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Sample records for activity impairment questionnaire

  1. Construct Validity of the Work Productivity and Activity Impairment Questionnaire across Informal Caregivers of Chronically Ill Older Patients

    PubMed Central

    Giovannetti, Erin R.; Wolff, Jennifer L.; Frick, Kevin D.; Boult, Chad

    2011-01-01

    Objectives To assess the validity of the Work Productivity and Activity Impairment questionnaire as adapted for caregiving (WPAI:CG) to measure productivity loss (hours missed from work, impairment while at work, and impairment in regular activities) due to unpaid caregiving for medically complex older adults. Methods The WPAI:CG was administered along with the Caregiver Strain Index (CSI) and Center for Epidemiologic Studies Depression Scale (CESD) to a caregiving population (N = 308) enrolled with their older, medically complex care-recipient in a cluster-randomized controlled study. Correlation coefficients were calculated between each productivity variable derived from the WPAI:CG and CSI/CESD scores. Nonparametric tests for trend across ordered groups were carried out to examine the relationship between each productivity variable and the intensity of the caregiving. Results Significant positive correlations were found between work productivity loss and caregiving-related strain (r = 0.45) and depression (r = 0.30). Measures of productivity loss were also highly associated with caregiving intensity (P < 0.05) and care-recipient medical care use (P < 0.05). The average employed caregiver reported 1.5 hours absence from work in the previous week and 18.5% reduced productivity while at work due to caregiving. Employed and nonemployed caregivers reported 27.2% reduced productivity in regular activities in the previous week. Conclusion The results indicate high convergent validity of the WPAI:CG questionnaire. This measure could facilitate research on the cost-effectiveness of caregiver-workplace interventions and provide employers and policy experts with a more accurate and comprehensive estimate of caregiving-related costs incurred by employers and society. PMID:19402853

  2. A Physical Activity Questionnaire: Reproducibility and Validity

    PubMed Central

    Barbosa, Nicolas; Sanchez, Carlos E.; Vera, Jose A.; Perez, Wilson; Thalabard, Jean-Christophe; Rieu, Michel

    2007-01-01

    This study evaluates the Quantification de L’Activite Physique en Altitude chez les Enfants (QAPACE) supervised self-administered questionnaire reproducibility and validity on the estimation of the mean daily energy expenditure (DEE) on Bogotá’s schoolchildren. The comprehension was assessed on 324 students, whereas the reproducibility was studied on a different random sample of 162 who were exposed twice to it. Reproducibility was assessed using both the Bland-Altman plot and the intra-class correlation coefficient (ICC). The validity was studied in a sample of 18 girls and 18 boys randomly selected, which completed the test - re-test study. The DEE derived from the questionnaire was compared with the laboratory measurement results of the peak oxygen uptake (Peak VO2) from ergo-spirometry and Leger Test. The reproducibility ICC was 0.96 (95% C.I. 0.95-0.97); by age categories 8-10, 0.94 (0.89-0. 97); 11-13, 0.98 (0.96- 0.99); 14-16, 0.95 (0.91-0.98). The ICC between mean TEE as estimated by the questionnaire and the direct and indirect Peak VO2 was 0.76 (0.66) (p<0.01); by age categories, 8-10, 11-13, and 14-16 were 0.89 (0.87), 0.76 (0.78) and 0.88 (0.80) respectively. The QAPACE questionnaire is reproducible and valid for estimating PA and showed a high correlation with the Peak VO2 uptake. Key pointsThe presence of a supervisor, the limited size of the group with the possibility of answering to their questions could explain the high reproducibility for this questionnaire.No study in the literature had directly addressed the issue of estimating a yearly average PA including school and vacation period.A two step procedure, in the population of schoolchildren of Bogotá, gives confidence in the use of the QAPACE questionnaire in a large epidemiological survey in related populations. PMID:24149485

  3. Internal consistency and factor structure of 12-item general health questionnaire in visually impaired students

    PubMed Central

    Bakhla, Ajay Kumar; Verma, Vijay; Hembram, Mahesh; Praharaj, Samir Kumar; Sinha, Vinod Kumar

    2013-01-01

    Background: As there are no instruments to measure psychological wellness or distress in visually impaired students, we studied internal consistency and factor structure of GHQ-12 in visually impaired children. Materials and Methods: Internal consistency analysis (Cronbach's alpha and item total correlation) and exploratory factor analysis (principal component analysis) were carried out to identify factor structure of 12-item general health questionnaire (GHQ-12). Results: All items of GHQ-12 were significantly associated with each other and the Cronbach's alpha coefficient for the scale was 0.7. On analysis of principal component, three-factor solution was found that accounted for 47.92% of the total variance. The factors included, ‘general well-being’, ‘depression’ and ‘cognitive’, with Cronbach's alpha coefficients being 0.70, 0.59, and 0.34, respectively. Conclusion: Our study findings suggest GHQ-12 is a reliable with adequate internal consistency scale and multidimensional factor structure in visually impaired students. PMID:25013310

  4. 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. PMID:25839732

  5. The Learning Activities Questionnaire: A Tool to Enhance Teaching

    ERIC Educational Resources Information Center

    Ager, Richard

    2012-01-01

    This article describes the Learning Activities Questionnaire (LAQ) and how it can be employed to evaluate learning tasks not typically examined in course evaluation instruments such as readings and assignments. Drawing from behavioral theory in its focus on specific activities, this instrument is simple to interpret and provides clear direction…

  6. Space Activities for the Visually Impaired

    NASA Astrophysics Data System (ADS)

    Ries, J. G.; Baguio, M.

    2005-12-01

    To a visually impaired person celestial objects or concepts of space exploration are likely to be more abstract than to other people, but they encounter news about the universe through their daily life. A partnership between Texas Space Grant Consortium, The University of Texas at Austin, and the Texas School for the Blind and Visually Impaired provided the opportunity to assist visually impaired students increase their understanding of astronomy and space science. The activities helped visually impaired students activity engage in inquiry-based, hands-on astronomy activities. The experiences provided during the educator workshops, adapted instructional classroom activities, and tactile learning aids will be shared in the hopes that others may be able to incorporate these lessons into their regular teaching activities.

  7. 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. PMID:27061198

  8. Validity and reliability of activities coaching context questionnaire

    PubMed Central

    Koohpayehzadeh, Jalil; Haji Ahmadi, Maryam; Dehnad, Afsaneh; Soltani Arabshahi, Seyed kamran; Bigdeli, Shoaleh; Yadollahi, Sohrab

    2014-01-01

    Background: Learning in a clinical environment is an inseparable part of a training program in medical education. To evaluate the quality of training in a clinical environment, a comprehensive questionnaire which is adjusted for local purposes is essential. This study was conducted to determine the validity and reliability of Activities Coaching Context (ACC)-questionnaire from the perspective of residents and students in a clinical learning environment. Methods: This was a cross-sectional study conducted with 65 residents and students of Semnan University of Medical Sciences. The Content Validity of the questionnaire was confirmed by the judgment of a panel of ten experts in medical education. The construct validity of the questionnaire was determined by factor analysis. Data were collected and analyzed by SPSS16. Results: The ratio and index of content validity calculated by experts’ view were quite acceptable (0.31 and 0.7, respectively). Construct validity was examined by factor analysis which confirmed seven first order factors. Cronbach’s Alfa coefficient revealed a high degree of internal consistency (0.932). The reliability of the questionnaire was measured by test - retest (0.9). Conclusions: The ACC questionnaire appeared to be a valid, reliable and also appropriate tool to evaluate the educational quality of a clinical learning environment. PMID:25405107

  9. 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 results…

  10. [Conception and Content Validation of a Questionnaire Relating to the Potential Need for Information of Visually Impaired Persons with Regard to Services and Contact Persons].

    PubMed

    Hahn, U; Hechler, T; Witt, U; Krummenauer, F

    2015-12-01

    A questionnaire was drafted to identify the needs of visually impaired persons and to optimize their access to non-medical support and services. Subjects had to rate a list of 15 everyday activities that are typically affected by visual impairment (for example, being able to orient themselves in the home environment), by indicating the degree to which they perceive each activity to be affected, using a four-stage scale. They had to evaluate these aspects by means of a relevance assessment. The needs profile derived from this is then correlated with individualized information for assistance and support. The questionnaire shall be made available for use by subjects through advisers in some ophthalmic practices and via the internet. The validity of the content of the proposed tool was evaluated on the basis of a survey of 59 experts in the fields of medical, optical and psychological care and of persons involved in training initiatives. The experts were asked to rate the activities by relevance and clarity of the wording and to propose methods to further develop and optimize the content. The validity of the content was quantified according to a process adopted in the literature, based on the parameters Interrater Agreement (IRA) and Content Validity Index (CVI). The results of all responses (n = 19) and the sub-group analysis suggest that the questionnaire adequately reflects the potential needs profile of visually impaired persons. Overall, there was at least 80% agreement among the 19 experts for 93% of the proposed parameterisation of the activities relating to the relevance and clarity of the wording. Individual proposals for optimization of the design of the questionnaire were adopted. PMID:26678903

  11. 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…

  12. 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…

  13. 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...

  14. 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...

  15. 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...

  16. U.S.-MEXICO BORDER PROGRAM ARIZONA BORDER STUDY--TIME AND ACTIVITY DIARY QUESTIONNAIRE DATA

    EPA Science Inventory

    The Time and Activity Diary Questionnaire data set provides information about the daily activities of the respondents during the sampling week. The information is from 260 Time and Activity Diary Questionnaires for 91 households. Supplemental pages were provided. The informati...

  17. 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

  18. 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

  19. Validation of a self-report questionnaire version of the Child Activity Limitations Interview (CALI): The CALI-21

    PubMed Central

    Palermo, Tonya M.; Lewandowski, Amy S.; Long, Anna C.; Burant, Christopher J.

    2011-01-01

    The Child Activity Limitations Interview (CALI) is a measure designed to assess functional impairment due to chronic pain in school-age children. In this study, we present a self-report questionnaire version of the CALI (the CALI-21) that extends the original interview measure. The purpose of the current study was to provide internal consistency, cross-informant reliability and construct validity of the CALI-21 on a clinical sample of children and adolescents with chronic pain conditions. One hundred fifty-five children and adolescents (65 males, 90 females; ages 8–18 years, M = 14.31, SD =2.45) with chronic pain completed questionnaires as part of their clinic intake procedures at their consultation visit in a pediatric pain management clinic. An exploratory factor analysis was conducted to measure latent constructs within the broader domain of functional impairment. Results of the exploratory factor analysis yielded two factors representing limitation in Active and Routine activities on both parent and child report. Parent and child total CALI scores correlated with measures of pain intensity, however, different patterns of correlations emerged between age, pain intensity, depressive symptoms, and the Active and Routine factors. The CALI-21 showed good internal consistency, high cross-informant reliability, and demonstrated construct validity. The CALI-21 provides increased flexibility via the questionnaire format in the assessment of pain-related activity limitations in children. Factor analysis extends information about specific types of activity limitations experienced by children. PMID:18692316

  20. 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...

  1. 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...

  2. 75 FR 61248 - Proposed Information Collection (Pension Claim Questionnaire for Farm Income) Activity: Comment...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-04

    ... 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...

  3. 78 FR 24469 - Proposed Information Collection (Marital Status Questionnaire) Activity; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-25

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

  4. 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...

  5. 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,...

  6. The Ages and Stages Questionnaire and Neurodevelopmental Impairment in Two-Year-Old Preterm-Born Children

    PubMed Central

    Kerstjens, Jorien M.; Nijhuis, Ard; Hulzebos, Christian V.; van Imhoff, Deirdre E.; van Wassenaer-Leemhuis, Aleid G.; van Haastert, Ingrid C.; Lopriore, Enrico; Katgert, Titia; Swarte, Renate M.; van Lingen, Richard A.; Mulder, Twan L.; Laarman, Céleste R.; Steiner, Katerina; Dijk, Peter H.

    2015-01-01

    Objective To test the ability of the Ages and Stages Questionnaire, Third Edition (ASQ3) to help identify or exclude neurodevelopmental impairment (NDI) in very preterm-born children at the corrected age of two. Methods We studied the test results of 224 children, born at <32 postmenstrual weeks, who had scores on ASQ3 and Bayley Scales of Infant and Toddler Development, Third Edition (BSIDIII) and neurological examination at 22–26 months’ corrected age. We defined NDI as a score of <70 on the cognitive—or motor composite scale of BSIDIII, or impairment on neurological examination or audiovisual screening. We compared NDI with abnormal ASQ3 scores, i.e., < -2SDs on any domain, and with ASQ3 total scores. To correct for possible overestimation of BSIDIII, we also analyzed the adjusted BSIDIII thresholds for NDI, i.e., scores <80 and <85. Results We found 61 (27%) children with abnormal ASQ3 scores, and 10 (4.5%) children who had NDI with original BSIDIII thresholds (<70). Twelve children had NDI at BSIDIII thresholds at <80, and 15 had <85. None of the 163 (73%) children who passed ASQ3 had NDI. The sensitivity of ASQ3 to detect NDI was excellent (100%), its specificity was acceptable (76%), and its negative predictive value (NPV) was 100%. Sensitivity and NPV remained high with the adjusted BSIDIII thresholds. Conclusion The Ages and Stages Questionnaire is a simple, valid and cost-effective screening tool to help identify and exclude NDI in very preterm-born children at the corrected age of two years. PMID:26193474

  7. 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. PMID:20230157

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

    PubMed Central

    Demirturk, Funda; Kaya, Mustafa

    2015-01-01

    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/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. PMID:26568173

  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. [Measurement of activities of daily living in patients with dementia living at home: development of a questionnaire].

    PubMed

    Teunisse, S; Derix, M M

    1991-04-01

    In clinical practice and for scientific research a method is needed for the assessment of changes in functioning in daily life of dementia patients living at home. As existing methods have their limitations, a questionnaire was developed (the Interview for Deterioration in Daily life in Dementia: IDDD), to be answered by caregivers. The questionnaire concerns self-care and complex activities, that are usually performed by men as well as women. Attention is paid to the difference between lack of initiative and impaired performance itself. Caregivers are interviewed in a structured interview. A study among 30 caregivers of dementia patients living at home, showed the relevance and usefulness of the questions. The questionnaire shows high internal consistency, which may be the result of our structured interview technique. PMID:2042235

  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...

  12. 78 FR 36307 - Proposed Information Collection (Wrist Conditions Disability Benefits Questionnaire) Activity...

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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...

    Federal Register 2010, 2011, 2012, 2013, 2014

    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. NHEXAS PHASE I REGION 5 STUDY--TIME-ACTIVITY DIARY QUESTIONNAIRE DATA (MONITORING PERIOD 1)

    EPA Science Inventory

    This data set includes responses for 249 time-activity diary questionnaires. The Time Diary and Activity Questionnaire was used for collecting data on detailed (daily) time and location information and activity patterns (for relatively frequent activities when recalling events ov...

  15. Assessment of Physical Activity by Applying IPAQ Questionnaire

    ERIC Educational Resources Information Center

    Biernat, Elzbieta; Stupnicki, Romuald; Lebiedzinski, Bartlomiej; Janczewska, Lidia

    2008-01-01

    Study aim: To assess the suitability of the short 7-day IPAQ (self-completed) adapted to Polish population. Material and methods: Two surveys were conducted in 2005 on 296 random subjects (aged 20-60 years) from Warsaw and the Mazowiecki region. From these, 54 men and 79 women were requested to fill questionnaires, and 70 men and 93 women, were…

  16. The Persian Version of Eating Disorder Examination Questionnaire and Clinical Impairment Assessment: Norms and Psychometric Properties for Undergraduate Women

    PubMed Central

    Mahmoodi, Maryam; Ghaderi, Ata; babai, Zahra; Saleh, Zeinab; Alasti, Haniye; Naghashian, Farnush; Mohammadpour, Zinat

    2016-01-01

    Objective: The aim of this study was to provide norms of Eating Disorder Examination Questionnaire (EDE-Q) and Clinical Impairment Assessment (CIA) for undergraduate women in Iran. Materials and Methods: Undergraduate women (N = 516) completed the EDE-Q, CIA, and the Binge Eating Scale (BES). Results: Average score, standard deviation, and percentile rank of EDE-Q and its subscale as well as CIA were reported. In addition, the frequency of key eating disordered behaviors was presented. Both EDE-Q and CIA demonstrated strong internal consistency. In addition to the significant correlation between the EDE-Q and CIA (0.59), they both showed a moderate to strong correlation with the BES (r = 0.33 to 0.61). The EDE-Q and CIA successfully differentiated underweight, normal weight, and overweight women. Moreover, women who reported higher level of restraint or regular binge eating episodes obtained higher score on the CIA than women who did not have such behaviors across the same period. Conclusion: This study provided preliminary support for the reliability and validity of the Persian version of the EDE-Q and CIA. The obtained norms for the EDE-Q and the CIA are helpful in clinical practice and intercultural studies of eating disorders. PMID:27437002

  17. Correlation between pedometer and the Global Physical Activity Questionnaire on physical activity measurement in office workers

    PubMed Central

    2014-01-01

    Background This study aimed to examine the correlation of physical activity levels assessed by pedometer and those by the Global Physical Activity Questionnaire (GPAQ) in a population of office workers. Methods A cross-sectional study was conducted on 320 office workers. A self-administered questionnaire was distributed to each office worker by hand. Physical activity level was objectively assessed by a pedometer for 7 consecutive days and subjectively assessed by the GPAQ. Based on the pedometer and GPAQ outcomes, participants were classified into 3 groups: inactive, moderately active, and highly active. Results No correlation in the physical activity level assessed by the pedometer and GPAQ was found (rs = .08, P = 0.15). When considering the pedometer as the criterion for comparison, 65.3% of participants had underestimated their physical activity level using the GPAQ, whereas 9.3% of participants overestimated their physical activity level. Conclusions Physical activity level in office workers assessed by a subjective measure was greatly different from assessed by an objective tool. Consequently, research on physical activity level, especially in those with sedentary lifestyle, should consider using an objective measure to ensure that it closely reflects a person’s physical activity level. PMID:24886593

  18. 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

  19. 75 FR 77957 - Agency Information Collection (Pension Claim Questionnaire for Farm Income) Activity Under OMB...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-14

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    Federal Register 2010, 2011, 2012, 2013, 2014

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  8. Assessment of impairment in activities of daily living in mild cognitive impairment using an individualized scale.

    PubMed

    Chaves, Giseli de Fátima Dos Santos; Oliveira, Alexandra Martini; Chaves, Juliana Aparecida Dos Santos; Forlenza, Orestes Vicente; Aprahamian, Ivan; Nunes, Paula Villela

    2016-07-01

    Mild impairment in activities of daily living (ADL) can occur in Mild Cognitive Impairment (MCI), but the nature and extent of these difficulties need to be further explored. The Canadian occupational performance measure (COPM) is one of the few individualized scales designed to identify self-perceived difficulties in ADL. The present study investigated impairments in ADL using the COPM in elderly with MCI. A total of 58 MCI patients were submitted to the COPM for studies of its validity and reliability. The COPM proved a valid and consistent instrument for evaluating ADL in elderly MCI patients. A total of 74.6% of the MCI patients reported difficulties in ADL. Of these problems, 41.2% involved self-care, 31.4% productivity and 27.4% leisure. This data further corroborates recent reports of possible functional impairment in complex ADL in MCI. PMID:27487375

  9. 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

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

    PubMed

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

    2015-12-01

    [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

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

    PubMed

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

    2015-10-01

    [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

  12. 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…

  13. 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

  14. 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…

  15. 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…

  16. 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...

  17. NHEXAS PHASE I REGION 5 STUDY--TIME-ACTIVITY DIARY QUESTIONNAIRE DATA (ALL MONITORING PERIODS)

    EPA Science Inventory

    This data set includes responses for 249 participants with a total of 428 time-activity diaries. Some participants were studied for more than one monitoring period. The Time Diary and Activity Questionnaire was used for collecting data on detailed (daily) time and location inform...

  18. 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…

  19. 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

  20. 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)

  1. 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…

  2. 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…

  3. 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…

  4. Pedometer-Determined Physical Activity and Its Comparison with the International Physical Activity Questionnaire in a Sample of Belgian Adults

    ERIC Educational Resources Information Center

    De Cocker, Katrien; Cardon, Greet; De Bourdeaudhuij, Ilse

    2007-01-01

    Pedometer-determined physical activity (PA) levels in Belgian adults were provided and compared to PA scores reported in the International Physical Activity Questionnaire (IPAQ). The representative sample (N = 1,239) of the Belgian population took on average 9,655 (4,526) steps/day. According to pedometer indices 58.4% were insufficiently active.…

  5. 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,…

  6. Validity and Reliability of the International Physical Activity Questionnaire in College Students

    ERIC Educational Resources Information Center

    Dinger, Mary K.; Behrens, Timothy K.; Han, Jennifer L.

    2006-01-01

    The purpose of this study was to examine the validity and reliability of the self-administered International Physical Activity Questionnaire (IPAQ) short form in college students. One hundred twenty-three undergraduate students (20.8 [plus or minus] 1.5 years of age, 76% Caucasian, 74% female) wore an accelerometer and pedometer at their waists…

  7. 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

  8. Validity of two brief physical activity questionnaires with accelerometers among African-American women

    PubMed Central

    Joseph, Rodney P.; Keller, Colleen; Adams, Marc A.; Ainsworth, Barbara E.

    2015-01-01

    Aim To evaluate the validity of the Stanford Brief Activity Survey (SBAS) and Exercise Vital Sign (EVS) questionnaire against accelerometer-determined time in moderate-to-vigorous physical activity (MVPA) among African-American (AA) women. Background Limited research has evaluated the validity of brief physical activity (PA) questionnaires among AA women. Since the validity of PA questionnaires may differ among members of varying racial/ethnic groups, research is needed to explore the validity of self-report PA measures among AA women. Methods A total of 30 AA women [M age = 35.5 ± 5.3; M body mass index (BMI) = 31.1 ± 7.8] wore ActiGraph GT3X + accelerometers (ActiGraph, LLC, Pensacola FL, USA) for seven days and completed both the SBAS and EVS at two different assessment periods (T1 and T2). Criterion validity was calculated using Spearman's rank order correlations between each questionnaire score and accelerometer-measured MVPA. Sensitivity, specificity, and positive and negative predictive values were calculated using accelerometer-measured MVPA as the criterion to determine the ability of each questionnaire to predict whether or not a participant was meeting the 2008 US PA Guidelines Findings Spearman correlation coefficients between questionnaire scores and minutes of accelerometer-measured MVPA were low (EVS, r = 0.27 at T1 and r = 0.26 at T2; SBAS, r = 0.10 at T1 and r = 0.28 at T2) and not statistically significant (P's > 0.05). The EVS had sensitivity, specificity, and negative and positive predictive values of 27, 89, 59, and 68% at T1 and 33, 74, 38, and 70% at T2, respectively. The SBAS had sensitivity, specificity, and negative and positive predictive values were 18, 79, 33, and 62% at T1 and 67, 58, 43, and 79% at T2. While both questionnaires may be useful in identifying AA women who do not meet the 2008 PA Guidelines, using the questionnaires to identify AA women meeting the PA Guidelines should be done with caution. PMID:26178779

  9. 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…

  10. Assessing the Validity of a Physical Activity Questionnaire Developed for Parents of Preschool Children in Mexico

    PubMed Central

    Bacardi-Gascón, Montserrat; Reveles-Rojas, Claudia; Woodward-Lopez, Gail; Crawford, Patricia

    2012-01-01

    To assess the validity of a questionnaire developed for parents of preschool children to know their physical activity (PA) status, we compared the questionnaire results with the measures of accelerometer for children's activities. Thirty-five preschoolers who wore the accelerometer for at least 10 hours daily on 3 weekdays and one weekend day were included in the analyses. Time spent in activities of varied intensity was calculated by applying 15-second ActiGraph count cutoffs (ACC). Parents’ perceptions of their children's PA were associated with the percentage of vigorous and moderate physical activity recorded with ACC at r=0.62 (p=0.0001). An association was shown between the percentage of a child's time spent in vigorous physical activity, as reported by parents, with that measured by ACC at r=0.53 (p=0.001). Results of this study suggest that the designed questionnaire might be a useful tool for assessing children's activity while, additionally, it warrants further investigation on larger samples of children. PMID:23304910

  11. 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. PMID:26520214

  12. Exploring the Relation Between Impairment Rating by AMA Guide and Activity and Participation Based on ICF in the Patients with Hand Injuries.

    PubMed

    Farzad, Maryam; Asgari, Ali; Layeghi, Fereydoun; Yazdani, Farzaneh; Hosseini, Seyyed Ali; Rassafiani, Mehdi; Kus, Sandra

    2015-12-01

    The aim of this paper is to analyze the relation between components of disability with distinguished score of impairment, activity and participation questionnaire based on clinical data of persons with hand injuries. Impairment was evaluated by use of AMA guide 6th edition and disability by DASH questionnaire on Convenience sample of patients (N = 117), with chronic hand injuries. Linking and allocating items of the DASH were done based on the ICF Core Set for Hand Conditions and the opinions of a group of experts from different related fields. Data was analyses by using Kappa index, Chi square test and a set of Pearson, Part and Partial correlations coefficient. Most of the DASH items were allocated to the activity; one to four of the items could not be classified and 0 to 22 were classified as having overlap. Participation and activity scores correlated positively with each other (r > 0.80). Impairment had high correlation with activity and participation scores (>73). With controlling the effect of each or both construct, this relation between them with impairment diminished but still significant between activity and impairment. There is a huge overlap in definition of activity and participation. The most effecting item in relation of disability and impairment is activity restriction. Participation had no relation with impairment. PMID:26578828

  13. Comparing participation in out of school activities between children with visual impairments, children with hearing impairments and typical peers.

    PubMed

    Engel-Yeger, Batya; Hamed-Daher, Shaima

    2013-10-01

    Hearing or visual impairments may negatively affect child's development and participation. Yet the literature about participation of children with hearing or visual impairments is insufficient. The present study aimed to compare participation patterns of children with visual impairments to those of children with hearing impairments and to typical peers and to examine the correlations between participation and socio-demographic parameters in each group. Participants were 70 children between the ages of 6-11: 25 with hearing impairments, 20 with visual impairments and 25 typical peers. All children filled the Children's Assessment of Participation and Enjoyment (CAPE). This self-report refers to participation in daily out of school activities. Children with hearing or visual impairments showed significant limited participation compared to typical peers, expressed in lower number of activities, lower participation intensity; more activities performed at home and with someone else. The limited participation was more emphasized among children with visual impairments. Socio-demographic variables (age, mother's education and socio-economic level) correlated with participation dimensions in both study groups. In conclusion, children with hearing or visual impairments may have restricted participation in out of school activities. Socio-demographic parameters may play a role in encouraging child's participation. Participation among these populations should be further studied in order to assist service providers to create intervention programs together with the child, for enhancing his/her inclusion in the community. PMID:23880031

  14. 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 ±…

  15. Postnatal TLR2 activation impairs learning and memory in adulthood.

    PubMed

    Madar, Ravit; Rotter, Aviva; Waldman Ben-Asher, Hiba; Mughal, Mohamed R; Arumugam, Thiruma V; Wood, W H; Becker, K G; Mattson, Mark P; Okun, Eitan

    2015-08-01

    Neuroinflammation in the central nervous system is detrimental for learning and memory, as evident form epidemiological studies linking developmental defects and maternal exposure to harmful pathogens. Postnatal infections can also induce neuroinflammatory responses with long-term consequences. These inflammatory responses can lead to motor deficits and/or behavioral disabilities. Toll like receptors (TLRs) are a family of innate immune receptors best known as sensors of microbial-associated molecular patterns, and are the first responders to infection. TLR2 forms heterodimers with either TLR1 or TLR6, is activated in response to gram-positive bacterial infections, and is expressed in the brain during embryonic development. We hypothesized that early postnatal TLR2-mediated neuroinflammation would adversely affect cognitive behavior in the adult. Our data indicate that postnatal TLR2 activation affects learning and memory in adult mice in a heterodimer-dependent manner. TLR2/6 activation improved motor function and fear learning, while TLR2/1 activation impaired spatial learning and enhanced fear learning. Moreover, developmental TLR2 deficiency significantly impairs spatial learning and enhances fear learning, stressing the involvement of the TLR2 pathway in learning and memory. Analysis of the transcriptional effects of TLR2 activation reveals both common and unique transcriptional programs following heterodimer-specific TLR2 activation. These results imply that adult cognitive behavior could be influenced in part, by activation or alterations in the TLR2 pathway at birth. PMID:26021559

  16. Postnatal TLR2 activation impairs learning and memory in adulthood

    PubMed Central

    Madar, Ravit; Rotter, Aviva; Ben-Asher, Hiba Waldman; Mughal, Mohamed R.; Arumugam, Thiruma V.; Wood, WH; Becker, KG; Mattson, Mark P.; Okun, Eitan

    2015-01-01

    Neuroinflammation in the central nervous system is detrimental for learning and memory, as evident form epidemiological studies linking developmental defects and maternal exposure to harmful pathogens. Postnatal infections can also induce neuroinflammatory responses with long-term consequences. These inflammatory responses can lead to motor deficits and/or behavioral disabilities. Toll like receptors (TLRs) are a family of innate immune receptors best known as sensors of microbial-associated molecular patterns, and are the first responders to infection. TLR2 forms heterodimers with either TLR1 or TLR6, is activated in response to gram-positive bacterial infections, and is expressed in the brain during embryonic development. We hypothesized that early postnatal TLR2-mediated neuroinflammation would adversely affect cognitive behavior in the adult. Our data indicate that postnatal TLR2 activation affects learning and memory in adult mice in a heterodimer-dependent manner. TLR2/6 activation improved motor function and fear learning, while TLR2/1 activation impaired spatial learning and enhanced fear learning. Moreover, developmental TLR2 deficiency significantly impairs spatial learning and enhances fear learning, stressing the involvement of the TLR2 pathway in learning and memory. Analysis of the transcriptional effects of TLR2 activation reveals both common and unique transcriptional programs following heterodimer-specific TLR2 activation. These results imply that adult cognitive behavior could be influenced in part, by activation or alterations in the TLR2 pathway at birth. PMID:26021559

  17. 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

  18. 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

  19. 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...

  20. The Bahasa Melayu version of the Global Physical Activity Questionnaire: reliability and validity study in Malaysia.

    PubMed

    Soo, K L; Wan Abdul Manan, W M; Wan Suriati, W N

    2015-03-01

    This study aimed to assess the reliability and concurrent validity of the Bahasa Melayu version of the Global Physical Activity Questionnaire (GPAQ-M) by comparing it with the short form of the International Physical Activity Questionnaire (IPAQ-S) and objectively measuring physical activity using a Yamax DigiWalker (Yamax, Tokyo, Japan) pedometer. A total of 100 adults aged between 20 and 58 years from Kelantan in Malaysia voluntarily participated in this study. The Wilcoxon signed-rank analysis showed no significant differences in 2-week test-retest scores for total metabolic equivalent∙minutes∙per week and 4 domains of the GPAQ-M. There was a low but significant relationship between time spent on total physical activity measured by the GPAQ-M and average steps per day recorded using the pedometer (r s = .265, P = .013). Significant correlations were also found between GPAQ-M and the IPAQ-S for varying levels of intensity during physical activities (r s = .309-.466, P < .01). PMID:22234832

  1. A Validation Study of the Web-Based Physical Activity Questionnaire Active-Q Against the GENEA Accelerometer

    PubMed Central

    Bergman, Patrick; Trolle Lagerros, Ylva; Sjölander, Arvid; Bälter, Katarina

    2015-01-01

    Background Valid physical activity assessment in epidemiological studies is essential to study associations with various health outcomes. Objective To validate the Web-based physical activity questionnaire Active-Q by comparing results of time spent at different physical activity levels with results from the GENEA accelerometer and to assess the reproducibility of Active-Q by comparing two admissions of the questionnaire. Methods A total of 148 men (aged 33 to 86 years) responded to Active-Q twice and wore the accelerometer during seven consecutive days on two occasions. Time spent on six different physical activity levels including sedentary, light (LPA), moderate (MPA), and vigorous (VPA) as well as additional combined categories of sedentary-to-light and moderate-to-vigorous (MVPA) physical activity was assessed. Validity of Active-Q was determined using Spearman correlation coefficients with 95% confidence intervals (CI) and the Bland-Altman method. Reproducibility was assessed using intraclass correlation coefficients (ICCs) comparing two admissions of the questionnaire. Results The validity correlation coefficients were statistically significant for time spent at all activity levels; sedentary (r=0.19, 95% CI: 0.04-0.34), LPA (r=0.15, 95% CI: 0.00-0.31), sedentary-to-light (r=0.35, 95% CI: 0.19-0.51), MPA (r=0.27, 95% CI: 0.12-0.42), VPA (r=0.54, 95% CI: 0.42-0.67), and MVPA (r=0.35, 95% CI: 0.21-0.48). The Bland-Altman plots showed a negative mean difference for time in LPA and positive mean differences for time spent in MPA, VPA and MVPA. The ICCs of test-retest reliability ranged between r=0.51-0.80 for the different activity levels in Active-Q. Conclusions More moderate and vigorous activities and less light activities were reported in Active-Q compared to accelerometer measurements. Active-Q shows comparable validity and reproducibility to other physical activity questionnaires used today. PMID:26183896

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

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-23

    ... following collection of information, VBA invites comments on: (1) Whether the proposed collection of... Questionnaire, VA Form 21- 0960E-1. f. Scar/Disfigurement Disability Benefits Questionnaire, VA Form 21-0960F-1... Benefits Questionnaire, VA Form 21-0960M- 1. i. Ankle Conditions Disability Benefits Questionnaire, VA...

  3. Impairment of NFkappaB activity by unsaturated fatty acids.

    PubMed

    Schumann, Julia; Fuhrmann, Herbert

    2010-08-01

    Using a luciferase reporter gene assay, we identified polyunsaturated fatty acids (PUFA) to impair NF kappaB signaling. Furthermore, we could demonstrate the PUFA ability to derogate NF kappaB activity to be independent from the family the fatty acid belongs to. Instead, we found a relation between the number of bis-allyl-methylene positions of the PUFA added and the NF kappaB activity of stimulated, long-term supplemented cells. The data presented provide new insights into the biological mechanisms PUFA exert their anti-inflammatory effects. Since suppression of NF kappaB activity could be of benefit in a number of inflammatory diseases as well as cancer, our findings are of clinical implication. According to our data dietary supplementation with PUFA-containing oils is likely to provide an at least palliative therapy for disorders linked to inappropriate NF kappaB signaling. PMID:20580946

  4. Memory activation enhances EEG abnormality in mild cognitive impairment.

    PubMed

    van der Hiele, K; Vein, A A; Kramer, C G S; Reijntjes, R H A M; van Buchem, M A; Westendorp, R G J; Bollen, E L E M; van Dijk, J G; Middelkoop, H A M

    2007-01-01

    This exploratory study investigated EEG power changes during memory activation in patients with amnestic mild cognitive impairment (MCI). Twelve MCI patients and 16 age-matched controls underwent EEG registration during two conventional EEG conditions ('eyes closed' and 'eyes open') and three memory conditions ('word memory', 'picture memory' and 'animal fluency'). For all conditions, EEG power in the theta (4-8 Hz), lower alpha (8-10.5 Hz) and upper alpha (10.5-13 Hz) bands were expressed as percentile changes compared to 'eyes closed'. MCI patients showed significantly less decrease in the lower alpha band than controls (p=0.04) during picture memory activation. The word memory task showed a trend towards a similar effect (p=0.09). This study suggests that memory activation reveals EEG differences between MCI patients and controls while conventional EEG conditions do not. PMID:16406153

  5. Lipid-induced NOX2 activation inhibits autophagic flux by impairing lysosomal enzyme activity[S

    PubMed Central

    Jaishy, Bharat; Zhang, Quanjiang; Chung, Heaseung S.; Riehle, Christian; Soto, Jamie; Jenkins, Stephen; Abel, Patrick; Cowart, L. Ashley; Van Eyk, Jennifer E.; Abel, E. Dale

    2015-01-01

    Autophagy is a catabolic process involved in maintaining energy and organelle homeostasis. The relationship between obesity and the regulation of autophagy is cell type specific. Despite adverse consequences of obesity on cardiac structure and function, the contribution of altered cardiac autophagy in response to fatty acid overload is incompletely understood. Here, we report the suppression of autophagosome clearance and the activation of NADPH oxidase (Nox)2 in both high fat-fed murine hearts and palmitate-treated H9C2 cardiomyocytes (CMs). Defective autophagosome clearance is secondary to superoxide-dependent impairment of lysosomal acidification and enzyme activity in palmitate-treated CMs. Inhibition of Nox2 prevented superoxide overproduction, restored lysosome acidification and enzyme activity, and reduced autophagosome accumulation in palmitate-treated CMs. Palmitate-induced Nox2 activation was dependent on the activation of classical protein kinase Cs (PKCs), specifically PKCβII. These findings reveal a novel mechanism linking lipotoxicity with a PKCβ-Nox2-mediated impairment in pH-dependent lysosomal enzyme activity that diminishes autophagic turnover in CMs. PMID:25529920

  6. Impaired antipneumococcal activity of bronchoalveolar lining material of neonatal rats.

    PubMed Central

    Coonrod, J D; Jarrells, M C

    1989-01-01

    Pulmonary clearance of inhaled pneumococci is markedly impaired in neonatal rats compared with that in adult rats. To determine whether this impairment is due to a deficiency of extracellular bactericidal factors, the antipneumococcal activity of free fatty acids (FFA) in lung surfactant and the levels of lysozyme and transferrin in lavage fluids were quantified. Surfactant from adult rats averaged 68 U of antipneumococcal activity per g (dry weight) of lung, compared with less than 0.25 U for rats less than 1 week old (P less than 0.001). The kinds of FFA in surfactant of neonatal and adult rats were essentially identical, and the antipneumococcal activity of highly purified FFA from surfactant of neonatal and adult rats was also the same. However, the quantity of FFA in surfactant varied significantly with age, and rats less than 3 weeks old had much lower levels of surfactant FFA than did adults (P less than 0.001). In addition, lavage fluids from neonatal rats inhibited the antipneumococcal activity of surfactant FFA more than lavage fluids from adults did (P less than 0.02). This inhibitory activity did not appear to be due to protein binding. Lavage fluids from neonates showed an age-related deficiency of lysozyme (P less than 0.001), but lysozyme appeared to play no role in pneumococcal killing by the surfactant fraction of lavage fluids in vitro. Transferrin levels in lavage fluids were similar for neonates and adults. It was concluded that lung surfactant from neonatal rats was deficient in antipneumococcal activity, due mostly to low levels of FFA and to a lesser degree to increased levels of inhibitor(s) in lavage fluids. PMID:2912894

  7. An audit questionnaire that examines specifically the management of technical activities clauses in ISO 15189.

    PubMed

    Hartley, T F

    2010-01-01

    The aim of this study was to design an audit questionnaire that focuses on the management of the technical activities in a Diagnostic Pathology Laboratory. The ISO 15189 Standard is written in such a way that it continually moves back and forth from topics where the auditor needs to question bench level staff, to topics where the auditor needs to question Technical Management Staff. This makes for a disjointed audit process - both Bench Staff and Technical Managers are repeatedly interrupted. The solution was to do a clause by clause analysis of the Standard and assign the major responsibility for the compliance to each clause to either Technical Managers or Bench Staff. The Clauses were then grouped under four topic headings regardless of whether they were a Section 4 or Section 5 Clause. Two questionnaires have emerged - the one described in this work and one directed primarily towards the activities of bench staff. There are 95 questions and it takes approximately two hours to complete. PMID:23105892

  8. 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.

  9. Unobtrusive assessment of activity patterns associated with mild cognitive impairment

    PubMed Central

    Hayes, T.L.; Abendroth, F.; Adami, A.; Pavel, M.; Zitzelberger, T.A.; Kaye, J.A.

    2008-01-01

    Background Timely detection of early cognitive impairment is difficult. Measures taken in the clinic reflect a single snapshot of performance that may be confounded by the increased variability typical in aging and disease. We evaluated the use of continuous, long-term and unobtrusive in-home monitoring to assess neurological function in healthy and cognitively impaired elders. Methods Fourteen older adults 65 years and older living independently in the community were monitored in their homes using an unobtrusive sensor system. Measures of walking speed and amount of activity in the home were obtained. Wavelet analysis was used to examine variance in activity at multiple timescales. Results More than 108,000 person-hours of continuous activity data were collected over periods as long as 418 days (mean 315 ± 82 days). The coefficient of variation in the median walking speed was twice as high in the MCI group (0.147 ± 0.074) as compared to the healthy group (0.079 ± 0.027; t11 = 2.266, p<0.03). Furthermore, the 24-hour wavelet variance was greater in the MCI group (MCI: 4.07 ± 0.14, Healthy elderly: 3.79± 0.23; F = 7.58, p=<0.008), indicating that the day-to-day pattern of activity of subjects in the MCI group was more variable than that of the cognitively healthy controls. Conclusions The results not only demonstrate the feasibility of these methods, but also suggest clear potential advantages to this new methodology. This approach may provide an improved means of detecting the earliest transition to MCI compared to conventional episodic testing in a clinic environment. PMID:19012864

  10. Effects of the 5-HT2A Antagonist Sarpogrelate on Walking Ability in Patients with Intermittent Claudication as Measured Using the Walking Impairment Questionnaire

    PubMed Central

    2008-01-01

    Background: The Walking Impairment Questionnaire (WIQ) measures walking ability in daily life in patients with peripheral arterial disease causing intermittent claudication. We investigated the efficacy of sarpogrelate, a 5-HT2A receptor antagonist, in improving walking ability, as measured using new Japanese version of the WIQ. Patients and Methods: A nationwide multicenter study was conducted at 80 institutions in Japan involving 586 patients with stable symptoms of intermittent claudication. Patients received open-label sarpogrelate 300 mg/day. A total of 419 patients were evaluated in the full analysis set (FAS) following the intention to treat principle, and 354 patients were evaluated in the per-protocol set (PPS). The FAS data are emphasized here. Results: The mean follow-up was 27.7 ± 10.1 weeks. Each subscale of the WIQ score showed improvement after sarpogrelate treatment (p < 0.0001), and the resting ankle-brachial index increased significantly (p < 0.0001). The incidence of adverse reactions of the entire series of 559 patients was 4.83% (27 patients), but there were no clinically significant safety concerns. Conclusions: We have for the first time demonstrated that sarpogrelate may improve walking ability in daily life in Japanese patients with intermittent claudication. The drug had a good safety profile. PMID:23555346

  11. Immunomodulation of phloretin by impairing dendritic cell activation and function.

    PubMed

    Lin, Chi-Chen; Chu, Ching-Liang; Ng, Chin-Sheng; Lin, Ching-Yen; Chen, Der-Yuan; Pan, I-Hong; Huang, Kao-Jean

    2014-05-01

    Dietary compounds in fruits and vegetables have been shown to exert many biological activities. In addition to antioxidant effects, a number of flavonoids are able to modulate inflammatory responses. Here, we demonstrated that phloretin (PT), a natural dihydrochalcone found in many fruits, suppressed the activation and function of mouse dendritic cells (DCs). Phloretin disturbed the multiple intracellular signaling pathways in DCs induced by the Toll-like receptor 4 (TLR4) agonist lipopolysaccharide (LPS), including ROS, MAPKs (ERK, JNK, p38 MAPK), and NF-κB, and thereby reducing the production of inflammatory cytokines and chemokines. Phloretin also effectively suppressed the activation of DCs treated with different dosages of LPS or various TLR agonists. The LPS-induced DC maturation was attenuated by phloretin because the expression levels of the MHC class II and the co-stimulatory molecules were down-regulated, which then inhibited the LPS-stimulating DCs and the subsequent naïve T cell activation in a mixed lymphocyte reaction. Moreover, in vivo administration of phloretin suppressed the phenotypic maturation of the LPS-challenged splenic DCs and decreased the IFN-γ production from the activated CD4 T cells. Thus, we suggest that phloretin may potentially be an immunomodulator by impairing the activation and function of DCs and phloretin-contained fruits may be helpful in the improvement of inflammation and autoimmune diseases. PMID:24651121

  12. 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 ] Neuropathy), Disability Benefits Questionnaire, VA Form 21-0960C-4. e. Diabetes Mellitus Disability...

  13. 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

    ... Temporomandibular Joint Conditions) Disability Benefits Questionnaire, VA Form 21-0960D1. Endocrine Diseases (other... System) Disability Benefits Questionnaire, VA Form 21- 0960-J-4. Respiratory Conditions (other...

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

    PubMed Central

    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. PMID:26078715

  15. The Diabetes Intention, Attitude, and Behavior Questionnaire: evaluation of a brief questionnaire to measure physical activity, dietary control, maintenance of a healthy weight, and psychological antecedents

    PubMed Central

    Traina, Shana B; Mathias, Susan D; Colwell, Hilary H; Crosby, Ross D; Abraham, Charles

    2016-01-01

    Background This study assessed measurement properties of the 17-item Diabetes Intention, Attitude, and Behavior Questionnaire (DIAB-Q), which measures intention to engage in self-care behaviors, including following a diabetes diet and engaging in appropriate physical activity. Methods The DIAB-Q includes questions based on the Theory of Planned Behavior. Items were developed using published literature, input from health care professionals, and qualitative research findings in patients with and without type 2 diabetes mellitus (T2DM). In Stage I of the study, 23 adults with T2DM were interviewed to evaluate the content and clarity of the DIAB-Q. In Stage II 1,015 individuals with T2DM completed the DIAB-Q and supplemental questionnaires, including the Short Form-36 acute (SF-36), section III of the Multidimensional Diabetes Questionnaire, the Summary of Diabetes Self-Care Activities questionnaire, and self-administered items relevant to the treatment and management of T2DM (eg, blood pressure and glycated hemoglobin [HbA1c]) at baseline and 3–7 days later. Once the DIAB-Q scale structure was determined, its test–retest reliability, construct validity, and known-groups validity were evaluated, and minimal clinically important change was estimated. Results In Stage I, the 23 respondents surveyed generally reported that the DIAB-Q was clear and comprehensive and endorsed questions as relevant to their intentions to engage in diabetes-related self-care activities. Most subjects in Stage II were male, Caucasian, and married. Mean age was 63 years. Factor analysis revealed six psychological constructs (Behavior, Planning, Intention, Perceived Behavioral Control, Attitude, and Subjective Norm). Test–retest reliability was acceptable (≥0.70) for all scales, except Perceived Behavioral Control. Construct validity was demonstrated based on correlations with diabetes-specific items/scales and the SF-36. Known-groups validity was confirmed for Behavior, Planning, and

  16. 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...

  17. Does Physical Activity Influence Semantic Memory Activation in Amnestic Mild Cognitive Impairment?

    PubMed Central

    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.

    2011-01-01

    The effect of physical activity (PA) on functional brain activation for semantic memory in amnestic mild cognitive impairment (aMCI) was examined using event-related fMRI during fame discrimination. 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. PMID:21601432

  18. Adapting and Validating the Global Physical Activity Questionnaire (GPAQ) for Trivandrum, India, 2013

    PubMed Central

    Salvo, Deborah; Sarma, Prabhakaran Sankara; Thankappan, Kavumpurathu Raman; Pratt, Michael

    2016-01-01

    Introduction A limitation of the Global Physical Activity Questionnaire (GPAQ) in assessing physical activity in India is that it does not capture the diversity of activities across cultures and by sex. The purpose of this study was to culturally adapt and validate the GPAQ by using an accelerometer in Thiruvananthapuram City, India. Methods We developed a modified version of the GPAQ by adding a physical activity chart specific to the locale. We identified local physical activities through in-depth interviews, group discussions, and observation, and used Actigraph GT3X accelerometers to validate the modified GPAQ for a subsample of 47 women. Participants were drawn from a cross-sectional survey of 1,303 women aged 18 to 64 years, selected by multistage cluster sampling. Spearman rank correlation coefficients and intraclass correlation coefficients (ICC) were calculated to determine the correlation and level of agreement in moderate-to-vigorous physical activity (MVPA) on the basis of accelerometer measurement and the modified GPAQ. Results The correlation for MVPA between the modified GPAQ (overall) and the accelerometer (non-bouted MVPA) was 0.69 (95% confidence interval [CI], 0.39–0.85) with a moderately high ICC of 0.78 (95% CI, 0.56–0.90). The correlation for MVPA between the modified GPAQ and the accelerometer-based MVPA within bouts of at least 10 minutes was 0.60 (95% CI, 0.26–0.80) with an ICC of 0.55 (95% CI, 0.20–0.77) indicating a moderate level of agreement. Conclusion The GPAQ can be used for assessing physical activity among women in India, and its adaptation and validation may be useful in other low-income or middle-income countries where activities are diverse in type and intensity. PMID:27103263

  19. 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

  20. Development and initial validation of the determinants of physical activity questionnaire

    PubMed Central

    2013-01-01

    Background Physical activity interventions are more likely to be effective if they target causal determinants of behaviour change. Targeting requires accurate identification of specific theoretical determinants of physical activity. Two studies were undertaken to develop and validate the Determinants of Physical Activity Questionnaire. Methods In Study 1, 832 male and female university staff and students were recruited from 49 universities across the UK and completed the 66-item measure, which is based on the Theoretical Domains Framework. Confirmatory factor analysis was undertaken on a calibration sample to generate the model, which resulted in a loss of 31 items. A validation sample was used to cross-validate the model. 20 new items were added and Study 2 tested the revised model in a sample of 466 male and female university students together with a physical activity measure. Results The final model consisted of 11 factors and 34 items, and CFA produced a reasonable fit χ2 (472) = 852.3, p < .001, CFI = .933, SRMR = .105, RMSEA = .042 (CI = .037-.046), as well as generally acceptable levels of discriminant validity, internal consistency, and test-retest reliability. Eight subscales significantly differentiated between high and low exercisers, indicating that those who exercise less report more barriers for physical activity. Conclusions A theoretically underpinned measure of determinants of physical activity has been developed with reasonable reliability and validity. Further work is required to test the measure amongst a more representative sample. This study provides an innovative approach to identifying potential barriers to physical activity. This approach illustrates a method for moving from diagnosing implementation difficulties to designing and evaluating interventions. PMID:23758912

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

    PubMed Central

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

    2016-01-01

    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. PMID:26891705

  2. 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

    2016-01-01

    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. PMID:26891705

  3. 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…

  4. Non-exercise estimation of VO2max using the International Physical Activity Questionnaire

    PubMed Central

    Schembre, Susan M.; Riebe, Deborah A.

    2011-01-01

    Non-exercise equations developed from self-reported physical activity can estimate maximal oxygen uptake (VO2max) as well as submaximal exercise testing. The International Physical Activity Questionnaire (IPAQ) is the most widely used and validated self-report measure of physical activity. This study aimed to develop and test a VO2max estimation equation derived from the IPAQ-Short Form (IPAQ-S). College-aged males and females (n = 80) completed the IPAQ-S and performed a maximal exercise test. The estimation equation was created with multivariate regression in a gender-balanced subsample of participants, equally representing five levels of fitness (n = 50) and validated in the remaining participants (n = 30). The resulting equation explained 43% of the variance in measured VO2max (SEE = 5.45 ml·kg-1·min-1). Estimated VO2max for 87% of individuals fell within acceptable limits of error observed with submaximal exercise testing (20% error). The IPAQ-S can be used to successfully estimate VO2max as well as submaximal exercise tests. Development of other population-specific estimation equations is warranted. PMID:21927551

  5. 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. PMID:26265337

  6. 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. PMID:23376587

  7. Examining the spatial congruence between data obtained with a novel activity location questionnaire, continuous GPS tracking, and prompted recall surveys

    PubMed Central

    2013-01-01

    Background Place and health researchers are increasingly interested in integrating individuals’ mobility and the experience they have with multiple settings in their studies. In practice, however, few tools exist which allow for rapid and accurate gathering of detailed information on the geographic location of places where people regularly undertake activities. We describe the development and validation of a new activity location questionnaire which can be useful in accounting for multiple environmental influences in large population health investigations. Methods To develop the questionnaire, we relied on a literature review of similar data collection tools and on results of a pilot study wherein we explored content validity, test-retest reliability, and face validity. To estimate convergent validity, we used data from a study of users of a public bicycle share program conducted in Montreal, Canada in 2011. We examined the spatial congruence between questionnaire data and data from three other sources: 1) one-week GPS tracks; 2) activity locations extracted from the GPS tracks; and 3) a prompted recall survey of locations visited during the day. Proximity and convex hull measures were used to compare questionnaire-derived data and GPS and prompted recall survey data. Results In the sample, 75% of questionnaire-reported activity locations were located within 400 meters of an activity location recorded on the GPS track or through the prompted recall survey. Results from convex hull analyses suggested questionnaire activity locations were more concentrated in space than GPS or prompted-recall locations. Conclusions The new questionnaire has high convergent validity and can be used to accurately collect data on regular activity spaces in terms of locations regularly visited. The methods, measures, and findings presented provide new material to further study mobility in place and health research. PMID:24025119

  8. 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. PMID:23936636

  9. Development and validation of a Spanish translation of the Yale activity questionnaire

    PubMed Central

    2014-01-01

    Background Valid measures of physical activity are critical research tools. The objective of this study was to develop a Spanish translation of the Yale Physical Activity Survey, and to provide preliminary evidence of its validity in a population of Dominican patients with lower extremity arthritis. Methods A Dominican bilingual health care professional translated the Yale Physical Activity Survey (YPAS) from English to Spanish. Several Dominican adults reviewed the translation to ensure it was linguistically and culturally appropriate. The questionnaire was back-translated to English by a North American researcher who is fluent in Spanish. Discrepancies between the original and back-translated versions were resolved by the translator and back-translator. The Spanish translation was administered to 108 Dominican subjects with advanced hip or knee arthritis prior to (N = 44) or one to four years following (N = 64) total joint replacement. We assessed construct validity by examining the association of YPAS scores and measures of functional status and pain (WOMAC), quality of life (EQ-5D) and the number of painful lower extremity joints. Results A higher YPAS Part II Activity Dimensions Summary Index score had weak to modest correlations with worse function and quality of life as measured with the WOMAC function scale (r = 0.21, p = 0.03), SF-36 Physical Activity Scale (r = 0.29, p = 0.004) and EQ-5D (r = 0.34, p = 0.0007). Total minutes of vigorous activity and walking had weak to modest correlation with these measures (WOMAC Function Scale (r = 0.15, p = 0.15), SF-36 Physical Activity Scale (r = 0.21, p = 0.04) and EQ-5D utility (r = 0.24, p = 0.02)). Correlations between the YPAS Part I energy expenditure score and these measures were lower (WOMAC Function Scale (r = 0.07, p = 0.49), SF-36 Physical Activity Scale (r = 0.03, p = 0.74) and EQ-5D utility (r = 0.18, p = 0.07)). Conclusions We have developed a new Spanish translation of the Yale Physical Activity Survey

  10. 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...

  11. 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,...

  12. 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....

  13. 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

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

    PubMed

    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

  15. Validity of a short questionnaire to assess physical activity in 10 European countries.

    PubMed

    Peters, Tricia; Brage, Soren; Westgate, Kate; Franks, Paul W; Gradmark, Anna; Tormo Diaz, Maria Jose; Huerta, Jose Maria; Bendinelli, Benedetta; Vigl, Mattheaus; Boeing, Heiner; Wendel-Vos, Wanda; Spijkerman, Annemieke; Benjaminsen-Borch, Kristin; Valanou, Elisavet; de Lauzon Guillain, Blandine; Clavel-Chapelon, Françoise; Sharp, Stephen; Kerrison, Nicola; Langenberg, Claudia; Arriola, Larraitz; Barricarte, Aurelio; Gonzales, Carlos; Grioni, Sara; Kaaks, Rudolf; Key, Timothy; Khaw, Kay Tee; May, Anne; Nilsson, Peter; Norat, Teresa; Overvad, Kim; Palli, Domenico; Panico, Salvatore; Ramón Quirós, Jose; Ricceri, Fulvio; Sanchez, Maria-Jose; Slimani, Nadia; Tjonneland, Anne; Tumino, Rosario; Feskins, Edith; Riboli, Elio; Ekelund, Ulf; Wareham, Nick

    2012-01-01

    To accurately examine associations of physical activity (PA) with disease outcomes, a valid method of assessing free-living activity is required. We examined the validity of a brief PA questionnaire (PAQ) used in the European Prospective Investigation into Cancer and Nutrition (EPIC). PA energy expenditure (PAEE) and time spent in moderate and vigorous physical activity (MVPA) was measured in 1,941 healthy individuals from 10 European countries using individually-calibrated combined heart-rate and movement sensing. Participants also completed the short EPIC-PAQ, which refers to past year's activity. Pearson (r) and Spearman (σ) correlation coefficients were calculated for each country, and random effects meta-analysis was used to calculate the combined correlation across countries to estimate the validity of two previously- and one newly-derived ordered, categorical PA indices ("Cambridge index", "total PA index", and "recreational index") that categorized individuals as inactive, moderately inactive, moderately active, or active. The strongest associations with PAEE and MVPA were observed for the Cambridge index (r = 0.33 and r = 0.25, respectively). No significant heterogeneity by country was observed for this index (I(2) = 36.3%, P = 0.12; I(2) = 0.0%, P = 0.85), whereas heterogeneity was suggested for other indices (I(2) > 48%, P < 0.05, I(2) > 47%, P < 0.05). PAEE increased linearly across self-reported PA categories (P for trend <0.001), with an average difference of approximately 460 kJ/d for men and 365 kJ/d for women, between categories of the Cambridge index. The EPIC-PAQ is suitable for categorizing European men and women into four distinct categories of overall physical activity. The difference in PAEE between categories may be useful when estimating effect sizes from observational research. PMID:22089423

  16. 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…

  17. 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…

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

    PubMed

    Helmerhorst, Hendrik J F; Brage, Søren; Warren, Janet; Besson, Herve; Ekelund, Ulf

    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

  19. 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

  20. 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

  1. 76 FR 21429 - Proposed Information Collection (Disability Benefits Questionnaires-Group 3) Activity: Comment...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-15

    .... Titles a. Central Nervous System and Neuromusculo Diseases, Disability Benefits Questionnaire, VA Form 21... Management System (FDMS) at http://www.Regulations.gov or to Nancy J. Kessinger, Veterans...

  2. 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...

  3. 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

  4. Validity of Electronically Administered Recent Physical Activity Questionnaire (RPAQ) in Ten European Countries

    PubMed Central

    Golubic, Rajna; May, Anne M.; Benjaminsen Borch, Kristin; Overvad, Kim; Charles, Marie-Aline; Diaz, Maria Jose Tormo; Amiano, Pilar; Palli, Domenico; Valanou, Elisavet; Vigl, Matthaeus; Franks, Paul W.; Wareham, Nicholas; Ekelund, Ulf; Brage, Soren

    2014-01-01

    Objective To examine the validity of the Recent Physical Activity Questionnaire (RPAQ) which assesses physical activity (PA) in 4 domains (leisure, work, commuting, home) during past month. Methods 580 men and 1343 women from 10 European countries attended 2 visits at which PA energy expenditure (PAEE), time at moderate-to-vigorous PA (MVPA) and sedentary time were measured using individually-calibrated combined heart-rate and movement sensing. At the second visit, RPAQ was administered electronically. Validity was assessed using agreement analysis. Results RPAQ significantly underestimated PAEE in women [median(IQR) 34.1 (22.1, 52.2) vs. 40.6 (32.4, 50.9) kJ/kg/day, 95%LoA: −44.4, 63.4 kJ/kg/day) and in men (43.7 (29.0, 69.0) vs. 45.5 (34.1, 57.6) kJ/kg/day, 95%LoA: −47.2, 101.3 kJ/kg/day]. Using individualised definition of 1MET, RPAQ significantly underestimated MVPA in women [median(IQR): 62.1 (29.4, 124.3) vs. 73.6 (47.8, 107.2) min/day, 95%LoA: −130.5, 305.3 min/day] and men [82.7 (38.8, 185.6) vs. 83.3 (55.1, 125.0) min/day, 95%LoA: −136.4, 400.1 min/day]. Correlations (95%CI) between subjective and objective estimates were statistically significant [PAEE: women, rho = 0.20 (0.15–0.26); men, rho = 0.37 (0.30–0.44); MVPA: women, rho = 0.18 (0.13–0.23); men, rho = 0.31 (0.24–0.39)]. When using non-individualised definition of 1MET (3.5 mlO2/kg/min), MVPA was substantially overestimated (∼30 min/day). Revisiting occupational intensity assumptions in questionnaire estimation algorithms with occupational group-level empirical distributions reduced median PAEE-bias in manual (25.1 kJ/kg/day vs. −9.0 kJ/kg/day, p<0.001) and heavy manual workers (64.1 vs. −4.6 kJ/kg/day, p<0.001) in an independent hold-out sample. Conclusion Relative validity of RPAQ-derived PAEE and MVPA is comparable to previous studies but underestimation of PAEE is smaller. Electronic RPAQ may be used in large-scale epidemiological studies including surveys

  5. 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. PMID:24216343

  6. 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…

  7. 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…

  8. Active Learning for Children with Visual Impairments and Additional Disabilities.

    ERIC Educational Resources Information Center

    Johnson, Kenalea; Griffin-Shirley, Nora; Koenig, Alan J.

    2000-01-01

    A survey found a majority of 93 workshop participants used Nielsen's Little Room, an educational method involving placing a structure on a resonance board that acts like a drum and gives tactile and auditory feedback as the child with visual impairments interacts with objects in it and on the board. (Contains references.) (CR)

  9. 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.)

  10. The Experience of Choice in Physical Activity Contexts for Adults with Mobility Impairments

    ERIC Educational Resources Information Center

    Morphy, Lorraine Y.; Goodwin, Donna L.

    2012-01-01

    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.…

  11. The child play behavior and activity questionnaire: a parent-report measure of childhood gender-related behavior in China.

    PubMed

    Yu, Lu; Winter, Sam; Xie, Dong

    2010-06-01

    Boys and girls establish relatively stable gender stereotyped behavior patterns by middle childhood. Parent-report questionnaires measuring children's gender-related behavior enable researchers to conduct large-scale screenings of community samples of children. For school-aged children, two parent-report instruments, the Child Game Participation Questionnaire (CGPQ) and the Child Behavior and Attitude Questionnaire (CBAQ), have long been used for measuring children's sex-dimorphic behaviors in Western societies, but few studies have been conducted using these measures for Chinese populations. The current study aimed to empirically examine and modify the two instruments for their applications to Chinese society. Parents of 486 Chinese boys and 417 Chinese girls (6-12 years old) completed a questionnaire comprising items from the CGPQ and CBAQ, and an additional 14 items specifically related to Chinese gender-specific games. Items revealing gender differences in a Chinese sample were identified and used to construct a Child Play Behavior and Activity Questionnaire (CPBAQ). Four new scales were generated through factor analysis: a Gender Scale, a Girl Typicality Scale, a Boy Typicality Scale, and a Cross-Gender Scale (CGS). These scales had satisfactory internal reliabilities and large effect sizes for gender. The CPBAQ is believed to be a promising instrument for measuring children's gender-related behavior in China. PMID:18719986

  12. The Child Play Behavior and Activity Questionnaire: A Parent-Report Measure of Childhood Gender-Related Behavior in China

    PubMed Central

    Winter, Sam; Xie, Dong

    2008-01-01

    Boys and girls establish relatively stable gender stereotyped behavior patterns by middle childhood. Parent-report questionnaires measuring children’s gender-related behavior enable researchers to conduct large-scale screenings of community samples of children. For school-aged children, two parent-report instruments, the Child Game Participation Questionnaire (CGPQ) and the Child Behavior and Attitude Questionnaire (CBAQ), have long been used for measuring children’s sex-dimorphic behaviors in Western societies, but few studies have been conducted using these measures for Chinese populations. The current study aimed to empirically examine and modify the two instruments for their applications to Chinese society. Parents of 486 Chinese boys and 417 Chinese girls (6–12 years old) completed a questionnaire comprising items from the CGPQ and CBAQ, and an additional 14 items specifically related to Chinese gender-specific games. Items revealing gender differences in a Chinese sample were identified and used to construct a Child Play Behavior and Activity Questionnaire (CPBAQ). Four new scales were generated through factor analysis: a Gender Scale, a Girl Typicality Scale, a Boy Typicality Scale, and a Cross-Gender Scale (CGS). These scales had satisfactory internal reliabilities and large effect sizes for gender. The CPBAQ is believed to be a promising instrument for measuring children’s gender-related behavior in China. PMID:18719986

  13. Screening Physical Activity in Family Practice: Validity of the Spanish Version of a Brief Physical Activity Questionnaire

    PubMed Central

    Puig-Ribera, Anna; Martín-Cantera, Carlos; Puigdomenech, Elisa; Real, Jordi; Romaguera, Montserrat; Magdalena-Belio, José Félix; Recio-Rodríguez, Jose Ignacio; Rodriguez-Martin, Beatriz; Arietaleanizbeaskoa, Maria Soledad; Repiso–Gento, Irene; Garcia-Ortiz, Luis

    2015-01-01

    Objectives The use of brief screening tools to identify inactive patients is essential to improve the efficiency of primary care-based physical activity (PA) programs. However, the current employment of short PA questionnaires within the Spanish primary care pathway is unclear. This study evaluated the validity of the Spanish version of a Brief Physical Activity Assessment Tool (SBPAAT). Methods A validation study was carried out within the EVIDENT project. A convenience sample of patients (n = 1,184; age 58.9±13.7 years; 60.5% female) completed the SBPAAT and the 7-day Physical Activity Recall (7DPAR) and, in addition, wore an accelerometer (ActiGraph GT3X) for seven consecutive days. Validity was evaluated by measuring agreement, Kappa correlation coefficients, sensitivity and specificity in achieving current PA recommendations with the 7DPAR. Pearson correlation coefficients with the number of daily minutes engaged in moderate and vigorous intensity PA according to the accelerometer were also assessed. Comparison with accelerometer counts, daily minutes engaged in sedentary, light, moderate, and vigorous intensity PA, total daily kilocalories, and total PA and leisure time expenditure (METs-hour-week) between the sufficiently and insufficiently active groups identified by SBPAAT were reported. Results The SBPAAT identified 41.3% sufficiently active (n = 489) and 58.7% insufficiently active (n = 695) patients; it showed moderate validity (k = 0.454, 95% CI: 0.402–0.505) and a specificity and sensitivity of 74.3% and 74.6%, respectively. Validity was fair for identifying daily minutes engaged in moderate (r = 0.215, 95% CI:0.156 to 0.272) and vigorous PA (r = 0.282, 95% CI:0.165 to 0.391). Insufficiently active patients according to the SBPAAT significantly reported fewer counts/minute (-22%), fewer minutes/day of moderate (-11.38) and vigorous PA (-2.69), spent fewer total kilocalories/day (-753), and reported a lower energy cost (METs-hour-week) of physical

  14. 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...

  15. 78 FR 44625 - Proposed Information Collection (Wrist Conditions Disability Benefits Questionnaire) Activity...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-24

    ... 17, 2013 (78 FR 36307), inviting the public to comment on a proposed information collection titled ``Wrist Conditions Disability Benefits Questionnaire, VA Form 21-0960M-16.'' On June 18, 2013 (78 FR 36643... corrects that error by withdrawing the FR notice that published on June 18, 2013 (FR Doc 2013-14412)....

  16. 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. PMID:26189585

  17. Translation and validation of the Child and the Adolescent HARDSHIP (Headache-attributed restriction, disability, social handicap and impaired participation) questionnaire into Danish language

    PubMed Central

    McGirr, Kate A.; Korsgaard, Hanne Oertved; Rathleff, Michael S.

    2016-01-01

    Background. The prevalence of headaches among children and adolescents varies considerably between countries. This may be due to a lack of appropriate instruments to capture the prevalence. The purpose of this study was to translate the Child and Adolescent HARDSHIP questionnaires from English into Danish language, conduct cross-cultural adaptation, face validation by cognitive interviewing and conduct a pilot study exploring time requirements. Methods. The questionnaire was translated using the guidelines proposed by “The Global Campaign to Reduce the Burden of Headache.” A total of 25 children from 6 to 12 years of age completed the questionnaire with 24 h between test and retest to assess reliability. A total of 169 children and adolescents from 6 to 17 years of age completed the translated questionnaire to assess time requirements for completing it. Results. Only minor discrepancies were observed in the translation process. Test-retest reliability of the translated questionnaire showed substantial agreement (kappa: 0.65–0.78). The questionnaires were completed within 30 min (age 6–11 years of age) and within 15 min (age 12–17 years of age) respectively. Discussion. No major problems were observed in the forward translations of the questionnaires. The face validation prompted no major changes in the questionnaire. The face-to-face interviews showed that pupils of different ethnic backgrounds than Danish and pupils in the age group of 6–11 had more difficulty in understanding a minority of the questions. The Danish Child and Adolescent HARDSHIP questionnaire therefore complies with the intentions of the originators, aiming at a maximal completion time of 45 min and in comparison with actual completion time. The test-retest study showed substantial agreement between test and retest in the headache, migraine and MOH domains and questions referring to time.The Child and Adolescent HARDSHIP questionnaire, includes a section specifically recording a four

  18. Translation and validation of the Child and the Adolescent HARDSHIP (Headache-attributed restriction, disability, social handicap and impaired participation) questionnaire into Danish language.

    PubMed

    Jorgensen, Jens Erik; McGirr, Kate A; Korsgaard, Hanne Oertved; Rathleff, Michael S

    2016-01-01

    Background. The prevalence of headaches among children and adolescents varies considerably between countries. This may be due to a lack of appropriate instruments to capture the prevalence. The purpose of this study was to translate the Child and Adolescent HARDSHIP questionnaires from English into Danish language, conduct cross-cultural adaptation, face validation by cognitive interviewing and conduct a pilot study exploring time requirements. Methods. The questionnaire was translated using the guidelines proposed by "The Global Campaign to Reduce the Burden of Headache." A total of 25 children from 6 to 12 years of age completed the questionnaire with 24 h between test and retest to assess reliability. A total of 169 children and adolescents from 6 to 17 years of age completed the translated questionnaire to assess time requirements for completing it. Results. Only minor discrepancies were observed in the translation process. Test-retest reliability of the translated questionnaire showed substantial agreement (kappa: 0.65-0.78). The questionnaires were completed within 30 min (age 6-11 years of age) and within 15 min (age 12-17 years of age) respectively. Discussion. No major problems were observed in the forward translations of the questionnaires. The face validation prompted no major changes in the questionnaire. The face-to-face interviews showed that pupils of different ethnic backgrounds than Danish and pupils in the age group of 6-11 had more difficulty in understanding a minority of the questions. The Danish Child and Adolescent HARDSHIP questionnaire therefore complies with the intentions of the originators, aiming at a maximal completion time of 45 min and in comparison with actual completion time. The test-retest study showed substantial agreement between test and retest in the headache, migraine and MOH domains and questions referring to time.The Child and Adolescent HARDSHIP questionnaire, includes a section specifically recording a four-week period

  19. 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…

  20. 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

  1. 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…

  2. Instrumental Activities of Daily Living Impairment Is Associated with Increased Amyloid Burden

    PubMed Central

    Marshall, Gad A.; Olson, Lauren E.; Frey, Meghan T.; Maye, Jacqueline; Becker, J. Alex; Rentz, Dorene M.; Sperling, Reisa A.; Johnson, Keith A.

    2011-01-01

    Background/Aims Instrumental activities of daily living (IADL) impairment in Alzheimer's disease has been associated with global amyloid deposition in postmortem studies. We sought to determine whether IADL impairment is associated with increased cortical Pittsburgh Compound B (PiB) retention. Methods Fifty-five subjects (19 normal older controls, NC, and 36 with mild cognitive impairment, MCI) underwent clinical assessments and dynamic PiB positron emission tomography imaging. Results A linear multiple regression model showed that greater IADL impairment was associated with greater global PiB retention in all subjects (R2 = 0.40; unstandardized partial regression coefficient, β = 5.8; p = 0.0002) and in MCI subjects only (R2 = 0.28; β = 6.1; p = 0.003), but not in NC subjects only. Conclusion These results suggest that daily functional impairment is related to greater amyloid burden in MCI. PMID:21778725

  3. 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…

  4. Systematic review of the measurement properties of self-report physical activity questionnaires in healthy adult populations

    PubMed Central

    Silsbury, Zoë; Goldsmith, Robert; Rushton, Alison

    2015-01-01

    Objective This systematic review evaluated the measurement properties of current self-report physical activity questionnaires (SRPAQs) completed within healthy adult populations. Design Two reviewers independently searched seven electronic databases and hand searched for articles investigating measurement properties of a SRPAQ evaluating physical activity over the previous 6 months. Articles published from 1 May 2001 to 4 December 2014 were systematically screened and eligible studies were not limited to English language sources. Articles investigating specific race, gender or socioeconomic populations were excluded. Results 10 studies investigating 10 SRPAQs were included. The methodological quality of the included studies was evaluated using COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) and ranged from ‘poor’ to ‘good’. The Recent Physical Activity Questionnaire, International Physical Activity Questionnaires and Physical Activity Assessment Tool demonstrated good/excellent test–retest reliability (intra-class coefficient (ICC)=0.76, p<0.0001; r=0.627–0.91; r=0.618, p<0.001, respectively), but variable criterion validity (r=0.67, p<0.0001; r=−0.02–0.43; r=0.392, p<0.01, respectively). The single-item measure showed significant criterion validity against an accelerometer (for moderate to vigorous physical activity (MVPA) k=0.23, 95% CI 0.05 to 0.41; and physical activity ≥10 min bouts 0.39 (95% CI 0.14 to 0.64). Construct validity of the six-point scale and Human Activity Profile varied significantly with age, marital status and presence of comorbidities (p<0.05, <0.01, <0.000 and p<0.05, <0.05, <0.000, respectively). The 1 week Godlin-Shephard recall demonstrated ‘moderate’ validity with the gold standard measure of accelerometry (r=0.43). Conclusions Inconclusive evidence exists. Further investigation of criterion validity of the short-form International Physical Activity Questionnaire is

  5. Concurrent Validity of a Self-Reported Physical Activity “Vital Sign” Questionnaire With Adult Primary Care Patients

    PubMed Central

    Joy, Elizabeth A.; Gren, Lisa H.; Shaw, Janet M.

    2016-01-01

    Introduction No tool currently used by primary health care providers to assess physical activity has been evaluated for its ability to determine whether or not patients achieve recommended levels of activity. The purpose of this study was to assess concurrent validity of physical activity self-reported to the brief (<30 sec) Physical Activity “Vital Sign” questionnaire (PAVS) compared with responses to the lengthier (3–5 min), validated Modifiable Activity Questionnaire (MAQ). Methods Agreement between activity reported to the PAVS and MAQ by primary care patients at 2 clinics in 2014 was assessed by using percentages and κ coefficients. Agreement consisted of meeting or not meeting the 2008 Aerobic Physical Activity Guidelines for Americans (PA Guidelines) of the US Department of Health and Human Services. We compared self-reported usual minutes per week of moderate-to-vigorous physical activity among patients at a primary care clinic in 2014 who reported to PAVS and to MAQ by using Pearson correlation and Bland–Altman plots of agreement. Results Among 269 consenting patients who reported physical activity, PAVS results agreed with those of MAQ 89.6% of the time and demonstrated good agreement in identifying patients who did not meet PA Guidelines recommendations (κ = 0.55, ρ = 0.57; P < .001). Usual minutes per week of moderate-to-vigorous physical activity reported to PAVS had a high positive correlation with the same reported to MAQ (r = 0.71; P < .001). Conclusion PAVS may be a valid tool for identifying primary care patients who need counseling about physical activity. PAVS should be assessed further for agreement with repeated objective measures of physical activity in the patient population. PMID:26851335

  6. Specific marker of feigned memory impairment: The activation of left superior frontal gyrus.

    PubMed

    Chen, Zi-Xiang; Xue, Li; Liang, Chun-Yu; Wang, Li-Li; Mei, Wei; Zhang, Qiang; Zhao, Hu

    2015-11-01

    Faking memory impairment means normal people complain lots of memory problems without organic damage in forensic assessments. Using alternative forced-choice paradigm, containing digital or autobiographical information, previous neuroimaging studies have indicated that faking memory impairment could cause the activation in the prefrontal and parietal regions, and might involve a fronto-parietal-subcortical circuit. However, it is still unclear whether different memory types have influence on faking or not. Since different memory types, such as long-term memory (LTM) and short-term memory (STM), were found supported by different brain areas, we hypothesized that feigned STM or LTM impairment had distinct neural activation mapping. Besides that, some common neural correlates may act as the general characteristic of feigned memory impairment. To verify this hypothesis, the functional magnetic resonance imaging (fMRI) combined with an alternative word forced-choice paradigm were used in this study. A total of 10 right-handed participants, in this study, had to perform both STW and LTM tasks respectively under answering correctly, answering randomly and feigned memory impairment conditions. Our results indicated that the activation of the left superior frontal gyrus and the left medial frontal gyrus was associated with feigned LTM impairment, whereas the left superior frontal gyrus, the left precuneus and the right anterior cingulate cortex (ACC) were highly activated while feigning STM impairment. Furthermore, an overlapping was found in the left superior frontal gyrus, and it suggested that the activity of the left superior frontal gyrus might be acting as a specific marker of feigned memory impairment. PMID:26479324

  7. U.S.-MEXICO BORDER PROGRAM ARIZONA BORDER STUDY--STANDARD OPERATING PROCEDURE FOR CLEANING: TIME DIARY AND ACTIVITY QUESTIONNAIRE (UA-D-20.0)

    EPA Science Inventory

    The purpose of this SOP is to define the steps involved in cleaning the electronic data generated from data entry of the Time Diary and Activity Questionnaire. It applies to electronic data corresponding to the Time Diary and Activity Questionnaire that was scanned and verified ...

  8. NHEXAS PHASE I ARIZONA STUDY--STANDARD OPERATING PROCEDURE FOR CLEANING: TIME DIARY AND ACTIVITY QUESTIONNAIRE (UA-D-20.0)

    EPA Science Inventory

    The purpose of this SOP is to define the steps involved in cleaning the electronic data generated from data entry of the Time Diary and Activity Questionnaire. It applies to electronic data corresponding to the Time Diary and Activity Questionnaire that was scanned and verified ...

  9. ASSESSMENT OF UPPER EXTREMITY IMPAIRMENT, FUNCTION, AND ACTIVITY FOLLOWING STROKE: FOUNDATIONS FOR CLINICAL DECISION MAKING

    PubMed Central

    Lang, Catherine E.; Bland, Marghuretta D.; Bailey, Ryan R.; Schaefer, Sydney Y.; Birkenmeier, Rebecca L.

    2012-01-01

    The purpose of this review is to provide a comprehensive approach for assessing the upper extremity (UE) after stroke. First, common upper extremity impairments and how to assess them are briefly discussed. While multiple UE impairments are typically present after stroke, the severity of one impairment, paresis, is the primary determinant of UE functional loss. Second, UE function is operationally defined and a number of clinical measures are discussed. It is important to consider how impairment and loss of function affect UE activity outside of the clinical environment. Thus, this review also identifies accelerometry as an objective method for assessing UE activity in daily life. Finally, the role that each of these levels of assessment should play in clinical decision making is discussed in order to optimize the provision of stroke rehabilitation services. PMID:22975740

  10. The validity and reliability of a home environment preschool-age physical activity questionnaire (Pre-PAQ)

    PubMed Central

    2011-01-01

    Background There is a need for valid population level measures of physical activity in young children. The aim of this paper is to report the development, and the reliability and validity, of the Preschool-age Children's Physical Activity Questionnaire (Pre-PAQ) which was designed to measure activity of preschool-age children in the home environment in population studies. Methods Pre-PAQ was completed by 103 families, and validated against accelerometry for 67 children (mean age 3.8 years, SD 0.74; males 53%). Pre-PAQ categorizes activity into five progressive levels (stationary no movement, stationary with limb or trunk movement, slow, medium, or fast-paced activity). Pre-PAQ Levels 1-2 (stationary activities) were combined for analyses. Accelerometer data were categorized for stationary, sedentary (SED), non-sedentary (non-SED), light (LPA), moderate (MPA) and vigorous (VPA) physical activity using manufacturer's advice (stationary) or the cut-points described by Sirard et al and Reilly et al. Bland-Altman methods were used to assess agreement between the questionnaire and the accelerometer measures for corresponding activity levels. Reliability of the Pre-PAQ over one week was determined using intraclass correlations (ICC) or kappa (κ) values and percentage of agreement of responses between the two questionnaire administrations. Results Pre-PAQ had good agreement with LPA (mean difference 1.9 mins.day-1) and VPA (mean difference -4.8 mins.day-1), was adequate for stationary activity (mean difference 7.6 mins.day-1) and poor for sedentary activity, whether defined using the cut-points of Sirard et al (mean difference -235.4 mins.day-1) or Reilly et al (mean difference -208.6 mins.day-1) cut-points. Mean difference between the measures for total activity (i.e. Reilly's non-sedentary or Sirard's LMVPA) was 20.9 mins.day-1 and 45.2 mins.day-1. The limits of agreement were wide for all categories. The reliability of Pre-PAQ question responses ranged from 0

  11. Reliability of the modified child and adolescent physical activity and nutrition survey, physical activity (CAPANS-PA) questionnaire among chinese-australian youth

    PubMed Central

    2011-01-01

    Background Evidence suggests that differences exist in physical activity (PA) participation among Culturally and Linguistically Diverse (CALD) children and adolescents. It is possible that these differences could be influenced by variations in measurement technique and instrument reliability. However, culturally sensitive instruments for examining PA behaviour among CALD populations are lacking. This study tested the reliability of the Child and Adolescent Physical Activity and Nutrition Survey (CAPANS-PA) recall questionnaire among a sample of Chinese-Australian youth. Methods The psychometric property of the CAPANS-PA questionnaire was examined among a sample of 77 Chinese-Australian youth (aged 11 - 14 y) who completed the questionnaire twice within 7 days. Test-retest reliability of individual items and scales within the CAPANS-PA questionnaire was determined using Kappa statistics for categorical variables and intraclass correlation coefficients (ICC) for continuous variables. Results The CAPANS-PA questionnaire demonstrated acceptable test-retest reliability for frequency and duration of time spent in weekly Moderate to Vigorous Physical Activity (MVPA) (ICC ≥ 0.70) for all participants. Test-retest reliability for time spent in weekly sedentary activities was acceptable for females (ICC = 0.82) and males (ICC = 0.72). Conclusions The results suggest the CAPANS-PA questionnaire provides reliable estimates for type, frequency and duration of MVPA participation among Chinese-Australian youth. Further investigation into the reliability of the sedentary items within the CAPANS-PA is required before these items can be used with confidence. This study is novel in that the reliability of instruments among CALD groups nationally and internationally remains sparse and this study contributes to the wider body of available psychometrically tested instruments. In addition, this study is the first to our knowledge to successfully engage and investigate the basic health

  12. Punicalagin, an active component in pomegranate, ameliorates cardiac mitochondrial impairment in obese rats via AMPK activation

    PubMed Central

    Cao, Ke; Xu, Jie; Pu, Wenjun; Dong, Zhizhong; Sun, Lei; Zang, Weijin; Gao, Feng; Zhang, Yong; Feng, Zhihui; Liu, Jiankang

    2015-01-01

    Obesity is associated with an increasing prevalence of cardiovascular diseases and metabolic syndrome. It is of paramount importance to reduce obesity-associated cardiac dysfunction and impaired energy metabolism. In this study, the activation of the AMP-activated protein kinase (AMPK) pathway by punicalagin (PU), a major ellagitannin in pomegranate was investigated in the heart of a rat obesity model. In male SD rats, eight-week administration of 150 mg/kg pomegranate extract (PE) containing 40% punicalagin sufficiently prevented high-fat diet (HFD)-induced obesity associated accumulation of cardiac triglyceride and cholesterol as well as myocardial damage. Concomitantly, the AMPK pathway was activated, which may account for prevention of mitochondrial loss via upregulating mitochondrial biogenesis and amelioration of oxidative stress via enhancing phase II enzymes in the hearts of HFD rats. Together with the normalized expression of uncoupling proteins and mitochondrial dynamic regulators, PE significantly prevented HFD-induced cardiac ATP loss. Through in vitro cultures, we showed that punicalagin was the predominant component that activated AMPK by quickly decreasing the cellular ATP/ADP ratio specifically in cardiomyocytes. Our findings demonstrated that punicalagin, the major active component in PE, could modulate mitochondria and phase II enzymes through AMPK pathway to prevent HFD-induced cardiac metabolic disorders. PMID:26369619

  13. 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

  14. Effortful retrieval reduces hippocampal activity and impairs incidental encoding.

    PubMed

    Reas, Emilie T; Brewer, James B

    2013-05-01

    Functional imaging studies frequently report that the hippocampus is engaged by successful episodic memory retrieval. However, considering that concurrent encoding of the background environment occurs during retrieval and influences medial temporal lobe activity, it is plausible that hippocampal encoding functions are reduced with increased attentional engagement during effortful retrieval. Expanding upon evidence that retrieval efforts suppress activity in hippocampal regions implicated in encoding, this study examines the influence of retrieval effort on encoding performance and the interactive effects of encoding and retrieval on hippocampal and neocortical activity. Functional magnetic resonance imaging was conducted while subjects performed a word recognition task with incidental picture encoding. Both lower memory strength and increased search duration were associated with encoding failure and reduced hippocampal and default network activity. Activity in the anterior hippocampus tracked encoding, which was more strongly deactivated when incidental encoding was unsuccessful. These findings highlight potential contributions from background encoding processes to hippocampal activations during neuroimaging studies of episodic memory retrieval. PMID:23378272

  15. “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

  16. Motor speech impairment, activity, and participation in children with cerebral palsy.

    PubMed

    Mei, Cristina; Reilly, Sheena; Reddihough, Dinah; Mensah, Fiona; Morgan, Angela

    2014-08-01

    The present study used a population-based sample of children with cerebral palsy (CP) to estimate the prevalence of motor speech impairment and its association with activity and participation. A sample of 79 Victorian children aged 4 years 11 months to 6 years 5 months was recruited through the Victorian CP Register. The presence of motor speech impairment was recorded using the Viking Speech Scale (VSS). Activity and participation outcomes included speech intelligibility (the National Technical Institute for the Deaf rating scale, NTID), the Functional Communication Classification System (FCCS) and Communication Function Classification System (CFCS). A parent completed rating scale was used to examine the association between motor speech impairment and participation. Ninety per cent (71/79) of children demonstrated a motor speech impairment. Strong associations were found between the VSS and NTID (< .001), CFCS (< .001), and FCCS levels (<.001). VSS levels III-IV were significantly associated with restrictions in home, school, and community-based participation as perceived by parents. Although some diversity in activity and participation outcomes was observed within specific VSS levels, the results of this study suggested that children with mild motor speech impairments are more likely to demonstrate superior activity and participation outcomes compared to children with moderate or severe deficits. PMID:24910254

  17. Metabolic Cost of Daily Activities and Effect of Mobility Impairment in Older Adults

    PubMed Central

    Knaggs, Jeffrey D; Larkin, Kelly A; Manini, Todd M

    2013-01-01

    OBJECTIVES There is a shortage of information on metabolic costs of daily physical activities in older adults and the effect of having mobility impairments. The primary purpose of this study was to evaluate metabolic equivalent (MET) values on common daily tasks in men and women aged > 70 years compared to normative criteria. A secondary purpose was to determine the effect of having mobility impairments. DESIGN Cross-sectional observational study. SETTING University based research clinic PARTICIPANTS Forty-five participants aged 70 to 90 years of age (mean: 76.3 ± 5.1) volunteered to complete 17 daily activities, each lasting 10 minutes. MEASUREMENTS Oxygen consumption (VO2 = ml•kg−1•min−1) was measured through a mask by a portable gas analyzer and MET values were calculated as measured VO2/3.5 ml•kg−1•min−1. Values were compared to both normative values and between participants with and without mobility impairments. RESULTS Compared to the established normative criteria, measured METs were different in 14 of 17 tasks performed. Compared to measured METs, normative values underestimated walking leisurely (0.87 ± 0.12 METs) walking briskly (0.87 ± 0.12 METs ), and bed making (1.07 ± 0.10 METs ), but overestimated gardening (1.46 ± 0.12 METs) and climbing stairs (0.73 ± 0.18). Participants with impairments had significantly lower METs while gardening, vacuuming/sweeping, stair climbing, and walking briskly. However, when METs were adjusted for performance speed the metabolic costs were 16–27% higher for those with mobility impairments. CONCLUSION Compared to normative values, metabolic costs of daily activities are substantially different in older adults and having mobility impairments increases this metabolic cost. These results may have implications for practitioners to appropriately prescribe daily physical activities for healthy and mobility impaired older adults. PMID:22091979

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

    PubMed

    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

  19. 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

  20. 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…

  1. Mitochondrial impairment by PPAR agonists and statins identified via immunocaptured OXPHOS complex activities and respiration.

    PubMed

    Nadanaciva, Sashi; Dykens, James A; Bernal, Autumn; Capaldi, Roderick A; Will, Yvonne

    2007-09-15

    Mitochondrial impairment is increasingly implicated in the etiology of toxicity caused by some thiazolidinediones, fibrates, and statins. We examined the effects of members of these drug classes on respiration of isolated rat liver mitochondria using a phosphorescent oxygen sensitive probe and on the activity of individual oxidative phosphorylation (OXPHOS) complexes using a recently developed immunocapture technique. Of the six thiazolidinediones examined, ciglitazone, troglitazone, and darglitazone potently disrupted mitochondrial respiration. In accord with these data, ciglitazone and troglitazone were also potent inhibitors of Complexes II+III, IV, and V, while darglitazone predominantly inhibited Complex IV. Of the six statins evaluated, lovastatin, simvastatin, and cerivastatin impaired mitochondrial respiration the most, with simvastatin and lovastatin impairing multiple OXPHOS Complexes. Within the class of fibrates, gemfibrozil more potently impaired respiration than fenofibrate, clofibrate, or ciprofibrate. Gemfibrozil only modestly inhibited Complex I, fenofibrate inhibited Complexes I, II+III, and V, and clofibrate inhibited Complex V. Our findings with the two complementary methods indicate that (1) some members of each class impair mitochondrial respiration, whereas others have little or no effect, and (2) the rank order of mitochondrial impairment accords with clinical adverse events observed with these drugs. Since the statins are frequently co-prescribed with the fibrates or thiazolidinediones, various combinations of these three drug classes were also analyzed for their mitochondrial effects. In several cases, the combination additively uncoupled or inhibited respiration, suggesting that some combinations are more likely to yield clinically relevant drug-induced mitochondrial side effects than others. PMID:17658574

  2. Mitochondrial impairment by PPAR agonists and statins identified via immunocaptured OXPHOS complex activities and respiration

    SciTech Connect

    Nadanaciva, Sashi; Dykens, James A.; Bernal, Autumn; Capaldi, Roderick A.; Will, Yvonne

    2007-09-15

    Mitochondrial impairment is increasingly implicated in the etiology of toxicity caused by some thiazolidinediones, fibrates, and statins. We examined the effects of members of these drug classes on respiration of isolated rat liver mitochondria using a phosphorescent oxygen sensitive probe and on the activity of individual oxidative phosphorylation (OXPHOS) complexes using a recently developed immunocapture technique. Of the six thiazolidinediones examined, ciglitazone, troglitazone, and darglitazone potently disrupted mitochondrial respiration. In accord with these data, ciglitazone and troglitazone were also potent inhibitors of Complexes II + III, IV, and V, while darglitazone predominantly inhibited Complex IV. Of the six statins evaluated, lovastatin, simvastatin, and cerivastatin impaired mitochondrial respiration the most, with simvastatin and lovastatin impairing multiple OXPHOS Complexes. Within the class of fibrates, gemfibrozil more potently impaired respiration than fenofibrate, clofibrate, or ciprofibrate. Gemfibrozil only modestly inhibited Complex I, fenofibrate inhibited Complexes I, II + III, and V, and clofibrate inhibited Complex V. Our findings with the two complementary methods indicate that (1) some members of each class impair mitochondrial respiration, whereas others have little or no effect, and (2) the rank order of mitochondrial impairment accords with clinical adverse events observed with these drugs. Since the statins are frequently co-prescribed with the fibrates or thiazolidinediones, various combinations of these three drug classes were also analyzed for their mitochondrial effects. In several cases, the combination additively uncoupled or inhibited respiration, suggesting that some combinations are more likely to yield clinically relevant drug-induced mitochondrial side effects than others.

  3. 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...

  4. 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…

  5. Reliability and Validity of the Self- and Interviewer-Administered Versions of the Global Physical Activity Questionnaire (GPAQ)

    PubMed Central

    Chu, Anne H. Y.; Ng, Sheryl H. X.; Koh, David; Müller-Riemenschneider, Falk

    2015-01-01

    Objective The Global Physical Activity Questionnaire (GPAQ) was originally designed to be interviewer-administered by the World Health Organization in assessing physical activity. The main aim of this study was to compare the psychometric properties of a self-administered GPAQ with the original interviewer-administered approach. Additionally, this study explored whether using different accelerometry-based physical activity bout definitions might affect the questionnaire’s validity. Methods A total of 110 participants were recruited and randomly allocated to an interviewer- (n = 56) or a self-administered (n = 54) group for test-retest reliability, of which 108 participants who met the wear time criteria were included in the validity study. Reliability was assessed by administration of questionnaires twice with a one-week interval. Criterion validity was assessed by comparing against seven-day accelerometer measures. Two definitions for accelerometry-data scoring were employed: (1) total-min of activity, and (2) 10-min bout. Results Participants had similar baseline characteristics in both administration groups and no significant difference was found between the two formats in terms of validity (correlations between the GPAQ and accelerometer). For validity, the GPAQ demonstrated fair-to-moderate correlations for moderate-to-vigorous physical activity (MVPA) for self-administration (rs = 0.30) and interviewer-administration (rs = 0.46). Findings were similar when considering 10-min activity bouts in the accelerometer analysis for MVPA (rs = 0.29 vs. 0.42 for self vs. interviewer). Within each mode of administration, the strongest correlations were observed for vigorous-intensity activity. However, Bland-Altman plots illustrated bias toward overestimation for higher levels of MVPA, vigorous- and moderate-intensity activities, and underestimation for lower levels of these measures. Reliability for MVPA revealed moderate correlations (rs = 0.61 vs. 0.63 for self vs

  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. PMID:25613020

  7. Impaired consciousness in temporal lobe seizures: role of cortical slow activity

    PubMed Central

    Englot, Dario J.; Yang, Li; Hamid, Hamada; Danielson, Nathan; Bai, Xiaoxiao; Marfeo, Anthony; Yu, Lissa; Gordon, Aliza; Purcaro, Michael J.; Motelow, Joshua E.; Agarwal, Ravi; Ellens, Damien J.; Golomb, Julie D.; Shamy, Michel C. F.; Zhang, Heping; Carlson, Chad; Doyle, Werner; Devinsky, Orrin; Vives, Kenneth; Spencer, Dennis D.; Spencer, Susan S.; Schevon, Catherine; Zaveri, Hitten P.

    2010-01-01

    Impaired consciousness requires altered cortical function. This can occur either directly from disorders that impair widespread bilateral regions of the cortex or indirectly through effects on subcortical arousal systems. It has therefore long been puzzling why focal temporal lobe seizures so often impair consciousness. Early work suggested that altered consciousness may occur with bilateral or dominant temporal lobe seizure involvement. However, other bilateral temporal lobe disorders do not impair consciousness. More recent work supports a ‘network inhibition hypothesis’ in which temporal lobe seizures disrupt brainstem–diencephalic arousal systems, leading indirectly to depressed cortical function and impaired consciousness. Indeed, prior studies show subcortical involvement in temporal lobe seizures and bilateral frontoparietal slow wave activity on intracranial electroencephalography. However, the relationships between frontoparietal slow waves and impaired consciousness and between cortical slowing and fast seizure activity have not been directly investigated. We analysed intracranial electroencephalography recordings during 63 partial seizures in 26 patients with surgically confirmed mesial temporal lobe epilepsy. Behavioural responsiveness was determined based on blinded review of video during seizures and classified as impaired (complex-partial seizures) or unimpaired (simple-partial seizures). We observed significantly increased delta-range 1–2 Hz slow wave activity in the bilateral frontal and parietal neocortices during complex-partial compared with simple-partial seizures. In addition, we confirmed prior work suggesting that propagation of unilateral mesial temporal fast seizure activity to the bilateral temporal lobes was significantly greater in complex-partial than in simple-partial seizures. Interestingly, we found that the signal power of frontoparietal slow wave activity was significantly correlated with the temporal lobe fast seizure

  8. Impaired consciousness in temporal lobe seizures: role of cortical slow activity.

    PubMed

    Englot, Dario J; Yang, Li; Hamid, Hamada; Danielson, Nathan; Bai, Xiaoxiao; Marfeo, Anthony; Yu, Lissa; Gordon, Aliza; Purcaro, Michael J; Motelow, Joshua E; Agarwal, Ravi; Ellens, Damien J; Golomb, Julie D; Shamy, Michel C F; Zhang, Heping; Carlson, Chad; Doyle, Werner; Devinsky, Orrin; Vives, Kenneth; Spencer, Dennis D; Spencer, Susan S; Schevon, Catherine; Zaveri, Hitten P; Blumenfeld, Hal

    2010-12-01

    Impaired consciousness requires altered cortical function. This can occur either directly from disorders that impair widespread bilateral regions of the cortex or indirectly through effects on subcortical arousal systems. It has therefore long been puzzling why focal temporal lobe seizures so often impair consciousness. Early work suggested that altered consciousness may occur with bilateral or dominant temporal lobe seizure involvement. However, other bilateral temporal lobe disorders do not impair consciousness. More recent work supports a 'network inhibition hypothesis' in which temporal lobe seizures disrupt brainstem-diencephalic arousal systems, leading indirectly to depressed cortical function and impaired consciousness. Indeed, prior studies show subcortical involvement in temporal lobe seizures and bilateral frontoparietal slow wave activity on intracranial electroencephalography. However, the relationships between frontoparietal slow waves and impaired consciousness and between cortical slowing and fast seizure activity have not been directly investigated. We analysed intracranial electroencephalography recordings during 63 partial seizures in 26 patients with surgically confirmed mesial temporal lobe epilepsy. Behavioural responsiveness was determined based on blinded review of video during seizures and classified as impaired (complex-partial seizures) or unimpaired (simple-partial seizures). We observed significantly increased delta-range 1-2 Hz slow wave activity in the bilateral frontal and parietal neocortices during complex-partial compared with simple-partial seizures. In addition, we confirmed prior work suggesting that propagation of unilateral mesial temporal fast seizure activity to the bilateral temporal lobes was significantly greater in complex-partial than in simple-partial seizures. Interestingly, we found that the signal power of frontoparietal slow wave activity was significantly correlated with the temporal lobe fast seizure activity in

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

    PubMed Central

    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

    2016-01-01

    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. PMID:26218293

  10. How Pupils with Severe Visual Impairment Describe Coping with Reading Activities in the Norwegian Inclusive School

    ERIC Educational Resources Information Center

    Vik, Astrid Kristin; Lassen, Liv M.

    2010-01-01

    This article explores how 11 pupils with severe visual impairment cope with reading activities in inclusive Norwegian schools. All pupils received instruction in braille and print, and used an audio-text format. Having multiple reading options provided possibilities for pupils to achieve reading skills, but also generated stress. Theories of…

  11. 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

  12. Abnormal intrinsic brain activity patterns in leukoaraiosis with and without cognitive impairment.

    PubMed

    Li, Chuanming; Yang, Jun; Yin, Xuntao; Liu, Chen; Zhang, Lin; Zhang, Xiaochun; Gui, Li; Wang, Jian

    2015-10-01

    The amplitude of low frequency fluctuations (ALFF) from resting-state functional MRI (rs-fMRI) signals can be used to detect intrinsic spontaneous brain activity and provide valuable insights into the pathomechanism of neural disease. In this study, we recruited 56 patients who had been diagnosed as having mild to severe leukoaraiosis. According to the neuropsychological tests, they were subdivided into a leukoaraiosis with cognitive impairment group (n = 28) and a leukoaraiosis without cognitive impairment group (n = 28). 28 volunteers were included as normal controls. We found that the three groups showed significant differences in ALFF in the brain regions of the right inferior occipital gyrus (IOG_R), left middle temporal gyrus (MTG_L), left precuneus (Pcu_L), right superior frontal gyrus (SFG_R) and right superior occipital gyrus (SOG_R). Compared with normal controls, the leukoaraiosis without cognitive impairment group exhibited significantly increased ALFF in the IOG_R, Pcu_L, SFG_R and SOG_R. While compared with leukoaraiosis without cognitive impairment group, the leukoaraiosis with cognitive impairment group showed significantly decreased ALFF in IOG_R, MTG_L, Pcu_L and SOG_R. A close negative correlation was found between the ALFF values of the MTG_L and the Montreal Cognitive Assessment (MoCA) scores. Our data demonstrate that white matter integrity and cognitive impairment are associated with different amplitude fluctuations of rs-fMRI signals. Leukoaraiosis is related to ALFF increases in IOG_R, Pcu_L, SFG_Orb_R and SOG_R. Decreased ALFF in MTG_L is characteristic of cognitive impairment and may aid in its early detection. PMID:26116811

  13. Impaired Macrophage Migration Inhibitory Factor (MIF)-AMPK Activation and Ischemic Recovery in the Senescent Heart

    PubMed Central

    Ma, Heng; Wang, Jingying; Thomas, D Paul; Tong, Chao; Leng, Lin; Wang, Wenkui; Merk, Melanie; Zierow, Swen; Bernhagen, Jürgen; Ren, Jun; Bucala, Richard; Li, Ji

    2010-01-01

    Background Elderly patients are more sensitive to myocardial ischemia, which results in higher mortality. We investigated how aging impacts the cardioprotective AMP-activated protein kinase (AMPK) signaling pathway. Methods and Results Ischemic AMPK activation was impaired in aged compared to young murine hearts. The expression and secretion of the AMPK upstream regulator, macrophage migration inhibitory factor (MIF), were lower in aged compared to young adult hearts. Additionally, the levels of hypoxia-inducible factor 1α (HIF-1α), a known transcriptional activator of MIF, were reduced in aged compared to young hearts. Ischemia-induced AMPK activation in MIF knock-out (MIF KO) mice was blunted, leading to greater contractile dysfunction in MIF-deficient than in wild type (WT) hearts. Furthermore, intra-myocardial injection of adenovirus encoding MIF (Adv-MIF) in aged mice increased MIF expression and ischemic AMPK activation, and reduced infarct size. Conclusions An impaired MIF-AMPK activation response in senescence thus may be attributed to an aging-associated defect in the transcription factor for MIF, HIF-1α. In the clinical setting, impaired cardiac HIF-1α activation and consequent reduced MIF expression may play an important role in the increased susceptibility to myocardial ischemia observed in older cardiac patients. PMID:20606117

  14. Serotonin impairs copulation and attenuates ejaculation-induced glutamate activity in the medial preoptic area.

    PubMed

    Dominguez, Juan M; Hull, Elaine M

    2010-08-01

    The medial preoptic area (MPOA) is critical for male sexual behavior. Glutamate is released in the MPOA of male rats during copulation, and increasing glutamate levels by reverse dialysis of glutamate uptake inhibitors facilitates mating. Conversely, increased release of serotonin (5-HT) inhibits sexual behavior. In both rats and men, selective serotonin reuptake inhibitors (SSRIs) impair erection, ejaculation, and libido. Here we reverse-dialyzed 5-HT through concentric microdialysis probes in the MPOA of male rats; concurrently we collected 2-min samples for analysis of glutamate and measured sexual behavior. Sexual activity, and especially ejaculation, increased levels of glutamate in the MPOA. However, reverse dialysis of 5-HT into the MPOA impaired ejaculatory ability and attenuated glutamate release. Implications of these results for impairment of sexual behavior that results from administration of SSRIs are discussed. PMID:20695654

  15. Aging Impairs Interferon Regulatory Factor 7 Upregulation in Plasmacytoid DCs during TLR9 Activation

    PubMed Central

    Stout-Delgado, Heather W.; Yang, Xin; Walker, Wendy E.; Tesar, Bethany M.; Goldstein, Daniel R.

    2008-01-01

    Plasmacytoid dendritic cells (pDCs) are innate sensors that produce IFN-α in response to viral infections. Determining how aging alters the cellular and molecular function of these cells may provide an explanation of increased susceptibility of older people to viral infections. Hence, we examined whether aging critically impairs pDC function during infection with herpes simplex virus type 2 (HSV-2), a viral pathogen that activates TLR9. We found that impaired IFN-α production by aged murine pDCs led to impaired viral clearance with aging. Upon TLR9 activation, aged pDCs displayed defective upregulation of interferon regulatory factor 7 (IRF-7), a key adaptor in the type I IFN pathway, as compared to younger counterparts. Aged pDCs had more oxidative stress, and reducing oxidative stress in aged pDCs partly recovered the age-induced IFN-α defect during TLR9 activation. In sum, aging impairs the type I IFN pathway in pDCs, and this alteration may contribute to the increased susceptibility of older people to certain viral infections. PMID:18981092

  16. Vision of the active limb impairs bimanual motor tracking in young and older adults

    PubMed Central

    Boisgontier, Matthieu P.; Van Halewyck, Florian; Corporaal, Sharissa H. A.; Willacker, Lina; Van Den Bergh, Veerle; Beets, Iseult A. M.; Levin, Oron; Swinnen, Stephan P.

    2014-01-01

    Despite the intensive investigation of bimanual coordination, it remains unclear how directing vision toward either limb influences performance, and whether this influence is affected by age. To examine these questions, we assessed the performance of young and older adults on a bimanual tracking task in which they matched motor-driven movements of their right hand (passive limb) with their left hand (active limb) according to in-phase and anti-phase patterns. Performance in six visual conditions involving central vision, and/or peripheral vision of the active and/or passive limb was compared to performance in a no vision condition. Results indicated that directing central vision to the active limb consistently impaired performance, with higher impairment in older than young adults. Conversely, directing central vision to the passive limb improved performance in young adults, but less consistently in older adults. In conditions involving central vision of one limb and peripheral vision of the other limb, similar effects were found to those for conditions involving central vision of one limb only. Peripheral vision alone resulted in similar or impaired performance compared to the no vision (NV) condition. These results indicate that the locus of visual attention is critical for bimanual motor control in young and older adults, with older adults being either more impaired or less able to benefit from a given visual condition. PMID:25452727

  17. Involvement of microglia activation in the lead induced long-term potentiation impairment.

    PubMed

    Liu, Ming-Chao; Liu, Xin-Qin; Wang, Wen; Shen, Xue-Feng; Che, Hong-Lei; Guo, Yan-Yan; Zhao, Ming-Gao; Chen, Jing-Yuan; Luo, Wen-Jing

    2012-01-01

    Exposure of Lead (Pb), a known neurotoxicant, can impair spatial learning and memory probably via impairing the hippocampal long-term potentiation (LTP) as well as hippocampal neuronal injury. Activation of hippocampal microglia also impairs spatial learning and memory. Thus, we raised the hypothesis that activation of microglia is involved in the Pb exposure induced hippocampal LTP impairment and neuronal injury. To test this hypothesis and clarify its underlying mechanisms, we investigated the Pb-exposure on the microglia activation, cytokine release, hippocampal LTP level as well as neuronal injury in in vivo or in vitro model. The changes of these parameters were also observed after pretreatment with minocycline, a microglia activation inhibitor. Long-term low dose Pb exposure (100 ppm for 8 weeks) caused significant reduction of LTP in acute slice preparations, meanwhile, such treatment also significantly increased hippocampal microglia activation as well as neuronal injury. In vitro Pb-exposure also induced significantly increase of microglia activation, up-regulate the release of cytokines including tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β) and inducible nitric oxide synthase (iNOS) in microglia culture alone as well as neuronal injury in the co-culture with hippocampal neurons. Inhibiting the microglia activation with minocycline significantly reversed the above-mentioned Pb-exposure induced changes. Our results showed that Pb can cause microglia activation, which can up-regulate the level of IL-1β, TNF-α and iNOS, these proinflammatory factors may cause hippocampal neuronal injury as well as LTP deficits. PMID:22952811

  18. The short international physical activity questionnaire: cross-cultural adaptation, validation and reliability of the Hausa language version in Nigeria

    PubMed Central

    2011-01-01

    Background Accurate assessment of physical activity is important in determining the risk for chronic diseases such as cardiovascular disease, stroke, type 2 diabetes, cancer and obesity. The absence of culturally relevant measures in indigenous languages could pose challenges to epidemiological studies on physical activity in developing countries. The purpose of this study was to translate and cross-culturally adapt the Short International Physical Activity Questionnaire (IPAQ-SF) to the Hausa language, and to evaluate the validity and reliability of the Hausa version of IPAQ-SF in Nigeria. Methods The English IPAQ-SF was translated into the Hausa language, synthesized, back translated, and subsequently subjected to expert committee review and pre-testing. The final product (Hausa IPAQ-SF) was tested in a cross-sectional study for concurrent (correlation with the English version) and construct validity, and test-retest reliability in a sample of 102 apparently healthy adults. Results The Hausa IPAQ-SF has good concurrent validity with Spearman correlation coefficients (ρ) ranging from 0.78 for vigorous activity (Min Week-1) to 0.92 for total physical activity (Metabolic Equivalent of Task [MET]-Min Week-1), but poor construct validity, with cardiorespiratory fitness (ρ = 0.21, p = 0.01) and body mass index (ρ = 0.22, p = 0.04) significantly correlated with only moderate activity and sitting time (Min Week-1), respectively. Reliability was good for vigorous (ICC = 0.73, 95% C.I = 0.55-0.84) and total physical activity (ICC = 0.61, 95% C.I = 0.47-0.72), but fair for moderate activity (ICC = 0.33, 95% C.I = 0.12-0.51), and few meaningful differences were found in the gender and socioeconomic status specific analyses. Conclusions The Hausa IPAQ-SF has acceptable concurrent validity and test-retest reliability for vigorous-intensity activity, walking, sitting and total physical activity, but demonstrated only fair construct validity for moderate and sitting

  19. 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. PMID:27092470

  20. Anhedonia in the psychosis risk syndrome: associations with social impairment and basal orbitofrontal cortical activity

    PubMed Central

    Cressman, Victoria L; Schobel, Scott A; Steinfeld, Sara; Ben-David, Shelly; Thompson, Judy L; Small, Scott A; Moore, Holly; Corcoran, Cheryl M

    2015-01-01

    Background/Objectives: Anhedonia is associated with poor social function in schizophrenia. Here, we examined this association in individuals at clinical high risk (CHR) for schizophrenia and related psychotic disorders, taking into account social anxiety. We then explored correlations between anhedonia and basal metabolic activity in selected forebrain regions implicated in reward processing. Methods: In 62 CHR individuals and 37 healthy controls, we measured social adjustment (Social Adjustment Self-Report Scale), social and physical anhedonia (Chapman Revised Anhedonia Scales), and social anxiety (Social Anxiety Scale for Adolescents) in cross-section. In a subgroup of 25 CHR individuals for whom high-spatial-resolution basal-state functional magnetic resonance imaging data were available, we also assessed correlations of these socio-affective constructs with basal cerebral blood volume in orbitofrontal cortex and related regions involved in reward processing. Results: Relative to controls, CHR individuals reported social impairment, greater social and physical anhedonia, and more social anxiety, exhibiting impairments comparable to schizophrenia. Regression analyses showed that anhedonia predicted social impairment and correlated negatively with basal cerebral blood volume within the orbitofrontal cortex (all P’s<0.05). Conclusions: Anhedonia and social anxiety are prominent in CHR individuals. Trait-like anhedonia may be a core phenotype related to orbitofrontal cortical function that, independent of symptoms, predicts social impairment. These data provide a rationale for interventions that target anhedonia and related activity in orbitofrontal cortical circuits in CHR individuals. PMID:27336033

  1. Development of an instrument for measuring activities of daily living in persons with suspected cognitive impairment.

    PubMed

    Johansson, Maria M; Marcusson, Jan; Wressle, Ewa

    2016-05-01

    Background According to the Swedish National Board of Health and Welfare, structured assessment of function and activity has high priority when evaluating suspected cognitive impairment or dementia. Aim/objectives The aim was to develop and psychometrically test an instrument to measure the ability to perform activities of daily living tasks in patients with suspected cognitive impairment. Material and methods The Cognitive Impairment in Daily Life (CID) instrument (for self-reported and informant-based assessments) has been developed in several phases. Content validity was achieved through five expert panels using a Content Validity Index (CVI). The content was tested further in a pilot study of 49 patients and 49 relatives from primary care or a specialist memory clinic. Results Content validity was good with a CVI index of 0.83. All patients considered that the included activities were relevant to them and reflected the difficulties they were experiencing. Most relatives considered the activities included in the instrument as adequate and captured the patients' difficulties in daily life. Some adjustments of the tasks and scale were suggested and these were implicated after each phase. In general, relatives reported that patients had more difficulties performing the activities than the patients reported themselves. Conclusion The CID instrument seems promising in terms of content validity. Further testing of reliability and construct validity is ongoing. PMID:26853384

  2. The Perceived Deficits Questionnaire

    PubMed Central

    Binder, Allison; Nikelshpur, Olga M.; Chiaravalloti, Nancy; DeLuca, John

    2016-01-01

    Background: Cognitive dysfunction affects approximately 43% to 70% of individuals with multiple sclerosis (MS) and is an important determinant of several functional outcomes in MS and quality of life. Brief neuropsychological test batteries have been developed specifically for use in MS and are widely used to aid clinicians in assessing levels of cognitive impairment in MS. Neuropsychologists and neurologists also frequently use briefer screening measures, such as the Perceived Deficits Questionnaire (PDQ), to assist in determining whether a more extensive neuropsychological evaluation is warranted. However, despite the ease of such measures, the relationship between self-report and objective cognitive impairment has been inconsistent, at best. Moreover, factors such as depression, fatigue, anxiety, and personality have been found to be more related to reports of cognitive difficulties. The purpose of the present study was to clarify the relationship between subjective cognitive concerns and objective cognitive impairment while accounting for related symptoms. Methods: We examined the association of self-reported cognitive concerns on the PDQ with objective cognitive measures, as well as depression, anxiety, fatigue, and self-efficacy. Results: There was no relationship between self-reported cognitive concerns and objective performance. Rather, reports on the PDQ were more correlated with reports of depression, anxiety, fatigue, and self-efficacy. Conclusions: Depression and poor self-efficacy can contribute to reports of cognitive difficulties. Effective treatment to improve these factors seems warranted given the impact of perceived cognitive impairment on outcomes in MS and the potential for more accurate self-reports. PMID:27551243

  3. 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

  4. Sexual Activity and Impairment in Women with Systemic Sclerosis Compared to Women from a General Population Sample

    PubMed Central

    Levis, Brooke; Burri, Andrea; Hudson, Marie; Baron, Murray; Thombs, Brett D.

    2012-01-01

    Objective Reports of low sexual activity rates and high impairment rates among women with chronic diseases have not included comparisons to general population data. The objective of this study was to compare sexual activity and impairment rates of women with systemic sclerosis (SSc) to general population data and to identify domains of sexual function driving impairment in SSc. Methods Canadian women with SSc were compared to women from a UK population sample. Sexual activity and, among sexually active women, sexual impairment were evaluated with a 9-item version of the Female Sexual Function Index (FSFI). Results Among women with SSc (mean age = 57.0 years), 296 of 730 (41%) were sexually active, 181 (61%) of whom were sexually impaired, resulting in 115 of 730 (16%) who were sexually active without impairment. In the UK population sample (mean age = 55.4 years), 956 of 1,498 women (64%) were sexually active, 420 (44%) of whom were impaired, with 536 of 1,498 (36%) sexually active without impairment. Adjusting for age and marital status, women with SSc were significantly less likely to be sexually active (OR = 0.34, 95%CI = 0.28–0.42) and, among sexually active women, significantly more likely to be sexually impaired (OR = 1.88, 95%CI = 1.42–2.49) than general population women. Controlling for total FSFI scores, women with SSc had significantly worse lubrication and pain scores than general population women. Conclusions Sexual functioning is a problem for many women with scleroderma and is associated with pain and poor lubrication. Evidence-based interventions to support sexual activity and function in women with SSc are needed. PMID:23251692

  5. Oxidized LDL impair adipocyte response to insulin by activating serine/threonine kinases.

    PubMed

    Scazzocchio, Beatrice; Varì, Rosaria; D'Archivio, Massimo; Santangelo, Carmela; Filesi, Carmelina; Giovannini, Claudio; Masella, Roberta

    2009-05-01

    Oxidized LDL (oxLDL) increase in patients affected by type-2 diabetes, obesity, and metabolic syndrome. Likewise, insulin resistance, an impaired responsiveness of target tissues to insulin, is associated with those pathological conditions. To investigate a possible causal relationship between oxLDL and the onset of insulin resistance, we evaluated the response to insulin of 3T3-L1 adipocytes treated with oxLDL. We observed that oxLDL inhibited glucose uptake (-40%) through reduced glucose transporter 4 (GLUT4) recruitment to the plasma membrane (-70%), without affecting GLUT4 gene expression. These findings were associated to the impairment of insulin signaling. Specifically, in oxLDL-treated cells insulin receptor (IR) substrate-1 (IRS-1) was highly degraded likely because of the enhanced Ser(307)phosphorylation. This process was largely mediated by the activation of the inhibitor of kappaB-kinase beta (IKKbeta) and the c-Jun NH(2)-terminal kinase (JNK). Moreover, the activation of IKKbeta positively regulated the nuclear content of nuclear factor kappaB (NF-kappaB), by inactivating the inhibitor of NF-kappaB (IkappaBalpha). The activated NF-kappaB further impaired per se GLUT4 functionality. Specific inhibitors of IKKbeta, JNK, and NF-kappaB restored insulin sensitivity in adipocytes treated with oxLDL. These data provide the first evidence that oxLDL, by activating serine/threonine kinases, impaired adipocyte response to insulin affecting pathways involved in the recruitment of GLUT4 to plasma membranes (PM). This suggests that oxLDL might participate in the development of insulin resistance. PMID:19136667

  6. Oxidized LDL impair adipocyte response to insulin by activating serine/threonine kinases

    PubMed Central

    Scazzocchio, Beatrice; Varì, Rosaria; D'Archivio, Massimo; Santangelo, Carmela; Filesi, Carmelina; Giovannini, Claudio; Masella, Roberta

    2009-01-01

    Oxidized LDL (oxLDL) increase in patients affected by type-2 diabetes, obesity, and metabolic syndrome. Likewise, insulin resistance, an impaired responsiveness of target tissues to insulin, is associated with those pathological conditions. To investigate a possible causal relationship between oxLDL and the onset of insulin resistance, we evaluated the response to insulin of 3T3-L1 adipocytes treated with oxLDL. We observed that oxLDL inhibited glucose uptake (−40%) through reduced glucose transporter 4 (GLUT4) recruitment to the plasma membrane (−70%), without affecting GLUT4 gene expression. These findings were associated to the impairment of insulin signaling. Specifically, in oxLDL-treated cells insulin receptor (IR) substrate-1 (IRS-1) was highly degraded likely because of the enhanced Ser307phosphorylation. This process was largely mediated by the activation of the inhibitor of κB-kinase β (IKKβ) and the c-Jun NH2-terminal kinase (JNK). Moreover, the activation of IKKβ positively regulated the nuclear content of nuclear factor κB (NF-κB), by inactivating the inhibitor of NF-κB (IκBα). The activated NF-κB further impaired per se GLUT4 functionality. Specific inhibitors of IKKβ, JNK, and NF-κB restored insulin sensitivity in adipocytes treated with oxLDL. These data provide the first evidence that oxLDL, by activating serine/threonine kinases, impaired adipocyte response to insulin affecting pathways involved in the recruitment of GLUT4 to plasma membranes (PM). This suggests that oxLDL might participate in the development of insulin resistance. PMID:19136667

  7. Intermonomer disulfide bonds impair the fusion activity of influenza virus hemagglutinin.

    PubMed Central

    Kemble, G W; Bodian, D L; Rosé, J; Wilson, I A; White, J M

    1992-01-01

    At a low pH, the influenza virus hemagglutinin (HA) undergoes conformational changes that promote membrane fusion. While the critical role of fusion peptide release from the trimer interface has been demonstrated previously, the role of globular head dissociation in the overall fusion mechanism remains unclear. To investigate this question, we have analyzed in detail the fusion activity and low pH-induced conformational changes of a mutant, Cys-HA, in which the globular head domains are locked together by engineered intermonomer disulfide bonds (L. Godley, J. Pfeifer, D. Steinhauer, B. Ely, G. Shaw, R. Kaufmann, E. Suchanek, C. Pabo, J. J. Skehel, D. C. Wiley, and S. Wharton, Cell 68:635-645, 1992). In this paper, we show that Cys-HA expressed on the cell surface is predominantly a disulfide-bonded trimer. Cell surface Cys-HA is impaired in its membrane fusion activity, as demonstrated by both content-mixing and lipid-mixing fusion assays. It is also impaired in its ability to change conformation at a low pH, as assessed by proteinase K sensitivity. The fusion activity and low pH-induced conformational changes of cell surface Cys-HA are, however, restored to nearly wild-type levels upon reduction of the intermonomer disulfide bonds. By using a set of conformation-specific monoclonal and anti-peptide antibodies, we found that purified Cys-HA trimers are impaired in changes that occur in the globular head domain interface. In addition, changes that occur at a great distance from the engineered intermonomer disulfide bonds, notably release of the fusion peptides, are also impaired. Our results are discussed with respect to current views of the fusion-active conformation of the HA trimer. Images PMID:1629960

  8. Clustering Home Activity Distributions for Automatic Detection of Mild Cognitive Impairment in Older Adults1

    PubMed Central

    Akl, Ahmad; Chikhaoui, Belkacem; Mattek, Nora; Kaye, Jeffrey; Austin, Daniel; Mihailidis, Alex

    2016-01-01

    The public health implications of growing numbers of older adults at risk for dementia places pressure on identifying dementia at its earliest stages so as to develop proactive management plans. The prodromal dementia phase commonly identified as mild cognitive impairment is an important target for this early detection of impending dementia amenable to treatment. In this paper, we propose a method for home-based automatic detection of mild cognitive impairment in older adults through continuous monitoring via unobtrusive sensing technologies. Our method is composed of two main stages: a training stage and a test stage. For training, room activity distributions are estimated for each subject using a time frame of ω weeks, and then affinity propagation is employed to cluster the activity distributions and to extract exemplars to represent the different emerging clusters. For testing, room activity distributions belonging to a test subject with unknown cognitive status are compared to the extracted exemplars and get assigned the labels of the exemplars that result in the smallest normalized Kullbak–Leibler divergence. The labels of the activity distributions are then used to determine the cognitive status of the test subject. Using the sensor and clinical data pertaining to 85 homes with single occupants, we were able to automatically detect mild cognitive impairment in older adults with an F0.5 score of 0.856. Also, we were able to detect the non-amnestic sub-type of mild cognitive impairment in older adults with an F0.5 score of 0.958.

  9. Hypoxia-Mediated Impairment of the Mitochondrial Respiratory Chain Inhibits the Bactericidal Activity of Macrophages

    PubMed Central

    Wiese, Melanie; Gerlach, Roman G.; Popp, Isabel; Matuszak, Jasmin; Mahapatro, Mousumi; Castiglione, Kirstin; Chakravortty, Dipshikha; Willam, Carsten; Hensel, Michael; Bogdan, Christian

    2012-01-01

    In infected tissues oxygen tensions are low. As innate immune cells have to operate under these conditions, we analyzed the ability of macrophages (Mϕ) to kill Escherichia coli or Staphylococcus aureus in a hypoxic microenvironment. Oxygen restriction did not promote intracellular bacterial growth but did impair the bactericidal activity of the host cells against both pathogens. This correlated with a decreased production of reactive oxygen intermediates (ROI) and reactive nitrogen intermediates. Experiments with phagocyte NADPH oxidase (PHOX) and inducible NO synthase (NOS2) double-deficient Mϕ revealed that in E. coli- or S. aureus-infected cells the reduced antibacterial activity during hypoxia was either entirely or partially independent of the diminished PHOX and NOS2 activity. Hypoxia impaired the mitochondrial activity of infected Mϕ. Inhibition of the mitochondrial respiratory chain activity during normoxia (using rotenone or antimycin A) completely or partially mimicked the defective antibacterial activity observed in hypoxic E. coli- or S. aureus-infected wild-type Mϕ, respectively. Accordingly, inhibition of the respiratory chain of S. aureus-infected, normoxic PHOX−/− NOS2−/− Mϕ further raised the bacterial burden of the cells, which reached the level measured in hypoxic PHOX−/− NOS2−/− Mϕ cultures. Our data demonstrate that the reduced killing of S. aureus or E. coli during hypoxia is not simply due to a lack of PHOX and NOS2 activity but partially or completely results from an impaired mitochondrial antibacterial effector function. Since pharmacological inhibition of the respiratory chain raised the generation of ROI but nevertheless phenocopied the effect of hypoxia, ROI can be excluded as the mechanism underlying the antimicrobial activity of mitochondria. PMID:22252868

  10. Reduced cholesterol levels impair Smoothened activation in Smith–Lemli–Opitz syndrome

    PubMed Central

    Blassberg, Robert; Macrae, James I.; Briscoe, James; Jacob, John

    2016-01-01

    Smith–Lemli–Opitz syndrome (SLOS) is a common autosomal-recessive disorder that results from mutations in the gene encoding the cholesterol biosynthetic enzyme 7-dehydrocholesterol reductase (DHCR7). Impaired DHCR7 function is associated with a spectrum of congenital malformations, intellectual impairment, epileptiform activity and autism spectrum disorder. Biochemically, there is a deficit in cholesterol and an accumulation of its metabolic precursor 7-dehydrocholesterol (7DHC) in developing tissues. Morphological abnormalities in SLOS resemble those seen in congenital Sonic Hedgehog (SHH)-deficient conditions, leading to the proposal that the pathogenesis of SLOS is mediated by aberrant SHH signalling. SHH signalling is transduced through the transmembrane protein Smoothened (SMO), which localizes to the primary cilium of a cell on activation and is both positively and negatively regulated by sterol molecules derived from cholesterol biosynthesis. One proposed mechanism of SLOS involves SMO dysregulation by altered sterol levels, but the salient sterol species has not been identified. Here, we clarify the relationship between disrupted cholesterol metabolism and reduced SHH signalling in SLOS by modelling the disorder in vitro. Our results indicate that a deficit in cholesterol, as opposed to an accumulation of 7DHC, impairs SMO activation and its localization to the primary cilium. PMID:26685159

  11. Neuronal activity topography parameters as a marker for differentiating vascular cognitive impairment in carotid stenosis.

    PubMed

    Shibata, Takashi; Musha, Toshimitu; Kubo, Michiya; Horie, Yukio; Asahi, Takashi; Kuwayama, Naoya; Kuroda, Satoshi; Hayashi, Karin; Kobayashi, Yohei; Tanaka, Mieko; Matsuzaki, Haruyasu; Asada, Takashi

    2014-10-01

    Previously, we reported on the differentiation between patients with Alzheimer disease and normal controls using a quantitative electroencephalographic technique called neuronal activity topography (NAT). In this technique, cerebral neuronal activities are characterized by the signal intensity and coherence (sNAT and vNAT, respectively). In the present study, we examined 47 patients with vascular cognitive impairment in carotid stenosis and 52 normal controls. All subjects underwent electroencephalography in a resting state with closed eyes for 5 minutes. Electroencephalographic markers of the differential likelihood, that is, the sensitivity-versus-specificity characteristics, sL(x:VCI-NLc) and vL(x:VCI-NLc), were assessed with neuronal activity topography and were compared between the 2 groups. sL(x:VCI-NLc) and vL(x:VCI-NLc) crossed each other at a cutoff value of the differential likelihood. Separation of the patients and controls was made with a sensitivity of 92% and 88%, as well as a false-positive rate of 8% and 12% for sL(x:VCI-NLc) and vL(x:VCI-NLc), respectively. Using sNAT, we accurately differentiated 92% patients with vascular cognitive impairment. We recommend that sNAT, rather than vNAT, should be used in detecting vascular cognitive impaired patients. PMID:25174560

  12. 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

  13. Treatment of Hypophosphatemic Rickets with Phosphate and Active Vitamin D in Japan: A Questionnaire-based Survey

    PubMed Central

    Fujiwara, Makoto; Namba, Noriyuki; Ozono, Keiichi; Arisaka, Osamu; Yokoya, Susumu

    2013-01-01

    Hereditary hypophosphatemic rickets represented by X-linked hypophosphatemic rickets (XLH) is a rare disorder characterized by hypophosphatemia, elevated alkaline phosphatase (ALP) and undermineralization of bone. Active vitamin D and phosphate are administered to correct hypophosphatemia and elevation of ALP. Overtreatment with phosphate leads to secondary hyperparathyroidism, and a large dose of active vitamin D has a risk of hypercalciuria. To understand the situation concerning treatment of patients with hereditary hypophosphatemic rickets in Japan, we conducted a questionnaire survey of pediatric endocrinologists. Answers were obtained from 53 out of 68 hospitals where the pediatric endocrinologists worked. One hundred and thirty-five patients were treated in 28 hospitals during November 2009 and May 2010; 126 patients suffered from hereditary hypophosphatemic rickets, and 9 had hypophosphatemia caused by other miscellaneous reasons. The distribution of patient age was as follows: 27 (21%) were between 6 mo and 6 yr of age, 39 (31%) were between 6 and 12 yr of age, and 60 (48%) were more than 12 yr of age. Active vitamin D was given to 123 patients, and phosphate was given to 106 patients. As for the dose of phosphorus, 37.2–58.1 mg/kg/d was given divided into 2 to 6 aliquots. There were various control targets of treatment, including serum phosphate, serum ALP, rachitic change, urinary Ca/Cr, parathyroid hormone and growth. It is very important to avoid side effects of these treatments. No evidence is available about the optimal dose of phosphate or number of administrations in the treatment of patients with hypophosphatemic rickets. Although there is a recommendation for clinical management of patients with hypophosphatemic rickets, we should set a clinical guideline for it in Japan. PMID:23966755

  14. BACE1 activity impairs neuronal glucose oxidation: rescue by beta-hydroxybutyrate and lipoic acid

    PubMed Central

    Findlay, John A.; Hamilton, David L.; Ashford, Michael L. J.

    2015-01-01

    Glucose hypometabolism and impaired mitochondrial function in neurons have been suggested to play early and perhaps causative roles in Alzheimer's disease (AD) pathogenesis. Activity of the aspartic acid protease, beta-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1), responsible for beta amyloid peptide generation, has recently been demonstrated to modify glucose metabolism. We therefore examined, using a human neuroblastoma (SH-SY5Y) cell line, whether increased BACE1 activity is responsible for a reduction in cellular glucose metabolism. Overexpression of active BACE1, but not a protease-dead mutant BACE1, protein in SH-SY5Y cells reduced glucose oxidation and the basal oxygen consumption rate, which was associated with a compensatory increase in glycolysis. Increased BACE1 activity had no effect on the mitochondrial electron transfer process but was found to diminish substrate delivery to the mitochondria by inhibition of key mitochondrial decarboxylation reaction enzymes. This BACE1 activity-dependent deficit in glucose oxidation was alleviated by the presence of beta hydroxybutyrate or α-lipoic acid. Consequently our data indicate that raised cellular BACE1 activity drives reduced glucose oxidation in a human neuronal cell line through impairments in the activity of specific tricarboxylic acid cycle enzymes. Because this bioenergetic deficit is recoverable by neutraceutical compounds we suggest that such agents, perhaps in conjunction with BACE1 inhibitors, may be an effective therapeutic strategy in the early-stage management or treatment of AD. PMID:26483636

  15. Functional impairment of activated protein C in breast cancer - relationship to survival outcomes

    PubMed Central

    Roselli, Mario; Ferroni, Patrizia; Riondino, Silvia; Mariotti, Sabrina; Portarena, Ilaria; Alessandroni, Jhessica; Ialongo, Cristiano; Massoud, Renato; Costarelli, Leopoldo; Cavaliere, Francesco; Bernardini, Sergio; Guadagni, Fiorella

    2016-01-01

    An impairment of the activated protein C (APC) system has been occasionally reported in breast cancer (BC). However, the clinical significance and prognostic value of an impaired APC functionality in BC patients is still poorly understood. Thus, the present study was aimed at investigating the prognostic value of altered APC functionality for progression-free (PFS) and overall survival (OS) in a cohort study of BC patients. APC functionality was retrospectively analyzed by a coagulation inhibition assay (ThromboPath) in 290 consecutive patients with primary (n=246) or relapsing/recurrent (n=44) BC. All patients were prospectively followed for a median time of 3.5 years (14% recurrence rate). As control group, 145 age-matched healthy women were also investigated. The results obtained demonstrated that APC function was impaired in roughly 20% of all BC at baseline. BC women with stage I/II had a significantly lower rate of APC impairment (13%) than women with stage III (22%) or distant metastases (44%, p=0.001). At univariate analyses, an impairment of APC function had a negative prognostic impact in terms of PFS (5-year PFS rates 53% vs. 70%; HR=2.5; p<0.001) and OS (5-year OS rates 79% vs. 93%; HR=3.9; p=0.005). However, prognostic significance was retained in multivariate models only for PFS (HR=2.0; p=0.017). We may, thus, conclude that BC patients are in a prothrombotic condition, which could play a role in the progression of the disease. Monitoring coagulation changes in BC women could provide important prognostic information especially in patients with advanced stages. PMID:27429857

  16. Mutation in E1, the Ubiquitin Activating Enzyme, Reduces Drosophila Lifespan and Results in Motor Impairment

    PubMed Central

    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. PMID:23382794

  17. 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

    2016-05-01

    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. PMID:27553398

  18. Memory impairment and alterations in prefrontal cortex gamma band activity following methamphetamine sensitization

    PubMed Central

    Linsenbardt, David N.; Lapish, Christopher C.

    2015-01-01

    Rationale Repeated methamphetamine (MA) use leads to increases in the incentive motivational properties of the drug as well as cognitive impairments. These behavioral alterations persist for some time following abstinence, and neuroadaptations in the structure and function of the prefrontal cortex (PFC) are particularly important for their expression. However, there is a weak understanding of the changes in neural firing and oscillatory activity in the PFC evoked by repeated drug use, thus complicating the development of novel treatment strategies for addiction. Objectives The purpose of the current study was to assess changes in cognitive and brain function following MA sensitization. Methods Sensitization was induced in rats, then temporal and recognition memory were assessed after 1 or 30 days of abstinence. Electrophysiological recordings from the medial PFC were also acquired from rats whereupon simultaneous measures of oscillatory and spiking activity were examined. Results Impaired temporal memory was observed after 1 and 30 days of abstinence. However, recognition memory was only impaired after 1 day of abstinence. An injection of MA profoundly decreased neuronal firing rate and the anesthesia-induced slow oscillation (SO) in both sensitized (SENS) and control (CTRL) rats. Strong correlations were observed between the SO and gamma band power, which was altered in SENS animals. A decrease in the number of neurons phase-locked to the gamma oscillation was also observed in SENS animals. Conclusions The changes observed in PFC function may play an integral role in the expression of the altered behavioral phenotype evoked by MA sensitization. PMID:25572530

  19. PPARγ activation prevents impairments in spatial memory and neurogenesis following transient illness

    PubMed Central

    Ormerod, Brandi K.; Hanft, Simon J.; Asokan, Aditya; Haditsch, Ursula; Lee, Star W.; Palmer, Theo D.

    2012-01-01

    The detrimental effects of illness on cognition are familiar to virtually everyone. Some effects resolve quickly while others may linger after the illness resolves. We found that a transient immune response stimulated by lipopolysaccharide (LPS) compromised hippocampal neurogenesis and impaired hippocampus-dependent spatial memory. The immune event caused a 50% reduction in the number of neurons generated during the illness and the onset of the memory impairment was delayed and coincided with the time when neurons generated during the illness would have become functional within the hippocampus. Broad spectrum non-steroidal anti-inflammatory drugs attenuated these effects but selective Cox-2 inhibition was ineffective while PPARγ activation was surprisingly effective at protecting both neurogenesis and memory from the effects of LPS-produced transient illness. These data may highlight novel mechanisms behind chronic inflammatory and neuroinflammatory episodes that are known to compromise hippocampus-dependent forms of learning and memory. PMID:23108061

  20. Reliability of the ALPHA environmental questionnaire and its association with physical activity in female fibromyalgia patients: the al-Ándalus project.

    PubMed

    Herrador-Colmenero, Manuel; Ruiz, Jonatan R; Ortega, Francisco B; Segura-Jiménez, Víctor; Álvarez-Gallardo, Inmaculada C; Camiletti-Moirón, Daniel; Estévez-López, Fernando; Delgado-Fernández, Manuel; Chillón, Palma

    2015-01-01

    Physical activity attenuates the symptoms of fibromyalgia, and its level is oftentimes associated with the perceived environment of fibromyalgia patients. Within this context, we aimed to study the reliability of the Spanish version of the Assessing Levels of Physical Activity (ALPHA) environmental questionnaire and the mode of commuting questionnaire. We also studied the association between the perceived environment and mode of commuting with physical activity levels among female fibromyalgia patients in Spain. Test-retest reliability was judged by the intra-class correlation coefficient (ICC), weighted kappa statistic, Spearman correlations and the proportion of agreement. We calculated bivariate Pearson's correlations between environmental sum scores and physical activity measured by both International Physical Activity Questionnaire (IPAQ) and accelerometry. More than 70% of the scales and items showed a good reliability regarding the ICC, the weighted kappa, the Spearman correlation and the percentage of inter-agreement (higher than 50%). The perceived environment assessed with the ALPHA showed a low correlation with both IPAQ and accelerometry. The Spanish version of the ALPHA environmental questionnaire proved to be reliable and showed a weak degree of association with physical activity in female fibromyalgia patients. PMID:25357996

  1. The Depression Coping Questionnaire.

    ERIC Educational Resources Information Center

    Kleinke, Chris L.

    College students (N=396), chronic pain patients (N=319), and schizophrenic veterans (N=43) completed the Depression Coping Questionnaire (DCQ) and the Beck Depression Inventory (BDI). Factor analysis of the DCQ identified eleven coping responses: social support, problem solving, self-blame/escape, aggression, indulgence, activities, medication,…

  2. Oxidative Stress Impairs the Stimulatory Effect of S100 Proteins on Protein Phosphatase 5 Activity.

    PubMed

    Yamaguchi, Fuminori; Tsuchiya, Mitsumasa; Shimamoto, Seiko; Fujimoto, Tomohito; Tokumitsu, Hiroshi; Tokuda, Masaaki; Kobayashi, Ryoji

    2016-01-01

    Oxidative stress is the consequence of an imbalance between the production of harmful reactive oxygen species and the cellular antioxidant system for neutralization, and it activates multiple intracellular signaling pathways, including apoptosis signal-regulating kinase 1 (ASK1). Protein phosphatase 5 (PP5) is a serine/threonine phosphatase involved in oxidative stress responses. Previously, we reported that S100 proteins activate PP5 in a calcium-dependent manner. S100 proteins belong to a family of small EF-hand calcium-binding proteins involved in many processes such as cell proliferation, differentiation, apoptosis, and inflammation. Therefore, we investigated the effects of oxidative stress on S100 proteins, their interaction with PP5, and PP5 enzyme activity. Recombinant S100A2 was easily air-oxidized or Cu-oxidized, and oxidized S100A2 formed cross-linked dimers and higher molecular-mass complexes. The binding of oxidized S100A2 to PP5 was reduced, resulting in decreased PP5 activation in vitro. Oxidation also impaired S100A1, S100A6, S100B, and S100P to activate PP5, although the low dose of oxidized S100 proteins still activated PP5. Hydrogen peroxide (H2O2) induced S100A2 oxidation in human keratinocytes (HaCaT) and human hepatocellular carcinoma (Huh-7) cells. Furthermore, H2O2 reduced the binding of S100A2 to PP5 and decreased PP5 activation in HaCaT and Huh-7 cells. Importantly, even the low dose of S100A2 achieved by knocking down increased dephosphorylation of ASK1 and reduced caspase 3/7 activity in Huh-7 cells treated with H2O2. These results indicate that oxidative stress impairs the ability of S100 proteins to bind and activate PP5, which in turn modulates the ASK1-mediated signaling cascades involved in apoptosis. PMID:27600583

  3. Reentrainment Impairs Spatial Working Memory until Both Activity Onset and Offset Reentrain.

    PubMed

    Ruby, Norman F; Patton, Danica F; Bane, Shalmali; Looi, David; Heller, H Craig

    2015-10-01

    Compression of the active phase (α) during reentrainment to phase-shifted light-dark (LD) cycles is a common feature of circadian systems, but its functional consequences have not been investigated. This study tested whether α compression in Siberian hamsters (Phodopus sungorus) impaired their spatial working memory as assessed by spontaneous alternation (SA) behavior in a T-maze. Animals were exposed to a 1- or 3-h phase delay of the LD cycle (16 h light/8 h dark). SA behavior was tested at 4 multiday intervals after the phase shift, and α was quantified for those days. All animals failed at the SA task while α was decompressing but recovered spatial memory ability once α returned to baseline levels. A second experiment exposed hamsters to a 2-h light pulse either early or late at night to compress α without phase-shifting the LD cycle. SA behavior was impaired until α decompressed to baseline levels. In a third experiment, α was compressed by changing photoperiod (LD 16:8, 18:6, 20:4) to see if absolute differences in α were related to spatial memory ability. Animals performed the SA task successfully in all 3 photoperiods. These data show that the dynamic process of α compression and decompression impairs spatial working memory and suggests that α modulation is a potential biomarker for assessing the impact of transmeridian flight or shift work on memory. PMID:26224657

  4. Daily Physical Activities and Sports in Adult Survivors of Childhood Cancer and Healthy Controls: A Population-Based Questionnaire Survey

    PubMed Central

    Rueegg, Corina S.; von der Weid, Nicolas X.; Rebholz, Cornelia E.; Michel, Gisela; Zwahlen, Marcel; Grotzer, Michael; Kuehni, Claudia E.

    2012-01-01

    Background Healthy lifestyle including sufficient physical activity may mitigate or prevent adverse long-term effects of childhood cancer. We described daily physical activities and sports in childhood cancer survivors and controls, and assessed determinants of both activity patterns. Methodology/Principal Findings The Swiss Childhood Cancer Survivor Study is a questionnaire survey including all children diagnosed with cancer 1976–2003 at age 0–15 years, registered in the Swiss Childhood Cancer Registry, who survived ≥5years and reached adulthood (≥20years). Controls came from the population-based Swiss Health Survey. We compared the two populations and determined risk factors for both outcomes in separate multivariable logistic regression models. The sample included 1058 survivors and 5593 controls (response rates 78% and 66%). Sufficient daily physical activities were reported by 52% (n = 521) of survivors and 37% (n = 2069) of controls (p<0.001). In contrast, 62% (n = 640) of survivors and 65% (n = 3635) of controls reported engaging in sports (p = 0.067). Risk factors for insufficient daily activities in both populations were: older age (OR for ≥35years: 1.5, 95CI 1.2–2.0), female gender (OR 1.6, 95CI 1.3–1.9), French/Italian Speaking (OR 1.4, 95CI 1.1–1.7), and higher education (OR for university education: 2.0, 95CI 1.5–2.6). Risk factors for no sports were: being a survivor (OR 1.3, 95CI 1.1–1.6), older age (OR for ≥35years: 1.4, 95CI 1.1–1.8), migration background (OR 1.5, 95CI 1.3–1.8), French/Italian speaking (OR 1.4, 95CI 1.2–1.7), lower education (OR for compulsory schooling only: 1.6, 95CI 1.2–2.2), being married (OR 1.7, 95CI 1.5–2.0), having children (OR 1.3, 95CI 1.4–1.9), obesity (OR 2.4, 95CI 1.7–3.3), and smoking (OR 1.7, 95CI 1.5–2.1). Type of diagnosis was only associated with sports. Conclusions/Significance Physical activity levels in survivors were lower than recommended, but

  5. Neuroblastoma arginase activity creates an immunosuppressive microenvironment that impairs autologous and engineered immunity

    PubMed Central

    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

    2015-01-01

    Neuroblastoma is the most common extra cranial solid tumour 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 tumour 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 TCR and GD2-specific CAR engineered T cell proliferation and cytotoxicity. High arginase II expression correlates with poor survival for neuroblastoma patients. The results support the hypothesis that neuroblastoma creates an arginase-dependent immunosuppressive microenvironment in both the tumour and blood that leads to impaired immune surveillance and sub-optimal efficacy of immunotherapeutic approaches. PMID:26054597

  6. 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

  7. Expression of CD39 on Activated T Cells Impairs their Survival in Older Individuals.

    PubMed

    Fang, Fengqin; Yu, Mingcan; Cavanagh, Mary M; Hutter Saunders, Jessica; Qi, Qian; Ye, Zhongde; Le Saux, Sabine; Sultan, William; Turgano, Emerson; Dekker, Cornelia L; Tian, Lu; Weyand, Cornelia M; Goronzy, Jörg J

    2016-02-01

    In an immune response, CD4(+) T cells expand into effector T cells and then contract to survive as long-lived memory cells. To identify age-associated defects in memory cell formation, we profiled activated CD4(+) T cells and found an increased induction of the ATPase CD39 with age. CD39(+) CD4(+) T cells resembled effector T cells with signs of metabolic stress and high susceptibility to undergo apoptosis. Pharmacological inhibition of ATPase activity dampened effector cell differentiation and improved survival, suggesting that CD39 activity influences T cell fate. Individuals carrying a low-expressing CD39 variant responded better to vaccination with an increase in vaccine-specific memory T cells. Increased inducibility of CD39 after activation may contribute to the impaired vaccine response with age. PMID:26832412

  8. Bipolar disorder course, impaired glucose metabolism and antioxidant enzymes activities: A preliminary report.

    PubMed

    Mansur, Rodrigo B; Rizzo, Lucas B; Santos, Camila M; Asevedo, Elson; Cunha, Graccielle R; Noto, Mariane N; Pedrini, Mariana; Zeni-Graiff, Maiara; Gouvea, Eduardo S; Cordeiro, Quirino; Reininghaus, Eva Z; McIntyre, Roger S; Brietzke, Elisa

    2016-09-01

    This study aimed to examine the role of oxidative stress in bipolar disorder (BD) by evaluating the relationship among antioxidant enzymes activities, impaired glucose metabolism (IGM) and illness course. We measured the activities of plasma superoxide dismutase (SOD) and glutathione peroxidase (GPx) in individuals with BD (N = 55) and healthy controls (N = 28). Information related to current and past psychiatric/medical history, as well as prescription of any pharmacological treatments was captured. Impaired glucose metabolism was operationalized as pre-diabetes or type 2 diabetes mellitus. Our results showed that, after adjustment for age, gender, alcohol use, smoking and current medication, both BD (p < 0.001) and IGM (p = 0.019) were associated with increased GPx activity, whereas only BD was associated with decreased SOD activity (p = 0.008). We also observed an interaction between BD and IGM on SOD activity (p = 0.017), whereas the difference between BD and controls was only significant in individuals with IGM (p = 0.009). IGM, GPx and SOD activity were independently associated with variables of illness course. Moreover, IGM moderated the association between SOD activity and number of mood episodes (p < 0.001), as a positive correlation between SOD activity and mood episodes was observed only in participants with IGM. In conclusion, BD and IGM are associated with independent and synergistic effects on markers of oxidative stress. The foregoing observations suggest that the heterogeneity observed in previous studies evaluating antioxidant enzymes in BD may be a function of concurrent IGM; and that imbalances in the oxidative system may subserve the association between BD and IGM, as well as its relationship with illness course. PMID:27281261

  9. Rubus coreanus Miquel Inhibits Acetylcholinesterase Activity and Prevents Cognitive Impairment in a Mouse Model of Dementia

    PubMed Central

    Kim, Cho Rong; Choi, Soo Jung; Oh, Seung Sang; Kwon, Yoon Kyung; Lee, Na Young; Park, Gwi Gun; Kim, Youn-Jung; Heo, Ho Jin; Jun, Woo Jin; Park, Cheung-Seog; Shin, Dong-Hoon

    2013-01-01

    Abstract To find acetylcholinesterase (AChE) inhibitors for the prevention of neurological disorders, such as Alzheimer's disease, ethanol extracts of promising traditional edible Korean plants were tested. Among them, Rubus coreanus Miquel extract exhibited the most significant AChE inhibitory activity. The effect of R. coreanus extract on trimethyltin-induced memory impairment in mice was investigated using Y-maze and passive avoidance tests. Our results showed that administration of R. coreanus extract significantly improved alternation behavior and step-through latency. In addition, R. coreanus extract was sequentially fractionated, and the purified constituent was determined to be 3,4,5-trihydroxybenzoic acid. PMID:24044488

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

    PubMed

    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 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. PMID:27434501

  11. 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

  12. 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. PMID:26577527

  13. 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

  14. 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

  15. Hyperglycemia induces memory impairment linked to increased acetylcholinesterase activity in zebrafish (Danio rerio).

    PubMed

    Capiotti, Katiucia Marques; De Moraes, Daiani Almeida; Menezes, Fabiano Peres; Kist, Luiza Wilges; Bogo, Maurício Reis; Da Silva, Rosane Souza

    2014-11-01

    Diabetes mellitus, which causes hyperglycemia, affects the central nervous system and can impairs cognitive functions, such as memory. The aim of this study was to investigate the effects of hyperglycemia on memory as well as on the activity of acethylcholinesterase. Hyperglycemia was induced in adult zebrafish by immersion in glucose 111mM by 14 days. The animals were divided in 4 groups: control, glucose-treated, glucose-washout 7-days and glucose-washout 14-days. We evaluated the performance in inhibitory avoidance task and locomotor activity. We also determined acethylcholinesterase activity and gene expression from whole brain. In order to counteract the effect of hyperglycemia underlined by effects on acethylcholinesterase activity, we treated the animals with galantamine (0.05ng/g), an inhibitor of this enzyme. Also we evaluated the gene expression of insulin receptor and glucose transporter from zebrafish brain. The hyperglycemia promoted memory deficit in adult zebrafish, which can be explained by increased AChE activity. The ache mRNA levels from zebrafish brain were decrease in 111mM glucose group and returned to normal levels after 7 days of glucose withdrawal. Insulin receptors (insra-1, insra-2, insrb-1 and insrb-2) and glut-3 mRNA levels were not significantly changed. Our results also demonstrated that galantamine was able to reverse the memory deficit caused by hyperglycemia, demonstrating that these effects involve modulation of AChE activity. These data suggest that the memory impairment induced by hyperglycemia is underlined by the cholinergic dysfunction caused by the mechanisms involving the control of acetylcholinesterase function and gene expression. PMID:25157430

  16. Compensatory elevation of voluntary activity in mouse mutants with impaired mitochondrial energy metabolism

    PubMed Central

    Lapointe, Jérôme; G. Hughes, Bryan; Bigras, Eve; Hekimi, Siegfried

    2014-01-01

    Abstract Mitochondria play a crucial role in determining whole‐body metabolism and exercise capacity. Genetic mouse models of mild mitochondrial dysfunction provide an opportunity to understand how mitochondrial function affects these parameters. MCLK1 (a.k.a. Coq7) is an enzyme implicated in the biosynthesis of ubiquinone (UQ; Coenzyme Q). Low levels of MCLK1 in Mclk1+/− heterozygous mutants lead to abnormal sub‐mitochondrial distribution of UQ, impaired mitochondrial function, elevated mitochondrial oxidative stress, and increased lifespan. Here, we report that young Mclk1+/− males, but not females, show a significant decrease in whole‐body metabolic rate as measured by indirect calorimetry. Such a sex‐specific effect of mitochondrial dysfunction on energy metabolism has also been reported for heterozygous mice carrying a mutation for the gene encoding the “Rieske” protein of mitochondrial complex III (RISP+/P224S). We find that both Mclk1+/− and RISP+/P224S males are capable of restoring their defective metabolic rates by making significantly more voluntary use of a running wheel compared to wild type. However, this increase in voluntary activity does not reflect their exercise capacity, which we found to be impaired as revealed by a shorter treadmill distance run before exhaustion. In contrast to what is observed in Mclk1+/− and RISP+/P224S mutants, Sod2+/− mice with elevated oxidative stress and major mitochondrial dysfunction did not increase voluntary activity. Our study reveals a sex‐specific effect on how impaired mitochondrial function impacts whole‐body energy metabolism and locomotory behavior, and contributes to the understanding of the metabolic and behavioral consequences of mitochondrial disorders. PMID:25413331

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

    PubMed

    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

  18. 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.

  19. 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

  20. Impaired Activity of Blood Coagulant Factor XIII in Patients with Necrotizing Enterocolitis

    PubMed Central

    Tao, Guo-Zhong; Liu, Bo; Zhang, Rong; Liu, Gigi; Abdullah, Fizan; Harris, Mary Cay; Brandt, Mary L.; Ehrenkranz, Richard A.; Bowers, Corinna; Martin, Camilia R.; Moss, R. Lawrence; Sylvester, Karl G.

    2015-01-01

    Necrotizing enterocolitis (NEC) is the most common gastrointestinal (GI) medical/surgical emergency of the newborn and a leading cause of preterm neonate morbidity and mortality. NEC is a challenge to diagnose since it often shares similar clinical features with neonatal sepsis. In the present study, plasma protein profiling was compared among NEC, sepsis and control cohorts using gel electrophoresis, immunoblot and mass spectrometry. We observed significant impairment in the formation of fibrinogen-γ dimers (FGG-dimer) in the plasma of newborns with NEC that could efficiently differentiate NEC and sepsis with a high level of sensitivity and specificity. Interestingly, the impaired FGG-dimer formation could be restored in NEC plasma by the addition of exogenous active factor XIII (FXIII). Enzymatic activity of FXIII was determined to be significantly lower in NEC subject plasma for crosslinking FGG when compared to sepsis. These findings demonstrate a potential novel biomarker and related biologic mechanism for diagnosing NEC, as well as suggest a possible therapeutic strategy. PMID:26277871

  1. Increased Intrathecal Immune Activation in Virally Suppressed HIV-1 Infected Patients with Neurocognitive Impairment

    PubMed Central

    Edén, Arvid; Marcotte, Thomas D.; Heaton, Robert K.; Nilsson, Staffan; Zetterberg, Henrik; Fuchs, Dietmar; Franklin, Donald; Price, Richard W.; Grant, Igor; Letendre, Scott L.; Gisslén, Magnus

    2016-01-01

    Objective Although milder forms of HIV-associated neurocognitive disorder (HAND) remain prevalent, a correlation to neuronal injury has not been established in patients on antiretroviral therapy (ART). We examined the relationship between mild HAND and CSF neurofilament light protein (NFL), a biomarker of neuronal injury; and CSF neopterin, a biomarker of CNS immunoactivation, in virally suppressed patients on antiretroviral therapy (ART). Design and Methods We selected 99 subjects on suppressive ART followed longitudinally from the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study. Based on standardized comprehensive neurocognitive performance (NP) testing, subjects were classified as neurocognitively normal (NCN; n = 29) or impaired (NCI; n = 70). The NCI group included subjects with asymptomatic (ANI; n = 37) or mild (MND; n = 33) HAND. CSF biomarkers were analyzed on two occasions. Results Geometric mean CSF neopterin was 25% higher in the NCI group (p = 0.04) and NFL and neopterin were significantly correlated within the NCI group (r = 0.30; p<0.001) but not in the NCN group (r = -0.13; p = 0.3). Additionally, a trend towards higher NFL was seen in the NCI group (p = 0.06). Conclusions Mild HAND was associated with increased intrathecal immune activation, and the correlation between neopterin and NFL found in NCI subjects indicates an association between neurocognitive impairment, CNS inflammation and neuronal damage. Together these findings suggest that NCI despite ART may represent an active pathological process within the CNS that needs further characterization in prospective studies. PMID:27295036

  2. 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

  3. Altered Brain Activities Associated with Neural Repetition Effects in Mild Cognitive Impairment Patients.

    PubMed

    Yu, Jing; Li, Rui; Jiang, Yang; Broster, Lucas S; Li, Juan

    2016-05-11

    Older adults with mild cognitive impairment (MCI) manifest impaired explicit memory. However, studies on implicit memory such as repetition effects in persons with MCI have been limited. In the present study, 17 MCI patients and 16 healthy normal controls (NC) completed a modified delayed-match-to-sample task while undergoing functional magnetic resonance imaging. We aim to examine the neural basis of repetition; specifically, to elucidate whether and how repetition-related brain responses are altered in participants with MCI. When repeatedly rejecting distracters, both NC and MCI showed similar behavioral repetition effects; however, in both whole-brain and region-of-interest analyses of functional data, persons with MCI showed reduced repetition-driven suppression in the middle occipital and middle frontal gyrus. Further, individual difference analysis found that activation in the left middle occipital gyrus was positively correlated with rejecting reaction time and negatively correlated with accuracy rate, suggesting a predictor of repetition behavioral performance. These findings provide new evidence to support the view that neural mechanisms of repetition effect are altered in MCI who manifests compensatory repetition-related brain activities along with their neuropathology. PMID:27176074

  4. 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

    2016-01-01

    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

  5. 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

  6. Vitamin C Attenuates Isoflurane-Induced Caspase-3 Activation and Cognitive Impairment.

    PubMed

    Cheng, Baiqi; Zhang, Yiying; Wang, Arthur; Dong, Yuanlin; Xie, Zhongcong

    2015-12-01

    Anesthetic isoflurane has been reported to induce caspase-3 activation. The underlying mechanism(s) and targeted intervention(s), however, remain largely to be determined. Vitamin C (VitC) inhibits oxidative stress and apoptosis. We therefore employed VitC to further determine the up-stream mechanisms and the down-stream consequences of the isoflurane-induced caspase-3 activation. H4 human neuroglioma cells overexpressed human amyloid precursor protein (H4-APP cells) and rat neuroblastoma cells were treated either with (1) 2% isoflurane or (2) with the control condition, plus saline or 400 μM VitC for 3 or 6 h. Western blot analysis and fluorescence assay were utilized at the end of the experiments to determine caspase-3 activation, levels of reactive oxygen species and ATP, and mitochondrial function. The interaction of isoflurane (1.4% for 2 h) and VitC (100 mg/kg) on cognitive function in mice was also assessed in the fear conditioning system. Here, we show for the first time that the VitC treatment attenuated the isoflurane-induced caspase-3 activation. Moreover, VitC mitigated the isoflurane-induced increases in the levels of reactive oxygen species, opening of mitochondrial permeability transition pore, reduction in mitochondrial membrane potential, and the reduction in ATP levels in the cells. Finally, VitC ameliorated the isoflurane-induced cognitive impairment in the mice. Pending confirmation from future studies, these results suggested that VitC attenuated the isoflurane-induced caspase-3 activation and cognitive impairment by inhibiting the isoflurane-induced oxidative stress, mitochondrial dysfunction, and reduction in ATP levels. These findings would promote further research into the underlying mechanisms and targeted interventions of anesthesia neurotoxicity. PMID:25367886

  7. 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. PMID:27230230

  8. Inhibition of Rac1 activity in the hippocampus impaired extinction of contextual fear.

    PubMed

    Jiang, Lizhu; Mao, Rongrong; Tong, Jianbin; Li, Jinnan; Chai, Anping; Zhou, Qixin; Yang, Yuexiong; Wang, Liping; Li, Lingjiang; Xu, Lin

    2016-10-01

    Promoting extinction of fear memory is the main treatment of fear disorders, especially post-traumatic stress disorder (PTSD). However, fear extinction is often incomplete in these patients. Our previous study had shown that Rac1 activity in hippocampus plays a crucial role in the learning of contextual fear memory in rats. Here, we further investigated whether Rac1 activity also modulated the extinction of contextual fear memory. We found that massed extinction obviously upregulated hippocampal Rac1 activity and induced long-term extinction of contextual fear in rats. Intrahippocampal injection of the Rac1 inhibitor NSC23766 prevents extinction of contextual fear in massed extinction training rats. In contrast, long-spaced extinction downregulated Rac1 activity and caused less extinction. And Rac1 activator CN04-A promotes extinction of contextual fear in long-spaced extinction rats. Our study demonstrates that inhibition of Rac1 activity in the hippocampus impaired extinction of contextual fear, suggesting that modulating Rac1 activity of the hippocampus may be promising therapy of fear disorders. PMID:27329554

  9. Reduced Cortical Activity Impairs Development and Plasticity after Neonatal Hypoxia Ischemia

    PubMed Central

    Ranasinghe, Sumudu; Or, Grace; Wang, Eric Y.; Ievins, Aiva; McLean, Merritt A.; Niell, Cristopher M.; Chau, Vann; Wong, Peter K. H.; Glass, Hannah C.; Sullivan, Joseph

    2015-01-01

    Survivors of preterm birth are at high risk of pervasive cognitive and learning impairments, suggesting disrupted early brain development. The limits of viability for preterm birth encompass the third trimester of pregnancy, a “precritical period” of activity-dependent development characterized by the onset of spontaneous and evoked patterned electrical activity that drives neuronal maturation and formation of cortical circuits. Reduced background activity on electroencephalogram (EEG) is a sensitive marker of brain injury in human preterm infants that predicts poor neurodevelopmental outcome. We studied a rodent model of very early hypoxic–ischemic brain injury to investigate effects of injury on both general background and specific patterns of cortical activity measured with EEG. EEG background activity is depressed transiently after moderate hypoxia–ischemia with associated loss of spindle bursts. Depressed activity, in turn, is associated with delayed expression of glutamate receptor subunits and transporters. Cortical pyramidal neurons show reduced dendrite development and spine formation. Complementing previous observations in this model of impaired visual cortical plasticity, we find reduced somatosensory whisker barrel plasticity. Finally, EEG recordings from human premature newborns with brain injury demonstrate similar depressed background activity and loss of bursts in the spindle frequency band. Together, these findings suggest that abnormal development after early brain injury may result in part from disruption of specific forms of brain activity necessary for activity-dependent circuit development. SIGNIFICANCE STATEMENT Preterm birth and term birth asphyxia result in brain injury from inadequate oxygen delivery and constitute a major and growing worldwide health problem. Poor outcomes are noted in a majority of very premature (<25 weeks gestation) newborns, resulting in death or life-long morbidity with motor, sensory, learning, behavioral

  10. Killing of Staphylococci by θ-Defensins Involves Membrane Impairment and Activation of Autolytic Enzymes

    PubMed Central

    Wilmes, Miriam; Stockem, Marina; Bierbaum, Gabriele; Schlag, Martin; Götz, Friedrich; Tran, Dat Q.; Schaal, Justin B.; Ouellette, André J.; Selsted, Michael E.; Sahl, Hans-Georg

    2014-01-01

    θ-Defensins are cyclic antimicrobial peptides expressed in leukocytes of Old world monkeys. To get insight into their antibacterial mode of action, we studied the activity of RTDs (rhesus macaque θ-defensins) against staphylococci. We found that in contrast to other defensins, RTDs do not interfere with peptidoglycan biosynthesis, but rather induce bacterial lysis in staphylococci by interaction with the bacterial membrane and/or release of cell wall lytic enzymes. Potassium efflux experiments and membrane potential measurements revealed that the membrane impairment by RTDs strongly depends on the energization of the membrane. In addition, RTD treatment caused the release of Atl-derived cell wall lytic enzymes probably by interaction with membrane-bound lipoteichoic acid. Thus, the premature and uncontrolled activity of these enzymes contributes strongly to the overall killing by θ-defensins. Interestingly, a similar mode of action has been described for Pep5, an antimicrobial peptide of bacterial origin. PMID:25632351

  11. 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

  12. PROKR2 missense mutations associated with Kallmann syndrome impair receptor signalling activity.

    PubMed

    Monnier, Carine; Dodé, Catherine; Fabre, Ludovic; Teixeira, Luis; Labesse, Gilles; Pin, Jean-Philippe; Hardelin, Jean-Pierre; Rondard, Philippe

    2009-01-01

    Kallmann syndrome (KS) combines hypogonadism due to gonadotropin-releasing hormone deficiency, and anosmia or hyposmia, related to defective olfactory bulb morphogenesis. In a large series of KS patients, ten different missense mutations (p.R85C, p.R85H, p.R164Q, p.L173R, p.W178S, p.Q210R, p.R268C, p.P290S, p.M323I, p.V331M) have been identified in the gene encoding the G protein-coupled receptor prokineticin receptor-2 (PROKR2), most often in the heterozygous state. Many of these mutations were, however, also found in clinically unaffected individuals, thus raising the question of their actual implication in the KS phenotype. We reproduced each of the ten mutations in a recombinant murine Prokr2, and tested their effects on the signalling activity in transfected HEK-293 cells, by measuring intracellular calcium release upon ligand-activation of the receptor. We found that all mutated receptors except one (M323I) had decreased signalling activities. These could be explained by different defective mechanisms. Three mutations (L173R, W178S, P290S) impaired cell surface-targeting of the receptor. One mutation (Q210R) abolished ligand-binding. Finally, five mutations (R85C, R85H, R164Q, R268C, V331M) presumably impaired G protein-coupling of the receptor. In addition, when wild-type and mutant receptors were coexpressed in HEK-293 cells, none of the mutant receptors that were retained within the cells did affect cell surface-targeting of the wild-type receptor, and none of the mutant receptors properly addressed at the plasma membrane did affect wild-type receptor signalling activity. This argues against a dominant negative effect of the mutations in vivo. PMID:18826963

  13. PROKR2 missense mutations associated with Kallmann syndrome impair receptor signalling activity

    PubMed Central

    Monnier, Carine; Dodé, Catherine; Fabre, Ludovic; Teixeira, Luis; Labesse, Gilles; Pin, Jean-Philippe; Hardelin, Jean-Pierre; Rondard, Philippe

    2009-01-01

    Kallmann syndrome (KS) combines hypogonadism due to gonadotropin-releasing hormone deficiency, and anosmia or hyposmia, related to defective olfactory bulb morphogenesis. In a large series of KS patients, ten different missense mutations (p.R85C, p.R85H, p.R164Q, p.L173R, p.W178S, p.Q210R, p.R268C, p.P290S, p.M323I, p.V331M) have been identified in the gene encoding the G protein-coupled receptor prokineticin receptor-2 (PROKR2), most often in the heterozygous state. Many of these mutations were, however, also found in clinically unaffected individuals, thus raising the question of their actual implication in the KS phenotype. We reproduced each of the ten mutations in a recombinant murine Prokr2, and tested their effects on the signalling activity in transfected HEK-293 cells, by measuring intracellular calcium release upon ligand-activation of the receptor. We found that all mutated receptors except one (M323I) had decreased signalling activities. These could be explained by different defective mechanisms. Three mutations (L173R, W178S, P290S) impaired cell surface-targeting of the receptor. One mutation (Q210R) abolished ligand-binding. Finally, five mutations (R85C, R85H, R164Q, R268C, V331M) presumably impaired G protein-coupling of the receptor. In addition, when wild-type and mutant receptors were coexpressed in HEK-293 cells, none of the mutant receptors that were retained within the cells did affect cell surface-targeting of the wild-type receptor, and none of the mutant receptors properly addressed at the plasma membrane did affect wild-type receptor signalling activity. This argues against a dominant negative effect of the mutations in vivo. PMID:18826963

  14. 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.

  15. 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

  16. Platelet phospholipase A(2) activity in Alzheimer's disease and mild cognitive impairment.

    PubMed

    Gattaz, W F; Forlenza, O V; Talib, L L; Barbosa, N R; Bottino, C M C

    2004-05-01

    Phospholipase A(2) (PLA(2)) controls the metabolism of phospholipids in cell membranes. In the brain, PLA(2) influences the processing of the amyloid precursor protein (APP) and thus the production of the amyloid-beta peptides (Abeta), which are the major components of the senile plaques in Alzheimer's disease (AD). Reduced PLA(2) activity has been reported in brain and in platelets of AD patients. In the present study we investigated PLA(2) activity in platelets from 21 AD patients as compared to 17 healthy elderly controls and 11 individuals with mild cognitive impairment (MCI). Subjects were cognitively assessed by the Mini-Mental State Examination (MMSE) and the CAMDEX schedule. Platelet PLA(2) activity was determined by radio-enzymatic assay, which mainly detected a calcium-independent form of the enzyme present also in the brain (iPLA(2)). PLA(2) activity was significantly lower in AD than in controls (p < 0.001). Mean PLA(2) activity in MCI individuals was between the values of AD patients and controls, with a subgroup showing PLA as low as the lowest AD patients, but the differences from MCI were not significant from AD and control groups. Lower PLA(2) activity was significantly correlated with a worse cognitive performance both at the MMSE (p = 0.001) and the cognitive sub-scale of the CAMDEX inventory (p = 0.002). Our data replicate previous findings of reduced platelet PLA(2) activity in AD. Both reduced PLA(2) activity and the correlation with impaired cognition were also reported in brain tissue of AD patients, suggesting thus that the present determinations in platelets may be related to a reduction in the brain. In the brain the inhibition of PLA(2) inhibits the physiological secretion of the APP, a mechanism that increases Abeta formation. Further longitudinal studies should investigate whether those MCI individuals with the lowest PLA(2) values in platelets would be at a higher risk to develop AD during a longitudinal follow up. PMID:15088152

  17. NF-κB activation impairs somatic cell reprogramming in ageing.

    PubMed

    Soria-Valles, Clara; Osorio, Fernando G; Gutiérrez-Fernández, Ana; De Los Angeles, Alejandro; Bueno, Clara; Menéndez, Pablo; Martín-Subero, José I; Daley, George Q; Freije, José M P; López-Otín, Carlos

    2015-08-01

    Ageing constitutes a critical impediment to somatic cell reprogramming. We have explored the regulatory mechanisms that constitute age-associated barriers, through derivation of induced pluripotent stem cells (iPSCs) from individuals with premature or physiological ageing. We demonstrate that NF-κB activation blocks the generation of iPSCs in ageing. We also show that NF-κB repression occurs during cell reprogramming towards a pluripotent state. Conversely, ageing-associated NF-κB hyperactivation impairs the generation of iPSCs by eliciting the reprogramming repressor DOT1L, which reinforces senescence signals and downregulates pluripotency genes. Genetic and pharmacological NF-κB inhibitory strategies significantly increase the reprogramming efficiency of fibroblasts from Néstor-Guillermo progeria syndrome and Hutchinson-Gilford progeria syndrome patients, as well as from normal aged donors. Finally, we demonstrate that DOT1L inhibition in vivo extends lifespan and ameliorates the accelerated ageing phenotype of progeroid mice, supporting the interest of studying age-associated molecular impairments to identify targets of rejuvenation strategies. PMID:26214134

  18. Inhibition of inflammasome activation improves the impaired pattern of healing in genetically diabetic mice

    PubMed Central

    Bitto, Alessandra; Altavilla, Domenica; Pizzino, Gabriele; Irrera, Natasha; Pallio, Giovanni; Colonna, Michele R; Squadrito, Francesco

    2014-01-01

    Background and Purpose Type 2 diabetes impairs the healing process because of an exaggerated and persistent inflammatory response, and an altered expression pattern of angiogenic molecules. We investigated the effects of inflammasome blockade in diabetes-related wound-healings defects, in genetically diabetic mice. Experimental Approach An incisional skin wound model was produced on the back of female diabetic C57BL/KsJ-m +/+ Leptdb mice (db+/db+) and their normal littermates (db+/m+). Animals were treated daily with two inflammasome blocking agents, BAY 11-7082 (20 mg·kg−1 i.p.), or Brilliant Blue G (BBG, 45.5 mg·kg−1 i.p.), or vehicle. Mice were killed on 3, 6 and 12 days after skin injury to measure expression of the NOD-like receptor NLRP3, caspase-1, VEGF, the inflammasome adapter protein apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and the chemokine CXCL12. Wound levels of IL-1β and IL-18 were also measured, along with histological assessments of wound tissue and the time to complete wound closure. Key Results During healing, the diabetic mice exhibited increased activation of NLRP3, caspase-1, ASC, IL-1β and IL-18. They also showed a reduced expression of VEGF and CXCL12.Treatment with BAY 11-7082 or BBG, to block activation of the inflammasome, decreased the levels of pro-inflammatory molecules. Histological evaluation indicated that inflammasome blockade improved the impaired healing pattern, at day 12 in diabetic mice, along with a decreased time to complete skin healing. Conclusions and Implications These data strongly suggest that activation of the NLRP3 inflammasome is one of the key contributors to the delayed healing of wounds in diabetic mice. PMID:24329484

  19. Characterization of Activities of Daily Living in Individuals With Mild Cognitive Impairment

    PubMed Central

    Jefferson, Angela L.; Byerly, Laura K.; Vanderhill, Susan; Lambe, Susan; Wong, Sarah; Ozonoff, Al; Karlawish, Jason H.

    2009-01-01

    Objective To determine whether participants with mild cognitive impairment (MCI) differ from cognitively normal (NC) older adults on traditional and novel informant-based measures of activities of daily living (ADL) and to identify cognitive correlates of ADLs among participants with MCI. Design Cross-sectional. Setting University medical setting. Participants Seventy-seven participants (NC: N = 39; MCI: N = 38), 60 to 90 years old (73.5 ± 6.6 years; 53% female). Measurements Neuropsychological and ADL measures. Methods Neuropsychological tests were administered to NC and MCI participants. Informants completed the Lawton and Brody Instrumental Activities of Daily Living and Physical Self-Maintenance Scale, including instrumental (IADL) and basic ADL (BADL) scales, as well as the Functional Capacities for Activities of Daily Living (FC-ADL), an error-based ADL measure. Results No statistically or clinically significant between-group differences emerged for the BADL or IADL subscales. However, a robust difference was noted for the FC-ADL scale (MCI errors > NC errors; F(1,75) = 13.6, p <0.001; d = 0.84). Among MCI participants, correlations revealed that a measure of verbal learning was the only neuropsychological correlate of FC-ADL total score (r =-0.39, df = 36, p = 0.007). No neuropsychological measures were significantly associated with the IADL or BADL subscale score. Conclusion Traditional measures assessing global ADLs may not be sensitive to early functional changes related to MCI; however, error-based measures may capture the subtle evolving functional decline associated with MCI. Among MCI participants, early functional difficulties are associated with verbal learning performance, possibly secondary to the hallmark cognitive impairment associated with this cohort. PMID:18332397

  20. Suppressing Emotions Impairs Subsequent Stroop Performance and Reduces Prefrontal Brain Activation

    PubMed Central

    Luechinger, Roger; Boesiger, Peter; Rasch, Björn

    2013-01-01

    Abundant behavioral evidence suggests that the ability to self-control is limited, and that any exertion of self-control will increase the likelihood of subsequent self-control failures. Here we investigated the neural correlates underlying the aftereffects of self-control on future control processes using functional magnetic resonance imaging (fMRI). An initial act of self-control (suppressing emotions) impaired subsequent performance in a second task requiring control (Stroop task). On the neural level, increased activity during emotion suppression was followed by a relative decrease in activity during the Stroop task in a cluster in the right lateral prefrontal cortex (PFC) including the dorsolateral prefrontal cortex (DLPFC), an area engaged in the effortful implementation of control. There was no reliable evidence for reduced activity in the medial frontal cortex (MFC) including the anterior cingulate cortex (ACC), which is involved in conflict detection processes and has previously also been implicated in self-control. Follow-up analyses showed that the detected cluster in the right lateral PFC and an area in the MFC were involved in both the emotion suppression task and the Stroop task, but only the cluster in the right lateral PFC showed reduced activation after emotion suppression during the Stroop task. Reduced activity in lateral prefrontal areas relevant for the implementation of control may be a critical consequence of prior self-control exertion if the respective areas are involved in both self-control tasks. PMID:23565239

  1. Patterns of Communicative Interaction between a Child with Severe Speech and Physical Impairments and Her Caregiver during a Mealtime Activity

    ERIC Educational Resources Information Center

    Ferm, Ulrika; Ahlsen, Elisabeth; Bjorck-Akesson, Eva

    2012-01-01

    Background: Interaction between caregivers and children with severe impairments is closely related to the demands of daily activities. This study examines the relationship between interaction and the routine mealtime activity at home. Method: Patterns of interaction between a child (aged 6 years and 6 months) with severe speech and physical…

  2. An Age-Cohort Study of Older Adults with and without Visual Impairments: Activity, Independence, and Life Satisfaction

    ERIC Educational Resources Information Center

    Good, Gretchen A.; LaGrow, Steven; Alpass, Fiona

    2008-01-01

    This survey of 560 older adults who were visually impaired or sighted analyzed whether the two groups differed in their levels of activity, independence, and life satisfaction and the degree to which activity and independence contribute to the prediction of life satisfaction. Implications for rehabilitation services are discussed. (Contains 5…

  3. Photoproduction of Hydrogen by Sulfur-Deprived Chlamydomonas reinhardtii Mutants with Impaired Photosystem II Photochemical Activity

    SciTech Connect

    Makarova, V. V.; Kosourov, S.; Krendeleva, T. E.; Semin, B. K.; Kukarskikh, G. P.; Rubin, A. B.; Sayre, R. T.; Ghirardi, M. L.; Seibert, M.

    2007-01-01

    Photoproduction of H2 was examined in a series of sulfur-deprived Chlamydomonas reinhardtii D1-R323 mutants with progressively impaired PSII photochemical activity. In the R323H, R323D, and R323E D1 mutants, replacement of arginine affects photosystem II (PSII) function, as demonstrated by progressive decreases in O2-evolving activity and loss of PSII photochemical activity. Significant changes in PSII activity were found when the arginine residue was replaced by negatively charged amino acid residues (R323D and R323E). However, the R323H (positively charged or neutral, depending on the ambient pH) mutant had minimal changes in PSII activity. The R323H, R323D, and R323E mutants and the pseudo-wild-type (pWt) with restored PSII function were used to study the effects of sulfur deprivation on H2-production activity. All of these mutants exhibited significant changes in the normal parameters associated with the H2-photoproduction process, such as a shorter aerobic phase, lower accumulation of starch, a prolonged anaerobic phase observed before the onset of H2-production, a shorter duration of H2-production, lower H2 yields compared to the pWt control, and slightly higher production of dark fermentation products such as acetate and formate. The more compromised the PSII photochemical activity, the more dramatic was the effect of sulfur deprivation on the H2-production process, which depends both on the presence of residual PSII activity and the amount of stored starch.

  4. Photoproduction of hydrogen by sulfur-deprived C. reinhardtii mutants with impaired photosystem II photochemical activity.

    PubMed

    Makarova, Valeria V; Kosourov, Sergey; Krendeleva, Tatiana E; Semin, Boris K; Kukarskikh, Galina P; Rubin, Andrei B; Sayre, Richard T; Ghirardi, Maria L; Seibert, Michael

    2007-10-01

    Photoproduction of H2 was examined in a series of sulfur-deprived Chlamydomonas reinhardtii D1-R323 mutants with progressively impaired PSII photochemical activity. In the R323H, R323D, and R323E D1 mutants, replacement of arginine affects photosystem II (PSII) function, as demonstrated by progressive decreases in O2-evolving activity and loss of PSII photochemical activity. Significant changes in PSII activity were found when the arginine residue was replaced by negatively charged amino acid residues (R323D and R323E). However, the R323H (positively charged or neutral, depending on the ambient pH) mutant had minimal changes in PSII activity. The R323H, R323D, and R323E mutants and the pseudo-wild-type (pWt) with restored PSII function were used to study the effects of sulfur deprivation on H2-production activity. All of these mutants exhibited significant changes in the normal parameters associated with the H2-photoproduction process, such as a shorter aerobic phase, lower accumulation of starch, a prolonged anaerobic phase observed before the onset of H2-production, a shorter duration of H2-production, lower H2 yields compared to the pWt control, and slightly higher production of dark fermentation products such as acetate and formate. The more compromised the PSII photochemical activity, the more dramatic was the effect of sulfur deprivation on the H2-production process, which depends both on the presence of residual PSII activity and the amount of stored starch. PMID:17701084

  5. Change in daily ambulatory activity and cardiovascular events in people with impaired glucose tolerance.

    PubMed

    Popp Switzer, Maryna; Elhanafi, Sherif; San Juan, Zinnia T

    2015-03-01

    Patients with pre-diabetes have a tenfold higher risk of developing Type 2 DM and a twofold higher risk of developing coronary heart disease compared to non-diabetics. Interventions targeted at those in an early stage of impaired glucose metabolism can delay or prevent diabetes. Effects of these interventions on cardiovascular outcome are unknown. This article aims to review current and available data on lifestyle intervention, specifically physical activity, on cardiovascular outcomes in populations at risk for diabetes. We searched PubMed database from 1990 to present with focus on more recent literature published over the last 2 years. Various permutations of keywords used included glucose intolerance, pre-diabetes, diabetes, lifestyle modifications, physical activity, and cardiovascular disease. Intensive glycemic control, specific medications, and lifestyle intervention including increase in physical activity have been evaluated in diabetes and pre-diabetes. Most studies we reviewed showed that these interventions prevented progression of pre-diabetes to diabetes and improved cardiovascular risk surrogate measures. Direct decrease in cardiovascular mortality, non-fatal stroke, and non-fatal myocardial infarctions was shown in one recent trial. Increase in physical activity has a positive effect on decreasing cardiovascular risk by modifying several important risk factors and may decrease risk of events in pre-diabetics. More randomized high power trials are needed to verify and characterize these effects. PMID:25638410

  6. 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

  7. Hippocampal inactivation with TTX impairs long-term spatial memory retrieval and modifies brain metabolic activity.

    PubMed

    Conejo, Nélida María; Cimadevilla, José Manuel; González-Pardo, Héctor; Méndez-Couz, Marta; Arias, Jorge Luis

    2013-01-01

    Functional inactivation techniques enable studying the hippocampal involvement in each phase of spatial memory formation in the rat. In this study, we applied tetrodotoxin unilaterally or bilaterally into the dorsal hippocampus to evaluate the role of this brain structure in retrieval of memories acquired 28 days before in the Morris water maze. We combined hippocampal inactivation with the assessment of brain metabolism using cytochrome oxidase histochemistry. Several brain regions were considered, including the hippocampus and other related structures. Results showed that both unilateral and bilateral hippocampal inactivation impaired spatial memory retrieval. Hence, whereas subjects with bilateral hippocampal inactivation showed a circular swim pattern at the side walls of the pool, unilateral inactivation favoured swimming in the quadrants adjacent to the target one. Analysis of cytochrome oxidase activity disclosed regional differences according to the degree of hippocampal functional blockade. In comparison to control group, animals with bilateral inactivation showed increased CO activity in CA1 and CA3 areas of the hippocampus during retrieval, while the activity of the dentate gyrus substantially decreased. However, unilateral inactivated animals showed decreased CO activity in Ammon's horn and the dentate gyrus. This study demonstrated that retrieval recruits differentially the hippocampal subregions and the balance between them is altered with hippocampal functional lesions. PMID:23724089

  8. Hippocampal Inactivation with TTX Impairs Long-Term Spatial Memory Retrieval and Modifies Brain Metabolic Activity

    PubMed Central

    Conejo, Nélida María; Cimadevilla, José Manuel; González-Pardo, Héctor; Méndez-Couz, Marta; Arias, Jorge Luis

    2013-01-01

    Functional inactivation techniques enable studying the hippocampal involvement in each phase of spatial memory formation in the rat. In this study, we applied tetrodotoxin unilaterally or bilaterally into the dorsal hippocampus to evaluate the role of this brain structure in retrieval of memories acquired 28 days before in the Morris water maze. We combined hippocampal inactivation with the assessment of brain metabolism using cytochrome oxidase histochemistry. Several brain regions were considered, including the hippocampus and other related structures. Results showed that both unilateral and bilateral hippocampal inactivation impaired spatial memory retrieval. Hence, whereas subjects with bilateral hippocampal inactivation showed a circular swim pattern at the side walls of the pool, unilateral inactivation favoured swimming in the quadrants adjacent to the target one. Analysis of cytochrome oxidase activity disclosed regional differences according to the degree of hippocampal functional blockade. In comparison to control group, animals with bilateral inactivation showed increased CO activity in CA1 and CA3 areas of the hippocampus during retrieval, while the activity of the dentate gyrus substantially decreased. However, unilateral inactivated animals showed decreased CO activity in Ammon's horn and the dentate gyrus. This study demonstrated that retrieval recruits differentially the hippocampal subregions and the balance between them is altered with hippocampal functional lesions. PMID:23724089

  9. Ceramide-Activated Phosphatase Mediates Fatty Acid–Induced Endothelial VEGF Resistance and Impaired Angiogenesis

    PubMed Central

    Mehra, Vishal C.; Jackson, Elias; Zhang, Xian M.; Jiang, Xian-Cheng; Dobrucki, Lawrence W.; Yu, Jun; Bernatchez, Pascal; Sinusas, Albert J.; Shulman, Gerald I.; Sessa, William C.; Yarovinsky, Timur O.; Bender, Jeffrey R.

    2014-01-01

    Endothelial dysfunction, including endothelial hyporesponsiveness to prototypical angiogenic growth factors and eNOS agonists, underlies vascular pathology in many dysmetabolic states. We investigated effects of a saturated free fatty acid, palmitic acid (PA), on endothelial cell responses to VEGF. PA-pretreated endothelial cells had markedly diminished Akt, eNOS, and ERK activation responses to VEGF, despite normal VEGFR2 phosphorylation. PA inhibited VEGF-induced angiogenic cord formation in Matrigel, and PA-treated endothelial cells accumulated early species (C16) ceramide. The serine palmitoyltransferase inhibitor myriocin reversed these defects. Protein phosphatase 2A (PP2A) became more eNOS-associated in PA-treated cells; the PP2A inhibitor okadaic acid reversed PA-induced signaling defects. Mice fed a diet high in saturated fat for 2 to 3 weeks had impaired i) aortic Akt and eNOS phosphorylation to infused VEGF, ii) ear angiogenic responses to intradermal adenoviral-VEGF injection, and iii) vascular flow recovery to hindlimb ischemia as indicated by laser Doppler and αVβ3 SPECT imaging. High-fat feeding did not impair VEGF-induced signaling or angiogenic responses in mice with reduced serine palmitoyltransferase expression. Thus, de novo ceramide synthesis is required for these detrimental PA effects. The findings demonstrate an endothelial VEGF resistance mechanism conferred by PA, which comprises ceramide-induced, PP2A-mediated dephosphorylation of critical activation sites on enzymes central to vascular homeostasis and angiogenesis. This study defines potential molecular targets for preservation of endothelial function in metabolic syndrome. PMID:24606881

  10. Cathepsin L maturation and activity is impaired in macrophages harboring M. avium and M. tuberculosis.

    PubMed

    Nepal, Rajeev M; Mampe, Stephanie; Shaffer, Brian; Erickson, Ann H; Bryant, Paula

    2006-06-01

    Mycobacterium tuberculosis-infected macrophages demonstrate diminished capacity to present antigens via class II MHC molecules. Since successful class II MHC-restricted antigen presentation relies on the actions of endocytic proteases, we asked whether the activities of cathepsins (Cat) B, S and L-three major lysosomal cysteine proteases-are modulated in macrophages infected with pathogenic Mycobacterium spp. Infection of murine bone marrow-derived macrophages with either Mycobacterium avium or M. tuberculosis had no obvious effect on Cat B or Cat S activity. In contrast, the activity of Cat L was altered in infected cells. Specifically, whereas the 24-kDa two-chain mature form of active Cat L predominated in uninfected cells, we observed an increase in the steady-state activity of the precursor single-chain (30 kDa) and 25-kDa two-chain forms of the enzyme in cells infected with either M. avium or M. tuberculosis. Pulse-chase analyses revealed that maturation of nascent, single-chain Cat L into the 25-kDa two-chain form was impaired in infected macrophages, and that maturation into the 24-kDa two-chain form did not occur. Consistent with these data, M. avium infection inhibited the IFNgamma-induced secretion of active two-chain Cat L by macrophages. Viable bacilli were not required to disrupt Cat L maturation, suggesting that a constitutively expressed mycobacterial component was responsible. The absence of the major active form of lysosomal Cat L in M. avium- and M. tuberculosis-infected macrophages may influence the types of T cell epitopes generated in these antigen-presenting cells, and/or the rate of class II MHC peptide loading. PMID:16636015

  11. Mitogen-Activated Protein Kinase Phosphatase-2 Deletion Impairs Synaptic Plasticity and Hippocampal-Dependent Memory

    PubMed Central

    Abdul Rahman, Nor Zaihana; Greenwood, Sam M.; Brett, Ros R.; Tossell, Kyoko; Ungless, Mark A.; Plevin, Robin

    2016-01-01

    Mitogen-activated protein kinases (MAPKs) regulate brain function and their dysfunction is implicated in a number of brain disorders, including Alzheimer's disease. Thus, there is great interest in understanding the signaling systems that control MAPK function. One family of proteins that contribute to this process, the mitogen-activated protein kinase phosphatases (MKPs), directly inactivate MAPKs through dephosphorylation. Recent studies have identified novel functions of MKPs in development, the immune system, and cancer. However, a significant gap in our knowledge remains in relation to their role in brain functioning. Here, using transgenic mice where the Dusp4 gene encoding MKP-2 has been knocked out (MKP-2−/− mice), we show that long-term potentiation is impaired in MKP-2−/− mice compared with MKP-2+/+ controls whereas neuronal excitability, evoked synaptic transmission, and paired-pulse facilitation remain unaltered. Furthermore, spontaneous EPSC (sEPSC) frequency was increased in acute slices and primary hippocampal cultures prepared from MKP-2−/− mice with no effect on EPSC amplitude observed. An increase in synapse number was evident in primary hippocampal cultures, which may account for the increase in sEPSC frequency. In addition, no change in ERK activity was detected in both brain tissue and primary hippocampal cultures, suggesting that the effects of MKP-2 deletion were MAPK independent. Consistent with these alterations in hippocampal function, MKP-2−/− mice show deficits in spatial reference and working memory when investigated using the Morris water maze. These data show that MKP-2 plays a role in regulating hippocampal function and that this effect may be independent of MAPK signaling. SIGNIFICANCE STATEMENT Recently, there has been significant focus on proteins that control mitogen-activated protein kinases' (MAPKs) function, namely the mitogen-activated protein kinase phosphatases (MKPs). Recent studies have revealed novel

  12. A dual mechanism for impairment of GABAA receptor activity by NMDA receptor activation in rat cerebellum granule cells.

    PubMed

    Robello, M; Amico, C; Cupello, A

    1997-01-01

    The function of the GABAA receptor has been studied using the whole cell voltage clamp recording technique in rat cerebellum granule cells in culture. Activation of NMDA-type glutamate receptors causes a reduction in the effect of GABA. Full GABAA receptor activity was recovered after washing out NMDA and NMDA action was prevented in a Mg+2 containing medium. The NMDA effect was also absent when extracellular Ca+2 was replaced by Ba+2 and when 10 mM Bapta was present in the intracellular solution. Charge accumulations via voltage activated Ca+2 channels greater than the ones via NMDA receptors do not cause any reduction in GABAA receptor function, suggesting that Ca+2 influx through NMDA receptor channels is critical for the effect. The NMDA effect was reduced by including adenosine-5'-O-3-thiophosphate (ATP-gamma-S) in the internal solution and there was a reduction in the NMDA effect caused by deltamethrin, a calcineurin inhibitor. Part of the NMDA induced GABAA receptor impairment was prevented by prior treatment with L-arginine. Analogously, part of the NMDA effect was prevented by blockage of NO-synthase activity by N omega-nitro-L-arginine. A combination of NO-synthase and calcineurin inhibitors completely eliminated the NMDA action. An analogous result was obtained by combining the NO-synthase inhibitor with the addition of ATP-gamma-S to the pipette medium. The additivity of the prevention of the NMDA impairment of GABAA receptor by blocking the L-arginine/NO pathway and inhibiting calcineurin activity suggests an independent involvement of these two pathways in the interaction between NMDA and the GABAA receptor. On the one hand Ca+2 influx across NMDA channels activates calcineurin and dephosphorylates the GABAA receptor complex directly or dephosphorylates proteins critical for the function of the receptor. On the other hand, Ca+2 influx activates NO-synthase and induces nitric oxide production, which regulates such receptors via protein kinase G

  13. Monocyte Activation in HIV/HCV Coinfection Correlates with Cognitive Impairment

    PubMed Central

    Rempel, Hans; Sun, Bing; Calosing, Cyrus; Abadjian, Linda; Monto, Alexander; Pulliam, Lynn

    2013-01-01

    Coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) challenges the immune system with two viruses that elicit distinct immune responses. Chronic immune activation is a hallmark of HIV infection and an accurate indicator of disease progression. Suppressing HIV viremia by antiretroviral therapy (ART) effectively prolongs life and significantly improves immune function. HIV/HCV coinfected individuals have peripheral immune activation despite effective ART control of HIV viral load. Here we examined freshly isolated CD14 monocytes for gene expression using high-density cDNA microarrays and analyzed T cell subsets, CD4 and CD8, by flow cytometry to characterize immune activation in monoinfected HCV and HIV, and HIV-suppressed coinfected subjects. To determine the impact of coinfection on cognition, subjects were evaluated in 7 domains for neuropsychological performance, which were summarized as a global deficit score (GDS). Monocyte gene expression analysis in HIV-suppressed coinfected subjects identified 43 genes that were elevated greater than 2.5 fold. Correlative analysis of subjects’ GDS and gene expression found eight genes with significance after adjusting for multiple comparisons. Correlative expression of six genes was confirmed by qPCR, five of which were categorized as type 1 IFN response genes. Global deficit scores were not related to plasma lipopolysaccharide levels. In the T cell compartment, coinfection significantly increased expression of activation markers CD38 and HLADR on both CD4 and CD8 T cells but did not correlate with GDS. These findings indicate that coinfection is associated with a type 1 IFN monocyte activation profile which was further found to correlate with cognitive impairment, even in subjects with controlled HIV infection. HIV-suppressed coinfected subjects with controlled HIV viral load experiencing immune activation could benefit significantly from successful anti-HCV therapy and may be considered as

  14. Cumulative disease activity predicts incidental hearing impairment in patients with rheumatoid arthritis (RA).

    PubMed

    Pascual-Ramos, Virginia; Contreras-Yáñez, Irazú; Rivera-Hoyos, Paula; Enríquez, Lorena; Ramírez-Anguiano, Jaqueline

    2014-03-01

    We previously reported that 24% of 113 rheumatoid arthritis (RA) patients had hearing impairment (HI). We investigated if disease activity was a predictor of incidental HI. One hundred and four patients completed three consecutive 6 months-apart rheumatic evaluations and concomitant audiometric evaluations which included at least an interview, an otoscopic evaluation, and a pure tone audiometry. HI was defined if the average thresholds for at least one of low-, mid-, or high-frequency ranges were ≥25 decibels (dB) hearing level in one or both ears. Appropriated statistics was used. Internal review board approval was obtained. Patients were most frequently middle-aged (43.4 ± 13.3 years), female (89.4%), and had median disease duration of 5 years and low disease activity. All were receiving RA treatment. At inclusion, 24 patients had HI which was sensorineural in 91.7% of them. Among the 80 patients without HI at baseline, 10 (12.5%) developed incidental HI, and they had more disease activity either at baseline ([median, range] disease activity score-28 joints evaluated-C-reactive protein [DAS28-CRP], 3.9 [1.6-7.3] vs. 2.1 [1-8.7], p = 0.006) or cumulative previous incidental HI (3.4 [1.8-4.8] vs. 2 [1-6.2], p = 0.007) and were more frequently on combined methotrexate and sulfasalazine (20 vs. 1.4%, p = 0.05) than their counterparts. In the adjusted Cox proportional model, cumulative DAS28-CRP was the only variable to predict incidental HI (odds ratio, 1.8; 95% confidence interval, 1.1-2.7; p = 0.01). Almost 13% of RA patients with short disease duration and low disease activity developed incidental HI during 1 year. Cumulative disease activity predicted incidental HI. PMID:24435352

  15. Hypoxia in Leishmania major skin lesions impairs the NO-dependent leishmanicidal activity of macrophages.

    PubMed

    Mahnke, Alexander; Meier, Robert J; Schatz, Valentin; Hofmann, Julian; Castiglione, Kirstin; Schleicher, Ulrike; Wolfbeis, Otto S; Bogdan, Christian; Jantsch, Jonathan

    2014-09-01

    Cure of infections with Leishmania major is critically dependent on the ability of macrophages to induce the type 2 nitic oxide (NO) synthase (NOS2) that produces high levels of NO in the presence of ample oxygen. Therefore, we analyzed the oxygen levels found in leishmanial skin lesions and their effect on the NOS2-dependent leishmanicidal activity of macrophages (MΦ). When L. major skin lesions of self-healing C57BL/6 mice reached their maximum size, the infected tissue displayed low oxygen levels (pO2∼21 Torr). MΦ activated under these oxygen tensions failed to produce sufficient amounts of NO to clear L. major. Nos2-deficient and hypoxic wild-type macrophages displayed a similar phenotype. Killing was restored when MΦ were reoxygenated or exposed to a NO donor. The resolution of the lesion in C57BL/6 mice was paralleled by an increase of lesional pO2. When mice were kept under normobaric hypoxia, this caused a persistent suppression of the lesional pO2 and a concurrent increase of the parasite load. In Nos2-deficient mice, there was no effect of atmospheric hypoxia. Low oxygen levels found at leishmanial skin lesions impaired the NOS2-dependent leishmanicidal activity of MΦ. Hence, tissue oxygenation represents an underestimated local milieu factor that participates in the persistence of Leishmania. PMID:24583949

  16. Korean Red Ginseng Water Extract Restores Impaired Endothelial Function by Inhibiting Arginase Activity in Aged Mice

    PubMed Central

    Choi, Kwanhoon; Yoon, Jeongyeon

    2014-01-01

    Cardiovascular disease is the prime cause of morbidity and mortality and the population ages that may contribute to increase in the occurrence of cardiovascular disease. Arginase upregulation is associated with impaired endothelial function in aged vascular system and thus may contribute to cardiovascular disease. According to recent research, Korean Red Ginseng water extract (KRGE) may reduce cardiovascular disease risk by improving vascular system health. The purpose of this study was to examine mechanisms contributing to age-related vascular endothelial dysfunction and to determine whether KRGE improves these functions in aged mice. Young (10±3 weeks) and aged (55±5 weeks) male mice (C57BL/6J) were orally administered 0, 10, or 20 mg/mouse/day of KRGE for 4 weeks. Animals were sacrificed and the aortas were removed. Endothelial arginase activity, nitric oxide (NO) generation and reactive oxygen species (ROS) production, endothelial nitric oxide synthase (eNOS) coupling, vascular tension, and plasma peroxynitrite production were measured. KRGE attenuated arginase activity, restored nitric oxide (NO) generation, reduced ROS production, and enhanced eNOS coupling in aged mice. KRGE also improved vascular tension in aged vessels, as indicated by increased acetylcholine-induced vasorelaxation and improved phenylephrine-stimulated vasoconstriction. Furthermore, KRGE prevented plasma peroxynitrite formation in aged mice, indicating reduced lipid peroxidation. These results suggest KRGE exerts vasoprotective effects by inhibiting arginase activity and augmenting NO signaling and may be a useful treatment for age-dependent vascular diseases. PMID:24757370

  17. 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

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

    PubMed

    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

    2015-11-15

    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

  19. ADAR1 Activation Drives Leukemia Stem Cell Self-Renewal by Impairing Let-7 Biogenesis.

    PubMed

    Zipeto, Maria Anna; Court, Angela C; Sadarangani, Anil; Delos Santos, Nathaniel P; Balaian, Larisa; Chun, Hye-Jung; Pineda, Gabriel; Morris, Sheldon R; Mason, Cayla N; Geron, Ifat; Barrett, Christian; Goff, Daniel J; Wall, Russell; Pellecchia, Maurizio; Minden, Mark; Frazer, Kelly A; Marra, Marco A; Crews, Leslie A; Jiang, Qingfei; Jamieson, Catriona H M

    2016-08-01

    Post-transcriptional adenosine-to-inosine RNA editing mediated by adenosine deaminase acting on RNA1 (ADAR1) promotes cancer progression and therapeutic resistance. However, ADAR1 editase-dependent mechanisms governing leukemia stem cell (LSC) generation have not been elucidated. In blast crisis chronic myeloid leukemia (BC CML), we show that increased JAK2 signaling and BCR-ABL1 amplification activate ADAR1. In a humanized BC CML mouse model, combined JAK2 and BCR-ABL1 inhibition prevents LSC self-renewal commensurate with ADAR1 downregulation. Lentiviral ADAR1 wild-type, but not an editing-defective ADAR1(E912A) mutant, induces self-renewal gene expression and impairs biogenesis of stem cell regulatory let-7 microRNAs. Combined RNA sequencing, qRT-PCR, CLIP-ADAR1, and pri-let-7 mutagenesis data suggest that ADAR1 promotes LSC generation via let-7 pri-microRNA editing and LIN28B upregulation. A small-molecule tool compound antagonizes ADAR1's effect on LSC self-renewal in stromal co-cultures and restores let-7 biogenesis. Thus, ADAR1 activation represents a unique therapeutic vulnerability in LSCs with active JAK2 signaling. PMID:27292188

  20. Metacognitive impairment in active cocaine use disorder is associated with individual differences in brain structure.

    PubMed

    Moeller, Scott J; Fleming, Stephen M; Gan, Gabriela; Zilverstand, Anna; Malaker, Pias; d'Oleire Uquillas, Federico; Schneider, Kristin E; Preston-Campbell, Rebecca N; Parvaz, Muhammad A; Maloney, Thomas; Alia-Klein, Nelly; Goldstein, Rita Z

    2016-04-01

    Dysfunctional self-awareness has been posited as a key feature of drug addiction, contributing to compromised control over addictive behaviors. In the present investigation, we showed that, compared with healthy controls (n=13) and even individuals with remitted cocaine use disorder (n=14), individuals with active cocaine use disorder (n=8) exhibited deficits in basic metacognition, defined as a weaker link between objective performance and self-reported confidence of performance on a visuo-perceptual accuracy task. This metacognitive deficit was accompanied by gray matter volume decreases, also most pronounced in individuals with active cocaine use disorder, in the rostral anterior cingulate cortex, a region necessary for this function in health. Our results thus provide a direct unbiased measurement - not relying on long-term memory or multifaceted choice behavior - of metacognition deficits in drug addiction, which are further mapped onto structural deficits in a brain region that subserves metacognitive accuracy in health and self-awareness in drug addiction. Impairments of metacognition could provide a basic mechanism underlying the higher-order self-awareness deficits in addiction, particularly among recent, active users. PMID:26948669

  1. Constitutive activation of IKK2/NF-κB impairs osteogenesis and skeletal development.

    PubMed

    Swarnkar, Gaurav; Zhang, Kaihua; Mbalaviele, Gabriel; Long, Fanxin; Abu-Amer, Yousef

    2014-01-01

    Pathologic conditions impair bone homeostasis. The transcription factor NF-κB regulates bone homeostasis and is central to bone pathologies. Whereas contribution of NF-κB to heightened osteoclast activity is well-documented, the mechanisms underlying NF-κB impact on chondrocytes and osteoblasts are scarce. In this study, we examined the effect of constitutively active IKK2 (IKK2ca) on chondrogenic and osteogenic differentiation. We show that retroviral IKK2ca but not GFP, IKK2WT, or the inactive IKK2 forms IKK2KM and IKK2SSAA, strongly suppressed osteogenesis and chondrogenesis, in vitro. In order to explore the effect of constitutive NF-κB activation on bone formation in vivo, we activated this pathway in a conditional fashion. Specifically, we crossed the R26StopIKK2ca mice with mice carrying the Col2-cre in order to express IKK2ca in osteoblasts and chondrocytes. Both chondrocytes and osteoblasts derived from Col2Cre/IKK2ca expressed IKK2ca. Mice were born alive yet died shortly thereafter. Histologically, newborn Col2Cre+/RosaIKK2ca heterozygotes (Cre+IKK2ca_w/f (het)) and homozygotes (Cre+IKK2ca_f/f (KI)) showed smaller skeleton, deformed vertebrate and reduced or missing digit ossification. The width of neural arches, as well as ossification in vertebral bodies of Cre+IKK2ca_w/f and Cre+IKK2ca_f/f, was reduced or diminished. H&E staining of proximal tibia from new born pups revealed that Cre+IKK2ca_f/f displayed disorganized hypertrophic zones within the smaller epiphysis. Micro-CT analysis indicated that 4-wk old Cre+IKK2ca_w/f has abnormal trabecular bone in proximal tibia compared to WT littermates. Mechanistically, ex-vivo experiments showed that expression of differentiation markers in calvarial osteoblasts derived from newborn IKK2ca knock-in mice was diminished compared to WT-derived cells. In situ hybridization studies demonstrated that the hypertrophic chondrocyte marker type-X collagen, the pre-hypertrophic chondrocyte markers Indian hedgehog

  2. 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

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

    PubMed

    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

  4. Physical Activity Over the Life Course and its Association with Cognitive Performance and Impairment in Old Age

    PubMed Central

    Middleton, Laura E; Barnes, Deborah E; Lui, Li-Yung; Yaffe, Kristine

    2012-01-01

    Objective To determine how physical activity at various ages over the life course is associated with cognitive impairment in late life. Design Cross-sectional study Setting Four US sites. Participants We administered a modified Mini-Mental State Examination (mMMSE) to 9344 women ≥65 years (mean 71.6 years) who self-reported teenage, age 30, age 50, and late life physical activity. Measurements We used logistic regressions to determine the association between physical activity status at each age and likelihood of cognitive impairment (mMMSE score >1.5SD below the mean, mMMSE≤22). Models were adjusted for age, education, marital status, diabetes, hypertension, depressive symptoms, smoking, and body mass index. Results Women who reported being physically active had lower prevalence of cognitive impairment in late life compared to women who were inactive at each time (teenage: 8.5% vs. 16.7%; adjusted Odds Ratio (95% Confidence Interval): 0.65 (0.53–0.80); age 30: 8.9% vs. 12.0%; 0.80 (0.67–0.96); age 50: 8.5% vs. 13.1%; 0.71 (0.59–0.85); old age: 8.2% vs. 15.9%; 0.74 (0.61–0.91)). When the four times were analyzed together, teenage physical activity was most strongly associated with lower odds of late-life cognitive impairment (OR=0.73 (0.58–0.92)). However, women who were physically inactive at teenage and became active in later life had lower risk than those who remained inactive. Conclusions Women who reported being physically active at any point over the life course, and especially at teenage, have lower likelihood of cognitive impairment in late life. Interventions should promote physical activity early in life and throughout the life course. PMID:20609030

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

    PubMed

    Ledoux, Sarah; Guthrie, Christine

    2016-06-01

    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. PMID:27072132

  6. The absence of the transcription activator TFE3 impairs activation of B cells in vivo.

    PubMed Central

    Merrell, K; Wells, S; Henderson, A; Gorman, J; Alt, F; Stall, A; Calame, K

    1997-01-01

    TFE3 is a ubiquitously expressed member of the TFE3/mi family of basic helix loop helix zipper transcription factors. TFE3 binds to muE3 sites located in the immunoglobulin heavy-chain (IgH) intronic enhancer, heavy-chain variable region promoters, the Ig kappa intronic enhancer, and regulatory sites in other genes. To understand the role of TFE3 in Ig expression and lymphoid development, we used embryonic stem (ES) cell-mediated gene targeting and RAG2-/- blastocyst complementation to generate mice which lack TFE3 in their B and T lymphocytes. TFE3- ES cells fully reconstitute the B- and T-cell compartments, giving rise to normal patterns of IgM+ B220+ B cells and CD4+ and CD8+ T cells. However, TFE3- B cells show several defects consistent with poor B-cell activation. Serum IgM levels are reduced twofold and IgG and IgA isotypes are reduced three- to sixfold in the TFE3- chimeras even though in vitro, the TFE3- splenocytes secrete normal levels of all isotypes in response to lipopolysaccharide activation. Peripheral TFE3- B cells also show reduced surface expression of CD23 and CD24 (heat-stable antigen). PMID:9154832

  7. Perindopril Attenuates Lipopolysaccharide-Induced Amyloidogenesis and Memory Impairment by Suppression of Oxidative Stress and RAGE Activation.

    PubMed

    Goel, Ruby; Bhat, Shahnawaz Ali; Hanif, Kashif; Nath, Chandishwar; Shukla, Rakesh

    2016-02-17

    Clinical and preclinical studies account hypertension as a risk factor for dementia. We reported earlier that angiotensin-converting enzyme (ACE) inhibition attenuated the increased vulnerability to neurodegeneration in hypertension and prevented lipopolysaccharide (LPS)-induced memory impairment in normotensive wistar rats (NWRs) and spontaneously hypertensive rats (SHRs). Recently, a receptor for advanced glycation end products (RAGE) has been reported to induce amyloid beta (Aβ1-42) deposition and memory impairment in hypertensive animals. However, the involvement of ACE in RAGE activation and amyloidogenesis in the hypertensive state is still unexplored. Therefore, in this study, we investigated the role of ACE on RAGE activation and amyloidogenesis in memory-impaired NWRs and SHRs. Memory impairment was induced by repeated (on days 1, 4, 7, and 10) intracerebroventricular (ICV) injections of LPS in SHRs (25 μg) and NWRs (50 μg). Our data showed that SHRs exhibited increased oxidative stress (increased gp91-phox/NOX-2 expression and ROS generation), RAGE, and β-secretase (BACE) expression without Aβ1-42 deposition. LPS (25 μg, ICV) further amplified oxidative stress, RAGE, and BACE activation, culminating in Aβ1-42 deposition and memory impairment in SHRs. Similar changes were observed at the higher dose of LPS (50 μg, ICV) in NWRs. Further, LPS-induced oxidative stress was associated with endothelial dysfunction and reduction in cerebral blood flow (CBF), more prominently in SHRs than in NWRs. Finally, we showed that perindopril (0.1 mg/kg, 15 days) prevented memory impairment by reducing oxidative stress, RAGE activation, amyloidogenesis, and improved CBF in both SHRs and NWRs. These findings suggest that perindopril might be used as a therapeutic strategy for the early stage of dementia. PMID:26689453

  8. 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.

  9. [DIACYLGLYCEROL ACCUMULATION IMPAIRS SHORT-TERM ACTIVATION OF PHOSPHOLIPASE D BY THYROXINE IN THE LIVER CELLS].

    PubMed

    Hassouneh, Loay Kh M

    2015-01-01

    Thyroid hormones (TG) are known modulators of signal transduction. Phospholipase D (PLD) is one of the targets of TG in the stimulated cells. Response of cells to the short-term TG action significantly reduces at old age. Taking into account that diacylglycerol (DAG) accumulation induces the resistance of cells to some of regulatory factors in the target cells the aim of the present study was to determine if DAG content increase in hepatocytes impairs the L-thyroxine (L-T4) short-term action. The experiments were performed in either the [14C]palmitic acid- labeled hepatocytes or [14C]oleic acid-pre-labeled liver cells of 3- and 24-month-old rats. To study the short-term L-T4 action on cells the PLD activation was determined. The DAG production and content in hepatocytes significantly increased at old age and in the young cells pre-treated with palmitic acid. The reduction of DAG level in cells by means of DAG-kinase activator, alfa-tocoferol acetate, or long-term L-T4 treatment improved the short-term hormone action. The above data have indicated that DAG play important role in the L-T4 PLD regulation. The cross-talk between classic and non-genomic pathways of TG regulation of lipid metabolism has been determined. PMID:26387163

  10. 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

  11. Activation of the tumor suppressor p53 upon impairment of ribosome biogenesis.

    PubMed

    Bursac, Sladana; Brdovcak, Maja Cokaric; Donati, Giulio; Volarevic, Sinisa

    2014-06-01

    Errors in ribosome biogenesis can result in quantitative or qualitative defects in protein synthesis and consequently lead to improper execution of the genetic program and the development of specific diseases. Evidence has accumulated over the last decade suggesting that perturbation of ribosome biogenesis triggers a p53-activating checkpoint signaling pathway, often referred to as the ribosome biogenesis stress checkpoint pathway. Although it was originally suggested that p53 has a prominent role in preventing diseases by monitoring the fidelity of ribosome biogenesis, recent work has demonstrated that p53 activation upon impairment of ribosome biogenesis also mediates pathological manifestations in humans. Perturbations of ribosome biogenesis can trigger a p53-dependent checkpoint signaling pathway independent of DNA damage and the tumor suppressor ARF through inhibitory interactions of specific ribosomal components with the p53 negative regulator, Mdm2. Here we review the recent advances made toward understanding of this newly-recognized checkpoint signaling pathway, its role in health and disease, and discuss possible future directions in this exciting research field. This article is part of a Special Issue entitled: Role of the Nucleolus in Human Disease. PMID:24514102

  12. 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

  13. Naturalistic assessment of everyday activities and prompting technologies in mild cognitive impairment.

    PubMed

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

    2013-04-01

    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

  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. 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.

  16. 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…

  17. [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

  18. 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

  19. 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

  20. 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.

  1. Neostigmine but not sugammadex impairs upper airway dilator muscle activity and breathing

    PubMed Central

    Eikermann, M.; Zaremba, S.; Malhotra, A.; Jordan, A. S.; Rosow, C.; Chamberlin, N. L.

    2008-01-01

    Background Cholinesterase inhibitor-based reversal agents, given in the absence of neuromuscular block, evoke a partial upper airway obstruction by decreasing skeletal upper airway muscle function. Sugammadex reverses neuromuscular block by encapsulating rocuronium. However, its effects on upper airway integrity and breathing are unknown. Methods Fifty-one adult male rats were anaesthetized with isoflurane, tracheostomized, and a femoral artery and vein were cannulated. First, we compared the efficacy of sugammadex 15 mg kg−1 and neostigmine 0.06 mg kg−1 to reverse respiratory effects of rocuronium-induced partial paralysis [train-of-four ratio (T4/T1)=0.5]. Subsequently, we compared the safety of sugammadex and neostigmine given after recovery of the T4/T1 to 1, by measuring phasic genioglossus activity and breathing. Results During partial paralysis (T4/T1=0.5), time to recovery of minute volume to baseline values was 10.9 (2), 75.8 (18), and 153 (54) s with sugammadex, neostigmine, and placebo, respectively (sugammadex was significantly faster than neostigmine and placebo, P<0.05). Recovery of T4/T1 was also faster for sugammadex than neostigmine and placebo. Neostigmine administration after complete recovery of T4/T1 decreased upper airway dilator muscle activity to 64 (30)% of baseline and decreased tidal volume (P<0.05 for both variables), whereas sugammadex had no effect on either variable. Conclusions In contrast to neostigmine, which significantly impairs upper airway dilator muscle activity when given after recovery from neuromuscular block, a reversal dose of sugammadex given under the same conditions does not affect genioglossus muscle activity and normal breathing. Human studies will be required to evaluate the clinical relevance of our findings. PMID:18559352

  2. 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

  3. Amyloid-β deposition in mild cognitive impairment is associated with increased hippocampal activity, atrophy and clinical progression.

    PubMed

    Huijbers, Willem; Mormino, Elizabeth C; Schultz, Aaron P; Wigman, Sarah; Ward, Andrew M; Larvie, Mykol; Amariglio, Rebecca E; Marshall, Gad A; Rentz, Dorene M; Johnson, Keith A; Sperling, Reisa A

    2015-04-01

    Cross-sectional functional magnetic resonance imaging studies using a memory task in patients with mild cognitive impairment have produced discordant results, with some studies reporting increased hippocampal activity--consistent with findings in genetic at-risk populations--and other studies reporting decreased hippocampal activity, relative to normal controls. However, previous studies in mild cognitive impairment have not included markers of amyloid-β, which may be particularly important in prediction of progression along the Alzheimer's disease continuum. Here, we examine the contribution of amyloid-β deposition to cross-sectional and longitudinal measures of hippocampal functional magnetic resonance imaging activity, hippocampal volume, global cognition and clinical progression over 36 months in 33 patients with mild cognitive impairment. Amyloid-β status was examined with positron emission tomography imaging using Pittsburg compound-B, hippocampal functional magnetic resonance imaging activity was assessed using an associative face-name memory encoding task, and hippocampal volume was quantified with structural magnetic resonance imaging. Finally global cognition was assessed using the Mini-Mental State Examination and clinical progression was assessed using the Clinical Dementia Rating (Sum of Boxes). At baseline, amyloid-β positive patients with mild cognitive impairment showed increased hippocampal activation, smaller hippocampal volumes, and a trend towards lower Mini-Mental State Examination scores and higher Clinical Dementia Ratings compared to amyloid-β negative patients with mild cognitive impairment. Longitudinally, amyloid-β positive patients with mild cognitive impairment continued to show high levels of hippocampal activity, despite increasing rates of hippocampal atrophy, decline on the Mini-Mental State Examination and faster progression on the Clinical Dementia Ratings. When entered simultaneously into the same linear mixed model

  4. 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…

  5. Student Attitudes toward Impairment: An Assessment of Passive and Active Learning Methods in Urban Planning Education

    ERIC Educational Resources Information Center

    Lewis, John L.

    2011-01-01

    Designing for the needs of people with impairments has rarely been a significant feature of urban planning theory and education. Given the role of urban planners as shapers of the built environment and public policy, the prevalence of negative and misinformed attitudes among planners toward impaired populations has been highlighted as requiring…

  6. Amyloid-β deposition in mild cognitive impairment is associated with increased hippocampal activity, atrophy and clinical progression

    PubMed Central

    Mormino, Elizabeth C.; Schultz, Aaron P.; Wigman, Sarah; Ward, Andrew M.; Larvie, Mykol; Amariglio, Rebecca E.; Marshall, Gad A.; Rentz, Dorene M.; Johnson, Keith A.; Sperling, Reisa A.

    2015-01-01

    Cross-sectional functional magnetic resonance imaging studies using a memory task in patients with mild cognitive impairment have produced discordant results, with some studies reporting increased hippocampal activity—consistent with findings in genetic at-risk populations—and other studies reporting decreased hippocampal activity, relative to normal controls. However, previous studies in mild cognitive impairment have not included markers of amyloid-β, which may be particularly important in prediction of progression along the Alzheimer’s disease continuum. Here, we examine the contribution of amyloid-β deposition to cross-sectional and longitudinal measures of hippocampal functional magnetic resonance imaging activity, hippocampal volume, global cognition and clinical progression over 36 months in 33 patients with mild cognitive impairment. Amyloid-β status was examined with positron emission tomography imaging using Pittsburg compound-B, hippocampal functional magnetic resonance imaging activity was assessed using an associative face-name memory encoding task, and hippocampal volume was quantified with structural magnetic resonance imaging. Finally global cognition was assessed using the Mini-Mental State Examination and clinical progression was assessed using the Clinical Dementia Rating (Sum of Boxes). At baseline, amyloid-β positive patients with mild cognitive impairment showed increased hippocampal activation, smaller hippocampal volumes, and a trend towards lower Mini-Mental State Examination scores and higher Clinical Dementia Ratings compared to amyloid-β negative patients with mild cognitive impairment. Longitudinally, amyloid-β positive patients with mild cognitive impairment continued to show high levels of hippocampal activity, despite increasing rates of hippocampal atrophy, decline on the Mini-Mental State Examination and faster progression on the Clinical Dementia Ratings. When entered simultaneously into the same linear mixed model

  7. Repurposing psychiatric medicines to target activated microglia in anxious mild cognitive impairment and early Parkinson's disease.

    PubMed

    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. Mitogen-Activated Protein Kinase Phosphatase-2 Deletion Impairs Synaptic Plasticity and Hippocampal-Dependent Memory.

    PubMed

    Abdul Rahman, Nor Zaihana; Greenwood, Sam M; Brett, Ros R; Tossell, Kyoko; Ungless, Mark A; Plevin, Robin; Bushell, Trevor J

    2016-02-24

    Mitogen-activated protein kinases (MAPKs) regulate brain function and their dysfunction is implicated in a number of brain disorders, including Alzheimer's disease. Thus, there is great interest in understanding the signaling systems that control MAPK function. One family of proteins that contribute to this process, the mitogen-activated protein kinase phosphatases (MKPs), directly inactivate MAPKs through dephosphorylation. Recent studies have identified novel functions of MKPs in development, the immune system, and cancer. However, a significant gap in our knowledge remains in relation to their role in brain functioning. Here, using transgenic mice where the Dusp4 gene encoding MKP-2 has been knocked out (MKP-2(-/-) mice), we show that long-term potentiation is impaired in MKP-2(-/-) mice compared with MKP-2(+/+) controls whereas neuronal excitability, evoked synaptic transmission, and paired-pulse facilitation remain unaltered. Furthermore, spontaneous EPSC (sEPSC) frequency was increased in acute slices and primary hippocampal cultures prepared from MKP-2(-/-) mice with no effect on EPSC amplitude observed. An increase in synapse number was evident in primary hippocampal cultures, which may account for the increase in sEPSC frequency. In addition, no change in ERK activity was detected in both brain tissue and primary hippocampal cultures, suggesting that the effects of MKP-2 deletion were MAPK independent. Consistent with these alterations in hippocampal function, MKP-2(-/-) mice show deficits in spatial reference and working memory when investigated using the Morris water maze. These data show that MKP-2 plays a role in regulating hippocampal function and that this effect may be independent of MAPK signaling. PMID:26911683

  9. Changes in everyday function among individuals with psychometrically defined Mild Cognitive Impairment in the ACTIVE Study

    PubMed Central

    Wadley, Virginia G.; Crowe, Michael; Marsiske, Michael; Cook, Sarah E.; Unverzagt, Frederick W.; Rosenberg, Adrienne L.; Rexroth, Daniel

    2007-01-01

    Objectives. Because many individuals with Mild Cognitive Impairment (MCI) will progress to a dementia diagnosis, this population is at high risk for losing functional independence. We examine trajectories of change in everyday function for individuals with cognitive deficits suggestive of MCI. Design. We utilized data from the longitudinal, multi-site Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study, which allowed for post-hoc classification of MCI status at baseline using psycho metric definitions for amnestic MCI, non-amnestic MCI, multi-domain MCI, and no MCI. Setting. Six U.S. cities. Participants. 2832 volunteers (mean age 74 years; 26% African American) living independently, recruited from senior housing, community centers, and hospitals and clinics. Measurements. Mixed effect models examined changes in self-reported instrumental and basic activities of daily living (IADLs and ADLs) from the MDS Home Care Interview in 2,358 participants over a three-year period. Results. In models for IADL performance, IADL difficulty, and a Daily Functioning Composite, there was a significant time by MCI classification interaction for each MCI subtype, indicating that all MCI groups showed faster rates of decline in everyday function relative to cognitively normal participants with no MCI. Conclusion. Results demonstrate the importance of MCI as a clinical entity that not only predicts progression to dementia but also predicts functional declines in activities that are key to autonomy and quality of life. MCI classification guidelines should allow for functional changes in MCI, and clinicians should monitor for such changes. Preservation of function may serve as a meaningful outcome for intervention efforts. PMID:17661957

  10. 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

  11. NK Cells are Activated in Amnestic Mild Cognitive Impairment but not in Mild Alzheimer's Disease Patients.

    PubMed

    Le Page, Aurélie; Bourgade, Karine; Lamoureux, Julie; Frost, Eric; Pawelec, Graham; Larbi, Anis; Witkowski, Jacek M; Dupuis, Gilles; Fülöp, Tamás

    2015-01-01

    Alzheimerś disease (AD) is a progressive irreversible neurological brain disorder characterized by accumulation of amyloid-β, amyloid plaques, and neurofibrillary tangles. Inflammation and immune alterations have been linked to AD, suggesting that the peripheral immune system plays a role during the asymptomatic period of AD. NK cells participate in innate immune surveillance against intracellular pathogens and malignancy but their role in AD remains controversial. We have investigated changes in peripheral NK cell phenotypes and functions in amnestic mild cognitive impairment (aMCI, n = 10), patients with mild AD (mAD, n = 11), and healthy elderly controls (n = 10). Patients selected according to NINCDS-ADRDA criteria were classified using neuropsychological assessment tests. Phenotype analysis revealed differences in expression of CD16 (increased in mAD), NKG2A (decreased in aMCI), and TLR2 and TLR9 (both decreased in mAD). Functional assays revealed that NK cell killing activity and degranulation (CD107 expression) were unchanged in the three groups. In contrast, expression of the CD95 receptor was increased in aMCI and mAD. Granzyme B expression and cytokine production (TNFα, IFNγ) were increased in aMCI but not in mAD. CCL19- but not CCL21-dependent chemotaxis was decreased in aMCI and mAD, despite the fact that CCR7 expression was increased in aMCI. Our data suggest that the number of alterations observed in peripheral NK cells in aMCI represent an activation state compared to mAD patients and that may reflect an active immune response against a still to be defined aggression. PMID:25720398

  12. 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...

  13. 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…

  14. Development and psychometric properties of the Y-PASS questionnaire to assess correlates of lunchtime and after-school physical activity in children

    PubMed Central

    2014-01-01

    Background To frame interventions, it is useful to understand context- and time-specific correlates of children’s physical activity. To do this, we need accurate assessment of these correlates. There are currently no measures that assess correlates at all levels of the social ecological model, contain items that are specifically worded for the lunchtime and/or after-school time periods, and assess correlates that have been conceptualised and defined by children. The aim of this study was to develop and evaluate the psychometric properties of the lunchtime and after-school Youth Physical Activity Survey for Specific Settings (Y-PASS) questionnaires. Methods The Y-PASS questionnaire was administered to 264 South Australian children (146 boys, 118 girls; mean age = 11.7 ± 0.93 years). Factorial structure and internal consistency of the intrapersonal, sociocultural and physical environmental/policy lunchtime and after-school subscales were examined through an exploratory factor analysis. The test-retest reliability of the Y-PASS subscales was assessed over a one-week period on a subsample of children (lunchtime Y-PASS: n = 12 boys, 12 girls, mean age of 11.6 ± 0.8 years; after-school Y-PASS: n = 9 boys, 13 girls; mean age = 11.4 ± 0.9 years). Results For the lunchtime Y-PASS, three factors were identified under each of the intrapersonal, sociocultural and physical environmental/policy subscales. For the after-school Y-PASS, six factors were identified in the intrapersonal subscale, four factors in the sociocultural subscale and seven factors in the physical environmental/policy subscale. Following item reduction, all subscales demonstrated acceptable internal consistency (Cronbach alpha = 0.78 – 0.85), except for the lunchtime sociocultural subscale (Cronbach alpha = 0.55). The factors and items demonstrated fair to very high test-retest reliability (ICC = 0.26 – 0.93). Conclusion The preliminary reliability and

  15. Development and validation of a questionnaire assessing volitional competencies to enhance the performance of physical activities in chronic low back pain patients

    PubMed Central

    2011-01-01

    Background Motivation has long been emphasized as the most important determinant of action. However, there is a substantial gap between people's goals and their attainment. Patients may be motivated and yet unable to take action if their volitional competencies are insufficient. One of the important tasks of volition is goal-maintenance. Research has stressed the importance of a volitional tool, the implementation intentions. Implementation intentions indicate where, when, and how the action leading to the goal will be performed. Forming implementation intentions favours the execution of goal-directed efforts, and reinforces the relationship between intentions and behaviours. Results from various studies clearly suggest that volitional competencies and implementation intentions could play a role in low back pain (LBP) patients. However, there is at present no questionnaire allowing assessing the capacity of implementation intentions of physical activities in LBP patients. Methods/Design This study will develop such a questionnaire, using a 3-step approach. A first qualitative step to build categories and generate items; 30 patients suffering chronic LBP will be invited to participate in semi-structured interviews; verbatim and derived items will then be submitted to a panel of experts, using a Delphi method; a second quantitative step to examine the properties of items, and determine the factorial structure of the questionnaire; 100 patients suffering chronic LBP will be recruited to respond to this phase; and third, preliminary psychometric analyses (item-scale correlations, construct validity, reliability); 180 chronic LBP patients will be recruited for this phase of the study. The relationships between implementation intentions and variables affecting physical activity on chronic LBP patients, i.e. pain, physical capacities, fear-avoidance beliefs, kinesiophobia, work status, and level of physical activity will be considered. Discussion Developing a

  16. 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.

  17. Age- and Sex-Specific Criterion Validity of the Health Survey for England Physical Activity and Sedentary Behavior Assessment Questionnaire as Compared With Accelerometry

    PubMed Central

    Scholes, Shaun; Coombs, Ngaire; Pedisic, Zeljko; Mindell, Jennifer S.; Bauman, Adrian; Rowlands, Alex V.; Stamatakis, Emmanuel

    2014-01-01

    The criterion validity of the 2008 Physical Activity and Sedentary Behavior Assessment Questionnaire (PASBAQ) was examined in a nationally representative sample of 2,175 persons aged ≥16 years in England using accelerometry. Using accelerometer minutes/day greater than or equal to 200 counts as a criterion, Spearman's correlation coefficient (ρ) for PASBAQ-assessed total activity was 0.30 (95% confidence interval (CI): 0.25, 0.35) in women and 0.20 (95% CI: 0.15, 0.26) in men. Correlations between accelerometer counts/minute of wear time and questionnaire-assessed relative energy expenditure (metabolic equivalent-minutes/day) were higher in women (ρ = 0.41, 95% CI: 0.36, 0.46) than in men (ρ = 0.32, 95% CI: 0.26, 0.38). Similar correlations were observed for minutes/day spent in vigorous activity (women: ρ = 0.39, 95% CI: 0.33, 0.46; men: ρ = 0.31, 95% CI: 0.26, 0.36) and moderate-to-vigorous activity (women: ρ = 0.42, 95% CI: 0.36, 0.48; men: ρ = 0.38, 95% CI: 0.32, 0.45). Correlations for time spent being sedentary (<100 counts/minute) were 0.30 (95% CI: 0.24, 0.35) and 0.25 (95% CI: 0.19, 0.30) in women and men, respectively. Sedentary behavior correlations showed no sex difference. The validity of sedentary behavior and total physical activity was higher in older age groups, but validity was higher in younger persons for vigorous-intensity activity. The PASBAQ is a useful and valid instrument for ranking individuals according to levels of physical activity and sedentary behavior. PMID:24863551

  18. Constitutive activation of MET signaling impairs myogenic differentiation of rhabdomyosarcoma and promotes its development and progression

    PubMed Central

    Szewczyk, Barbara; Adamus, Tomasz; Lukasiewicz, Ewa; Miekus, Katarzyna; Majka, Marcin

    2015-01-01

    Rhabdomyosarcoma (RMS) is a soft tissue sarcoma, which may originate from impaired differentiation of mesenchymal stem cells (MSC). Expression of MET receptor is elevated in alveolar RMS subtype (ARMS) which is associated with worse prognosis, compared to embryonal RMS (ERMS). Forced differentiation of ARMS cells diminishes MET level and, as shown previously, MET silencing induces differentiation of ARMS. In ERMS cells introduction of TPR-MET oncogene leads to an uncontrolled overstimulation of the MET receptor downstream signaling pathways. In vivo, tumors formed by those cells in NOD-SCID mice display inhibited differentiation, enhanced proliferation, diminished apoptosis and increased infiltration of neutrophils. Consequently, tumors grow significantly faster and they display enhanced ability to metastasize to lungs and to vascularize due to elevated VEGF, MMP9 and miR-378 expression. In vitro, TPR-MET ERMS cells display enhanced migration, chemotaxis and invasion toward HGF and SDF-1. Introduction of TPR-MET into MSC increases survival and may induce expression of early myogenic factors depending on the genetic background, and it blocks terminal differentiation of skeletal myoblasts. To conclude, our results suggest that activation of MET signaling may cause defects in myogenic differentiation leading to rhabdomyosarcoma development and progression. PMID:26384300

  19. Constitutive activation of MET signaling impairs myogenic differentiation of rhabdomyosarcoma and promotes its development and progression.

    PubMed

    Skrzypek, Klaudia; Kusienicka, Anna; Szewczyk, Barbara; Adamus, Tomasz; Lukasiewicz, Ewa; Miekus, Katarzyna; Majka, Marcin

    2015-10-13

    Rhabdomyosarcoma (RMS) is a soft tissue sarcoma, which may originate from impaired differentiation of mesenchymal stem cells (MSC). Expression of MET receptor is elevated in alveolar RMS subtype (ARMS) which is associated with worse prognosis, compared to embryonal RMS (ERMS). Forced differentiation of ARMS cells diminishes MET level and, as shown previously, MET silencing induces differentiation of ARMS. In ERMS cells introduction of TPR-MET oncogene leads to an uncontrolled overstimulation of the MET receptor downstream signaling pathways. In vivo, tumors formed by those cells in NOD-SCID mice display inhibited differentiation, enhanced proliferation, diminished apoptosis and increased infiltration of neutrophils. Consequently, tumors grow significantly faster and they display enhanced ability to metastasize to lungs and to vascularize due to elevated VEGF, MMP9 and miR-378 expression. In vitro, TPR-MET ERMS cells display enhanced migration, chemotaxis and invasion toward HGF and SDF-1. Introduction of TPR-MET into MSC increases survival and may induce expression of early myogenic factors depending on the genetic background, and it blocks terminal differentiation of skeletal myoblasts. To conclude, our results suggest that activation of MET signaling may cause defects in myogenic differentiation leading to rhabdomyosarcoma development and progression. PMID:26384300

  20. Analysis of spontaneous MEG activity in mild cognitive impairment using spectral entropies and disequilibrium measures.

    PubMed

    Bruña, Ricardo; Poza, Jesús; Gómez, Carlos; Fernández, Alberto; Hornero, Roberto

    2010-01-01

    The aim of this study was to explore the ability of several spectral entropies and disequilibrium measures to discriminate between spontaneous magnetoencephalographic (MEG) oscillations from 18 mild cognitive impairment (MCI) patients and 24 controls. The Shannon spectral entropy (SSE), Tsallis spectral entropy (TSE), and Rényi spectral entropy (RSE) were calculated from the normalized power spectral density to evaluate the irregularity patterns. In addition, the Euclidean (ED) and Wootters (WD) distances were computed as disequilibrium measures. Results revealed statistically significant lower SSE and TSE(2) values for MCI patients than for controls (p < 0.05) in the right lateral region of the brain. ED also obtained statistically significant lower values for MCI patients than for controls using the (p < 0.05) in the right lateral region of the brain. These findings suggest that MCI is associated with a significant decrease in irregularity of MEG activity. In addition, the highest accuracy of 64.3% was achieved by the SSE. We conclude that measures from information theory can be useful to both characterize abnormal brain dynamics and help in MCI detection. PMID:21097360

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

    PubMed

    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. 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

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

    PubMed

    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. 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

  5. Cadmium Impairs p53 Activity in HepG2 Cells.

    PubMed

    Urani, C; Melchioretto, P; Fabbri, M; Bowe, G; Maserati, E; Gribaldo, L

    2014-01-01

    Cadmium and cadmium compounds are contaminants of the environment, food, and drinking water and are important constituents of cigarette smoke. Cd exposure has also been associated with airborne particulate CdO and with Cd-containing quantum dots in medical therapy. Adverse cadmium effects reported in the literature have stimulated during recent years an ongoing discussion to better elucidate cadmium outcomes at cell and molecular level. The present work is designed to gain an insight into the mechanism of p53 impairment at gene and protein level to understand Cd-induced resistance to apoptosis. We used a hepatoma cell line (HepG2) derived from liver, known to be metal responsive. At genotoxic cadmium concentrations no cell cycle arrest was observed. The p53 at gene and protein level was not regulated. Fluorescence images showed that p53 was correctly translocated into the nucleus but that the p21(Cip1/WAF-1), a downstream protein of p53 network involved in cell cycle regulation, was not activated at the highest cadmium concentrations used. The miRNAs analysis revealed an upregulation of mir-372, an miRNA able to affect p21(Cip1/WAF-1) expression and promote cell cycle progression and proliferation. The role of metallothioneins and possible conformational changes of p53 are discussed. PMID:25101185

  6. 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

  7. 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

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

    PubMed Central

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

    2015-01-01

    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. PMID:26157174

  9. GLUT1 activity contributes to the impairment of PEDF secretion by the RPE

    PubMed Central

    Calado, Sofia M.; Alves, Liliana S.; Simão, Sónia

    2016-01-01

    Purpose In this study, we aimed to understand whether glucose transporter 1 (GLUT1) activity affects the secretion capacity of antiangiogenic factor pigment epithelium-derived factor (PEDF) by the RPE cells, thus explaining the reduction in PEDF levels observed in patients with diabetic retinopathy (DR). Methods Analysis of GLUT1 expression, localization, and function was performed in vitro in RPE cells (D407) cultured with different glucose concentrations, corresponding to non-diabetic (5 mM of glucose) and diabetic (25 mM of glucose) conditions, further subjected to normoxia or hypoxia. The expression of PEDF was also evaluated in the secretome of the cells cultured in these conditions. Analysis of GLUT1 and PEDF expression was also performed in vivo in the RPE of Ins2Akita diabetic mice and age-matched wild-type (WT) controls. Results We observed an increase in GLUT1 under hypoxia in a glucose-dependent manner, which we found to be directly associated with the translocation and stabilization of GLUT1 in the cell membrane. This stabilization led to an increase in glucose uptake by RPE cells. This increase was followed by a decrease in PEDF expression in RPE cells cultured in conditions that simulated DR. Compared with non-diabetic WT mice, the RPE of Ins2Akita mice showed increased GLUT1 overexpression with a concomitant decrease in PEDF expression. Conclusions Collectively, our data show that expression of GLUT1 is stimulated by hyperglycemia and low oxygen supply, and this overexpression was associated with increased activity of GLUT1 in the cell membrane that contributes to the impairment of the RPE secretory function of PEDF. PMID:27440994

  10. Myeloma cells can corrupt senescent mesenchymal stromal cells and impair their anti-tumor activity

    PubMed Central

    Özcan, Servet; Alessio, Nicola; Acar, Mustafa Burak; Toprak, Güler; Gönen, Zeynep Burcin; Peluso, Gianfranco; Galderisi, Umberto

    2015-01-01

    Senescent cells secrete several molecules that help to prevent the progression of cancer. However, cancer cells can also misuse these secreted elements to survive and grow. Since the molecular and functional bases of these different elements remain poorly understood, we analyzed the effect of senescent mesenchymal stromal cell (MSC) secretome on the biology of ARH-77 myeloma cells. In addition to differentiating in mesodermal derivatives, MSCs have sustained interest among researchers by supporting hematopoiesis, contributing to tissue homeostasis, and modulating inflammatory response, all activities accomplished primarily by the secretion of cytokines and growth factors. Moreover, senescence profoundly affects the composition of MSC secretome. In this study, we induced MSC senescence by oxidative stress, DNA damage, and replicative exhaustion. While the first two are considered to induce acute senescence, extensive proliferation triggers replicative (i.e., chronic) senescence. We cultivated cancer cells in the presence of acute and chronic senescent MSC-conditioned media and evaluated their proliferation, DNA damage, apoptosis, and senescence. Our findings revealed that senescent secretomes induced apoptosis or senescence, if not both, to different extents. This anti-tumor activity became heavily impaired when secretomes were collected from senescent cells previously in contact (i.e., primed) with cancer cells. Our analysis of senescent MSC secretomes with LC-MS/MS followed by Gene Ontology classification further indicated that priming with cancer profoundly affected secretome composition by abrogating the production of pro-senescent and apoptotic factors. We thus showed for the first time that compared with cancer-primed MSCs, naïve senescent MSCs can exert different effects on tumor progression. PMID:26498687

  11. 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. PMID:26157174

  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. 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...

  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. PMID:26971628

  15. Enhanced resting-state functional connectivity between core memory-task activation peaks is associated with memory impairment in MCI.

    PubMed

    Zhang, Yifei; Simon-Vermot, Lee; Araque Caballero, Miguel Á; Gesierich, Benno; Taylor, Alexander N W; Duering, Marco; Dichgans, Martin; Ewers, Michael

    2016-09-01

    Resting-state functional connectivity (FC) is altered in Alzheimer's disease (AD) but its predictive value for episodic memory impairment is debated. Here, we aimed to assess whether resting-state FC in core brain regions activated during memory-task functional magnetic resonance imaging is altered and predictive of memory performance in AD and amnestic mild cognitive impairment (aMCI). Twenty-three elderly cognitively healthy controls (HC), 76 aMCI subjects, and 19 AD dementia patients were included. We computed resting-state FC between 18 meta-analytically determined peak coordinates of brain activation during successful memory retrieval. Higher FC between the parahippocampus, parietal cortex, and the middle frontal gyrus was observed in both AD and mild cognitive impairment compared to HC (false-discovery rate-corrected p < 0.05). The increase in FC between the parahippocampus and middle frontal gyrus was associated with reduced episodic memory in aMCI, independent of amyloid-beta positron emission tomography binding and apolipoprotein E ε4-carrier status. In conclusion, increased parahippocampal-prefrontal FC is predictive of impaired episodic memory in aMCI and may reflect a dysfunctional change within the episodic memory-related neural network. PMID:27459924

  16. 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 ...

  17. Impaired activation of Stat1 and c-Jun as a possible defect in macrophages of patients with active tuberculosis.

    PubMed

    Esquivel-Solís, H; Quiñones-Falconi, F; Zarain-Herzberg, A; Amieva-Fernández, R I; López-Vidal, Y

    2009-10-01

    Studies of patients with active tuberculosis (TB) and infected healthy individuals have shown that interferon (IFN)-gamma is present in sites of Mycobacterium tuberculosis infection in comparable levels. This suggests that there is a deficiency in the macrophage response to IFN-gamma in TB patients. We used recombinant human IFN-gamma to stimulate adherent monocyte-derived macrophages from three groups of people: patients with active tuberculosis (TBP), their healthy household contacts (HHC) and healthy uninfected controls from the community (CC). We then evaluated the ability of the macrophages to inhibit the growth of M. tuberculosis H37Rv as well as their cytokine profile at early in infection (48 h). After IFN-gamma treatment, macrophages of healthy individuals (HHC and CC) controlled M. tuberculosis growth and produced mainly nitric oxide (NO) and interleukin (IL)-12p70, whereas TBP macrophages did not kill M. tuberculosis. Additionally, TBP macrophages produced low levels of NO and IL-12p70 and high levels of tumour necrosis factor (TNF)-alpha and IL-10. Transforming growth factor (TGF)-beta levels were similar among all three groups. M. tuberculosis infection had little effect on the cytokine response after IFN-gamma stimulus, but infection alone induced more IL-10 and TGF-beta in TBP macrophages. There were no differences in Stat1 nuclear translocation and DNA binding between the groups. However, the phosphorylated Stat1 and c-Jun (AP-1) in nuclear protein extracts was diminished in TBP macrophages compared to macrophages of healthy individuals. These results indicate an impairment of Stat1-dependent and Stat1-independent IFN-gamma signalling in macrophages of people with active tuberculosis, suggesting a different molecular regulation that could impact macrophage functionality and disease outcome. PMID:19737230

  18. 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

  19. 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

  20. MDA-5 activation by cytoplasmic double-stranded RNA impairs endothelial function and aggravates atherosclerosis.

    PubMed

    Asdonk, Tobias; Steinmetz, Martin; Krogmann, Alexander; Ströcker, Christine; Lahrmann, Catharina; Motz, Inga; Paul-Krahe, Kathrin; Flender, Anna; Schmitz, Theresa; Barchet, Winfried; Hartmann, Gunther; Nickenig, Georg; Zimmer, Sebastian

    2016-09-01

    Recent studies have highlighted the relevance of viral nucleic acid immunorecognition by pattern recognition receptors in atherogenesis. Melanoma differentiation associated gene 5 (MDA-5) belongs to the intracellular retinoic acid inducible gene-I like receptors and its activation promotes pro-inflammatory mechanisms. Here, we studied the effect of MDA-5 stimulation in vascular biology. To gain insights into MDA-5 dependent effects on endothelial function, cultured human coronary artery endothelial cells (HCAEC) were transfected with the synthetic MDA-5 agonist polyIC (long double-stranded RNA). Human coronary endothelial cell expressed MDA-5 and reacted with receptor up-regulation upon stimulation. Reactive oxygen species formation, apoptosis and the release of pro-inflammatory cytokines was enhanced, whereas migration was significantly reduced in response to MDA-5 stimulation. To test these effects in vivo, wild-type mice were transfected with 32.5 μg polyIC/JetPEI or polyA/JetPEI as control every other day for 7 days. In polyIC-treated wild-type mice, endothelium-dependent vasodilation and re-endothelialization was significantly impaired, vascular oxidative stress significantly increased and circulating endothelial microparticles and circulating endothelial progenitor cells significantly elevated compared to controls. Importantly, these effects could be abrogated by MDA-5 deficiency in vivo. Finally, chronic MDA-5 stimulation in Apolipoprotein E/toll-like receptor 3 (TLR3) double(-) deficient (ApoE(-/-) /TLR3(-/-) ) mice-enhanced atherosclerotic plaque formation. This study demonstrates that MDA-5 stimulation leads to endothelial dysfunction, and has the potential to aggravate atherosclerotic plaque burden in murine atherosclerosis. Thus, the spectrum of relevant innate immune receptors in vascular diseases and atherogenesis might not be restricted to TLRs but also encompasses the group of RLRs including MDA-5. PMID:27130701

  1. Patient Acceptable Symptom State in Self-Report Questionnaires and Composite Clinical Disease Index for Assessing Rheumatoid Arthritis Activity: Identification of Cut-Off Points for Routine Care

    PubMed Central

    Salaffi, Fausto; Carotti, Marina; Gutierrez, Marwin; Di Carlo, Marco; De Angelis, Rossella

    2015-01-01

    Objective. To provide information on the value of Patient Acceptable Symptom State (PASS) in rheumatoid arthritis (RA) by the identification of PASS thresholds for patient-reported outcomes (PROs) composite scores. Methods. The characteristics of RA patients with affirmative and negative assignment to PASS were compared. Contributors to physician response were estimated by logistic regression models and PASS thresholds by the 75th percentile and receiver-operating characteristic (ROC) curve methods. Results. 303 RA patients completed the study. All PROs were different between the PASS (+) and PASS (−) groups (p < 0.0001). The thresholds with the 75th percentile approach were 2.0 for the RA Impact of Disease (RAID) score, 2.5 for the PRO-CLinical ARthritis Activity (PRO-CLARA) index, and 1.0 for the Recent-Onset Arthritis Disability (ROAD) questionnaire. The cut-off values for Clinical Disease Activity Index (CDAI) were in the moderate range of disease activity. Assessing the size of the logistic regression coefficients, the strongest predictors of PASS were the disease activity (p = 0.0007) and functional state level (0.006). Conclusion. PASS thresholds were relatively high and many patients in PASS had moderate disease activity states according to CDAI. Factors such as disease activity and physical function may influence a negative PASS. PMID:26167506

  2. 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. PMID:26500222

  3. The PACE Study: A randomised clinical trial of cognitive activity (CA) for older adults with mild cognitive impairment (MCI)

    PubMed Central

    2009-01-01

    Background Research evidence from observational studies suggests that cognitive activity reduces the risk of cognitive impairment in later life as well as the rate of cognitive decline of people with dementia. The Promoting Healthy Ageing with Cognitive Exercise (PACE) study has been designed to determine whether a cognitive activity intervention decreases the rate of cognitive decline amongst older adults with mild cognitive impairment (MCI). Methods/Design The study will recruit 160 community-dwelling men and women aged 65 years of age or over with mild cognitive impairment (MCI). Participants will be randomly allocated to two treatment groups: non-specific education and cognitive activity. The intervention will consist of ten 90-minute sessions delivered twice per week over a period of five weeks. The primary outcome measure of the study is the change from baseline in the total score on the Cambridge Cognitive Score (CAMCOG). Secondary outcomes of interest include changes in memory, attention, executive functions, mood and quality of life. Primary endpoints will be collected 12, 52 and 104 weeks after the baseline assessment. Discussion The proposed project will produce the best available evidence on the merits of increased cognitive activity as a strategy to prevent cognitive decline among older adults with MCI. We anticipate that the results of this study will have implications for the development of evidence-based preventive strategies to reduce the rate of cognitive decline amongst older people at risk of dementia. Trial registration ACTRN12608000556347 PMID:20003398

  4. Hepatic Glycogen Supercompensation Activates AMP-Activated Protein Kinase, Impairs Insulin Signaling, and Reduces Glycogen Deposition in the Liver

    PubMed Central

    Winnick, Jason J.; An, Zhibo; Ramnanan, Christopher J.; Smith, Marta; Irimia, Jose M.; Neal, Doss W.; Moore, Mary Courtney; Roach, Peter J.; Cherrington, Alan D.

    2011-01-01

    OBJECTIVE The objective of this study was to determine how increasing the hepatic glycogen content would affect the liver’s ability to take up and metabolize glucose. RESEARCH DESIGN AND METHODS During the first 4 h of the study, liver glycogen deposition was stimulated by intraportal fructose infusion in the presence of hyperglycemic-normoinsulinemia. This was followed by a 2-h hyperglycemic-normoinsulinemic control period, during which the fructose infusion was stopped, and a 2-h experimental period in which net hepatic glucose uptake (NHGU) and disposition (glycogen, lactate, and CO2) were measured in the absence of fructose but in the presence of a hyperglycemic-hyperinsulinemic challenge including portal vein glucose infusion. RESULTS Fructose infusion increased net hepatic glycogen synthesis (0.7 ± 0.5 vs. 6.4 ± 0.4 mg/kg/min; P < 0.001), causing a large difference in hepatic glycogen content (62 ± 9 vs. 100 ± 3 mg/g; P < 0.001). Hepatic glycogen supercompensation (fructose infusion group) did not alter NHGU, but it reduced the percent of NHGU directed to glycogen (79 ± 4 vs. 55 ± 6; P < 0.01) and increased the percent directed to lactate (12 ± 3 vs. 29 ± 5; P = 0.01) and oxidation (9 ± 3 vs. 16 ± 3; P = NS). This change was associated with increased AMP-activated protein kinase phosphorylation, diminished insulin signaling, and a shift in glycogenic enzyme activity toward a state discouraging glycogen accumulation. CONCLUSIONS These data indicate that increases in hepatic glycogen can generate a state of hepatic insulin resistance, which is characterized by impaired glycogen synthesis despite preserved NHGU. PMID:21270252

  5. 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

  6. Cross-cultural, age and gender validation of a computerised questionnaire measuring personal, social and environmental associations with children's physical activity: the European Youth Heart Study

    PubMed Central

    Ommundsen, Yngvar; Page, Angie; Ku, Po-Wen; Cooper, Ashley R

    2008-01-01

    Objective This study investigated the construct validity of a computerised self-assessment tool to measure psychological, social and environmental influences of young peoples' physical activity. First, analyses of the measure's factorial validity, invariance across, age, gender culture were conducted. Second, the ability of the derived subscales to discriminate between children representing different levels of self-reported and objectively measured physical activity behaviour was examined. Methods Participants were 1875 boys and 2078 girls (total = 3958) aged 9–10 years (n = 1955, mean age = 9.65 ± 0.42) and 15–16 years (n = 2003, mean age = 15.49 ± 0.50) from four European countries in Northern, Southern and Eastern Europe who took part in the European Youth Heart Study (EYHS). Children completed the computerised self-assessment tool with support from the researcher if requested. Self-reported exercise and an objective measure of physical activity (Actigraph model 7164) were used for additional construct validation purposes. Results Overall evidence of good fit indicating satisfactory factorial validity and cross-cultural, age and gender invariance for 3 of the 4 measurement models were obtained. The majority of measures were also significantly different for those with high versus low levels of physical activity. Conclusion Overall, the computerised questionnaire holds promise for use cross-culturally with male and female children and adolescents to measure perceived personal, social and environmental influences on physical activity. Further development of the measures pertaining to perceived environmental influences seems warranted. PMID:18489736

  7. 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. PMID:25143549

  8. Objective assessment of intensity categorization of the previous day physical activity recall questionnaire in 11-13 year old children.

    PubMed

    McBrearty, Donough; McCrorie, Paul; Granat, Malcolm; Duncan, Elaine; Stansfield, Ben

    2014-11-01

    The Previous Day Physical Activity Recall (PDPAR) self-report questionnaire asks children to categories their time in 30 min blocks under activity codes and activity intensity (ActInt). Text and visual descriptors of ActInt are used which include posture and stepping intensity. This study aimed to objectively examine postures and stepping activity associated with PDPAR ActInt. Forty-three (19M/24F) 11-13 year children completed the PDPAR and wore a physical activity monitor (8 d). Within 30 min blocks the % sitting/lying, standing and stepping, steps, cadence and sit-to-stand transitions (STS) were examined by PDPAR ActInt across and within all activity codes. Data (14 083 30 min blocks) showed from light to moderate ActInt lower sedentary time, higher standing and stepping time, steps, sit-to-stand transitions and cadence (all P < 0.001). Between moderate and hard ActInt, time sedentary was lower and time stepping, steps and STS higher (all P < 0.005). No significant differences between hard and very hard. There was a wide variation of activity levels between activity codes within ActInt. ActInt within the PDPAR was not used consistently between activity codes. However, over all codes children demonstrated that they could distinguish between light and moderate and in some objective measures between moderate and hard, but not between hard and very hard ActInt. PMID:25340303

  9. Role of hypothalamic adenosine 5'-monophosphate-activated protein kinase in the impaired counterregulatory response induced by repetitive neuroglucopenia.

    PubMed

    Alquier, Thierry; Kawashima, Junji; Tsuji, Youki; Kahn, Barbara B

    2007-03-01

    Antecedent hypoglycemia blunts counterregulatory responses that normally restore glycemia, a phenomenon known as hypoglycemia-associated autonomic failure (HAAF). The mechanisms leading to impaired counterregulatory responses are largely unknown. Hypothalamic AMP-activated protein kinase (AMPK) acts as a glucose sensor. To determine whether failure to activate AMPK could be involved in the etiology of HAAF, we developed a model of HAAF using repetitive intracerebroventricular (icv) injection of 2-deoxy-D-glucose (2DG) resulting in transient neuroglucopenia in normal rats. Ten minutes after a single icv injection of 2DG, both alpha1- and alpha2-AMPK activities were increased 30-50% in arcuate and ventromedial/dorsomedial hypothalamus but not in other hypothalamic regions, hindbrain, or cortex. Increased AMPK activity persisted in arcuate hypothalamus at 60 min after 2DG injection when serum glucagon and corticosterone levels were increased 2.5- to 3.4-fold. When 2DG was injected icv daily for 4 d, hypothalamic alpha1- and alpha2-AMPK responses were markedly blunted in arcuate hypothalamus, and alpha1-AMPK was also blunted in mediobasal hypothalamus 10 min after 2DG on d 4. Both AMPK isoforms were activated normally in arcuate hypothalamus at 60 min. Counterregulatory hormone responses were impaired by recurrent neuroglucopenia and were partially restored by icv injection of 5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside, an AMPK activator, before 2DG. Glycogen content increased 2-fold in hypothalamus after recurrent neuroglucopenia, suggesting that glycogen supercompensation could be involved in down-regulating the AMPK glucose-sensing pathway in HAAF. Thus, activation of hypothalamic AMPK may be important for the full counterregulatory hormone response to neuroglucopenia. Furthermore, impaired or delayed AMPK activation in specific hypothalamic regions may play a critical role in the etiology of HAAF. PMID:17185376

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

    PubMed Central

    Liang, Yan; Lau, Patrick W.C.; Huang, Wendy Y.J.; Maddison, Ralph; Baranowski, Tom

    2014-01-01

    Background Physical activity (PA) correlates have not been extensively studied in Hong Kong children. Objective 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. Methods Sample 1 (n = 273, aged 8–12 years) was recruited (May–June, 2013) from two primary schools. Confirmatory factor analyses (CFA) were conducted to assess factorial validity. Criterion validity was assessed by correlating measured constructs with self-reported PA. Cronbach's alpha was computed to assess scale internal consistency. The intraclass correlation coefficient (ICC) was performed to assess scale test–retest reliability. Criterion validity was further examined in Sample 2 (n = 84, aged 8–12 years) from a third school by correlating measured constructs with objectively measured PA collected in September 2013 and February 2014. Results The CFA results supported the one-factor structure of the scales. All PA correlates were significantly (p < 0.01) associated with self-reported PA in Sample 1. Self-efficacy and enjoyment were significantly (p < 0.05) correlated with objectively measured PA in Sample 2. All the scales demonstrated acceptable internal consistency. All ICC values of the scales suggested acceptable test–retest reliability. Conclusion The results provide psychometric support for using the scales to measure PA correlates among Hong Kong Chinese children. PMID:26844039

  11. Preliminary cognitive scale of basic and instrumental activities of daily living for dementia and mild cognitive impairment.

    PubMed

    Rodríguez-Bailón, María; Montoro-Membila, Nuria; Garcia-Morán, Tamara; Arnedo-Montoro, María Luisa; Funes Molina, María Jesús

    2015-01-01

    In the present study we explored cognitive and functional deficits in patients with multidomain mild cognitive impairment (MCI), patients with dementia, and healthy age-matched control participants using the Cognitive Scale for Basic and Instrumental Activities of Daily Living, a new preliminary informant-based assessment tool. This tool allowed us to evaluate four key cognitive abilities-task memory schema, error detection, problem solving, and task self-initiation-in a range of basic and instrumental activities of daily living (BADL and IADL, respectively). The first part of the present study was devoted to testing the psychometric adequateness of this new informant-based tool and its convergent validity with other global functioning and neuropsychological measures. The second part of the study was aimed at finding the patterns of everyday cognitive factors that best discriminate between the three groups. We found that patients with dementia exhibited impairment in all cognitive abilities in both basic and instrumental activities. By contrast, patients with MCI were found to have preserved task memory schema in both types of ADL; however, such patients exhibited deficits in error detection and task self-initiation but only in IADL. Finally, patients with MCI also showed a generalized problem solving deficit that affected even BADL. Studying various cognitive processes instantiated in specific ADL differing in complexity seems a promising strategy to further understand the specific relationships between cognition and function in these and other cognitively impaired populations. PMID:25805061

  12. Caspase-6 activity in the CA1 region of the hippocampus induces age-dependent memory impairment

    PubMed Central

    LeBlanc, A C; Ramcharitar, J; Afonso, V; Hamel, E; Bennett, D A; Pakavathkumar, P; Albrecht, S

    2014-01-01

    Active Caspase-6 is abundant in the neuropil threads, neuritic plaques and neurofibrillary tangles of Alzheimer disease brains. However, its contribution to the pathophysiology of Alzheimer disease is unclear. Here, we show that higher levels of Caspase-6 activity in the CA1 region of aged human hippocampi correlate with lower cognitive performance. To determine whether Caspase-6 activity, in the absence of plaques and tangles, is sufficient to cause memory deficits, we generated a transgenic knock-in mouse that expresses a self-activated form of human Caspase-6 in the CA1. This Caspase-6 mouse develops age-dependent spatial and episodic memory impairment. Caspase-6 induces neuronal degeneration and inflammation. We conclude that Caspase-6 activation in mouse CA1 neurons is sufficient to induce neuronal degeneration and age-dependent memory impairment. These results indicate that Caspase-6 activity in CA1 could be responsible for the lower cognitive performance of aged humans. Consequently, preventing or inhibiting Caspase-6 activity in the aged may provide an efficient novel therapeutic approach against Alzheimer disease. PMID:24413155

  13. Thromboxane-insensitive dog platelets have impaired activation of phospholipase C due to receptor-linked G protein dysfunction.

    PubMed Central

    Johnson, G J; Leis, L A; Dunlop, P C

    1993-01-01

    Human platelet thromboxane A2/prostaglandin H2 (TXA2/PGH2) receptors are linked to phosphoinositide-specific phospholipase C (PI-PLC) via a G protein tentatively identified as a member of the Gq class. In contrast, platelet thrombin receptors appear to activate PI-PLC via other unidentified G proteins. Platelets from most dogs are TXA2 insensitive (TXA2-); i.e., they do not aggregate irreversibly or secrete although they bind TXA2, but they respond normally to thrombin. In contrast, a minority of dogs have TXA2-sensitive (TXA2+) platelets that are responsive to TXA2. To determine the mechanism responsible for TXA2- platelets, we evaluated receptor activation of PI-PLC. Equilibrium binding of TXA2/PGH2 receptor agonists, [125I]BOP and [3H]U46619, and antagonist, [3H]SQ29,548, revealed comparable high-affinity binding to TXA2-, TXA2+, and human platelets. U46619-induced PI-PLC activation was impaired in TXA2- platelets as evidenced by reduced (a) phosphorylation of the 47-kD substrate of protein kinase C, (b) phosphatidic acid (PA) formation, (c) rise in cytosolic calcium concentration, and (d) inositol 1,4,5 trisphosphate (IP3) formation, while thrombin-induced PI-PLC activation was not impaired. GTPase activity stimulated by U46619, but not by thrombin, was markedly reduced in TXA2- platelets. Antisera to Gq class alpha subunits abolished U46619-induced GTPase activity in TXA2-, TXA2+, and human platelets. Direct G protein stimulation by GTP gamma S yielded significantly less PA and IP3 in TXA2- platelets. Immunotransfer blotting revealed comparable quantities of Gq class alpha-subunits in all three platelet types. Thus, TXA2- dog platelets have impaired PI-PLC activation in response to TXA2/PGH2 receptor agonists secondary to G protein dysfunction, presumably involving a member of the Gq class. Images PMID:8227362

  14. Nitric oxide pathway activity modulation alters the protective effects of (-)Epigallocatechin-3-gallate on reserpine-induced impairment in rats.

    PubMed

    Chen, Cheng-Neng; Chang, Kuo-Chi; Lin, Rui-Feng; Wang, Mao-Hsien; Shih, Ruoh-Lan; Tseng, Hsiang-Chien; Soung, Hung-Sheng; Tsai, Cheng-Chia

    2016-05-15

    Reserpine (RES) has been reported to increase the brain's neural oxidative stress and cause cognitive dysfunction. Having powerful antioxidative properties, green tea catechins, especially (-)epigallocatechin-3-gallate (EGCG), are able to protect against many oxidative injuries. In this study, we examined the protecting properties of EGCG on RES-induced impairment of short-term memory in three-month-old male Wistar rats. RES (1mg/kg i.p.) induced memory impairment (p<0.001) as evaluated by the social recognition task. EGCG treatment (100mg/kg i.p. for 7days, starting 6days before RES injection) was able to improve the impaired memory caused by RES. RES treatment increased the nitric oxide (NO) level and lipid peroxidation (LPO) production, and decreased the antioxidation power in hippocampi. EGCG treatment was able to counteract the RES-induced NO level and LPO production, as well as enhanced the hippocampal antioxidation power in RES-treated rats. In order to examine the implication of NO pathway activity in RES treatment, either NO precursor (L-arginine; L-A) or NO synthase inhibitor (L-NAME; L-N) was co-pretreated with EGCG; NO precursor treatment eliminated the protective effect of EGCG, in contrast to that NO synthase inhibitor treatment significantly increased the EGCG effects on cognitive and biochemical protection in RES-treated rats. These results suggested that the NO pathway was implicated, at least in part, in the RES-induced impairment, as well as in the protective effect of EGCG in treating RES-induced impairment of memory. The above evidence provides a clinically relevant value for EGCG in preventing RES-induced cognitive dysfunction. PMID:26944334

  15. 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

  16. 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…

  17. 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.…

  18. Developmental Levels and Suggested Learning Activities for the Visually Impaired Preschool Child. A Special Report.

    ERIC Educational Resources Information Center

    Harrell, Lois, Comp.

    The paper presents developmental charts detailing the needs and patterns of very young visually impaired children. Five age levels are considered (0-6 months, 6-12 months, 1-.25 years, 2.5-4 years, and 4-5 years) within the context of auditory awareness, body image, development of meaningful language, tactual awareness and manipulative skills,…

  19. Impairment in Instrumental Activities of Daily Living and the Geriatric Syndrome of Self-Neglect

    ERIC Educational Resources Information Center

    Naik, Aanand D.; Burnett, Jason; Pickens-Pace, Sabrina; Dyer, Carmel B.

    2008-01-01

    Purpose: We sought to characterize self-neglect definitively as a geriatric syndrome by identifying an association with functional impairment. Design and Methods: We performed a cross-sectional home evaluation of 100 community-living older adults referred by Adult Protective Services for geriatric self-neglect and 100 matched adults from a…

  20. 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…

  1. Nitric oxide associated with iNOS expression inhibits acetylcholinesterase activity and induces memory impairment during acute hypobaric hypoxia.

    PubMed

    Udayabanu, M; Kumaran, D; Nair, R Unnikrishnan; Srinivas, P; Bhagat, Neeta; Aneja, R; Katyal, Anju

    2008-09-16

    The mechanisms responsible for cholinergic dysfunction associated learning and memory impairment during hypoxia are not well-understood. However it is known that inflammatory mediators like inducible nitric oxide synthase (iNOS) hamper the functions of cholinergic neurons. In this present experiment we made an effort to study the iNOS expression mediated retrograde and anterograde memory impairment in Balb/c mice following acute hypobaric hypoxia (at an altitude of 23,000ft for 6h) using elevated plus maze and passive avoidance step-through tasks. Our results demonstrated that hypoxia transiently impairs the retrograde memory without affecting the anterograde memory functions, accompanied with a substantial rise in iNOS expression and nitric oxide levels in cerebral cortex on days 2 and 3 post hypoxia. Treatment with aminoguanidine (iNOS inhibitor ), resulted in down-regulation of the iNOS expression, attenuation of the surge of nitric oxide (NO) in cerebral cortex and reversal of retrograde memory impairment due to hypoxia. Moreover the reduced AChE activity and elevated lipid peroxidation in cerebral cortex were evident during post hypoxia re-oxygenation period, which was not observed in the hippocampus. Additionally, NO donor spermine NONOate could inhibit the AChE activity in brain homogenates in a concentration-dependent manner, which further substantiate that nitric oxide produced during post hypoxia re-oxygenation, primarily contributes to the observed inhibition of cortical AChE activity. Based on these experiments we hypothesize that the NO burst as a result of iNOS upregulation during hypoxia interrupts the memory consolidation by altering the cholinergic functions. PMID:18639532

  2. Activation of endocannabinoid system in the rat basolateral amygdala improved scopolamine-induced memory consolidation impairment.

    PubMed

    Nedaei, Seyed Ershad; Rezayof, Ameneh; Pourmotabbed, Ali; Nasehi, Mohammad; Zarrindast, Mohammad-Reza

    2016-09-15

    The current study was designed to examine the involvement of cannabinoid CB1 receptors in the basolateral amygdala (BLA) in scopolamine-induced memory impairment in adult male Wistar rats. The animals were bilaterally implanted with the cannulas in the BLA and submitted to a step-through type passive avoidance task to measure the memory formation. The results showed that intraperitoneal (i.p.) administration of different doses of scopolamine (0.5-1.5mg/kg) immediately after the training phase (post-training) impaired memory consolidation. Bilateral microinjection of the cannabinoid CB1 receptor agonist, arachydonilcyclopropylamide (ACPA; 1-4ng/rat), into the BLA significantly improved scopolamine-induced memory consolidation impairment. On the other hand, co-administration of AM251, a cannabinoid CB1 receptor antagonist (0.25-1ng/rat, intra-BLA), with an ineffective dose of scopolamine (0.5mg/kg, i.p.), significantly impaired memory consolidation and mimicked the response of a higher dose of scopolamine. It is important to note that post-training intra-BLA microinjections of the same doses of ACPA or AM251 alone had no effect on memory consolidation. Moreover, the blockade of the BLA CB1 receptors by 0.3ng/rat of AM251 prevented ACPA-induced improvement of the scopolamine response. In view of the known actions of the drugs used, the present data pointed to the involvement of the BLA CB1 receptors in scopolamine-induced memory consolidation impairment. Furthermore, it seems that a functional interaction between the BLA endocannabinoid and cholinergic muscarinic systems may be critical for memory formation. PMID:27230394

  3. 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

  4. 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

  5. Repeated Isoflurane Exposures Impair Long-Term Potentiation and Increase Basal GABAergic Activity in the Basolateral Amygdala

    PubMed Central

    Long II, Robert P.; Aroniadou-Anderjaska, Vassiliki; Prager, Eric M.; Pidoplichko, Volodymyr I.; Figueiredo, Taiza H.; Braga, Maria F. M.

    2016-01-01

    After surgery requiring general anesthesia, patients often experience emotional disturbances, but it is unclear if this is due to anesthetic exposure. In the present study, we examined whether isoflurane anesthesia produces long-term pathophysiological alterations in the basolateral amygdala (BLA), a brain region that plays a central role in emotional behavior. Ten-week-old, male rats were administered either a single, 1 h long isoflurane (1.5%) anesthesia or three, 1 h long isoflurane exposures, separated by 48 h. Long-term potentiation (LTP) and spontaneous GABAergic activity in the BLA were studied 1 day, 1 week, and 1 month later. Single isoflurane anesthesia had no significant effect on the magnitude of LTP. In contrast, after repeated isoflurane exposures, LTP was dramatically impaired at both 1 day and 1 week after the last exposure but was restored by 1 month after the exposures. Spontaneous GABAA receptor-mediated IPSCs were increased at 1 day and 1 week after repeated exposures but had returned to control levels by 1 month after exposure. Thus, repeated exposures to isoflurane cause a long-lasting—but not permanent—impairment of synaptic plasticity in the BLA, which could be due to increased basal GABAergic activity. These pathophysiological alterations may produce emotional disturbances and impaired fear-related learning. PMID:27313904

  6. Impaired hippocampal activity at the goal zone on the place preference task in a DISC1 mouse model.

    PubMed

    Hayashi, Yuichiro; Sawa, Akira; Hikida, Takatoshi

    2016-05-01

    Learning deficit is a clinical feature of many mental disorders and is hypothesized to result from an inability to integrate information in neural systems. We showed that transgenic mice expressing a dominant-negative form of DISC1, a risk gene for neuropsychiatric disorders, exhibited impaired performance in a reward-place association task when combined with a mild isolation stress. CA1 cells in the mutant mice showed normal place cell properties, but their activity at the goal zone was diminished. This abnormality in hippocampal activity at the goal zone during the task may underlie the learning deficit observed in the DISC1 mutant mice. PMID:26497623

  7. 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. PMID:26498697

  8. 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

  9. 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. PMID:27162345

  10. Inhibition of glutamate carboxypeptidase II (GCPII) activity as a treatment for cognitive impairment in multiple sclerosis.

    PubMed

    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

    2012-12-01

    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

  11. Effects of late visual impairment on mental representations activated by visual and tactile stimuli.

    PubMed

    Cattaneo, Zaira; Vecchi, Tomaso; Monegato, Maura; Pece, Alfredo; Cornoldi, Cesare

    2007-05-01

    Similarly to sighted people, individuals congenitally affected by a severe visual impairment can maintain and mentally manipulate spatial information about tactile stimuli [Vecchi, T., Cattaneo, Z., Monegato, M., Pece, A., Cornoldi, C., Pietrini, P., 2006. Why Cyclops could not compete with Ulysses: monocular vision and mental images. NeuroReport 17, 723-726]. The aim of the present study was to assess whether the onset timing of a severe (but not total) sight loss may influence spatial imagery abilities based on haptic input. To this purpose, a group of late severe visually impaired people and a matched group of normally sighted participants (all blindfolded) were presented with an imagery task requiring to memorize and retrieve a number of locations presented on tactile matrices. Results indicate that a severe visual deficit occurring later in life significantly impairs spatial imagery abilities to a greater extent than in the case of congenital blindness, probably as a consequence of a modest development of specific compensatory mechanisms associated with congenital deficits. PMID:17368576

  12. Persistent Hepatitis C Virus Infection Impairs Ribavirin Antiviral Activity through Clathrin-Mediated Trafficking of Equilibrative Nucleoside Transporter 1

    PubMed Central

    Panigrahi, Rajesh; Chandra, Partha K.; Ferraris, Pauline; Kurt, Ramazan; Song, Kyoungsub; Garry, Robert F.; Reiss, Krzysztof; Coe, Imogen R.; Furihata, Tomomi; Balart, Luis A.; Wu, Tong

    2014-01-01

    ABSTRACT Ribavirin (RBV) continues to be an important component of interferon-free hepatitis C treatment regimens, as RBV alone does not inhibit hepatitis C virus (HCV) replication effectively; the reason for this ineffectiveness has not been established. In this study, we investigated the RBV resistance mechanism using a persistently HCV-infected cell culture system. The antiviral activity of RBV against HCV was progressively impaired in the persistently infected culture, whereas interferon lambda 1 (IFN-λ1), a type III IFN, showed a strong antiviral response and induced viral clearance. We found that HCV replication in persistently infected cultures induces an autophagy response that impairs RBV uptake by preventing the expression of equilibrative nucleoside transporter 1 (ENT1). The Huh-7.5 cell line treated with an autophagy inducer, Torin 1, downregulated membrane expression of ENT1 and terminated RBV uptake. In contrast, the autophagy inhibitors hydroxychloroquine (HCQ), 3-methyladenine (3-MA), and bafilomycin A1 (BafA1) prevented ENT1 degradation and enhanced RBV antiviral activity. The HCV-induced autophagy response, as well as treatment with Torin 1, degrades clathrin heavy chain expression in a hepatoma cell line. Reduced expression of the clathrin heavy chain by HCV prevents ENT1 recycling to the plasma membrane and forces ENT1 to the lysosome for degradation. This study provides a potential mechanism for the impairment of RBV antiviral activity in persistently HCV-infected cell cultures and suggests that inhibition of the HCV-induced autophagy response could be used as a strategy for improving RBV antiviral activity against HCV infection. IMPORTANCE The results from this work will allow a review of the competing theories of antiviral therapy development in the field of HCV virology. Ribavirin (RBV) remains an important component of interferon-free hepatitis C treatment regimens. The reason why RBV alone does not inhibit HCV replication effectively has

  13. 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)

  14. 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…

  15. Henry County School Questionnaire.

    ERIC Educational Resources Information Center

    Goolsby, Thomas M., Jr.; Frary, Robert B.

    This 14-item questionnaire was designed to measure parent opinion regarding the effect of integration on third grade pupils in Henry County Schools. The questionnaire is not standardized, and field testing has been on a small scale. (See also TM 000 940 for a description of the study, and 942, 943 for the desegregation and school integration…

  16. 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…

  17. Questionnaire for Parents.

    ERIC Educational Resources Information Center

    Purdue Univ., Lafayette, IN. Educational Research Center.

    The 116-item parent questionnaire is designed for parents of elementary school children. It is intended to be used with the child's mother, or the person acting as the child's mother. The questionnaire consists of a section devoted to demographic variables and scales measuring 14 parent variables: (1) parent's achievement aspirations for the…

  18. 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

  19. Venom of Parasitoid Pteromalus puparum Impairs Host Humoral Antimicrobial Activity by Decreasing Host Cecropin and Lysozyme Gene Expression.

    PubMed

    Fang, Qi; Wang, Bei-Bei; Ye, Xin-Hai; Wang, Fei; Ye, Gong-Yin

    2016-02-01

    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

  20. Does the Five Facet Mindfulness Questionnaire measure what we think it does? Construct validity evidence from an active controlled randomized clinical trial.

    PubMed

    Goldberg, Simon B; Wielgosz, Joseph; Dahl, Cortland; Schuyler, Brianna; MacCoon, Donal S; Rosenkranz, Melissa; Lutz, Antoine; Sebranek, Chad A; Davidson, Richard J

    2016-08-01

    The current study attempted a rigorous test of the construct validity of a widely used self-report measure of dispositional mindfulness, the Five Facet Mindfulness Questionnaire (FFMQ), within the context of an active controlled randomized trial (n = 130). The trial included three arms: mindfulness-based stress reduction (MBSR), an active control condition that did not include instruction in mindfulness meditation (Health Enhancement Program [HEP]), and a waitlist control condition. Partial evidence for the convergent validity of the FFMQ was shown in correlations at baseline between FFMQ facets and measures of psychological symptoms and psychological well-being. In addition, facets of the FFMQ were shown to increase over the course of an MBSR intervention relative to a waitlist control condition. However, the FFMQ failed to show discriminant validity. Specifically, facets of the FFMQ were shown to increase over the course of the HEP intervention relative to the waitlist control condition. MBSR and HEP, in contrast, did not differ in changes in FFMQ score over time. Implications of these findings for the measurement and theory of mindfulness and MBSR are discussed. (PsycINFO Database Record PMID:26460893

  1. Translating the Dutch Walking Stairs, Walking Ability and Rising and Sitting Questionnaires into German and assessing their concurrent validity with VAS measures of pain and activities in daily living

    PubMed Central

    2010-01-01

    Background The Dutch Walking Stairs, Walking Ability and Rising and Sitting Questionnaires are three validated instruments to measure physical activity and limitations in daily living in patients with lower extremity disorders living at home of which no German equivalents are available. Our scope was to translate the Walking Stairs, Walking Ability and Rising and Sitting Questionnaires into German and to verify its concurrent validity in the two domains pain and activities in daily living by comparing them with the corresponding measures on the Visual Analogue Scale. Methods We translated the Walking Stairs, Walking Ability and Rising and Sitting Questionnaires according to published guidelines. Demographic data and validity were assessed in 52 consecutive patients with Complex Regional Pain Syndrome 1 of the lower extremity. Information on age, duration of symptoms, type of Complex Regional Pain Syndrome 1 and type of initiating event were obtained. We assessed the concurrent validity in the two domains pain and activities in daily living by comparing them with the corresponding measures on the Visual Analogue Scale. Results We found that variability in the German Walking Stairs, Walking Ability and Rising and Sitting Questionnaires was largely explained by measures of pain and activities in daily living on the Visual Analogue Scale. Conclusion Our study shows that the domains pain and activities in daily living are properly represented in the German versions of the Walking Stairs, Walking Ability and Raising and Sitting Questionnaires. We would like to propagate their use in clinical practice and research alike. PMID:20515456

  2. Impaired activity-dependent FMRP translation and enhanced mGluR-dependent LTD in Fragile X premutation mice.

    PubMed

    Iliff, Adam J; Renoux, Abigail J; Krans, Amy; Usdin, Karen; Sutton, Michael A; Todd, Peter K

    2013-03-15

    Fragile X premutation-associated disorders, including Fragile X-associated Tremor Ataxia Syndrome, result from unmethylated CGG repeat expansions in the 5' untranslated region (UTR) of the FMR1 gene. Premutation-sized repeats increase FMR1 transcription but impair rapid translation of the Fragile X mental retardation protein (FMRP), which is absent in Fragile X Syndrome (FXS). Normally, FMRP binds to RNA and regulates metabotropic glutamate receptor (mGluR)-mediated synaptic translation, allowing for dendritic synthesis of several proteins. FMRP itself is also synthesized at synapses in response to mGluR activation. However, the role of activity-dependent translation of FMRP in synaptic plasticity and Fragile X-premutation-associated disorders is unknown. To investigate this question, we utilized a CGG knock-in mouse model of the Fragile X premutation with 120-150 CGG repeats in the mouse Fmr1 5' UTR. These mice exhibit increased Fmr1 mRNA production but impaired FMRP translational efficiency, leading to a modest reduction in basal FMRP expression. Cultured hippocampal neurons and synaptoneurosomes derived from CGG KI mice demonstrate impaired FMRP translation in response to the group I mGluR agonist 3,5-dihydroxyphenylglycine. Electrophysiological analysis reveals enhanced mGluR-mediated long-term depression (mGluR-LTD) at CA3-CA1 synapses in acute hippocampal slices prepared from CGG KI mice relative to wild-type littermates, similar to Fmr1 knockout mice. However, unlike mGluR-LTD in mice completely lacking FMRP, mGluR-LTD in CGG knock-in mice remains dependent on new protein synthesis. These studies demonstrate partially overlapping synaptic plasticity phenotypes in mouse models of FXS and Fragile X premutation disorders and support a role for activity-dependent synthesis of FMRP in enduring forms of synaptic plasticity. PMID:23250915

  3. Development of a Proxy-Free Objective Assessment Tool of Instrumental Activities of Daily Living in Mild Cognitive Impairment Using Smart Home Technologies

    PubMed Central

    Jekel, Katrin; Damian, Marinella; Storf, Holger; Hausner, Lucrezia; Frölich, Lutz

    2016-01-01

    Background: The assessment of activities of daily living (ADL) is essential for dementia diagnostics. Even in mild cognitive impairment (MCI), subtle deficits in instrumental ADL (IADL) may occur and signal a higher risk of conversion to dementia. Thus, sensitive and reliable ADL assessment tools are important. Smart homes equipped with sensor technology and video cameras may provide a proxy-free assessment tool for the detection of IADL deficits. Objective:The aim of this paper is to investigate the potential of a smart home environment for the assessment of IADL in MCI. Method: The smart home consisted of a two-room flat equipped with activity sensors and video cameras. Participants with either MCI or healthy controls (HC) had to solve a standardized set of six tasks, e.g., meal preparation, telephone use, and finding objects in the flat. Results: MCI participants needed more time (1384 versus 938 seconds, p <  0.001) and scored less total points (48 versus 57 points, p <  0.001) while solving the tasks than HC. Analyzing the subtasks, intergroup differences were observed for making a phone call, operating the television, and retrieving objects. MCI participants showed more searching and task-irrelevant behavior than HC. Task performance was correlated with cognitive status and IADL questionnaires but not with participants’ age. Conclusion: This pilot study showed that smart home technologies offer the chance for an objective and ecologically valid assessment of IADL. It can be analyzed not only whether a task is successfully completed but also how it is completed. Future studies should concentrate on the development of automated detection of IADL deficits. PMID:27031479

  4. Impaired Peroxisome Proliferator-activated Receptor-γ Contributes to Phenotypic Modulation of Vascular Smooth Muscle Cells during Hypertension*

    PubMed Central

    Zhang, Lili; Xie, Peng; Wang, Jingzhou; Yang, Qingwu; Fang, Chuanqin; Zhou, Shuang; Li, Jingcheng

    2010-01-01

    The phenotypic modulation of vascular smooth muscle cells (VSMCs) plays a pivotal role in hypertension-induced vascular changes including vascular remodeling. The precise mechanisms underlying VSMC phenotypic modulation remain elusive. Here we test the role of peroxisome proliferator-activated receptor (PPAR)-γ in the VSMC phenotypic modulation during hypertension. Both spontaneously hypertensive rat (SHR) aortas and SHR-derived VSMCs exhibited reduced PPAR-γ expression and excessive VSMC phenotypic modulation identified by reduced contractile proteins, α-smooth muscle actin (α-SMA) and smooth muscle 22α (SM22α), and enhanced proliferation and migration. PPAR-γ overexpression rescued the expression of α-SMA and SM22α, and inhibited the proliferation and migration in SHR-derived VSMCs. In contrast, PPAR-γ silencing exerted the opposite effect. Activating PPAR-γ using rosiglitazone in vivo up-regulated aortic α-SMA and SM22α expression and attenuated aortic remodeling in SHRs. Increased activation of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling was observed in SHR-derived VSMCs. PI3K inhibitor LY294002 rescued the impaired expression of contractile proteins, and inhibited proliferation and migration in VSMCs from SHRs, whereas constitutively active PI3K mutant had the opposite effect. Overexpression or silencing of PPAR-γ inhibited or excited PI3K/Akt activity, respectively. LY294002 counteracted the PPAR-γ silencing induced proliferation and migration in SHR-derived VSMCs, whereas active PI3K mutant had the opposite effect. In contrast, reduced proliferation and migration by PPAR-γ overexpression were reversed by the active PI3K mutant, and further inhibited by LY294002. We conclude that PPAR-γ inhibits VSMC phenotypic modulation through inhibiting PI3K/Akt signaling. Impaired PPAR-γ expression is responsible for VSMC phenotypic modulation during hypertension. These findings highlight an attractive therapeutic target for

  5. 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. PMID:23163595

  6. 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

  7. Minocycline attenuates post-operative cognitive impairment in aged mice by inhibiting microglia activation.

    PubMed

    Wang, Hui-Lin; Liu, Hua; Xue, Zhang-Gang; Liao, Qing-Wu; Fang, Hao

    2016-09-01

    Although it is known that isoflurane exposure or surgery leads to post-operative cognitive dysfunction in aged rodents, there are few clinical interventions and treatments available to prevent this disorder. Minocycline (MINO) produces neuroprotection from several neurodegenerative diseases and various experimental animal models. Therefore, we set out to investigate the effects of MINO pre-treatment on isoflurane or surgery induced cognitive impairment in aged mice by assessing the hippocampal-dependent spatial memory performance using the Morris water maze task. Hippocampal tissues were isolated from mice and evaluated by Western blot analysis, immunofluorescence procedures and protein array system. Our results elucidate that MINO down-regulated the isoflurane-induced and surgery-induced enhancement in the protein levels of pro-inflammatory cytokine tumour necrosis factor alpha, interleukin (IL)-1β, interferon-γ and microglia marker Iba-1, and up-regulated protein levels of the anti-inflammatory cytokine IL-4 and IL-10. These findings suggest that pre-treatment with MINO attenuated isoflurane or surgery induced cognitive impairment by inhibiting the overactivation of microglia in aged mice. PMID:27061744

  8. Timing Tasks Synchronize Cerebellar and Frontal Ramping Activity and Theta Oscillations: Implications for Cerebellar Stimulation in Diseases of Impaired Cognition

    PubMed Central

    Parker, Krystal L.

    2016-01-01

    Timing is a fundamental and highly conserved mammalian capability, yet the underlying neural mechanisms are widely debated. Ramping activity of single neurons that gradually increase or decrease activity to encode the passage of time has been speculated to predict a behaviorally relevant temporal event. Cue-evoked low-frequency activity has also been implicated in temporal processing. Ramping activity and low-frequency oscillations occur throughout the brain and could indicate a network-based approach to timing. Temporal processing requires cognitive mechanisms of working memory, attention, and reasoning, which are dysfunctional in neuropsychiatric disease. Therefore, timing tasks could be used to probe cognition in animals with disease phenotypes. The medial frontal cortex and cerebellum are involved in cognition. Cerebellar stimulation has been shown to influence medial frontal activity and improve cognition in schizophrenia. However, the mechanism underlying the efficacy of cerebellar stimulation is unknown. Here, we discuss how timing tasks can be used to probe cerebellar interactions with the frontal cortex and the therapeutic potential of cerebellar stimulation. The goal of this theory and hypothesis manuscript is threefold. First, we will summarize evidence indicating that in addition to motor learning, timing tasks involve cognitive processes that are present within both the cerebellum and medial frontal cortex. Second, we propose methodologies to investigate the connections between these areas in patients with Parkinson’s disease, autism, and schizophrenia. Lastly, we hypothesize that cerebellar transcranial stimulation may rescue medial frontal ramping activity, theta oscillations, and timing abnormalities, thereby restoring executive function in diseases of impaired cognition. This hypothesis could inspire the use of timing tasks as biomarkers for neuronal and cognitive abnormalities in neuropsychiatric disease and promote the therapeutic potential of

  9. Impairment of the mitochondrial respiratory chain activity in diethylnitrosamine-induced rat hepatomas: possible involvement of oxygen free radicals.

    PubMed

    Boitier, E; Merad-Boudia, M; Guguen-Guillouzo, C; Defer, N; Ceballos-Picot, I; Leroux, J P; Marsac, C

    1995-07-15

    Alterations in the energy metabolism of cancer cells have been reported for many years. However, the deleterious mechanisms involved in these deficiencies have not yet been clearly proved. The main goal of this study was to decipher the harmful mechanisms responsible for the respiratory chain deficiencies in the course of diethylnitrosamine (DENA)-induced rat hepatocarcinogenesis, where mitochondrial DNA abnormalities had been previously reported. The respiratory activity of freshly isolated hepatoma mitochondria, assessed by oxygen consumption experiments and enzymatic assays, presented a severe complex I deficiency 19 months after DENA treatment, and later on, in addition, a defective complex III activity. Since respiratory complex subunits are encoded by both nuclear and mitochondrial genes, we checked whether the respiratory chain defects were due to impaired synthesis processes. The specific immunodetection of complex I failed to show any alterations in the steady-state levels of both nuclear and mitochondrial encoded subunits in the hepatomas. Moreover, in vitro protein synthesis experiments carried out on freshly isolated hepatoma mitochondria did not bring to light any modifications in the synthesis of the mitochondrial subunits of the respiratory complexes, whatever the degree of tumor progression. Finally, Southern blot analysis of mitochondrial DNA did not show any major mitochondrial DNA rearrangements in DENA-induced hepatomas. Because the synthetic processes of respiratory complexes did not seem to be implicated in the respiratory chain impairment, these deficiencies could be partly ascribed to a direct toxic impact of highly reactive molecules on these complexes, thus impairing their function. The mitochondrial respiratory chain is an important generator of noxious, reactive oxygen free radicals such as superoxide and H2O2, which are normally catabolized by powerful antioxidant scavengers. Nineteen months after DENA treatment, a general collapse of

  10. 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. PMID:25257696

  11. Augmented EGF receptor tyrosine kinase activity impairs vascular function by NADPH oxidase-dependent mechanism in type 2 diabetic mouse.

    PubMed

    Kassan, Modar; Ait-Aissa, Karima; Ali, Maha; Trebak, Mohamed; Matrougui, Khalid

    2015-10-01

    We previously determined that augmented EGFR tyrosine kinase (EGFRtk) impairs vascular function in type 2 diabetic mouse (TD2). Here we determined that EGFRtk causes vascular dysfunction through NADPH oxidase activity in TD2. Mesenteric resistance arteries (MRA) from C57/BL6 and db-/db- mice were mounted in a wired myograph and pre-incubated for 1h with either EGFRtk inhibitor (AG1478) or exogenous EGF. The inhibition of EGFRtk did not affect the contractile response to phenylephrine-(PE) and thromboxane-(U46619) or endothelium-dependent relaxation (EDR) to acetylcholine in MRA from control group. However, in TD2 mice, AG1478 reduced the contractile response to U46619, improved vasodilatation and reduced p22phox-NADPH expression, but had no effect on the contractile response to PE. The incubation of MRA with exogenous EGF potentiated the contractile response to PE in MRA from control and diabetic mice. However, EGF impaired the EDR and potentiated the vasoconstriction to U46619 only in the control group. Interestingly, NADPH oxidase inhibition in the presence of EGF restored the normal contraction to PE and improved the EDR but had no effect on the potentiated contraction to U46619. Vascular function improvement was associated with the rescue of eNOS and Akt and reduction in phosphorylated Rho-kinase, NOX4 mRNA levels, and NADPH oxidase activity. MRA from p47phox-/- mice incubated with EGF potentiated the contraction to U46619 but had no effect to PE or ACh responses. The present study provides evidence that augmented EGFRtk impairs vascular function by NADPH oxidase-dependent mechanism. Therefore, EGFRtk and oxidative stress should be potential targets to treat vascular dysfunction in TD2. PMID:26036345

  12. Impaired Systemic Tetrahydrobiopterin Bioavailability and Increased Dihydrobiopterin in Adult Falciparum Malaria: Association with Disease Severity, Impaired Microvascular Function and Increased Endothelial Activation

    PubMed Central

    Yeo, Tsin W.; Lampah, Daniel A.; Kenangalem, Enny; Tjitra, Emiliana; Price, Ric N.; Weinberg, J. Brice; Hyland, Keith; Granger, Donald L.; Anstey, Nicholas M.

    2015-01-01

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

  13. 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

  14. Naringenin Mitigates Iron-Induced Anxiety-Like Behavioral Impairment, Mitochondrial Dysfunctions, Ectonucleotidases and Acetylcholinesterase Alteration Activities in Rat Hippocampus.

    PubMed

    Chtourou, Yassine; Slima, Ahlem Ben; Gdoura, Radhouane; Fetoui, Hamadi

    2015-08-01

    Studies demonstrated that the iron chelating antioxidant restores brain dysfunction induced by iron toxicity in animals. Earlier, we found that iron overload-induced cerebral cortex apoptosis correlated with oxidative stress could be protected by naringenin (NGEN). In this respect, the present study is focused on the mechanisms associated with the protective efficacy of NGEN, natural flavonoid compound abundant in the peels of citrus fruit, on iron induced impairment of the anxiogenic-like behaviour, purinergic and cholinergic dysfunctions with oxidative stress related disorders on mitochondrial function in the rat hippocampus. Results showed that administration of NGEN (50 mg/kg/day) by gavage significantly ameliorated anxiogenic-like behaviour impairment induced by the exposure to 50 mg of Fe-dextran/kg/day intraperitoneally for 28 days in rats, decreased iron-induced reactive oxygen species formation and restored the iron-induced decrease of the acetylcholinesterase expression level, mitochondrial membrane potential and mitochondrial complexes activities in the hippocampus of rats. Moreover, NGEN was able to restore the alteration on the activity and expression of ectonucleotidases such as adenosine triphosphate diphosphohydrolase and 5'-nucleotidase, enzymes which hydrolyze and therefore control extracellular ATP and adenosine concentrations in the synaptic cleft. These results may contribute to a better understanding of the neuroprotective role of NGEN, emphasizing the influence of including this flavonoid in the diet for human health, possibly preventing brain injury associated with iron overload. PMID:26050208

  15. Endomorphin analog analgesics with reduced abuse liability, respiratory depression, motor impairment, tolerance, and glial activation relative to morphine.

    PubMed

    Zadina, James E; Nilges, Mark R; Morgenweck, Jenny; Zhang, Xing; Hackler, Laszlo; Fasold, Melita B

    2016-06-01

    Opioids acting at the mu opioid receptor (MOR) are the most effective analgesics, however adverse side effects severely limit their use. Of particular importance, abuse liability results in major medical, societal, and economic problems, respiratory depression is the cause of fatal overdoses, and tolerance complicates treatment and increases the risk of side effects. Motor and cognitive impairment are especially problematic for older adults. Despite the host of negative side effects, opioids such as morphine are commonly used for acute and chronic pain conditions. Separation of analgesia from unwanted effects has long been an unmet goal of opioid research. Novel MOR agonist structures may prove critical for greater success. Here we tested metabolically stable analogs of the endomorphins, endogenous opioids highly selective for the MOR. Compared to morphine, the analogs showed dramatically improved analgesia-to-side-effect ratios. At doses providing equal or greater antinociception than morphine in the rat, the analogs showed reduced a) respiratory depression, b) impairment of motor coordination, c) tolerance and hyperalgesia, d) glial p38/CGRP/P2X7 receptor signaling, and e) reward/abuse potential in both conditioned place preference and self-administration tests. Differential effects on glial activation indicate a mechanism for the relative lack of side effects by the analogs compared to morphine. The results suggest that endomorphin analogs described here could provide gold standard pain relief mediated by selective MOR activation, but with remarkably safer side effect profiles compared to opioids like morphine. PMID:26748051

  16. Impairment of the catalytic activity of Escherichia coli ribonucleic acid polymerase by a unique reaction of 4-chloro-7-nitrobenzofurazan.

    PubMed Central

    Bratcher, S C; Nitta, K; Kronman, M J

    1979-01-01

    Escherichia coli RNA polymerase loses 55-65% of its catalytic activity on reaction with Nbf-Cl (4-choro-7-nitrobenzofurazan). This partial inactivation was shown to be the result of specific impairment of RNA-chain elongation, since initiation of RNA chains was not altered after treatment with Nbf-Cl. The site of reaction was shown to be a unique thiol on the beta-subunit. This thiol is not accessible to reaction with 5,5'-dithiobis-(2-nitrobenzoic acid). No protection of the enzyme against reaction with Nbf-Cl could be obtained with the inhibitor rifamycin nor with calf thymus DNA, GTP or 1,10-phenanthroline, indicating that the unique thiol is probably not within the active site. The specific impairment of RNA-chain elongation thus appears to be the result of a local conformational change which leaves chain initiation unimpaired. Changes observed in the tryptophan fluorescence spectrum of the enzyme or reaction with Nbf-Cl are consistent with formation of a Meisenheimer complex of the reagent with a nucleophilic group on the enzyme near the reactive thiol. It is proposed that formation of such a complex and a subsequent conformational change renders this thiol unusually susceptible to reaction with Nbf-Cl. PMID:393251

  17. Intra-amygdala microinfusion of IL-6 impairs the auditory fear conditioning of rats via JAK/STAT activation.

    PubMed

    Hao, Yongxin; Jing, He; Bi, Qiang; Zhang, Jiaozhen; Qin, Ling; Yang, Pingting

    2014-12-15

    Though accumulating literature implicates that cytokines are involved in the pathophysiology of mental disorders, the role of interleukin-6 (IL-6) in learning and memory functions remains unresolved. The present study was undertaken to investigate the effect of IL-6 on amygdala-dependent fear learning. Adult Wistar rats were used along with the auditory fear conditioning test and pharmacological techniques. The data showed that infusions of IL-6, aimed at the amygdala, dose-dependently impaired the acquisition and extinction of conditioned fear. In addition, the results in the Western blot analysis confirmed that JAK/STAT was temporally activated-phosphorylated by the IL-6 treatment. Moreover, the rats were treated with JSI-124, a JAK/STAT3 inhibitor, prior to the IL-6 treatment showed a significant decrease in the IL-6 induced impairments of fear conditioning. Taken together, our results demonstrate that the learning behavior of rats in the auditory fear conditioning could be modulated by IL-6 via the amygdala. Furthermore, the JAK/STAT3 activation in the amygdala seemed to play a role in the IL-6 mediated behavioral alterations of rats in auditory fear learning. PMID:25193320

  18. 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. PMID:26948151

  19. Impairment of social behavior and communication in mice lacking the Uba6-dependent ubiquitin activation system.

    PubMed

    Lee, Ji Yeon; Kwak, Minseok; Lee, Peter C W

    2015-03-15

    The Uba6-Use1 ubiquitin enzyme cascade is a poorly understood arm of the ubiquitin-proteasome system required for mouse development. Recently, we reported that Uba6 brain-specific knockout (termed NKO) mice display abnormal social behavior and neuronal development due to a decreased spine density and accumulation of Ube3a and Shank3. To better characterize a potential role for NKO mice in autism spectrum disorders (ASDs), we performed a comprehensive behavioral characterization of the social behavior and communication of NKO mice. Our behavioral results confirmed that NKO mice display social impairments, as indicated by fewer vocalizations and decreased social interaction. We conclude that UBA6 NKO mice represent a novel ASD mouse model of anti-social and less verbal behavioral symptoms. PMID:25523030

  20. Inhibition of Proteasome Activity Impairs Centrosome-dependent Microtubule Nucleation and Organization

    PubMed Central

    Didier, Christine; Merdes, Andreas; Gairin, Jean-Edouard

    2008-01-01

    Centrosomes are dynamic organelles that consist of a pair of cylindrical centrioles, surrounded by pericentriolar material. The pericentriolar material contains factors that are involved in microtubule nucleation and organization, and its recruitment varies during the cell cycle. We report here that proteasome inhibition in HeLa cells induces the accumulation of several proteins at the pericentriolar material, including gamma-tubulin, GCP4, NEDD1, ninein, pericentrin, dynactin, and PCM-1. The effect of proteasome inhibition on centrosome proteins does not require intact microtubules and is reversed after removal of proteasome inhibitors. This accrual of centrosome proteins is paralleled by accumulation of ubiquitin in the same area and increased polyubiquitylation of nonsoluble gamma-tubulin. Cells that have accumulated centrosome proteins in response to proteasome inhibition are impaired in microtubule aster formation. Our data point toward a role of the proteasome in the turnover of centrosome proteins, to maintain proper centrosome function. PMID:18094058

  1. Impaired mast cell activation in gene-targeted mice lacking the serum- and glucocorticoid-inducible kinase SGK1.

    PubMed

    Sobiesiak, Malgorzata; Shumilina, Ekaterina; Lam, Rebecca S; Wölbing, Florian; Matzner, Nicole; Kaesler, Susanne; Zemtsova, Irina M; Lupescu, Adrian; Zahir, Naima; Kuhl, Dietmar; Schaller, Martin; Biedermann, Tilo; Lang, Florian

    2009-10-01

    The PI3K pathway plays a pivotal role in the stimulation of mast cells. PI3K-dependent kinases include the serum- and glucocorticoid-inducible kinase 1 (SGK1). The present study explored the role of SGK1 in mast cell function. Mast cells were isolated from bone marrow (BMMC) of SGK1 knockout mice (sgk1(-/-)) and their wild-type littermates (sgk1(+/+)). The BMMC number as well as CD117, CD34, and FcepsilonRI expression in BMCCs were similar in both genotypes. Upon Ag stimulation of the FcepsilonRI receptor, Ca(2+) entry but not Ca(2+) release from intracellular stores was markedly impaired in sgk1(-/-) BMMCs. The currents through Ca(2+)-activated K+ channels induced by Ag were significantly higher in sgk1(+/+) BMMCs than in sgk1(-/-) BMMCs. Treatment with the Ca(2+) ionophore ionomycin (1 microM) led to activation of the K+ channels in both genotypes, indicating that the Ca(2+)-activated K+ channels are similarly expressed and sensitive to activation by Ca(2+) in sgk1(+/+) and sgk1(-/-) BMMCs, and that blunted stimulation of Ca(2+)-activated K+ channels was secondary to decreased Ca(2+) entry. Ag-IgE-induced degranulation and early IL-6 secretion were also significantly blunted in sgk1(-/-) BMMCs. The decrease in body temperature following Ag treatment, which reflects an anaphylactic reaction, was substantially reduced in sgk1(-/-) mice, pointing to impaired mast cell function in vivo. Serum histamine levels measured 30 min after induction of an anaphylactic reaction were significantly lower in sgk1(-/-) than in sgk1(+/+)mice. The observations reveal a critical role for SGK1 in ion channel regulation and the function of mast cells, and thus disclose a completely novel player in the regulation of allergic reaction. PMID:19748978

  2. 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…

  3. 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

  4. Small Molecule APY606 Displays Extensive Antitumor Activity in Pancreatic Cancer via Impairing Ras-MAPK Signaling.

    PubMed

    Guo, Na; Liu, Zuojia; Zhao, Wenjing; Wang, Erkang; Wang, Jin

    2016-01-01

    Pancreatic cancer has been found with abnormal expression or mutation in Ras proteins. Oncogenic Ras activation exploits their extensive signaling reach to affect multiple cellular processes, in which the mitogen-activated protein kinase (MAPK) signaling exerts important roles in tumorigenesis. Therapies targeted Ras are thus of major benefit for pancreatic cancer. Although small molecule APY606 has been successfully picked out by virtual drug screening based on Ras target receptor, its in-depth mechanism remains to be elucidated. We herein assessed the antitumor activity of APY606 against human pancreatic cancer Capan-1 and SW1990 cell lines and explored the effect of Ras-MAPK and apoptosis-related signaling pathway on the activity of APY606. APY606 treatment resulted in a dose- and time-dependent inhibition of cancer cell viability. Additionally, APY606 exhibited strong antitumor activity, as evidenced not only by reduction in tumor cell invasion, migration and mitochondrial membrane potential but also by alteration in several apoptotic indexes. Furthermore, APY606 treatment directly inhibited Ras-GTP and the downstream activation of MAPK, which resulted in the down-regulation of anti-apoptotic protein Bcl-2, leading to the up-regulation of mitochondrial apoptosis pathway-related proteins (Bax, cytosolic Cytochrome c and Caspase 3) and of cyclin-dependent kinase 2 and Cyclin A, E. These data suggest that impairing Ras-MAPK signaling is a novel mechanism of action for APY606 during therapeutic intervention in pancreatic cancer. PMID:27223122

  5. Small Molecule APY606 Displays Extensive Antitumor Activity in Pancreatic Cancer via Impairing Ras-MAPK Signaling

    PubMed Central

    Guo, Na; Liu, Zuojia; Zhao, Wenjing; Wang, Erkang; Wang, Jin

    2016-01-01

    Pancreatic cancer has been found with abnormal expression or mutation in Ras proteins. Oncogenic Ras activation exploits their extensive signaling reach to affect multiple cellular processes, in which the mitogen-activated protein kinase (MAPK) signaling exerts important roles in tumorigenesis. Therapies targeted Ras are thus of major benefit for pancreatic cancer. Although small molecule APY606 has been successfully picked out by virtual drug screening based on Ras target receptor, its in-depth mechanism remains to be elucidated. We herein assessed the antitumor activity of APY606 against human pancreatic cancer Capan-1 and SW1990 cell lines and explored the effect of Ras-MAPK and apoptosis-related signaling pathway on the activity of APY606. APY606 treatment resulted in a dose- and time-dependent inhibition of cancer cell viability. Additionally, APY606 exhibited strong antitumor activity, as evidenced not only by reduction in tumor cell invasion, migration and mitochondrial membrane potential but also by alteration in several apoptotic indexes. Furthermore, APY606 treatment directly inhibited Ras-GTP and the downstream activation of MAPK, which resulted in the down-regulation of anti-apoptotic protein Bcl-2, leading to the up-regulation of mitochondrial apoptosis pathway-related proteins (Bax, cytosolic Cytochrome c and Caspase 3) and of cyclin-dependent kinase 2 and Cyclin A, E. These data suggest that impairing Ras-MAPK signaling is a novel mechanism of action for APY606 during therapeutic intervention in pancreatic cancer. PMID:27223122

  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. 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

  8. 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

  9. Elastase levels and activity are increased in dystrophic muscle and impair myoblast cell survival, proliferation and differentiation

    PubMed Central

    Arecco, N.; Clarke, C. J.; Jones, F. K.; Simpson, D. M.; Mason, D.; Beynon, R. J.; Pisconti, A.

    2016-01-01

    In Duchenne muscular dystrophy, progressive loss of muscle tissue is accompanied by fibrosis, chronic inflammation and reduced muscle regenerative capacity. Although much is known about the development of fibrosis and chronic inflammation in muscular dystrophy, less is known about how they are mechanistically linked to loss of muscle regenerative capacity. We have developed a proteomics method to discover dystrophy-associated changes in the muscle progenitor cell niche, which identified serine proteases, and especially neutrophil elastase, as candidates. We show that elastase activity is increased in dystrophic (mdx4cv) muscle and impairs myoblast survival in culture. While the effect of elastase on C2C12 cell survival correlates with the kinetics of elastase-mediated degradation of the substrate to which the cells adhere, the effect of elastase on satellite cell-derived primary myoblast growth and differentiation is substrate-independent and even more dramatic than the effect on C2C12 cells, suggesting a detrimental role for elastase on myogenesis in vivo. Additionally, elastase impairs differentiation of both primary and C2C12 myoblasts into myotubes. Our findings evidence the importance of neutrophil-mediated inflammation in muscular dystrophy and indicate elastase-mediated regulation of myoblast behaviour as a potential mechanism underlying loss of regenerative capacity in dystrophic muscle. PMID:27241590

  10. Elastase levels and activity are increased in dystrophic muscle and impair myoblast cell survival, proliferation and differentiation.

    PubMed

    Arecco, N; Clarke, C J; Jones, F K; Simpson, D M; Mason, D; Beynon, R J; Pisconti, A

    2016-01-01

    In Duchenne muscular dystrophy, progressive loss of muscle tissue is accompanied by fibrosis, chronic inflammation and reduced muscle regenerative capacity. Although much is known about the development of fibrosis and chronic inflammation in muscular dystrophy, less is known about how they are mechanistically linked to loss of muscle regenerative capacity. We have developed a proteomics method to discover dystrophy-associated changes in the muscle progenitor cell niche, which identified serine proteases, and especially neutrophil elastase, as candidates. We show that elastase activity is increased in dystrophic (mdx(4cv)) muscle and impairs myoblast survival in culture. While the effect of elastase on C2C12 cell survival correlates with the kinetics of elastase-mediated degradation of the substrate to which the cells adhere, the effect of elastase on satellite cell-derived primary myoblast growth and differentiation is substrate-independent and even more dramatic than the effect on C2C12 cells, suggesting a detrimental role for elastase on myogenesis in vivo. Additionally, elastase impairs differentiation of both primary and C2C12 myoblasts into myotubes. Our findings evidence the importance of neutrophil-mediated inflammation in muscular dystrophy and indicate elastase-mediated regulation of myoblast behaviour as a potential mechanism underlying loss of regenerative capacity in dystrophic muscle. PMID:27241590

  11. Loss of activator of G-protein signaling 3 impairs renal tubular regeneration following acute kidney injury in rodents

    PubMed Central

    Regner, Kevin R.; Nozu, Kandai; Lanier, Stephen M.; Blumer, Joe B.; Avner, Ellis D.; Sweeney, William E.; Park, Frank

    2011-01-01

    The intracellular mechanisms underlying renal tubular epithelial cell proliferation and tubular repair following ischemia-reperfusion injury (IRI) remain poorly understood. In this report, we demonstrate that activator of G-protein signaling 3 (AGS3), an unconventional receptor-independent regulator of heterotrimeric G-protein function, influences renal tubular regeneration following IRI. In rat kidneys exposed to IRI, there was a temporal induction in renal AGS3 protein expression that peaked 72 h after reperfusion and corresponded to the repair and recovery phase following ischemic injury. Renal AGS3 expression was localized predominantly to the recovering outer medullary proximal tubular cells and was highly coexpressed with Ki-67, a marker of cell proliferation. Kidneys from mice deficient in the expression of AGS3 exhibited impaired renal tubular recovery 7 d following IRI compared to wild-type AGS3-expressing mice. Mechanistically, genetic knockdown of endogenous AGS3 mRNA and protein in renal tubular epithelial cells reduced cell proliferation in vitro. Similar reductions in renal tubular epithelial cell proliferation were observed following incubation with gallein, a selective inhibitor of Gβγ subunit activity, and lentiviral overexpression of the carboxyl-terminus of G-protein-coupled receptor kinase 2 (GRK2ct), a scavenger of Gβγ subunits. In summary, these data suggest that AGS3 acts through a novel receptor-independent mechanism to facilitate renal tubular epithelial cell proliferation and renal tubular regeneration.—Regner, K. R., Nozu, K., Lanier, S. M., Blumer, J. B., Avner, E. D., Sweeney, Jr., W. E., Park, F. Loss of activator of G-protein signaling 3 impairs renal tubular regeneration following acute kidney injury in rodents. PMID:21343176

  12. In vivo hydroquinone exposure alters circulating neutrophil activities and impairs LPS-induced lung inflammation in mice.

    PubMed

    Ribeiro, André Luiz Teroso; Shimada, Ana Lúcia Borges; Hebeda, Cristina Bichels; de Oliveira, Tiago Franco; de Melo Loureiro, Ana Paula; Filho, Walter Dos Reis Pereira; Santos, Alcinéa Meigikos Dos Anjos; de Lima, Wothan Tavares; Farsky, Sandra Helena Poliselli

    2011-10-01

    Hydroquinone (HQ) is an environmental contaminant which causes immune toxicity. In this study, the effects of exposure to low doses of HQ on neutrophil mobilization into the LPS-inflamed lung were investigated. Male Swiss mice were exposed to aerosolized vehicle (control) or 12.5, 25 or 50ppm HQ (1h/day for 5 days). One hour later, oxidative burst, cell cycle, DNA fragmentation and adhesion molecules expressions in circulating neutrophils were determined by flow cytometry, and plasma malondialdehyde (MDA) levels were measured by HPLC. Also, 1h later the last exposures, inflammation was induced by LPS inhalation (0.1mg/ml/10min) and 3h later, the numbers of leukocytes in peripheral blood and in the bronchoalveolar lavage fluid (BALF) were determined using a Neubauer chamber and stained smears; adhesion molecules expressed on lung microvessel endothelial cells were quantified by immunohistochemistry; myeloperoxidase (MPO) activity was measured in the lung tissue by colorimetric assay; and cytokines in the BALF were determined by ELISA. In vivo HQ exposure augmented plasma MDA levels and oxidative activity of neutrophils, but did not cause alterations in cell cycle and DNA fragmentation. Under these conditions, the number of circulating leukocytes was not altered, but HQ exposure reduced LPS-induced neutrophil migration into the alveolar space, as these cells remained in the lung tissue. The impaired neutrophil migration into BALF may not be dependent on reduced cytokines secretions in the BALF and lung endothelial adhesion molecules expressions. However, HQ exposure increased the expression of β(2) and β(3) integrins and platelet-endothelial cell adhesion molecule-1 (PECAM-1) in neutrophils, which were not further enhanced by fMLP in vitro stimulation, indicating that HQ exposure activates circulating neutrophils, impairing further stimulatory responses. Therefore, it has been shown, for the first time, that neutrophils are target of lower levels of in vivo HQ

  13. 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.

  14. 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

  15. Impaired telomerase activity hinders proliferation and in vitro transformation of Penaeus monodon lymphoid cells.

    PubMed

    Jayesh, P; Vrinda, S; Priyaja, P; Philip, Rosamma; Singh, I S Bright

    2016-08-01

    Retaining terminal transferase activity of telomerase, the ribonucleoprotein enzyme which add telomeric repeats on chromosome end is thought to be required to prevent cellular ageing. Additionally, telomerase considered as a marker for cell proliferation and immortalization in eukaryotes. We examined telomerase activity in tissues and lymphoid cell culture of Penaeus monodon. Along with telomerase activity, telomere repeats and an attempt on identification of telomerase reverse transcriptase (PmTERT) were made. Telomeric repeat amplification protocol revealed that telomerase-dependent telomeric lengthening has been taking place in P. monodon and the adult tissues were retaining this capacity throughout their lifespan with the highest activity in ovary, testis and lymphoid organ. However, telomerase activity could not be detected in lymphoid cells in culture. The canonical telomeric repeats added by telomerase of lymphoid tissue extract were identified as TTAGG, but pentameric repeats GGTTA and AGGTT were also added by the telomerase. PmTERT protein sequence (partial) shared 100 % identity with the TERT sequence of Daphnia pulex, 27 % sequence identity with Purple sea urchin and 24-25 % with Zebra fish. Undetectable telomerase activity in lymphoid cell culture supports the hypothesis that the inadequate telomerase activity or gene expression may be a reason that prevents neoplastic transformation and spontaneous immortalization of the cells in vitro. Thus, it is envisaged that telomerase activation in lymphoid cells may surmount cellular ageing for in vitro transformation and cell line establishment. PMID:26084784

  16. 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.

  17. Satisfaction With Teaching Questionnaire.

    ERIC Educational Resources Information Center

    Merwin, J. C.; DiVesta , F. J.

    As part of the instrumentation to assess the effectiveness of the Schools Without Failure (SEF) program in 10 elementary schools in the New Castle, Pa. School District, the Satisfaction with Teaching Questionnaire was used. In a study by its developers this scale discriminated between students choosing to be teachers and those choosing other…

  18. Postextinction Infusion of a Mitogen-Activated Protein Kinase Inhibitor into the Medial Prefrontal Cortex Impairs Memory of the Extinction of Conditioned Fear

    ERIC Educational Resources Information Center

    Hugues, Sandrine; Deschaux, Olivier; Garcia, Rene

    2004-01-01

    We investigated whether postextinction training infusion of PD098059, a selective inhibitor of mitogen-activated protein kinase (MAPK) activation, into the medial prefrontal cortex, would impair retention of extinction learning in rats. We found that immediate, but not late (2 or 4 h), postextinction infusion of PD098059 provoked a full return of…

  19. 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

  20. STAT3 Impairs STAT5 Activation in the Development of IL-9-Secreting T Cells.

    PubMed

    Olson, Matthew R; Verdan, Felipe Fortino; Hufford, Matthew M; Dent, Alexander L; Kaplan, Mark H

    2016-04-15

    Th cell subsets develop in response to multiple activating signals, including the cytokine environment. IL-9-secreting T cells develop in response to the combination of IL-4 and TGF-β, although they clearly require other cytokine signals, leading to the activation of transcription factors including STAT5. In Th17 cells, there is a molecular antagonism of STAT5 with STAT3 signaling, although whether this paradigm exists in other Th subsets is not clear. In this paper, we demonstrate that STAT3 attenuates the ability of STAT5 to promote the development of IL-9-secreting T cells. We demonstrate that production of IL-9 is increased in the absence of STAT3 and cytokines that result in a sustained activation of STAT3, including IL-6, have the greatest potency in repressing IL-9 production in a STAT3-dependent manner. Increased IL-9 production in the absence of STAT3 correlates with increased endogenous IL-2 production and STAT5 activation, and blocking IL-2 responses eliminates the difference in IL-9 production between wild-type and STAT3-deficient T cells. Moreover, transduction of developing Th9 cells with a constitutively active STAT5 eliminates the ability of IL-6 to reduce IL-9 production. Thus, STAT3 functions as a negative regulator of IL-9 production through attenuation of STAT5 activation and function. PMID:26976954

  1. 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.

  2. Phosphorylation of Leukotriene C4 Synthase at Serine 36 Impairs Catalytic Activity.

    PubMed

    Ahmad, Shabbir; Ytterberg, A Jimmy; Thulasingam, Madhuranayaki; Tholander, Fredrik; Bergman, Tomas; Zubarev, Roman; Wetterholm, Anders; Rinaldo-Matthis, Agnes; Haeggström, Jesper Z

    2016-08-26

    Leukotriene C4 synthase (LTC4S) catalyzes the formation of the proinflammatory lipid mediator leukotriene C4 (LTC4). LTC4 is the parent molecule of the cysteinyl leukotrienes, which are recognized for their pathogenic role in asthma and allergic diseases. Cellular LTC4S activity is suppressed by PKC-mediated phosphorylation, and recently a downstream p70S6k was shown to play an important role in this process. Here, we identified Ser(36) as the major p70S6k phosphorylation site, along with a low frequency site at Thr(40), using an in vitro phosphorylation assay combined with mass spectrometry. The functional consequences of p70S6k phosphorylation were tested with the phosphomimetic mutant S36E, which displayed only about 20% (20 μmol/min/mg) of the activity of WT enzyme (95 μmol/min/mg), whereas the enzyme activity of T40E was not significantly affected. The enzyme activity of S36E increased linearly with increasing LTA4 concentrations during the steady-state kinetics analysis, indicating poor lipid substrate binding. The Ser(36) is located in a loop region close to the entrance of the proposed substrate binding pocket. Comparative molecular dynamics indicated that Ser(36) upon phosphorylation will pull the first luminal loop of LTC4S toward the neighboring subunit of the functional homotrimer, thereby forming hydrogen bonds with Arg(104) in the adjacent subunit. Because Arg(104) is a key catalytic residue responsible for stabilization of the glutathione thiolate anion, this phosphorylation-induced interaction leads to a reduction of the catalytic activity. In addition, the positional shift of the loop and its interaction with the neighboring subunit affect active site access. Thus, our mutational and kinetic data, together with molecular simulations, suggest that phosphorylation of Ser(36) inhibits the catalytic function of LTC4S by interference with the catalytic machinery. PMID:27365393

  3. Diabetes impairs the vascular effects of aldosterone mediated by G protein-coupled estrogen receptor activation

    PubMed Central

    Ferreira, Nathanne S.; Cau, Stêfany B. A.; Silva, Marcondes A. B.; Manzato, Carla P.; Mestriner, Fabíola L. A. C.; Matsumoto, Takayuki; Carneiro, Fernando S.; Tostes, Rita C.

    2015-01-01

    Aldosterone promotes non-genomic effects in endothelial and vascular smooth muscle cells via activation of mineralocorticoid receptors (MR) and G protein-coupled estrogen receptors (GPER). GPER activation is associated with beneficial/protective effects in the vasculature. Considering that vascular dysfunction plays a major role in diabetes-associated complications, we hypothesized that the beneficial effects mediated by vascular GPER activation, in response to aldosterone, are decreased in diabetes. Mesenteric resistance arteries from female, 14–16 weeks-old, control and diabetic (db/db) mice were used. Phenylephrine (PhE)-induced contractions were greater in arteries from db/db vs. control mice. Aldosterone (10 nM) increased maximal contractile responses to PhE in arteries from control mice, an effect elicited via activation of GPER. Although aldosterone did not increase PhE responses in arteries from db/db mice, blockade of GPER, and MR decreased PhE-induced contractile responses in db/db mesenteric arteries. Aldosterone also reduced the potency of acetylcholine (ACh)-induced relaxation in arteries from both control and db/db mice via MR-dependent mechanisms. GPER antagonism further decreased ACh-induced relaxation in the control group, but did not affect ACh responses in the diabetic group. Aldosterone increased extracellular signal-regulated kinase 1/2 phosphorylation in arteries from control and db/db mice by a GPER-dependent mechanism. GPER, but not MR, gene, and protein expression, determined by RT-PCR and immunoblotting/immunofluorescence assays, respectively, were increased in arteries from db/db mice vs. control arteries. These findings indicate that aldosterone activates both vascular MR and GPER and that the beneficial effects of GPER activation are decreased in arteries from diabetic animals. Our results further elucidate the mechanisms by which aldosterone influences vascular function and contributes to vascular dysfunction in diabetes. Financial

  4. Mutation of a diacidic motif in SIV-PBj Nef impairs T-cell activation and enteropathic disease

    PubMed Central

    2011-01-01

    Background The non-pathogenic course of SIV infection in its natural host is characterized by robust viral replication in the absence of chronic immune activation and T cell proliferation. In contrast, acutely lethal enteropathic SIVsmm strain PBj induces a strong immune activation and causes a severe acute and lethal disease in pig-tailed macaques after cross-species transmission. One important pathogenicity factor of the PBj virus is the PBj-Nef protein, which contains a conserved diacidic motif and, unusually, an immunoreceptor tyrosine-based activation motif (ITAM). Results Mutation of the diacidic motif in the Nef protein of the SIVsmmPBj abolishes the acute phenotype of this virus. In vitro, wild-type and mutant PBj (PBj-Nef202/203GG) viruses replicated to similar levels in macaque PBMCs, but PBj-Nef202/203GG no longer triggers ERK mitogen-activated protein (MAP) kinase pathway including an alteration of a Nef-associated Raf-1/ERK-2 multiprotein signaling complex. Moreover, stimulation of IL-2 and down-modulation of CD4 and CD28 were impaired in the mutant virus. Pig-tailed macaques infected with PBj-Nef202/203GG did not show enteropathic complications and lethality as observed with wild-type PBj virus, despite efficient replication of both viruses in vivo. Furthermore, PBj-Nef202/203GG infected animals revealed reduced T-cell activation in periphery lymphoid organs and no detectable induction of IL-2 and IL-6. Conclusions In sum, we report here that mutation of the diacidic motif in the PBj-Nef protein abolishes disease progression in pig-tailed macaques despite efficient replication. These data suggest that alterations in the ability of a lentivirus to promote T cell activation and proliferation can have a dramatic impact on its pathogenic potential. PMID:21366921

  5. 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. PMID:25766677

  6. Gas6 Downregulation Impaired Cytoplasmic Maturation and Pronuclear Formation Independent to the MPF Activity

    PubMed Central

    Kim, Kyeoung-Hwa; Kim, Eun-Young; Kim, Yuna; Kim, Eunju; Lee, Hyun-Seo; Yoon, Sook-Young; Lee, Kyung-Ah

    2011-01-01

    Previously, we found that the growth arrest-specific gene 6 (Gas6) is more highly expressed in germinal vesicle (GV) oocytes than in metaphase II (MII) oocytes using annealing control primer (ACP)-PCR technology. The current study was undertaken to investigate the role of Gas6 in oocyte maturation and fertilization using RNA interference (RNAi). Interestingly, despite the specific and marked decrease in Gas6 mRNA and protein expression in GVs after Gas6 RNAi, nuclear maturation including spindle structures and chromosome segregation was not affected. The only discernible effect induced by Gas6 RNAi was a change in maturation promoting factor (MPF) activity. After parthenogenetic activation, Gas6 RNAi-treated oocytes at the MII stage had not developed further and arrested at MII (90.0%). After stimulation with Sr2+, Gas6-silenced MII oocytes had markedly reduced Ca2+ oscillation and exhibited no exocytosis of cortical granules. In these oocytes, sperm penetration occurred during fertilization but not pronucleus (PN) formation. By roscovitine and colcemid treatment, we found that the Gas6 knockdown affected cytoplasmic maturation directly, independent to the changed MPF activity. These results strongly suggest that 1) the Gas6 signaling itself is important to the cytoplasmic maturation, but not nuclear maturation, and 2) the decreased Gas6 expression and decreased MPF activity separately or mutually influence sperm head decondensation and PN formation. PMID:21850267

  7. 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…

  8. Thymosin beta4 targeting impairs tumorigenic activity of colon cancer stem cells.

    PubMed

    Ricci-Vitiani, Lucia; Mollinari, Cristiana; di Martino, Simona; Biffoni, Mauro; Pilozzi, Emanuela; Pagliuca, Alfredo; de Stefano, Maria Chiara; Circo, Rita; Merlo, Daniela; De Maria, Ruggero; Garaci, Enrico

    2010-11-01

    Thymosin β4 (Tβ4) is an actin-binding peptide overexpressed in several tumors, including colon carcinomas. The aim of this study was to investigate the role of Tβ4 in promoting the tumorigenic properties of colorectal cancer stem cells (CR-CSCs), which are responsible for tumor initiation and growth. We first found that CR-CSCs from different patients have higher Tβ4 levels than normal epithelial cells. Then, we used a lentiviral strategy to down-regulate Tβ4 expression in CR-CSCs and analyzed the effects of such modulation on proliferation, survival, and tumorigenic activity of CR-CSCs. Empty vector-transduced CR-CSCs were used as a control. Targeting of the Tβ4 produced CR-CSCs with a lower capacity to grow and migrate in culture and, interestingly, reduced tumor size and aggressiveness of CR-CSC-based xenografts in mice. Moreover, such loss in tumorigenic activity was accompanied by a significant increase of phosphatase and tensin homologue (PTEN) and a concomitant reduction of the integrin-linked kinase (ILK) expression, which resulted in a decreased activation of protein kinase B (Akt). Accordingly, exogenous expression of an active form of Akt rescued all the protumoral features lost after Tβ4 targeting in CR-CSCs. In conclusion, Tβ4 may have important implications for therapeutic intervention for treatment of human colon carcinoma. PMID:20566622

  9. 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…

  10. Acute cholesterol depletion impairs functional expression of tissue factor in fibroblasts: modulation of tissue factor activity by membrane cholesterol

    PubMed Central

    Mandal, Samir K.; Iakhiaev, Alexei; Pendurthi, Usha R.; Mohan Rao, L. Vijaya

    2010-01-01

    Cholesterol, in addition to providing rigidity to the fluid membrane, plays a critical role in receptor function, endocytosis, recycling, and signal transduction. In the present study, we examined the effect of membrane cholesterol on functional expression of tissue factor (TF), a cellular receptor for clotting factor VIIa. Depletion of cholesterol in human fibroblasts (WI-38) with methyl-β-cyclodextrin–reduced TF activity at the cell surface. Binding studies with radiolabeled VIIa and TF monoclonal antibody (mAB) revealed that reduced TF activity in cholesterol-depleted cells stems from the impairment of VIIa interaction with TF rather than the loss of TF receptors at the cell surface. Repletion of cholesterol-depleted cells with cholesterol restored TF function. Loss of caveolar structure on cholesterol removal is not responsible for reduced TF activity. Solubilization of cellular TF in different detergents indicated that a substantial portion of TF in fibroblasts is associated with noncaveolar lipid rafts. Cholesterol depletion studies showed that the TF association with these rafts is cholesterol dependent. Overall, the data presented herein suggest that membrane cholesterol functions as a positive regulator of TF function by maintaining TF receptors, probably in noncaveolar lipid rafts, in a high-affinity state for VIIa binding. PMID:15328160

  11. Nocturnal autonomic nervous system activity impairment in sickle cell trait carriers.

    PubMed

    Connes, Philippe; Martin, Cyril; Barthelemy, Jean-Claude; Monchanin, Géraldine; Atchou, Guillaume; Forsuh, Anthony; Massarelli, Raphaël; Wouassi, Dieudonné; Thiriet, Patrice; Pichot, Vincent

    2006-03-01

    Sickle cell trait (SCT) is a genetic disease affecting the synthesis of normal haemoglobin (Hb) and marked by the heterozygous presence of HbA and HbS. Some studies have suggested that SCT carriers might be prone to vascular alterations, cardiac ischaemia and arrhythmias leading, in some subjects, to sudden death. It is well known that a loss or a disequilibrium of autonomic activity are powerful predictors of sudden cardiac death. We hypothesized that SCT subjects might exhibit alterations in the activity of the autonomic nervous system that could constitute further risk factors for cardiac complications. Resting haemorheological parameters (eta(b), blood viscosity; eta(p), plasma viscosity; Hct, haematocrit; Tk, red blood cell rigidity), and sympathetic and parasympathetic indices of nocturnal autonomic activity (temporal and frequency analysis of heart rate variability) were thus compared between a group of nine SCT subjects and a group of nine control subjects. eta(b) was higher in the SCT group than in the control group while Hct, eta(p) and Tk were not different. Global variability (SDNN, SDNNIDX) and parasympathetic (PNN50, RMSSD, HF) indices were significantly lower in the SCT group compared with the control group, while the LF/HF ratio was highly increased, underlining a major sympathetic shift. The autonomic imbalance in SCT subjects was mainly related to lowered parasympathetic activity. Thus, our study suggests an additional global decrease and imbalance of autonomic nervous system activity to biological disorders of SCT carriers, that may constitute further risk factors for cardiac complications in this population. PMID:16494598

  12. Impaired 17,20-Lyase Activity in Male Mice Lacking Cytochrome b5 in Leydig Cells.

    PubMed

    Sondhi, Varun; Owen, Bryn M; Liu, Jiayan; Chomic, Robert; Kliewer, Steven A; Hughes, Beverly A; Arlt, Wiebke; Mangelsdorf, David J; Auchus, Richard J

    2016-04-01

    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 Cyb5(flox/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

  13. Impaired leaf litter processing in acidified streams : learning from microbial enzyme activities.

    PubMed

    Clivot, Hugues; Danger, Michael; Pagnout, Christophe; Wagner, Philippe; Rousselle, Philippe; Poupin, Pascal; Guérold, François

    2013-01-01

    Anthropogenic acidification in headwater streams is known to affect microbial assemblages involved in leaf litter breakdown. Far less is known about its potential effects on microbial enzyme activities. To assess the effects of acidification on microbial activities associated with decaying leaves, a 70-day litter bag experiment was conducted in headwater streams at six sites across an acidification gradient. The results revealed that microbial leaf decomposition was strongly and negatively correlated with total Al concentrations (r = -0.99, p < 0.001) and positively correlated with Ca(2+) concentrations (r = 0.94, p = 0.005) and pH (r = 0.93, p = 0.008). Denaturing gradient gel electrophoresis analyses showed that microbial assemblages differed between non-impacted and impacted sites, whereas fungal biomass associated with decaying leaves was unaffected. The nutrient content of leaf detritus and ecoenzymatic activities of carbon (C), nitrogen (N) and phosphorus (P) acquisition revealed that N acquisition was unaltered, while P acquisition was significantly reduced across the acidification gradient. The P content of leaf litter was negatively correlated with total Al concentrations (r = -0.94, p < 0.01) and positively correlated with decomposition rates (r = 0.95, p < 0.01). This potential P limitation of microbial decomposers in impacted sites was confirmed by the particularly high turnover activity for phosphatase and imbalanced ratios between the ecoenzymatic activities of C and P acquisition. The toxic form of Al has well-known direct effects on aquatic biota under acidic conditions, but in this study, Al was found to also potentially affect microbially mediated leaf processing by interfering with the P cycle. These effects may in turn have repercussions on higher trophic levels and whole ecosystem functioning. PMID:22903164

  14. 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

  15. Impaired platelet activation and cAMP homeostasis in MRP4-deficient mice

    PubMed Central

    Decouture, Benoit; Dreano, Elise; Belleville-Rolland, Tiphaine; Kuci, Orjeta; Dizier, Blandine; Bazaa, Amine; Coqueran, Bérard; Lompre, Anne-Marie; Denis, Cécile V.; Hulot, Jean-Sébastien; Gaussem, Pascale

    2015-01-01

    Molecules that reduce the level of cyclic adenosine 5′-monophosphate (cAMP) in the platelet cytosol, such as adenosine 5′-diphosphate (ADP) secreted from dense granules, trigger platelet activation. Therefore, any change in the distribution and/or availability of cyclic nucleotides or ADP may interfere with platelet reactivity. In this study, we evaluated the role of multidrug resistance protein 4 (MRP4, or ABCC4), a nucleotide transporter, in platelet functions in vivo and in vitro by investigating MRP4-deficient mice. MRP4 deletion resulted in a slight increase in platelet count but had no impact on platelet ultrastructure. In MRP4-deficient mice, the arterial occlusion was delayed and the tail bleeding time was prolonged. In a model of platelet depletion and transfusion mimicking a platelet-specific knockout, mice injected with MRP4−/− platelets also showed a significant increase in blood loss compared with mice injected with wild-type platelets. Defective thrombus formation and platelet activation were confirmed in vitro by studying platelet adhesion to collagen in flow conditions, integrin αIIbβ3 activation, washed platelet secretion, and aggregation induced by low concentrations of proteinase-activated receptor 4–activating peptide, U46619, or ADP. We found no role of MRP4 in ADP dense-granule storage, but MRP4 redistributed cAMP from the cytosol to dense granules, as confirmed by increased vasodilator-stimulated phosphoprotein phosphorylation in MRP4-deficient platelets. These data suggest that MRP4 promotes platelet aggregation by modulating the cAMP–protein kinase A signaling pathway, suggesting that MRP4 might serve as a target for novel antiplatelet agents. PMID:26316625

  16. 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

  17. Mild Cognitive Impairment

    MedlinePlus

    ... other people their age. This condition is called mild cognitive impairment, or MCI. People with MCI can take care of themselves and do their normal activities. MCI memory problems may include Losing things often Forgetting ...

  18. Overexpression of urokinase-type plasminogen activator in transgenic mice is correlated with impaired learning.

    PubMed Central

    Meiri, N; Masos, T; Rosenblum, K; Miskin, R; Dudai, Y

    1994-01-01

    Transgenic mice designated alpha MUPA overproduce in the brain murine urokinase-type plasminogen activator (uPA), an extracellular protease implicated in tissue remodeling. We have now localized, by in situ hybridization, extensive signal of uPA mRNA in the alpha MUPA cortex, hippocampus, and amygdala, sites that were not labeled in counterpart wild-type mice. Furthermore, biochemical measurements reveal a remarkably high level of enzymatic activity of uPA in the cortex and hippocampus of alpha MUPA compared with wild-type mice. We have used the alpha MUPA mice to examine whether the abnormal level of uPA in the cortex and the limbic system affects learning ability. We report that alpha MUPA mice perform poorly in tasks of spatial, olfactory, and taste-aversion learning, while displaying normal sensory and motor capabilities. Our results suggest that uPA is involved in neural processes subserving a variety of learning types. Images PMID:8159723

  19. 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. PMID:27351882

  20. 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. PMID:22942069

  1. 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. PMID:26386335

  2. Impaired autonomic nervous system activity during sleep in family caregivers of ambulatory dementia patients in Japan.

    PubMed

    Sakurai, Shihomi; Onishi, Joji; Hirai, Makoto

    2015-01-01

    The number of dementia patients requiring care is rapidly increasing in Japan. Consequently, a large percentage of family members, including spouses and children of those with dementia, are assuming the role of primary caregiver. Many caregivers develop health problems including sleep disorders. Some report poor quality of sleep even when sleep duration is normal. In the present study, we used actigraphy and heart rate variability spectral analysis to assess autonomic nervous system activity and quality of sleep in family caregivers of people with ambulatory dementia. The 20 caregivers who participated in our study exhibited significantly higher levels of sympathetic nervous system activity during sleep than noncaregivers. This abnormal activity was most prominent during the first half of the sleep period and was not related to overall sleep duration. We propose that relaxation is inhibited during the first half of the sleep period in this caregiver population. This may be due to increased stress, as caregivers of people with ambulatory dementia may worry about their patients waking and wandering at night, potentially injuring themselves. Our findings indicate a need for increased support for caregivers of people with dementia, including the assessment and treatment of sleep disorders. PMID:25504947

  3. Nitroxoline impairs tumor progression in vitro and in vivo by regulating cathepsin B activity.

    PubMed

    Mirković, Bojana; Markelc, Boštjan; Butinar, Miha; Mitrović, Ana; Sosič, Izidor; Gobec, Stanislav; Vasiljeva, Olga; Turk, Boris; Čemažar, Maja; Serša, Gregor; Kos, Janko

    2015-08-01

    Cathepsin B is a ubiquitously expressed lysosomal cysteine protease that participates in protein turnover within lysosomes. However, its protein and activity levels have been shown to be increased in cancer. Cathepsin B endopeptidase activity is involved in the degradation of extracellular matrix, a process that promotes tumor invasion, metastasis and angiogenesis. Previously, we reported an established antibiotic nitroxoline as a potent and selective inhibitor of cathepsin B. In the present study, we elucidated its anti-tumor properties in in vitro and in vivo tumor models. Tumor and endothelial cell lines with high levels of active cathepsin B were selected for functional analysis of nitroxoline in vitro. Nitroxoline significantly reduced extracellular DQ-collagen IV degradation by all evaluated cancer cell lines using spectrofluorimetry. Nitroxoline also markedly decreased tumor cell invasion monitored in real time and reduced the invasive growth of multicellular tumor spheroids, used as a 3D in vitro model of tumor invasion. Additionally, endothelial tube formation was significantly reduced by nitroxoline in an in vitro angiogenesis assay. Finally, nitroxoline significantly abrogated tumor growth, angiogenesis and metastasis in vivo in LPB fibrosarcoma and MMTV-PyMT breast cancer mouse models. Overall, our results designate nitroxoline as a promising drug candidate for anti-cancer treatment. PMID:25848918

  4. Compensatory role of inducible annexin A2 for impaired biliary epithelial anion-exchange activity of inflammatory cholangiopathy.

    PubMed

    Kido, Osamu; Fukushima, Koji; Ueno, Yoshiyuki; Inoue, Jun; Jefferson, Douglas M; Shimosegawa, Tooru

    2009-12-01

    The peribiliary inflammation of cholangiopathy affects the physiological properties of biliary epithelial cells (cholangiocyte), including bicarbonate-rich ductular secretion. We revealed the upregulation of annexin A2 (ANXA2) in cholangiocytes in primary biliary cirrhosis (PBC) by a proteomics approach and evaluated its physiological significance. Global protein expression profiles of a normal human cholangiocyte line (H69) in response to interferon-gamma (IFNgamma) were obtained by two-dimensional electrophoresis followed by MALDI-TOF-MS. Histological expression patterns of the identified molecules in PBC liver were confirmed by immunostaining. H69 cells stably transfected with doxycyclin-inducible ANXA2 were subjected to physiological evaluation. Recovery of the intracellular pH after acute alkalinization was measured consecutively by a pH indicator with a specific inhibitor of anion exchanger (AE), 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS). Protein kinase-C (PKC) activation was measured by PepTag Assay and immunoblotting. Twenty spots that included ANXA2 were identified as IFNgamma-responsive molecules. Cholangiocytes of PBC liver were decorated by the unique membranous overexpression of ANXA2. Apical ANXA2 of small ducts of PBC was directly correlated with the clinical cholestatic markers and transaminases. Controlled induction of ANXA2 resulted in significant increase of the DIDS-inhibitory fraction of AE activity of H69, which was accompanied by modulation of PKC activity. We, therefore, identified ANXA2 as an IFNgamma-inducible gene in cholangiocytes that could serve as a potential histological marker of inflammatory cholangiopathy, including PBC. We conclude that inducible ANXA2 expression in cholangiocytes may play a compensatory role for the impaired AE activity of cholangiocytes in PBC in terms of bicarbonate-rich ductular secretion and bile formation through modulation of the PKC activity. PMID:19823170

  5. 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

  6. RAI1 Transcription Factor Activity Is Impaired in Mutants Associated with Smith-Magenis Syndrome

    PubMed Central

    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. PMID:23028815

  7. Factors Associated with Leisure Activity among Young Adults with Developmental Disabilities

    ERIC Educational Resources Information Center

    Van Naarden Braun, Kim; Yeargin-Allsopp, Marshalyn; Lollar, Donald

    2006-01-01

    The framework of the International Classification of Functioning, Disability, and Health (ICF) was applied to examine the factors associated with childhood impairment and leisure activity. Information on leisure activity was obtained using a structured questionnaire from a population-based cohort of young adults with childhood impairment. The…

  8. Impaired Activation in Cognitive Control Regions Predicts Reversal Learning in Schizophrenia.

    PubMed

    Culbreth, Adam J; Gold, James M; Cools, Roshan; Barch, Deanna M

    2016-03-01

    Reinforcement learning deficits have been associated with schizophrenia (SZ). However, the pathophysiology that gives rise to these abnormalities remains unclear. To address this question, SZ patients (N = 58) and controls (CN; N = 36) completed a probabilistic reversal-learning paradigm during functional magnetic resonance imaging scanning. During the task, participants choose between 2 stimuli. Initially, 1 stimulus was frequently rewarded (80%); the other was infrequently rewarded (20%). The reward contingencies reversed periodically because the participant learned the more rewarded stimulus. The results indicated that SZ patients achieved fewer reversals than CN, and demonstrated decreased winstay-loseshift decision-making behavior. On loseshift compared to winstay trials, SZ patients showed reduced Blood Oxygen Level Dependent activation compared to CN in a network of brain regions widely associated with cognitive control, and striatal regions. Importantly, relationships between group membership and behavior were mediated by alterations in the activity of cognitive control regions, but not striatum. These findings indicate an important role for the cognitive control network in mediating the use and updating of value representations in SZ. Such results provide biological targets for further inquiry because researchers attempt to better characterize decision-making neural circuitry in SZ as a means to discover new pathways for interventions. PMID:26049083

  9. HIV enhancing activity of semen impairs the antiviral efficacy of microbicides

    PubMed Central

    Zirafi, Onofrio; Kim, Kyeong-Ae; Roan, Nadia R.; Kluge, Silvia F.; Müller, Janis A.; Jiang, Shibo; Mayer, Benjamin; Greene, Warner C.; Kirchhoff, Frank; Münch, Jan

    2015-01-01

    Topically applied microbicides potently inhibit HIV in vitro but have largely failed to exert protective effects in clinical trials. One possible reason for this discrepancy is that the preclinical testing of microbicides does not faithfully reflect the conditions of HIV sexual transmission. Here, we report that candidate microbicides that target HIV components show greatly reduced antiviral efficacy in the presence of semen, the main vector for HIV transmission. This diminished antiviral activity was dependent on the ability of amyloid fibrils in semen to enhance the infectivity of HIV. Thus, the anti-HIV efficacy of microbicides determined in the absence of semen greatly underestimated the drug concentrations needed to block semen-exposed virus. One notable exception was Maraviroc. This HIV entry inhibitor targets the host cell CCR5 coreceptor and was highly active against both untreated and semen-exposed HIV. These data help explain why microbicides have failed to protect against HIV in clinical trials and suggest that antiviral compounds targeting host factors hold promise for further development. These findings also suggest that the in vitro efficacy of candidate microbicides should be determined in the presence of semen to identify the best candidates for the prevention of HIV sexual transmission. PMID:25391483

  10. Inhibitors of SRC kinases impair antitumor activity of anti-CD20 monoclonal antibodies

    PubMed Central

    Winiarska, Magdalena; Bojarczuk, Kamil; Pyrzynska, Beata; Bil, Jacek; Siernicka, Marta; Dwojak, Michal; Bobrowicz, Malgorzata; Miazek, Nina; Zapala, Piotr; Zagozdzon, Agnieszka; Krol, Magdalena; Syta, Aleksandra; Podszywalow-Bartnicka, Paulina; Pilch, Zofia; Dabrowska-Iwanicka, Anna; Juszczynski, Przemyslaw; Efremov, Dimitar G; Slabicki, Mikolaj; Zenz, Thorsten; Roy, Aude Le; Olive, Daniel; Rygiel, Tomasz P; Leusen, Jeanette HW; Golab, Jakub

    2014-01-01

    Clinical trials with SRC family kinases (SFKs) inhibitors used alone or in a combination with anti-CD20 monoclonal antibodies (mAbs) are currently underway in the treatment of B-cell tumors. However, molecular interactions between these therapeutics have not been studied so far. A transcriptional profiling of tumor cells incubated with SFKs inhibitors revealed strong downregulation of MS4A1 gene encoding CD20 antigen. In a panel of primary and established B-cell tumors we observed that SFKs inhibitors strongly affect CD20 expression at the transcriptional level, leading to inhibition of anti-CD20 mAbs binding and increased resistance of tumor cells to complement-dependent cytotoxicity. Activation of the AKT signaling pathway significantly protected cells from dasatinib-triggered CD20 downregulation. Additionally, SFKs inhibitors suppressed antibody-dependent cell-mediated cytotoxicity by direct inhibition of natural killer cells. Abrogation of antitumor activity of rituximab was also observed in vivo in a mouse model. Noteworthy, the effects of SFKs inhibitors on NK cell function are largely reversible. The results of our studies indicate that development of optimal combinations of novel treatment modalities with anti-CD20 mAbs should be preceded by detailed preclinical evaluation of their effects on target cells. PMID:25517315

  11. 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

  12. Impaired Spatial Learning Memory after Isoflurane Anesthesia or Appendectomy in Aged Mice is Associated with Microglia Activation

    PubMed Central

    Wang, Hui-Lin; Ma, Rui-Hua; Fang, Hao; Xue, Zhang-Gang; Liao, Qing-Wu

    2015-01-01

    Postoperative cognitive dysfunction (POCD) has been one of the most common problems in elderly patients following surgery. But the specific mechanism of POCD is still not clear. To further understand the reason of these postoperative behavioral deficits, we evaluated the spatial learning memory of both adult (3 months) and aged (18 months) male mice, 3 or 28 days after isoflurane (Iso) exposure for two hours or appendectomy (App). Hippocampal microglia activation and IL-1β, TNF-α, and IFN-γ expression were also evaluated at day 3, day 14 and day 28 after Iso exposure or appendectomy. Results showed that spatial learning memory of aged, but not adult, mice was impaired after Iso exposure or appendectomy, accompanied with more hippocampal microglia activation and IL-1β, TNF-α, and IFN-γ overexpression. These findings suggest that the cognitive deficits of elderly patients who have undergone surgeries are quite possibly caused by hippocampal microglia overactivation and the subsequent inflammation. PMID:26380557

  13. Estrogen receptor β activation impairs mitochondrial oxidative metabolism and affects malignant mesothelioma cell growth in vitro and in vivo

    PubMed Central

    Manente, A G; Valenti, D; Pinton, G; Jithesh, P V; Daga, A; Rossi, L; Gray, S G; O'Byrne, K J; Fennell, D A; Vacca, R A; Nilsson, S; Mutti, L; Moro, L

    2013-01-01

    Estrogen receptor (ER)-β has been shown to possess a tumor suppressive effect, and is a potential target for cancer therapy. Using gene-expression meta-analysis of human malignant pleural mesothelioma, we identified an ESR2 (ERβ coding gene) signature. High ESR2 expression was strongly associated with low succinate dehydrogenase B (SDHB) (which encodes a mitochondrial respiratory chain complex II subunit) expression. We demonstrate that SDHB loss induced ESR2 expression, and that activated ERβ, by over-expression or by selective agonist stimulation, negatively affected oxidative phosphorylation compromising mitochondrial complex II and IV activity. This resulted in reduced mitochondrial ATP production, increased glycolysis dependence and impaired cell proliferation. The observed in vitro effects were phenocopied in vivo using a selective ERβ agonist in a mesothelioma mouse model. On the whole, our data highlight an unforeseen interaction between ERβ-mediated tumor suppression and energy metabolism that may be exploited to improve on the therapy for clinical management of malignant mesothelioma. PMID:24061575

  14. Adult-onset hyperthyroidism impairs spatial learning: possible involvement of mitogen-activated protein kinase signaling pathways.

    PubMed

    Bitiktaş, Soner; Kandemir, Başak; Tan, Burak; Kavraal, Şehrazat; Liman, Narin; Dursun, Nurcan; Dönmez-Altuntaş, Hamiyet; Aksan-Kurnaz, Işil; Suer, Cem

    2016-08-01

    Given evidence that mitogen-activated protein kinase (MAPK) activation is part of the nongenomic actions of thyroid hormones, we investigated the possible consequences of hyperthyroidism for the cognitive functioning of adult rats. Young adult rats were treated with L-thyroxine or saline. Twenty rats in each group were exposed to Morris water maze testing, measuring their performance in a hidden-platform spatial task. In a separate set of rats not exposed to Morris water maze testing (untrained rats), the expression and phosphorylated levels of p38-MAPK and of its two downstream effectors, Elk-1 and cAMP response element-binding protein, were evaluated using quantitative reverse transcriptase-PCR and western blotting. Rats with hyperthyroidism showed delayed acquisition of learning compared with their wild-type counterparts, as shown by increased escape latencies and distance moved on the last two trials of daily training in the water maze. The hyperthyroid rats, however, showed no difference during probe trials. Western blot analyses of the hippocampus showed that hyperthyroidism increased phosphorylated p38-MAPK levels in untrained rats. Although our study is correlative in nature and does not exclude the contribution of other molecular targets, our findings suggest that the observed impairments in acquisition during actual learning in rats with hyperthyroidism may result from the increased phosphorylation of p38-MAPK. PMID:27258653

  15. Children's performance on a false-belief task is impaired by activation of an evolutionarily-canalized response system.

    PubMed

    Keenan, Thomas; Ellis, Bruce J

    2003-07-01

    We examine whether children's performance on a false-belief task is impaired by task content that activates an early-developing, prepotent motivational system: predator-avoidance. In two studies (N = 46 and N = 37), children aged 3-4 years completed variants of a false-belief task that involved predator-avoidance, playmate-avoidance, prey-seeking, and playmate-seeking, respectively. The proportion of correct answers on the playmate-avoidance task (Study 1: 52%; Study 2: 51%) was significantly greater than the proportion of correct answers on the analogous predator-avoidance task (Study 1: 28%; Study 2: 22%). This difference was not an artifact of children generally performing better on playmate stories than on predator-prey stories. The findings are consistent with the hypothesis that activation of the predator-avoidance system generates prepotent response patterns that pre-empt full consideration of the mental states of the prey characters in false-belief stories. PMID:12810037

  16. The Beneficial Effects of Physical Activity on Impaired Adult Neurogenesis and Cognitive Performance

    PubMed Central

    Lafenetre, Pauline; Leske, Oliver; Wahle, Petra; Heumann, Rolf

    2011-01-01

    Neurogenesis occurs in two neurogenic zones in the adult brain: new neurons are born at the subventricular zone of the lateral ventricles and then migrate to the olfactory bulb, and at the subgranular zone to integrate the granular cell layer of the dentate gyrus. The hippocampus is involved in learning and memory and the generation of new hippocampal neurons has been suggested to be a new form of plasticity implicated in these processes. In the last decades, diverse intrinsic and epigenetic factors have been identified to influence adult neurogenesis but the underlying mechanisms remain unclear. In a recent study, Lafenetre et al. (2010) showed the beneficial influence of physical voluntary activity on adult neurogenesis and cognitive performance in a transgenic mouse, the synRas mouse via brain-derived neurotrophic factor. Here we review how hippocampal neurogenesis can be regulated by environmental factors and the possible role of the newly generated cells in learning and memory. PMID:21559064

  17. 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. PMID:23643981

  18. 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. PMID:16831232

  19. An Alteration in ELMOD3, an Arl2 GTPase-Activating Protein, Is Associated with Hearing Impairment in Humans

    PubMed Central

    Ivanova, Anna A.; Giese, Arnaud P. J.; Choo, Daniel I.; Khan, Shaheen N.; Riazuddin, Sheikh; Kahn, Richard A.; Riazuddin, Saima

    2013-01-01

    Exome sequencing coupled with homozygosity mapping was used to identify a transition mutation (c.794T>C; p.Leu265Ser) in ELMOD3 at the DFNB88 locus that is associated with nonsyndromic deafness in a large Pakistani family, PKDF468. The affected individuals of this family exhibited pre-lingual, severe-to-profound degrees of mixed hearing loss. ELMOD3 belongs to the engulfment and cell motility (ELMO) family, which consists of six paralogs in mammals. Several members of the ELMO family have been shown to regulate a subset of GTPases within the Ras superfamily. However, ELMOD3 is a largely uncharacterized protein that has no previously known biochemical activities. We found that in rodents, within the sensory epithelia of the inner ear, ELMOD3 appears most pronounced in the stereocilia of cochlear hair cells. Fluorescently tagged ELMOD3 co-localized with the actin cytoskeleton in MDCK cells and actin-based microvilli of LLC-PK1-CL4 epithelial cells. The p.Leu265Ser mutation in the ELMO domain impaired each of these activities. Super-resolution imaging revealed instances of close association of ELMOD3 with actin at the plasma membrane of MDCK cells. Furthermore, recombinant human GST-ELMOD3 exhibited GTPase activating protein (GAP) activity against the Arl2 GTPase, which was completely abolished by the p.Leu265Ser mutation. Collectively, our data provide the first insights into the expression and biochemical properties of ELMOD3 and highlight its functional links to sound perception and actin cytoskeleton. PMID:24039609

  20. Overexpression of Eukaryotic Translation Elongation Factor 3 Impairs Gcn2 Protein Activation*

    PubMed Central

    Visweswaraiah, Jyothsna; Lee, Su Jung; Hinnebusch, Alan G.; Sattlegger, Evelyn

    2012-01-01

    In eukaryotes, phosphorylation of translation initiation factor 2α (eIF2α) by the kinase Gcn2 (general control nonderepressible 2) is a key response to amino acid starvation. Sensing starvation requires that Gcn2 directly contacts its effector protein Gcn1, and both must contact the ribosome. We have proposed that Gcn2 is activated by uncharged tRNA bound to the ribosomal decoding (A) site, in a manner facilitated by ribosome-bound Gcn1. Protein synthesis requires cyclical association of eukaryotic elongation factors (eEFs) with the ribosome. Gcn1 and Gcn2 are large proteins, raising the question of whether translation and monitoring amino acid availability can occur on the same ribosome. Part of the ribosome-binding domain in Gcn1 has homology to one of the ribosome-binding domains in eEF3, suggesting that these proteins utilize overlapping binding sites on the ribosome and consequently cannot function simultaneously on the same ribosome. Supporting this idea, we found that eEF3 overexpression in Saccharomyces cerevisiae diminished growth on amino acid starvation medium (Gcn− phenotype) and decreased eIF2α phosphorylation, and that the growth defect associated with constitutively active Gcn2 was diminished by eEF3 overexpression. Overexpression of the eEF3 HEAT domain, or C terminus, was sufficient to confer a Gcn− phenotype, and both fragments have ribosome affinity. eEF3 overexpression did not significantly affect Gcn1-ribosome association, but it exacerbated the Gcn− phenotype of Gcn1-M7A that has reduced ribosome affinity. Together, this suggests that eEF3 blocks Gcn1 regulatory function on the ribosome. We propose that the Gcn1-Gcn2 complex only functions on ribosomes with A-site-bound uncharged tRNA, because eEF3 does not occupy these stalled complexes. PMID:22888004

  1. Overexpression of eukaryotic translation elongation factor 3 impairs Gcn2 protein activation.

    PubMed

    Visweswaraiah, Jyothsna; Lee, Su Jung; Hinnebusch, Alan G; Sattlegger, Evelyn

    2012-11-01

    In eukaryotes, phosphorylation of translation initiation factor 2α (eIF2α) by the kinase Gcn2 (general control nonderepressible 2) is a key response to amino acid starvation. Sensing starvation requires that Gcn2 directly contacts its effector protein Gcn1, and both must contact the ribosome. We have proposed that Gcn2 is activated by uncharged tRNA bound to the ribosomal decoding (A) site, in a manner facilitated by ribosome-bound Gcn1. Protein synthesis requires cyclical association of eukaryotic elongation factors (eEFs) with the ribosome. Gcn1 and Gcn2 are large proteins, raising the question of whether translation and monitoring amino acid availability can occur on the same ribosome. Part of the ribosome-binding domain in Gcn1 has homology to one of the ribosome-binding domains in eEF3, suggesting that these proteins utilize overlapping binding sites on the ribosome and consequently cannot function simultaneously on the same ribosome. Supporting this idea, we found that eEF3 overexpression in Saccharomyces cerevisiae diminished growth on amino acid starvation medium (Gcn(-) phenotype) and decreased eIF2α phosphorylation, and that the growth defect associated with constitutively active Gcn2 was diminished by eEF3 overexpression. Overexpression of the eEF3 HEAT domain, or C terminus, was sufficient to confer a Gcn(-) phenotype, and both fragments have ribosome affinity. eEF3 overexpression did not significantly affect Gcn1-ribosome association, but it exacerbated the Gcn(-) phenotype of Gcn1-M7A that has reduced ribosome affinity. Together, this suggests that eEF3 blocks Gcn1 regulatory function on the ribosome. We propose that the Gcn1-Gcn2 complex only functions on ribosomes with A-site-bound uncharged tRNA, because eEF3 does not occupy these stalled complexes. PMID:22888004

  2. Histamine impairs midbrain dopaminergic development in vivo by activating histamine type 1 receptors

    PubMed Central

    2014-01-01

    Background Histamine (HA) regulates the sleep-wake cycle, synaptic plasticity and memory in adult mammals. Dopaminergic specification in the embryonic ventral midbrain (VM) coincides with increased HA brain levels. To study the effect of HA receptor stimulation on dopamine neuron generation, we administered HA to dopamine progenitors, both in vitro and in vivo. Results Cultured embryonic day 12 (E12) VM neural stem/progenitor cells expressed transcripts for HA receptors H1R, H2R and H3R. These undifferentiated progenitors increased intracellular calcium upon HA addition. In HA-treated cultures, dopamine neurons significantly decreased after activation of H1R. We performed intrauterine injections in the developing VM to investigate HA effects in vivo. HA administration to E12 rat embryos notably reduced VM Tyrosine Hydroxylase (TH) staining 2 days later, without affecting GABA neurons in the midbrain, or serotonin neurons in the mid-hindbrain boundary. qRT-PCR and Western blot analyses confirmed that several markers important for the generation and maintenance of dopaminergic lineage such as TH, Lmx1a and Lmx1b were significantly diminished. To identify the cell type susceptible to HA action, we injected embryos of different developmental stages, and found that neural progenitors (E10 and E12) were responsive, whereas differentiated dopaminergic neurons (E14 and E16) were not susceptible to HA actions. Proliferation was significantly diminished, whereas neuronal death was not increased in the VM after HA administration. We injected H1R or H2R antagonists to identify the receptor responsible for the detrimental effect of HA on dopaminergic lineage and found that activation of H1R was required. Conclusion These results reveal a novel action of HA affecting dopaminergic lineage during VM development. PMID:25112718

  3. Piperine impairs the migration and T cell-activating function of dendritic cells.

    PubMed

    Rodgers, Gemma; Doucette, Carolyn D; Soutar, David A; Liwski, Robert S; Hoskin, David W

    2016-02-01

    Piperine, a major alkaloid found in the fruits of black and long pepper plants, has anti-inflammatory properties; however, piperine's effect on dendritic cell (DC) migration and T cell-activating function has not been investigated. Bone marrow-derived mouse DCs that were matured in the presence of 100 μM piperine showed reduced in vitro migration in response to CCL21, as well as reduced in vivo migration to lymph nodes. In addition, piperine-treated DCs had reduced CCR7 expression and elevated CCR5 expression, as well as reduced expression of CD40 and class II major histocompatibility complex molecules and decreased nuclear accumulation of RelB. DC production of interleukin (IL)-6, tumor necrosis factor α, and monocyte chemoattractant protein-1 in response to lipopolysaccharide stimulation was also reduced following piperine treatment. Exposure to piperine during maturation therefore caused DCs to retain an immature phenotype, which was associated with a reduced capacity to promote T cell activation since co-culture of ovalbumin (OVA323-339)-specific T cells with OVA323-339-pulsed DCs that were previously matured in the presence of piperine showed reduced interferon-γ and IL-2 expression. OVA323-339-specific T cell proliferation was also reduced in vivo in the presence of piperine-treated DCs. Inhibition of DC migration and function by piperine may therefore be a useful strategy to down-regulate potentially harmful DC-driven T cell responses to self-antigens and transplantation antigens. PMID:26640239

  4. Inactivation of mitogen-activated protein kinase signaling pathway reduces caspase-14 expression in impaired keratinocytes

    PubMed Central

    Dang, Ningning; Pang, Shuguang; Song, Haiyan; An, Liguo; Ma, Xiaoli

    2016-01-01

    Objective(s): Several investigations have revealed that caspase-14 is responsible for the epidermal differentiation and cornification, as well as the regulation of moisturizing effect. However, the precise regulation mechanism is still not clear. This study was aimed to investigate the expression of caspase-14 in filaggrin-deficient normal human epidermal keratinocytes (NHEKs) and to explore the possible mechanism that contributes to the regulation of caspase-14. Materials and Methods: The filaggrin-deficient NHEKs were induced by transfection with lentivirus (LV) vector encoding small hairpin RNAs (shRNA). The inhibitors SB203580, PD98059 and SP600125 were used for suppressing the expression of p38 mitogen-activated protein kinase (MAPK), p44/42 MAPK and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK). The expression of filaggrin, p38 MAPK, p44/42 MAPK and SAPK/JNK, caspase-14, keratin1and keratin2 were detected by western blot. Results: In filaggrin-deficient NHEKs, the expression of p38, p44/42 MAPK and SAPK/JNK and caspase-14 were significantly decreased. The inhibition of p38 and SAPK/JNK reduced the expression of caspase-14, while the p44/42 MAPK showed no consistent effects. Moreover, the filaggrin knockdown decreased the expression of keratin2, but had no effects on the level of keratin1. Conclusion: The decreased expression of caspase-14 in filaggrin-deficient NHEKs may be induced by the inactivation of MAPK signaling pathway. These provide a novel perspective to understand the mechanism for the protective effects of filaggrin and caspase-14 on skin barrier function. PMID:27096061

  5. 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

    2016-03-01

    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. PMID:26806515

  6. 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…

  7. An Introduction to Selecting Appropriate Goals and Activities for the Severely/Profoundly Impaired That Are Appropriate for Their Age. (Using Curricular Domains).

    ERIC Educational Resources Information Center

    Arnold, Yvonne

    Two introductory manuals, written as part of a practicum to meet the staff needs in the Philadelphia, Pennsylvania School District's severely/profoundly impaired (SPI) programs, focus on selecting goals and activities that are age appropriate for SPI students. Introductory materials review judicial rulings regarding Philadelphia's services for SPI…

  8. 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…

  9. 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

  10. 5-Azacytidine Promotes an Inhibitory T-Cell Phenotype and Impairs Immune Mediated Antileukemic Activity

    PubMed Central

    Stübig, Thomas; Luetkens, Tim; Hildebrandt, York; Atanackovic, Djordje; Binder, Thomas M. C.; Fehse, Boris; Kröger, Nicolaus

    2014-01-01

    Demethylating agent, 5-Azacytidine (5-Aza), has been shown to be active in treatment of myeloid malignancies. 5-Aza enhances anticancer immunity, by increasing expression of tumor-associated antigens. However, the impact of 5-Aza immune responses remains poorly understood. Here, T-cell mediated tumor immunity effects of 5-Aza, are investigated in vitro and in vivo. T-cells from healthy donors were treated with 5-Aza and analyzed by qRT-PCR and flow cytometry for changes in gene expression and phenotype. Functionality was assessed by a tumor lysis assay. Peripheral blood from patients treated with 5-Aza after alloSCT was monitored for changes in T-cell subpopulations. 5-Aza treatment resulted in a decrease in CD8+ T-cells, whereas CD4+ T-cells increased. Furthermore, numbers of IFN-γ+ T-helper 1 cells (Th1) were reduced, while Treg-cells showed substantial increase. Additionally, CD8+ T-cells exhibited limited killing capacity against leukemic target cells. In vivo data confirm the increase of Treg compartment, while CD8+ T-effector cell numbers were reduced. 5-Aza treatment results in a shift from cytotoxic to regulatory T-cells with a functional phenotype and a major reduction in proinflammatory Th1-cells, indicating a strong inhibition of tumor-specific T-cell immunity by 5-Aza. PMID:24757283

  11. 5-azacytidine promotes an inhibitory T-cell phenotype and impairs immune mediated antileukemic activity.

    PubMed

    Stübig, Thomas; Badbaran, Anita; Luetkens, Tim; Hildebrandt, York; Atanackovic, Djordje; Binder, Thomas M C; Fehse, Boris; Kröger, Nicolaus

    2014-01-01

    Demethylating agent, 5-Azacytidine (5-Aza), has been shown to be active in treatment of myeloid malignancies. 5-Aza enhances anticancer immunity, by increasing expression of tumor-associated antigens. However, the impact of 5-Aza immune responses remains poorly understood. Here, T-cell mediated tumor immunity effects of 5-Aza, are investigated in vitro and in vivo. T-cells from healthy donors were treated with 5-Aza and analyzed by qRT-PCR and flow cytometry for changes in gene expression and phenotype. Functionality was assessed by a tumor lysis assay. Peripheral blood from patients treated with 5-Aza after alloSCT was monitored for changes in T-cell subpopulations. 5-Aza treatment resulted in a decrease in CD8+ T-cells, whereas CD4+ T-cells increased. Furthermore, numbers of IFN-γ + T-helper 1 cells (Th1) were reduced, while Treg-cells showed substantial increase. Additionally, CD8+ T-cells exhibited limited killing capacity against leukemic target cells. In vivo data confirm the increase of Treg compartment, while CD8+ T-effector cell numbers were reduced. 5-Aza treatment results in a shift from cytotoxic to regulatory T-cells with a functional phenotype and a major reduction in proinflammatory Th1-cells, indicating a strong inhibition of tumor-specific T-cell immunity by 5-Aza. PMID:24757283

  12. Reduction Impairs the Antibacterial Activity but Benefits the LPS Neutralization Ability of Human Enteric Defensin 5.

    PubMed

    Wang, Cheng; Shen, Mingqiang; Zhang, Naixin; Wang, Song; Xu, Yang; Chen, Shilei; Chen, Fang; Yang, Ke; He, Ting; Wang, Aiping; Su, Yongping; Cheng, Tianmin; Zhao, Jinghong; Wang, Junping

    2016-01-01

    Oxidized human defensin 5 (HD5OX), a Paneth cell-secreted antibacterial peptide with three characteristic disulfide bonds, protects the host from invasion by morbigenous microbes in the small intestine. HD5OX can be reduced by thioredoxin (Trx) in vitro, while the biochemical properties of the reduced linear peptide, HD5RED, remain unclear. Here, we first confirm that HD5RED does exist in vivo. Furthermore, we reveal that the recruitment of HD5RED to the outer membrane of Gram-negative bacteria and to the anionic lipid A is lower than that of HD5OX, and HD5RED is less efficient in penetrating bacterial outer and inner membranes and inducing membrane depolarization, which confers an attenuated antibacterial activity to HD5RED. However, due to its higher structural flexibility, the binding of HD5RED to bacterial lipopolysaccharide (LPS) is markedly stronger than that of HD5OX. Consequently, HD5RED is more effective in suppressing the production of the pro-inflammatory cytokine TNF-α in LPS-stimulated macrophages by blocking the interaction between LPS and LPS-binding protein, thus suggesting that HD5RED might act as a scavenger to neutralize LPS in the gut. This study provides insights into the antibacterial and immunoregulatory effects of HD5RED and expands the known repertoire of the enteric defensins. PMID:26960718

  13. Reduction Impairs the Antibacterial Activity but Benefits the LPS Neutralization Ability of Human Enteric Defensin 5

    PubMed Central

    Wang, Cheng; Shen, Mingqiang; Zhang, Naixin; Wang, Song; Xu, Yang; Chen, Shilei; Chen, Fang; Yang, Ke; He, Ting; Wang, Aiping; Su, Yongping; Cheng, Tianmin; Zhao, Jinghong; Wang, Junping

    2016-01-01

    Oxidized human defensin 5 (HD5OX), a Paneth cell-secreted antibacterial peptide with three characteristic disulfide bonds, protects the host from invasion by morbigenous microbes in the small intestine. HD5OX can be reduced by thioredoxin (Trx) in vitro, while the biochemical properties of the reduced linear peptide, HD5RED, remain unclear. Here, we first confirm that HD5RED does exist in vivo. Furthermore, we reveal that the recruitment of HD5RED to the outer membrane of Gram-negative bacteria and to the anionic lipid A is lower than that of HD5OX, and HD5RED is less efficient in penetrating bacterial outer and inner membranes and inducing membrane depolarization, which confers an attenuated antibacterial activity to HD5RED. However, due to its higher structural flexibility, the binding of HD5RED to bacterial lipopolysaccharide (LPS) is markedly stronger than that of HD5OX. Consequently, HD5RED is more effective in suppressing the production of the pro-inflammatory cytokine TNF-α in LPS-stimulated macrophages by blocking the interaction between LPS and LPS-binding protein, thus suggesting that HD5RED might act as a scavenger to neutralize LPS in the gut. This study provides insights into the antibacterial and immunoregulatory effects of HD5RED and expands the known repertoire of the enteric defensins. PMID:26960718

  14. Mutant activated FGFR3 impairs endochondral bone growth by preventing SOX9 downregulation in differentiating chondrocytes.

    PubMed

    Zhou, Zi-Qiang; Ota, Sara; Deng, Chuxia; Akiyama, Haruhiko; Hurlin, Peter J

    2015-03-15

    Fibroblast growth factor receptor 3 (FGFR3) plays a critical role in the control of endochondral ossification, and bone growth and mutations that cause hyperactivation of FGFR3 are responsible for a collection of developmental disorders that feature poor endochondral bone growth. FGFR3 is expressed in proliferating chondrocytes of the cartilaginous growth plate but also in chondrocytes that have exited the cell cycle and entered the prehypertrophic phase of chondrocyte differentiation. Achondroplasia disorders feature defects in chondrocyte proliferation and differentiation, and the defects in differentiation have generally been considered to be a secondary manifestation of altered proliferation. By initiating a mutant activated knockin allele of FGFR3 (FGFR3K650E) that causes Thanatophoric Dysplasia Type II (TDII) specifically in prehypertrophic chondrocytes, we show that mutant FGFR3 induces a differentiation block at this stage independent of any changes in proliferation. The differentiation block coincided with persistent expression of SOX9, the master regulator of chondrogenesis, and reducing SOX9 dosage allowed chondrocyte differentiation to proceed and significantly improved endochondral bone growth in TDII. These findings suggest that a proliferation-independent and SOX9-dependent differentiation block is a key driving mechanism responsible for poor endochondral bone growth in achondroplasia disorders caused by mutations in FGFR3. PMID:25432534

  15. Impairment of visual function and retinal ER stress activation in Wfs1-deficient mice.

    PubMed

    Bonnet Wersinger, Delphine; Benkafadar, Nesrine; Jagodzinska, Jolanta; Hamel, Christian; Tanizawa, Yukio; Lenaers, Guy; Delettre, Cécile

    2014-01-01

    Wolfram syndrome is an early onset genetic disease (1/180,000) featuring diabetes mellitus and optic neuropathy, associated to mutations in the WFS1 gene. Wfs1-/- mouse model shows pancreatic beta cell atrophy, but its visual performance has not been investigated, prompting us to study its visual function and histopathology of the retina and optic nerve. Electroretinogram and visual evoked potentials (VEPs) were performed in Wfs1-/- and Wfs1+/+ mice at 3, 6, 9 and 12 months of age. Fundi were pictured with Micron III apparatus. Retinal ganglion cell (RGC) abundance was determined from Brn3a immunolabeling of retinal sections. RGC axonal loss was quantified by electron microscopy in transversal optic nerve sections. Endoplasmic reticulum stress was assessed using immunoglobulin binding protein (BiP), protein disulfide isomerase (PDI) and inositol-requiring enzyme 1 alpha (Ire1α) markers. Electroretinograms amplitudes were slightly reduced and latencies increased with time in Wfs1-/- mice. Similarly, VEPs showed decreased N+P amplitudes and increased N-wave latency. Analysis of unfolded protein response signaling revealed an activation of endoplasmic reticulum stress in Wfs1-/- mutant mouse retinas. Altogether, progressive VEPs alterations with minimal neuronal cell loss suggest functional alteration of the action potential in the Wfs1-/- optic pathways. PMID:24823368

  16. 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

  17. Impaired Vitamin D Activation and Association with CYP24A1 Haplotypes in Differentiated Thyroid Carcinoma

    PubMed Central

    Penna-Martinez, Marissa; Ramos-Lopez, Elizabeth; Stern, Julienne; Kahles, Heinrich; Hinsch, Nora; Hansmann, Martin-Leo; Selkinski, Ivan; Grünwald, Frank; Vorländer, Christian; Bechstein, Wolf O.; Zeuzem, Stefan; Holzer, Katharina

    2012-01-01

    Background Common polymorphisms of the vitamin D receptor gene have been reported to affect the risk of breast, colon, prostate, and differentiated thyroid cancer (DTC), but polymorphisms within the genes of vitamin D metabolizing enzymes have not been studied in DTC. The aim of the present study was to investigate the genes for vitamin D enzymes in patients with DTC and healthy controls (HC) as well as the vitamin D (25-hydroxyvitamin D3, and 1,25-hydroxyvitamin) status. Methods German patients (n=253) with DTC (papillary thyroid carcinoma [PTC] and follicular thyroid carcinoma [FTC]) and HC (n=302) were genotyped for polymorphisms within the vitamin D metabolizing enzymes such as 25-hydroxylase (CYP2R1[rs12794714, rs10741657]), 25-hydroxyvitamin D-1α-hydroxylase (CYP27B1[rs10877012, rs4646536]), and 25-hydroxyvitamin D 24-hydrolase (CYP24A1[rs927650, rs2248137, rs2296241]). Furthermore, the 25-hydroxyvitamin D3 [25(OH)D3] and 1,25-hydroxyvitamin [1,25(OH)2D3] plasma levels were measured by a radioimmunoassay. Results There was no difference in the genotypes; however, the CYP24A1 haplotype analysis showed that rs2248137C/rs2296241A (13.1% vs. 19.1%; corrected p [pc]=0.04) was less frequent in the PTC, whereas the haplotypes rs2248137C/rs2296241G (56.0% vs. 41.9%; pc=0.03), rs927650C/rs2296241G (22.5% vs. 8.4%; pc=1.6×10−3), and rs927650C/rs2248137C/rs2296241G (21.1% vs. 7.3%; pc=1.5×10−3) were more frequent in the FTC compared with HC. Furthermore, if patients and controls were grouped according to four 25(OH)D3 categories (severely deficient, deficient, insufficient, and sufficient), then the patients with both DTC subtypes had significantly lower levels of circulating 1,25(OH)2D3, especially in the group with a deficient 25(OH)D3 status compared with the controls. Although the polymorphisms showed no differences stratified for the four 25(OH)D3 categories, the activation status by 1,25(OH)2D3 differed significantly depending on the genotypes of the

  18. Rpl22 loss impairs the development of B lymphocytes by activating a p53-dependent checkpoint

    PubMed Central

    Fahl, Shawn P.; Harris, Bryan; Coffey, Francis; Wiest, David L.

    2014-01-01

    While ribosomal proteins facilitate the ribosome’s core function of translation, emerging evidence suggests that some ribosomal proteins are also capable of performing tissue restricted functions either from within specialized ribosomes or from outside of the ribosome. In particular, we have previously demonstrated that germline ablation of the gene encoding ribosomal protein Rpl22 causes a selective and p53 dependent arrest of αβ T cell progenitors at the β-selection checkpoint. We have now identified a crucial role for Rpl22 during early B cell development. Germline ablation of Rpl22 results in a reduction in the absolute number of B-lineage progenitors in the bone marrow beginning at the pro-B cell stage. Although Rpl22-deficient proB cells are hyporesponsive to IL-7, a key cytokine required for early B cell development, the arrest of B cell development does not result from disrupted IL-7 signaling. Instead, p53 induction appears to be responsible for the developmental defects, as Rpl22-deficiency causes increased expression of p53 and activation of downstream p53 target genes and p53-deficiency rescues the defect in B cell development in Rpl22-deficient mice. Interestingly, the requirement for Rpl22 in the B cell lineage appears to be developmentally restricted, since Rpl22-deficient splenic B cells proliferate normally in response to antigen receptor and toll receptor stimuli and undergo normal class switch recombination. These results indicate that Rpl22 performs a critical, developmentally restricted role in supporting early B cell development by preventing p53-induction. PMID:25416806

  19. Loss of Interleukin-21 Receptor Activation in Hypoxic Endothelial Cells Impairs Perfusion Recovery after Hindlimb Ischemia

    PubMed Central

    Wang, Tao; Cunningham, Alexis; Dokun, Ayotunde O; Hazarika, Surovi; Houston, Kevin; Chen, Lingdan; Lye, R. John; Spolski, Rosanne; Leonard, Warren J.; Annex, Brian H.

    2016-01-01

    Objective Surgical hindlimb ischemia (HLI) in mice has become a valuable preclinical model to study peripheral arterial disease (PAD). We previously identified that the different phenotypical outcomes following HLI across inbred mouse strains is related a region on the short arm of mouse chromosome 7. The gene coding the interleukin-21 receptor (IL-21R) lies at the peak of association in this region. Approach and Results With quantitative RT-PCR, we found that a mouse strain with a greater ability to up-regulate IL-21R following HLI had better perfusion recovery than a strain with no up-regulation after HLI. Immunofluorescent staining of ischemic hind-limb tissue showed IL-21R expression on endothelial cells (EC) from these C57BL/6 mice. An EC-enriched fraction isolated from ischemic hind-limb muscle showed higher Il-21R levels than an EC-enriched fraction from non-ischemic limbs. In-vitro, human umbilical vein EC (HUVEC) showed elevated IL-21R expression after hypoxia and serum starvation. Under these conditions, IL-21 treatment increased cell viability, decreased cell apoptosis, and augmented tube formation. In-vivo, either knockout Il21r or blocking IL-21 signaling by treating with IL-21R-Fc (fusion protein that blocks IL-21 binding to its receptor) in C57BL/6 mice resulted in less perfusion recovery after HLI. Both in-vitro and in-vivo modulation of the IL-21/IL-21R axis under hypoxic conditions resulted in increasedSTAT3 phosphorylation and a subsequent increase in the BCL-2/BAX ratio. Conclusion Our data indicate that IL-21R up-regulation and ligand activation in hypoxic endothelial cells may help perfusion recovery by limiting/preventing apoptosis and/or favoring cell survival and angiogenesis through the STAT3 pathway. PMID:25838422

  20. Pulmonary gas exchange is not impaired 24 h after extravehicular activity.

    PubMed

    Prisk, G Kim; Fine, Janelle M; Cooper, Trevor K; West, John B

    2005-12-01

    Extravehicular activity (EVA) during spaceflight involves a significant decompression stress. Previous studies have shown an increase in the inhomogeneity of ventilation-perfusion ratio (VA/Q) after some underwater dives, presumably through the embolic effects of venous gas microemboli in the lung. Ground-based chamber studies simulating EVA have shown that venous gas microemboli occur in a large percentage of the subjects undergoing decompression, despite the use of prebreathe protocols to reduce dissolved N(2) in the tissues. We studied eight crewmembers (7 male, 1 female) of the International Space Station who performed 15 EVAs (initial cabin pressure 748 mmHg, final suit pressure either approximately 295 or approximately 220 mmHg depending on the suit used) and who followed the denitrogenation procedures approved for EVA from the International Space Station. The intrabreath VA/Q slope was calculated from the alveolar Po(2) and Pco(2) in a prolonged exhalation maneuver on the day after EVA and compared with measurements made in microgravity on days well separated from the EVA. There were no significant changes in intrabreath VA/Q slope as a result of EVA, although there was a slight increase in metabolic rate and ventilation (approximately 9%) on the day after EVA. Vital capacity and other measures of pulmonary function were largely unaltered by EVA. Because measurements could only be performed on the day after EVA because of logistical constraints, we were unable to determine an acute effect of EVA on VA/Q inequality. The results suggest that current denitrogenation protocols do not result in any major lasting alteration to gas exchange in the lung. PMID:16123205

  1. Aryl hydrocarbon receptor activation leads to impairment of estrogen-driven chicken vitellogenin promoter activity in LMH cells.

    PubMed

    Bussmann, Ursula A; Pérez Sáez, Juan M; Bussmann, Leonardo E; Barañao, J Lino

    2013-03-01

    The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that mediates most of the toxic effects of environmental contaminants. Among the multiple pleiotropic responses elicited by AHR agonists, the antiestrogenic and endocrine-disrupting action of the receptor activation is one of the most studied. It has been demonstrated that some AHR agonists disrupt estradiol-induced vitellogenin synthesis in the fish liver via a mechanism that involves crosstalk between the AHR and the estrogen receptor (ER). Chicken hepatocytes have become a model for the study of AHR action in birds and the induction of the signal and its effect in these cells are well established. However, the impact of AHR activation on estradiol-regulated responses in the chicken liver remains to be demonstrated. The aim of the present study was, therefore, to determine the effect of AHR action on ER-driven transcription in a convenient model of chicken liver cells. For this purpose, we designed a reporter construct bearing the 5' regulatory region of the chicken vitellogenin II gene and used it to transfect chicken hepatoma LMH cells. We found that β-naphthoflavone represses ER-driven vitellogenin promoter activity and that this action is mediated by the AHR. This inhibitory crosstalk between both pathways appears to be unidirectional, since estradiol did not alter the transcript levels of an AHR target gene. Besides, and highly relevant, we show that LMH cell line transfected with a reporter construct bearing the chicken vitellogenin promoter sequence is a useful and convenient model for the study of AHR-ER interaction in chicken liver-derived cells. PMID:23103859

  2. Functional Activity and Connectivity Differences of Five Resting-State Networks in Patients with Alzheimer's Disease or Mild Cognitive Impairment.

    PubMed

    Chen, Yu; Yan, Hao; Han, Zaizhu; Bi, Yanchao; Chen, Hongyan; Liu, Jia; Wu, Meiru; Wang, Yongjun; Zhang, Yumei

    2016-01-01

    We aimed to investigate the activity within and the connectivity between resting state networks (RSNs) in healthy subjects and patients with Alzheimer's disease (AD) or mild cognitive impairment (MCI). Magnetic resonance imaging (MRI) and resting-state MRI were performed on patients diagnosed with AD (n=18) or MCI (n=16) and on healthy subjects (n=18) with matching demographic characteristics (age, sex, and education level). Independent component analysis and Granger causality analysis (GCA) were used during image postprocessing. We calculated 'In + Out degree' for each RSN. Then, we investigated the relationships between "In + Out degree" of each brain network and the cognitive behavioural data. RSNs were obtained using the optimal matching method. The core areas of the five RSNs were similar between the AD, MCI, and healthy control groups, but the activity within these five RSNs was significantly lower in the AD and MCI groups than in the healthy control group (P<0.01, false discovery rate corrected). The GCA results showed that the connectivity between the five RSNs, particularly the connectivity from the default mode network (DMN) to the other RSNs, was slightly lower in MCI patients and was significantly lower in AD patients than in healthy subjects. In contrast, increased connectivity was evident between the memory network and the executive control network in the AD and MCI patients. The "In + Out degree" of the DMN negatively correlated with the Montreal Cognitive Assessment score in AD patients (R=-0.43, P<0.05). In conclusion, the activity within RSNs and the connectivity between RSNs differed between AD patients, MCI patients, and normal individuals; these results provide an imaging reference for the diagnosis of AD and the measurement of disease progression and reveal insight into the pathogenesis of AD. PMID:26906355

  3. Endothelial TLR4 activation impairs intestinal microcirculatory perfusion in necrotizing enterocolitis via eNOS–NO–nitrite signaling

    PubMed Central

    Yazji, Ibrahim; Sodhi, Chhinder P.; Lee, Elizabeth K.; Good, Misty; Egan, Charlotte E.; Afrazi, Amin; Neal, Matthew D.; Jia, Hongpeng; Lin, Joyce; Branca, Maria F.; Prindle, Thomas; Richardson, Ward M.; Ozolek, John; Billiar, Timothy R.; Binion, David G.; Gladwin, Mark T.; Hackam, David J.

    2013-01-01

    Necrotizing enterocolitis (NEC) is a devastating disease of premature infants characterized by severe intestinal necrosis and for which breast milk represents the most effective protective strategy. Previous studies have revealed a critical role for the lipopolysaccharide receptor toll-like receptor 4 (TLR4) in NEC development through its induction of mucosal injury, yet the reasons for which intestinal ischemia in NEC occurs in the first place remain unknown. We hypothesize that TLR4 signaling within the endothelium plays an essential role in NEC development by regulating perfusion to the small intestine via the vasodilatory molecule endothelial nitric oxide synthase (eNOS). Using a unique mouse system in which we selectively deleted TLR4 from the endothelium, we now show that endothelial TLR4 activation is required for NEC development and that endothelial TLR4 activation impairs intestinal perfusion without effects on other organs and reduces eNOS expression via activation of myeloid differentiation primary response gene 88. NEC severity was significantly increased in eNOS−/− mice and decreased upon administration of the phosphodiesterase inhibitor sildenafil, which augments eNOS function. Strikingly, compared with formula, human and mouse breast milk were enriched in sodium nitrate—a precursor for enteral generation of nitrite and nitric oxide—and repletion of formula with sodium nitrate/nitrite restored intestinal perfusion, reversed the deleterious effects of endothelial TLR4 signaling, and reduced NEC severity. These data identify that endothelial TLR4 critically regulates intestinal perfusion leading to NEC and reveal that the protective properties of breast milk involve enhanced intestinal microcirculatory integrity via augmentation of nitrate–nitrite–NO signaling. PMID:23650378

  4. 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. PMID:26758875

  5. Inhibition of PHOSPHO1 activity results in impaired skeletal mineralization during limb development of the chick

    PubMed Central

    MacRae, Vicky E.; Davey, Megan G.; McTeir, Lynn; Narisawa, Sonoko; Yadav, Manisha C.; Millan, Jose Luis; Farquharson, Colin.

    2010-01-01

    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-non specific 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 co-expressed 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 talpid3 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

  6. Effects of task-oriented training on upper extremity function and performance of daily activities in chronic stroke patients with impaired cognition

    PubMed Central

    Park, JuHyung

    2016-01-01

    [Purpose] This study aimed to determine the effects of task-oriented training on upper extremity function and performance of daily activities in chronic stroke patients with impaired cognition. [Subjects and Methods] In this study, 2 chronic hemiplegic stroke patients underwent task-oriented training. The training was conducted once a day for 30 minutes, 5 times/week, for 2 weeks. The patients were evaluated 3 times before and after the task-oriented training. Changes in upper extremity function were assessed using the manual function test, and changes in the ability to carry out daily activities were assessed using the functional independence measure. [Results] The patients showed improvement in both the upper extremity function and ability to perform daily activities after task-oriented training. [Conclusion] Task-oriented training was proven effective in improving upper extremity function and ability to perform daily activities in chronic hemiplegic stroke patients with impaired cognition. PMID:26957782

  7. 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…

  8. Influence of physical activity and gender on arterial function in type 2 diabetes, normal and impaired glucose tolerance.

    PubMed

    Ring, Margareta; Eriksson, Maria J; Fritz, Tomas; Nyberg, Gunnar; Östenson, Claes Göran; Krook, Anna; Zierath, Juleen R; Caidahl, Kenneth

    2015-09-01

    To determine whether Nordic walking improves cardiovascular function in middle-aged women and men, we included 121 with normal glucose tolerance, 33 with impaired glucose tolerance and 47 with Type 2 diabetes mellitus in a randomized controlled study. The intervention group added Nordic walking 5 h/week for 4 months to their ordinary activities. Aortic pulse wave velocity, aortic augmentation index, stiffness index, reflection index, intima-media thickness in the radial and carotid arteries, echogenicity of the carotid intima-media and systemic vascular resistance were measured. While baseline blood pressure did not differ by gender or diagnosis, aortic augmentation index was found to be higher in women in all groups. Vascular function was unchanged with intervention, without differences by gender or diagnosis. In conclusion, 4 months of Nordic walking is an insufficient stimulus to improve vascular function. Future studies should consider hard endpoints in addition to measures of vascular health, as well as larger population groups, long-term follow-up and documented compliance to exercise training. PMID:26092821

  9. Instrumental Activities of Daily Living Performance and Role Satisfaction in People With and Without Mild Cognitive Impairment: A Pilot Project

    PubMed Central

    Anderson, Michael P.; Hershey, Linda A.; Prodan, Calin I.; Holm, Margo B.

    2015-01-01

    OBJECTIVE. We investigated differences in observed performance of instrumental activities of daily living (IADLs) and self-reported satisfaction with social role performance between people with amnestic mild cognitive impairment (a-MCI) and age- and gender-matched control participants. METHOD. We measured observed performance of 14 IADLs using the Independence, Safety, and Adequacy domains of the Performance Assessment of Self-Care Skills (PASS) and the Patient-Reported Outcomes Measurement Information Systems (PROMIS) to examine satisfaction with social role performance. RESULTS. Total PASS scores were significantly lower in participants with a-MCI (median = 40.6) than in control participants (median = 44.2; p = .006). Adequacy scores were also significantly lower. No significant differences were found between groups on the PROMIS measures. CONCLUSION. IADL differences between groups were related more to errors in adequacy than to safety and independence. Occupational therapy practitioners can play a key role in the diagnosis and treatment of subtle IADL deficits in people with MCI. PMID:25871600

  10. Influence of physical activity and gender on arterial function in type 2 diabetes, normal and impaired glucose tolerance

    PubMed Central

    Eriksson, Maria J.; Fritz, Tomas; Nyberg, Gunnar; Östenson, Claes Göran; Krook, Anna; Zierath, Juleen R.; Caidahl, Kenneth

    2015-01-01

    To determine whether Nordic walking improves cardiovascular function in middle-aged women and men, we included 121 with normal glucose tolerance, 33 with impaired glucose tolerance and 47 with Type 2 diabetes mellitus in a randomized controlled study. The intervention group added Nordic walking 5 h/week for 4 months to their ordinary activities. Aortic pulse wave velocity, aortic augmentation index, stiffness index, reflection index, intima–media thickness in the radial and carotid arteries, echogenicity of the carotid intima–media and systemic vascular resistance were measured. While baseline blood pressure did not differ by gender or diagnosis, aortic augmentation index was found to be higher in women in all groups. Vascular function was unchanged with intervention, without differences by gender or diagnosis. In conclusion, 4 months of Nordic walking is an insufficient stimulus to improve vascular function. Future studies should consider hard endpoints in addition to measures of vascular health, as well as larger population groups, long-term follow-up and documented compliance to exercise training. PMID:26092821

  11. Analysis of respiratory activity and carbon usage of a mutant of Azotobacter vinelandii impaired in poly-β-hydroxybutyrate synthesis.

    PubMed

    Jiménez, Lucero; Castillo, Tania; Flores, Celia; Segura, Daniel; Galindo, Enrique; Peña, Carlos

    2016-08-01

    In this study, the respiratory activity and carbon usage of the mutant strain of A. vinelandii AT6, impaired in poly-β-hydroxybutyrate (PHB) production, and their relationship with the synthesis of alginate were evaluated. The alginate yield and the specific oxygen uptake rate were higher (2.5-fold and 62 %, respectively) for the AT6 strain, compared to the control strain (ATCC 9046), both in shake flasks cultures and in bioreactor, under fixed dissolved oxygen tension (1 %). In contrast, the degree of acetylation was similar in both strains. These results, together with the analysis of carbon usage (% C-mol), suggest that in the case of the AT6 strain, the flux of acetyl-CoA (precursor molecule for PHB biosynthesis and alginate acetylation) was diverted to the respiratory chain passing through the tricarboxylic acids cycle, and an important % C-mol was directed through alginate biosynthesis, up to 25.9 % and to a lesser extent, to biomass production (19.7 %). PMID:27154760

  12. Kras activation in p53-deficient myoblasts results in high-grade sarcoma formation with impaired myogenic differentiation

    PubMed Central

    McKinnon, Timothy; Venier, Rosemarie; Dickson, Brendan C.; Kabaroff, Leah; Alkema, Manon; Chen, Li; Shern, Jack F.; Yohe, Marielle E.; Khan, Javed; Gladdy, Rebecca A.

    2015-01-01

    While genomic studies have improved our ability to classify sarcomas, the molecular mechanisms involved in the formation and progression of many sarcoma subtypes are unknown. To better understand developmental origins and genetic drivers involved in rhabdomyosarcomagenesis, we describe a novel sarcoma model system employing primary murine p53-deficient myoblasts that were isolated and lentivirally transduced with KrasG12D. Myoblast cell lines were characterized and subjected to proliferation, anchorage-independent growth and differentiation assays to assess the effects of transgenic KrasG12D expression. KrasG12D overexpression transformed p53−/− myoblasts as demonstrated by an increased anchorage-independent growth. Induction of differentiation in parental myoblasts resulted in activation of key myogenic regulators. In contrast, Kras-transduced myoblasts had impaired terminal differentiation. p53−/− myoblasts transformed by KrasG12D overexpression resulted in rapid, reproducible tumor formation following orthotopic injection into syngeneic host hindlimbs. Pathological analysis revealed high-grade sarcomas with myogenic differentiation based on the expression of muscle-specific markers, such as Myod1 and Myog. Gene expression patterns of murine