 (n = 58) examined the PAQ-C-It reliability, construct validity with BMI and VO2max as the objective measurement among a population of children with congenital heart defects (CHD). In study 2 and 3, the factor structure of the PAQ-C-It was then re-examined with an EFA. The PAQ-C-It showed acceptable to good reliability (alpha .70 to .83). Results on construct validity showed moderate but significant association with enjoyment perception (r = .30 and .36), with BMI (r = -.30 and -.79 for CHD simple form), and with the VO2max (r = .55 for CHD simple form). Significant concurrent validity with the objectively measured MVPA was reported (rho = .30, p < .05). Findings of the EFA suggested a two-factor structure for the PAQ-C-It, with items 2, 3, and 4 contributing little to the total score. This study supports the PAQ-C-It as an appropriate instrument to assess the MVPA levels of Italian children, including children with simple forms of CHD. Support is given to the possible instrument effectiveness on a large international perspective in order to level out data gathering across the globe. PMID:27228050

  6. Impaired toll like receptor-7 and 9 induced immune activation in chronic spinal cord injured patients contributes to immune dysfunction

    PubMed Central

    Gungor, Bilgi; Kahraman, Tamer; Gursel, Mayda; Yilmaz, Bilge

    2017-01-01

    Reduced immune activation or immunosuppression is seen in patients withneurological diseases. Urinary and respiratory infections mainly manifested as septicemia and pneumonia are the most frequent complications following spinal cord injuries and they account for the majority of deaths. The underlying reason of these losses is believed to arise due to impaired immune responses to pathogens. Here, we hypothesized that susceptibility to infections of chronic spinal cord injured (SCI) patients might be due to impairment in recognition of pathogen associated molecular patterns and subsequently declining innate and adaptive immune responses that lead to immune dysfunction. We tested our hypothesis on healthy and chronic SCI patients with a level of injury above T-6. Donor PBMCs were isolated and stimulated with different toll like receptor ligands and T-cell inducers aiming to investigate whether chronic SCI patients display differential immune activation to multiple innate and adaptive immune cell stimulants. We demonstrate that SCI patients' B-cell and plasmacytoid dendritic cells retain their functionality in response to TLR7 and TLR9 ligand stimulation as they secreted similar levels of IL6 and IFNα. The immune dysfunction is not probably due to impaired T-cell function, since neither CD4+ T-cell dependent IFNγ producing cell number nor IL10 producing regulatory T-cells resulted different outcomes in response to PMA-Ionomycin and PHA-LPS stimulation, respectively. We showed that TLR7 dependent IFNγ and IP10 levels and TLR9 mediated APC function reduced substantially in SCI patients compared to healthy subjects. More importantly, IP10 producing monocytes were significantly fewer compared to healthy subjects in response to TLR7 and TLR9 stimulation of SCI PBMCs. When taken together this work implicated that these defects could contribute to persistent complications due to increased susceptibility to infections of chronic SCI patients. PMID:28170444

  7. Impairments, activity limitations and participation restrictions experienced in the first year following a critical illness: protocol for a systematic review

    PubMed Central

    Coffey Scott, Jacqueline; Hinman, Rana S; Lee, Alan Chong; Smith, James M

    2017-01-01

    Introduction Critical illness requiring intensive care unit (ICU) management is a life-altering event with ∼25% of ICU survivors experiencing persistent reductions in physical functioning, impairments in mental health, cognitive dysfunction and decreased quality of life. This constellation of problems is known as ‘postintensive care syndrome’ (PICS) and may persist for months and/or years. The purpose of this systematic review is to identify the scope and magnitude of physical problems associated with PICS during the first year after discharge from ICU, using the International Classification of Functioning, Disability and Health framework to elucidate the impairments of body functions and structures, activity limitations and participation restrictions. Methods and analysis Medline (Ovid), Cochrane Database of Systematic Reviews (Ovid), Cochrane Central Register of Controlled Trials (Ovid), PubMed, CINAHL (EBSCO), Web of Science and EMBASE will be systematically searched for observational studies reporting the physical impairments of body functions and structures, activity limitations and participation restrictions associated with PICS. Two reviewers will assess the articles for eligibility according to prespecified selection criteria, after which an independent reviewer will perform data extraction which will be validated by a second independent reviewer. Quality appraisal will be performed by two independent reviewers. Outcomes of the included studies will be summarised in tables and in narrative format and meta-analyses will be conducted where appropriate. Ethics and dissemination Formal ethical approval is not required as no primary data is collected. This systematic review will identify the scope and magnitude of physical problems associated with PICS during the first year after discharge from ICU and will be disseminated through a peer-reviewed publication and at conference meetings, to inform practice and future research on the physical problems

  8. Activated Microglia-Induced Deficits in Excitatory Synapses Through IL-1β: Implications for Cognitive Impairment in Sepsis.

    PubMed

    Moraes, Carolina A; Santos, Gabriel; de Sampaio e Spohr, Tania Cristina Leite; D'Avila, Joana C; Lima, Flávia Regina Souza; Benjamim, Claudia Farias; Bozza, Fernando A; Gomes, Flávia Carvalho Alcantara

    2015-08-01

    Recent clinical studies have shown that sepsis survivors may develop long-term cognitive impairments. The cellular and molecular mechanisms involved in these events are not well understood. This study investigated synaptic deficits in sepsis and the involvement of glial cells in this process. Septic animals showed memory impairment and reduced numbers of hippocampal and cortical excitatory synapses, identified by synaptophysin/PSD-95 co-localization, 9 days after disease onset. The behavioral deficits and synaptophysin/PSD-95 co-localization were rescued to normal levels within 30 days post-sepsis. Septic mice presented activation of microglia and reactive astrogliosis, which are hallmarks of brain injury and could be involved in the associated synaptic deficits. We treated neuronal cultures with conditioned medium derived from cultured astrocytes (ACM) and microglia (MCM) that were either non-stimulated or stimulated with lipopolysaccharide (LPS) to investigate the molecular mechanisms underlying synaptic deficits in sepsis. ACM and MCM increased the number of synapses between cortical neurons in vitro, and these effects were antagonized by LPS stimulation. LPS-MCM reduced the number of synapses by 50%, but LPS-ACM increased the number of synapses by 500%. Analysis of the composition of these conditioned media revealed increased levels of IL-1β in LPS-MCM. Furthermore, inhibition of IL-1β signaling through the addition of a soluble IL-1β receptor antagonist (IL-1 Ra) fully prevented the synaptic deficit induced by LPS-MCM. These results suggest that sepsis induces a transient synaptic deficit associated with memory impairments mediated by IL-1β secreted by activated microglia.

  9. Whole genome expression profiling associates activation of unfolded protein response with impaired production and release of epinephrine after recurrent hypoglycemia

    PubMed Central

    Kim, Juhye Lena; La Gamma, Edmund F.; Estabrook, Todd; Kudrick, Necla

    2017-01-01

    Recurrent hypoglycemia can occur as a major complication of insulin replacement therapy, limiting the long-term health benefits of intense glycemic control in type 1 and advanced type 2 diabetic patients. It impairs the normal counter-regulatory hormonal and behavioral responses to glucose deprivation, a phenomenon known as hypoglycemia associated autonomic failure (HAAF). The molecular mechanisms leading to defective counter-regulation are not completely understood. We hypothesized that both neuronal (excessive cholinergic signaling between the splanchnic nerve fibers and the adrenal medulla) and humoral factors contribute to the impaired epinephrine production and release in HAAF. To gain further insight into the molecular mechanism(s) mediating the blunted epinephrine responses following recurrent hypoglycemia, we utilized a global gene expression profiling approach. We characterized the transcriptomes during recurrent (defective counter-regulation model) and acute hypoglycemia (normal counter-regulation group) in the adrenal medulla of normal Sprague-Dawley rats. Based on comparison analysis of differentially expressed genes, a set of unique genes that are activated only at specific time points after recurrent hypoglycemia were revealed. A complementary bioinformatics analysis of the functional category, pathway, and integrated network indicated activation of the unfolded protein response. Furthermore, at least three additional pathways/interaction networks altered in the adrenal medulla following recurrent hypoglycemia were identified, which may contribute to the impaired epinephrine secretion in HAAF: greatly increased neuropeptide signaling (proenkephalin, neuropeptide Y, galanin); altered ion homeostasis (Na+, K+, Ca2+) and downregulation of genes involved in Ca2+-dependent exocytosis of secretory vesicles. Given the pleiotropic effects of the unfolded protein response in different organs, involved in maintaining glucose homeostasis, these findings uncover

  10. Activating transcription factor 4 underlies the pathogenesis of arsenic trioxide-mediated impairment of macrophage innate immune functions.

    PubMed

    Srivastava, Ritesh K; Li, Changzhao; Wang, Yong; Weng, Zhiping; Elmets, Craig A; Harrod, Kevin S; Deshane, Jessy S; Athar, Mohammad

    2016-10-01

    Chronic arsenic exposure to humans is considered immunosuppressive with augmented susceptibility to several infectious diseases. The exact molecular mechanisms, however, remain unknown. Earlier, we showed the involvement of unfolded protein response (UPR) signaling in arsenic-mediated impairment of macrophage functions. Here, we show that activating transcription factor 4 (ATF4), a UPR transcription factor, regulates arsenic trioxide (ATO)-mediated dysregulation of macrophage functions. In ATO-treated ATF4(+/+) wild-type mice, a significant down-regulation of CD11b expression was associated with the reduced phagocytic functions of peritoneal and lung macrophages. This severe immuno-toxicity phenotype was not observed in ATO-treated ATF4(+/-) heterozygous mice. To confirm these observations, we demonstrated in Raw 264.7 cells that ATF4 knock-down rescues ATO-mediated impairment of macrophage functions including cytokine production, bacterial engulfment and clearance of engulfed bacteria. Sustained activation of ATF4 by ATO in macrophages induces apoptosis, while diminution of ATF4 expression protects against ATO-induced apoptotic cell death. Raw 264.7 cells treated with ATO also manifest dysregulated Ca(++) homeostasis. ATO induces Ca(++)-dependent calpain-1 and caspase-12 expression which together regulated macrophage apoptosis. Additionally, apoptosis was also induced by mitochondria-regulated pathway. Restoring ATO-impaired Ca(++) homeostasis in ER/mitochondria by treatments with the inhibitors of inositol 1,4,5-trisphosphate receptor (IP3R) and voltage-dependent anion channel (VDAC) attenuate innate immune functions of macrophages. These studies identify a novel role for ATF4 in underlying pathogenesis of macrophage dysregulation and immuno-toxicity of arsenic.

  11. Loss of hippocampal neurogenesis, increased novelty-induced activity, decreased home cage activity, and impaired reversal learning one year after irradiation of the young mouse brain.

    PubMed

    Kalm, Marie; Karlsson, Niklas; Nilsson, Marie K L; Blomgren, Klas

    2013-09-01

    Radiotherapy is a major cause of long-term complications in survivors of pediatric brain tumors. These complications include intellectual and memory impairments as well as perturbed growth and puberty. We investigated the long-term effects of a single 8 Gy irradiation dose to the brains of 14-day-old mice. Behavior was assessed one year after irradiation using IntelliCage and open field, followed by immunohistochemical investigation of proliferation and neurogenesis in the dentate gyrus of the hippocampus. We found a 61% reduction in proliferation and survival (BrdU incorporation 4 weeks prior to sacrifice), 99% decrease in neurogenesis (number of doublecortin-positive cells) and gliosis (12% higher astrocyte density) one year following irradiation. Irradiated animals displayed increased activity in a novel environment but decreased activity in their home cage. Place learning in the IntelliCage was unaffected by irradiation but reversal learning was impaired. Irradiated animals persevered in visiting previously correct corners to a higher extent compared to control animals. Hence, despite the virtual absence of neurogenesis in these old mice, spatial learning could take place. Reversal learning however, where a previous memory was replaced with a new one, was partly impaired. This model is useful to study the so called late effects of radiotherapy to the young brain and to evaluate possible interventions.

  12. CIA2 deficiency results in impaired oxidative stress response and enhanced intracellular basal UPR activity in Saccharomyces cerevisiae.

    PubMed

    Zhao, Wei; Zheng, Hua-Zhen; Niu, Yu-Jie; Yuan, Yuan; Fang, Bing-Xiong; Liu, Yi-Na; Cai, Lu-Hui; Zhou, Zhong-Jun; Liu, Xin-Guang

    2015-03-01

    Yeast Cia2p is a component of the cytosolic Fe/S protein assembly (CIA) machinery. Initial studies of the CIA machinery were performed in yeast, but the precise role of Cia2p in this eukaryote is still unknown. We report that CIA2 deficiency results in impaired oxidative stress response, as evidenced by increased sensitivity to the oxidant cumene hydroperoxide (CHP), impaired activities of superoxide dismutases and aconitase and decreased replicative lifespan in the mutants. Moreover, intracellular reactive oxygen species levels were significantly increased in CIA2-deficient cells after treatment with CHP. We also show that CIA2-deficient cells display an increased resistance to tunicamycin-induced endoplasmic reticulum (ER) stress, as evidenced by the upregulated splicing of the mRNA of HAC1, which encodes a functional transcription factor that regulates the transcription of unfolded protein response (UPR) target genes, suggesting enhanced intracellular UPR activity. Furthermore, the transcription of several canonical UPR target genes is strongly induced in CIA2-deficient cells as compared with wild-type controls. Taken together, these results suggest the involvement of Cia2p in oxidative and ER stress responses in yeast.

  13. Intracerebroventricular D-galactose administration impairs memory and alters activity and expression of acetylcholinesterase in the rat.

    PubMed

    Rodrigues, André Felipe; Biasibetti, Helena; Zanotto, Bruna Stela; Sanches, Eduardo Farias; Pierozan, Paula; Schmitz, Felipe; Parisi, Mariana Migliorini; Barbé-Tuana, Florencia; Netto, Carlos Alexandre; Wyse, Angela T S

    2016-05-01

    Tissue accumulation of galactose is a hallmark in classical galactosemia. Cognitive deficit is a symptom of this disease which is poorly understood. The aim of this study was to investigate the effects of intracerebroventricular administration of galactose on memory (inhibitory avoidance and novel object recognition tasks) of adult rats. We also investigated the effects of galactose on acetylcholinesterase (AChE) activity, immunocontent and gene expression in hippocampus and cerebral cortex. Wistar rats received a single injection of galactose (4mM) or saline (control). For behavioral parameters, galactose was injected 1h or 24h previously to the testing. For biochemical assessment, animals were decapitated 1h, 3h or 24h after galactose or saline injection; hippocampus and cerebral cortex were dissected. Results showed that galactose impairs the memory formation process in aversive memory (inhibitory avoidance task) and recognition memory (novel object recognition task) in rats. The activity of AChE was increased, whereas the gene expression of this enzyme was decreased in hippocampus, but not in cerebral cortex. These findings suggest that these changes in AChE may, at least in part, to lead to memory impairment caused by galactose. Taken together, our results can help understand the etiopathology of classical galactosemia.

  14. A cytoplasmic negative regulator isoform of ATF7 impairs ATF7 and ATF2 phosphorylation and transcriptional activity.

    PubMed

    Diring, Jessica; Camuzeaux, Barbara; Donzeau, Mariel; Vigneron, Marc; Rosa-Calatrava, Manuel; Kedinger, Claude; Chatton, Bruno

    2011-01-01

    Alternative splicing and post-translational modifications are processes that give rise to the complexity of the proteome. The nuclear ATF7 and ATF2 (activating transcription factor) are structurally homologous leucine zipper transcription factors encoded by distinct genes. Stress and growth factors activate ATF2 and ATF7 mainly via sequential phosphorylation of two conserved threonine residues in their activation domain. Distinct protein kinases, among which mitogen-activated protein kinases (MAPK), phosphorylate ATF2 and ATF7 first on Thr71/Thr53 and next on Thr69/Thr51 residues respectively, resulting in transcriptional activation. Here, we identify and characterize a cytoplasmic alternatively spliced isoform of ATF7. This variant, named ATF7-4, inhibits both ATF2 and ATF7 transcriptional activities by impairing the first phosphorylation event on Thr71/Thr53 residues. ATF7-4 indeed sequesters the Thr53-phosphorylating kinase in the cytoplasm. Upon stimulus-induced phosphorylation, ATF7-4 is poly-ubiquitinated and degraded, enabling the release of the kinase and ATF7/ATF2 activation. Our data therefore conclusively establish that ATF7-4 is an important cytoplasmic negative regulator of ATF7 and ATF2 transcription factors.

  15. A Cytoplasmic Negative Regulator Isoform of ATF7 Impairs ATF7 and ATF2 Phosphorylation and Transcriptional Activity

    PubMed Central

    Diring, Jessica; Camuzeaux, Barbara; Donzeau, Mariel; Vigneron, Marc; Rosa-Calatrava, Manuel; Kedinger, Claude; Chatton, Bruno

    2011-01-01

    Alternative splicing and post-translational modifications are processes that give rise to the complexity of the proteome. The nuclear ATF7 and ATF2 (activating transcription factor) are structurally homologous leucine zipper transcription factors encoded by distinct genes. Stress and growth factors activate ATF2 and ATF7 mainly via sequential phosphorylation of two conserved threonine residues in their activation domain. Distinct protein kinases, among which mitogen-activated protein kinases (MAPK), phosphorylate ATF2 and ATF7 first on Thr71/Thr53 and next on Thr69/Thr51 residues respectively, resulting in transcriptional activation. Here, we identify and characterize a cytoplasmic alternatively spliced isoform of ATF7. This variant, named ATF7-4, inhibits both ATF2 and ATF7 transcriptional activities by impairing the first phosphorylation event on Thr71/Thr53 residues. ATF7-4 indeed sequesters the Thr53-phosphorylating kinase in the cytoplasm. Upon stimulus-induced phosphorylation, ATF7-4 is poly-ubiquitinated and degraded, enabling the release of the kinase and ATF7/ATF2 activation. Our data therefore conclusively establish that ATF7-4 is an important cytoplasmic negative regulator of ATF7 and ATF2 transcription factors. PMID:21858082

  16. Applying Learning Strategy Questionnaires: Problems and Possibilities

    ERIC Educational Resources Information Center

    Schellings, Gonny

    2011-01-01

    This article discusses measuring learning strategies by means of questionnaires. In "multi-method" research, in which think-aloud measures are compared with questionnaires, low or moderate correlations are found. A conclusion often drawn is that learners are not able to verbally report on their learning activities. Alternative explanations concern…

  17. A Nutritional Questionnaire for Older Adults.

    ERIC Educational Resources Information Center

    Fanelli, Marie T.; Abernethy, Marilyn M.

    1986-01-01

    Describes a questionnaire assessing nutritional knowledge and eating behaviors of older adults. The questionnaire consists of six sections: demographic and personal information, food resources, food consumption patterns, dietary practices related to health, activity patterns, and nutritional knowledge. Study results demonstrating the…

  18. Objectively measured physical activity, brain atrophy, and white matter lesions in older adults with mild cognitive impairment.

    PubMed

    Doi, Takehiko; Makizako, Hyuma; Shimada, Hiroyuki; Tsutsumimoto, Kota; Hotta, Ryo; Nakakubo, Sho; Park, Hyuntae; Suzuki, Takao

    2015-02-01

    Physical activity may help to prevent or delay brain atrophy. Numerous studies have shown associations between physical activity and age-related changes in the brain. However, most of these studies involved self-reported physical activity, not objectively measured physical activity. Therefore, the aim of this study was to examine the association between objectively measured physical activity, as determined using accelerometers, and brain magnetic resonance imaging (MRI) measures in older adults with mild cognitive impairment (MCI). We analyzed 323 older subjects with MCI (mean age 71.4 years) who were recruited from the participants of the Obu Study of Health Promotion for the Elderly. We recorded demographic data and measured physical activity using a tri-axial accelerometer. Physical activity was classified as light-intensity physical activity (LPA) or moderate-to-vigorous physical activity (MVPA). Brain atrophy and the severity of white matter lesions (WML) were determined by MRI. Low levels of LPA and MVPA were associated with severe WML. Subjects with severe WML were older, had lower mobility, and had greater brain atrophy than subjects with mild WML (all P<0.05). Multivariate analysis revealed that more MVPA was associated with less brain atrophy, even after adjustment for WML (β=-0.126, P=0.015), but LPA was not (β=-0.102, P=0.136). Our study revealed that objectively measured physical activity, especially MVPA, was associated with brain atrophy in MCI subjects, even after adjusting for WML. These findings support the hypothesis that physical activity plays a crucial role in maintaining brain health.

  19. Aldosterone Increases Oxidant Stress to Impair Guanylyl Cyclase Activity by Cysteinyl Thiol Oxidation in Vascular Smooth Muscle Cells*S⃞

    PubMed Central

    Maron, Bradley A.; Zhang, Ying-Yi; Handy, Diane E.; Beuve, Annie; Tang, Shiow-Shih; Loscalzo, Joseph; Leopold, Jane A.

    2009-01-01

    Hyperaldosteronism is associated with impaired endothelium-dependent vascular reactivity owing to increased reactive oxygen species and decreased bioavailable nitric oxide (NO·); however, the effects of aldosterone on vasodilatory signaling pathways in vascular smooth muscle cells (VSMC) remain unknown. Soluble guanylyl cyclase (GC) is a heterodimer that is activated by NO· to convert cytosolic GTP to cGMP, a second messenger required for normal VSMC relaxation. Here, we show that aldosterone (10-9-10-7 mol/liter) diminishes GC activity by activating NADPH oxidase in bovine aortic VSMC to increase reactive oxygen species levels and induce oxidative posttranslational modification(s) of Cys-122, a β1-subunit cysteinyl residue demonstrated previously to modulate NO· sensing by GC. In VSMC treated with aldosterone, Western immunoblotting detected evidence of GC β1-subunit disulfide bonding, whereas mass spectrometry analysis of a homologous peptide containing the Cys-122-bearing sequence exposed to conditions of increased oxidant stress confirmed cysteinyl sulfinic acid (m/z 435), sulfonic acid (m/z 443), and disulfide (m/z 836) bond formation. The functional effect of these modifications was examined by transfecting COS-7 cells with wild-type GC or mutant GC containing an alanine substitution at Cys-122 (C122A). Exposure to aldosterone or hydrogen peroxide (H2O2) significantly decreased cGMP levels in cells expressing wild-type GC. In contrast, aldosterone or H2O2 did not influence cGMP levels in cells expressing the mutant C122A GC, confirming that oxidative modification of Cys-122 specifically impairs GC activity. These findings demonstrate that pathophysiologically relevant concentrations of aldosterone increase oxidant stress to convert GC to an NO·-insensitive state, resulting in disruption of normal vasodilatory signaling pathways in VSMC. PMID:19141618

  20. Exendin-4 induced glucagon-like peptide-1 receptor activation reverses behavioral impairments of mild traumatic brain injury in mice.

    PubMed

    Rachmany, Lital; Tweedie, David; Li, Yazhou; Rubovitch, Vardit; Holloway, Harold W; Miller, Jonathan; Hoffer, Barry J; Greig, Nigel H; Pick, Chaim G

    2013-10-01

    Mild traumatic brain injury (mTBI) represents a major and increasing public health concern and is both the most frequent cause of mortality and disability in young adults and a chief cause of morbidity in the elderly. Albeit mTBI patients do not show clear structural brain defects and, generally, do not require hospitalization, they frequently suffer from long-lasting cognitive, behavioral, and emotional problems. No effective pharmaceutical therapy is available, and existing treatment chiefly involves intensive care management after injury. The diffuse neural cell death evident after mTBI is considered mediated by oxidative stress and glutamate-induced excitotoxicity. Prior studies of the long-acting GLP-1 receptor agonist, exendin-4 (Ex-4), an incretin mimetic approved for type 2 diabetes mellitus treatment, demonstrated its neurotrophic/protective activity in cellular and animal models of stroke, Alzheimer's and Parkinson's diseases, and, consequent to commonalities in mechanisms underpinning these disorders, Ex-4 was assessed in a mouse mTBI model. In neuronal cultures in this study, Ex-4 ameliorated H2O2-induced oxidative stress and glutamate toxicity. To evaluate in vivo translation, we administered steady-state Ex-4 (3.5 pM/kg/min) or saline to control and mTBI mice over 7 days starting 48 h prior to or 1 h post-sham or mTBI (30 g weight drop under anesthesia). Ex-4 proved well-tolerated and fully ameliorated mTBI-induced deficits in novel object recognition 7 and 30 days post-trauma. Less mTBI-induced impairment was evident in Y-maze, elevated plus maze, and passive avoidance paradigms, but when impairment was apparent Ex-4 induced amelioration. Together, these results suggest that Ex-4 may act as a neurotrophic/neuroprotective drug to minimize mTBI impairment.

  1. Comparison of the EPIC Physical Activity Questionnaire with Combined Heart Rate and Movement Sensing in a Nationally Representative Sample of Older British Adults

    PubMed Central

    España-Romero, Vanesa; Golubic, Rajna; Martin, Kathryn R.; Hardy, Rebecca; Ekelund, Ulf; Kuh, Diana; Wareham, Nicholas J.; Cooper, Rachel; Brage, Soren

    2014-01-01

    Objectives To compare physical activity (PA) subcomponents from EPIC Physical Activity Questionnaire (EPAQ2) and combined heart rate and movement sensing in older adults. Methods Participants aged 60–64y from the MRC National Survey of Health and Development in Great Britain completed EPAQ2, which assesses self-report PA in 4 domains (leisure time, occupation, transportation and domestic life) during the past year and wore a combined sensor for 5 consecutive days. Estimates of PA energy expenditure (PAEE), sedentary behaviour, light (LPA) and moderate-to-vigorous PA (MVPA) were obtained from EPAQ2 and combined sensing and compared. Complete data were available in 1689 participants (52% women). Results EPAQ2 estimates of PAEE and MVPA were higher than objective estimates and sedentary time and LPA estimates were lower [bias (95% limits of agreement) in men and women were 32.3 (−61.5 to 122.6) and 29.0 (−39.2 to 94.6) kJ/kg/day for PAEE; −4.6 (−10.6 to 1.3) and −6.0 (−10.9 to −1.0) h/day for sedentary time; −171.8 (−454.5 to 110.8) and −60.4 (−367.5 to 246.6) min/day for LPA; 91.1 (−159.5 to 341.8) and 55.4 (−117.2 to 228.0) min/day for MVPA]. There were significant positive correlations between all self-reported and objectively assessed PA subcomponents (rho  = 0.12 to 0.36); the strongest were observed for MVPA (rho = 0.30 men; rho = 0.36 women) and PAEE (rho = 0.26 men; rho = 0.25 women). Conclusion EPAQ2 produces higher estimates of PAEE and MVPA and lower estimates of sedentary and LPA than objective assessment. However, both methodologies rank individuals similarly, suggesting that EPAQ2 may be used in etiological studies in this population. PMID:24516543

  2. Cognitive Impairments in Schizophrenia as Assessed Through Activation and Connectivity Measures of Magnetoencephalography (MEG) Data

    PubMed Central

    Hinkley, Leighton B. N.; Owen, Julia P.; Fisher, Melissa; Findlay, Anne M.; Vinogradov, Sophia; Nagarajan, Srikantan S.

    2009-01-01

    The cognitive dysfunction present in patients with schizophrenia is thought to be driven in part by disorganized connections between higher-order cortical fields. Although studies utilizing electroencephalography (EEG), PET and fMRI have contributed significantly to our understanding of these mechanisms, magnetoencephalography (MEG) possesses great potential to answer long-standing questions linking brain interactions to cognitive operations in the disorder. Many experimental paradigms employed in EEG and fMRI are readily extendible to MEG and have expanded our understanding of the neurophysiological architecture present in schizophrenia. Source reconstruction techniques, such as adaptive spatial filtering, take advantage of the spatial localization abilities of MEG, allowing us to evaluate which specific structures contribute to atypical cognition in schizophrenia. Finally, both bivariate and multivariate functional connectivity metrics of MEG data are useful for understanding how these interactions in the brain are impaired in schizophrenia, and how cognitive and clinical outcomes are affected as a result. We also present here data from our own laboratory that illustrates how some of these novel functional connectivity measures, specifically imaginary coherence (IC), are quite powerful in relating disconnectivity in the brain to characteristic behavioral findings in the disorder. PMID:21160543

  3. Longitudinal Alteration of Intrinsic Brain Activity in the Striatum in Mild Cognitive Impairment

    PubMed Central

    Ren, Ping; Lo, Raymond Y.; Chapman, Benjamin P.; Mapstone, Mark; Porsteinsson, Anton; Lin, Feng

    2016-01-01

    The striatum is a critical functional hub in understanding neurological disorders. However, the Alzheimer’s disease (AD)-associated striatal change is unclear, nor the relationship between striatal change and AD pathology. Three-year resting-state fMRI data from 15 healthy control (HC) and 20 mild cognitive impairment (MCI) participants were obtained. We analyzed the amplitude of low-frequency fluctuations (ALFF) (0.01–0.08 Hz) and two subdivided bands (slow-4: 0.027–0.073 Hz; slow-5: 0.01–0.027 Hz). We calculated Aβ/pTau ratio using baseline cerebrospinal fluid pTau and beta-amyloid1–42 to represent AD pathology. Compared to HC, MCI participants showed greater decline in right putaminal ALFF, including the slow-4 band. Greater decline of ALFF in the right putamen was significantly related to the memory decline over time and lower baseline Aβ/pTau ratio regardless of age or group. The slow-4 band, relative to slow-5 band, showed a stronger correlation between Aβ/pTau ratio and decline of ALFF in the right putamen. The results suggest that the putaminal function declines early in the AD-associated neurodegeneration. The continuous decline in putaminal ALFF, especially slow-4 band, may be a sensitive marker of AD pathology such as Aβ/pTau ratio regardless of clinical diagnosis. PMID:27472880

  4. Defective CFTR-dependent CREB activation results in impaired spermatogenesis and azoospermia.

    PubMed

    Xu, Wen Ming; Chen, Jing; Chen, Hui; Diao, Rui Ying; Fok, Kin Lam; Dong, Jian Da; Sun, Ting Ting; Chen, Wen Ying; Yu, Mei Kuen; Zhang, Xiao Hu; Tsang, Lai Ling; Lau, Ann; Shi, Qi Xian; Shi, Qing Hua; Huang, Ping Bo; Chan, Hsiao Chang

    2011-01-01

    Cystic fibrosis (CF) is the most common life-limiting recessive genetic disease among Caucasians caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) with over 95% male patients infertile. However, whether CFTR mutations could affect spermatogenesis and result in azoospermia remains an open question. Here we report compromised spermatogenesis, with significantly reduced testicular weight and sperm count, and decreased cAMP-responsive element binding protein (CREB) expression in the testes of CFTR knockout mice. The involvement of CFTR in HCO(3) (-) transport and the expression of the HCO(3) (-) sensor, soluble adenylyl cyclase (sAC), are demonstrated for the first time in the primary culture of rat Sertoli cells. Inhibition of CFTR or depletion of HCO(3) (-) could reduce FSH-stimulated, sAC-dependent cAMP production and phosphorylation of CREB, the key transcription factor in spermatogenesis. Decreased CFTR and CREB expression are also observed in human testes with azoospermia. The present study reveals a previously undefined role of CFTR and sAC in regulating the cAMP-CREB signaling pathway in Sertoli cells, defect of which may result in impaired spermatogenesis and azoospermia. Altered CFTR-sAC-cAMP-CREB functional loop may also underline the pathogenesis of various CF-related diseases.

  5. Questionnaire typography and production.

    PubMed

    Gray, M

    1975-06-01

    This article describes the typographic principles and practice which provide the basis of good design and print, the relevant printing processes which can be used, and the graphic designer's function in questionnaire production. As they impose constraints on design decisions to be discussed later in the text, the various methods of printing and production are discussed first.

  6. Regulatory role of microRNA-30b and plasminogen activator inhibitor-1 in the pathogenesis of cognitive impairment

    PubMed Central

    LI, XIUQIN; GAO, YONG; MENG, ZHAOYUN; ZHANG, CUI; QI, QINDE

    2016-01-01

    The present study aimed to investigate the role of plasminogen activator inhibitor-1 (PAI-1) in drug-induced early cognitive impairment and the underlying mechanism concerning microRNA (miR)-30b. A mouse model of cognitive impairment was established by intraperitoneal injection of scopolamine (2 mg/kg body weight) for 13 days. Behavioral performance was assessed using the Morris water maze (MWM) test. The mRNA expression levels of PAI-1 and miR-30b were detected using quantitative polymerase chain reaction (qPCR). The protein expression levels of PAI-1 in the hippocampus and blood were determined using western blot analysis and enzyme-linked immunosorbent assays. The MWM test demonstrated that, on days 3 and 4, the escape latency was significantly elevated in the model mice in comparison with control group (P<0.05). In addition, the length of swimming path was significantly increased (P<0.05), while the number of times of crossing the platform location was significantly reduced in the model mouse group (P<0.05) in comparison with the control group. qPCR demonstrated that the mRNA expression levels of PAI-1 in the model mice was significantly elevated in the hippocampus and blood in comparison with the control group (P<0.01). Furthermore, western blot analysis and enzyme-linked immunosorbent assay demonstrated that the protein expression levels of PAI-1 were significantly elevated in the hippocampus and blood in the model group, in comparison with the control group (P<0.05). Notably, the levels of miR-30b in the hippocampus and blood were significantly decreased in the model mice in comparison with the control group (P<0.01). To conclude, the expression levels of PAI-1 were significantly elevated in mice with scopolamine-induced cognitive impairment, which may be associated with the downregulation of miR-30b. The findings from the present study suggest that miR-30b may be involved in the regulation of PAI-1, which would contribute to the pathogenesis of cognitive

  7. Interferon-α inducible protein 6 impairs EGFR activation by CD81 and inhibits hepatitis C virus infection.

    PubMed

    Meyer, Keith; Kwon, Young-Chan; Liu, Shuanghu; Hagedorn, Curt H; Ray, Ratna B; Ray, Ranjit

    2015-03-11

    Viral entry requires co-operative interactions of several host cell factors. Interferon (IFN) and the IFN-stimulated genes (ISGs) play a central role in antiviral responses against hepatitis C virus (HCV) infection. We examined the effect of interferon-α inducible protein 6 (IFI6) against HCV infection in human hepatoma cells. HCV RNA level or infectious foci were inhibited significantly by ectopic expression of IFI6. IFI6 impaired CD81 co-localization with claudin-1 (CLDN1) upon HCV infection or CD81 cross-linking by specific antibody. Activation of epidermal growth factor receptor (EGFR), a co-factor involved in CD81/CLDN1 interactions, was reduced in IFI6 expressing cells in response to HCV infection or CD81 cross linking by antibody, but not by treatment with EGF. Taken together, the results from our study support a model where IFI6 inhibits HCV entry by impairing EGFR mediated CD81/CLDN1 interactions. This may be relevant to other virus entry processes employing EGFR.

  8. Anemia and Red Blood Cell Indices Predict HIV-Associated Neurocognitive Impairment in the Highly Active Antiretroviral Therapy Era

    PubMed Central

    Kallianpur, Asha R.; Wang, Quan; Jia, Peilin; Hulgan, Todd; Zhao, Zhongming; Letendre, Scott L.; Ellis, Ronald J.; Heaton, Robert K.; Franklin, Donald R.; Barnholtz-Sloan, Jill; Collier, Ann C.; Marra, Christina M.; Clifford, David B.; Gelman, Benjamin B.; McArthur, Justin C.; Morgello, Susan; Simpson, David M.; McCutchan, J. A.; Grant, Igor

    2016-01-01

    Background. Anemia has been linked to adverse human immunodeficiency virus (HIV) outcomes, including dementia, in the era before highly active antiretroviral therapy (HAART). Milder forms of HIV-associated neurocognitive disorder (HAND) remain common in HIV-infected persons, despite HAART, but whether anemia predicts HAND in the HAART era is unknown. Methods. We evaluated time-dependent associations of anemia and cross-sectional associations of red blood cell indices with neurocognitive impairment in a multicenter, HAART-era HIV cohort study (N = 1261), adjusting for potential confounders, including age, nadir CD4+ T-cell count, zidovudine use, and comorbid conditions. Subjects underwent comprehensive neuropsychiatric and neuromedical assessments. Results. HAND, defined according to standardized criteria, occurred in 595 subjects (47%) at entry. Mean corpuscular volume and mean corpuscular hemoglobin were positively associated with the global deficit score, a continuous measure of neurocognitive impairment (both P < .01), as well as with all HAND, milder forms of HAND, and HIV-associated dementia in multivariable analyses (all P < .05). Anemia independently predicted development of HAND during a median follow-up of 72 months (adjusted hazard ratio, 1.55; P < .01). Conclusions. Anemia and red blood cell indices predict HAND in the HAART era and may contribute to risk assessment. Future studies should address whether treating anemia may help to prevent HAND or improve cognitive function in HIV-infected persons. PMID:26690344

  9. Optogenetic silencing of locus coeruleus activity in mice impairs cognitive flexibility in an attentional set-shifting task

    PubMed Central

    Janitzky, Kathrin; Lippert, Michael T.; Engelhorn, Achim; Tegtmeier, Jennifer; Goldschmidt, Jürgen; Heinze, Hans-Jochen; Ohl, Frank W.

    2015-01-01

    The locus coeruleus (LC) is the sole source of noradrenergic projections to the cortex and essential for attention-dependent cognitive processes. In this study we used unilateral optogenetic silencing of the LC in an attentional set-shifting task (ASST) to evaluate the influence of the LC on prefrontal cortex-dependent functions in mice. We expressed the halorhodopsin eNpHR 3.0 to reversibly silence LC activity during task performance, and found that silencing selectively impaired learning of those parts of the ASST that most strongly rely on cognitive flexibility. In particular, extra-dimensional set-shifting (EDS) and reversal learning was impaired, suggesting an involvement of the medial prefrontal cortex (mPFC) and the orbitofrontal cortex. In contrast, those parts of the task that are less dependent on cognitive flexibility, i.e., compound discrimination (CD) and the intra-dimensional shifts (IDS) were not affected. Furthermore, attentional set formation was unaffected by LC silencing. Our results therefore suggest a modulatory influence of the LC on cognitive flexibility, mediated by different frontal networks. PMID:26582980

  10. Macrophage peroxisome proliferator-activated receptor γ deficiency delays skin wound healing through impairing apoptotic cell clearance in mice.

    PubMed

    Chen, H; Shi, R; Luo, B; Yang, X; Qiu, L; Xiong, J; Jiang, M; Liu, Y; Zhang, Z; Wu, Y

    2015-01-15

    Skin wound macrophages are key regulators of skin repair and their dysfunction causes chronic, non-healing skin wounds. Peroxisome proliferator-activated receptor gamma (PPARγ) regulates pleiotropic functions of macrophages, but its contribution in skin wound healing is poorly defined. We observed that macrophage PPARγ expression was upregulated during skin wound healing. Furthermore, macrophage PPARγ deficiency (PPARγ-knock out (KO)) mice exhibited impaired skin wound healing with reduced collagen deposition, angiogenesis and granulation formation. The tumor necrosis factor alpha (TNF-α) expression in wounds of PPARγ-KO mice was significantly increased and local restoration of TNF-α reversed the healing deficit in PPARγ-KO mice. Wound macrophages produced higher levels of TNF-α in PPARγ-KO mice compared with control. In vitro, the higher production of TNF-α by PPARγ-KO macrophages was associated with impaired apoptotic cell clearance. Correspondingly, increased apoptotic cell accumulation was found in skin wound of PPARγ-KO mice. Mechanically, peritoneal and skin wound macrophages expressed lower levels of various phagocytosis-related molecules. In addition, PPARγ agonist accelerated wound healing and reduced local TNF-α expression and wound apoptotic cells accumulation in wild type but not PPARγ-KO mice. Therefore, PPARγ has a pivotal role in controlling wound macrophage clearance of apoptotic cells to ensure efficient skin wound healing, suggesting a potential new therapeutic target for skin wound healing.

  11. Human carotid atherosclerotic plaque protein(s) change HDL protein(s) composition and impair HDL anti-oxidant activity.

    PubMed

    Cohen, Elad; Aviram, Michael; Khatib, Soliman; Volkova, Nina; Vaya, Jacob

    2016-01-01

    High density lipoprotein (HDL) anti-atherogenic functions are closely associated with cardiovascular disease risk factor, and are dictated by its composition, which is often affected by environmental factors. The present study investigates the effects of the human carotid plaque constituents on HDL composition and biological functions. To this end, human carotid plaques were homogenized and incubated with HDL. Results showed that after incubation, most of the apolipoprotein A1 (Apo A1) protein was released from the HDL, and HDL diameter increased by an average of approximately 2 nm. In parallel, HDL antioxidant activity was impaired. In response to homogenate treatment HDL could not prevent the accelerated oxidation of LDL caused by the homogenate. Boiling of the homogenate prior to its incubation with HDL abolished its effects on HDL composition changes. Moreover, tryptophan fluorescence quenching assay revealed an interaction between plaque component(s) and HDL, an interaction that was reduced by 50% upon using pre-boiled homogenate. These results led to hypothesize that plaque protein(s) interacted with HDL-associated Apo A1 and altered the HDL composition. Immuno-precipitation of Apo A1 that was released from the HDL after its incubation with the homogenate revealed a co-precipitation of three isomers of actin. However, beta-actin alone did not significantly affect the HDL composition, and yet the active protein within the plaque was elusive. In conclusion then, protein(s) in the homogenate interact with HDL protein(s), leading to release of Apo A1 from the HDL particle, a process that was associated with an increase in HDL diameter and with impaired HDL anti-oxidant activity.

  12. Jumping the gun: Smoking constituent BaP causes premature primordial follicle activation and impairs oocyte fusibility through oxidative stress

    SciTech Connect

    Sobinoff, A.P.; Pye, V.; Nixon, B.; Roman, S.D.; McLaughlin, E.A.

    2012-04-01

    Benzo(a)pyrene (BaP) is an ovotoxic constituent of cigarette smoke associated with pre-mature ovarian failure and decreased rates of conception in IVF patients. Although the overall effect of BaP on female fertility has been documented, the exact molecular mechanisms behind its ovotoxicity remain elusive. In this study we examined the effects of BaP exposure on the ovarian transcriptome, and observed the effects of in vivo exposure on oocyte dysfunction. Microarray analysis of BaP cultured neonatal ovaries revealed a complex mechanism of ovotoxicity involving a small cohort of genes associated with follicular growth, cell cycle progression, and cell death. Histomorphological and immunohistochemical analysis supported these results, with BaP exposure causing increased primordial follicle activation and developing follicle atresia in vitro and in vivo. Functional analysis of oocytes obtained from adult Swiss mice treated neonatally revealed significantly increased levels of mitochondrial ROS/lipid peroxidation, and severely reduced sperm-egg binding and fusion in both low (1.5 mg/kg/daily) and high (3 mg/kg/daily) dose treatments. Our results reveal a complex mechanism of BaP induced ovotoxicity involving developing follicle atresia and accelerated primordial follicle activation, and suggest short term neonatal BaP exposure causes mitochondrial leakage resulting in reduced oolemma fluidity and impaired fertilisation in adulthood. This study highlights BaP as a key compound which may be partially responsible for the documented effects of cigarette smoke on follicular development and sub-fertility. -- Highlights: ► BaP exposure up-regulates canonical pathways linked with follicular growth/atresia. ► BaP causes primordial follicle activation and developing follicle atresia. ► BaP causes oocyte mitochondrial ROS and lipid peroxidation, impairing fertilisation. ► Short term neonatal BaP exposure compromises adult oocyte quality.

  13. Vitamin A supplementation induces a prooxidative state in the striatum and impairs locomotory and exploratory activity of adult rats.

    PubMed

    de Oliveira, Marcos Roberto; de Bittencourt Pasquali, Matheus Augusto; Silvestrin, Roberta Bristot; Mello E Souza, Tadeu; Moreira, José Cláudio Fonseca

    2007-09-12

    Although vitamin A has been reported to be essential to brain homeostasis, some central nervous system (CNS)-associated deleterious effects may be induced by vitamin A or by its metabolites. In this work, we investigated the effects of acute and chronic vitamin A supplementation at therapeutic (1,000 or 2,500 IU/kg/day) or excessive (4,500 or 9,000 IU/kg/day) doses on the redox state of the rat striatum. We found a 1.8- to 2.7-fold increase of lipid peroxidation in the striatum after acute or chronic supplementation (TBARS method). Therapeutic doses induced a 1.6- to 2.2-fold increase of protein carbonylation (dinitrophenylhydrazine (DNPH) derivatization). Vitamin A supplementation induced a 1.2- to 1.4-fold decrease of protein thiol content acutely and chronically. Superoxide dismutase (SOD) activity, assessed through the inhibition of epinephrine's autoxidation, was increased in a dose-dependent manner chronically. Acutely, both therapeutic and excessive vitamin A doses induced a 1.8- to 2.2-fold decrease of catalase (CAT) activity, as determined through the rate of decrease of hydrogen peroxide (H(2)O(2)). Glutathione peroxidase (GPx) activity did not change in this experimental model. Some vitamin A doses decreased the non-protein thiol content only chronically. Vitamin A supplementation decreased the striatal non-enzymatic antioxidant defenses (TRAP assay). Furthermore, our results show that vitamin A supplementation impaired the SOD/CAT ratio. Moreover, we observed a 1.6- to 2.0-fold decrease of locomotion and exploration in an open field after vitamin A supplementation. Therefore, our results suggest that vitamin A supplementation induces oxidative stress in the rat striatum and that it may be related to a metabolic impairment in such brain area.

  14. Stress induces altered CRE/CREB pathway activity and BDNF expression in the hippocampus of glucocorticoid receptor-impaired mice.

    PubMed

    Alboni, Silvia; Tascedda, Fabio; Corsini, Daniela; Benatti, Cristina; Caggia, Federica; Capone, Giacomo; Barden, Nicholas; Blom, Joan M C; Brunello, Nicoletta

    2011-06-01

    The gene coding for the neurotrophin Brain-Derived Neurotrophic Factor (BDNF) is a stress-responsive gene. Changes in its expression may underlie some of the pathological effects of stress-related disorders like depression. Data on the stress-induced regulation of the expression of BDNF in pathological conditions are rare because often research is conducted using healthy animals. In our experiments, we used transgenic mice with glucocorticoid receptor impaired (GR-i) expression in the hypothalamus created as a tool to study the neuroendocrine changes occurring in stress-related disorders. First, under basal condition, GR-i mice displayed lower levels of BDNF exons IX and IV and decreased CRE(BDNF) binding activity with respect to wild-type (WT) mice in the hippocampus. Then, we exposed GR-i and WT mice to an acute restraint stress (ARS) to test the hypothesis that GR-i mice display: 1] different ARS induced expression of BDNF, and 2] altered activation of signaling pathways implicated in regulating BDNF gene expression in the hippocampus with respect to WT mice. Results indicate that ARS enhanced BDNF mRNA expression mainly in the CA3 hippocampal sub-region of GR-i mice in the presence of enhanced levels of pro-BDNF protein, while no effect was observed in WT mice. Moreover, ARS reduced CREB signaling and binding to the BDNF promoter in GR-i mice but enhanced signaling and binding, possibly through ERK1/2 activation, in WT mice. Thus, life-long central GR dysfunction resulted in an altered sensitivity at the transcriptional level that may underlie an impaired response to an acute psycho-physical stress. This article is part of a Special Issue entitled 'Trends in neuropharmacology: in memory of Erminio Costa'.

  15. Aryl hydrocarbon receptor activation by 2,3,7,8-tetrachlorodibenzo-p-dioxin impairs human B lymphopoiesis.

    PubMed

    Li, Jinpeng; Phadnis-Moghe, Ashwini S; Crawford, Robert B; Kaminski, Norbert E

    2017-03-01

    The homeostasis of peripheral B cell compartment requires lifelong B lymphopoiesis from hematopoietic stem cells (HSC). As a result, the B cell repertoire is susceptible to disruptions of hematopoiesis. Increasing evidence, primarily from rodent models, shows that the aryl hydrocarbon receptor (AHR) regulates hematopoiesis. To study the effects of persistent AHR activation on human B cell development, a potent AHR agonist and known environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was utilized. An in vitro B cell development model system was established by co-culturing human cord blood-derived HSCs with irradiated human primary bone marrow stromal cells. Using this in vitro model, we found that TCDD significantly suppressed the total number of hematopoietic stem and progenitor cells (HSPC) in a concentration-dependent manner. Cell death analysis demonstrated that the decrease in cell number was not due to cytotoxicity by TCDD. In addition, TCDD markedly decreased CD34 expression on HSPCs. Structure-activity relationship studies using dioxin congeners demonstrated a correlation between the relative AHR binding affinity and the magnitude of decrease in the number of HSPCs and CD34 expression, suggesting that AHR mediates the observed TCDD-elicited changes in HSPCs. Moreover, a significant reduction in lineage committed B cell-derived from HSCs was observed in the presence of TCDD, indicating impairment of human B cell development. Similar effects of TCDD were observed regardless of the use of stromal cells in cultures indicating a direct effect of TCDD on HSCs. Collectively, we demonstrate that AHR activation by TCDD on human HSCs impairs early stages of human B lymphopoiesis.

  16. Enhanced cognitive activity--over and above social or physical activity--is required to protect Alzheimer's mice against cognitive impairment, reduce Abeta deposition, and increase synaptic immunoreactivity.

    PubMed

    Cracchiolo, Jennifer R; Mori, Takashi; Nazian, Stanley J; Tan, Jun; Potter, Huntington; Arendash, Gary W

    2007-10-01

    Although social, physical, and cognitive activities have each been suggested to reduce the risk of Alzheimer's disease (AD), epidemiologic studies cannot determine which activity or combination of activities is most important. To address this question, mutant APP transgenic AD mice were reared long-term in one of four housing conditions (impoverished, social, social+physical, or complete enrichment) from 1(1/2) through 9 months of age. Thus, a stepwise layering of social, physical, and enhanced cognitive activity was created. Behavioral evaluation in a full battery of sensorimotor, anxiety, and cognitive tasks was carried out during the final 5 weeks of housing. Only AD mice raised in complete enrichment (i.e., enhanced cognitive activity) showed: (1) protection against cognitive impairment, (2) decreased brain beta-amyloid deposition, and (3) increased hippocampal synaptic immunoreactivity. The protection provided by enhanced cognitive activity spanned multiple cognitive domains (working memory, reference learning, and recognition/identification). Cognitive and neurohistologic benefits of complete enrichment occurred without any changes in blood cytokine or corticosterone levels, suggesting that enrichment-dependent mechanisms do not involve changes in the inflammatory response or stress levels, respectively. These results indicate that the enhanced cognitive activity of complete enrichment is required for cognitive and neurologic benefit to AD mice-physical and/or social activity are insufficient. Thus, our data suggest that humans who emphasize a high lifelong level of cognitive activity (over and above social and physical activities) will attain the maximal environmental protection against AD.

  17. Acute fatigue impairs neuromuscular activity of anterior cruciate ligament-agonist muscles in female team handball players.

    PubMed

    Zebis, M K; Bencke, J; Andersen, L L; Alkjaer, T; Suetta, C; Mortensen, P; Kjaer, M; Aagaard, P

    2011-12-01

    In sports, like team handball, fatigue has been associated with an increased risk of anterior cruciate ligament (ACL) injury. While effects of fatigue on muscle function are commonly assessed during maximal isometric voluntary contraction (MVC), such measurements may not relate to the muscle function during match play. The purpose of this study was to investigate the effect of muscle fatigue induced by a simulated handball match on neuromuscular strategy during a functional sidecutting movement, associated with the incidence of ACL injury. Fourteen female team handball players were tested for neuromuscular activity [electromyography (EMG)] during a sidecutting maneuver on a force plate, pre and post a simulated handball match. MVC was obtained during maximal isometric quadriceps and hamstring contraction. The simulated handball match consisted of exercises mimicking handball match activity. Whereas the simulated handball match induced a decrease in MVC strength for both the quadriceps and hamstring muscles (P<0.05), a selective decrease in hamstring neuromuscular activity was seen during sidecutting (P<0.05). This study shows impaired ACL-agonist muscle (i.e. hamstring) activity during sidecutting in response to acute fatigue induced by handball match play. Thus, screening procedures should involve functional movements to reveal specific fatigue-induced deficits in ACL-agonist muscle activation during high-risk phases of match play.

  18. The effects of core stability strength exercise on muscle activity and trunk impairment scale in stroke patients.

    PubMed

    Yu, Seong-Hun; Park, Seong-Doo

    2013-01-01

    The purpose of this study was to examine the effects of core stability-enhancing exercises on the lower trunk and muscle activity of stroke patients. The control group (n = 10) underwent standard exercise therapy, while the experiment group (n =10) underwent both the core stability-enhancing exercise and standard exercise therapy simultaneously. The standard exercise therapy applied to the two groups included weight bearing and weight shifts and joint movements to improve flexibility and the range of motion. The core stability-enhancing exercise was performed 5 times a week for 30 min over a period of 4 weeks in the room where the patients were treated. For all 20 subject, the items measured before the exercise were measured after the therapeutic intervention, and changes in muscle activity of the lower trunk were evaluated. The activity and stability of the core muscles were measured using surface electromyography and the trunk impairment scale (TIS). The mean TIS score and muscle activity of the lower trunk increased in the experiment group significantly after performing the core stability-enhancing exercise (P<0.05). The results of this study show that the core stability-enhancing exercise is effective in improving muscle activity of the lower trunk, which is affected by hemiplegia.

  19. Homocysteine and its thiolactone impair plasmin activity induced by urokinase or streptokinase in vitro.

    PubMed

    Kolodziejczyk-Czepas, Joanna; Talar, Beata; Nowak, Pawel; Olas, Beata; Wachowicz, Barbara

    2012-04-01

    Mechanisms of homocysteine (Hcy) contribution to thrombosis are complex and only partly recognized. The available data suggest that the prothrombotic activity of homocysteine may be not only a result of the changes in coagulation process and endothelial dysfunction, but also the dysfunction of fibrinolysis. The aim of the present work was to assess the effects of homocysteine (10-100 μM mM) and its thiolactone (HTL, 0.1-1 μM) on plasminogen and plasmin functions in vitro. The amidolytic activity of generated plasmin in Hcy or HTL-treated plasminogen and plasma samples was measured by the hydrolysis of chromogenic substrate. Effects of Hcy and HTL on proteolytic activity of plasmin were monitored electrophoretically, by using of fibrinogen as a substrate. The exposure of human plasma and purified plasminogen to Hcy or HTL resulted in the decrease of urokinase-induced plasmin activity. In plasminogen samples treated with the highest concentration of homocysteine (100 μM) or thiolactone (1 μM), the activity of plasmin was inhibited by about 50%. In plasma samples, a reduction of amidolytic activity by about 30% (for 100 μM Hcy) and 40% (for 1 μM HTL), was observed. Both Hcy and HTL were also able to diminish the streptokinase-induced proteolytic activity of plasmin. In conclusion, the results obtained in this study demonstrate that Hcy and HTL may affect fibrinolytic properties of plasminogen and plasma, leading to the decrease of plasmin activity.

  20. Activity recognition in patients with lower limb impairments: do we need training data from each patient?

    PubMed

    Lonini, Luca; Gupta, Aakash; Kording, Konrad; Jayaraman, Arun

    2016-08-01

    Machine learning allows detecting specific physical activities using data from wearable sensors. Such a quantification of patient mobility over time promises to accurately inform clinical decisions for physical rehabilitation. There are two strategies of setting up the machine learning problem: detect one patient's activities using data from the same patient (personal model) or detect their activities using data from other patients (global model), and we currently do not know if personal models are necessary. Here we consider the problem of detecting physical activities from a waist-worn accelerometer in patients who use a knee-ankle-foot orthosis (KAFO) to walk. We show that while a model based on healthy subjects has low accuracy, the global model performs as well as the personal model. This is encouraging because it suggests that condition-specific activity recognition algorithms are sufficient and that no data from individual patients is necessary.

  1. NADP+-dependent glutamate dehydrogenase activity is impaired in mutants of Saccharomyces cerevisiae that lack aconitase.

    PubMed

    González, A; Rodríguez, L; Olivera, H; Soberón, M

    1985-10-01

    A mutant of Saccharomyces cerevisiae lacking aconitase did not grow on minimal medium (MM) and had five- to tenfold less NADP+-dependent glutamate dehydrogenase (GDH) activity than the wild-type, although its glutamine synthetase (GS) activity was still inducible. When this mutant was incubated with glutamate as the sole nitrogen source, the 2-oxoglutarate content rose, and the NADP+-dependent GDH activity increased. Furthermore, carbon-limited cultures showed a direct relation between NADP+-dependent GDH activity and the intracellular 2-oxoglutarate content. We propose that the low NADP+-dependent GDH activity found in the mutant was due to the lack of 2-oxoglutarate or some other intermediate of the tricarboxylic acid cycle.

  2. Isolation and characterization of a Saccharomyces cerevisiae mutant with impaired glutamate synthase activity.

    PubMed

    Folch, J L; Antaramián, A; Rodríguez, L; Bravo, A; Brunner, A; González, A

    1989-12-01

    A mutant of Saccharomyces cerevisiae that lacks glutamate synthase (GOGAT) activity has been isolated. This mutant was obtained after chemical mutagenesis of a NADP-glutamate dehydrogenase-less mutant strain. The gdh gus mutant is a glutamate auxotroph. The genetic analysis of the gus mutant showed that the GOGAT-less phenotype is due to the presence of two loosely linked mutations. Evidence is presented which suggests the possibility that S. cerevisiae has two GOGAT activities, designated GOGAT A and GOGAT B. These activities can be distinguished by their pH optima and by their regulation by glutamate. Furthermore, one of the mutations responsible for the GOGAT-less phenotype affected GOGAT A activity, while the other mutation affected GOGAT B activity.

  3. Isolation and characterization of a Saccharomyces cerevisiae mutant with impaired glutamate synthase activity.

    PubMed Central

    Folch, J L; Antaramián, A; Rodríguez, L; Bravo, A; Brunner, A; González, A

    1989-01-01

    A mutant of Saccharomyces cerevisiae that lacks glutamate synthase (GOGAT) activity has been isolated. This mutant was obtained after chemical mutagenesis of a NADP-glutamate dehydrogenase-less mutant strain. The gdh gus mutant is a glutamate auxotroph. The genetic analysis of the gus mutant showed that the GOGAT-less phenotype is due to the presence of two loosely linked mutations. Evidence is presented which suggests the possibility that S. cerevisiae has two GOGAT activities, designated GOGAT A and GOGAT B. These activities can be distinguished by their pH optima and by their regulation by glutamate. Furthermore, one of the mutations responsible for the GOGAT-less phenotype affected GOGAT A activity, while the other mutation affected GOGAT B activity. PMID:2687252

  4. Triiodothyronine activates lactate oxidation without impairing fatty acid oxidation and improves weaning from extracorporeal membrane oxygenation

    SciTech Connect

    Kajimoto, Masaki; Ledee, Dolena R.; Xu, Chun; Kajimoto, Hidemi; Isern, Nancy G.; Portman, Michael A.

    2014-01-01

    Background: Extracorporeal membrane oxygenation (ECMO) provides a rescue for children with severe cardiac failure. We previously showed that triiodothyronine (T3) improves cardiac function by modulating pyruvate oxidation during weaning. This study was focused on fatty acid (FA) metabolism modulated by T3 for weaning from ECMO after cardiac injury. Methods: Nineteen immature piglets (9.1-15.3 kg) were separated into 3 groups with ECMO (6.5 hours) and wean: normal circulation (Group-C);transient coronary occlusion (10 minutes) followed by ECMO (Group-IR); and IR with T3 supplementation (Group-IR-T3). 13-Carbon labeled lactate, medium-chain and long-chain FAs were infused as oxidative substrates. Substrate fractional contribution to the citric acid cycle (FC) was analyzed by 13-Carbon nuclear magnetic resonance. Results: ECMO depressed circulating T3 levels to 40% baseline at 4 hours and were restored in Group-IR-T3. Group-IR decreased cardiac power, which was not fully restorable and 2 pigs were lost because of weaning failure. Group-IR also depressed FC-lactate, while the excellent contractile function and energy efficiency in Group-IR-T3 occurred along with a marked FC-lactate increase and [ATP]/[ADP] without either decreasing FC-FAs or elevating myocardial oxygen consumption over Group-C or -IR. Conclusions: T3 releases inhibition of lactate oxidation following ischemia-reperfusion injury without impairing FA oxidation. These findings indicate that T3 depression during ECMO is maladaptive, and that restoring levels improves metabolic flux and enhances contractile function during weaning.

  5. Resveratrol prevents the impairment of advanced glycosylation end products (AGE) on macrophage lipid homeostasis by suppressing the receptor for AGE via peroxisome proliferator-activated receptor gamma activation.

    PubMed

    Zhang, Yihua; Luo, Zhidan; Ma, Liqun; Xu, Qiang; Yang, Qihong; Si, Liangyi

    2010-05-01

    Advanced glycosylation end products (AGE) and its receptor (RAGE) axis is involved in the regulation of lipid homeostasis and is critical in the pathogenesis of diabetic atherosclerosis. We investigated the protective role of resveratrol against the AGE-induced impairment on macrophage lipid homeostasis. In THP-1-derived macrophages, RAGE was dose-dependently induced by AGE and played a key role in the AGE-induced cholesterol accumulation. Resveratrol markedly reduced RAGE expression via peroxisome proliferator-activated receptor (PPAR) gamma but not PPARalpha or AMP-activated protein kinase. Importantly, pretreatment with resveratrol significantly ameliorated AGE-induced up-regulation of scavenger receptor-A (SR-A) and down-regulation of ATP-binding cassette (ABC) A1 and ABCG1 and thus effectively prevented the cholesterol accumulation in macrophages as shown by cellular cholesterol analysis and oil red O staining. Moreover, blockade of PPARgamma abolished all these effects of resveratrol. Collectively, our results indicate that resveratrol prevents the impairment of AGE on macrophage lipid homeostasis partially by suppressing RAGE via PPARgamma activation, which might provide new insight into the protective role of resveratrol against diabetic atherosclerosis.

  6. Increased activity in frontal motor cortex compensates impaired speech perception in older adults

    PubMed Central

    Du, Yi; Buchsbaum, Bradley R.; Grady, Cheryl L.; Alain, Claude

    2016-01-01

    Understanding speech in noisy environments is challenging, especially for seniors. Although evidence suggests that older adults increasingly recruit prefrontal cortices to offset reduced periphery and central auditory processing, the brain mechanisms underlying such compensation remain elusive. Here we show that relative to young adults, older adults show higher activation of frontal speech motor areas as measured by functional MRI during a syllable identification task at varying signal-to-noise ratios. This increased activity correlates with improved speech discrimination performance in older adults. Multivoxel pattern classification reveals that despite an overall phoneme dedifferentiation, older adults show greater specificity of phoneme representations in frontal articulatory regions than auditory regions. Moreover, older adults with stronger frontal activity have higher phoneme specificity in frontal and auditory regions. Thus, preserved phoneme specificity and upregulation of activity in speech motor regions provide a means of compensation in older adults for decoding impoverished speech representations in adverse listening conditions. PMID:27483187

  7. The Role Of Physical Activity On The Prevention Of Cognitive Impairment

    PubMed Central

    Corbi, G.; Conti, V.; Filippelli, A.; Di Costanzo, A.; Ferrara, N.

    2015-01-01

    Physical exercise is associated with reduced risk of heart disease, type II diabetes mellitus, and overall mortality. However, growing evidence shows that physical activity can also improve cognitive function and may lower the risk of developing dementia, but Randomized Clinical Trials gave mixed results. Aim of this article was to review the knowledge available in literature on the effects of physical activity on cognition and the suggested possible mechanisms involved in these effects. Our group have planned a trial aiming to evaluate the effectiveness of physical activity in preventing or delaying the cognitive decline in individuals at risk of developing dementia. Beside the effects of exercise on cognition are not fully defined, also the mechanisms underlying the benefits of physical activity on cognitive sphere are not completely known. Recently the SIRT1 loss is both closely associated with accumulation of beta amyloid and tau protein in AD patients. Although there is no specific exercise that can be recommended, the available evidence suggests that practicing more types of physical activity is particularly advantageous. It is important to explore further mechanisms involved in the pathogenesis of the AD in order to be able to identify new and effective target treatment, including physical activity. PMID:27042432

  8. The Role Of Physical Activity On The Prevention Of Cognitive Impairment.

    PubMed

    Corbi, G; Conti, V; Filippelli, A; Di Costanzo, A; Ferrara, N

    2015-12-01

    Physical exercise is associated with reduced risk of heart disease, type II diabetes mellitus, and overall mortality. However, growing evidence shows that physical activity can also improve cognitive function and may lower the risk of developing dementia, but Randomized Clinical Trials gave mixed results. Aim of this article was to review the knowledge available in literature on the effects of physical activity on cognition and the suggested possible mechanisms involved in these effects. Our group have planned a trial aiming to evaluate the effectiveness of physical activity in preventing or delaying the cognitive decline in individuals at risk of developing dementia. Beside the effects of exercise on cognition are not fully defined, also the mechanisms underlying the benefits of physical activity on cognitive sphere are not completely known. Recently the SIRT1 loss is both closely associated with accumulation of beta amyloid and tau protein in AD patients. Although there is no specific exercise that can be recommended, the available evidence suggests that practicing more types of physical activity is particularly advantageous. It is important to explore further mechanisms involved in the pathogenesis of the AD in order to be able to identify new and effective target treatment, including physical activity.

  9. Central blockade of nitric oxide transmission impairs exercise-induced neuronal activation in the PVN and reduces physical performance.

    PubMed

    Lima, Paulo M A; Santiago, Henrique P; Szawka, Raphael E; Coimbra, Cândido C

    2014-09-01

    The blockade of central nitric oxide (NO) signaling modifies the thermoregulatory and metabolic adjustments that occur during exercise, thereby impairing physical performance. However, the brain areas involved in this response remain unknown. Nitrergic neurons are present in the hypothalamic areas that are activated during exercise and participate in autonomic and neuroendocrine responses, such as, the hypothalamic paraventricular nucleus (PVN) and the supraoptic nucleus (SON). To investigate whether brain NO signaling affects thermoregulation during exercise through the activation of hypothalamic neurons, rats underwent acute submaximal treadmill exercise (18 mmin(-1), 5% inclination) until fatigue received an intracerebroventricular injection of 1.43 μmol Nω-nitro-l-arginine metil ester (L-NAME), a nitric oxide synthase inhibitor, or saline (SAL). Skin tail temperature (Tsk) and internal body temperature (Ti) were continuously recorded and c-Fos expression was determined in the PVN and the SON. L-NAME treatment reduced physical performance by 48%, which was positively correlated with tail vasodilation capacity, which was reduced by 28%, and negatively correlated with heat storage rate (HSR), which was increased by 38%. Physical exercise until fatigue increased the number of c-Fos-immunoreactive (ir) neurons in the PVN and the SON. L-NAME-treatment significantly reduced the exercise-induced c-Fos expression in the PVN, whereas it had no effect in the SON. Interestingly, the number of c-Fos-ir neurons in the PVN was closely correlated with physical performance and inversely associated with HSR. Thus, the inhibition of central NO attenuates neuronal activation induced by exercise in the PVN, impairs the autonomic regulation of heat dissipation, and anticipates the fatigue. Brain NO seems to play a role in exercise performance through the regulation of neuronal activation in the PVN, but not in the SON, although the SON neurons are also activated by running

  10. Oral Cnm-positive Streptococcus Mutans Expressing Collagen Binding Activity is a Risk Factor for Cerebral Microbleeds and Cognitive Impairment

    PubMed Central

    Watanabe, Isao; Kuriyama, Nagato; Miyatani, Fumitaro; Nomura, Ryota; Naka, Shuhei; Nakano, Kazuhiko; Ihara, Masafumi; Iwai, Komei; Matsui, Daisuke; Ozaki, Etsuko; Koyama, Teruhide; Nishigaki, Masaru; Yamamoto, Toshiro; Tamura, Aiko; Mizuno, Toshiki; Akazawa, Kentaro; Takada, Akihiro; Takeda, Kazuo; Yamada, Kei; Nakagawa, Masanori; Tanaka, Tokutaro; Kanamura, Narisato; Friedland, Robert P.; Watanabe, Yoshiyuki

    2016-01-01

    Cerebral microbleeds (CMBs) are an important risk factor for stroke and dementia. We have shown that the collagen binding surface Cnm protein expressed on cnm-positive Streptococcus mutans is involved in the development of CMBs. However, whether the collagen binding activity of cnm-positive S. mutans is related to the nature of the CMBs or to cognitive impairment is unclear. Two-hundred seventy nine community residents (70.0 years) were examined for the presence or absence of cnm-positive S. mutans in the saliva by PCR and collagen binding activity, CMBs, and cognitive function were evaluated. Cnm-positive S. mutans was detected more often among subjects with CMBs (p < 0.01) than those without. The risk of CMBs was significantly higher (odds ratio = 14.3) in the group with S. mutans expressing collagen binding activity, as compared to the group without that finding. Deep CMBs were more frequent (67%) and cognitive function was lower among subjects with cnm-positive S. mutans expressing collagen binding activity. This work supports the role of oral health in stroke and dementia and proposes a molecular mechanism for the interaction. PMID:27934941

  11. Elevated Slit2 Activity Impairs VEGF-induced Angiogenesis and Tumor Neovascularization in EphA2-deficient Endothelium

    PubMed Central

    Youngblood, Victoria; Wang, Shan; Song, Wenqiang; Walter, Debra; Hwang, Yoonha; Chen, Jin; Brantley-Sieders, Dana M.

    2015-01-01

    Angiogenic remodeling during embryonic development and in adult tissue homeostasis is orchestrated by cooperative signaling between several distinct molecular pathways, which are often exploited by tumors. Indeed, tumors upregulate pro-angiogenic molecules while simultaneously suppressing angiostatic pathways in order to recruit blood vessels for growth, survival, and metastatic spread. Understanding how cancers exploit pro- and anti-angiogenic signals is a key step in developing new, molecularly targeted anti-angiogenic therapies. While EphA2, a receptor tyrosine kinase (RTK), is required for vascular endothelial growth factor (VEGF)-induced angiogenesis, the mechanism through which these pathways intersect remains unclear. Slit2 expression is elevated in EphA2-deficient endothelium, and here it is reported that inhibiting Slit activity rescues VEGF-induced angiogenesis in cell culture and in vivo, as well as VEGF-dependent tumor angiogenesis, in EphA2-deficient endothelial cells and animals. Moreover, blocking Slit activity or Slit2 expression in EphA2-deficient endothelial cells restores VEGF-induced activation of Src and Rac, both of which are required for VEGF-mediated angiogenesis. These data suggest that EphA2 suppression of Slit2 expression and Slit angiostatic activity enables VEGF-induced angiogenesis in vitro and in vivo, providing a plausible mechanism for impaired endothelial responses to VEGF in the absence of EphA2 function. PMID:25504371

  12. The Effects of Acupuncture at Real or Sham Acupoints on the Intrinsic Brain Activity in Mild Cognitive Impairment Patients

    PubMed Central

    Jia, Baohui; Min, Baoquan; Wang, Zhenchang; Zhou, Aihong; Li, Yong; Jia, Jianping

    2015-01-01

    Accumulating neuroimaging studies in humans have shown that acupuncture can modulate a widely distributed brain network in mild cognitive impairment (MCI) and Alzheimer's disease (AD) patients. Acupuncture at different acupoints could exert different modulatory effects on the brain network. However, whether acupuncture at real or sham acupoints can produce different effects on the brain network in MCI or AD patients remains unclear. Using resting-state fMRI, we reported that acupuncture at Taixi (KI3) induced amplitude of low-frequency fluctuation (ALFF) change of different brain regions in MCI patients from those shown in the healthy controls. In MCI patients, acupuncture at KI3 increased or decreased ALFF in the different regions from those activated by acupuncture in the healthy controls. Acupuncture at the sham acupoint in MCI patients activated the different brain regions from those in healthy controls. Therefore, we concluded that acupuncture displays more significant effect on neuronal activities of the above brain regions in MCI patients than that in healthy controls. Acupuncture at KI3 exhibits different effects on the neuronal activities of the brain regions from acupuncture at sham acupoint, although the difference is only shown at several regions due to the close distance between the above points. PMID:26064166

  13. Constitutive activation of transforming growth factor Beta receptor 1 in the mouse uterus impairs uterine morphology and function.

    PubMed

    Gao, Yang; Duran, Samantha; Lydon, John P; DeMayo, Francesco J; Burghardt, Robert C; Bayless, Kayla J; Bartholin, Laurent; Li, Qinglei

    2015-02-01

    Despite increasing evidence pointing to the essential involvement of the transforming growth factor beta (TGFB) superfamily in reproduction, a definitive role of TGFB signaling in the uterus remains to be unveiled. In this study, we generated a gain-of-function mouse model harboring a constitutively active (CA) TGFB receptor 1 (TGFBR1), the expression of which was conditionally induced by the progesterone receptor (Pgr)-Cre recombinase. Overactivation of TGFB signaling was verified by enhanced phosphorylation of SMAD2 and increased expression of TGFB target genes in the uterus. TGFBR1 Pgr-Cre CA mice were sterile. Histological, cellular, and molecular analyses demonstrated that constitutive activation of TGFBR1 in the mouse uterus promoted formation of hypermuscled uteri. Accompanying this phenotype was the upregulation of a battery of smooth muscle genes in the uterus. Furthermore, TGFB ligands activated SMAD2/3 and stimulated the expression of a smooth muscle maker gene, alpha smooth muscle actin (ACTA2), in human uterine smooth muscle cells. Immunofluorescence microscopy identified a marked reduction of uterine glands in TGFBR1 Pgr-Cre CA mice within the endometrial compartment that contained myofibroblast-like cells. Thus, constitutive activation of TGFBR1 in the mouse uterus caused defects in uterine morphology and function, as evidenced by abnormal myometrial structure, dramatically reduced uterine glands, and impaired uterine decidualization. These results underscore the importance of a precisely controlled TGFB signaling system in establishing a uterine microenvironment conducive to normal development and function.

  14. Health status in COPD cannot be measured by the St George's Respiratory Questionnaire alone: an evaluation of the underlying concepts of this questionnaire

    PubMed Central

    2010-01-01

    Background Improving patients' health status is one of the major goals in COPD treatment. Questionnaires could facilitate the guidance of patient-tailored disease management by exploring which aspects of health status are problematic, and which aspects are not. Health status consists of four main domains (physiological functioning, symptoms, functional impairment, and quality of life), and at least sixteen sub-domains. A prerequisite for patient-tailored treatment is a detailed assessment of all these sub-domains. Most questionnaires developed to measure health status consist of one or a few subscales and measure merely some aspects of health status. The question then rises which aspects of health status are measured by these instruments, and which aspects are not covered. As it is one of the most frequently used questionnaires in COPD, we evaluated which aspects of health status are measured and which aspects are not measured by the St George's Respiratory Questionnaire (SGRQ). Methods One hundred and forty-six outpatients with COPD participated. Correlations were calculated between the three sections of the SGRQ and ten sub-domains of the Nijmegen Integral Assessment Framework, covering Symptoms, Functional Impairment, and Quality of Life. As the SGRQ was not expected to measure physiological functioning, we did not include this main domain in the statistical analyses. Pearson's r ≥ 0.70 was used as criterion for conceptual similarity. Results The SGRQ sections Symptoms and Total showed conceptual similarity with the sub-domain Subjective Symptoms (main domain Symptoms). The sections Activity, Impacts and Total were conceptual similar to Subjective Impairment (main domain Functional Impairment). The SGRQ sections were not conceptual similar to other sub-domains of Symptoms, Functional Impairment, nor to any sub-domain of Quality of Life. Conclusions The SGRQ could facilitate the guidance of disease management in COPD only partially. The SGRQ is appropriately

  15. 1,25-dihydroxyvitamin D{sub 3} impairs NF-{kappa}B activation in human naive B cells

    SciTech Connect

    Geldmeyer-Hilt, Kerstin; Heine, Guido; Hartmann, Bjoern; Baumgrass, Ria; Radbruch, Andreas; Worm, Margitta

    2011-04-22

    Highlights: {yields} In naive B cells, VDR activation by calcitriol results in reduced NF-{kappa}B p105 and p50 protein expression. {yields} Ligating the VDR with calcitriol causes reduced nuclear translocation of NF-{kappa}B p65. {yields} Reduced nuclear amount of p65 after calcitriol incubation results in reduced binding of p65 on the p105 promoter. {yields} Thus, vitamin D receptor signaling may reduce or prevent activation of B cells and unwanted immune responses, e.g. in IgE dependent diseases such as allergic asthma. -- Abstract: 1{alpha},25-dihydroxyvitamin D{sub 3} (calcitriol), the bioactive metabolite of vitamin D, modulates the activation and inhibits IgE production of anti-CD40 and IL-4 stimulated human peripheral B cells. Engagement of CD40 results in NF-{kappa}B p50 activation, which is essential for the class switch to IgE. Herein, we investigated by which mechanism calcitriol modulates NF-{kappa}B mediated activation of human naive B cells. Naive B cells were predominantly targeted by calcitriol in comparison with memory B cells as shown by pronounced induction of the VDR target gene cyp24a1. Vitamin D receptor activation resulted in a strongly reduced p105/p50 protein and mRNA expression in human naive B cells. This effect is mediated by impaired nuclear translocation of p65 and consequently reduced binding of p65 to its binding site in the p105 promoter. Our data indicate that the vitamin D receptor reduces NF-{kappa}B activation by interference with NF-{kappa}B p65 and p105. Thus, the vitamin D receptor inhibits costimulatory signal transduction in naive B cells, namely by reducing CD40 signaling.

  16. Food frequency questionnaires.

    PubMed

    Pérez Rodrigo, Carmen; Aranceta, Javier; Salvador, Gemma; Varela-Moreiras, Gregorio

    2015-02-26

    Food Frequency Questionnaires are dietary assessment tools widely used in epidemiological studies investigating the relationship between dietary intake and disease or risk factors since the early '90s. The three main components of these questionnaires are the list of foods, frequency of consumption and the portion size consumed. The food list should reflect the food habits of the study population at the time the data is collected. The frequency of consumption may be asked by open ended questions or by presenting frequency categories. Qualitative Food Frequency Questionnaires do not ask about the consumed portions; semi-quantitative include standard portions and quantitative questionnaires ask respondents to estimate the portion size consumed either in household measures or grams. The latter implies a greater participant burden. Some versions include only close-ended questions in a standardized format, while others add an open section with questions about some specific food habits and practices and admit additions to the food list for foods and beverages consumed which are not included. The method can be self-administered, on paper or web-based, or interview administered either face-to-face or by telephone. Due to the standard format, especially closed-ended versions, and method of administration, FFQs are highly cost-effective thus encouraging its widespread use in large scale epidemiological cohort studies and also in other study designs. Coding and processing data collected is also less costly and requires less nutrition expertise compared to other dietary intake assessment methods. However, the main limitations are systematic errors and biases in estimates. Important efforts are being developed to improve the quality of the information. It has been recommended the use of FFQs with other methods thus enabling the adjustments required.

  17. Portosystemic hepatic encephalopathy model shows reversal learning impairment and dysfunction of neural activity in the prefrontal cortex and regions involved in motivated behavior.

    PubMed

    Méndez, M; Méndez-López, M; López, L; Aller, M A; Arias, J; Arias, J L

    2011-05-01

    Hepatic encephalopathy (HE) is a neurological complication that affects attention and memory. Experimental animal models have been used to study HE, the most frequent being the portacaval shunt (PCS). In order to investigate learning impairment and brain functional alterations in this model, we assessed reversal learning and neural metabolic activity in a PCS rat model. PCS and sham-operated rats were tested for reversal learning in the Morris water maze. Brains were then processed for cytochrome oxidase (CO) histochemistry. The PCS group had reversal learning impairment and a reduction in CO activity in the prefrontal cortex, ventral tegmental area and accumbens shell nucleus. These results suggest that this model of portosystemic HE shows learning impairments that could be linked to dysfunction in neural activity in the prefrontal cortex and regions involved in motivated behavior.

  18. Blockade of Dopamine Activity in the Nucleus Accumbens Impairs Learning Extinction of Conditioned Fear

    ERIC Educational Resources Information Center

    Holtzman-Assif, Orit; Laurent, Vincent; Westbrook, R. Frederick

    2010-01-01

    Three experiments used rats to investigate the role of dopamine activity in learning to inhibit conditioned fear responses (freezing) in extinction. In Experiment 1, rats systemically injected with the D2 dopamine antagonist, haloperidol, froze more across multiple extinction sessions and on a drug-free retention test than control rats. In…

  19. Using Haptic and Auditory Interaction Tools to Engage Students with Visual Impairments in Robot Programming Activities

    ERIC Educational Resources Information Center

    Howard, A. M.; Park, Chung Hyuk; Remy, S.

    2012-01-01

    The robotics field represents the integration of multiple facets of computer science and engineering. Robotics-based activities have been shown to encourage K-12 students to consider careers in computing and have even been adopted as part of core computer-science curriculum at a number of universities. Unfortunately, for students with visual…

  20. D1 dopamine receptor stimulation impairs striatal proteasome activity in Parkinsonism through 26S proteasome disassembly.

    PubMed

    Barroso-Chinea, Pedro; Thiolat, Marie-Laure; Bido, Simone; Martinez, Audrey; Doudnikoff, Evelyne; Baufreton, Jérôme; Bourdenx, Mathieu; Bloch, Bertrand; Bezard, Erwan; Martin-Negrier, Marie-Laure

    2015-06-01

    Among the mechanisms underlying the development of L-dopa-induced dyskinesia (LID) in Parkinson's disease, complex alterations in dopamine signaling in D1 receptor (D1R)-expressing medium spiny striatal neurons have been unraveled such as, but not limited to, dysregulation of D1R expression, lateral diffusion, intraneuronal trafficking, subcellular localization and desensitization, leading to a pathological anchorage of D1R at the plasma membrane. Such anchorage is partly due to a decreased proteasomal activity that is specific of the L-dopa-exposed dopamine-depleted striatum, results from D1R activation and feeds-back the D1R exaggerated cell surface abundance. The precise mechanisms by which L-dopa affects striatal proteasome activity remained however unknown. We here show, in a series of in vitro ex vivo and in vivo models, that such rapid modulation of striatal proteasome activity intervenes through D1R-mediated disassembly of the 26S proteasome rather than change in transcription or translation of proteasome or proteasome subunits intraneuronal relocalization.

  1. Impaired 17,20-Lyase Activity in Male Mice Lacking Cytochrome b5 in Leydig Cells

    PubMed Central

    Sondhi, Varun; Owen, Bryn M.; Liu, Jiayan; Chomic, Robert; Kliewer, Steven A.; Hughes, Beverly A.; Arlt, Wiebke; Mangelsdorf, David J.

    2016-01-01

    Androgen and estrogen biosynthesis in mammals requires the 17,20-lyase activity of cytochrome P450 17A1 (steroid 17-hydroxylase/17,20-lyase). Maximal 17,20-lyase activity in vitro requires the presence of cytochrome b5 (b5), and rare cases of b5 deficiency in human beings causes isolated 17,20-lyase deficiency. To study the consequences of conditional b5 removal from testicular Leydig cells in an animal model, we generated Cyb5flox/flox:Sf1-Cre (LeyKO) mice. The LeyKO male mice had normal body weights, testis and sex organ weights, and fertility compared with littermates. Basal serum and urine steroid profiles of LeyKO males were not significantly different than littermates. In contrast, marked 17-hydroxyprogesterone accumulation (100-fold basal) and reduced testosterone synthesis (27% of littermates) were observed after human chorionic gonadotropin stimulation in LeyKO animals. Testis homogenates from LeyKO mice showed reduced 17,20-lyase activity and a 3-fold increased 17-hydroxylase to 17,20-lyase activity ratio, which were restored to normal upon addition of recombinant b5. We conclude that Leydig cell b5 is required for maximal androgen synthesis and to prevent 17-hydroxyprogesterone accumulation in the mouse testis; however, the b5-independent 17,20-lyase activity of mouse steroid 17-hydroxylase/17,20-lyase is sufficient for normal male genital development and fertility. LeyKO male mice are a good model for the biochemistry but not the physiology of isolated 17,20-lyase deficiency in human beings. PMID:26974035

  2. Brain activation of lower extremity movement in chronically impaired stroke survivors.

    PubMed

    Luft, Andreas R; Forrester, Larry; Macko, Richard F; McCombe-Waller, Sandy; Whitall, Jill; Villagra, Federico; Hanley, Daniel F

    2005-05-15

    Lower extremity paresis poses significant disability to chronic stroke survivors. Unlike for the upper extremity, cortical adaptations in networks controlling the paretic leg have not been characterized after stroke. Here, the hypotheses are that brain activation associated with unilateral knee movement in chronic stroke survivors is abnormal, depends on lesion location, and is related to walking ability. Functional magnetic resonance imaging of unilateral knee movement was obtained in 31 patients 26.9 months (mean, IQ range: 11.3-68.1) after stroke and in 10 age-matched healthy controls. Strokes were stratified according to lesion location. Locomotor disability (30 ft walking speed) did not differ between patient groups (9 cortical, 12 subcortical, 10 brainstem lesions). Significant differences in brain activation as measured by voxel counts in 10 regions of interest were found between controls and patients with brainstem (P = 0.006) and cortical strokes (P = 0.002), and between subcortical and cortical patients (P = 0.026). Statistical parametric mapping of data per group revealed similar activation patterns in subcortical patients and controls with recruitment of contralateral primary motor cortex (M1), supplementary motor area (SMA), and bilateral somatosensory area 2 (S2). Cortical recruitment was reduced in brainstem and cortical stroke. Better walking was associated with lesser contralateral sensorimotor cortex activation in brainstem, but stronger recruitment of ipsilateral sensorimotor and bilateral somatosensory cortices in subcortical and cortical patients, respectively. A post hoc comparison of brainstem patients with and without mirror movements (50%) revealed lesser recruitment of ipsilateral cerebellum in the latter. Subcortical patients with mirror movements (58%) showed lesser bilateral sensorimotor cortex activation. No cortical patient had mirror movements. The data reveal adaptations in networks controlling unilateral paretic knee movement in

  3. Torque and Muscle Activation Impairment Along With Insulin Resistance Are Associated With Falls in Women With Fibromyalgia.

    PubMed

    Góes, Suelen M; Stefanello, Joice M F; Homann, Diogo; Lodovico, Angélica; Hubley-Kozey, Cheryl L; Rodacki, André L F

    2016-11-01

    Góes, SM, Stefanello, JMF, Homann, D, Lodovico, A, Hubley-Kozey, CL, and Rodacki, ALF. Torque and muscle activation impairment along with insulin resistance are associated with falls in women with fibromyalgia. J Strength Cond Res 30(11): 3155-3164, 2016-Fibromyalgia (FM) is a chronic pain condition associated with reduced muscle strength, which can lead to functional incapacity and higher risk of falls. The purpose of the study was to compare maximal ankle joint torque, muscle activation, and metabolic changes between women with and without FM. In addition, the relationship between those aspects and retrospectively reported falls in women with FM was determined. Twenty-nine middle-aged women with FM and 30 controls were recruited. Fall history, pain intensity, and pain threshold were assessed. Plasma glucose levels and insulin resistance (IR) were determined. Peak torque and rate of torque development (RTD) were calculated, and muscle activation was assessed from maximum isometric voluntary ankle dorsiflexion and plantar flexion contractions. In addition, voluntary muscle activation failure of the anterior tibialis muscle during maximal dorsiflexion was calculated. When compared to controls, women with FM reported higher number of retrospectively reported falls, exhibited higher IR, showed reduced plantar flexion and dorsiflexion RTD, had lower plantar flexion peak torque, and demonstrated more antagonist coactivation and higher muscle activation failure (p ≤ 0.05). Higher muscle activation failure was explained by glucose level and pain intensity (adj R = 0.28; p ≤ 0.05). Reduced plantar flexion and dorsiflexion peak torque explained 80% of retrospectively reported falls variance; also, high antagonist coactivation (odds ratio [OR] = 1.6; p ≤ 0.05) and high IR (OR = 1.8; p ≤ 0.05) increased the chance of falls in the FM group. A combination of metabolic factors and muscle function increased the odds of retrospectively reporting a fall in FM. Both aspects

  4. Decreased glutathione levels and impaired antioxidant enzyme activities in drug-naive first-episode schizophrenic patients

    PubMed Central

    2011-01-01

    Background The aim of this study was to determine glutathione levels and antioxidant enzyme activities in the drug-naive first-episode patients with schizophrenia in comparison with healthy control subjects. Methods It was a case-controlled study carried on twenty-three patients (20 men and 3 women, mean age = 29.3 ± 7.5 years) recruited in their first-episode of schizophrenia and 40 healthy control subjects (36 men and 9 women, mean age = 29.6 ± 6.2 years). In patients, the blood samples were obtained prior to the initiation of neuroleptic treatments. Glutathione levels: total glutathione (GSHt), reduced glutathione (GSHr) and oxidized glutathione (GSSG) and antioxidant enzyme activities: superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) were determined by spectrophotometry. Results GSHt and reduced GSHr were significantly lower in patients than in controls, whereas GSSG was significantly higher in patients. GPx activity was significantly higher in patients compared to control subjects. CAT activity was significantly lower in patients, whereas the SOD activity was comparable to that of controls. Conclusion This is a report of decreased plasma levels of GSHt and GSHr, and impaired antioxidant enzyme activities in drug-naive first-episode patients with schizophrenia. The GSH deficit seems to be implicated in psychosis, and may be an important indirect biomarker of oxidative stress in schizophrenia early in the course of illness. Finally, our results provide support for further studies of the possible role of antioxidants as neuroprotective therapeutic strategies for schizophrenia from early stages. PMID:21810251

  5. Less wiring, more firing: low-performing older adults compensate for impaired white matter with greater neural activity.

    PubMed

    Daselaar, Sander M; Iyengar, Vijeth; Davis, Simon W; Eklund, Karl; Hayes, Scott M; Cabeza, Roberto E

    2015-04-01

    The reliable neuroimaging finding that older adults often show greater activity (over-recruitment) than younger adults is typically attributed to compensation. Yet, the neural mechanisms of over-recruitment in older adults (OAs) are largely unknown. Rodent electrophysiology studies have shown that as number of afferent fibers within a circuit decreases with age, the fibers that remain show higher synaptic field potentials (less wiring, more firing). Extrapolating to system-level measures in humans, we proposed and tested the hypothesis that greater activity in OAs compensates for impaired white-matter connectivity. Using a neuropsychological test battery, we measured individual differences in executive functions associated with the prefrontal cortex (PFC) and memory functions associated with the medial temporal lobes (MTLs). Using event-related functional magnetic resonance imaging, we compared activity for successful versus unsuccessful trials during a source memory task. Finally, we measured white-matter integrity using diffusion tensor imaging. The study yielded 3 main findings. First, low-executive OAs showed greater success-related activity in the PFC, whereas low-memory OAs showed greater success-related activity in the MTLs. Second, low-executive OAs displayed white-matter deficits in the PFC, whereas low-memory OAs displayed white-matter deficits in the MTLs. Finally, in both prefrontal and MTL regions, white-matter decline and success-related activations occurred in close proximity and were negatively correlated. This finding supports the less-wiring-more-firing hypothesis, which provides a testable account of compensatory over-recruitment in OAs.

  6. Association of Increased Serum ACE Activity with Logical Memory Ability in Type 2 Diabetic Patients with Mild Cognitive Impairment.

    PubMed

    Tian, Sai; Han, Jing; Huang, Rong; Xia, Wenqing; Sun, Jie; Cai, Rongrong; Dong, Xue; Shen, Yanjue; Wang, Shaohua

    2016-01-01

    Background: Angiotensin-converting enzyme (ACE) is involved in the chronic complications of type 2 diabetes mellitus (T2DM) and Alzheimer's disease. This study aimed to assess the pathogenetic roles of ACE and the genetic predisposition of its insertion/deletion (I/D) polymorphism in mild cognitive impairment (MCI) among T2DM patients. Methods: A total of 210 T2DM patients were enrolled. Among these patients, 116 satisfied the MCI diagnostic criteria and 94 exhibited healthy cognition. The cognitive functions of the patients were extensively assessed. The serum level and activity of ACE were measured via enzyme-linked immunosorbent assay and ultraviolet spectrophotography. The single-nucleotide polymorphisms of I/D gene of ACE were analyzed. Results: The serum level and activity of ACE in diabetic MCI patients (p = 0.022 and p = 0.008, respectively) were both significantly higher than those in the healthy controls. A significant negative correlation was found between their ACE activity and logical memory test score (LMT) (p = 0.002). Multiple stepwise regression iterated the negative correlation between ACE activity and LMT score (p = 0.035). Although no significant difference was found in the genotype or allele distribution of ACE I/D polymorphism between the groups, the serum levels and activity of ACE were higher in the DD group than in the ID and II groups (p < 0.05). Conclusions: Serum ACE activity could better predict logical memory in T2DM patients than ACE level. Further investigations on a large population size are necessary to test whether the D-allele of the ACE gene polymorphism is susceptible to memory deterioration.

  7. Association of Increased Serum ACE Activity with Logical Memory Ability in Type 2 Diabetic Patients with Mild Cognitive Impairment

    PubMed Central

    Tian, Sai; Han, Jing; Huang, Rong; Xia, Wenqing; Sun, Jie; Cai, Rongrong; Dong, Xue; Shen, Yanjue; Wang, Shaohua

    2016-01-01

    Background: Angiotensin-converting enzyme (ACE) is involved in the chronic complications of type 2 diabetes mellitus (T2DM) and Alzheimer's disease. This study aimed to assess the pathogenetic roles of ACE and the genetic predisposition of its insertion/deletion (I/D) polymorphism in mild cognitive impairment (MCI) among T2DM patients. Methods: A total of 210 T2DM patients were enrolled. Among these patients, 116 satisfied the MCI diagnostic criteria and 94 exhibited healthy cognition. The cognitive functions of the patients were extensively assessed. The serum level and activity of ACE were measured via enzyme-linked immunosorbent assay and ultraviolet spectrophotography. The single-nucleotide polymorphisms of I/D gene of ACE were analyzed. Results: The serum level and activity of ACE in diabetic MCI patients (p = 0.022 and p = 0.008, respectively) were both significantly higher than those in the healthy controls. A significant negative correlation was found between their ACE activity and logical memory test score (LMT) (p = 0.002). Multiple stepwise regression iterated the negative correlation between ACE activity and LMT score (p = 0.035). Although no significant difference was found in the genotype or allele distribution of ACE I/D polymorphism between the groups, the serum levels and activity of ACE were higher in the DD group than in the ID and II groups (p < 0.05). Conclusions: Serum ACE activity could better predict logical memory in T2DM patients than ACE level. Further investigations on a large population size are necessary to test whether the D-allele of the ACE gene polymorphism is susceptible to memory deterioration. PMID:28066203

  8. Constitutive gp130 activation rapidly accelerates the transformation of human hepatocytes via an impaired oxidative stress response

    PubMed Central

    Herden, Johannes; Parplys, Ann Christin; Borgmann, Kerstin; Schmidt-Arras, Dirk; Lohse, Ansgar W.; Rose-John, Stefan; Wege, Henning

    2016-01-01

    Pro-inflammatory signaling pathways, especially interleukin 6 (IL-6), and reactive oxygen species (ROS) promote carcinogenesis in the liver. In order to elucidate the underlying oncogenic mechanism, we activated the IL-6 signal transducer glycoprotein 130 (gp130) via stable expression of a constitutively active gp130 construct (L-gp130) in untransformed telomerase-immortalized human fetal hepatocytes (FH-hTERT). As known from hepatocellular adenomas, forced gp130 activation alone was not sufficient to induce malignant transformation. However, additional challenge of FH-hTERT L-gp130 clones with oxidative stress resulted in 2- to 3-fold higher ROS levels and up to 6-fold more DNA-double strand breaks (DSB). Despite increased DNA damage, ROS-challenged FH-hTERT L-gp130 clones displayed an enhanced proliferation and rapidly developed colony growth capabilities in soft agar. As driving gp130-mediated oncogenic mechanism, we detected a decreased expression of antioxidant genes, in particular glutathione peroxidase 3 and apolipoprotein E, and an absence of P21 upregulation following ROS-conferred induction of DSB. In summary, an impaired oxidative stress response in hepatocytes with gp130 gain-of-function mutations, as detected in dysplastic intrahepatic nodules and hepatocellular adenomas, is one of the central oncogenic mechanisms in chronic liver inflammation. PMID:27489351

  9. The metabolic ER stress sensor IRE1α suppresses alternative activation of macrophages and impairs energy expenditure in obesity.

    PubMed

    Shan, Bo; Wang, Xiaoxia; Wu, Ying; Xu, Chi; Xia, Zhixiong; Dai, Jianli; Shao, Mengle; Zhao, Feng; He, Shengqi; Yang, Liu; Zhang, Mingliang; Nan, Fajun; Li, Jia; Liu, Jianmiao; Liu, Jianfeng; Jia, Weiping; Qiu, Yifu; Song, Baoliang; Han, Jing-Dong J; Rui, Liangyou; Duan, Sheng-Zhong; Liu, Yong

    2017-03-27

    Obesity is associated with metabolic inflammation and endoplasmic reticulum (ER) stress, both of which promote metabolic disease progression. Adipose tissue macrophages (ATMs) are key players orchestrating metabolic inflammation, and ER stress enhances macrophage activation. However, whether ER stress pathways underlie ATM regulation of energy homeostasis remains unclear. Here, we identified inositol-requiring enzyme 1α (IRE1α) as a critical switch governing M1-M2 macrophage polarization and energy balance. Myeloid-specific IRE1α abrogation in Ern1(f/f); Lyz2-Cre mice largely reversed high-fat diet (HFD)-induced M1-M2 imbalance in white adipose tissue (WAT) and blocked HFD-induced obesity, insulin resistance, hyperlipidemia and hepatic steatosis. Brown adipose tissue (BAT) activity, WAT browning and energy expenditure were significantly higher in Ern1(f/f); Lyz2-Cre mice. Furthermore, IRE1α ablation augmented M2 polarization of macrophages in a cell-autonomous manner. Thus, IRE1α senses protein unfolding and metabolic and immunological states, and consequently guides ATM polarization. The macrophage IRE1α pathway drives obesity and metabolic syndrome through impairing BAT activity and WAT browning.

  10. Methylphenidate Decreases ATP Levels and Impairs Glutamate Uptake and Na(+),K(+)-ATPase Activity in Juvenile Rat Hippocampus.

    PubMed

    Schmitz, Felipe; Pierozan, Paula; Rodrigues, André F; Biasibetti, Helena; Grings, Mateus; Zanotto, Bruna; Coelho, Daniella M; Vargas, Carmen R; Leipnitz, Guilhian; Wyse, Angela T S

    2016-11-14

    The study of the long-term neurological consequences of early exposure with methylphenidate (MPH) is very important since this psychostimulant has been widely misused by children and adolescents who do not meet full diagnostic criteria for ADHD. The aim of this study was to examine the effect of early chronic exposure with MPH on amino acids profile, glutamatergic and Na(+),K(+)-ATPase homeostasis, as well as redox and energy status in the hippocampus of juvenile rats. Wistar male rats received intraperitoneal injections of MPH (2.0 mg/kg) or saline solution (controls), once a day, from the 15th to the 45th day of age. Results showed that MPH altered amino acid profile in the hippocampus, decreasing glutamine levels. Glutamate uptake and Na(+),K(+)-ATPase activity were decreased after chronic MPH exposure in the hippocampus of rats. No changes were observed in the immunocontents of glutamate transporters (GLAST and GLT-1), and catalytic subunits of Na(+),K(+)-ATPase (α1, α2, and α3), as well as redox status. Moreover, MPH provoked a decrease in ATP levels in the hippocampus of chronically exposed rats, while citrate synthase, succinate dehydrogenase, respiratory chain complexes activities (II, II-III, and IV), as well as mitochondrial mass and mitochondrial membrane potential were not altered. Taken together, our results suggest that chronic MPH exposure at early age impairs glutamate uptake and Na(+),K(+)-ATPase activity probably by decreasing in ATP levels observed in rat hippocampus.

  11. Deficiency of Parkinson's disease-related gene Fbxo7 is associated with impaired mitochondrial metabolism by PARP activation

    PubMed Central

    Delgado-Camprubi, Marta; Esteras, Noemi; Soutar, Marc PM; Plun-Favreau, Helene; Abramov, Andrey Y

    2017-01-01

    The Parkinson's disease (PD)-related protein F-box only protein 7 (Fbxo7) is the substrate-recognition component of the Skp1-Cullin-F-box protein E3 ubiquitin ligase complex. We have recently shown that PD-associated mutations in Fbxo7 disrupt mitochondrial autophagy (mitophagy), suggesting a role for Fbxo7 in modulating mitochondrial homeostasis. Here we report that Fbxo7 deficiency is associated with reduced cellular NAD+ levels, which results in increased mitochondrial NADH redox index and impaired activity of complex I in the electron transport chain. Under these conditions of compromised respiration, mitochondrial membrane potential and ATP contents are reduced, and cytosolic reactive oxygen species (ROS) production is increased. ROS activates poly (ADP-ribose) polymerase (PARP) activity in Fbxo7-deficient cells. PARP inhibitor restores cellular NAD+ content and redox index and ATP pool, suggesting that PARP overactivation is cause of decreased complex I-driven respiration. These findings bring new insight into the mechanism of Fbxo7 deficiency, emphasising the importance of mitochondrial dysfunction in PD. PMID:27689878

  12. Complement activation and liver impairment in trichloroethylene-sensitized BALB/c mice.

    PubMed

    Zhang, Jiaxiang; Zha, Wansheng; Wang, Feng; Jiang, Tao; Xu, Shuhai; Yu, Junfeng; Zhou, Chengfan; Shen, Tong; Wu, Changhao; Zhu, Qixing

    2013-01-01

    Our recent studies have shown that trichloroethylene (TCE) was able to induce multisystem injuries in the form of occupational medicamentosa-like dermatitis, including skin, kidney, and liver damages. However, the role of complement activation in the immune-mediated liver injury is not known. This study examined the role of complement activation in the liver injury in a mouse model of TCE-induced sensitization. Treatment of female BALB/c mice with TCE under specific dosing protocols resulted in skin inflammation and sensitization. Skin edema and erythema occurred in TCE-sensitized groups. Trichloroethylene sensitization produced liver histopathological lesions, increased serum alanine aminotransferase, aspartate transaminase activities, and the relative liver weight. The concentrations of serum complement components C3a-desArg, C5a-desArg, and C5b-9 were significantly increased in 24-hour, 48-hour, and 72-hour sensitization-positive groups treated with TCE and peaked in the 72-hour sensitization-positive group. Depositions of C3a, C5a, and C5b-9 into the liver tissue were also revealed by immunohistochemistry. Immunofluorescence further verified high C5b-9 expression in 24-hour, 48-hour, and 72-hour sensitization-positive groups in response to TCE treatment. Reverse transcription-polymerase chain reaction detected C3 messenger RNA expression in the liver, and this was significantly increased in 24-hour and 48-hour sensitization-positive groups with a transient reduction at 72 hours. These results provide the first experimental evidence that complement activation may play a key role in the generation and progression of immune-mediated hepatic injury by exposure to TCE.

  13. C3 exoenzyme impairs cell proliferation and apoptosis by altering the activity of transcription factors.

    PubMed

    von Elsner, Leonie; Hagemann, Sandra; Just, Ingo; Rohrbeck, Astrid

    2016-09-01

    C3 exoenzyme from C. botulinum is an ADP-ribosyltransferase that inactivates selectively RhoA, B, and C by coupling an ADP-ribose moiety. Rho-GTPases are involved in various cellular processes, such as regulation of actin cytoskeleton, cell proliferation, and apoptosis. Previous studies of our group with the murine hippocampal cell line HT22 revealed a C3-mediated inhibition of cell proliferation after 48 h and a prevention of serum-starved cells from apoptosis. For both effects, alterations of various signaling pathways are already known, including also changes on the transcriptional level. Investigations on the transcriptional activity in HT22 cells treated with C3 for 48 h identified five out of 48 transcription factors namely Sp1, ATF2, E2F-1, CBF, and Stat6 with a significantly regulated activity. For validation of identified transcription factors, studies on the protein level of certain target genes were performed. Western blot analyses exhibited an enhanced abundance of Sp1 target genes p21 and COX-2 as well as an increase in phosphorylation of c-Jun. In contrast, the level of p53 and apoptosis-inducing GADD153, a target gene of ATF2, was decreased. Our results reveal that C3 regulates the transcriptional activity of Sp1 and ATF2 resulting downstream in an altered protein abundance of various target genes. As the affected proteins are involved in the regulation of cell proliferation and apoptosis, thus the C3-mediated anti-proliferative and anti-apoptotic effects are consequences of the Rho-dependent alterations of the activity of certain transcriptional factors.

  14. User experiences of mobile controlled games for activation, rehabilitation and recreation of elderly and physically impaired.

    PubMed

    Sirkka, Andrew; Merilampi, Sari; Koivisto, Antti; Leinonen, Markus; Leino, Mirka

    2012-01-01

    The purpose of this paper was to study how aged people experience mobile controlled game as a method of rehabilitation and recreation. The target group contained persons 70+ years of age living in assisted living conditions (N=34). The average age of the participants was 85.9 years. Women (n=17) and men (n=17) were equally presented in the sample group. Only 12 % (n=4) of participants were involved in an active weekly-based rehabilitation, light physical sitting exercises 38% (n=13). Three (n=3) of the participants (9%) used computers (net banking), and 20 (59%) used mobile phones on daily basis. Social activities and physical activation seem to be rather inadequate and traditional in assisted living organizations. The overall experiences of mobile controlled game described in this paper appeared to be a successful experiment also proving that the elderly are not as reluctant to use technical devices or playing virtual games as often thought. The game was reckoned very motivating, interesting, and entertaining both by the aged and the staff. Activation, rehabilitation and recreation in the elderly homes or assisted living organizations could benefit from utilization of new technology providing new ways and solutions that motivate the users and offer also possibilities for measuring and follow-up of the physical impacts. The future goals to improve the game were set according to the feedback given in this survey: a) wider variety of controlling modes for the game, b) developing various difficulty levels, c) developing the game to support different kinds of body movements, d) easily modified according to the individual user's exercising or rehabilitation needs as well as e) emphasizing the social aspects of the game by producing multiplayer versions.

  15. Static stretching does not impair performance in active middle-aged adults.

    PubMed

    Handrakis, John P; Southard, Veronica N; Abreu, Jairo M; Aloisa, Mariella; Doyen, Mellissa R; Echevarria, Licet M; Hwang, Hyun; Samuels, Christine; Venegas, Steven A; Douris, Peter C

    2010-03-01

    Recent investigations with young, healthy adult subjects suggest that static stretching before activity decreases performance and should, therefore, be avoided. The purpose of this study was to assess the effects of an acute static stretching protocol on balance and jump/hop performance in active middle-aged adults. Ten subjects (6 men and 4 women aged 40-60 yr) from a martial arts school volunteered to take part in this research study. This was a repeated measures design. Subjects who stretched for 10 minutes using a 30-second hold during 1 session sat quietly for 10 minutes during the alternate session. Sessions were randomly assigned. The following dependent variables were compared: Dynamic Stability Index (DSI) for single-leg dynamic balance (smaller DSI = improved balance); distances for broad jump, single hop, triple hop, and crossover hop; elapsed time for a 6-m timed hop. Group means for balance were significantly different between the stretch and no-stretch conditions (3.5 +/- 0.7 vs. 4.3 +/- 1.4 DSI, respectively; p < 0.05). No significant differences were found between the group means of the stretch and no-stretch conditions for the dependent measures of broad jump, single hop, triple hop, crossover hop, and 6-m timed hop performance. Ten minutes of acute static stretching enhances dynamic balance and does not affect jump/hop performance in active middle-aged adults. Static stretching should be included before competition and before exercise in fitness programs of active middle-aged adults.

  16. Copper acutely impairs behavioral function and muscle acetylcholinesterase activity in zebrafish (Danio rerio).

    PubMed

    Haverroth, Gabriela M B; Welang, Chariane; Mocelin, Riciéri N; Postay, Daniela; Bertoncello, Kanandra T; Franscescon, Francini; Rosemberg, Denis B; Dal Magro, Jacir; Dalla Corte, Cristiane L

    2015-12-01

    Copper is a heavy metal found at relatively high concentrations in surface waters around the world. Copper is a micronutrient at low concentrations and is essential to several organisms. At higher concentrations copper can become toxic, which reveal the importance of studying the toxic effects of this metal on the aquatic life. Thus, the objective of this study was to evaluate the toxic effects of copper on the behavior and biochemical parameters of zebrafish (Danio rerio). Zebrafish were exposed for 24h at a concentration of 0.006 mg/L Cu. After the exposure period, behavioral profile of animals was recorded through 6 min using two different apparatuses tests: the Novel Tank and the Light-Dark test. After behavioral testing, animals were euthanized with a solution of 250 mg/L of tricaine (MS-222). Brain, muscle, liver and gills were extracted for analysis of parameters related to oxidative stress and accumulation of copper in these tissues. Acetylcholinesterase (AChE) activity was determined in brain and muscle. Results showed acute exposure to copper induces significant changes in behavioral profile of zebrafish by changing locomotion and natural tendency to avoid brightly lit area. On the other hand, there were no significant effects on parameters related to oxidative stress. AChE activity decreased significantly in zebrafish muscle, but there were no significant changes in cerebral AChE activity. Copper levels in tissues did not increase significantly compared to the controls. Taken together, these results indicate that a low concentration of copper can acutely affect behavioral profile of adult zebrafish which could be partially related to an inhibition on muscle AChE activity. These results reinforce the need of additional tests to establishment of safe copper concentrations to aquatic organisms and the importance of behavioral parameters in ecotoxicological studies.

  17. Metabolism of Benzyladenine is Impaired in a Mutant of Arabidopsis thaliana Lacking Adenine Phosphoribosyltransferase Activity 1

    PubMed Central

    Moffatt, Barbara; Pethe, Claude; Laloue, Michel

    1991-01-01

    Formation of the riboside-5′-monophosphate is a general feature of the metabolism of cytokinins in plants. As part of a study of the biological significance of the nucleotide form of cytokinins, we analyzed a mutant of Arabidopsis thaliana deficient in adenine phosphoribosyltransferase (APRT) activity for its ability to metabolize N6-benzyladenine (BA). Formation of N6-benzyladenosine-5′-monophosphate (BAMP) was assayed in vivo, by feeding tritiated BA to wild-type and mutant plantlets, and in crude plantlet extracts. Metabolites were separated by high performance liquid chromatography and quantitated by on-line liquid scintillation spectrometry. BA was rapidly absorbed by A. thaliana plantlets and primarily converted to BAMP and to BA 7- and 9-glucosides. BA was also rapidly absorbed by APRT-deficient plantlets, but its conversion to BAMP was strongly reduced. Formation of BAMP from N6-benzyladenosine was not affected in the mutant plantlets. In vitro conversion of BA to its nucleoside-5′-monophosphate was detected in crude extracts of wild-type plantlets, but not in extracts of APRT-deficient plantlets. Therefore, results of both assays indicate that APRT-deficient tissue does not convert BA to BAMP to a significant extent. Further, nondenaturing isoelectric focusing analysis of APRT activity in leaf extracts indicated that the enzyme activities which metabolize adenine and BA into their corresponding riboside-5′-monophosphate in extracts of wild-type plantlets have the same apparent isoelectric point. These activities were not detected in extracts prepared from APRT-deficient plantlets. Thus, these results demonstrate that APRT is the main enzyme which converts BA to its nucleotide form in young A. thaliana plants and that the ribophosphorylation of BA is not a prerequisite of its absorption by the plantlets. Images Figure 4 PMID:16668070

  18. Fullerene Derivatives Strongly Inhibit HIV-1 Replication by Affecting Virus Maturation without Impairing Protease Activity

    PubMed Central

    Martinez, Zachary S.; Castro, Edison; Seong, Chang-Soo; Cerón, Maira R.

    2016-01-01

    Three compounds (1, 2, and 3) previously reported to inhibit HIV-1 replication and/or in vitro activity of reverse transcriptase were studied, but only fullerene derivatives 1 and 2 showed strong antiviral activity on the replication of HIV-1 in human CD4+ T cells. However, these compounds did not inhibit infection by single-round infection vesicular stomatitis virus glycoprotein G (VSV-G)-pseudotyped viruses, indicating no effect on the early steps of the viral life cycle. In contrast, analysis of single-round infection VSV-G-pseudotyped HIV-1 produced in the presence of compound 1 or 2 showed a complete lack of infectivity in human CD4+ T cells, suggesting that the late stages of the HIV-1 life cycle were affected. Quantification of virion-associated viral RNA and p24 indicates that RNA packaging and viral production were unremarkable in these viruses. However, Gag and Gag-Pol processing was affected, as evidenced by immunoblot analysis with an anti-p24 antibody and the measurement of virion-associated reverse transcriptase activity, ratifying the effect of the fullerene derivatives on virion maturation of the HIV-1 life cycle. Surprisingly, fullerenes 1 and 2 did not inhibit HIV-1 protease in an in vitro assay at the doses that potently blocked viral infectivity, suggesting a protease-independent mechanism of action. Highlighting the potential therapeutic relevance of fullerene derivatives, these compounds block infection by HIV-1 resistant to protease and maturation inhibitors. PMID:27431232

  19. Fructose supplementation impairs rat liver autophagy through mTORC activation without inducing endoplasmic reticulum stress.

    PubMed

    Baena, Miguel; Sangüesa, Gemma; Hutter, Natalia; Sánchez, Rosa M; Roglans, Núria; Laguna, Juan C; Alegret, Marta

    2015-02-01

    Supplementation with 10% liquid fructose to female rats for 2weeks caused hepatic steatosis through increased lipogenesis and reduced peroxisome proliferator activated receptor (PPAR) α activity and fatty acid catabolism, together with increased expression of the spliced form of X-binding protein-1 (Rebollo et al., 2014). In the present study, we show that some of these effects are preserved after sub-chronic (8weeks) fructose supplementation, specifically increased hepatic expression of lipid synthesis-related genes (stearoyl-CoA desaturase, ×6.7-fold; acetyl-CoA carboxylase, ×1.6-fold; glycerol-3-phosphate acyltransferase, ×1.65-fold), and reduced fatty acid β-oxidation (×0.77-fold), resulting in increased liver triglyceride content (×1.69-fold) and hepatic steatosis. However, hepatic expression of PPARα and its target genes was not modified and, further, livers of 8-week fructose-supplemented rats showed no sign of unfolded protein response activation, except for an increase in p-IRE1 levels. Hepatic mTOR phosphorylation was enhanced (×1.74-fold), causing an increase in the phosphorylation of UNC-51-like kinase 1 (ULK-1) (×2.8-fold), leading to a decrease in the ratio of LC3B-II/LC3B-I protein expression (×0.39-fold) and an increase in the amount of the autophagic substrate p62, indicative of decreased autophagy activity. A harmful cycle may be established in the liver of 8-week fructose-supplemented rats where lipid accumulation may cause defective autophagy, and reduced autophagy may result in decreased free fatty acid formation from triglyceride depots, thus reducing the substrates for β-oxidation and further increasing hepatic steatosis. In summary, the length of supplementation is a key factor in the metabolic disturbances induced by fructose: in short-term studies, PPARα inhibition and ER stress induction are critical events, whereas after sub-chronic supplementation, mTOR activation and autophagy inhibition are crucial.

  20. Oxidized High-Density Lipoprotein Impairs Endothelial Progenitor Cells' Function by Activation of CD36-MAPK-TSP-1 Pathways

    PubMed Central

    Wu, Jianxiang; He, Zhiqing; Gao, Xiang; Wu, Feng; Ding, Ru; Ren, Yusheng; Jiang, Qijun; Fan, Min

    2015-01-01

    Abstract Aims: High-density lipoprotein (HDL) levels inversely correlate with cardiovascular events due to the protective effects on vascular wall and stem cells, which are susceptible to oxidative modifications and then lead to potential pro-atherosclerotic effects. We proposed that oxidized HDL (ox-HDL) might lead to endothelial progenitor cells (EPCs) dysfunction and investigated underlying mechanisms. Results: ox-HDL was shown to increase apoptosis and intracellular reactive oxygen species levels, but to reduce migration, angiogenesis, and cholesterol efflux of EPCs in a dose-dependent manner. p38 mitogen-activated protein kinase (MAPK) and NF-κB were activated after ox-HDL stimulation, which also upregulated thrombospondin-1 (TSP-1) expression without affecting vascular endothelial growth factor. Effects caused by ox-HDL could be significantly attenuated by pretreatment with short hairpin RNA-mediated CD36 knockdown or probucol. Data of in vivo experiments and the inverse correlation of ox-HDL and circulating EPC numbers among patients with coronary artery diseases (CAD) or CAD and type 2 diabetes also supported it. Meanwhile, HDL separated from such patients could significantly increase cultured EPC's caspase 3 activity, further supporting our proposal. Innovation: This is the most complete study to date of how ox-HDL would impair EPCs function, which was involved with activation of CD36-p38 MAPK-TSP-1 pathways and proved by not only the inverse relationship between ox-HDL and circulating EPCs in clinic but also pro-apoptotic effects of HDL separated from patients' serum. Conclusion: Activation of CD36-p38 MAPK-TSP-1 pathways contributes to the pathological effects of ox-HDL on EPCs' dysfunction, which might be one of the potential etiological factors responsible for the disturbed neovascularization in chronic ischemic disease. Antioxid. Redox Signal. 22, 308–324. PMID:25313537

  1. Long-acting neuroleptics used in wildlife management do not impair thermoregulation or physical activity in goats (Capra hircus).

    PubMed

    Fick, Linda; Mitchell, Duncan; Fuller, Andrea

    2007-06-01

    Long-acting neuroleptics commonly are used in wildlife management to decrease stress-related mortality in wild animals, but with possible effects on thermoregulation, which may contribute to residual morbidity and mortality. We investigated the effects of haloperidol (0.01, 0.1, 1 mg kg(-1), n=4), zuclopenthixol (0.1, 1, 10 mg kg(-1), n=4) and perphenazine (0.1, 1, 10 mg kg(-1), n=8), as well as control injections of sunflower oil, on body temperature and physical activity of laboratory goats under hot, cold and thermoneutral ambient temperatures. Implanted data loggers continuously recorded abdominal temperature, and data loggers attached externally on the foreleg recorded movement of unrestrained goats, in a climatic chamber at 35 degrees C, 10 degrees C and 22 degrees C. Cycling ambient temperature between 35 degrees C in daytime and 10 degrees C at night time caused a significant increase in amplitude of the circadian rhythm of body temperature in goats given sunflower oil (P=0.0012, unpaired t-test, n=8), but the administration of zuclopenthixol or perphenazine did not affect this change in amplitude (P>0.05, two-way ANOVA, n=4). Mean daily body temperature after administration of zuclopenthixol or perphenazine, and mean daily activity after zuclopenthixol administration, were not significantly different to those after control injections, at any ambient temperature, for the expected duration of drug activity (all P>0.05, two-way ANOVA, n=4). Thermal response indices, and mean activity, during heat, cold or thermoneutral exposure, of goats for 7 h after haloperidol injection, were not significantly different, at any dose or any ambient temperature, to those following control injections (all P>0.05, repeated measures ANOVA, n=4). Long-acting neuroleptics did not impair activity or thermoregulation of goats subjected to inescapable thermal challenges.

  2. Sticking with the nice guy: trait warmth information impairs learning and modulates person perception brain network activity.

    PubMed

    Lee, Victoria K; Harris, Lasana T

    2014-12-01

    Social learning requires inferring social information about another person, as well as evaluating outcomes. Previous research shows that prior social information biases decision making and reduces reliance on striatal activity during learning (Delgado, Frank, & Phelps, Nature Neuroscience 8 (11): 1611-1618, 2005). A rich literature in social psychology on person perception demonstrates that people spontaneously infer social information when viewing another person (Fiske & Taylor, 2013) and engage a network of brain regions, including the medial prefrontal cortex, temporal parietal junction, superior temporal sulcus, and precuneus (Amodio & Frith, Nature Reviews Neuroscience, 7(4), 268-277, 2006; Haxby, Gobbini, & Montgomery, 2004; van Overwalle Human Brain Mapping, 30, 829-858, 2009). We investigate the role of these brain regions during social learning about well-established dimensions of person perception-trait warmth and trait competence. We test the hypothesis that activity in person perception brain regions interacts with learning structures during social learning. Participants play an investment game where they must choose an agent to invest on their behalf. This choice is guided by cues signaling trait warmth or trait competence based on framing of monetary returns. Trait warmth information impairs learning about human but not computer agents, while trait competence information produces similar learning rates for human and computer agents. We see increased activation to warmth information about human agents in person perception brain regions. Interestingly, activity in person perception brain regions during the decision phase negatively predicts activity in the striatum during feedback for trait competence inferences about humans. These results suggest that social learning may engage additional processing within person perception brain regions that hampers learning in economic contexts.

  3. Impaired surface expression of PAF receptors on human neutrophils is dependent upon cell activation.

    PubMed

    Zhou, W; Javors, M A; Olson, M S

    1994-02-01

    The capacity of human neutrophils to bind PAF was rapidly diminished upon cell stimulation with both physiological agonists (N-formylmethionylleucylphenylalanine (FMLP), leukotriene B4 (LTB4)) and pharmacologic agonists (phorbol 12-myristate 13-acetate (PMA), A23187). As a consequence, PAF responses in neutrophils were blunted, as monitored by an inhibition of intracellular Ca2+ mobilization. Downregulation of the PAF receptor in neutrophils by diverse agonists was temperature-sensitive and required intact cells. Scatchard analysis of binding data revealed that PAF binding sites were lost without an appreciable change in the affinity of the ligand for the receptor. The binding of the PAF receptor antagonist WEB2086 to neutrophils decreased in parallel with PAF binding. PMA-induced PAF receptor downregulation was staurosporine-sensitive while PAF receptor downregulation by A23187, FMLP, or LTB4 was staurosporine-resistant. Both neutrophil aggregation (a form of intercellular adhesion) and PAF receptor downregulation occurred only at high concentrations of agonists while other signaling processes such as the increase in [Ca2+]i, PKC activation, and PAF synthesis were stimulated at low concentrations of agonists. Furthermore, agonist-induced PAF receptor downregulation was observed only under conditions in which the activated neutrophils were stirred (or shaken) and were allowed to aggregate. Additionally, chelation of extracellular Ca2+ with EGTA minimized cell aggregation and also inhibited PAF receptor downregulation. While the nature of the biochemical signal or the physical changes in the plasma membrane associated with aggregation or that follow aggregation remain to be elucidated it is clear that full expression of cell activation (i.e., neutrophil aggregation) is required for PAF receptor downregulation.

  4. RAI1 transcription factor activity is impaired in mutants associated with Smith-Magenis Syndrome.

    PubMed

    Carmona-Mora, Paulina; Canales, Cesar P; Cao, Lei; Perez, Irene C; Srivastava, Anand K; Young, Juan I; Walz, Katherina

    2012-01-01

    Smith-Magenis Syndrome (SMS) is a complex genomic disorder mostly caused by the haploinsufficiency of the Retinoic Acid Induced 1 gene (RAI1), located in the chromosomal region 17p11.2. In a subset of SMS patients, heterozygous mutations in RAI1 are found. Here we investigate the molecular properties of these mutated forms and their relationship with the resulting phenotype. We compared the clinical phenotype of SMS patients carrying a mutation in RAI1 coding region either in the N-terminal or the C-terminal half of the protein and no significant differences were found. In order to study the molecular mechanism related to these two groups of RAI1 mutations first we analyzed those mutations that result in the truncated protein corresponding to the N-terminal half of RAI1 finding that they have cytoplasmic localization (in contrast to full length RAI1) and no ability to activate the transcription through an endogenous target: the BDNF enhancer. Similar results were found in lymphoblastoid cells derived from a SMS patient carrying RAI1 c.3103insC, where both mutant and wild type products of RAI1 were detected. The wild type form of RAI1 was found in the chromatin bound and nuclear matrix subcellular fractions while the mutant product was mainly cytoplasmic. In addition, missense mutations at the C-terminal half of RAI1 presented a correct nuclear localization but no activation of the endogenous target. Our results showed for the first time a correlation between RAI1 mutations and abnormal protein function plus they suggest that a reduction of total RAI1 transcription factor activity is at the heart of the SMS clinical presentation.

  5. The Toronto Empathy Questionnaire

    PubMed Central

    Spreng, R. Nathan; McKinnon, Margaret C.; Mar, Raymond A.; Levine, Brian

    2008-01-01

    In order to formulate a parsimonious tool to assess empathy, we used factor analysis on a combination of self-report measures to examine consensus and developed a brief self-report measure of this common factor. The Toronto Empathy Questionnaire (TEQ) represents empathy as a primarily emotional process. In three studies, the TEQ demonstrated strong convergent validity, correlating positively with behavioral measures of social decoding, self-report measures of empathy, and negatively with a measure of Autism symptomatology. Moreover, it exhibited good internal consistency and high test-retest reliability. The TEQ is a brief, reliable, and valid instrument for the assessment of empathy. PMID:19085285

  6. Ubc9 Impairs Activation of the Brown Fat Energy Metabolism Program in Human White Adipocytes.

    PubMed

    Hartig, Sean M; Bader, David A; Abadie, Kathleen V; Motamed, Massoud; Hamilton, Mark P; Long, Weiwen; York, Brian; Mueller, Michaela; Wagner, Martin; Trauner, Michael; Chan, Lawrence; Bajaj, Mandeep; Moore, David D; Mancini, Michael A; McGuire, Sean E

    2015-09-01

    Insulin resistance and type 2 diabetes mellitus (T2DM) result from an inability to efficiently store and catabolize surplus energy in adipose tissue. Subcutaneous adipocytes protect against insulin resistance and T2DM by coupling differentiation with the induction of brown fat gene programs for efficient energy metabolism. Mechanisms that disrupt these programs in adipocytes are currently poorly defined, but represent therapeutic targets for the treatment of T2DM. To gain insight into these mechanisms, we performed a high-throughput microscopy screen that identified ubiquitin carrier protein 9 (Ubc9) as a negative regulator of energy storage in human sc adipocytes. Ubc9 depletion enhanced energy storage and induced the brown fat gene program in human sc adipocytes. Induction of adipocyte differentiation resulted in decreased Ubc9 expression commensurate with increased brown fat gene expression. Thiazolidinedione treatment reduced the interaction between Ubc9 and peroxisome proliferator-activated receptor (PPAR)γ, suggesting a mechanism by which Ubc9 represses PPARγ activity. In support of this hypothesis, Ubc9 overexpression remodeled energy metabolism in human sc adipocytes by selectively inhibiting brown adipocyte-specific function. Further, Ubc9 overexpression decreased uncoupling protein 1 expression by disrupting PPARγ binding at a critical uncoupling protein 1 enhancer region. Last, Ubc9 is significantly elevated in sc adipose tissue isolated from mouse models of insulin resistance as well as diabetic and insulin-resistant humans. Taken together, our findings demonstrate a critical role for Ubc9 in the regulation of sc adipocyte energy homeostasis.

  7. Emotion Regulation and Excess Weight: Impaired Affective Processing Characterized by Dysfunctional Insula Activation and Connectivity.

    PubMed

    Steward, Trevor; Picó-Pérez, Maria; Mata, Fernanda; Martínez-Zalacaín, Ignacio; Cano, Marta; Contreras-Rodríguez, Oren; Fernández-Aranda, Fernando; Yucel, Murat; Soriano-Mas, Carles; Verdejo-García, Antonio

    2016-01-01

    Emotion-regulation strategies are understood to influence food intake. This study examined the neurophysiological underpinnings of negative emotion processing and emotion regulation in individuals with excess weight compared to normal-weight controls. Fifteen participants with excess-weight (body mass index >25) and sixteen normal-weight controls (body mass index 18-25) performed an emotion-regulation task during functional magnetic resonance imaging. Participants were exposed to 24 negative affective or neutral pictures that they were instructed to Observe (neutral pictures), Maintain (sustain the emotion elicited by negative pictures) or Regulate (down-regulate the emotion provoked by negative pictures through previously trained reappraisal techniques). When instructed to regulate negative emotions by means of cognitive reappraisal, participants with excess weight displayed persistently heightened activation in the right anterior insula. Decreased responsivity was also found in right anterior insula, the orbitofrontal cortex and cerebellum during negative emotion experience in participants with excess weight. Psycho-physiological interaction analyses showed that excess-weight participants had decreased negative functional coupling between the right anterior insula and the right dlPFC, and the bilateral dmPFC during cognitive reappraisal. Our findings support contentions that excess weight is linked to an abnormal pattern of neural activation and connectivity during the experience and regulation of negative emotions, with the insula playing a key role in these alterations. We posit that ineffective regulation of emotional states contributes to the acquisition and preservation of excess weight.

  8. Activity Pattern Profiles: Relationship With Affect, Daily Functioning, Impairment, and Variables Related to Life Goals.

    PubMed

    Esteve, Rosa; López-Martínez, Alicia E; Peters, Madelon L; Serrano-Ibáñez, Elena R; Ruíz-Párraga, Gema T; González-Gómez, Henar; Ramírez-Maestre, Carmen

    2017-01-04

    The aim of this cross-sectional study was to identify subgroups of patients on the basis of their activity patterns and to investigate their relationship with life goals, optimism, affect, and functioning. The sample was comprised of 276 patients with chronic musculoskeletal pain. Hierarchical cluster analysis was performed on the activity pattern variables and the resulting clusters were compared using 1-way analysis of variance. The 4-cluster was the optimal solution. The 4 clusters comprised: 1) avoiders: patients with high levels of avoidance and low levels of persistence, who use pacing to reduce pain, 2) doers: patients with high levels of persistence and low levels of pacing and avoidance, 3) extreme cyclers: patients with high levels of avoidance and persistence and low levels of pacing, and 4) medium cyclers: patients with moderately high levels of avoidance and persistence and high levels of pacing. Comparison of the clusters showed that doers had the most adaptive profile, whereas avoiders, followed by extreme cyclers, had unhealthy profiles. Doers showed a high level of optimism and a good balance between goal value, expectancy, and conflict.

  9. Emotion Regulation and Excess Weight: Impaired Affective Processing Characterized by Dysfunctional Insula Activation and Connectivity

    PubMed Central

    Mata, Fernanda; Martínez-Zalacaín, Ignacio; Cano, Marta; Contreras-Rodríguez, Oren; Fernández-Aranda, Fernando; Yucel, Murat; Soriano-Mas, Carles; Verdejo-García, Antonio

    2016-01-01

    Emotion-regulation strategies are understood to influence food intake. This study examined the neurophysiological underpinnings of negative emotion processing and emotion regulation in individuals with excess weight compared to normal-weight controls. Fifteen participants with excess-weight (body mass index >25) and sixteen normal-weight controls (body mass index 18–25) performed an emotion-regulation task during functional magnetic resonance imaging. Participants were exposed to 24 negative affective or neutral pictures that they were instructed to Observe (neutral pictures), Maintain (sustain the emotion elicited by negative pictures) or Regulate (down-regulate the emotion provoked by negative pictures through previously trained reappraisal techniques). When instructed to regulate negative emotions by means of cognitive reappraisal, participants with excess weight displayed persistently heightened activation in the right anterior insula. Decreased responsivity was also found in right anterior insula, the orbitofrontal cortex and cerebellum during negative emotion experience in participants with excess weight. Psycho-physiological interaction analyses showed that excess-weight participants had decreased negative functional coupling between the right anterior insula and the right dlPFC, and the bilateral dmPFC during cognitive reappraisal. Our findings support contentions that excess weight is linked to an abnormal pattern of neural activation and connectivity during the experience and regulation of negative emotions, with the insula playing a key role in these alterations. We posit that ineffective regulation of emotional states contributes to the acquisition and preservation of excess weight. PMID:27003840

  10. E2F6 Impairs Glycolysis and Activates BDH1 Expression Prior to Dilated Cardiomyopathy

    PubMed Central

    Major, Jennifer L.; Dewan, Aaraf; Salih, Maysoon; Leddy, John J.; Tuana, Balwant S.

    2017-01-01

    Rationale The E2F pathway plays a critical role in cardiac growth and development, yet its role in cardiac metabolism remains to be defined. Metabolic changes play important roles in human heart failure and studies imply the ketogenic enzyme β-hydroxybutyrate dehydrogenase I (BDH1) is a potential biomarker. Objective To define the role of the E2F pathway in cardiac metabolism and dilated cardiomyopathy (DCM) with a focus on BDH1. Methods and Results We previously developed transgenic (Tg) mice expressing the transcriptional repressor, E2F6, to interfere with the E2F/Rb pathway in post-natal myocardium. These Tg mice present with an E2F6 dose dependent DCM and deregulated connexin-43 (CX-43) levels in myocardium. Using the Seahorse platform, a 22% decrease in glycolysis was noted in neonatal cardiomyocytes isolated from E2F6-Tg hearts. This was associated with a 39% reduction in the glucose transporter GLUT4 and 50% less activation of the regulator of glucose metabolism AKT2. The specific reduction of cyclin B1 (70%) in Tg myocardium implicates its importance in supporting glycolysis in the postnatal heart. No changes in cyclin D expression (known to regulate mitochondrial activity) were noted and lipid metabolism remained unchanged in neonatal cardiomyocytes from Tg hearts. However, E2F6 induced a 40-fold increase of the Bdh1 transcript and 890% increase in its protein levels in hearts from Tg pups implying a potential impact on ketolysis. By contrast, BDH1 expression is not activated until adulthood in normal myocardium. Neonatal cardiomyocytes from Wt hearts incubated with the ketone β-hydroxybutyrate (β-OHB) showed a 100% increase in CX-43 protein levels, implying a role for ketone signaling in gap junction biology. Neonatal cardiomyocyte cultures from Tg hearts exhibited enhanced levels of BDH1 and CX-43 and were not responsive to β-OHB. Conclusions The data reveal a novel role for the E2F pathway in regulating glycolysis in the developing myocardium

  11. Object Perception Impairments Predict Instrumental Activities of Daily Living Dependence in Alzheimer's Disease

    PubMed Central

    JEFFERSON, ANGELA L.; BARAKAT, LAMIA P.; GIOVANNETTI, TANIA; PAUL, ROBERT H.; GLOSSER, GUILA

    2009-01-01

    This study examined the contribution of object perception and spatial localization to functional dependence among Alzheimer's disease (AD) patients. Forty patients with probable AD completed measures assessing verbal recognition memory, working memory, object perception, spatial localization, semantic knowledge, and global cognition. Primary caregivers completed a measure of activities of daily living (ADLs) that included instrumental and basic self-care subscales (i.e., IADLs and BADLs, respectively). Stepwise multiple regressions revealed that global cognition accounted for significant portions of variance among the ADL total, IADL, and BADL scores. However, when global cognition was removed from the model, object perception was the only significant cognitive predictor of the ADL total and IADL subscale scores, accounting for 18.5% and 19.3% of the variance, respectively. When considering multiple cognitive components simultaneously, object perception and the integrity of the inferotemporal cortex is important in the completion of functional abilities in general and IADLs in particular among AD patients. PMID:16822730

  12. Ablation of Y1 receptor impairs osteoclast bone-resorbing activity

    PubMed Central

    Sousa, Daniela M.; Conceição, Francisco; Silva, Diana I.; Leitão, Luís; Neto, Estrela; Alves, Cecília J.; Alencastre, Inês S.; Herzog, Herbert; Aguiar, Paulo; Lamghari, Meriem

    2016-01-01

    Y1 receptor (Y1R)-signalling pathway plays a pivotal role in the regulation of bone metabolism. The lack of Y1R-signalling stimulates bone mass accretion that has been mainly attributed to Y1R disruption from bone-forming cells. Still, the involvement of Y1R-signalling in the control of bone-resorbing cells remained to be explored. Therefore, in this study we assessed the role of Y1R deficiency in osteoclast formation and resorption activity. Here we demonstrate that Y1R germline deletion (Y1R−/−) led to increased formation of highly multinucleated (n > 8) osteoclasts and enhanced surface area, possibly due to monocyte chemoattractant protein-1 (MCP-1) overexpression regulated by RANKL-signalling. Interestingly, functional studies revealed that these giant Y1R−/− multinucleated cells produce poorly demineralized eroded pits, which were associated to reduce expression of osteoclast matrix degradation markers, such as tartrate-resistant acid phosphatase-5b (TRAcP5b), matrix metalloproteinase-9 (MMP-9) and cathepsin-K (CTSK). Tridimensional (3D) morphologic analyses of resorption pits, using an in-house developed quantitative computational tool (BonePit), showed that Y1R−/− resorption pits displayed a marked reduction in surface area, volume and depth. Together, these data demonstrates that the lack of Y1Rs stimulates the formation of larger multinucleated osteoclasts in vitro with reduced bone-resorbing activity, unveiling a novel therapeutic option for osteoclastic bone diseases based on Y1R-signalling ablation. PMID:27646989

  13. Impaired ergosterol biosynthesis mediated fungicidal activity of Co(II) complex with ligand derived from cinnamaldehyde.

    PubMed

    Shreaz, Sheikh; Shiekh, Rayees A; Raja, Vaseem; Wani, Waseem A; Behbehani, Jawad M

    2016-03-05

    In this study, we have used aldehyde function of cinnamaldehyde to synthesize N, N'-Bis (cinnamaldehyde) ethylenediimine [C20H20N2] and Co(II) complex of the type [Co(C40H40N4)Cl2]. The structures of the synthesized compounds were determined on the basis of physiochemical analysis and spectroscopic data ((1)H NMR, FTIR, UV-visible and mass spectra) along with molar conductivity measurements. Anticandidal activity of cinnamaldehyde its ligand [L] and Co(II) complex was investigated by determining MIC80, time-kill kinetics, disc diffusion assay and ergosterol extraction and estimation assay. Ligand [L] and Co(II) complex are found to be 4.55 and 21.0 folds more efficient than cinnamaldehyde in a liquid medium. MIC80 of Co(II) complex correlated well with ergosterol inhibition suggesting ergosterol biosynthesis to be the primary site of action. In comparison to fluconazole, the test compounds showed limited toxicity against H9c2 rat cardiac myoblasts. In confocal microscopy propidium iodide (PI) penetrates the yeast cells when treated with MIC of metal complex, indicating a disruption of cell membrane that results in imbibition of dye. TEM analysis of metal complex treated cells exhibited notable alterations or damage to the cell membrane and the cell wall. The structural disorganization within the cell cytoplasm was noted. It was concluded that fungicidal activity of Co(II) complex originated from loss of membrane integrity and a decrease in ergosterol content is only one consequence of this.

  14. Abelson murine leukemia virus transformation-defective mutants with impaired P120-associated protein kinase activity.

    PubMed Central

    Reynolds, F H; Van de Ven, W J; Stephenson, J R

    1980-01-01

    Several transformation-defective (td) mutants of Abelson murine leukemia virus (AbLV) are described. Cells nonproductively infected with such mutants exhibited a high degree of growth contact inhibition, failed to form colonies in soft agar, lacked rescuable transforming virus, and were as susceptible as uninfected control cells to transformation by wild-type (wt) AbLV pseudotype virus. In addition, each of several td AbLV nonproductively infected cell clones analyzed was found to be nontumorigenic in vivo. Biochemical analysis of td mutant AbLV-infected clones revealed levels of expression of the major AbLV translational product, P120, and a highly related 80,000-Mr AbLV-encoded protein, P80, at concentrations analogous to those in wt AbLV-transformed cells. Although the AbLV-specific 120,000-Mr polyproteins expressed in td mutant AbLV-infected clones were indistinguishable from those in wt AbLV-transformed lines with respect to molecular weight and [35S]methionine tryptic peptide composition, they each differed from wt AbLV P120 in their patterns of post-translational phosphorylation. A previously described AbLV-associated protein kinase activity is shown to recognize as substrate a major tyrosine-specific acceptor site(s) contained within a single well-resolved tryptic peptide common to both AbLV P120 and P80. In vitro [gamma-32P]ATP-mediated labeling of this phosphorylation site was reduced to below detectable levels in td mutant nonproductively infected cell clones. These findings establish that the AbLV-encoded polyprotein P120 and its associated protein kinase activity are involved in AbLV tumorigenesis. Images PMID:6253663

  15. Enhanced IL-1beta production in response to the activation of hippocampal glial cells impairs neurogenesis in aged mice.

    PubMed

    Kuzumaki, Naoko; Ikegami, Daigo; Imai, Satoshi; Narita, Michiko; Tamura, Rie; Yajima, Marie; Suzuki, Atsuo; Miyashita, Kazuhiko; Niikura, Keiichi; Takeshima, Hideyuki; Ando, Takayuki; Ushijima, Toshikazu; Suzuki, Tsutomu; Narita, Minoru

    2010-09-01

    A variety of mechanisms that contribute to the accumulation of age-related damage and the resulting brain dysfunction have been identified. Recently, decreased neurogenesis in the hippocampus has been recognized as one of the mechanisms of age-related brain dysfunction. However, the molecular mechanism of decreased neurogenesis with aging is still unclear. In the present study, we investigated whether aging decreases neurogenesis accompanied by the activation of microglia and astrocytes, which increases the expression of IL-1beta in the hippocampus, and whether in vitro treatment with IL-1beta in neural stem cells directly impairs neurogenesis. Ionized calcium-binding adaptor molecule 1 (Iba1)-positive microglia and glial fibrillary acidic protein (GFAP)-positive astrocytes were increased in the dentate gyrus of the hippocampus of 28-month-old mice. Furthermore, the mRNA level of IL-1beta was significantly increased without related histone modifications. Moreover, a significant increase in lysine 9 on histone H3 (H3K9) trimethylation at the promoter of NeuroD (a neural progenitor cell marker) was observed in the hippocampus of aged mice. In vitro treatment with IL-1beta in neural stem cells prepared from whole brain of E14.5 mice significantly increased H3K9 trimethylation at the NeuroD promoter. These findings suggest that aging may decrease hippocampal neurogenesis via epigenetic modifications accompanied by the activation of microglia and astrocytes with the increased expression of IL-1beta in the hippocampus.

  16. CpG-based immunotherapy impairs antitumor activity of BRAF inhibitors in a B-cell-dependent manner.

    PubMed

    Huang, L; Wang, Z; Liu, C; Xu, C; Mbofung, R M; McKenzie, J A; Khong, H; Hwu, P; Peng, W

    2017-03-06

    Combining immunotherapy with targeted therapy has increasingly become an appealing therapeutic paradigm for cancer treatment due to its great potential for generating durable and synergistic antitumor response. In this study, however, we unexpectedly found that two types of CpG-based tumor peptide vaccine treatments consistently negated the antitumor activity of a selective BRAF inhibitor in tumors with BRAF mutation rather than showing a synergistic antitumor effect. Our further studies demonstrated that CpG alone was sufficient to dampen BRAF inhibitor-induced antitumor responses, suggesting that the impaired antitumor activity of the BRAF inhibitor observed in mice receiving CpG-based peptide vaccine is mainly dependent upon the use of CpG. Mechanistically, CpG increased the number of circulating B cells, which produced elevated amounts of tumor necrosis factor-α (TNFα) that contributed to the increased tumor resistance to BRAF inhibitors. More importantly, B-cell depletion or TNFα neutralization can restore the antitumor effect of BRAF inhibition in mice receiving CpG treatment, indicating that TNFα-secreting B cells play an indispensable role in BRAF inhibitor resistance induced by CpG. Taken together, our results strongly suggest that precautions must be implemented when designing combinatorial approaches for cancer treatment, because distinct regimens, despite their respective therapeutic benefit as monotherapy, may together provide antagonistic clinical outcomes.Oncogene advance online publication, 6 March 2017; doi:10.1038/onc.2017.35.

  17. Amyloid beta-peptide impairs ion-motive ATPase activities: evidence for a role in loss of neuronal Ca2+ homeostasis and cell death.

    PubMed

    Mark, R J; Hensley, K; Butterfield, D A; Mattson, M P

    1995-09-01

    The amyloid beta-peptide (A beta) that accumulates as insoluble plaques in the brain in Alzheimer's disease can be directly neurotoxic and can increase neuronal vulnerability to excitotoxic insults. The mechanism of A beta toxicity is unclear but is believed to involve generation of reactive oxygen species (ROS) and loss of calcium homeostasis. We now report that exposure of cultured rat hippocampal neurons to A beta 1-40 or A beta 25-35 causes a selective reduction in Na+/K(+)-ATPase activity which precedes loss of calcium homeostasis and cell degeneration. Na+/K(+)-ATPase activity was reduced within 30 min of exposure to A beta 25-35 and declined to less than 40% of basal level by 3 hr. A beta did not impair other Mg(2+)-dependent ATPase activities or Na+/Ca2+ exchange. Experiments with ouabain, a specific inhibitor of the Na+/K(+)-ATPase, demonstrated that impairment of this enzyme was sufficient to induce an elevation of [Ca2+]i and neuronal injury. Impairment of Na+/K(+)-ATPase activity appeared to be causally involved in the elevation of [Ca2+]i and neurotoxicity since suppression of Na+ influx significantly reduced A beta- and ouabain-induced [Ca2+]i elevation and neuronal death. Neuronal degeneration induced by ouabain appeared to be of an apoptotic form as indicated by nuclear condensation and DNA fragmentation. The antioxidant free radical scavengers vitamin E and propylgallate significantly attenuated A beta-induced impairment of Na+/K(+)-ATPase activity, elevation of [Ca2+]i and neurotoxicity, suggesting a role for ROS. Finally, exposure of synaptosomes from postmortem human hippocampus to A beta resulted in a significant and specific reduction in Na+/K(+)-ATPase and Ca(2+)-ATPase activities, without affecting other Mg(2+)-dependent ATPase activities or Na+/Ca2+ exchange. These data suggest that impairment of ion-motive ATPases may play a role in the pathogenesis of neuronal injury in Alzheimer's disease.

  18. Mitochondrial impairment induced by 3-nitropropionic acid is enhanced by endogenous metalloprotease activity inhibition in cultured rat striatal neurons.

    PubMed

    de Oca Balderas, Pavel Montes; Ospina, Gabriel Gutiérrez; Del Ángel, Abel Santamaría

    2013-06-24

    Metalloproteases from the metzincin family mediate molecule processing at the cell membrane termed ectodomain shedding (ES). This mechanism enables the generation of intracellular and extracellular fragments from cell membrane molecules that exert additional functions involved in cell processes including cell death, beyond those of full length molecules. Micotoxin 3-nitropropionic acid (3-NP) induces striatal neuronal degeneration in vivo and in vitro through mitochondrial complex II inhibition. In this study, we hypothesized that metalloproteases regulate mitochondrial activity in cultured rat striatal neurons undergoing degeneration. To test this idea, striatal neuronal cultures characterized by NeuN and GAD-67 expression were treated with 3-NP together with the metalloprotease inhibitor GM6001 and their mitochondrial activity was evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Our results showed that metalloprotease inhibition potentiated mitochondrial activity impairment induced by 3-NP whereas the inhibitor alone had no effect. These results indicate that metalloproteases regulate and promote mitochondrial functionality in striatal neurons undergoing degeneration induced by 3-NP. Since NMDA receptor is involved in the excitotoxic neuronal death triggered by 3-NP and is known to undergo ES, we analyzed NMDAR subunit NR1 phenotypic distribution by immunofluorescence. 3-NP and GM6001 induced abnormal perinuclear NR1 accumulation that was not observed with 3-NP or GM6001 alone. This observation suggests that metalloproteases are involved in NR1 cellular reorganization induced by 3-NP, and that their inhibition results in abnormal NR1 distribution. Together results indicate that endogenous metalloproteases are activated during striatal neurodegeneration induced by 3-NP eliciting an adaptative or compensatory response that protects mitochondrial functionality.

  19. Impairment of chondrocyte biosynthetic activity by exposure to 3-tesla high-field magnetic resonance imaging is temporary.

    PubMed

    Sunk, Ilse-Gerlinde; Trattnig, Siegfried; Graninger, Winfried B; Amoyo, Love; Tuerk, Birgit; Steiner, Carl-Walter; Smolen, Josef S; Bobacz, Klaus

    2006-01-01

    The influence of magnetic resonance imaging (MRI) devices at high field strengths on living tissues is unknown. We investigated the effects of a 3-tesla electromagnetic field (EMF) on the biosynthetic activity of bovine articular cartilage. Bovine articular cartilage was obtained from juvenile and adult animals. Whole joints or cartilage explants were subjected to a pulsed 3-tesla EMF; controls were left unexposed. Synthesis of sulfated glycosaminoglycans (sGAGs) was measured by using [35S]sulfate incorporation; mRNA encoding the cartilage markers aggrecan and type II collagen, as well as IL-1beta, were analyzed by RT-PCR. Furthermore, effects of the 3-tesla EMF were determined over the course of time directly after exposure (day 0) and at days 3 and 6. In addition, the influence of a 1.5-tesla EMF on cartilage sGAG synthesis was evaluated. Chondrocyte cell death was assessed by staining with Annexin V and TdT-mediated dUTP nick end labelling (TUNEL). Exposure to the EMF resulted in a significant decrease in cartilage macromolecule synthesis. Gene expression of both aggrecan and IL-1beta, but not of collagen type II, was reduced in comparison with controls. Staining with Annexin V and TUNEL revealed no evidence of cell death. Interestingly, chondrocytes regained their biosynthetic activity within 3 days after exposure, as shown by proteoglycan synthesis rate and mRNA expression levels. Cartilage samples exposed to a 1.5-tesla EMF remained unaffected. Although MRI devices with a field strength of more than 1.5 T provide a better signal-to-noise ratio and thereby higher spatial resolution, their high field strength impairs the biosynthetic activity of articular chondrocytes in vitro. Although this decrease in biosynthetic activity seems to be transient, articular cartilage exposed to high-energy EMF may become vulnerable to damage.

  20. Visual impairment, visual functioning, and quality of life assessments in patients with glaucoma.

    PubMed Central

    Parrish, R K

    1996-01-01

    BACKGROUND/PURPOSE: To determine the relation between visual impairment, visual functioning, and the global quality of life in patients with glaucoma. METHODS: Visual impairment, defined with the American Medical Association Guides to the Evaluation of Permanent Impairment; visual functioning, measured with the VF-14 and the Field Test Version of the National Eye Institute-Visual Functioning Questionnaire (NEI-VFQ); and the global quality of life, assessed with the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), were determined in 147 consecutive patients with glaucoma. RESULTS: None of the SF-36 domains demonstrated more than a weak correlation with visual impairment. The VF-14 scores were moderately correlated with visual impairment. Of the twelve NEI-VFQ scales, distance activities and vision specific dependency were moderately correlated with visual impairment. Of the twelve NEI-VFQ scales, distance activities and vision specific dependency were moderately correlated with visual field impairment; vision specific social functioning, near activities, vision specific role difficulties, general vision, vision specific mental health, color vision, and driving were modestly correlated; visual pain was weakly correlated; and two were not significantly correlated. Correcting for visual actuity weakened the strength of the correlation coefficients. CONCLUSIONS: The SF-36 is unlikely to be useful in determining visual impairment in patients with glaucoma. Based on the moderate correlation between visual field impairment and the VF-14 score, this questionnaire may be generalizable to patients with glaucoma. Several of the NEI-VFQ scales correlate with visual field impairment scores in patients with a wide range of glaucomatous damage. PMID:8981717

  1. Increasing Acetylcholine Levels in the Hippocampus or Entorhinal Cortex Reverses the Impairing Effects of Septal GABA Receptor Activation on Spontaneous Alternation

    PubMed Central

    Degroot, Aldemar; Parent, Marise B.

    2000-01-01

    Intra-septal infusions of the γ-aminobutyric acid (GABA) agonist muscimol impair learning and memory in a variety of tasks. This experiment determined whether hippocampal or entorhinal infusions of the acetylcholinesterase inhibitor physostigmine would reverse such impairing effects on spontaneous alternation performance, a measure of spatial working memory. Male Sprague-Dawley rats were given intra-septal infusions of vehicle or muscimol (1 nmole/0.5 μL) combined with unilateral intra-hippocampal or intra-entorhinal infusions of vehicle or physostigmine (10 μg/μL for the hippocampus; 7.5 μg/μL or 1.875 μg/0.25 μL for the entorhinal cortex). Fifteen minutes later, spontaneous alternation performance was assessed. The results indicated that intra-septal infusions of muscimol significantly decreased percentage-of-alternation scores, whereas intra-hippocampal or intra-entorhinal infusions of physostigmine had no effect. More importantly, intra-hippocampal or intra-entorhinal infusions of physostigmine, at doses that did not influence performance when administered alone, completely reversed the impairing effects of the muscimol infusions. These findings indicate that increasing cholinergic levels in the hippocampus or entorhinal cortex is sufficient to reverse the impairing effects of septal GABA receptor activation and support the hypothesis that the impairing effects of septal GABAergic activity involve cholinergic processes in the hippocampus and the entorhinal cortex. PMID:11040261

  2. Active immunization with amyloid-beta 1-42 impairs memory performance through TLR2/4-dependent activation of the innate immune system.

    PubMed

    Vollmar, Patrick; Kullmann, Jennifer S; Thilo, Barbara; Claussen, Malte C; Rothhammer, Veit; Jacobi, Hortenzia; Sellner, Johann; Nessler, Stefan; Korn, Thomas; Hemmer, Bernhard

    2010-11-15

    Active immunization with amyloid-β (Aβ) peptide 1-42 reverses amyloid plaque deposition in the CNS of patients with Alzheimer's disease and in amyloid precursor protein transgenic mice. However, this treatment may also cause severe, life-threatening meningoencephalitis. Physiological responses to immunization with Aβ(1-42) are poorly understood. In this study, we characterized cognitive and immunological consequences of Aβ(1-42)/CFA immunization in C57BL/6 mice. In contrast to mice immunized with myelin oligodendrocyte glycoprotein (MOG)(35-55)/CFA or CFA alone, Aβ(1-42)/CFA immunization resulted in impaired exploratory activity, habituation learning, and spatial-learning abilities in the open field. As morphological substrate of this neurocognitive phenotype, we identified a disseminated, nonfocal immune cell infiltrate in the CNS of Aβ(1-42)/CFA-immunized animals. In contrast to MOG(35-55)/CFA and PBS/CFA controls, the majority of infiltrating cells in Aβ(1-42)/CFA-immunized mice were CD11b(+)CD14(+) and CD45(high), indicating their blood-borne monocyte/macrophage origin. Immunization with Aβ(1-42)/CFA was significantly more potent than immunization with MOG(35-55)/CFA or CFA alone in activating macrophages in the secondary lymphoid compartment and peripheral tissues. Studies with TLR2/4-deficient mice revealed that the TLR2/4 pathway mediated the Aβ(1-42)-dependent proinflammatory cytokine release from cells of the innate immune system. In line with this, TLR2/4 knockout mice were protected from cognitive impairment upon immunization with Aβ(1-42)/CFA. Thus, this study identifies adjuvant effects of Aβ(1-42), which result in a clinically relevant neurocognitive phenotype highlighting potential risks of Aβ immunotherapy.

  3. Activation of the arousal response can impair performance on a simple motor task.

    PubMed

    Noteboom, J T; Fleshner, M; Enoka, R M

    2001-08-01

    The purpose of this study was to determine the effect of arousal in men and women on the moment-to-moment performance of a simple motor task. We examined the control of a precision task in the presence and absence of imposed stressors. Twenty-nine subjects (14 men, 15 women; 18--44 yr) were randomly assigned to either a control group or one of two stressor groups, Mental Math or Electric Shock. Subjects presented with Math and Shock stressors, which lasted 10 min, experienced significant increases in cognitive and physiological arousal compared with baseline and control subjects. Heart rate, systolic blood pressure, and electrodermal activity were elevated 5--80% with presentation of the stressors, whereas diastolic blood pressure and salivary cortisol were unchanged. The greater levels of cognitive and physiological arousal were associated with reductions in steadiness of a pinch grip for the Shock subjects (approximately 130% reduction from baseline) but not for the subjects in the Math group, who experienced heightened arousal but no change in steadiness (10% reduction from baseline). Although women exhibited more of a reduction in steadiness than men, the effect was largely unrelated to the magnitude of the change in arousal.

  4. Impaired PRC2 activity promotes transcriptional instability and favors breast tumorigenesis.

    PubMed

    Wassef, Michel; Rodilla, Veronica; Teissandier, Aurélie; Zeitouni, Bruno; Gruel, Nadege; Sadacca, Benjamin; Irondelle, Marie; Charruel, Margaux; Ducos, Bertrand; Michaud, Audrey; Caron, Matthieu; Marangoni, Elisabetta; Chavrier, Philippe; Le Tourneau, Christophe; Kamal, Maud; Pasmant, Eric; Vidaud, Michel; Servant, Nicolas; Reyal, Fabien; Meseure, Dider; Vincent-Salomon, Anne; Fre, Silvia; Margueron, Raphaël

    2015-12-15

    Alterations of chromatin modifiers are frequent in cancer, but their functional consequences often remain unclear. Focusing on the Polycomb protein EZH2 that deposits the H3K27me3 (trimethylation of Lys27 of histone H3) mark, we showed that its high expression in solid tumors is a consequence, not a cause, of tumorigenesis. In mouse and human models, EZH2 is dispensable for prostate cancer development and restrains breast tumorigenesis. High EZH2 expression in tumors results from a tight coupling to proliferation to ensure H3K27me3 homeostasis. However, this process malfunctions in breast cancer. Low EZH2 expression relative to proliferation and mutations in Polycomb genes actually indicate poor prognosis and occur in metastases. We show that while altered EZH2 activity consistently modulates a subset of its target genes, it promotes a wider transcriptional instability. Importantly, transcriptional changes that are consequences of EZH2 loss are predominantly irreversible. Our study provides an unexpected understanding of EZH2's contribution to solid tumors with important therapeutic implications.

  5. Impaired PRC2 activity promotes transcriptional instability and favors breast tumorigenesis

    PubMed Central

    Wassef, Michel; Rodilla, Veronica; Teissandier, Aurélie; Zeitouni, Bruno; Gruel, Nadege; Sadacca, Benjamin; Irondelle, Marie; Charruel, Margaux; Ducos, Bertrand; Michaud, Audrey; Caron, Matthieu; Marangoni, Elisabetta; Chavrier, Philippe; Le Tourneau, Christophe; Kamal, Maud; Pasmant, Eric; Vidaud, Michel; Servant, Nicolas; Reyal, Fabien; Meseure, Dider; Vincent-Salomon, Anne; Fre, Silvia; Margueron, Raphaël

    2015-01-01

    Alterations of chromatin modifiers are frequent in cancer, but their functional consequences often remain unclear. Focusing on the Polycomb protein EZH2 that deposits the H3K27me3 (trimethylation of Lys27 of histone H3) mark, we showed that its high expression in solid tumors is a consequence, not a cause, of tumorigenesis. In mouse and human models, EZH2 is dispensable for prostate cancer development and restrains breast tumorigenesis. High EZH2 expression in tumors results from a tight coupling to proliferation to ensure H3K27me3 homeostasis. However, this process malfunctions in breast cancer. Low EZH2 expression relative to proliferation and mutations in Polycomb genes actually indicate poor prognosis and occur in metastases. We show that while altered EZH2 activity consistently modulates a subset of its target genes, it promotes a wider transcriptional instability. Importantly, transcriptional changes that are consequences of EZH2 loss are predominantly irreversible. Our study provides an unexpected understanding of EZH2's contribution to solid tumors with important therapeutic implications. PMID:26637281

  6. Anaerobic homolactate fermentation with Saccharomyces cerevisiae results in depletion of ATP and impaired metabolic activity.

    PubMed

    Abbott, Derek A; van den Brink, Joost; Minneboo, Inge M K; Pronk, Jack T; van Maris, Antonius J A

    2009-05-01

    Conversion of glucose to lactic acid is stoichiometrically equivalent to ethanol formation with respect to ATP formation from substrate-level phosphorylation, redox equivalents and product yield. However, anaerobic growth cannot be sustained in homolactate fermenting Saccharomyces cerevisiae. ATP-dependent export of the lactate anion and/or proton, resulting in net zero ATP formation, is suspected as the underlying cause. In an effort to understand the mechanisms behind the decreased lactic acid production rate in anaerobic homolactate cultures of S. cerevisiae, aerobic carbon-limited chemostats were performed and subjected to anaerobic perturbations in the presence of high glucose concentrations. Intracellular measurements of adenosine phosphates confirmed ATP depletion and decreased energy charge immediately upon anaerobicity. Unexpectedly, readily available sources of carbon and energy, trehalose and glycogen, were not activated in homolactate strains as they were in reference strains that produce ethanol. Finally, the anticipated increase in maximal velocity (V(max)) of glycolytic enzymes was not observed in homolactate fermentation suggesting the absence of protein synthesis that may be attributed to decreased energy availability. Essentially, anaerobic homolactate fermentation results in energy depletion, which, in turn, hinders protein synthesis, central carbon metabolism and subsequent energy generation.

  7. Repurposing psychiatric medicines to target activated microglia in anxious mild cognitive impairment and early Parkinson’s disease

    PubMed Central

    Lauterbach, Edward C

    2016-01-01

    Anxiety is common in the Mild Cognitive Impairment (MCI) stage of Alzheimer’s disease (AD) and the pre-motor stages of Parkinson’s disease (PD). A concomitant and possible cause of this anxiety is microglial activation, also considered a key promoter of neurodegeneration in MCI and early PD via inflammatory mechanisms and the generation of degenerative proinflammatory cytokines. Psychiatric disorders, prevalent in AD and PD, are often treated with psychiatric drugs (psychotropics), raising the question of whether psychotropics might therapeutically affect microglial activation, MCI, and PD. The literature of common psychotropics used in treating psychiatric disorders was reviewed for preclinical and clinical findings regarding microglial activation. Findings potentially compatible with reduced microglial activation or reduced microglial inflammogen release were evident for: antipsychotics including neuroleptics (chlorpromazine, thioridazine, loxapine) and atypicals (aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone); mood stabilizers (carbamazepine, valproate, lithium); antidepressants including tricyclics (amitriptyline, clomipramine, imipramine, nortriptyline), SSRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline), venlafaxine, and bupropion; benzodiazepine anxiolytics (clonazepam, diazepam); cognitive enhancers (donepezil, galantamine, memantine); and other drugs (dextromethorphan, quinidine, amantadine). In contrast, pramipexole and methylphenidate might promote microglial activation. The most promising replicated findings of reduced microglial activation are for quetiapine, valproate, lithium, fluoxetine, donepezil, and memantine but further study is needed and translation of their microglial effects to human disease still requires investigation. In AD-relevant models, risperidone, valproate, lithium, fluoxetine, bupropion, donepezil, and memantine have therapeutic microglial effects in need of replication. Limited

  8. A Nationally Representative Study of the Association between Communication Impairment at 4-5 Years and Children's Life Activities at 7-9 Years

    ERIC Educational Resources Information Center

    McCormack, Jane; Harrison, Linda J.; McLeod, Sharynne; McAllister, Lindy

    2011-01-01

    Purpose: To examine the longitudinal association between communication impairment (primary or secondary diagnosis) and children's Activities and Participation (International Classification of Functioning, Disability and Health-Children and Youth [ICF-CY]; World Health Organization [WHO], 2007). Method: Participants were 4,329 children in the…

  9. Intra-Amygdala ZIP Injections Impair the Memory of Learned Active Avoidance Responses and Attenuate Conditioned Taste-Aversion Acquisition in Rats

    ERIC Educational Resources Information Center

    Gamiz, Fernando; Gallo, Milagros

    2011-01-01

    We have investigated the effect of protein kinase Mzeta (PKM[zeta]) inhibition in the basolateral amygdala (BLA) upon the retention of a nonspatial learned active avoidance response and conditioned taste-aversion (CTA) acquisition in rats. ZIP (10 nmol/[mu]L) injected into the BLA 24 h after training impaired retention of a learned…

  10. Spatial learning and memory impairments are associated with increased neuronal activity in 5XFAD mouse as measured by manganese-enhanced magnetic resonance imaging

    PubMed Central

    Gu, Li-Hua; Nie, Bin-Bin; Qi, Xin-Yang; Wang, Yan-Juan; Wu, Fang-Fang; Li, Xiao-Li; Bai, Feng; Chen, Xiao-Chun; Xu, Lin; Ren, Qing-Guo; Zhang, Zhi-Jun

    2016-01-01

    Dysfunction of neuronal activity is a major and early contributor to cognitive impairment in Alzheimer's disease (AD). To investigate neuronal activity alterations at early stage of AD, we encompassed behavioral testing and in vivo manganese-enhanced magnetic resonance imaging (MEMRI) in 5XFAD mice at early ages (1-, 2-, 3- and 5-month). The 5XFAD model over-express human amyloid precursor protein (APP) and presenilin 1 (PS1) harboring five familial AD mutations, which have a high APP expression correlating with a high burden and an accelerated accumulation of the 42 amino acid species of amyloid-β. In the Morris water maze, 5XFAD mice showed longer escape latency and poorer memory retention. In the MEMRI, 5XFAD mice showed increased signal intensity in the brain regions involved in spatial cognition, including the entorhinal cortex, the hippocampus, the retrosplenial cortex and the caudate putamen. Of note, the observed alterations in spatial cognition were associated with increased MEMRI signal intensity. These findings indicate that aberrant increased basal neuronal activity may contribute to the spatial cognitive function impairment at early stage of AD, and may further suggest the potential use of MEMRI to predict cognitive impairments. Early intervention that targets aberrant neuronal activity may be crucial to prevent cognitive impairment. PMID:27542275

  11. Inhibition of PHOSPHO1 activity results in impaired skeletal mineralization during limb development of the chick.

    PubMed

    Macrae, Vicky E; Davey, Megan G; McTeir, Lynn; Narisawa, Sonoko; Yadav, Manisha C; Millan, Jose Luis; Farquharson, Colin

    2010-04-01

    PHOSPHO1 is a bone-specific phosphatase implicated in the initiation of inorganic phosphate generation for matrix mineralization. The control of mineralization is attributed to the actions of tissue-nonspecific alkaline phosphatase (TNAP). However, matrix vesicles (MVs) containing apatite crystals are present in patients with hypophosphatasia as well as TNAP null (Akp2(-/-)) mice. It is therefore likely that other phosphatases work with TNAP to regulate matrix mineralization. Although PHOSPHO1 and TNAP expression is associated with MVs, it is not known if PHOSPHO1 and TNAP are coexpressed during the early stages of limb development. Furthermore, the functional in vivo role of PHOSPHO1 in matrix mineralization has yet to be established. Here, we studied the temporal expression and functional role of PHOSPHO1 within chick limb bud mesenchymal micromass cultures and also in wild-type and talpid(3) chick mutants. These mutants are characterized by defective hedgehog signalling and the absence of endochondral mineralization. The ability of in vitro micromass cultures to differentiate and mineralize their matrix was temporally associated with increased expression of PHOSPHO1 and TNAP. Comparable changes in expression were noted in developing embryonic legs (developmental stages 23-36HH). Micromass cultures treated with lansoprazole, a small-molecule inhibitor of PHOSPHO1 activity, or FGF2, an inhibitor of chondrocyte differentiation, resulted in reduced alizarin red staining (P<0.05). FGF2 treatment also caused a reduction in PHOSPHO1 (P<0.001) and TNAP (P<0.001) expression. Expression analysis by whole-mount RNA in situ hybridization correlated with qPCR micromass data and demonstrated the existence of a tightly regulated pattern of Phospho1 and Tnap expression which precedes mineralization. Treatment of developing embryos for 5 days with lansoprazole completely inhibited mineralization of all leg and wing long bones as assessed by alcian blue/alizarin red staining

  12. Auditory evoked potentials and impairments to psychomotor activity evoked by falling asleep.

    PubMed

    Dorokhov, V B; Verbitskaya, Yu S; Lavrova, T P

    2010-05-01

    Sounds provide the most suitable stimuli for studies of information processes occurring in the brain during falling asleep and at different stages of sleep. The widely used analysis of evoked potentials averaged for groups of subjects has a number of disadvantages associated with their individual variability. Thus, in the present study, measures of the individual components of auditory evoked potentials were determined and selectively summed for individual subjects, with subsequent analysis by group. The aim of the present work was to identify measures of auditory evoked potentials providing quantitative assessment of the dynamics of the brain's functional state during the appearance of errors in activity associated with decreases in the level of waking and falling asleep. A monotonous psychomotor test was performed in the lying position with the eyes closed; this consisted of two alternating parts: the first was counting auditory stimuli from 1 to 10 with simultaneous pressing of a button, and the second was counting stimuli from 1 to 5 silently without pressing the button, and so on. Computer-generated sound stimuli (duration 50 msec, envelope filling frequency 1000 Hz, intensity 60 dB) were presented binaurally with interstimulus intervals of 2.4-2.7 sec. A total of 41 subjects took part (both genders, mean age 25 years), of which only 23 fell asleep; data for 14 subjects with sufficient episodes of falling asleep were analyzed. Comparison of measures of auditory evoked potentials (the latencies and amplitudes of the N1, P2, N2, and P3 components) during correct and erroneous psychomotor test trials showed that decreases in the level of consciousness elicited significant increases in the amplitudes of the components of the vertex N1-P2-N2 complex in series without button pressing. The greatest changes in auditory evoked potentials in both series were seen in the N2 component, with latency 330-360 msec, which has a common origin with the EEG theta rhythm and is

  13. Questionnaire Translation and Questionnaire Validation: Are They the Same?

    ERIC Educational Resources Information Center

    Griffee, Dale T.

    The purpose of this paper is to give evidence for the thesis that if teachers using a questionnaire as a data collection instrument have the questionnaire items translated from one language into another, they cannot assume that the translated items are valid simply because they were translated. Even if the original questionnaire items were…

  14. Palmitic Acid Reduces Circulating Bone Formation Markers in Obese Animals and Impairs Osteoblast Activity via C16-Ceramide Accumulation.

    PubMed

    Alsahli, Ahmad; Kiefhaber, Kathryn; Gold, Tziporah; Muluke, Munira; Jiang, Hongfeng; Cremers, Serge; Schulze-Späte, Ulrike

    2016-05-01

    Obesity and impaired lipid metabolism increase circulating and local fatty acid (FA) levels. Our previous studies showed that a high high-saturated -fat diet induced greater bone loss in mice than a high high-unsaturated-fat diet due to increased osteoclast numbers and activity. The impact of elevated FA levels on osteoblasts is not yet clear. We induced obesity in 4 week old male mice using a palmitic acid (PA)- or oleic acid (OA)-enriched high fat high-fat diet (HFD) (20 % of calories from FA), and compared them to mice on a normal (R) caloric diet (10 % of calories from FA). We collected serum to determine FA and bone metabolism marker levels. Primary osteoblasts were isolated; cultured in PA, OA, or control (C) medium; and assessed for mineralization activity, gene expression, and ceramide levels. Obese animals in the PA and OA groups had significantly lower serum levels of bone formation markers P1NP and OC compared to normal weight animals (*p < 0.001), with the lowest marker levels in animals on an PA-enriched HFD (*p < 0.001). Accordingly, elevated levels of PA significantly reduced osteoblast mineralization activity in vitro (*p < 0.05). Elevated PA intake significantly increased C16 ceramide accumulation. This accumulation was preventable through inhibition of SPT2 (serine palmitoyl transferase 2) using myriocin. Elevated levels of PA reduce osteoblast function in vitro and bone formation markers in vivo. Our findings suggest that saturated PA can compromise bone health by affecting osteoblasts, and identify a potential mechanism through which obesity promotes bone loss.

  15. Long term potentiation is impaired in membrane glycoprotein CD200-deficient mice: a role for Toll-like receptor activation.

    PubMed

    Costello, Derek A; Lyons, Anthony; Denieffe, Stephanie; Browne, Tara C; Cox, F Fionnuala; Lynch, Marina A

    2011-10-07

    The membrane glycoprotein CD200 is expressed on several cell types, including neurons, whereas expression of its receptor, CD200R, is restricted principally to cells of the myeloid lineage, including microglia. The interaction between CD200 and CD200R maintains microglia and macrophages in a quiescent state; therefore, CD200-deficient mice express an inflammatory phenotype exhibiting increased macrophage or microglial activation in models of arthritis, encephalitis, and uveoretinitis. Here, we report that lipopolysaccharide (LPS) and Pam(3)CysSerLys(4) exerted more profound effects on release of the proinflammatory cytokines, interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNFα), in glia prepared from CD200(-/-) mice compared with wild type mice. This effect is explained by the loss of CD200 on astrocytes, which modulates microglial