Sample records for early functional results

  1. Early executive function predicts reasoning development.

    PubMed

    Richland, Lindsey E; Burchinal, Margaret R

    2013-01-01

    Analogical reasoning is a core cognitive skill that distinguishes humans from all other species and contributes to general fluid intelligence, creativity, and adaptive learning capacities. Yet its origins are not well understood. In the study reported here, we analyzed large-scale longitudinal data from the Study of Early Child Care and Youth Development to test predictors of growth in analogical-reasoning skill from third grade to adolescence. Our results suggest an integrative resolution to the theoretical debate regarding contributory factors arising from smaller-scale, cross-sectional experiments on analogy development. Children with greater executive-function skills (both composite and inhibitory control) and vocabulary knowledge in early elementary school displayed higher scores on a verbal analogies task at age 15 years, even after adjusting for key covariates. We posit that knowledge is a prerequisite to analogy performance, but strong executive-functioning resources during early childhood are related to long-term gains in fundamental reasoning skills.

  2. Factors associated with a bad functional prognosis in early inflammatory back pain: results from the DESIR cohort.

    PubMed

    Lukas, C; Dougados, M; Combe, B

    2016-01-01

    Spondyloarthritis (SpA) is a heterogeneous disease with hardly predictable potential courses. We aimed at determining prognostic factors of bad functional outcome at 2 years in patients with early inflammatory back pain (IBP). Data from patients included in the French multicentre devenir des spondylarthropathies indifférenciées récentes (DESIR) cohort, that is, suffering from IBP starting before 50 years of age and lasting for 3-36 months, were used. A bad functional outcome at 24 months was defined as an increase in bath ankylosing spondylitis functional index (BASFI), or BASFI at 2 years higher than the 75th centile in the cohort. Demographic, clinical, biological and radiological data collected at inclusion were compared in patients with bad functional outcome versus others, by χ(2) test, then by a multivariate logistic regression model with stepwise selection of relevant factors. 513 patients (54.4% females, 72.2% fulfilling ASAS criteria) were assessed. Of those, 130 (25.3%) fulfilled the aforementioned criteria of a bad functional outcome (BASFI increase ≥4 units or ≥36 at 2 years). Multivariate analysis revealed that not fulfilling ASAS criteria, female sex, age >33 years, lower educational level, active smoking status and high disease activity according to bath ankylosing spondylitis disease activity index (BASDAI) at baseline were independently associated with a bad functional outcome at 24 months. Sensitivity analyses restricted to patients fulfilling ASAS criteria for SpA resulted in similar results. We observed, in a large prospective cohort of patients with early IBP, formerly described bad prognostic factors, especially a low educational level, an older age and a high disease activity at onset, and revealed that active smoking status and female sex were also independently associated with a poor outcome. Fulfilment of ASAS criteria, on the other hand, was predictive of a better outcome, most likely due to the more consensual

  3. Atlas-based functional radiosurgery: Early results

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

    Stancanello, J.; Romanelli, P.; Pantelis, E.

    2009-02-15

    Functional disorders of the brain, such as dystonia and neuropathic pain, may respond poorly to medical therapy. Deep brain stimulation (DBS) of the globus pallidus pars interna (GPi) and the centromedian nucleus of the thalamus (CMN) may alleviate dystonia and neuropathic pain, respectively. A noninvasive alternative to DBS is radiosurgical ablation [internal pallidotomy (IP) and medial thalamotomy (MT)]. The main technical limitation of radiosurgery is that targets are selected only on the basis of MRI anatomy, without electrophysiological confirmation. This means that, to be feasible, image-based targeting must be highly accurate and reproducible. Here, we report on the feasibility ofmore » an atlas-based approach to targeting for functional radiosurgery. In this method, masks of the GPi, CMN, and medio-dorsal nucleus were nonrigidly registered to patients' T1-weighted MRI (T1w-MRI) and superimposed on patients' T2-weighted MRI (T2w-MRI). Radiosurgical targets were identified on the T2w-MRI registered to the planning CT by an expert functional neurosurgeon. To assess its feasibility, two patients were treated with the CyberKnife using this method of targeting; a patient with dystonia received an IP (120 Gy prescribed to the 65% isodose) and a patient with neuropathic pain received a MT (120 Gy to the 77% isodose). Six months after treatment, T2w-MRIs and contrast-enhanced T1w-MRIs showed edematous regions around the lesions; target placements were reevaluated by DW-MRIs. At 12 months post-treatment steroids for radiation-induced edema and medications for dystonia and neuropathic pain were suppressed. Both patients experienced significant relief from pain and dystonia-related problems. Fifteen months after treatment edema had disappeared. Thus, this work shows promising feasibility of atlas-based functional radiosurgery to improve patient condition. Further investigations are indicated for optimizing treatment dose.« less

  4. Subcortical functional reorganization due to early blindness

    PubMed Central

    Jiang, Fang; Fine, Ione; Watkins, Kate E.; Bridge, Holly

    2015-01-01

    Lack of visual input early in life results in occipital cortical responses to auditory and tactile stimuli. However, it remains unclear whether cross-modal plasticity also occurs in subcortical pathways. With the use of functional magnetic resonance imaging, auditory responses were compared across individuals with congenital anophthalmia (absence of eyes), those with early onset (in the first few years of life) blindness, and normally sighted individuals. We find that the superior colliculus, a “visual” subcortical structure, is recruited by the auditory system in congenital and early onset blindness. Additionally, auditory subcortical responses to monaural stimuli were altered as a result of blindness. Specifically, responses in the auditory thalamus were equally strong to contralateral and ipsilateral stimulation in both groups of blind subjects, whereas sighted controls showed stronger responses to contralateral stimulation. These findings suggest that early blindness results in substantial reorganization of subcortical auditory responses. PMID:25673746

  5. Functional Recovery in Major Depressive Disorder: Focus on Early Optimized Treatment.

    PubMed

    Habert, Jeffrey; Katzman, Martin A; Oluboka, Oloruntoba J; McIntyre, Roger S; McIntosh, Diane; MacQueen, Glenda M; Khullar, Atul; Milev, Roumen V; Kjernisted, Kevin D; Chokka, Pratap R; Kennedy, Sidney H

    2016-09-01

    This article presents the case that a more rapid, individualized approach to treating major depressive disorder (MDD) may increase the likelihood of achieving full symptomatic and functional recovery for individual patients and that studies show it is possible to make earlier decisions about appropriateness of treatment in order to rapidly optimize that treatment. A PubMed search was conducted using terms including major depressive disorder, early improvement, predictor, duration of untreated illness, and function. English-language articles published before September 2015 were included. Additional studies were found within identified research articles and reviews. Thirty antidepressant studies reporting predictor criteria and outcome measures are included in this review. Studies were reviewed to extract definitions of predictors, outcome measures, and results of the predictor analysis. Results were summarized separately for studies reporting effects of early improvement, baseline characteristics, and duration of untreated depression. Shorter duration of the current depressive episode and duration of untreated depression are associated with better symptomatic and functional outcomes in MDD. Early improvement of depressive symptoms predicts positive symptomatic outcomes (response and remission), and early functional improvement predicts an increased likelihood of functional remission. The approach to treatment of depression that exhibits the greatest potential for achieving full symptomatic and functional recovery is early optimized treatment: early diagnosis followed by rapid individualized treatment. Monitoring symptoms and function early in treatment is crucial to ensuring that patients do not remain on ineffective or poorly tolerated treatment, which may delay recovery and heighten the risk of residual functional deficits. © Copyright 2016 Physicians Postgraduate Press, Inc.

  6. Subcortical functional reorganization due to early blindness.

    PubMed

    Coullon, Gaelle S L; Jiang, Fang; Fine, Ione; Watkins, Kate E; Bridge, Holly

    2015-04-01

    Lack of visual input early in life results in occipital cortical responses to auditory and tactile stimuli. However, it remains unclear whether cross-modal plasticity also occurs in subcortical pathways. With the use of functional magnetic resonance imaging, auditory responses were compared across individuals with congenital anophthalmia (absence of eyes), those with early onset (in the first few years of life) blindness, and normally sighted individuals. We find that the superior colliculus, a "visual" subcortical structure, is recruited by the auditory system in congenital and early onset blindness. Additionally, auditory subcortical responses to monaural stimuli were altered as a result of blindness. Specifically, responses in the auditory thalamus were equally strong to contralateral and ipsilateral stimulation in both groups of blind subjects, whereas sighted controls showed stronger responses to contralateral stimulation. These findings suggest that early blindness results in substantial reorganization of subcortical auditory responses. Copyright © 2015 the American Physiological Society.

  7. The development of functional network organization in early childhood and early adolescence: A resting-state fNIRS study.

    PubMed

    Cai, Lin; Dong, Qi; Niu, Haijing

    2018-04-01

    Early childhood (7-8 years old) and early adolescence (11-12 years old) constitute two landmark developmental stages that comprise considerable changes in neural cognition. However, very limited information from functional neuroimaging studies exists on the functional topological configuration of the human brain during specific developmental periods. In the present study, we utilized continuous resting-state functional near-infrared spectroscopy (rs-fNIRS) imaging data to examine topological changes in network organization during development from early childhood and early adolescence to adulthood. Our results showed that the properties of small-worldness and modularity were not significantly different across development, demonstrating the developmental maturity of important functional brain organization in early childhood. Intriguingly, young children had a significantly lower global efficiency than early adolescents and adults, which revealed that the integration of the distributed networks strengthens across the developmental stages underlying cognitive development. Moreover, local efficiency of young children and adolescents was significantly lower than that of adults, while there was no difference between these two younger groups. This finding demonstrated that functional segregation remained relatively steady from early childhood to early adolescence, and the brain in these developmental periods possesses no optimal network configuration. Furthermore, we found heterogeneous developmental patterns in the regional nodal properties in various brain regions, such as linear increased nodal properties in the frontal cortex, indicating increasing cognitive capacity over development. Collectively, our results demonstrated that significant topological changes in functional network organization occurred during these two critical developmental stages, and provided a novel insight into elucidating subtle changes in brain functional networks across development. Copyright

  8. Early Child Care and Adolescent Functioning at the End of High School: Results from the NICHD Study of Early Child Care and Youth Development

    ERIC Educational Resources Information Center

    Vandell, Deborah Lowe; Burchinal, Margaret; Pierce, Kim M.

    2016-01-01

    Relations between early child care and adolescent functioning at the end of high school (EOHS; M age = 18.3 years) were examined in a prospective longitudinal study of 1,214 children. Controlling for extensive measures of family background, early child care was associated with academic standing and behavioral adjustment at the EOHS. More…

  9. Impact of early diagnosis on functional disability in rheumatoid arthritis

    PubMed Central

    Kim, Dam; Choi, Chan-Bum; Lee, Jiyoung; Cho, Soo-Kyung; Won, Soyoung; Bang, So-Young; Cha, Hoon-Suk; Choe, Jung-Yoon; Chung, Won Tae; Hong, Seung-Jae; Jun, Jae-Bum; Jung, Young Ok; Kim, Jinseok; Kim, Seong-Kyu; Kim, Tae-Hwan; Kim, Tae-Jong; Koh, Eunmi; Lee, Hye-Soon; Lee, Jaejoon; Lee, Jisoo; Lee, Sang-Heon; Lee, Shin-Seok; Lee, Sung Won; Shim, Seung-Cheol; Yoo, Dae-Hyun; Yoon, Bo Young; Sung, Yoon-Kyoung; Bae, Sang-Cheol

    2017-01-01

    Background/Aims To determine whether early diagnosis is beneficial for functional status of various disease durations in rheumatoid arthritis (RA) patients. Methods A total of 4,540 RA patients were enrolled as part of the Korean Observational Study Network for Arthritis (KORONA). We defined early diagnosis as a lag time between symptom onset and RA diagnosis of ≤ 12 months, whereas patients with a longer lag time comprised the delayed diagnosis group. Demographic characteristics and outcomes were compared between early and delayed diagnosis groups. Logistic regression analyses were performed to identify the impact of early diagnosis on the development of functional disability in RA patients. Results A total of 2,597 patients (57.2%) were included in the early diagnosis group. The average Health Assessment Questionnaire-Disability Index (HAQ-DI) score was higher in the delayed diagnosis group (0.64 ± 0.63 vs. 0.70 ± 0.66, p < 0.01), and the proportion of patients with no functional disability (HAQ = 0) was higher in the early diagnosis group (22.9% vs. 20.0%, p = 0.02). In multivariable analyses, early diagnosis was independently associated with no functional disability (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.01 to 1.40). In a subgroup analysis according to disease duration, early diagnosis was associated with no functional disability in patients with disease duration < 5 years (OR, 1.37; 95% CI, 1.09 to 1.72) but not in patients with longer disease duration (for 5 to 10 years: OR, 1.07; 95% CI, 0.75 to 1.52; for ≥ 10 years: OR, 0.92; 95% CI, 0.65 to 1.28). Conclusions Early diagnosis is associated with no functional disability, especially in patients with shorter disease duration. PMID:27618867

  10. Brief Report: Predicting Functional Disability: One-Year Results From the Scottish Early Rheumatoid Arthritis Inception Cohort.

    PubMed

    Kronisch, Caroline; McLernon, David J; Dale, James; Paterson, Caron; Ralston, Stuart H; Reid, David M; Tierney, Ann; Harvie, John; McKay, Neil; Wilson, Hilary E; Munro, Robin; Saunders, Sarah; Richmond, Ruth; Baxter, Derek; McMahon, Mike; Kumar, Vinod; McLaren, John; Siebert, Stefan; McInnes, Iain B; Porter, Duncan; Macfarlane, Gary J; Basu, Neil

    2016-07-01

    To identify baseline prognostic indicators of disability at 1 year within a contemporary early inflammatory arthritis inception cohort and then develop a clinically useful tool to support early patient education and decision-making. The Scottish Early Rheumatoid Arthritis (SERA) inception cohort is a multicenter, prospective study of patients with newly presenting RA or undifferentiated arthritis. SERA data were analyzed to determine baseline predictors of disability (defined as a Health Assessment Questionnaire [HAQ] score of ≥1) at 1 year. Clinical and psychosocial baseline exposures were entered into a forward stepwise logistic regression model. The model was externally validated using newly accrued SERA data and subsequently converted into a prediction tool. Of the 578 participants (64.5% female), 36.7% (n = 212) reported functional disability at 1 year. Functional disability was independently predicted by baseline disability (odds ratio [OR] 2.67 [95% confidence interval (95% CI) 1.98, 3.59]), depression (OR 2.52 [95% CI 1.18, 5.37]), anxiety (OR 2.37 [95% CI 1.33, 4.21]), being in paid employment with absenteeism during the last week (OR 1.19 [95% CI 0.63, 2.23]), not being in paid employment (OR 2.36 [95% CI 1.38, 4.03]), and being overweight (OR 1.61 [95% CI 1.04, 2.50]). External validation (using 113 newly acquired patients) evidenced good discriminative performance with a C statistic of 0.74, and the calibration slope showed no evidence of model overfit (P = 0.31). In the context of modern early inflammatory arthritis treatment paradigms, predictors of disability at 1 year appear to be dominated by psychosocial rather than more traditional clinical measures. This indicates the potential benefit of early access to nonpharmacologic interventions targeting key psychosocial factors, such as mental health and work disability. © 2016, American College of Rheumatology.

  11. Early Hormonal Influences on Cognitive Functioning in Congenital Adrenal Hyperplasia.

    ERIC Educational Resources Information Center

    Resnick, Susan M.; And Others

    1986-01-01

    Reports the results of cognitive test performance and early childhood activities in individuals with congenital adrenal hyperplasia, an autosomal recessive disorder associated with elevated prenatal adrenal androgen levels, demonstrating the effects of early exposure to excess androgenizing hormones on sexually dimorphic cognitive functioning.…

  12. Clinical symptoms predict concurrent social and global functioning in an early psychosis sample.

    PubMed

    Cacciotti-Saija, Cristina; Langdon, Robyn; Ward, Philip B; Hickie, Ian B; Guastella, Adam J

    2018-04-01

    Although well established in chronic schizophrenia, the key determinants of functioning remain unknown during the early phase of a psychotic disorder. The aim of this study was to comprehensively examine the social cognitive, basic neurocognitive and clinical predictors of concurrent social functioning and global functioning in an early psychosis sample. This study examined the relationship between social cognition, basic neurocognition and clinical symptoms with concurrent functioning in 51 early psychosis individuals. Assessments included a range of self-report, observational and clinician-rated measures of cognitive, symptom severity and functioning domains. Results revealed a significant association between self-reported social function and lower levels of both social interaction anxiety and negative psychotic symptoms. A significant association was also observed between lower levels of negative psychotic symptoms and observed social functioning. Lastly, results demonstrated a significant association between reduced negative psychotic symptoms and clinician-rated global functioning. Clinical domains such as negative symptoms and social interaction anxiety significantly contribute to an optimal model predicting outcome during the early phase of a psychotic disorder. These clinical features may also provide useful markers of an individual's capacity for social participation. Clinical implications include the need for early targeted intervention to address social anxiety and negative psychotic symptoms to facilitate optimum patient outcome. © 2015 Wiley Publishing Asia Pty Ltd.

  13. Which early life events or current environmental and lifestyle factors influence lung function in adolescents? - results from the GINIplus & LISAplus studies.

    PubMed

    Luzak, Agnes; Fuertes, Elaine; Flexeder, Claudia; Standl, Marie; von Berg, Andrea; Berdel, Dietrich; Koletzko, Sibylle; Heinrich, Joachim; Nowak, Dennis; Schulz, Holger

    2017-07-12

    Various factors may affect lung function at different stages in life. Since investigations that simultaneously consider several factors are rare, we examined the relative importance of early life, current environmental/lifestyle factors and allergic diseases on lung function in 15-year-olds. Best subset selection was performed for linear regression models to investigate associations between 21 diverse early life events and current factors with spirometric parameters (forced vital capacity, forced expiratory volume in 1 s and maximal mid-expiratory flow (FEF 25-75 )) in 1326 participants of the German GINIplus and LISAplus birth cohorts. To reduce model complexity, one model for each spirometric parameter was replicated 1000 times in random subpopulations (N = 884). Only those factors that were included in >70% of the replication models were retained in the final analysis. A higher peak weight velocity and early lung infections were the early life events prevalently associated with airflow limitation and FEF 25-75 . Current environmental/lifestyle factors at age 15 years and allergic diseases that were associated with lung function were: indoor second-hand smoke exposure, vitamin D concentration, body mass index (BMI) and asthma status. Sex and height captured the majority of the explained variance (>75%), followed by BMI (≤23.7%). The variance explained by early life events was comparatively low (median: 4.8%; range: 0.2-22.4%), but these events were consistently negatively associated with airway function. Although the explained variance was mainly captured by well-known factors included in lung function prediction equations, our findings indicate early life and current factors that should be considered in studies on lung health among adolescents.

  14. Cognitive function in early HIV infection.

    PubMed

    Prakash, Aanchal; Hou, Jue; Liu, Lei; Gao, Yi; Kettering, Casey; Ragin, Ann B

    2017-04-01

    This study aimed to examine cognitive function in acute/early HIV infection over the subsequent 2 years. Fifty-six HIV+ subjects and 21 seronegative participants of the Chicago Early HIV Infection Study were evaluated using a comprehensive neuropsychological assessment at study enrollment and at 2-year follow-up. Cognitive performance measures were compared in the groups using t tests and mixed-effect models. Patterns of relationship with clinical measures were determined between cognitive function and clinical status markers using Spearman's correlations. At the initial timepoint, the HIV group demonstrated significantly weaker performance on measures of verbal memory, visual memory, psychomotor speed, motor speed, and executive function. A similar pattern was found when cognitive function was examined at follow-up and across both timepoints. The HIV subjects had generally weaker performance on psychomotor speed, executive function, motor speed, visual memory, and verbal memory. The rate of decline in cognitive function across the 2-year follow-up period did not differ between groups. Correlations between clinical status markers and cognitive function at both timepoints showed weaker performance associated with increased disease burden. Neurocognitive difficulty in chronic HIV infection may have very early onset and reflect consequences of initial brain viral invasion and neuroinflammation during the intense, uncontrolled viremia of acute HIV infection. Further characterization of the changes occurring in initial stages of infection and the risk and protective factors for cognitive function could inform new strategies for neuroprotection.

  15. Association between anthropometry, cardiometabolic risk factors, & early life factors & adult measures of endothelial function: Results from the New Delhi Birth Cohort

    PubMed Central

    Huffman, Mark D.; Khalil, Anita; Osmond, Clive; Fall, Caroline H. D.; Tandon, Nikhil; Lakshmy, Ramakrishnan; Ramji, Siddharth; Gera, Tarun; Prabhakaran, Poornima; Dey Biswas, S. K.; Reddy, K. Srinath; Bhargava, Santosh K.; Sachdev, Harshpal S.; Prabhakaran, Dorairaj

    2015-01-01

    Background & objectives: Abnormal endothelial function represents a preclinical marker of atherosclerosis. This study was conducted to evaluate associations between anthropometry, cardiometabolic risk factors, and early life factors and adult measures of endothelial function in a young urban Indian cohort free of clinical cardiovascular disease. Methods: Absolute changes in brachial artery diameter following cuff inflation and sublingual nitroglycerin (400 µg) were recorded to evaluate endothelium-dependent and -independent measures of endothelial function in 600 participants (362 men; 238 women) from the New Delhi Birth Cohort (2006-2009). Data on anthropometry, cardiometabolic risk factors, medical history, socio-economic position, and lifestyle habits were collected. Height and weight were recorded at birth, two and 11 yr of age. Age- and sex-adjusted linear regression models were developed to evaluate these associations. Results: The mean age of participants was 36±1 yr. Twenty two per cent men and 29 per cent women were obese (BMI > 30 kg/m2). Mean systolic blood pressure (SBP) was 131±14 and 119±13 mmHg, and diabetes prevalence was 12 and 8 per cent for men and women, respectively. Brachial artery diameter was higher for men compared with women both before (3.48±0.37 and 2.95±0.35 cm) and after hyperaemia (3.87±0.37 vs. 3.37±0.35 cm). A similar difference was seen before and after nitroglycerin. Markers of increased adiposity, smoking, SBP, and metabolic syndrome, but not early life anthropometry, were inversely associated with endothelial function after adjustment for age and sex. Interpretation & conclusions: The analysis of the current prospective data from a young urban Indian cohort showed that cardiometabolic risk factors, but not early life anthropometry, were associated with worse endothelial function. PMID:26831418

  16. Perinatal stress and early life programming of lung structure and function

    PubMed Central

    Wright, Rosalind J.

    2010-01-01

    Exposure to environmental toxins during critical periods of prenatal and/or postnatal development may alter the normal course of lung morphogenesis and maturation, potentially resulting in changes that affect both structure and function of the respiratory system. Moreover, these early effects may persist into adult life magnifying the potential public health impact. Aberrant or excessive pro-inflammatory immune responses, occurring both locally and systemically, that result in inflammatory damage to the airway are a central determinant of lung structure-function changes throughout life. Disruption of neuroendocrine function in early development, specifically the hypothalamic-pituitary-adrenal (HPA) axis, may alter functional status of the immune system. Autonomic nervous system (ANS) function (sympathovagal imbalance) is another integral component of airway function and immunity in childhood. This overview discusses the evidence linking psychological factors to alterations in these interrelated physiological processes that may, in turn, influence childhood lung function and identifies gaps in our understanding. PMID:20080145

  17. Early Blindness Results in Developmental Plasticity for Auditory Motion Processing within Auditory and Occipital Cortex

    PubMed Central

    Jiang, Fang; Stecker, G. Christopher; Boynton, Geoffrey M.; Fine, Ione

    2016-01-01

    Early blind subjects exhibit superior abilities for processing auditory motion, which are accompanied by enhanced BOLD responses to auditory motion within hMT+ and reduced responses within right planum temporale (rPT). Here, by comparing BOLD responses to auditory motion in hMT+ and rPT within sighted controls, early blind, late blind, and sight-recovery individuals, we were able to separately examine the effects of developmental and adult visual deprivation on cortical plasticity within these two areas. We find that both the enhanced auditory motion responses in hMT+ and the reduced functionality in rPT are driven by the absence of visual experience early in life; neither loss nor recovery of vision later in life had a discernable influence on plasticity within these areas. Cortical plasticity as a result of blindness has generally be presumed to be mediated by competition across modalities within a given cortical region. The reduced functionality within rPT as a result of early visual loss implicates an additional mechanism for cross modal plasticity as a result of early blindness—competition across different cortical areas for functional role. PMID:27458357

  18. [Disorders of higher mental functions in the early stages of hydrocephalus].

    PubMed

    Simernitskaia, E G; Simernitskiĭ, B P

    1981-01-01

    The authors have carried out neuropsychological examinations of 32 children operated for hydrocephalus on the first year of the life. A syndrome of the higher psychic function disturbances characteristics for children with early hydrocephalus is described, and the results of the neuropsychological function examinations were compared with the character, etiology, and gravity of the hydrocephalus. In the children with the early hydrocephalus a high incidence of sinistrality was revealed, the fact, that gives one grounds to explain the peculiarities of the syndrome observed in them by an anomaly of the development of the brain functional asymmetry.

  19. Executive Function and Early Reading Skills

    ERIC Educational Resources Information Center

    Foy, Judith G.; Mann, Virginia A.

    2013-01-01

    The purpose of this study was to examine how executive function skills in verbal and nonverbal auditory tasks are related to early reading skills in beginning readers. Kindergarteners (N = 41, aged 5 years) completed verbal (phonemes) and nonverbal (environmental sounds) Continuous Performance tasks yielding measures of executive function (misses,…

  20. Validation of the Early Functional Abilities scale: An assessment of four dimensions in early recovery after traumatic brain injury.

    PubMed

    Poulsen, Ingrid; Kreiner, Svend; Engberg, Aase W

    2018-02-13

    The Early Functional Abilities scale assesses the restoration of brain function after brain injury, based on 4 dimensions. The primary objective of this study was to evaluate the validity, objectivity, reliability and measurement precision of the Early Functional Abilities scale by Rasch model item analysis. A secondary objective was to examine the relationship between the Early Functional Abilities scale and the Functional Independence Measurement™, in order to establish the criterion validity of the Early Functional Abilities scale and to compare the sensitivity of measurements using the 2 instruments. The Rasch analysis was based on the assessment of 408 adult patients at admission to sub-acute rehabilitation in Copenhagen, Denmark after traumatic brain injury. The Early Functional Abilities scale provides valid and objective measurement of vegetative (autonomic), facio-oral, sensorimotor and communicative/cognitive functions. Removal of one item from the sensorimotor scale confirmed unidimensionality for each of the 4 subscales, but not for the entire scale. The Early Functional Abilities subscales are sensitive to differences between patients in ranges in which the Functional Independence Measurement™ has a floor effect. The Early Functional Abilities scale assesses the early recovery of important aspects of brain function after traumatic brain injury, but is not unidimensional. We recommend removal of the "standing" item and calculation of summary subscales for the separate dimensions.

  1. Blastomere biopsy influences epigenetic reprogramming during early embryo development, which impacts neural development and function in resulting mice.

    PubMed

    Wu, Yibo; Lv, Zhuo; Yang, Yang; Dong, Guoying; Yu, Yang; Cui, Yiqiang; Tong, Man; Wang, Liu; Zhou, Zuomin; Zhu, Hui; Zhou, Qi; Sha, Jiahao

    2014-05-01

    Blastomere biopsy is used in preimplantation genetic diagnosis; however, the long-term implications on the offspring are poorly characterized. We previously reported a high risk of memory defects in adult biopsied mice. Here, we assessed nervous function of aged biopsied mice and further investigated the mechanism of neural impairment after biopsy. We found that aged biopsied mice had poorer spatial learning ability, increased neuron degeneration, and altered expression of proteins involved in neural degeneration or dysfunction in the brain compared to aged control mice. Furthermore, the MeDIP assay indicated a genome-wide low methylation in the brains of adult biopsied mice when compared to the controls, and most of the genes containing differentially methylated loci in promoter regions were associated with neural disorders. When we further compared the genomic DNA methylation profiles of 7.5-days postconception (dpc) embryos between the biopsy and control group, we found the whole genome low methylation in the biopsied group, suggesting that blastomere biopsy was an obstacle to de novo methylation during early embryo development. Further analysis on mRNA profiles of 4.5-dpc embryos indicated that reduced expression of de novo methylation genes in biopsied embryos may impact de novo methylation. In conclusion, we demonstrate an abnormal neural development and function in mice generated after blastomere biopsy. The impaired epigenetic reprogramming during early embryo development may be the latent mechanism contributing to the impairment of the nervous system in the biopsied mice, which results in a hypomethylation status in their brains.

  2. Determinants of early-life lung function in African infants

    PubMed Central

    Willemse, Lauren; Visagie, Ane; Czövek, Dorottya; Nduru, Polite; Vanker, Aneesa; Stein, Dan J; Koen, Nastassja; Sly, Peter D; Hantos, Zoltán; Hall, Graham L; Zar, Heather J

    2017-01-01

    Background Low lung function in early life is associated with later respiratory illness. There is limited data on lung function in African infants despite a high prevalence of respiratory disease. Aim To assess the determinants of early lung function in African infants. Method Infants enrolled in a South African birth cohort, the Drakenstein child health study, had lung function measured at 6–10 weeks of age. Measurements, made with the infant breathing via a facemask during natural sleep, included tidal breathing, sulfur hexafluoride multiple breath washout and the forced oscillation technique. Information on antenatal and early postnatal exposures was collected using questionnaires and urine cotinine. Household benzene exposure was measured antenatally. Results Successful tests were obtained in 645/675 (95%) infants, median (IQR) age of 51 (46–58) days. Infant size, age and male gender were associated with larger tidal volume. Infants whose mothers smoked had lower tidal volumes (−1.6 mL (95% CI −3.0 to −0.1), p=0.04) and higher lung clearance index (0.1 turnovers (95% CI 0.01 to 0.3), p=0.03) compared with infants unexposed to tobacco smoke. Infants exposed to alcohol in utero or household benzene had lower time to peak tidal expiratory flow over total expiratory time ratios, 10% (95% CI −15.4% to −3.7%), p=0.002) and 3.0% (95% CI −5.2% to −0.7%, p=0.01) lower respectively compared with unexposed infants. HIV-exposed infants had higher tidal volumes (1.7 mL (95% CI 0.06 to 3.3) p=0.04) compared with infants whose mothers were HIV negative. Conclusion We identified several factors including infant size, sex, maternal smoking, maternal alcohol, maternal HIV and household benzene associated with altered early lung function, many of which are factors amenable to public health interventions. Long-term study of lung function and respiratory disease in these children is a priority to develop strategies to strengthen child health. PMID:27856821

  3. Interocular suppression in strabismic amblyopia results in an attenuated and delayed hemodynamic response function in early visual cortex.

    PubMed

    Farivar, Reza; Thompson, Benjamin; Mansouri, Behzad; Hess, Robert F

    2011-12-20

    Factors such as strabismus or anisometropia during infancy can disrupt normal visual development and result in amblyopia, characterized by reduced visual function in an otherwise healthy eye and often associated with persistent suppression of inputs from the amblyopic eye by those from the dominant eye. It has become evident from fMRI studies that the cortical response to stimulation of the amblyopic eye is also affected. We were interested to compare the hemodynamic response function (HRF) of early visual cortex to amblyopic vs. dominant eye stimulation. In the first experiment, we found that stimulation of the amblyopic eye resulted in a signal that was both attenuated and delayed in its time to peak. We postulated that this delay may be due to suppressive effects of the dominant eye and, in our second experiment, measured the cortical response of amblyopic eye stimulation under two conditions--where the dominant eye was open and seeing a static pattern (high suppression) or where the dominant eye was patched and closed (low suppression). We found that the HRF in response to amblyopic eye stimulation depended on whether the dominant eye was open. This effect was manifested as both a delayed HRF under the suppressed condition and an amplitude reduction.

  4. Amotivation and functional outcomes in early schizophrenia.

    PubMed

    Fervaha, Gagan; Foussias, George; Agid, Ofer; Remington, Gary

    2013-12-15

    Negative symptoms, particularly amotivation/apathy, are intimately tied to functional outcomes. In the present study, apathy strongly predicted psychosocial functioning in a sample of early course schizophrenia patients. This relationship remained robust even after controlling for other clinical variables. These data suggest amotivation is core to functioning across the disease course. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  5. Trial-Based Functional Analysis and Functional Communication Training in an Early Childhood Setting

    ERIC Educational Resources Information Center

    Lambert, Joseph M.; Bloom, Sarah E.; Irvin, Jennifer

    2012-01-01

    Problem behavior is common in early childhood special education classrooms. Functional communication training (FCT; Carr & Durand, 1985) may reduce problem behavior but requires identification of its function. The trial-based functional analysis (FA) is a method that can be used to identify problem behavior function in schools. We conducted…

  6. Attention and executive functions in the early course of pediatric epilepsy.

    PubMed

    Reuner, Gitta; Kadish, Navah Esther; Doering, Jan Henje; Balke, Doreen; Schubert-Bast, Susanne

    2016-07-01

    Our prospective study aimed at exploring attention and executive functions in children with new-onset epilepsy prior to and during the early course of antiepileptic treatment. Sociodemographic and epilepsy-related factors were analyzed as potential predictors both of impaired cognitive functions as well as for changes in cognitive functioning in the early course of illness. From a total group of 115 children aged six to 17years without major disabilities, 76 children were assessed longitudinally with a screening tool for attention and executive functions (EpiTrack Junior®). Sociodemographic variables (gender, age at epilepsy onset, need of special education) and epilepsy-related variables (etiology of epilepsy, semiology of seizures, number of seizures) were considered as potential predictors for impaired functions prior to treatment and for deterioration/amelioration in cognitive functions in the early course. Attention and executive functions of children with new-onset epilepsy were significantly more often impaired when compared with a healthy population, but less often when compared with children with chronic epilepsy. The majority of children showed stable cognitive functioning in the early course of treatment. The risk of impaired cognitive functions was significantly heightened when etiology of epilepsy was unknown or not classifiable. The chance for improvement of functioning was lowered by having a genetic epilepsy, or an unknown semiology of seizures. Children with new-onset epilepsy are at high risk for impaired attention and executive functions even prior to antiepileptic treatment, especially when etiology of their epilepsy remains unclear. The high stability of cognitive functioning in the early course can be used in counseling of families who worry about negative side effects of drug treatment. Finally, a systematic assessment of cognitive functions in children with new-onset epilepsy is necessary to detect subtle deficits in the early course and

  7. Long term effects of early adversity on cognitive function.

    PubMed

    Richards, M; Wadsworth, M E J

    2004-10-01

    To investigate long term effects of early adverse circumstances on cognitive function. Associations between early material home circumstances, parental divorce, maternal management and understanding, and cognitive function in childhood, adolescence, and adulthood were analysed using multiple linear regression, controlling for sex, parental SES, and birth order in 1339 males and females from the MRC National Survey of Health and Development. Early adverse circumstances were strongly associated with lower cognitive ability in childhood and adolescence, and were detectable on measures of verbal ability, memory, and speed and concentration in midlife. However, these long term effects were mostly explained by the effects of adversity on childhood or adolescent cognitive ability or by differences in educational attainment and adult social class. An exception was the effect of poor material home conditions on visual search speed at 53 years, which was maintained after controlling for adolescent ability, as well as further control for educational attainment, adult social class, physical growth, cigarette smoking, and affective state. There was no evidence of more rapid decline in memory and psychomotor function across middle age in those exposed to early adversity. The effect of early adversity on cognitive function tracks across the life course at least as far as middle age, although there was little evidence from this study of effect amplification over this interval. Nevertheless, in view of the persistence of child poverty in the industrialised world, these findings give cause for concern.

  8. Structural and Functional Evaluations for the Early Detection of Glaucoma.

    PubMed

    Lucy, Katie A; Wollstein, Gadi

    2016-01-01

    The early detection of glaucoma is imperative in order to preserve functional vision. Structural and functional methods are utilized to detect and monitor glaucomatous damage and the vision loss it causes. The relationship between these detection measures is complex and differs between individuals, especially in early glaucoma. Using both measures together is advised in order to ensure the highest probability of glaucoma detection, and new testing methods are continuously developed with the goals of earlier disease detection and improvement of disease monitoring. The purpose of this review is to explore the relationship between structural and functional glaucoma detection and discuss important technological advances for early glaucoma detection.

  9. Structural and Functional Evaluations for the Early Detection of Glaucoma

    PubMed Central

    Lucy, Katie A.; Wollstein, Gadi

    2016-01-01

    The early detection of glaucoma is imperative in order to preserve functional vision. Structural and functional methods are utilized to detect and monitor glaucomatous damage and the vision loss it causes. The relationship between these detection measures is complex and differs between individuals, especially in early glaucoma. Using both measures together is advised in order to ensure the highest probability of glaucoma detection, and new testing methods are continuously developed with the goals of earlier disease detection and improvement of disease monitoring. The purpose of this review is to explore the relationship between structural and functional glaucoma detection and discuss important technological advances for early glaucoma detection. PMID:28603546

  10. Association between anthropometry, cardiometabolic risk factors, & early life factors & adult measures of endothelial function: Results from the New Delhi Birth Cohort.

    PubMed

    Huffman, Mark D; Khalil, Anita; Osmond, Clive; Fall, Caroline H D; Tandon, Nikhil; Lakshmy, Ramakrishnan; Ramji, Siddharth; Gera, Tarun; Prabhakaran, Poornima; Dey Biswas, S K; Reddy, K Srinath; Bhargava, Santosh K; Sachdev, Harshpal S; Prabhakaran, Dorairaj

    2015-12-01

    Abnormal endothelial function represents a preclinical marker of atherosclerosis. This study was conducted to evaluate associations between anthropometry, cardiometabolic risk factors, and early life factors and adult measures of endothelial function in a young urban Indian cohort free of clinical cardiovascular disease. Absolute changes in brachial artery diameter following cuff inflation and sublingual nitroglycerin (400 µg) were recorded to evaluate endothelium-dependent and -independent measures of endothelial function in 600 participants (362 men; 238 women) from the New Delhi Birth Cohort (2006-2009). Data on anthropometry, cardiometabolic risk factors, medical history, socio-economic position, and lifestyle habits were collected. Height and weight were recorded at birth, two and 11 yr of age. Age- and sex-adjusted linear regression models were developed to evaluate these associations. The mean age of participants was 36±1 yr. Twenty two per cent men and 29 per cent women were obese (BMI th > 30 kg/m [2] ). Mean systolic blood pressure (SBP) was 131±14 and 119±13 mmHg, and diabetes prevalence was 12 and 8 per cent for men and women, respectively. Brachial artery diameter was higher for men compared with women both before (3.48±0.37 and 2.95±0.35 cm) and after hyperaemia (3.87±0.37 vs. 3.37±0.35 cm). A similar difference was seen before and after nitroglycerin. Markers of increased adiposity, smoking, SBP, and metabolic syndrome, but not early life anthropometry, were inversely associated with endothelial function after adjustment for age and sex. The analysis of the current prospective data from a young urban Indian cohort showed that cardiometabolic risk factors, but not early life anthropometry, were associated with worse endothelial function.

  11. Technology-Aided Assessment of Sensorimotor Function in Early Infancy

    PubMed Central

    Allievi, Alessandro G.; Arichi, Tomoki; Gordon, Anne L.; Burdet, Etienne

    2014-01-01

    There is a pressing need for new techniques capable of providing accurate information about sensorimotor function during the first 2 years of childhood. Here, we review current clinical methods and challenges for assessing motor function in early infancy, and discuss the potential benefits of applying technology-assisted methods. We also describe how the use of these tools with neuroimaging, and in particular functional magnetic resonance imaging (fMRI), can shed new light on the intra-cerebral processes underlying neurodevelopmental impairment. This knowledge is of particular relevance in the early infant brain, which has an increased capacity for compensatory neural plasticity. Such tools could bring a wealth of knowledge about the underlying pathophysiological processes of diseases such as cerebral palsy; act as biomarkers to monitor the effects of possible therapeutic interventions; and provide clinicians with much needed early diagnostic information. PMID:25324827

  12. Understanding the Contribution of Zinc Transporters in the Function of the Early Secretory Pathway

    PubMed Central

    Matsunaga, Mayu; Takeda, Taka-aki

    2017-01-01

    More than one-third of newly synthesized proteins are targeted to the early secretory pathway, which is comprised of the endoplasmic reticulum (ER), Golgi apparatus, and other intermediate compartments. The early secretory pathway plays a key role in controlling the folding, assembly, maturation, modification, trafficking, and degradation of such proteins. A considerable proportion of the secretome requires zinc as an essential factor for its structural and catalytic functions, and recent findings reveal that zinc plays a pivotal role in the function of the early secretory pathway. Hence, a disruption of zinc homeostasis and metabolism involving the early secretory pathway will lead to pathway dysregulation, resulting in various defects, including an exacerbation of homeostatic ER stress. The accumulated evidence indicates that specific members of the family of Zn transporters (ZNTs) and Zrt- and Irt-like proteins (ZIPs), which operate in the early secretory pathway, play indispensable roles in maintaining zinc homeostasis by regulating the influx and efflux of zinc. In this review, the biological functions of these transporters are discussed, focusing on recent aspects of their roles. In particular, we discuss in depth how specific ZNT transporters are employed in the activation of zinc-requiring ectoenzymes. The means by which early secretory pathway functions are controlled by zinc, mediated by specific ZNT and ZIP transporters, are also subjects of this review. PMID:29048339

  13. Understanding the Contribution of Zinc Transporters in the Function of the Early Secretory Pathway.

    PubMed

    Kambe, Taiho; Matsunaga, Mayu; Takeda, Taka-Aki

    2017-10-19

    More than one-third of newly synthesized proteins are targeted to the early secretory pathway, which is comprised of the endoplasmic reticulum (ER), Golgi apparatus, and other intermediate compartments. The early secretory pathway plays a key role in controlling the folding, assembly, maturation, modification, trafficking, and degradation of such proteins. A considerable proportion of the secretome requires zinc as an essential factor for its structural and catalytic functions, and recent findings reveal that zinc plays a pivotal role in the function of the early secretory pathway. Hence, a disruption of zinc homeostasis and metabolism involving the early secretory pathway will lead to pathway dysregulation, resulting in various defects, including an exacerbation of homeostatic ER stress. The accumulated evidence indicates that specific members of the family of Zn transporters (ZNTs) and Zrt- and Irt-like proteins (ZIPs), which operate in the early secretory pathway, play indispensable roles in maintaining zinc homeostasis by regulating the influx and efflux of zinc. In this review, the biological functions of these transporters are discussed, focusing on recent aspects of their roles. In particular, we discuss in depth how specific ZNT transporters are employed in the activation of zinc-requiring ectoenzymes. The means by which early secretory pathway functions are controlled by zinc, mediated by specific ZNT and ZIP transporters, are also subjects of this review.

  14. Transactional relations between caregiving stress, executive functioning, and problem behavior from early childhood to early adolescence

    PubMed Central

    LaGasse, Linda L.; Conradt, Elisabeth; Karalunas, Sarah L.; Dansereau, Lynne M.; Butner, Jonathan E.; Shankaran, Seetha; Bada, Henrietta; Bauer, Charles R.; Whitaker, Toni M.; Lester, Barry M.

    2016-01-01

    Developmental psychopathologists face the difficult task of identifying the environmental conditions that may contribute to early childhood behavior problems. Highly stressed caregivers can exacerbate behavior problems, while children with behavior problems may make parenting more difficult and increase caregiver stress. Unknown is: (1) how these transactions originate, (2) whether they persist over time to contribute to the development of problem behavior and (3) what role resilience factors, such as child executive functioning, may play in mitigating the development of problem behavior. In the present study, transactional relations between caregiving stress, executive functioning, and behavior problems were examined in a sample of 1,388 children with prenatal drug exposures at three developmental time points: early childhood (birth-age 5), middle childhood (ages 6 to 9), and early adolescence (ages 10 to 13). Transactional relations differed between caregiving stress and internalizing versus externalizing behavior. Targeting executive functioning in evidence-based interventions for children with prenatal substance exposure who present with internalizing problems and treating caregiving psychopathology, depression, and parenting stress in early childhood may be particularly important for children presenting with internalizing behavior. PMID:27427803

  15. Early identification: Language skills and social functioning in deaf and hard of hearing preschool children.

    PubMed

    Netten, Anouk P; Rieffe, Carolien; Theunissen, Stephanie C P M; Soede, Wim; Dirks, Evelien; Korver, Anna M H; Konings, Saskia; Oudesluys-Murphy, Anne Marie; Dekker, Friedo W; Frijns, Johan H M

    2015-12-01

    Permanent childhood hearing impairment often results in speech and language problems that are already apparent in early childhood. Past studies show a clear link between language skills and the child's social-emotional functioning. The aim of this study was to examine the level of language and communication skills after the introduction of early identification services and their relation with social functioning and behavioral problems in deaf and hard of hearing children. Nationwide cross-sectional observation of a cohort of 85 early identified deaf and hard of hearing preschool children (aged 30-66 months). Parents reported on their child's communicative abilities (MacArthur-Bates Communicative Development Inventory III), social functioning and appearance of behavioral problems (Strengths and Difficulties Questionnaire). Receptive and expressive language skills were measured using the Reynell Developmental Language Scale and the Schlichting Expressive Language Test, derived from the child's medical records. Language and communicative abilities of early identified deaf and hard of hearing children are not on a par with hearing peers. Compared to normative scores from hearing children, parents of deaf and hard of hearing children reported lower social functioning and more behavioral problems. Higher communicative abilities were related to better social functioning and less behavioral problems. No relation was found between the degree of hearing loss, age at amplification, uni- or bilateral amplification, mode of communication and social functioning and behavioral problems. These results suggest that improving the communicative abilities of deaf and hard of hearing children could improve their social-emotional functioning. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. Early Fathering as a Predictor of Later Psychosocial Functioning Among Preschool Children with Behavior Problems

    PubMed Central

    Herbert, Sharonne D.; Harvey, Elizabeth A.; Lugo-Candelas, Claudia I.; Breaux, Rosanna P.

    2015-01-01

    Objective The present study examined the role of early fathering in subsequent trajectories of social emotional and academic functioning of preschool children with behavior problems. Method Participants were 128 preschool-aged children (73 boys, 55 girls) with behavior problems whose biological fathers took part in a longitudinal study. Children were 3 years of age at the beginning of the study and were assessed annually for 3 years. Results Early paternal depressive symptoms predicted many aspects of children’s outcome 3 years later, including externalizing and internalizing problems, social skills deficits, and lower cognitive and academic functioning, and predicted changes in children’s externalizing, internalizing, and social problems across the preschool years. Paternal socioeconomic status (SES) also consistently predicted children’s later functioning across these domains. Furthermore, self-reported paternal attention deficit hyperactivity disorder (ADHD) symptoms and laxness, as well as observed frequent commands were associated with later externalizing problems in children. Paternal depressive symptoms and laxness mediated the relation between paternal ADHD symptoms and child functioning. Conclusions Results suggest that aspects of early father functioning play an important role in the psychosocial, cognitive, and academic development of preschool-aged children with behavior problems. PMID:23269560

  17. Functional selectivity for face processing in the temporal voice area of early deaf individuals

    PubMed Central

    van Ackeren, Markus J.; Rabini, Giuseppe; Zonca, Joshua; Foa, Valentina; Baruffaldi, Francesca; Rezk, Mohamed; Pavani, Francesco; Rossion, Bruno; Collignon, Olivier

    2017-01-01

    Brain systems supporting face and voice processing both contribute to the extraction of important information for social interaction (e.g., person identity). How does the brain reorganize when one of these channels is absent? Here, we explore this question by combining behavioral and multimodal neuroimaging measures (magneto-encephalography and functional imaging) in a group of early deaf humans. We show enhanced selective neural response for faces and for individual face coding in a specific region of the auditory cortex that is typically specialized for voice perception in hearing individuals. In this region, selectivity to face signals emerges early in the visual processing hierarchy, shortly after typical face-selective responses in the ventral visual pathway. Functional and effective connectivity analyses suggest reorganization in long-range connections from early visual areas to the face-selective temporal area in individuals with early and profound deafness. Altogether, these observations demonstrate that regions that typically specialize for voice processing in the hearing brain preferentially reorganize for face processing in born-deaf people. Our results support the idea that cross-modal plasticity in the case of early sensory deprivation relates to the original functional specialization of the reorganized brain regions. PMID:28652333

  18. Factors Associated With Early Functional Outcome After Hip Fracture Surgery

    PubMed Central

    Cong, Guang-Ting; Nwachukwu, Benedict U.; Patt, Minda L.; Desai, Pingal; Zambrana, Lester; Lane, Joseph M.

    2016-01-01

    Background: Hip fractures are common in the elderly and are likely to become more prevalent as the US population ages. Early functional status is an indicator of longer term outcome, yet in-hospital predictors of functional recovery, particularly time of surgery and composition of support staff, after hip fracture surgery have not been well studied. Methods: Ninety-nine consecutive patients underwent hip fracture surgery by a single surgeon between 2009 and 2013. Surgery after 48 hours was deemed as surgical delay, and surgery after 5 pm was deemed as after hours. Surgical support staff experience was determined by experts from our institution as well as documented level of training. Functional status was determined by independent ambulation on postoperative day (POD) 3. Results: On POD3, 48 (79%) of 62 patients with no delay were able to ambulate, whereas only 14 (38%) of 37 patients with delayed surgery were able to ambulate (P < .001). This relationship persisted when adjusted for American Society of Anesthesiologist classification. No delay in patients older than 80 (odds ratio [OR], 6.91; 95% confidence interval [CI], 2.16-22.10) and females (OR, 7.05; 95% CI, 2.34-21.20) was associated with greater chance of early ambulation. After-hours surgery was not associated with ambulation (P = .35). Anesthesiologist and circulating nurse experience had no impact on patient’s ambulatory status; however, nonorthopedic scrub technicians were associated with worse functional status (OR 7.50; 95% CI, 1.46-38.44, P = .01). Conclusion: Surgical delay and nonorthopedic scrub technicians are associated with worse early functional outcome after hip fracture surgery. Surgical delay should be avoided in older patients and women. More work should be done to understand the impact of surgical team composition on outcome. PMID:26929850

  19. The Little Brain That Could: Understanding Executive Function in Early Childhood

    ERIC Educational Resources Information Center

    Blasco, Patricia M.; Saxton, Sage; Gerrie, Mary

    2014-01-01

    Executive functions (EFs) involve a number of interconnected systems that, when compromised, can result in difficulties that affect a child's ability to perform tasks across early childhood settings, including the home and community-based settings. In retrospective research studies, researchers have found that a young child's…

  20. Executive Function Buffers the Association between Early Math and Later Academic Skills.

    PubMed

    Ribner, Andrew D; Willoughby, Michael T; Blair, Clancy B

    2017-01-01

    Extensive evidence has suggested that early academic skills are a robust indicator of later academic achievement; however, there is mixed evidence of the effectiveness of intervention on academic skills in early years to improve later outcomes. As such, it is clear there are other contributing factors to the development of academic skills. The present study tests the role of executive function (EF) (a construct made up of skills complicit in the achievement of goal-directed tasks) in predicting 5th grade math and reading ability above and beyond math and reading ability prior to school entry, and net of other cognitive covariates including processing speed, vocabulary, and IQ. Using a longitudinal dataset of N = 1292 participants representative of rural areas in two distinctive geographical parts of the United States, the present investigation finds EF at age 5 strongly predicts 5th grade academic skills, as do cognitive covariates. Additionally, investigation of an interaction between early math ability and EF reveals the magnitude of the association between early math and later math varies as a function of early EF, such that participants who have high levels of EF can "catch up" to peers who perform better on assessments of early math ability. These results suggest EF is pivotal to the development of academic skills throughout elementary school. Implications for further research and practice are discussed.

  1. Fathers' sensitive parenting and the development of early executive functioning.

    PubMed

    Towe-Goodman, Nissa R; Willoughby, Michael; Blair, Clancy; Gustafsson, Hanna C; Mills-Koonce, W Roger; Cox, Martha J

    2014-12-01

    Using data from a diverse sample of 620 families residing in rural, predominately low-income communities, this study examined longitudinal links between fathers' sensitive parenting in infancy and toddlerhood and children's early executive functioning, as well as the contribution of maternal sensitive parenting. After accounting for the quality of concurrent and prior parental care, children's early cognitive ability, and other child and family factors, fathers' and mothers' sensitive and supportive parenting during play at 24 months predicted children's executive functioning at 3 years of age. In contrast, paternal parenting quality during play at 7 months did not make an independent contribution above that of maternal care, but the links between maternal sensitive and supportive parenting and executive functioning seemed to operate in similar ways during infancy and toddlerhood. These findings add to prior work on early experience and children's executive functioning, suggesting that both fathers and mothers play a distinct and complementary role in the development of these self-regulatory skills.

  2. Fathers’ Sensitive Parenting and the Development of Early Executive Functioning

    PubMed Central

    Towe-Goodman, Nissa R.; Willoughby, Michael; Blair, Clancy; Gustafsson, Hanna C.; Mills-Koonce, W. Roger; Cox, Martha J.

    2014-01-01

    Using data from a diverse sample of 620 families residing in rural, predominately low-income communities, this study examined longitudinal links between fathers’ sensitive parenting in infancy and toddlerhood and children’s early executive functioning, as well as the contribution of maternal sensitive parenting. After accounting for the quality of concurrent and prior parental care, children’s early cognitive ability, and other child and family factors, fathers’ and mothers’ sensitive and supportive parenting during play at 24-months predicted children’s executive functioning at 3-years of age. In contrast, paternal parenting quality during play at 7-months did not make an independent contribution above that of maternal care, but the links between maternal sensitive and supportive parenting and executive functioning seemed to operate in similar ways during infancy and toddlerhood. These findings add to prior work on early experience and children’s executive functioning, suggesting that both fathers and mothers play a distinct and complementary role in the development of these self-regulatory skills. PMID:25347539

  3. Early results of patellofemoral inlay resurfacing arthroplasty using the HemiCap Wave prosthesis.

    PubMed

    Patel, Akash; Haider, Zakir; Anand, Amarjit; Spicer, Dominic

    2017-01-01

    Common surgical treatment options for isolated patellofemoral osteoarthritis include arthroscopic procedures, total knee replacement and patellofemoral replacement. The HemiCap Wave patellofemoral resurfacing prosthesis is a novel inlay design introduced in 2009 with scarce published data on its functional outcomes. We aim to prospectively evaluate early functional outcomes and complications, for patients undergoing a novel inlay resurfacing arthroplasty for isolated patellofemoral arthrosis in an independent centre. From 2010 to 2013, 16 consecutive patients underwent patellofemoral resurfacing procedures using HemiCap Wave (Arthrosurface Inc., Franklin, Massachusetts, USA) for anterior knee pain with confirmed radiologically and/or arthroscopically isolated severe patellofemoral arthrosis. Standardized surgical technique, as recommended by the implant manufacturer, was followed. Outcome measures included range of movement, functional knee scores (Oxford Knee Score (OKS), Knee Injury and Osteoarthritis Outcome Score (KOOS) and Short Form-36 (SF-36)), radiographic disease progression, revision rates and complications. Eight men and eight women underwent patellofemoral HemiCap Wave resurfacing, with an average age of 63 years (range: 46-83). Average follow-up was 24.1 months (6-34). Overall, post-operative scores were excellent. There was a statistically significant improvement in the post-operative OKS, KOOS and SF-36 scores ( p < 0.01). One patient had radiological disease progression. One patient underwent revision for deep infection. Two other minor complications were observed and treated conservatively. The HemiCap Wave patellofemoral resurfacing prosthesis has excellent early results in terms of functional outcomes, radiological outcomes and low complication rates. At the very least, early results show that the HemiCap Wave is comparable to more established onlay prostheses. The HemiCap Wave thus provides a safe and effective surgical option in the treatment

  4. Interactions between callous unemotional behaviors and executive function in early childhood predict later socioemotional functioning

    PubMed Central

    Waller, Rebecca; Hyde, Luke W.; Baskin-Sommers, Arielle; Olson, Sheryl L.

    2018-01-01

    Callous unemotional (CU) behaviors are linked to aggression, behavior problems, and difficulties in peer relationships in children and adolescents. However, few studies have examined whether early childhood CU behaviors predict aggression or peer-rejection during late-childhood or potential moderation of this relationship by executive function. The current study examined whether the interaction of CU behaviors and executive function in early childhood predicted different forms of aggression in late-childhood, including proactive, reactive, and relational aggression, as well as how much children were liked by their peers. Data from cross-informant reports and multiple observational tasks were collected from a high-risk sample (N=240; female=118) at ages 3 and 10 years old. Parent reports of CU behaviors at age 3 predicted teacher reports of reactive, proactive, and relational aggression, as well as lower peer-liking at age 10. Moderation analysis showed that specifically at high levels of CU behaviors and low levels of observed executive function, children were reported by teachers as showing greater reactive and proactive aggression, and were less-liked by peers. Findings demonstrate that early childhood CU behaviors and executive function have unique main and interactive effects on both later aggression and lower peer-liking even when taking into account stability in behavior problems over time. By elucidating how CU behaviors and deficits in executive function potentiate each other during early childhood, we can better characterize the emergence of severe and persistent behavior and interpersonal difficulties across development. PMID:27418255

  5. Radiographic and functional results in the treatment of early stages of Charcot neuroarthropathy with a walker boot and immediate weight bearing.

    PubMed

    Parisi, Maria Candida Ribeiro; Godoy-Santos, Alexandre Leme; Ortiz, Rafael Trevisan; Sposeto, Rafael Barban; Sakaki, Marcos Hideyo; Nery, Marcia; Fernandes, Tulio Diniz

    2013-01-01

    One of the most common gold standards for the treatment of Charcot neuroarthropathy (CN) in the early Eichenholtz stages I and II is immobilization with the total contact casting and lower limb offloading. However, the total amount of offloading is still debatable. This study evaluates the clinical and radiographic findings in the treatment of early stages of CN (Eichenholtz stages I and II) with a walker boot and immediate total weight-bearing status. Twenty-two patients with type 2 diabetes mellitus (DM) and CN of Eichenholtz stages I and II were selected for non-operative treatment. All patients were educated about their condition, and full weight bearing was allowed as tolerated. Patients were monitored on a fortnightly basis in the earlier stages, with clinical examination, temperature measurement, and standardized weight-bearing radiographs. Their American Orthopedic Foot and Ankle Society (AOFAS) scores were determined before and after the treatment protocol. No cutaneous ulcerations or infections were observed in the evaluated cases. The mean measured angles at the beginning and end of the study, although showing relative increase, did not present a statistically significant difference (p > 0.05). Mean AOFAS scores showed a statistically significant improvement by the end of the study (p < 0.005). The treatment of early stages of CN (Eichenholtz stages I and II) with emphasis on walker boot and immediate weight bearing has shown a good functional outcome, non-progressive deformity on radiographic assessment, and promising results as a safe treatment option.

  6. Functional neuroanatomical correlates of episodic memory impairment in early phase psychosis

    PubMed Central

    Hummer, Tom A.; Vohs, Jenifer L.; Yung, Matthew G.; Liffick, Emily; Mehdiyoun, Nicole F.; Radnovich, Alexander J.; McDonald, Brenna C.; Saykin, Andrew J.; Breier, Alan

    2015-01-01

    Studies have demonstrated that episodic memory (EM) is often preferentially disrupted in schizophrenia. The neural substrates that mediate EM impairment in this illness are not fully understood. Several functional magnetic resonance imaging (fMRI) studies have employed EM probe tasks to elucidate the neural underpinnings of impairment, though results have been inconsistent. The majority of EM imaging studies have been conducted in chronic forms of schizophrenia with relatively few studies in early phase patients. Early phase schizophrenia studies are important because they may provide information regarding when EM deficits occur and address potential confounds more frequently observed in chronic populations. In this study, we assessed brain activation during the performance of visual scene encoding and recognition fMRI tasks in patients with earlyphase psychosis (n=35) and age, sex, and race matched healthy control subjects (n = 20). Patients demonstrated significantly lower activation than controls in the right hippocampus and left fusiform gyrus during scene encoding and lower activation in the posterior cingulate, precuneus, and left middle temporal cortex during recognition of target scenes. Symptom levels were not related to the imaging findings, though better cognitive performance in patients was associated with greater right hippocampal activation during encoding. These results provide evidence of altered function in neuroanatomical circuitry subserving EM early in the course of psychotic illness, which may have implications for pathophysiological models of this illness. PMID:25749917

  7. Peritransplant Soluble CD30 as a Risk Factor for Slow Kidney Allograft Function, Early Acute Rejection, Worse Long-Term Allograft Function, and Patients' Survival

    PubMed Central

    Ostapenko, Tetyana I.; Nykonenko, Tamara N.; Nesterenko, Svitlana N.; Nykonenko, Olexandr S.

    2017-01-01

    Background We aimed to determine whether serum soluble CD30 (sCD30) could identify recipients at high risk for unfavorable early and late kidney transplant outcomes. Methods Serum sCD30 was measured on the day of kidney transplantation and on the 4th day posttransplant. We assessed the value of these measurements in predicting delayed graft function, slow graft function (SGF), acute rejection (AR), pyelonephritis, decline of allograft function after 6 months, and graft and patient survival during 5 years of follow-up in 45 recipients. Results We found the association between low pretransplant serum levels of sCD30 and SGF. The absence of significant decrease of sCD30 on the 4th day posttransplant was characteristic for SGF, early AR (the 8th day–6 months), late AR (>6 months), and early pyelonephritis (the 8th day–2 months). Lower pretransplant and posttransplant sCD30 predicted worse allograft function at 6 months and 2 years, respectively. Higher pretransplant sCD30 was associated with higher frequency of early AR, and worse patients' survival, but only in the recipients of deceased-donor graft. Pretransplant sCD30 also allowed to differentiate patients with early pyelonephritis and early AR. Conclusions Peritransplant sCD30 is useful in identifying patients at risk for unfavorable early and late transplant outcomes. PMID:28694560

  8. Early light deprivation effects on human cone-driven retinal function.

    PubMed

    Esposito Veneruso, Paolo; Ziccardi, Lucia; Magli, Giulia; Parisi, Vincenzo; Falsini, Benedetto; Magli, Adriano

    2017-03-01

    To assess whether the early light deprivation induced by congenital cataract may influence the cone-driven retinal function in humans. Forty-one patients affected by congenital cataract (CC) who had undergone uncomplicated cataract extraction surgery and intraocular lens implant, and 14 healthy subjects (HS) were enrolled. All patients underwent complete ophthalmological and orthoptic evaluations and best-corrected visual acuity (BCVA) measurement; light-adapted full-field electroretinograms (ERG) and photopic negative responses (PhNR) were recorded to obtain a reliable measurement of the outer/inner retinal function and of the retinal ganglion cells' function respectively. Mean values of light-adapted ERG a- and b-wave and PhNR amplitude of CC eyes were significantly reduced and photopic ERG b-wave implicit time mean values were significantly delayed when compared to HS ones. When studying photopic ERG mean amplitudes at 5 ms, significant differences were found when comparing CC and control eyes. In CC eyes, statistically significant correlations were found between a- and b- wave amplitudes and PhNR amplitudes. No significant correlations were found between ERG parameters and BCVA, as well as between the age of CC patients at surgery and the time elapsed from lens extraction. No significant differences were found when functional parameters of bilateral and unilateral congenital cataract (uCC) eyes were compared, however uCC eyes showed significant differences when compared with contralateral healthy eyes. We found a significant impairment of cone-driven retinal responses in patients with a history of congenital cataract. These changes might result from the long-lasting effects of early light deprivation on the cone retinal pathways. Our findings support the relevance of retinal involvement in deficits induced by early light deprivation. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  9. Early physics results.

    PubMed

    Jenni, Peter

    2012-02-28

    For the past year, experiments at the Large Hadron Collider (LHC) have started exploring physics at the high-energy frontier. Thanks to the superb turn-on of the LHC, a rich harvest of initial physics results have already been obtained by the two general-purpose experiments A Toroidal LHC Apparatus (ATLAS) and the Compact Muon Solenoid (CMS), which are the subject of this report. The initial data have allowed a test, at the highest collision energies ever reached in a laboratory, of the Standard Model (SM) of elementary particles, and to make early searches Beyond the Standard Model (BSM). Significant results have already been obtained in the search for the Higgs boson, which would establish the postulated electro-weak symmetry breaking mechanism in the SM, as well as for BSM physics such as Supersymmetry (SUSY), heavy new particles, quark compositeness and others. The important, and successful, SM physics measurements are giving confidence that the experiments are in good shape for their journey into the uncharted territory of new physics anticipated at the LHC.

  10. Infant Attention and Early Childhood Executive Function

    ERIC Educational Resources Information Center

    Cuevas, Kimberly; Bell, Martha Ann

    2014-01-01

    Individual differences in infant attention are theorized to reflect the speed of information processing and are related to later cognitive abilities (i.e., memory, language, and intelligence). This study provides the first systematic longitudinal analysis of infant attention and early childhood executive function (EF; e.g., working memory,…

  11. Early adversity and neural correlates of executive function: implications for academic adjustment.

    PubMed

    McDermott, Jennifer M; Westerlund, Alissa; Zeanah, Charles H; Nelson, Charles A; Fox, Nathan A

    2012-02-15

    Early adversity can negatively impact the development of cognitive functions, although little is known about whether such effects can be remediated later in life. The current study examined one facet of executive functioning - inhibitory control - among children who experienced institutional care and explored the impact of a foster care intervention within the context of the Bucharest Early Intervention Project (BEIP). Specifically, a go/nogo task was administered when children were eight years old and behavioral and event-related potential (ERP) measures were collected. Results revealed that children assigned to care as usual (i.e. institutional care) were less accurate and exhibited slower neural responses compared to children assigned to the foster care intervention and children who had never been institutionalized. However, children in both the care as usual and foster care groups exhibited diminished attention processing of nogo cues as assessed via P300 amplitude. Foster care children also showed differential reactivity between correct and error responses via the error-related negativity (ERN) as compared to children in the care as usual group. Combined, the results highlight perturbations in neural sources of behavioral and attention problems among children experiencing early adversity. Potential implications for academic adjustment in at risk children are discussed. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. T59. VIRTUAL REALTY ASSESSMENT OF FUNCTIONAL CAPACITY IN EARLY SCHIZOPHRENIA: ASSOCIATIONS WITH NEUROCOGNITION, FUNCTIONAL CAPACITY PERFORMANCE, AND DAILY FUNCTIONING

    PubMed Central

    Ventura, Joseph; Welikson, Tamara; Subotnik, Kenneth L; Ered, Arielle; Keefe, Richard; Hellemann, Gerhard H; Nuechterlein, Keith H

    2018-01-01

    Abstract Background Research using virtual reality assessment of functional capacity has shown promise as a reliable and valid way to assess treatment response in patients with established schizophrenia. There has been little work on virtual reality based assessments of functional capacity for patients in the early phase of schizophrenia. We examined whether virtual reality based assessment methods reveal functional capacity deficits in young patients and relevant relationships with established measures of neurocognition, functional capacity performance, and daily functioning. Methods The sample consisted of UCLA Aftercare Research Program patients (n=42) who were diagnosed by trained raters administering the SCID and who met criteria for schizophrenia, schizoaffective disorder, or schizophreniform disorder, and screened normal control subjects (n=13). Patients were within 2 years of their first psychotic episode upon clinic entry, were an average of 23.2 years old, and had an average of 12.9 years of education. The Virtual Reality Functional Capacity Assessment Tool (VRFCAT) was the computer-based measure of functional capacity. We used the MATRICS Consensus Cognitive Battery (MCCB) as an objective measure of neurocognition and the UCSD Performance-Based Skills Assessment (UPSA) to assess functional capacity performance. The Global Functioning Scale: Role and Social, and the Role Functioning Scale were used to assess work and school performance, familial interactions, and social functioning. Results We were able to confirm that the deficit in functional capacity performance measured using VRFCAT is present in the early course of schizophrenia in that the patients were slower and committed more errors (M=830.41) as compared with normal controls (M=716.84; t=3.0, p<.01). Virtual reality based assessment of functional capacity was correlated with objective measures of neurocognition (MCCB Overall Composite), r=-.71, p=<.01, standard approaches to functional capacity

  13. Inter-subject synchrony as an index of functional specialization in early childhood.

    PubMed

    Moraczewski, Dustin; Chen, Gang; Redcay, Elizabeth

    2018-02-02

    Early childhood is a time of significant change within multiple cognitive domains including social cognition, memory, executive function, and language; however, the corresponding neural changes remain poorly understood. This is likely due to the difficulty in acquiring artifact-free functional MRI data during complex task-based or unconstrained resting-state experiments in young children. In addition, task-based and resting state experiments may not capture dynamic real-world processing. Here we overcome both of these challenges through use of naturalistic viewing (i.e., passively watching a movie in the scanner) combined with inter-subject neural synchrony to examine functional specialization within 4- and 6-year old children. Using a novel and stringent crossed random effect statistical analysis, we find that children show more variable patterns of activation compared to adults, particularly within regions of the default mode network (DMN). In addition, we found partial evidence that child-to-adult synchrony increased as a function of age within a DMN region: the temporoparietal junction. Our results suggest age-related differences in functional brain organization within a cross-sectional sample during an ecologically valid context and demonstrate that neural synchrony during naturalistic viewing fMRI can be used to examine functional specialization during early childhood - a time when neural and cognitive systems are in flux.

  14. An Analysis of Risk and Function Information in Early Stage Design

    NASA Technical Reports Server (NTRS)

    Barrientos, Francesca; Tumer, Irem; Grantham, Katie; VanWie, Michael; Stone, Robert

    2005-01-01

    The concept of function offers a high potential for thinking and reasoning about designs as well as providing a common thread for relating together other design information. This paper focuses specifically on the relation between function and risk by examining how this information is addressed for a design team conducting early stage design for space missions. Risk information is decomposed into a set of key attributes which are then used to scrutinize the risk information using three approaches from the pragmatics sub-field of linguistics: i) Gricean, ii) Relevance Theory, and Functional Analysis. Results of this linguistics-based approach descriptively account for the context of designer communication with respect to function and risk, and offer prescriptive guidelines for improving designer communication.

  15. Comparison of endoscopic and microscopic trans-sphenoidal pituitary surgery: early results in a single centre.

    PubMed

    Razak, Adam A; Horridge, Michelle; Connolly, Daniel J; Warren, Daniel J; Mirza, Showkat; Muraleedharan, Vakkat; Sinha, Saurabh

    2013-02-01

    Pituitary surgery has seen a recent shift from a microscopic to an endoscopic trans-sphenoidal approach. We present our early experience with endoscopic surgery and compare the outcome with our recent microscopic experience. From January 2008 until present time, 80 consecutive patients underwent trans-sphenoidal pituitary surgery in our institution. Until September 2009, all patients had a microscopic trans-septal approach. After this time, the patients underwent endoscopic trans-sphenoidal surgery. All patients underwent pre- and post-operative MRI and full endocrinological evaluation. Data was collected prospectively including tumour volume, endocrine function, visual function, length of stay and complications. There were 40 patients in each group. In the microscopic group, there were 26 non-functioning tumours and 14 functioning tumours. In the endoscopic group, there were 24 non-functioning and 16 functioning tumours. There were significantly better results in terms of tumour resection (p = 0.002) and remission (p = 0.018) in the endoscopic group. In this group there was also a lower incidence of CSF leaks and a shorter length of stay for secreting tumours (p = 0.005). 1 patient in the endoscopic group died at day 43 post-operatively, having initially presented in a poor clinical state with pituitary apoplexy. Microscopic trans-sphenoidal surgery remains the benchmark for future surgical techniques. Our early results suggest that endoscopic trans-sphenoidal surgery provides favourable results in both tumour resection and control of secreting tumours in comparison with microscopic surgery. Further longer-term evaluation is required to ensure the outcome of endoscopic surgery.

  16. Form and Function in Early Clause-Combining

    ERIC Educational Resources Information Center

    Lustigman, Lyle; Berman, Ruth A.

    2016-01-01

    The study characterizes developmental trends in early Hebrew clause-combining (CC) by analyzing the interplay between linguistic form and communicative function in different interactional settings. Analysis applied to all utterances produced by three children aged 2;0-3;0 who combined two or more clauses, either self-initiated or on the basis of…

  17. Using Immediate-Early Genes to Map Hippocampal Subregional Functions

    ERIC Educational Resources Information Center

    Kubik, Stepan; Miyashita, Teiko; Guzowski, John F.

    2007-01-01

    Different functions have been suggested for the hippocampus and its subdivisions along both transversal and longitudinal axes. Expression of immediate-early genes (IEGs) has been used to map specific functions onto neuronal activity in different areas of the brain including the hippocampus (IEG imaging). Here we review IEG studies on hippocampal…

  18. Studying Individual Plant AOX Gene Functionality in Early Growth Regulation: A New Approach.

    PubMed

    Arnholdt-Schmitt, Birgit; Patil, Vinod Kumar

    2017-01-01

    AOX1 and AOX2 genes are thought to play different physiological roles. Whereas AOX1 is typically expected to associate to stress and growth responses, AOX2 was more often found to be linked to development and housekeeping functions. However, this view is questioned by several adverse observations. For example, co-regulated expression for DcAOX1 and DcAOX2a genes was recently reported during growth induction in carrot (Daucus carota L.). Early expression peaks for both genes during the lag phase of growth coincided with a critical time point for biomass prediction, a result achieved by applying calorespirometry. The effect of both AOX family member genes cannot easily be separated. However, separate functional analysis is required in order to identify important gene-specific polymorphisms or patterns of polymorphisms for functional marker development and its use in breeding. Specifically, a methodology is missing that enables studying functional effects of individual genes or polymorphisms/polymorphic patterns on early growth regulation.This protocol aims to provide the means for identifying plant alternative oxidase (AOX) gene variants as functional markers for early growth regulation. Prerequisite for applying this protocol is available Schizosaccharomyces pombe strains that were transformed with individual AOX genes following published protocols from Anthony Moore's group (Albury et al., J Biol Chem 271:17062-17066, 1996; Affourtit et al., J Biol Chem 274:6212-6218, 1999). The novelty of the present protocol comes by modifying yeast cell densities in a way that allows studying critical qualitative and quantitative effects of AOX gene variants (isoenzymes or polymorphic genes) during the early phase of growth. Calorimetry is used as a novel tool to confirm differences obtained by optical density measurements in early growth regulation by metabolic phenotyping (released heat rates). This protocol enables discriminating between AOX genes that inhibit growth and

  19. Early fathering as a predictor of later psychosocial functioning among preschool children with behavior problems.

    PubMed

    Herbert, Sharonne D; Harvey, Elizabeth A; Lugo-Candelas, Claudia I; Breaux, Rosanna P

    2013-07-01

    The present study examined the role of early fathering in subsequent trajectories of social emotional and academic functioning of preschool children with behavior problems. Participants were 128 preschool-aged children (73 boys, 55 girls) with behavior problems whose biological fathers took part in a longitudinal study. Children were 3 years of age at the beginning of the study and were assessed annually for 3 years. Early paternal depressive symptoms predicted many aspects of children's outcome 3 years later, including externalizing and internalizing problems, social skills deficits, and lower cognitive and academic functioning, and predicted changes in children's externalizing, internalizing, and social problems across the preschool years. Paternal socioeconomic status (SES) also consistently predicted children's later functioning across these domains. Furthermore, self-reported paternal attention-deficit hyperactivity disorder (ADHD) symptoms and laxness, as well as observed frequent commands were associated with later externalizing problems in children. Paternal depressive symptoms and laxness mediated the relation between paternal ADHD symptoms and child functioning. Results suggest that aspects of early father functioning play an important role in the psychosocial, cognitive, and academic development of preschool-aged children with behavior problems.

  20. Identification of a transitional fibroblast function in very early rheumatoid arthritis

    PubMed Central

    Filer, Andrew; Ward, Lewis S C; Kemble, Samuel; Davies, Christopher S; Munir, Hafsa; Rogers, Rebekah; Raza, Karim; Buckley, Christopher Dominic; Nash, Gerard B; McGettrick, Helen M

    2017-01-01

    Objectives Synovial fibroblasts actively regulate the inflammatory infiltrate by communicating with neighbouring endothelial cells (EC). Surprisingly, little is known about how the development of rheumatoid arthritis (RA) alters these immunomodulatory properties. We examined the effects of phase of RA and disease outcome (resolving vs persistence) on fibroblast crosstalk with EC and regulation of lymphocyte recruitment. Methods Fibroblasts were isolated from patients without synovitis, with resolving arthritis, very early RA (VeRA; symptom ≤12 weeks) and established RA undergoing joint replacement (JRep) surgery. Endothelial-fibroblast cocultures were formed on opposite sides of porous filters. Lymphocyte adhesion from flow, secretion of soluble mediators and interleukin 6 (IL-6) signalling were assessed. Results Fibroblasts from non-inflamed and resolving arthritis were immunosuppressive, inhibiting lymphocyte recruitment to cytokine-treated endothelium. This effect was lost very early in the development of RA, such that fibroblasts no longer suppressed recruitment. Changes in IL-6 and transforming growth factor beta 1 (TGF-β1) signalling appeared critical for the loss of the immunosuppressive phenotype. In the absence of exogenous cytokines, JRep, but not VeRA, fibroblasts activated endothelium to support lymphocyte. Conclusions In RA, fibroblasts undergo two distinct changes in function: first a loss of immunosuppressive responses early in disease development, followed by the later acquisition of a stimulatory phenotype. Fibroblasts exhibit a transitional functional phenotype during the first 3 months of symptoms that contributes to the accumulation of persistent infiltrates. Finally, the role of IL-6 and TGF-β1 changes from immunosuppressive in resolving arthritis to stimulatory very early in the development of RA. Early interventions targeting ‘pathogenic’ fibroblasts may be required in order to restore protective regulatory processes. PMID:28847766

  1. Evolution of cystic fibrosis lung function in the early years.

    PubMed

    Bush, Andrew; Sly, Peter D

    2015-11-01

    Most treatment of newborn screening-diagnosed cystic fibrosis is not evidence-based; there are very few randomized controlled trials (RCTs). Furthermore, the advent of novel molecular therapies, which could be started at diagnosis, mandates performing RCTs in very young children. However, unless the natural history of early cystic fibrosis lung disease is known, RCTs are impossible. Here, we review the results of two large prospective cohorts of these infants - London Cystic Fibrosis Collaboration (LCFC) (London, UK) and Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST-CF) (Australia). Nutritional status remained excellent in both the cohorts. Both cohorts reported abnormal lung function aged at 3 months. AREST-CF, which previously reported rapidly declining preschool lung function, now report good conventional school-age spirometry. LCFC reported improvement between 3 months and 1 year, and stability in the second year. AREST-CF also reported a high prevalence of high resolution computed tomographic abnormalities related to free neutrophil elastase in bronchoalveolar lavage; LCFC reported high resolution computed tomographic changes at 1 year, which were too mild to be scored reproducibly. At least in the first 2 years of life, lung function is not a good end-point for RCTs; routine bronchoalveolar lavage and HRCT cannot be justified. Newborn screening has greatly improved outcomes, but we need better point-of-care biomarkers.

  2. An Early Years Toolbox for Assessing Early Executive Function, Language, Self-Regulation, and Social Development: Validity, Reliability, and Preliminary Norms

    PubMed Central

    Howard, Steven J.; Melhuish, Edward

    2016-01-01

    Several methods of assessing executive function (EF), self-regulation, language development, and social development in young children have been developed over previous decades. Yet new technologies make available methods of assessment not previously considered. In resolving conceptual and pragmatic limitations of existing tools, the Early Years Toolbox (EYT) offers substantial advantages for early assessment of language, EF, self-regulation, and social development. In the current study, results of our large-scale administration of this toolbox to 1,764 preschool and early primary school students indicated very good reliability, convergent validity with existing measures, and developmental sensitivity. Results were also suggestive of better capture of children’s emerging abilities relative to comparison measures. Preliminary norms are presented, showing a clear developmental trajectory across half-year age groups. The accessibility of the EYT, as well as its advantages over existing measures, offers considerably enhanced opportunities for objective measurement of young children’s abilities to enable research and educational applications. PMID:28503022

  3. Mapping thalamocortical functional connectivity in chronic and early stages of psychotic disorders

    PubMed Central

    Woodward, Neil D.; Heckers, Stephan

    2015-01-01

    Objective There is considerable evidence that the thalamus is abnormal in psychotic disorders. Resting-state fMRI (RS-fMRI) has revealed an intriguing pattern of thalamic dysconnectivity in psychosis characterized by reduced prefrontal cortex (PFC) connectivity and increased somatomotor-thalamic connectivity. However, critical knowledge gaps remain with respect to the onset, anatomical specificity, and clinical correlates of thalamic dysconnectivity in psychosis. Method RS-fMRI was collected on 105 healthy subjects and 148 individuals with psychosis, including 53 early stage psychosis patients. Using all 253 subjects, the thalamus was parceled into functional regions-of-interest (ROIs) on the basis of connectivity with six a-priori defined cortical ROIs covering most of the cortical mantle. Functional connectivity between each cortical ROI and its corresponding thalamic ROI was quantified and compared across groups. Significant differences in the ROI-to-ROI analysis were followed up with voxel-wise seed-based analyses to further localize thalamic dysconnectivity. Results ROI analysis revealed reduced PFC-thalamic connectivity and increased somatomotor-thalamic connectivity in both chronic and early stages psychosis patients. PFC hypo-connectivity and motor cortex hyper-connectivity correlated in patients suggesting they result from a common pathophysiological mechanism. Seed-based analyses revealed thalamic hypo-connectivity in psychosis localized to dorsolateral PFC, medial PFC, and cerebellar areas of the well-described ‘executive control’ network. Across all subjects, thalamic connectivity with areas of the fronto-parietal network correlated with cognitive functioning, including verbal learning and memory. Conclusions Thalamocortical dysconnectivity is present in both chronic and early stages of psychosis, includes reduced thalamic connectivity with the executive control network, and is related to cognitive impairment. PMID:26248537

  4. Linking Executive Function and Peer Problems from Early Childhood Through Middle Adolescence.

    PubMed

    Holmes, Christopher J; Kim-Spoon, Jungmeen; Deater-Deckard, Kirby

    2016-01-01

    Peer interactions and executive function play central roles in the development of healthy children, as peer problems have been indicative of lower cognitive competencies such as self-regulatory behavior and poor executive function has been indicative of problem behaviors and social dysfunction. However, few studies have focused on the relation between peer interactions and executive function and the underlying mechanisms that may create this link. Using a national sample (n = 1164, 48.6% female) from the Study of Early Child Care and Youth Development (SECCYD), we analyzed executive function and peer problems (including victimization and rejection) across three waves within each domain (executive function or peer problems), beginning in early childhood and ending in middle adolescence. Executive function was measured as a multi-method, multi-informant composite including reports from parents on the Children's Behavior Questionnaire and Child Behavior Checklist and child's performance on behavioral tasks including the Continuous Performance Task, Woodcock-Johnson, Tower of Hanoi, Operation Span Task, Stroop, and Tower of London. Peer problems were measured as a multi-informant composite including self, teacher, and afterschool caregiver reports on multiple peer-relationship scales. Using a cross-lagged design, our Structural Equation Modeling findings suggested that experiencing peer problems contributed to lower executive function later in childhood and better executive function reduced the likelihood of experiencing peer problems later in childhood and middle adolescence, although these relations weakened as a child moves into adolescence. The results highlight that peer relationships are involved in the development of strengths and deficits in executive function and vice versa.

  5. Linking Executive Function and Peer Problems from Early Childhood through Middle Adolescence

    PubMed Central

    Holmes, Christopher J.; Kim-Spoon, Jungmeen; Deater-Deckard, Kirby

    2015-01-01

    Peer interactions and executive function play central roles in the development of healthy children, as peer problems have been indicative of lower cognitive competencies such as self-regulatory behavior and poor executive function has been indicative of problem behaviors and social dysfunction. However, few studies have focused on the relation between peer interactions and executive function and the underlying mechanisms that may create this link. Using a national sample (n = 1,164, 48.6% female) from the Study of Early Child Care and Youth Development (SECCYD), we analyzed executive function and peer problems (including victimization and rejection) across three waves within each domain (executive function or peer problems), beginning in early childhood and ending in middle adolescence. Executive function was measured as a multi-method, multi-informant composite including reports from parents on the Children’s Behavior Questionnaire and Child Behavior Checklist and child’s performance on behavioral tasks including the Continuous Performance Task, Woodcock-Johnson, Tower of Hanoi, Operation Span Task, Stroop, and Tower of London. Peer problems were measured as a multi-informant composite including self, teacher, and after school caregiver reports on multiple peer-relationship scales. Using a cross-lagged design, our Structural Equation Modeling findings suggested that experiencing peer problems contributed to lower executive function later in childhood and better executive function reduced the likelihood of experiencing peer problems later in childhood and middle adolescence, although these relations weakened as a child moves into adolescence. The results highlight that peer relationships are involved in the development of strengths and deficits in executive function and vice versa. PMID:26096194

  6. [A Comparison Study on Early Damage Detection of Left Ventricular Function Based on Doppler Imaging Method for Children with Tumor].

    PubMed

    Liu, Ying; Zhang, Haowei; Zhang, Hang

    2015-12-01

    The early damage detection and evaluation are of great significance in treatment and prognosis to the left ventricular function for children with tumor. In this paper, it is reported that the early damage of the left ventricular function was observed by pulsed wave Doppler (PWD) and tissue Doppler imaging (TDI) in our laboratory. Eighty children half a year to fourteen years old were included in this study. The cardiac function indices in chemotherapy group and control group were measured and compared. The results showed that there was significant difference in mitral and tricuspid annulus flow spectrum between the two groups. Compared with PWD,TDI is more prompt, objective and accurate in detecting early damage of left ventricular function in children with tumor. And TDI is a good method for early identification of ventricular function damage in children with tumor.

  7. Early Childhood Teacher Research: From Questions to Results

    ERIC Educational Resources Information Center

    Castle, Kathryn

    2011-01-01

    What is early childhood teacher research and why is it important? How does a teacher researcher formulate a research question and a plan for doing research? How do teachers apply research results to effect change? "Early Childhood Teacher Research" is an exciting new resource that will address the sorts of questions and concerns that pre- and…

  8. Functional Connectivity of the Amygdala in Early Childhood Onset Depression

    PubMed Central

    Luking, Katherine R.; Repovs, Grega; Belden, Andy C.; Gaffrey, Michael S.; Botteron, Kelly N.; Luby, Joan L.; Barch, Deanna M.

    2011-01-01

    Objective Adult major depressive disorder (MDD) is associated with reduced cortico-limbic functional connectivity thought to indicate decreased top-down control of emotion. However, it is unclear whether such connectivity alterations are also present in early childhood onset MDD. Method Fifty-one children ages 7–11 years, prospectively studied since preschool age, completed resting state fMRI and were assigned to four groups: 1) C-MDD (N=13) personal history of early childhood onset MDD; 2) M-MDD (N=11) a maternal history of affective disorders; 3) CM-MDD (N=13) both maternal and early childhood onset MDD or 4) CON (N=14) without either a personal or maternal history. We used seed-based resting state functional connectivity (rsfcMRI) analysis in an independent sample of adults to identify networks showing both positive (e.g., limbic regions) and negative (e.g., dorsal frontal/parietal regions) connectivity with the amygdala. These regions were then used in ROI based analyses of our child sample. Results We found a significant interaction between maternal affective disorder history and the child's MDD history for both positive and negative rsfcMRI networks. Specifically, when copared to CON, we found reduced connectivity between the amygdala and the “Negative Network” in children with C-MDD, M-MDD and CM-MDD. Children with either C-MDD or a maternal history of MDD (but not CM-MDD) displayed reduced connectivity between the amygdala and the “Positive Network”. Conclusions Our finding of an attenuated relationship between the amygdala, a region affected in MDD and involved in emotion processing, and cognitive control regions is consistent with a hypothesis of altered regulation of emotional processing in C-MDD suggesting developmental continuity of this alteration into early childhood. PMID:21961777

  9. Early Childhood Practitioner Involvement in Functional Behavioral Assessment and Function-Based Interventions: A Literature Review

    ERIC Educational Resources Information Center

    Wood, Brenna K.; Drogan, Robin R.; Janney, Donna M.

    2014-01-01

    Reviewers analyzed studies published from 1990 to 2012 to determine early childhood practitioner involvement in functional behavioral assessment (FBA) and function-based behavioral intervention plans (BIP) for children with challenging behavior, age 6 and younger. Coding of 30 studies included practitioner involvement in FBA and BIP processes,…

  10. Developmental disruption of medial prefrontal cortical GABAergic function by non-contingent cocaine exposure during early adolescence

    PubMed Central

    Cass, Daryn K.; Thomases, Daniel R.; Caballero, Adriana; Tseng, Kuei Y.

    2013-01-01

    Background Drug experimentation during adolescence is associated with increased risk of drug addiction relative to any other age group. To further our understanding on the neurobiology underlying such liability, we investigate how early adolescent cocaine experience impacts the overall medial prefrontal cortex (mPFC) network function in adulthood. Methods A non-contingent administration paradigm was used to assess the impact of early adolescent cocaine treatment (rats; postnatal days -PD- 35-40) on the overall inhibitory regulation of mPFC activity in adulthood (PD65-75) by means of histochemical and in vivo electrophysiological measures combined with pharmacological manipulations. Results Cocaine exposure during early adolescence yields a distinctive hyper-metabolic PFC state that was not observed in adult (PD75-80)-treated rats. Local field potential recordings expand upon these findings by showing that early adolescent cocaine exposure is associated with an attenuation of mPFC GABAergic inhibition evoked by ventral hippocampal stimulation at beta and gamma frequencies that endures throughout adulthood. Such cocaine-induced mPFC disinhibition was not observed in adult-exposed animals. Furthermore, the normal developmental upregulation of parvalbumin immunoreactivity observed in the mPFC from PD35 to PD65 is lacking following early adolescent cocaine treatment. Conclusion Our data indicate that repeated cocaine exposure during early adolescence can elicit a state of mPFC disinhibition resulting from a functional impairment of the local prefrontal GABAergic network that endures through adulthood. A lack of acquisition of prefrontal GABAergic function during adolescence could trigger long-term deficits in the mPFC that may increase the susceptibility for the onset of substance abuse and related psychiatric disorders. PMID:23558299

  11. Maternally derived trypsin may have multiple functions in the early development of turbot (Scopthalmus maximus).

    PubMed

    Chi, Liang; Liu, Qinghua; Xu, Shihong; Xiao, Zhizhong; Ma, Daoyuan; Li, Jun

    2015-10-01

    Trypsin is an important serine protease that is considered to be involved in digestion of protein in teleost fish. Nevertheless, studies on trypsin/trypsinogen in fish embryos are very limited. In this study, the trypsinogen of turbot (Scophthalmus maximus) (tTG) was identified and the expression patterns and activity of trypsinogen/trypsin were investigated. The results showed that the tTG mRNA was evenly distributed in the oocytes and was also expressed along the yolk periphery in early embryos. At later embryo stages and 1 days after hatching (dph), the tTG mRNA concentrated at the alimentary tract and head. Quantitative expression analysis showed that the tTG transcripts decreased after fertilization until the gastrula stage, then increased with the embryo and larvae development. This result was also confirmed by the specific activity analysis of trypsin and in-situ-hybridization (ISH). All of the results indicated that tTG in early embryo stages was maternally derived and expressed by itself after gastrula stages. Additionally, location of tTG mRNA in embryos and larvae was investigated; we considered that trypsin may have multiple functions during the embryo development process. Based on our results regarding trypsinogen in embryos and early development, we concluded that the trypsin/trypsinogen in turbot embryos was inherited from a maternal source and we suggested that trypsin in early development has multiple functions in the process of development. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Early Immune Function and Duration of Organ Dysfunction in Critically Ill Septic Children.

    PubMed

    Muszynski, Jennifer A; Nofziger, Ryan; Moore-Clingenpeel, Melissa; Greathouse, Kristin; Anglim, Larissa; Steele, Lisa; Hensley, Josey; Hanson-Huber, Lisa; Nateri, Jyotsna; Ramilo, Octavio; Hall, Mark W

    2018-02-22

    Late immune suppression is associated with nosocomial infection and mortality in septic adults and children. Relationships between early immune suppression and outcomes in septic children remain unclear. Prospective observational study to test the hypothesis that early innate and adaptive immune suppression are associated with longer duration of organ dysfunction in children with severe sepsis/septic shock. Methods, Measurements and Main Results: Children aged < 18 years meeting consensus criteria for severe sepsis or septic shock were sampled within 48 hours of sepsis onset. Healthy controls were sampled once. Innate immune function was quantified by whole blood ex vivo lipopolysaccharide-induced TNFα production capacity. Adaptive immune function was quantified by ex vivo phytohemagglutinin-induced IFNγ production capacity. 102 septic children and 35 healthy children were enrolled. Compared to healthy children, septic children demonstrated lower LPS-induced TNFα production (p < 0.0001) and lower PHA-induced IFNγ production (p<0.0001). Among septic children, early innate and adaptive immune suppression were associated with greater number of days with multiple organ dysfunction (MODS) and greater number of days with any organ dysfunction. On multivariable analyses, early innate immune suppression remained independently associated with increased MODS days [aRR 1.2 (1.03, 1.5)] and organ dysfunction days [aRR 1.2 (1.1, 1.3)]. Critically ill children with severe sepsis or septic shock demonstrate early innate and adaptive immune suppression. Early suppression of both innate and adaptive immunity are associated with longer duration of organ dysfunction and may be useful markers to guide investigations of immunomodulatory therapies in septic children.

  13. Hippocampal functional connectivity and episodic memory in early childhood

    PubMed Central

    Riggins, Tracy; Geng, Fengji; Blankenship, Sarah L.; Redcay, Elizabeth

    2016-01-01

    Episodic memory relies on a distributed network of brain regions, with the hippocampus playing a critical and irreplaceable role. Few studies have examined how changes in this network contribute to episodic memory development early in life. The present addressed this gap by examining relations between hippocampal functional connectivity and episodic memory in 4-and 6-year-old children (n=40). Results revealed similar hippocampal functional connectivity between age groups, which included lateral temporal regions, precuneus, and multiple parietal and prefrontal regions, and functional specialization along the longitudinal axis. Despite these similarities, developmental differences were also observed. Specifically, 3 (of 4) regions within the hippocampal memory network were positively associated with episodic memory in 6-year-old children, but negatively associated with episodic memory in 4-year-old children. In contrast, all 3 regions outside the hippocampal memory network were negatively associated with episodic memory in older children, but positively associated with episodic memory in younger children. These interactions are interpreted within an interactive specialization framework and suggest the hippocampus becomes functionally integrated with cortical regions that are part of the hippocampal memory network in adults and functionally segregated from regions unrelated to memory in adults, both of which are associated with age-related improvements in episodic memory ability. PMID:26900967

  14. Effect of Early Rehabilitation during Intensive Care Unit Stay on Functional Status: Systematic Review and Meta-Analysis

    PubMed Central

    Castro-Avila, Ana Cristina; Serón, Pamela; Fan, Eddy; Gaete, Mónica; Mickan, Sharon

    2015-01-01

    Background and Aim Critically ill survivors may have functional impairments even five years after hospital discharge. To date there are four systematic reviews suggesting a beneficial impact for mobilisation in mechanically ventilated and intensive care unit (ICU) patients, however there is limited information about the influence of timing, frequency and duration of sessions. Earlier mobilisation during ICU stay may lead to greater benefits. This study aims to determine the effect of early rehabilitation for functional status in ICU/high-dependency unit (HDU) patients. Design Systematic review and meta-analysis. MEDLINE, EMBASE, CINALH, PEDro, Cochrane Library, AMED, ISI web of science, Scielo, LILACS and several clinical trial registries were searched for randomised and non-randomised clinical trials of rehabilitation compared to usual care in adult patients admitted to an ICU/HDU. Results were screened by two independent reviewers. Primary outcome was functional status. Secondary outcomes were walking ability, muscle strength, quality of life, and healthcare utilisation. Data extraction and methodological quality assessment using the PEDro scale was performed by primary reviewer and checked by two other reviewers. The authors of relevant studies were contacted to obtain missing data. Results 5733 records were screened. Seven articles were included in the narrative synthesis and six in the meta-analysis. Early rehabilitation had no significant effect on functional status, muscle strength, quality of life, or healthcare utilisation. However, early rehabilitation led to significantly more patients walking without assistance at hospital discharge (risk ratio 1.42; 95% CI 1.17-1.72). There was a non-significant effect favouring intervention for walking distance and incidence of ICU-acquired weakness. Conclusions Early rehabilitation during ICU stay was not associated with improvements in functional status, muscle strength, quality of life or healthcare utilisation

  15. Modeling Deficits From Early Auditory Information Processing to Psychosocial Functioning in Schizophrenia.

    PubMed

    Thomas, Michael L; Green, Michael F; Hellemann, Gerhard; Sugar, Catherine A; Tarasenko, Melissa; Calkins, Monica E; Greenwood, Tiffany A; Gur, Raquel E; Gur, Ruben C; Lazzeroni, Laura C; Nuechterlein, Keith H; Radant, Allen D; Seidman, Larry J; Shiluk, Alexandra L; Siever, Larry J; Silverman, Jeremy M; Sprock, Joyce; Stone, William S; Swerdlow, Neal R; Tsuang, Debby W; Tsuang, Ming T; Turetsky, Bruce I; Braff, David L; Light, Gregory A

    2017-01-01

     = 0.26, P < .001) and experiential negative symptoms (β = -0.75, P < .001) had direct effects on functional outcome. The indirect effect of EAP on functional outcome was significant as well (β = 0.14, P < .001). Overall, EAP had a fully mediated effect on functional outcome, engaging general rather than modality-specific cognition, with separate pathways that involved or bypassed negative symptoms. The data support a model in which EAP deficits lead to poor functional outcome via impaired cognition and increased negative symptoms. Results can be used to help guide mechanistically informed, personalized treatments and support the strategy of using EAP measures as surrogate end points in early-stage procognitive intervention studies.

  16. Maternal Thyroid Function in Early Pregnancy and Neuropsychological Performance of the Child at 5 Years of Age.

    PubMed

    Andersen, Stine Linding; Andersen, Stig; Liew, Zeyan; Vestergaard, Peter; Olsen, Jørn

    2018-02-01

    Abnormal maternal thyroid function in pregnancy may impair fetal brain development, but more evidence is needed to refine and corroborate the hypothesis. To estimate the association between maternal thyroid function in early pregnancy and neuropsychological performance of the child at 5 years of age. Follow-up study. A cohort of 1153 women and their children sampled from the Danish National Birth Cohort. Maternal thyroid-stimulating hormone (TSH) and free thyroxine (fT4) were measured in stored biobank sera from early pregnancy. Child neuropsychological test results (Wechsler Intelligence Scale/Test of Everyday Attention), test of motor function (Movement Assessment Battery), and results of parent and teacher reports (Behavior Rating Inventory of Executive Function/Strengths and Difficulties Questionnaire). Altogether 145 children (12.6%) were born to mothers with abnormal thyroid function in the early pregnancy. High maternal TSH and low fT4 were associated with lower child verbal intelligence quotient (adjusted mean difference TSH ≥ 10 mIU/L vs 0.1 to 2.49 mIU/L, -8.9 [95% confidence interval (CI), -15 to -2.4]; fT4 < 10 pmol/l vs 12.0 to 18.99 pmol/l, -13 [95% CI, -19 to -7.3]). Abnormal maternal thyroid function was also associated with adverse motor function and teacher-reported problems of executive function and behavior, and these associations were dominated by exposure to maternal hypothyroxinemia. Maternal thyroid hormone abnormalities were associated with adverse neuropsychological function of the child at 5 years of age. For intelligence, marked hypothyroidism was important, whereas for motor function and executive and behavior problems, maternal hypothyroxinemia was predominant. Copyright © 2017 Endocrine Society

  17. Towards an Early Software Effort Estimation Based on Functional and Non-Functional Requirements

    NASA Astrophysics Data System (ADS)

    Kassab, Mohamed; Daneva, Maya; Ormandjieva, Olga

    The increased awareness of the non-functional requirements as a key to software project and product success makes explicit the need to include them in any software project effort estimation activity. However, the existing approaches to defining size-based effort relationships still pay insufficient attention to this need. This paper presents a flexible, yet systematic approach to the early requirements-based effort estimation, based on Non-Functional Requirements ontology. It complementarily uses one standard functional size measurement model and a linear regression technique. We report on a case study which illustrates the application of our solution approach in context and also helps evaluate our experiences in using it.

  18. Attentional avoidance of fearful facial expressions following early life stress is associated with impaired social functioning.

    PubMed

    Humphreys, Kathryn L; Kircanski, Katharina; Colich, Natalie L; Gotlib, Ian H

    2016-10-01

    Early life stress is associated with poorer social functioning. Attentional biases in response to threat-related cues, linked to both early experience and psychopathology, may explain this association. To date, however, no study has examined attentional biases to fearful facial expressions as a function of early life stress or examined these biases as a potential mediator of the relation between early life stress and social problems. In a sample of 154 children (ages 9-13 years) we examined the associations among interpersonal early life stressors (i.e., birth through age 6 years), attentional biases to emotional facial expressions using a dot-probe task, and social functioning on the Child Behavior Checklist. High levels of early life stress were associated with both greater levels of social problems and an attentional bias away from fearful facial expressions, even after accounting for stressors occurring in later childhood. No biases were found for happy or sad facial expressions as a function of early life stress. Finally, attentional biases to fearful faces mediated the association between early life stress and social problems. Attentional avoidance of fearful facial expressions, evidenced by a bias away from these stimuli, may be a developmental response to early adversity and link the experience of early life stress to poorer social functioning. © 2016 Association for Child and Adolescent Mental Health.

  19. Motor, cognitive, and functional declines contribute to a single progressive factor in early HD.

    PubMed

    Schobel, Scott A; Palermo, Giuseppe; Auinger, Peggy; Long, Jeffrey D; Ma, Shiyang; Khwaja, Omar S; Trundell, Dylan; Cudkowicz, Merit; Hersch, Steven; Sampaio, Cristina; Dorsey, E Ray; Leavitt, Blair R; Kieburtz, Karl D; Sevigny, Jeffrey J; Langbehn, Douglas R; Tabrizi, Sarah J

    2017-12-12

    To identify an improved measure of clinical progression in early Huntington disease (HD) using data from prospective observational cohort studies and placebo group data from randomized double-blind clinical trials. We studied Unified Huntington Disease Rating Scale (UHDRS) and non-UHDRS clinical measures and brain measures of progressive atrophy in 1,668 individuals with early HD followed up prospectively for up to 30 to 36 months of longitudinal clinical follow-up. The results demonstrated that a composite measure of motor, cognitive, and global functional decline best characterized clinical progression and was most strongly associated with brain measures of progressive corticostriatal atrophy. Use of a composite motor, cognitive, and global functional clinical outcome measure in HD provides an improved measure of clinical progression more related to measures of progressive brain atrophy and provides an opportunity for enhanced clinical trial efficiency relative to currently used individual motor, cognitive, and functional outcome measures. © 2017 American Academy of Neurology.

  20. How Homes Influence Schools: Early Parenting Predicts African American Children's Classroom Social-Emotional Functioning

    ERIC Educational Resources Information Center

    Baker, Claire E.; Rimm-Kaufman, Sara E.

    2014-01-01

    Data from the Early Childhood Longitudinal Study, Kindergarten Cohort were used to examine the extent to which early parenting predicted African American children's kindergarten social-emotional functioning. Teachers rated children's classroom social-emotional functioning in four areas (i.e., approaches to learning, self-control, interpersonal…

  1. Modeling Deficits from Early Auditory Information Processing to Psychosocial Functioning in Schizophrenia

    PubMed Central

    Thomas, Michael L.; Green, Michael F.; Hellemann, Gerhard; Sugar, Catherine A.; Tarasenko, Melissa; Calkins, Monica E.; Greenwood, Tiffany A.; Gur, Raquel E.; Gur, Ruben C.; Lazzeroni, Laura C.; Nuechterlein, Keith H.; Radant, Allen D.; Seidman, Larry J.; Shiluk, Alexandra L.; Siever, Larry J.; Silverman, Jeremy M.; Sprock, Joyce; Stone, William S.; Swerdlow, Neal R.; Tsuang, Debby W.; Tsuang, Ming T.; Turetsky, Bruce I.; Braff, David L.; Light, Gregory A.

    2017-01-01

    Importance Neurophysiological measures of early auditory information processing (EAP) are used as endophenotypes in genomic studies and biomarkers in clinical intervention studies. Research in schizophrenia has established correlations among measures of EAP, cognition, clinical symptoms, and functional outcome. Clarifying these relationships by determining the pathways through which deficits in EAP affect functioning would suggest when and where to therapeutically intervene. Objective We sought to characterize the pathways from EAP to outcome and to estimate the extent to which enhancement of basic information processing might improve both cognition and psychosocial functioning in schizophrenia. Design Cross-sectional data were analyzed using structural equation modeling to examine the associations between EAP, cognition, negative symptoms, and functional outcome. Setting Participants were recruited from the community at five geographically distributed laboratories as part of the Consortium on the Genetics of Schizophrenia-2 (COGS-2). Participants This well-characterized cohort of schizophrenia patients (N = 1,415) underwent EAP and cognitive testing as well as thorough clinical and functional assessment. Main Outcome and Measures EAP was measured by mismatch negativity, P3a, and reorienting negativity. Cognition was measured by the Letter Number Span test and scales from the California Verbal Learning Test - Second Edition, the Wechsler Memory Scale Third Edition, and the Penn Computerized Neurocognitive Battery. Negative symptoms were measured by the Scale for the Assessment of Negative Symptoms. Functional outcome was measured by the Role Functioning Scale. Results EAP had a direct effect on cognition (β = 0.37, p < .001), cognition had a direct effect on negative symptoms (β = −0.16, p < .001), and both cognition (β = 0.26, p < .001) and experiential negative symptoms (β = −0.75, p < .001) had direct effects on functional outcome. Overall, EAP had a

  2. Abnormal early dynamic individual patterns of functional networks in low gamma band for depression recognition.

    PubMed

    Bi, Kun; Chattun, Mahammad Ridwan; Liu, Xiaoxue; Wang, Qiang; Tian, Shui; Zhang, Siqi; Lu, Qing; Yao, Zhijian

    2018-06-13

    The functional networks are associated with emotional processing in depression. The mapping of dynamic spatio-temporal brain networks is used to explore individual performance during early negative emotional processing. However, the dysfunctions of functional networks in low gamma band and their discriminative potentialities during early period of emotional face processing remain to be explored. Functional brain networks were constructed from the MEG recordings of 54 depressed patients and 54 controls in low gamma band (30-48 Hz). Dynamic connectivity regression (DCR) algorithm analyzed the individual change points of time series in response to emotional stimuli and constructed individualized spatio-temporal patterns. The nodal characteristics of patterns were calculated and fed into support vector machine (SVM). Performance of the classification algorithm in low gamma band was validated by dynamic topological characteristics of individual patterns in comparison to alpha and beta band. The best discrimination accuracy of individual spatio-temporal patterns was 91.01% in low gamma band. Individual temporal patterns had better results compared to group-averaged temporal patterns in all bands. The most important discriminative networks included affective network (AN) and fronto-parietal network (FPN) in low gamma band. The sample size is relatively small. High gamma band was not considered. The abnormal dynamic functional networks in low gamma band during early emotion processing enabled depression recognition. The individual information processing is crucial in the discovery of abnormal spatio-temporal patterns in depression during early negative emotional processing. Individual spatio-temporal patterns may reflect the real dynamic function of subjects while group-averaged data may neglect some individual information. Copyright © 2018. Published by Elsevier B.V.

  3. Hippocampal functional connectivity and episodic memory in early childhood.

    PubMed

    Riggins, Tracy; Geng, Fengji; Blankenship, Sarah L; Redcay, Elizabeth

    2016-06-01

    Episodic memory relies on a distributed network of brain regions, with the hippocampus playing a critical and irreplaceable role. Few studies have examined how changes in this network contribute to episodic memory development early in life. The present addressed this gap by examining relations between hippocampal functional connectivity and episodic memory in 4- and 6-year-old children (n=40). Results revealed similar hippocampal functional connectivity between age groups, which included lateral temporal regions, precuneus, and multiple parietal and prefrontal regions, and functional specialization along the longitudinal axis. Despite these similarities, developmental differences were also observed. Specifically, 3 (of 4) regions within the hippocampal memory network were positively associated with episodic memory in 6-year-old children, but negatively associated with episodic memory in 4-year-old children. In contrast, all 3 regions outside the hippocampal memory network were negatively associated with episodic memory in older children, but positively associated with episodic memory in younger children. These interactions are interpreted within an interactive specialization framework and suggest the hippocampus becomes functionally integrated with cortical regions that are part of the hippocampal memory network in adults and functionally segregated from regions unrelated to memory in adults, both of which are associated with age-related improvements in episodic memory ability. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. Motivational impairment predicts functional remission in first-episode psychosis: 3-Year follow-up of the randomized controlled trial on extended early intervention.

    PubMed

    Chang, Wing Chung; Kwong, Vivian Wing Yan; Or Chi Fai, Philip; Lau, Emily Sin Kei; Chan, Gloria Hoi Kei; Jim, Olivia Tsz Ting; Hui, Christy Lai Ming; Chan, Sherry Kit Wa; Lee, Edwin Ho Ming; Chen, Eric Yu Hai

    2018-02-01

    achieve functional remission. Functional impairment remains an unmet treatment need in the early stage of psychotic illness. Our results further suggest that amotivation may represent a critical therapeutic target for functional remission attainment in early psychosis.

  5. Multimodal MR-imaging reveals large-scale structural and functional connectivity changes in profound early blindness

    PubMed Central

    Bauer, Corinna M.; Hirsch, Gabriella V.; Zajac, Lauren; Koo, Bang-Bon; Collignon, Olivier

    2017-01-01

    between occipital and frontal and somatosensory-motor areas and between temporal (mainly fusiform and parahippocampus) and parietal, frontal, and other temporal areas. Correlations in white matter connectivity and functional connectivity observed between early blind and sighted controls showed an overall high degree of association. However, comparing the relative changes in white matter and functional connectivity between early blind and sighted controls did not show a significant correlation. In summary, these findings provide complimentary evidence, as well as highlight potential contradictions, regarding the nature of regional and large scale neuroplastic reorganization resulting from early onset blindness. PMID:28328939

  6. Restrictive annuloplasty to treat functional mitral regurgitation: optimize the restriction to improve the results?

    PubMed

    Totaro, Pasquale; Adragna, Nicola; Argano, Vincenzo

    2008-03-01

    Today, the 'gold standard' treatment of functional mitral regurgitation (MR) is the subject of much discussion. Although restrictive annuloplasty is currently considered the most reproducible technique, the means by which the degree of annular restriction is optimized remains problematic. The study was designed in order to identify whether the degree of restriction of the mitral annulus could influence early and midterm results following the treatment of functional MR using restrictive annuloplasty. A total of 32 consecutive patients with functional MR grade > or = 3+ was enrolled, among whom the mean anterior-posterior (AP) mitral annulus diameter was 39 +/- 3 mm. Restrictive mitral annuloplasty (combined with coronary artery bypass grafting) was performed in all patients using a Carpentier-Edwards Classic or Physio ring (size 26 or 28). The degree of AP annular restriction was calculated for each patient, and correlated with early and mid-term residual MR and left ventricular (LV) reverse remodeling (in terms of LV end-diastolic diameter (LVEDD) and LV end-diastolic volume (LVEDV) reduction). All surviving patients were examined at a one-year follow up. The mean AP mitral annulus restriction achieved was 48 +/- 4%. Intraoperatively, transesophageal echocardiography showed no residual MR in any patient. Before discharge from hospital, transthoracic echocardiography confirmed an absence of residual MR and showed significant LV reverse remodeling (LVEDV from 121 +/- 25 ml to 97 +/- 26 ml; LVEDD from 55 +/- 6 mm to 47 +/- 8 mm). A significant correlation (r = 0.57, p < 0.001) was identified between the degree of AP annulus restriction and LVEDV reduction. A cut-off of annular restriction of 40% (based on AP annulus measurement) correlated with a more significant reverse remodeling. The early postoperative data, with no recurrence of significant MR, was confirmed at a one-year follow up examination. A marked restriction of the AP mitral annulus diameter (> 40% of

  7. Effects of Cognitive Enhancement Therapy on Employment Outcomes in Early Schizophrenia: Results From a Two-Year Randomized Trial

    PubMed Central

    Eack, Shaun M.; Hogarty, Gerard E.; Greenwald, Deborah P.; Hogarty, Susan S.; Keshavan, Matcheri S.

    2013-01-01

    Objective To examine the effects of psychosocial cognitive rehabilitation on employment outcomes in a randomized controlled trial for individuals with early course schizophrenia. Method Early course schizophrenia outpatients (N = 58) were randomly assigned to Cognitive Enhancement Therapy (CET) or an Enriched Supportive Therapy (EST) control and treated for two years. Comprehensive data on cognition and employment were collected annually. Results Individuals treated with CET were significantly more likely to be competitively employed, had greater earnings from employment, and were more satisfied with their employment status by the end of treatment compared to EST recipients. Mediator analyses revealed that improvements in both social and non-social cognition mediated the CET effects on employment. Conclusion CET can help facilitate employment in early schizophrenia, by addressing the cognitive impairments that limit functioning in the disorder. Inclusion of cognitive rehabilitation in social work practice can support more optimal functional recovery from schizophrenia. PMID:23885163

  8. Gene function in early mouse embryonic stem cell differentiation

    PubMed Central

    Sene, Kagnew Hailesellasse; Porter, Christopher J; Palidwor, Gareth; Perez-Iratxeta, Carolina; Muro, Enrique M; Campbell, Pearl A; Rudnicki, Michael A; Andrade-Navarro, Miguel A

    2007-01-01

    Background Little is known about the genes that drive embryonic stem cell differentiation. However, such knowledge is necessary if we are to exploit the therapeutic potential of stem cells. To uncover the genetic determinants of mouse embryonic stem cell (mESC) differentiation, we have generated and analyzed 11-point time-series of DNA microarray data for three biologically equivalent but genetically distinct mESC lines (R1, J1, and V6.5) undergoing undirected differentiation into embryoid bodies (EBs) over a period of two weeks. Results We identified the initial 12 hour period as reflecting the early stages of mESC differentiation and studied probe sets showing consistent changes of gene expression in that period. Gene function analysis indicated significant up-regulation of genes related to regulation of transcription and mRNA splicing, and down-regulation of genes related to intracellular signaling. Phylogenetic analysis indicated that the genes showing the largest expression changes were more likely to have originated in metazoans. The probe sets with the most consistent gene changes in the three cell lines represented 24 down-regulated and 12 up-regulated genes, all with closely related human homologues. Whereas some of these genes are known to be involved in embryonic developmental processes (e.g. Klf4, Otx2, Smn1, Socs3, Tagln, Tdgf1), our analysis points to others (such as transcription factor Phf21a, extracellular matrix related Lama1 and Cyr61, or endoplasmic reticulum related Sc4mol and Scd2) that have not been previously related to mESC function. The majority of identified functions were related to transcriptional regulation, intracellular signaling, and cytoskeleton. Genes involved in other cellular functions important in ESC differentiation such as chromatin remodeling and transmembrane receptors were not observed in this set. Conclusion Our analysis profiles for the first time gene expression at a very early stage of mESC differentiation, and

  9. The role of pregnancy awareness on female sexual function in early gestation.

    PubMed

    Corbacioglu, Aytul; Bakir, Vuslat Lale; Akbayir, Ozgur; Cilesiz Goksedef, Behiye Pinar; Akca, Aysu

    2012-07-01

    Female sexual function is negatively influenced by pregnancy due to the physical and emotional changes. Although the most significant effect is seen in the third trimester of pregnancy, a considerable decrease in the frequency of intercourse and sexual desire in the first trimester has also been shown. To investigate the factors that affect sexuality in early pregnancy and the impact of awareness of pregnancy on female sexual function in the first trimester of pregnancy using two self-reported questionnaires. In this cross-sectional study, 130 healthy, married pregnant women who were admitted to the gynecology clinic between the 4th and 10th week of gestation were asked to complete a self-administered questionnaire and the female sexual function index (FSFI). The factors associated with FSFI score and monthly sexual activity frequency in the first trimester, as well as the differences in sexual activity frequency and FSFI scores between the women who were previously aware of their pregnancy and those who were yet unaware of their pregnancy. Women who were unaware of their pregnancy had significantly higher coitus frequency in comparison with the aware group (P = 0.002). Total FSFI score was 21.99 ± 8.13 in the aware group and 24.66 ± 3.76 in the unaware group (P = 0.02). None of the obstetric and sociodemographic variables had an influence on desire and pain scores. Arousal, lubrication, and satisfaction scores were adversely affected by awareness of pregnancy. Orgasm scores were influenced negatively by awareness and positively by love marriage; however, in multivariate linear regression analysis none of these were defined as independent factor for orgasm scores. Overall FSFI scores and monthly frequency of sexual activity were only affected by awareness. The results of this study suggest that in early gestation, awareness of pregnancy is associated with lower female sexual function. Furthermore, obstetric and sociodemographic factors seem to be

  10. Development and Application of a Tendon Prosthesis for Early Functional Restoration of the Hand.

    DTIC Science & Technology

    1975-09-01

    AD-ARSA 323 JEFFERSON MEDICAL COLL PHILADELP HIA PA F/6 6/5 DEVELOFHNT AND APPLICATION OF A TENDON PROSTHESIS FOR EARLY FU--ETCU, SEP 75 .1 M HUNTER...THIS SHEET S LEVELINETR S DEVELOPEN AND APPLICATION OF A TENDON PROSTESIS FOR EARLY FUNCTIONAL RTORATION OF THE HAND DOCUMENT IDENTIFICATION...OF A TENDON PROSTHESIS * (B.l FOR EARLY FUNCTIONAL RESTORATION OF THE HArD ANNUAL REPORT by James M. Hunter, M.D. September 1975 (For the period 1 July

  11. Contributions of Motivation, Early Numeracy Skills, and Executive Functioning to Mathematical Performance. A Longitudinal Study.

    PubMed

    Mercader, Jessica; Miranda, Ana; Presentación, M Jesús; Siegenthaler, Rebeca; Rosel, Jesús F

    2017-01-01

    The main goal of this longitudinal study is to examine the power of different variables and its dynamic interactions in predicting mathematical performance. The model proposed in this study includes indicators of motivational constructs (learning motivation and attributions), executive functioning (inhibition and working memory), and early numeracy skills (logical operations, counting, and magnitude comparison abilities), assessed during kindergarten, and mathematical performance in the second year of Primary Education. The sample consisted of 180 subjects assessed in two moments (5-6 and 7-8 years old). The results showed an indirect effect of initial motivation on later mathematical performance. Executive functioning and early numeracy skills mediated the effect of motivation on later mathematic achievement. Practical implications of these findings for mathematics education are discussed.

  12. Contributions of Motivation, Early Numeracy Skills, and Executive Functioning to Mathematical Performance. A Longitudinal Study

    PubMed Central

    Mercader, Jessica; Miranda, Ana; Presentación, M. Jesús; Siegenthaler, Rebeca; Rosel, Jesús F.

    2018-01-01

    The main goal of this longitudinal study is to examine the power of different variables and its dynamic interactions in predicting mathematical performance. The model proposed in this study includes indicators of motivational constructs (learning motivation and attributions), executive functioning (inhibition and working memory), and early numeracy skills (logical operations, counting, and magnitude comparison abilities), assessed during kindergarten, and mathematical performance in the second year of Primary Education. The sample consisted of 180 subjects assessed in two moments (5–6 and 7–8 years old). The results showed an indirect effect of initial motivation on later mathematical performance. Executive functioning and early numeracy skills mediated the effect of motivation on later mathematic achievement. Practical implications of these findings for mathematics education are discussed. PMID:29379462

  13. Insight as a social identity process in the evolution of psychosocial functioning in the early phase of psychosis.

    PubMed

    Klaas, H S; Clémence, A; Marion-Veyron, R; Antonietti, J-P; Alameda, L; Golay, P; Conus, P

    2017-03-01

    Awareness of illness (insight) has been found to have contradictory effects for different functional outcomes after the early course of psychosis. Whereas it is related to psychotic symptom reduction and medication adherence, it is also associated with increased depressive symptoms. In this line, the specific effects of insight on the evolution of functioning over time have not been identified, and social indicators, such as socio-occupational functioning have barely been considered. Drawing from social identity theory we investigated the impact of insight on the development of psychosocial outcomes and the interactions of these variables over time. The participants, 240 patients in early phase of psychosis from the Treatment and Early Intervention in Psychosis Program (TIPP) of the University Hospital of Lausanne, Switzerland, were assessed at eight time points over 3 years. Cross-lagged panel analyses and multilevel analyses were conducted on socio-occupational and general functioning [Social and Occupational Functioning Assessment Scale (SOFAS) and Global Assessment of Functioning (GAF)] with insight, time and depressive symptoms as independent variables. Results from multilevel analyses point to an overall positive impact of insight on psychosocial functioning, which increases over time. Yet the cross-lagged panel analysis did not reveal a systematic positive and causal effect of insight on SOFAS and GAF scores. Depressive symptoms seem only to be relevant in the beginning of the treatment process. Our results point to a complex process in which the positive impact of insight on psychosocial functioning increases over time, even when considering depressive symptoms. Future studies and treatment approaches should consider the procedural aspect of insight.

  14. Analysis of the Developmental Functioning of Early Intervention and Early Childhood Special Education Populations in Oregon. Issues & Answers. REL 2009-078

    ERIC Educational Resources Information Center

    Nave, Gary; Nishioka, Vicki; Burke, Arthur

    2009-01-01

    This study reports on the developmental functioning levels of children from birth through age 2 in early intervention services and children ages 3-5 in early childhood special education services at the time of entry into services, using data from the Oregon Early Childhood Assessment System. The assessment system contains data on the assessed…

  15. Longitudinal development of prefrontal function during early childhood.

    PubMed

    Moriguchi, Yusuke; Hiraki, Kazuo

    2011-04-01

    This is a longitudinal study on development of prefrontal function in young children. Prefrontal areas have been observed to develop dramatically during early childhood. To elucidate this development, we gave children cognitive shifting tasks related to prefrontal function at 3 years of age (Time 1) and 4 years of age (Time 2). We then monitored developmental changes in behavioral performance and examined prefrontal activation using near infrared spectroscopy. We found that children showed better behavioral performance and significantly stronger inferior prefrontal activation at Time 2 than they did at Time 1. Moreover, we demonstrated individual differences in prefrontal activation for the same behavioral tasks. Children who performed better in tasks at Time 1 showed significant activation of the right inferior prefrontal regions at Time 1 and significant activation of the bilateral inferior prefrontal regions at Time 2. Children who showed poorer performance at Time 1 exhibited no significant inferior prefrontal activation at Time 1 but significant left inferior prefrontal activation at Time 2. These results indicate the importance of the longitudinal method to address the link between cognitive and neural development. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Predictors of Behavioral Regulation in Kindergarten: Household Chaos, Parenting and Early Executive Functions

    PubMed Central

    Vernon-Feagans, Lynne; Willoughby, Michael; Garrett-Peters, Patricia

    2015-01-01

    Behavioral regulation is an important school readiness skill that has been linked to early executive function (EF) and later success in learning and school achievement. Although poverty and related risks as well as negative parenting have been associated with poorer EF and behavioral regulation, chaotic home environments may also play a role in understanding both early EF and later behavioral regulation at school age. To explore these relationships, a unique longitudinal and representative sample was used of 1292 children born to mothers who lived in low wealth rural America who were followed from birth into early elementary school. This study examined whether household chaos, which was measured across the first three years of life, predicted behavioral regulation in kindergarten above and beyond poverty related variables. In addition, this study tested whether parent responsivity and acceptance behaviors, measured during the first three years of life, as well as EF skills, which were measured when children were three to five years of age, mediated the relationship between early household chaos and kindergarten behavioral regulation. Results suggested that household chaos disorganization indirectly predicted kindergarten behavioral regulation through intermediate impacts on parenting behaviors and children's early EF skills. These findings suggest the importance of early household chaos disorganization, the parenting environment and early EF skills in understanding behavioral regulation, above and beyond poverty related risks. PMID:26751500

  17. Lactobacillus frumenti Facilitates Intestinal Epithelial Barrier Function Maintenance in Early-Weaned Piglets

    PubMed Central

    Hu, Jun; Chen, Lingli; Zheng, Wenyong; Shi, Min; Liu, Liu; Xie, Chunlin; Wang, Xinkai; Niu, Yaorong; Hou, Qiliang; Xu, Xiaofan; Xu, Baoyang; Tang, Yimei; Zhou, Shuyi; Yan, Yiqin; Yang, Tao; Ma, Libao; Yan, Xianghua

    2018-01-01

    Increased intestinal epithelial barrier function damages caused by early weaning stress have adverse effects on swine health and feed utilization efficiency. Probiotics have emerged as the promising antibiotic alternatives used for intestinal barrier function damage prevention. Our previous data showed that Lactobacillus frumenti was identified as a predominant Lactobacillus in the intestinal microbiota of weaned piglets. However, whether the intestinal epithelial barrier function in piglets was regulated by L. frumenti is still unclear. Here, piglets received a PBS vehicle or PBS suspension (2 ml, 108 CFU/ml) containing the L. frumenti by oral gavage once a day during the period of 6–20 days of age prior to early weaning. Our data demonstrated that oral administration of L. frumenti significantly improved the intestinal mucosal integrity and decreased the serum endotoxin and D-lactic acid levels in early-weaned piglets (26 days of age). The intestinal tight junction proteins (including ZO-1, Occludin, and Claudin-1) were significantly up-regulated by L. frumenti administration. The serum immunoglobulin G (IgG) levels, intestinal secretory immunoglobulin A (sIgA) levels, and interferon-γ (IFN-γ) levels were significantly increased by L. frumenti administration. Furthermore, our data revealed that oral administration of L. frumenti significantly increased the relative abundances of health-promoting microbes (including L. frumenti, Lactobacillus gasseri LA39, Parabacteroides distasonis, and Kazachstania telluris) and decreased the relative abundances of opportunistic pathogens (including Desulfovibrio desulfuricans and Candida humilis). Functional alteration of the intestinal bacterial community by L. frumenti administration was characterized by the significantly increased fatty acids and protein metabolism and decreased diseases-associated metabolic pathways. These findings suggest that L. frumenti facilitates intestinal epithelial barrier function maintenance

  18. Early-Life Exposure to Perfluoroalkyl Substances and Childhood Metabolic Function

    PubMed Central

    Fleisch, Abby F.; Rifas-Shiman, Sheryl L.; Mora, Ana M.; Calafat, Antonia M.; Ye, Xiaoyun; Luttmann-Gibson, Heike; Gillman, Matthew W.; Oken, Emily; Sagiv, Sharon K.

    2016-01-01

    Background: Perfluoroalkyl substances (PFASs) are synthetic chemicals that may persist in the environment and in humans. There is a possible association between early-life PFAS exposure and metabolic dysfunction in later life, but data are limited. Methods: We studied 665 mother–child pairs in Project Viva, a Boston, Massachusetts-area cohort recruited 1999–2002. We quantified concentrations of PFASs [perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoate (PFNA), perfluorohexane sulfonate (PFHxS), and perfluorodecanoate (PFDeA)] in maternal plasma collected at the first prenatal visit (median, 9.6 weeks gestation) and in child plasma from the mid-childhood research visit (median, 7.7 years). We assessed leptin, adiponectin, and homeostatic model assessment of insulin resistance (HOMA-IR) in mid-childhood. We fit covariate-adjusted linear regression models and conducted stratified analyses by child sex. Results: Children with higher PFAS concentrations had lower HOMA-IR [e.g., –10.1% (95% CI: –17.3, –2.3) per interquartile range increment in PFOA]. This inverse association between child PFAS and HOMA-IR was more pronounced in females [e.g., PFOA: –15.6% (95% CI: –25.4, –4.6) vs. –6.1% (95% CI: –16.2, 5.2) for males]. Child PFAS plasma concentrations were not associated with leptin or adiponectin. Prenatal PFAS plasma concentrations were not associated with leptin, adiponectin, or HOMA-IR in offspring. Conclusions: We found no evidence for an adverse effect of early-life PFAS exposure on metabolic function in mid-childhood. In fact, children with higher PFAS concentrations had lower insulin resistance. Citation: Fleisch AF, Rifas-Shiman SL, Mora AM, Calafat AM, Ye X, Luttmann-Gibson H, Gillman MW, Oken E, Sagiv SK. 2017. Early-life exposure to perfluoroalkyl substances and childhood metabolic function. Environ Health Perspect 125:481–487; http://dx.doi.org/10.1289/EHP303 PMID:27586368

  19. Determinants of Objectively Measured Physical Functional Performance in Early to Mid-stage Parkinson Disease

    PubMed Central

    Kluger, Benzi M.; Brown, R. Preston; Aerts, Shanae; Schenkman, Margaret

    2014-01-01

    Background Parkinson disease (PD) may lead to functional limitations through both motor and non-motor symptoms. While patients with advanced disease have well-documented and profound functional limitations, less is known about the determinants of function in early to mid-stage disease where interventions may be more likely to benefit and preserve function. Objective The objective of the current study was to identify motor, cognitive and gait determinants of physical functional performance in patients with early to mid-stage PD. Design Secondary analysis of cross-sectional baseline data from a randomized clinical trial of exercise. Setting Tertiary academic medical center. Participants 121 patients with early to mid-stage PD. Methods Our functional performance outcomes included: 1) the Continuous Scale Functional Performance Test (CS-PFP; primary outcome); 2) the timed up and go (TUG) tests; and Section 2 (Activities of Daily Living) of the Unified Parkinson's Disease Rating Scale (UPDRS). Explanatory variables included measures of disease severity, motor function, cognitive function, balance and gait. Step-wise linear regression models were used to determine correlations between explanatory variables and outcome measures. Results In our regression models the CS-PFP significantly correlated with walking endurance (six minute walk; r2 = 0.12, p < .0001), turning ability (360 degree turn; r2 = .03, p = .002), attention (brief test of attention; r2 = .01, p = .03), overall cognitive status (Mini-mental State Examination; r2 = .01, p = .04) and bradykinesia (timed tapping; r2 = .02, p = .02). The TUG significantly correlated with walking speed (5 meter walk; r2 = 0.33, p <.0001), stride length (r2 = 0.25, p <.0001), turning ability (360 turn r2 = .05, p = .0003) and attention (r2 = .016, p = .03). Section 2 of the UPDRS was significantly correlated with endurance (r2 = .09, p < .0001), turning ability (r2 = .03, p = .001) and attention (r2 = .01, p = .03). Conclusions

  20. The Typical Developmental Trajectory of Social and Executive Functions in Late Adolescence and Early Adulthood

    ERIC Educational Resources Information Center

    Taylor, Sophie Jane; Barker, Lynne Ann; Heavey, Lisa; McHale, Sue

    2013-01-01

    Executive functions and social cognition develop through childhood into adolescence and early adulthood and are important for adaptive goal-oriented behavior (Apperly, Samson, & Humphreys, 2009; Blakemore & Choudhury, 2006). These functions are attributed to frontal networks known to undergo protracted maturation into early adulthood…

  1. The effects of very early mirror therapy on functional improvement of the upper extremity in acute stroke patients.

    PubMed

    Yeldan, Ipek; Huseyınsınoglu, Burcu Ersoz; Akıncı, Buket; Tarakcı, Ela; Baybas, Sevim; Ozdıncler, Arzu Razak

    2015-11-01

    [Purpose] The aim of the study was to evaluate the effects of a very early mirror therapy program on functional improvement of the upper extremity in acute stroke patients. [Subjects] Eight stroke patients who were treated in an acute neurology unit were included in the study. [Methods] The patients were assigned alternatively to either the mirror therapy group receiving mirror therapy and neurodevelopmental treatment or the neurodevelopmental treatment only group. The primary outcome measures were the upper extremity motor subscale of the Fugl-Meyer Assessment, Motricity Index upper extremity score, and the Stroke Upper Limb Capacity Scale. Somatosensory assessment with the Ayres Southern California Sensory Integration Test, and the Barthel Index were used as secondary outcome measures. [Results] No statistically significant improvements were found for any measures in either group after the treatment. In terms of minimally clinically important differences, there were improvements in Fugl-Meyer Assessment and Barthel Index in both mirror therapy and neurodevelopmental treatment groups. [Conclusion] The results of this pilot study revealed that very early mirror therapy has no additional effect on functional improvement of upper extremity function in acute stroke patients. Multicenter trials are needed to determine the results of early application of mirror therapy in stroke rehabilitation.

  2. The Relationship between Media Multitasking and Executive Function in Early Adolescents

    ERIC Educational Resources Information Center

    Baumgartner, Susanne E.; Weeda, Wouter D.; van der Heijden, Lisa L.; Huizinga, Mariëtte

    2014-01-01

    The increasing prevalence of media multitasking among adolescents is concerning because it may be negatively related to goal-directed behavior. This study investigated the relationship between media multitasking and executive function in 523 early adolescents (aged 11-15; 48% girls). The three central components of executive functions (i.e.,…

  3. White Matter Integrity Linked To Functional Impairments in Aging and Early Alzheimer’s Disease

    PubMed Central

    Kavcic, Voyko; Ni, Hongyan; Zhu, Tong; Zhong, Jianhui; Duffy, Charles J.

    2008-01-01

    Background Alzheimer’s disease (AD) is associated with changes in cerebral white matter (WM) but the functional significance of such findings is not yet established. We hypothesized that diffusion tensor imaging (DTI) might reveal links between regional WM changes and specific neuropsychologically and psychophysically defined impairments in early AD. Methods Older adult control subjects (OA, n=18) and mildly impaired AD patients (n=14) underwent neuropsychological and visual perceptual testing along with DTI of cerebral WM. DTI yielded factional anisotropy (FA) and mean diffusivity () maps for nine ROIs in three brain regions that were then compared to the performance measures. Results AD patients showed non-significant trends toward lower FAs in the posterior region’s callosal and sub-cortical ROIs. However, posterior callosal FA was significantly correlated with verbal fluency and figural memory impairments, whereas posterior subcortical FA was correlated with delayed verbal memory, figural memory, and optic flow perceptual impairments. Conclusions WM changes in early AD are concentrated in posterior cerebral areas with distributions that correspond to specific functional impairments. DTI can be used to assess regional pathology related to individual’s deficits in early AD. PMID:19012862

  4. The Relationship Between Midday Napping And Neurocognitive Function in Early Adolescents.

    PubMed

    Ji, Xiaopeng; Li, Junxin; Liu, Jianghong

    2018-02-01

    The impact of midday napping on neurocognitive function in adolescents has not been well established. This study aimed to investigate the relationship between self-reported midday-napping behaviors and neurocognitive function in early adolescents. The sample was comprised of 363 early adolescents (12.00 ± 0.38 years old) from Jintan, China. Midday napping, nighttime sleep duration, and sleep quality were measured by self-reported questionnaires. Neurocognitive function was measured by the Penn Computerized Neurocognitive Battery (accuracy and reaction times). Generalized linear regression was used to analyze the relationships. Sixty-four percent of our sample took more than 3 naps per week, and 70.11% reported nap durations of over 30 min. Participants with higher frequencies or longer durations of midday napping reported significantly better nighttime sleep quality (p < 0.05). Adjusted models showed that frequent nappers (5-7d/week) were significantly associated with heightened accuracy on tasks that measured sustained attention and nonverbal reasoning and faster reaction times on spatial memory compared with other frequency groups (ps < 0.05). For napping duration subgroups, early adolescents who took naps of any length were estimated to have faster reaction speeds on the sustained attention task compared with participants who never napped (ps < 0.05). However, only nappers with a moderate duration (31-60 min) tended to achieve both faster speeds (β = -38.28, p = 0.02) and better accuracy (β = 3.90, p = 0.04) on the sustained attention task. Our findings suggest that there is an association between habitual midday napping and neurocognitive function in early adolescents, especially in China, where midday napping is a cultural practice.

  5. A measure of early physical functioning (EPF) post-stroke.

    PubMed

    Finch, Lois E; Higgins, Johanne; Wood-Dauphinee, Sharon; Mayo, Nancy E

    2008-07-01

    To develop a comprehensive measure of Early Physical Functioning (EPF) post-stroke quantified through Rasch analysis and conceptualized using the International Classification of Functioning Disability and Health (ICF). An observational cohort study. A cohort of 262 subjects (mean age 71.6 (standard deviation 12.5) years) hospitalized post-acute stroke. Functional assessments were made within 3 days of stroke with items from valid and reliable indices commonly utilized to evaluate stroke survivors. Information on important variables was also collected. Principal component and Rasch analysis confirmed the factor structure, and dimensionality of the measure. Rasch analysis combined items across ICF components to develop the measure. Items were deleted iteratively, those retained fit the model and were related to the construct; reliability and validity were assessed. A 38-item unidimensional measure of the EPF met all Rasch model requirements. The item difficulty matched the person ability (mean person measure: -0.31; standard error 0.37 logits), reliability of the person-item-hierarchy was excellent at 0.97. Initial validity was adequate. The 38-item EPF measure was developed. It expands the range of assessment post acute stroke; it covers a broad spectrum of difficulty with good initial psychometric properties that, once revalidated, can assist in planning and evaluating early interventions.

  6. Early exposure to ultraviolet-B radiation decreases immune function later in life

    PubMed Central

    Ceccato, Emma; Cramp, Rebecca L.; Seebacher, Frank; Franklin, Craig E.

    2016-01-01

    Amphibians have declined dramatically worldwide. Many of these declines are occurring in areas where no obvious anthropogenic stressors are present. It is proposed that in these areas, environmental factors such as elevated solar ultraviolet-B (UV-B) radiation could be responsible. Ultraviolet-B levels have increased in many parts of the world as a consequence of the anthropogenic destruction of the ozone layer. Amphibian tadpoles are particularly sensitive to the damaging effects of UV-B radiation, with exposure disrupting growth and fitness in many species. Given that UV-B can disrupt immune function in other animals, we tested the hypothesis that early UV-B exposure suppresses the immune responses of amphibian tadpoles and subsequent juvenile frogs. We exposed Limnodynastes peronii tadpoles to sublethal levels of UV-B radiation for 6 weeks after hatching, then examined indices of immune function in both the tadpoles and the subsequent metamorphs. There was no significant effect of UV-B on tadpole leucocyte counts or on their response to an acute antigen (phytohaemagglutinin) challenge. However, early UV-B exposure resulted in a significant reduction in both metamorph leucocyte abundance and their response to an acute phytohaemagglutinin challenge. These data demonstrate that early UV-B exposure can have carry-over effects on later life-history traits even if the applied stressor has no immediately discernible effect. These findings have important implications for our understanding of the effects of UV-B exposure on amphibian health and susceptibility to diseases such as chytridiomycosis. PMID:27668081

  7. Early life social stress and resting state functional connectivity in postpartum rat anterior cingulate circuits.

    PubMed

    Nephew, Benjamin C; Febo, Marcelo; Huang, Wei; Colon-Perez, Luis M; Payne, Laurellee; Poirier, Guillaume L; Greene, Owen; King, Jean A

    2018-03-15

    Continued development and refinement of resting state functional connectivity (RSFC) fMRI techniques in both animal and clinical studies has enhanced our comprehension of the adverse effects of stress on psychiatric health. The objective of the current study was to assess both maternal behavior and resting state functional connectivity (RSFC) changes in these animals when they were dams caring for their own young. It was hypothesized that ECSS exposed dams would express depressed maternal care and exhibit similar (same networks), yet different specific changes in RSFC (different individual nuclei) than reported when they were adult females. We have developed an ethologically relevant transgenerational model of the role of chronic social stress (CSS) in the etiology of postpartum depression and anxiety. Initial fMRI investigation of the CSS model indicates that early life exposure to CSS (ECSS) induces long term changes in functional connectivity in adult nulliparous female F1 offspring. ECSS in F1 dams resulted in depressed maternal care specifically during early lactation, consistent with previous CSS studies, and induced changes in functional connectivity in regions associated with sensory processing, maternal and emotional responsiveness, memory, and the reward pathway, with robust changes in anterior cingulate circuits. The sample sizes for the fMRI groups were low, limiting statistical power. This behavioral and functional neuroanatomical foundation can now be used to enhance our understanding of the neural etiology of early life stress associated disorders and test preventative measures and treatments for stress related disorders. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Computer simulation on the cooperation of functional molecules during the early stages of evolution.

    PubMed

    Ma, Wentao; Hu, Jiming

    2012-01-01

    It is very likely that life began with some RNA (or RNA-like) molecules, self-replicating by base-pairing and exhibiting enzyme-like functions that favored the self-replication. Different functional molecules may have emerged by favoring their own self-replication at different aspects. Then, a direct route towards complexity/efficiency may have been through the coexistence/cooperation of these molecules. However, the likelihood of this route remains quite unclear, especially because the molecules would be competing for limited common resources. By computer simulation using a Monte-Carlo model (with "micro-resolution" at the level of nucleotides and membrane components), we show that the coexistence/cooperation of these molecules can occur naturally, both in a naked form and in a protocell form. The results of the computer simulation also lead to quite a few deductions concerning the environment and history in the scenario. First, a naked stage (with functional molecules catalyzing template-replication and metabolism) may have occurred early in evolution but required high concentration and limited dispersal of the system (e.g., on some mineral surface); the emergence of protocells enabled a "habitat-shift" into bulk water. Second, the protocell stage started with a substage of "pseudo-protocells", with functional molecules catalyzing template-replication and metabolism, but still missing the function involved in the synthesis of membrane components, the emergence of which would lead to a subsequent "true-protocell" substage. Third, the initial unstable membrane, composed of prebiotically available fatty acids, should have been superseded quite early by a more stable membrane (e.g., composed of phospholipids, like modern cells). Additionally, the membrane-takeover probably occurred at the transition of the two substages of the protocells. The scenario described in the present study should correspond to an episode in early evolution, after the emergence of single

  9. Cognitive Enhancement Therapy Improves Resting-State Functional Connectivity in Early Course Schizophrenia

    PubMed Central

    Eack, Shaun M.; Newhill, Christina E.; Keshavan, Matcheri S.

    2016-01-01

    Objective Cognitive remediation is emerging as an effective psychosocial intervention for addressing untreated cognitive and functional impairments in persons with schizophrenia, and might achieve its benefits through neuroplastic changes in brain connectivity. This study seeks to examine the effects of cognitive enhancement therapy (CET) on fronto-temporal brain connectivity in a randomized controlled trial with individuals in the early course of schizophrenia. Method Stabilized, early course outpatients with schizophrenia or schizoaffective disorder (N = 41) were randomly assigned to CET (n = 25) or an active enriched supportive therapy (EST) control (n = 16) and treated for 2 years. Functional MRI data were collected annually, and pseudo resting-state functional connectivity analysis was used to examine differential changes in fronto-temporal connectivity between those treated with CET compared with EST. Results Individuals receiving CET evidenced significantly less functional connectivity loss between the resting-state network and the left dorsolateral prefrontal cortex as well as significantly increased connectivity with the right insular cortex compared to EST (all corrected p < .01). These neural networks are involved in emotion processing and problem-solving. Increased connectivity with the right insula significantly mediated CET effects on improved emotion perception (z′ = −1.96, p = .021), and increased connectivity with the left dorsolateral prefrontal cortex mediated CET-related improvements in emotion regulation (z′ = −1.71, p = .052). Conclusions These findings provide preliminary evidence that CET, a psychosocial cognitive remediation intervention, may enhance connectivity between frontal and temporal brain regions implicated in problem-solving and emotion processing in service of cognitive enhancement in schizophrenia. PMID:27713804

  10. Elevated pretransplantation soluble CD30 is associated with decreased early allograft function after human lung transplantation.

    PubMed

    Shah, Ashish S; Leffell, M Sue; Lucas, Donna; Zachary, Andrea A

    2009-02-01

    Early allograft function after lung transplantation is variable. Clinical criteria have limited predictive value for early graft function. Recipient immunologic state before LTx may affect early lung function. We investigated the association between pretransplantation soluble CD30 (sCD30), a marker of Th2-type T-cell activation, and early clinical parameters of allograft function. Between September 2002 and January 2007, a total of 80 transplantations were performed at Johns Hopkins Hospital. Of the patients, 43 had a pretransplantation sCD30 level determined. Pre- and postoperative patient variables were collected, and patients were stratified into two groups: sCD30 <20 (low sCD30) and >20 (high sCD30). High sCD30 (n = 26) and low sCD30 (n = 17) groups were similar in age, gender, and ischemia time. In the high sCD30 group, a higher percentage of patients had pulmonary fibrosis and a lower percentage had emphysema. Oxygenation at 48 hours was significantly worse in the high sCD30 group as compared with the low sCD30 (p = 0.003). Moreover, prolonged intubation and 90-day mortality were greater in the high sCD30 group. This represents the first report of the use of sCD30 as a marker for early allograft function in human lung transplanation. Increased pretransplantation recipient sCD30 appears to be associated with decreased early post-transplantation gas exchange, prolonged intubation, and early mortality.

  11. Auto-inhibitory regulation of angiotensin II functionality in hamster aorta during the early phases of dyslipidemia.

    PubMed

    Pereira, Priscila Cristina; Pernomian, Larissa; Côco, Hariane; Gomes, Mayara Santos; Franco, João José; Marchi, Kátia Colombo; Hipólito, Ulisses Vilela; Uyemura, Sergio Akira; Tirapelli, Carlos Renato; de Oliveira, Ana Maria

    2016-06-15

    Emerging data point the crosstalk between dyslipidemia and renin-angiotensin system (RAS). Advanced dyslipidemia is described to induce RAS activation in the vasculature. However, the interplay between early dyslipidemia and the RAS remains unexplored. Knowing that hamsters and humans have a similar lipid profile, we investigated the effects of early and advanced dyslipidemia on angiotensin II-induced contraction. Cumulative concentration-response curves for angiotensin II (1.0pmol/l to 1.0µmol/l) were obtained in the hamster thoracic aorta. We also investigated the modulatory action of NAD(P)H oxidase on angiotensin II-induced contraction using ML171 (Nox-1 inhibitor, 0.5µmol/l) and VAS2870 (Nox-4 inhibitor, 5µmol/l). Early dyslipidemia was detected in hamsters treated with a cholesterol-rich diet for 15 days. Early dyslipidemia decreased the contraction induced by angiotensin II and the concentration of Nox-4-derived hydrogen peroxide. Advanced dyslipidemia, observed in hamsters treated with cholesterol-rich diet for 30 days, restored the contractile response induced by angiotensin II by compensatory mechanism that involves Nox-4-mediated oxidative stress. The hyporresponsiveness to angiotensin II may be an auto-inhibitory regulation of the angiotensinergic function during early dyslipidemia in an attempt to reduce the effects of the upregulation of the vascular RAS during the advanced stages of atherogenesis. The recovery of vascular angiotensin II functionality during the advanced phases of dyslipidemia is the result of the upregulation of redox-pro-inflammatory pathway that might be most likely involved in atherogenesis progression rather than in the recovery of vascular function. Taken together, our findings show the early phase of dyslipidemia may be the most favorable moment for effective atheroprotective therapeutic interventions. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Hypothalamic-pituitary-adrenal axis genetic variation and early stress moderates amygdala function.

    PubMed

    Di Iorio, Christina R; Carey, Caitlin E; Michalski, Lindsay J; Corral-Frias, Nadia S; Conley, Emily Drabant; Hariri, Ahmad R; Bogdan, Ryan

    2017-06-01

    Early life stress may precipitate psychopathology, at least in part, by influencing amygdala function. Converging evidence across species suggests that links between childhood stress and amygdala function may be dependent upon hypothalamic-pituitary-adrenal (HPA) axis function. Using data from college-attending non-Hispanic European-Americans (n=308) who completed the Duke Neurogenetics Study, we examined whether early life stress (ELS) and HPA axis genetic variation interact to predict threat-related amygdala function as well as psychopathology symptoms. A biologically-informed multilocus profile score (BIMPS) captured HPA axis genetic variation (FKBP5 rs1360780, CRHR1 rs110402; NR3C2 rs5522/rs4635799) previously associated with its function (higher BIMPS are reflective of higher HPA axis activity). BOLD fMRI data were acquired while participants completed an emotional face matching task. ELS and depression and anxiety symptoms were measured using the childhood trauma questionnaire and the mood and anxiety symptom questionnaire, respectively. The interaction between HPA axis BIMPS and ELS was associated with right amygdala reactivity to threat-related stimuli, after accounting for multiple testing (empirical-p=0.016). Among individuals with higher BIMPS (i.e., the upper 21.4%), ELS was positively coupled with threat-related amygdala reactivity, which was absent among those with average or low BIMPS. Further, higher BIMPS were associated with greater self-reported anxious arousal, though there was no evidence that amygdala function mediated this relationship. Polygenic variation linked to HPA axis function may moderate the effects of early life stress on threat-related amygdala function and confer risk for anxiety symptomatology. However, what, if any, neural mechanisms may mediate the relationship between HPA axis BIMPS and anxiety symptomatology remains unclear. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Early meteorological results from the viking 2 lander.

    PubMed

    Hess, S L; Henry, R M; Leovy, C B; Mitchell, J L; Ryan, J A; Tillman, J E

    1976-12-11

    Early results from the meteorological instruments on the Viking 2 lander are presented. As on lander 1, the daily patterns of temperature, wind, and pressure have been highly repetitive during the early summer period. The average daily maximum temperature was 241 degrees K and the diurnal minimum was 191 degrees K. The wind has a vector mean of 0.7 meter per second from the southeast with a diurnal amplitude of 3 meters per second. Pressure exhibits both diurnal and semidiurnal oscillations, although of substantially smaller amplitude than those of lander 1. Departures from the repetitive diurnal patterns begin to appear on sol 37.

  14. Early Predictors of Global Functional Outcome After Traumatic Spinal Cord Injury: A Systematic Review.

    PubMed

    Richard-Denis, Andréane; Beauséjour, Marie; Thompson, Cynthia; Nguyen, Bich-Han; Mac-Thiong, Jean-Marc

    2018-04-17

    Accurately predicting functional recovery is an asset for all clinicians and decision makers involved in the care of patients with acute traumatic spinal cord injury (TSCI). Unfortunately, there is a lack of information on the relative importance of significant predictors of global functional outcome. There is also a need for identifying functional predictors that can be timely optimized by the medical and rehabilitation teams throughout the hospitalizations phases. The main objective of this work was to systematically review and rate early factors that are consistently and independently associated with global functional outcome in individuals with TSCI. A literature search using MEDLINE, EMBASE, and Cochrane databases from January 1, 1970 to April 1, 2017 was performed. Two authors independently reviewed the titles and abstracts yielded by this literature search and subsequently selected studies to be included based on predetermined eligibility criteria. Disagreements were resolved by a consensus-based discussion, and if not, by an external reviewer. Data were extracted by three independent reviewers using a standardized table. The quality of evidence of the individual studies was assessed based on the Oxford Center for Evidence-Based Medicine modified by Wright and colleagues (2000) as well as the National Institutes of Health (2014). Fifteen articles identifying early clinical predictors of functional outcome using multiple regression analyses were included in this systematic review. Based on the compiled data, this review proposes a rating of early factors associated to global functional outcome according to their importance and their potential to be modified by the medical/rehabilitation team throughout the early phases of hospitalization. It also proposes a new conceptual framework that illustrates the impact of specific categories of factors and their interaction with each other. Ultimately, this review aims to guide clinicians and researchers in improving

  15. Early Executive Function at Age Two Predicts Emergent Mathematics and Literacy at Age Five

    PubMed Central

    Mulder, Hanna; Verhagen, Josje; Van der Ven, Sanne H. G.; Slot, Pauline L.; Leseman, Paul P. M.

    2017-01-01

    Previous work has shown that individual differences in executive function (EF) are predictive of academic skills in preschoolers, kindergartners, and older children. Across studies, EF is a stronger predictor of emergent mathematics than literacy. However, research on EF in children below age three is scarce, and it is currently unknown whether EF, as assessed in toddlerhood, predicts emergent academic skills a few years later. This longitudinal study investigates whether early EF, assessed at two years, predicts (emergent) academic skills, at five years. It examines, furthermore, whether early EF is a significantly stronger predictor of emergent mathematics than of emergent literacy, as has been found in previous work on older children. A sample of 552 children was assessed on various EF and EF-precursor tasks at two years. At age five, these children performed several emergent mathematics and literacy tasks. Structural Equation Modeling was used to investigate the relationships between early EF and academic skills, modeled as latent factors. Results showed that early EF at age two was a significant and relatively strong predictor of both emergent mathematics and literacy at age five, after controlling for receptive vocabulary, parental education, and home language. Predictive relations were significantly stronger for mathematics than literacy, but only when a verbal short-term memory measure was left out as an indicator to the latent early EF construct. These findings show that individual differences in emergent academic skills just prior to entry into the formal education system can be traced back to individual differences in early EF in toddlerhood. In addition, these results highlight the importance of task selection when assessing early EF as a predictor of later outcomes, and call for further studies to elucidate the mechanisms through which individual differences in early EF and precursors to EF come about. PMID:29075209

  16. Early Executive Function at Age Two Predicts Emergent Mathematics and Literacy at Age Five.

    PubMed

    Mulder, Hanna; Verhagen, Josje; Van der Ven, Sanne H G; Slot, Pauline L; Leseman, Paul P M

    2017-01-01

    Previous work has shown that individual differences in executive function (EF) are predictive of academic skills in preschoolers, kindergartners, and older children. Across studies, EF is a stronger predictor of emergent mathematics than literacy. However, research on EF in children below age three is scarce, and it is currently unknown whether EF, as assessed in toddlerhood, predicts emergent academic skills a few years later. This longitudinal study investigates whether early EF, assessed at two years, predicts (emergent) academic skills, at five years. It examines, furthermore, whether early EF is a significantly stronger predictor of emergent mathematics than of emergent literacy, as has been found in previous work on older children. A sample of 552 children was assessed on various EF and EF-precursor tasks at two years. At age five, these children performed several emergent mathematics and literacy tasks. Structural Equation Modeling was used to investigate the relationships between early EF and academic skills, modeled as latent factors. Results showed that early EF at age two was a significant and relatively strong predictor of both emergent mathematics and literacy at age five, after controlling for receptive vocabulary, parental education, and home language. Predictive relations were significantly stronger for mathematics than literacy, but only when a verbal short-term memory measure was left out as an indicator to the latent early EF construct. These findings show that individual differences in emergent academic skills just prior to entry into the formal education system can be traced back to individual differences in early EF in toddlerhood. In addition, these results highlight the importance of task selection when assessing early EF as a predictor of later outcomes, and call for further studies to elucidate the mechanisms through which individual differences in early EF and precursors to EF come about.

  17. Impact cratering calculations. Part 1: Early time results

    NASA Technical Reports Server (NTRS)

    Thomsen, J. M.; Sauer, F. N.; Austin, M. G.; Ruhl, S. F.; Shultz, P. H.; Orphal, D. L.

    1979-01-01

    Early time two dimensional finite difference calculations of laboratory scale hypervelocity impact of 0.3 g spherical 2024 aluminum projectiles into homogeneous plasticene clay targets were performed. Analysis of resulting material motions showed that energy and momentum were coupled quickly from the aluminum projectile to the target material. In the process of coupling, some of the plasticene clay target was vaporized while the projectile become severely deformed. The velocity flow field developed within the target was shown to have features similar to those found in calculations of near surface explosion cratering. Specific application of Maxwell's analytic Z-Model showed that this model can be used to describe the early time flow fields resulting from the impact cratering calculations as well, provided the flow field centers are located beneath the target surface and most of the projectile momentum is dissipated before the model is applied.

  18. PTT functional recovery in early stage II PTTD after tendon balancing and calcaneal lengthening osteotomy.

    PubMed

    Brilhault, Jean; Noël, Vincent

    2012-10-01

    The decision to offer surgery for Stage II posterior tibial tendon deficiency (PTTD) is a difficult one since orthotic treatment has been documented to be a viable alternative to surgery at this stage. Taking this into consideration we limited our treatment to bony realignment by a lengthening calcaneus Evans osteotomy and tendon balancing. The goal of the study was to clinically evaluate PTT functional recovery with this procedure. The patient population included 17 feet in 13 patients. Inclusion was limited to early Stage II PTTD flatfeet with grossly intact but deficient PTT. Deficiency was assessed by the lack of hindfoot inversion during single heel rise test. The surgical procedure included an Evans calcaneal opening wedge osteotomy with triceps surae and peroneus brevis tendon lengthening. PTT function at follow up was evaluated by an independent examiner. Evaluation was performed at an average of 4 (range, 2 to 6.3) years. One case presented postoperative subtalar pain that required subtalar fusion. Every foot could perform a single heel rise with 13 feet having active inversion of the hindfoot during elevation. The results of this study provide evidence of PTT functional recovery without augmentation in early Stage II. It challenges our understanding of early Stage II PTTD as well as the surgical guidelines recommending PTT augmentation at this specific stage.

  19. Social Environmental Moderators of Long-term Functional Outcomes of Early Childhood Brain Injury

    PubMed Central

    Wade, Shari L.; Zhang, Nanhua; Yeates, Keith Owen; Stancin, Terry; Taylor, H. Gerry

    2017-01-01

    IMPORTANCE Pediatric traumatic brain injury (TBI) contributes to impairments in behavior and academic performance. However, the long-term effects of early childhood TBI on functioning across settings remain poorly understood. OBJECTIVE To examine the long-term functional outcomes of early childhood TBI relative to early childhood orthopedic injuries (OIs). We also examine the moderating role of the social environment as defined by parent report and observational measures of family functioning, parenting practices, and home environment. DESIGN, SETTING, AND PARTICIPANTS A prospective, longitudinal, observational cohort study conducted at each child’s home, school, and hospital, including 3 children’s hospitals and 1 general hospital in the Midwest. Patients were enrolled in the initial study between January 2003 and October 2006. Follow-ups were completed between January 2010 and April 2015. Fifty-eight children who sustained a TBI (67%of original enrolled cohort) and 72 children who sustained an OI (61% of the original enrolled cohort) were prospectively followed up from shortly after injury (between the ages of 3 and 7 years at enrollment) to an average of 6.7 years after injury, with assessments occurring at multiple points. MAIN OUTCOMES AND MEASURES Long-term functional outcomes in everyday settings, as assessed through the Child and Adolescent Functional Assessment Scale (CAFAS). RESULTS Of the 130 children included, the median age for those with OIs was 11.72 years and 11.97, 12.21, and 11.72 years for those with complicated mild, moderate, and severe TBIs, respectively. Children with moderate and severe TBI were rated as having more functional impairments in multiple domains than those with OIs (P < .05). Children with complicated mild TBI had greater impairments in school (odds ratio = 2.93; 95%CI = 1.10–7.82) and with thinking (odds ratio = 15.72; 95%CI = 3.31–74.73) than those with OIs. Functional impairments in children with TBI were more

  20. Peritransplant Soluble CD30 as a Risk Factor for Slow Kidney Allograft Function, Early Acute Rejection, Worse Long-Term Allograft Function, and Patients' Survival.

    PubMed

    Trailin, Andriy V; Ostapenko, Tetyana I; Nykonenko, Tamara N; Nesterenko, Svitlana N; Nykonenko, Olexandr S

    2017-01-01

    We aimed to determine whether serum soluble CD30 (sCD30) could identify recipients at high risk for unfavorable early and late kidney transplant outcomes. Serum sCD30 was measured on the day of kidney transplantation and on the 4th day posttransplant. We assessed the value of these measurements in predicting delayed graft function, slow graft function (SGF), acute rejection (AR), pyelonephritis, decline of allograft function after 6 months, and graft and patient survival during 5 years of follow-up in 45 recipients. We found the association between low pretransplant serum levels of sCD30 and SGF. The absence of significant decrease of sCD30 on the 4th day posttransplant was characteristic for SGF, early AR (the 8th day-6 months), late AR (>6 months), and early pyelonephritis (the 8th day-2 months). Lower pretransplant and posttransplant sCD30 predicted worse allograft function at 6 months and 2 years, respectively. Higher pretransplant sCD30 was associated with higher frequency of early AR, and worse patients' survival, but only in the recipients of deceased-donor graft. Pretransplant sCD30 also allowed to differentiate patients with early pyelonephritis and early AR. Peritransplant sCD30 is useful in identifying patients at risk for unfavorable early and late transplant outcomes.

  1. The Development of Executive Function and Language Skills in the Early School Years

    ERIC Educational Resources Information Center

    Gooch, Debbie; Thompson, Paul; Nash, Hannah M.; Snowling, Margaret J.; Hulme, Charles

    2016-01-01

    Background: The developmental relationships between executive functions (EF) and early language skills are unclear. This study explores the longitudinal relationships between children's early EF and language skills in a sample of children with a wide range of language abilities including children at risk of dyslexia. In addition, we investigated…

  2. Does early communication mediate the relationship between motor ability and social function in children with cerebral palsy?

    PubMed

    Lipscombe, Belinda; Boyd, Roslyn N; Coleman, Andrea; Fahey, Michael; Rawicki, Barry; Whittingham, Koa

    2016-01-01

    Children diagnosed with neurodevelopmental conditions such as cerebral palsy (CP) are at risk of experiencing restrictions in social activities negatively impacting their subsequent social functioning. Research has identified motor and communication ability as being unique determinants of social function capabilities in children with CP, to date, no research has investigated whether communication is a mediator of the relationship between motor ability and social functioning. To investigate whether early communication ability at 24 months corrected age (ca.) mediates the relationship between early motor ability at 24 months ca. and later social development at 60 months ca. in a cohort of children diagnosed with cerebral palsy (CP). A cohort of 71 children (43 male) diagnosed with CP (GMFCS I=24, 33.8%, II=9, 12.7%, III=12, 16.9%, IV=10, 14.1%, V=16, 22.5%) were assessed at 24 and 60 months ca. Assessments included the Gross Motor Function Measure (GMFM), the Communication and Symbolic Behaviour Scales-Developmental Profile (CSBS-DP) Infant-Toddler Checklist and the Paediatric Evaluation of Disability Inventory (PEDI). A mediation model was examined using bootstrapping. Early communication skills mediated the relationship between early motor abilities and later social functioning, b=0.24 (95% CI=0.08-0.43 and the mediation model was significant, F (2, 68)=32.77, p<0.001, R(2)=0.49. Early communication ability partially mediates the relationship between early motor ability and later social function in children with CP. This demonstrates the important role of early communication in ongoing social development. Early identification of communication delay and enriched language exposure is crucial in this population. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Two functions of early language experience.

    PubMed

    Arshavsky, Yuri I

    2009-05-01

    The unique human ability of linguistic communication, defined as the ability to produce a practically infinite number of meaningful messages using a finite number of lexical items, is determined by an array of "linguistic" genes, which are expressed in neurons forming domain-specific linguistic centers in the brain. In this review, I discuss the idea that infants' early language experience performs two complementary functions. In addition to allowing infants to assimilate the words and grammar rules of their mother language, early language experience initiates genetic programs underlying language production and comprehension. This hypothesis explains many puzzling characteristics of language acquisition, such as the existence of a critical period for acquiring the first language and the absence of a critical period for the acquisition of additional language(s), a similar timetable for language acquisition in children belonging to families of different social and cultural status, the strikingly similar timetables in the acquisition of oral and sign languages, and the surprisingly small correlation between individuals' final linguistic competence and the intensity of their training. Based on the studies of microcephalic individuals, I argue that genetic factors determine not only the number of neurons and organization of interneural connections within linguistic centers, but also the putative internal properties of neurons that are not limited to their electrophysiological and synaptic properties.

  4. Predicting the Development of Interrogative Forms and Functions in Early Years: A Corpus-Based Study of Mandarin-Speaking Young Children

    ERIC Educational Resources Information Center

    Li, Hui; Jing, Mengguo; Wong, Eileen Chin Mei

    2017-01-01

    This study examined the development of and possible predictors of interrogative forms and functions in early childhood Mandarin. All the interrogatives drawn from the Early Child Mandarin Corpus (168 children 2;6, 3;6, 4;6, and 5;6) were analyzed. The main results indicated that (i) there were significant age effects in interrogative forms and…

  5. Form, function and environments of the early angiosperms: merging extant phylogeny and ecophysiology with fossils.

    PubMed

    Feild, Taylor S; Arens, Nan Crystal

    2005-05-01

    The flowering plants--angiosperms--appeared during the Early Cretaceous period and within 10-30 Myr dominated the species composition of many floras worldwide. Emerging insights into the phylogenetics of development and discoveries of early angiosperm fossils are shedding increased light on the patterns and processes of early angiosperm evolution. However, we also need to integrate ecology, in particular how early angiosperms established a roothold in pre-existing Mesozoic plant communities. These events were critical in guiding subsequent waves of angiosperm diversification during the Aptian-Albian. Previous pictures of the early flowering plant ecology have been diverse, ranging from large tropical rainforest trees, weedy drought-adapted and colonizing shrubs, disturbance- and sun-loving rhizomatous herbs, and, more recently, aquatic herbs; however, none of these images were tethered to a robust hypothesis of angiosperm phylogeny. Here, we synthesize our current understanding of early angiosperm ecology, focusing on patterns of functional ecology, by merging recent molecular phylogenetic studies and functional studies on extant 'basal angiosperms' with the picture of early angiosperm evolution drawn by the fossil record.

  6. Functional and Radiographic Outcomes Following Growth-Sparing Management of Early-Onset Scoliosis.

    PubMed

    Johnston, Charles E; Tran, Dong-Phuong; McClung, Anna

    2017-06-21

    In this study, we sought to evaluate radiographic, functional, and quality-of-life outcomes of patients who have completed growth-sparing management of early-onset scoliosis. This prospective study involved patients with early-onset scoliosis who underwent growth-sparing treatment and either "final" fusion or observation for ≥2 years since the last lengthening procedure. Demographics, radiographic parameters, pulmonary function test (PFT) values, and scores of patient-reported assessments (Early-Onset Scoliosis Questionnaire [EOSQ] and Scoliosis Research Society [SRS]-30) were obtained. At the most recent follow-up, patients performed 2 additional functional outcome tests: step-activity monitoring and a treadmill exercise-tolerance test. Twelve patients were evaluated as "graduates" of growth-sparing management of early-onset scoliosis (mean of 37 months since the most recent surgery). The major scoliosis curve measurement averaged 88° before treatment and 47° at the most recent follow-up. T1-S1 height increased from a mean of 22.3 cm to 34.7 cm and T1-T12 height, from 13.3 to 22.3 cm. At the most recent follow-up, the mean forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) as a percentage of the predicted volume were 52.1% and 55.3%, respectively, and were essentially unchanged from the earliest PFT that patients could perform (FEV1 = 53.8% of predicted and FVC = 53.5% of predicted). There was no difference between graduates and controls with respect to activity time or total steps in step-activity monitoring, and in the exercise-tolerance test, graduates walked at the same speed but at a higher heart rate and at a significantly higher (p <0.001) VO2 cost (rate of oxygen consumed per distance traveled). The EOSQ mean score was 102.2 of a possible 120 points, and the SRS mean score was 4.1 of a possible 5 points. A realistic long-term goal for the management of early-onset scoliosis appears to be spine elongation and maintenance of

  7. Cognitive function in early clinical phase huntington disease after rivastigmine treatment.

    PubMed

    Sešok, Sanja; Bolle, Nika; Kobal, Jan; Bucik, Valentin; Vodušek, David B

    2014-09-01

    In Huntington disease (HD) patients receiving rivastigmine treatment improvement of behavioral symptoms and of cognitive function (assessed with screening diagnostic instruments) has been reported. The aim of the present study was to verify such improvement in cognitive function by cognitive function assessment with a detailed neuropsychological battery covering all relevant cognitive systems expected to be impaired in early phase HD. Eighteen (18) HD patients entered the study and were randomly allocated to the rivastigmine and placebo group. All subjects underwent neuropsychological assessment at baseline. Follow-up neuropsychological assessment was applied after 6 months of rivastigmine or placebo treatment. Eighteen (18) healthy controls entered the study to control for practice effect and underwent neuropsychological assessment at baseline and after 6 months, without treatment. The neuropsychological battery consisted of assessment tools that are sensitive to cognitive impairment seen in early phase HD: CTMT, SDMT, Stroop (attention and information control), RFFT, TOL, Verbal fluency (executive functioning), CVLT-II, RCFT (learning and memory). Effect of rivastigmine and possible effect of practice was assessed using the mixed ANOVA model. No statistically significant effect of rivastigmine treatment on cognitive function in HD patients was detected. There was no evidence for practice or placebo effect. Detailed neuropsychological assessment did not confirm previously reported effect of rivastigmine treatment on cognitive function in HD patients. The limitations of our study are, in particular, small sample size and the lack of a single measure of relevant cognitive functioning in HD patients. Instead of focusing solely on statistical significance, a clinical relevance study is proposed to clarify the issue of rivastigmine effects in HD.

  8. Functional Connectivity of the Amygdala in Early-Childhood-Onset Depression

    ERIC Educational Resources Information Center

    Luking, Katherine R.; Repovs, Grega; Belden, Andy C.; Gaffrey, Michael S.; Botteron, Kelly N.; Luby, Joan L.; Barch, Deanna M.

    2011-01-01

    Objective: Adult major depressive disorder (MDD) is associated with reduced cortico-limbic functional connectivity thought to indicate decreased top-down control of emotion. However, it is unclear whether such connectivity alterations are also present in early-childhood-onset MDD. Method: A total of 51 children 7 through 11 years of age who had…

  9. Early life stress and physical and psychosocial functioning in late adulthood.

    PubMed

    Alastalo, Hanna; von Bonsdorff, Mikaela B; Räikkönen, Katri; Pesonen, Anu-Katriina; Osmond, Clive; Barker, David J P; Heinonen, Kati; Kajantie, Eero; Eriksson, Johan G

    2013-01-01

    Severe stress experienced in early life may have long-term effects on adult physiological and psychological health and well-being. We studied physical and psychosocial functioning in late adulthood in subjects separated temporarily from their parents in childhood during World War II. The 1803 participants belong to the Helsinki Birth Cohort Study, born 1934-44. Of them, 267 (14.8%) had been evacuated abroad in childhood during WWII and the remaining subjects served as controls. Physical and psychosocial functioning was assessed with the Short Form 36 scale (SF-36) between 2001 and 2004. A test for trends was based on linear regression. All analyses were adjusted for age at clinical examination, social class in childhood and adulthood, smoking, alcohol intake, physical activity, body mass index, cardiovascular disease and diabetes. Physical functioning in late adulthood was lower among the separated men compared to non-separated men (b = -0.40, 95% confidence interval [95% CI]: -0.71 to -0.08). Those men separated in school age (>7 years) and who were separated for a duration over 2 years had the highest risk for lower physical functioning (b = -0.89, 95% CI: -1.58 to -0.20) and (b = -0.65, 95% CI: -1.25 to -0.05), respectively). Men separated for a duration over 2 years also had lower psychosocial functioning (b = -0.70, 95% CI: -1.35 to -0.06). These differences in physical and psychosocial functioning were not observed among women. Early life stress may increase the risk for impaired physical functioning in late adulthood among men. Timing and duration of the separation influenced the physical and psychosocial functioning in late adulthood.

  10. Accessing Autonomic Function Can Early Screen Metabolic Syndrome

    PubMed Central

    Dai, Meng; Li, Mian; Yang, Zhi; Xu, Min; Xu, Yu; Lu, Jieli; Chen, Yuhong; Liu, Jianmin; Ning, Guang; Bi, Yufang

    2012-01-01

    Background Clinical diagnosis of the metabolic syndrome is time-consuming and invasive. Convenient instruments that do not require laboratory or physical investigation would be useful in early screening individuals at high risk of metabolic syndrome. Examination of the autonomic function can be taken as a directly reference and screening indicator for predicting metabolic syndrome. Methodology and Principal Findings The EZSCAN test, as an efficient and noninvasive technology, can access autonomic function through measuring electrochemical skin conductance. In this study, we used EZSCAN value to evaluate autonomic function and to detect metabolic syndrome in 5,887 participants aged 40 years or older. The EZSCAN test diagnostic accuracy was analyzed by receiver operating characteristic curves. Among the 5,815 participants in the final analysis, 2,541 were diagnosed as metabolic syndrome and the overall prevalence was 43.7%. Prevalence of the metabolic syndrome increased with the elevated EZSCAN risk level (p for trend <0.0001). Moreover, EZSCAN value was associated with an increase in the number of metabolic syndrome components (p for trend <0.0001). Compared with the no risk group (EZSCAN value 0–24), participants at the high risk group (EZSCAN value: 50–100) had a 2.35 fold increased risk of prevalent metabolic syndrome after the multiple adjustments. The area under the curve of the EZSCAN test was 0.62 (95% confidence interval [CI], 0.61–0.64) for predicting metabolic syndrome. The optimal operating point for the EZSCAN value to detect a high risk of prevalent metabolic syndrome was 30 in this study, while the sensitivity and specificity were 71.2% and 46.7%, respectively. Conclusions and Significance In conclusion, although less sensitive and accurate when compared with the clinical definition of metabolic syndrome, we found that the EZSCAN test is a good and simple screening technique for early predicting metabolic syndrome. PMID:22916265

  11. Predicting the development of interrogative forms and functions in early years: a corpus-based study of Mandarin-speaking young children.

    PubMed

    Li, Hui; Jing, Mengguo; Wong, Eileen Chin Mei

    2017-01-01

    This study examined the development of and possible predictors of interrogative forms and functions in early childhood Mandarin. All the interrogatives drawn from the Early Child Mandarin Corpus (168 children 2;6, 3;6, 4;6, and 5;6) were analyzed. The main results indicated that (i) there were significant age effects in interrogative forms and functions, with the periods between the ages of 3;6 and 4;6 and between the ages of 2;6 and 3;6 being critical in the early acquisition of interrogative forms and functions, respectively; (ii) the form-function preference was verified, with wh-questions being primarily used to seek information (RfI), and intonation/echo and rhetorical questions being used to request action (RfA); (iii) more than half (59·5%) of the Mandarin interrogatives were used for RfI, whereas only 38·9% of them were used for RfA; and (iv) age, TV viewing time, and parent-child conversation time were the significant predictors of interrogative development.

  12. Early functional outcome of two different orthotic concepts in ankle sprains: a randomized controlled trial.

    PubMed

    Best, Raymond; Böhle, Caroline; Schiffer, Thorsten; Petersen, Wolf; Ellermann, Andree; Brueggemann, Gert Peter; Liebau, Christian

    2015-07-01

    Purpose of the study was the evaluation of the early functional outcome of patients with an acute ankle sprain treated either with a semirigid, variable, phase-adapted modular ankle orthosis or an invariable orthotic reference device. Forty-seven patients with acute ankle sprain grade II or more were included. In addition, 77 healthy controls as a reference were investigated. The injured subjects were treated with one of the two devices by random for 6 weeks. Ankle scores (FAOS, AOFAS) were taken at baseline after injury, 1 and 3 months after injury. Functional performance tests (balance platform, zig zag run, shuttle run, vertical drop jump) were performed at 1 and 3 months after injury. No significant score differences could be found between the two intervention groups except for achieving a preinjury activity level after 3 months only in the modular orthosis group. Postural functional performances (balance test) also showed no significant differences whereas the results of the agility tests revealed small but significant better results in the modular orthosis group in comparison to the invariable orthosis group. Cohen's effect sizes were high. Differences between the two intervention groups were marginal and very small but significant and--regarding Cohen's effect sizes--effective. Especially relating to functional performance, this might be a careful indication that a more effective strategy for promoting a protected, rapid recovery to physical activity after ankle sprains might be achieved by applying a phase-adapted ankle orthosis. Especially in athletic patients, phase-adapted orthosis should be further investigated and considered to ensure fully protected ligament healing as well as to regain early functional recovery.

  13. [Cognitive functions of school children with normal IQ and histories of severe and early malnutrition].

    PubMed

    Perales, C G; Heresi, E; Pizarro, F; Colombo, M

    1996-12-01

    This is a cross section study designed to evaluate the long lasting consequences of early and severe undernutrition on the development of basic cognitive functions. Attention, memory and problem-solving capacity were assessed in a group of 16 school children, who were severely undernourished during the first two years of age. They were compared with a group of 16 children with a normal growth. All subjects, age 8 to 10, had a normal intellectual coefficient and they belonged to the me same socioeconomical level. Memory was measured with a modified version of subtest of digits from WISC; attention was evaluated with a modified version of the Continuous Performance Task and problem-solving was measured with the Anstey Domino Test. A personal computer was used to assess the cognitive functions. The children who were undernourished during infancy presented lower scores in memory (number of the digits) and in problems solving (number of correct answers). They also had a worse performance than the control group in the same response time, when attention was evaluated. These results suggest that early severe undernutrition had deletereous effects on basic cognitive functions.

  14. Early exercise in critically ill patients enhances short-term functional recovery.

    PubMed

    Burtin, Chris; Clerckx, Beatrix; Robbeets, Christophe; Ferdinande, Patrick; Langer, Daniel; Troosters, Thierry; Hermans, Greet; Decramer, Marc; Gosselink, Rik

    2009-09-01

    : To investigate whether a daily exercise session, using a bedside cycle ergometer, is a safe and effective intervention in preventing or attenuating the decrease in functional exercise capacity, functional status, and quadriceps force that is associated with prolonged intensive care unit stay. A prolonged stay in the intensive care unit is associated with muscle dysfunction, which may contribute to an impaired functional status up to 1 yr after hospital discharge. No evidence is available concerning the effectiveness of an early exercise training intervention to prevent these detrimental complications. : Randomized controlled trial. : Medical and surgical intensive care unit at University Hospital Gasthuisberg. : Ninety critically ill patients were included as soon as their cardiorespiratory condition allowed bedside cycling exercise (starting from day 5), given they still had an expected prolonged intensive care unit stay of at least 7 more days. : Both groups received respiratory physiotherapy and a daily standardized passive or active motion session of upper and lower limbs. In addition, the treatment group performed a passive or active exercise training session for 20 mins/day, using a bedside ergometer. : All outcome data are reflective for survivors. Quadriceps force and functional status were assessed at intensive care unit discharge and hospital discharge. Six-minute walking distance was measured at hospital discharge. No adverse events were identified during and immediately after the exercise training. At intensive care unit discharge, quadriceps force and functional status were not different between groups. At hospital discharge, 6-min walking distance, isometric quadriceps force, and the subjective feeling of functional well-being (as measured with "Physical Functioning" item of the Short Form 36 Health Survey questionnaire) were significantly higher in the treatment group (p < .05). : Early exercise training in critically ill intensive care unit

  15. Super elongation complex promotes early HIV transcription and its function is modulated by P-TEFb.

    PubMed

    Kuzmina, Alona; Krasnopolsky, Simona; Taube, Ran

    2017-05-27

    Early work on the control of transcription of the human immunodeficiency virus (HIV) laid the foundation for our current knowledge of how RNA Polymerase II is released from promoter-proximal pausing sites and transcription elongation is enhanced. The viral Tat activator recruits Positive Transcription Elongation Factor b (P-TEFb) and Super Elongation Complex (SEC) that jointly drive transcription elongation. While substantial progress in understanding the role of SEC in HIV gene transcription elongation has been obtained, defining of the mechanisms that govern SEC functions is still limited, and the role of SEC in controlling HIV transcription in the absence of Tat is less clear. Here we revisit the contribution of SEC in early steps of HIV gene transcription. In the absence of Tat, the AF4/FMR2 Family member 4 (AFF4) of SEC efficiently activates HIV transcription, while gene activation by its homolog AFF1 is substantially lower. Differential recruitment to the HIV promoter and association with Human Polymerase-Associated Factor complex (PAFc) play key role in this functional distinction between AFF4 and AFF1. Moreover, while depletion of cyclin T1 expression has subtle effects on HIV gene transcription in the absence of Tat, knockout (KO) of AFF1, AFF4, or both proteins slightly repress this early step of viral transcription. Upon Tat expression, HIV transcription reaches optimal levels despite KO of AFF1 or AFF4 expression. However, double AFF1/AFF4 KO completely diminishes Tat trans-activation. Significantly, our results show that P-TEFb phosphorylates AFF4 and modulates SEC assembly, AFF1/4 dimerization and recruitment to the viral promoter. We conclude that SEC promotes both early steps of HIV transcription in the absence of Tat, as well as elongation of transcription, when Tat is expressed. Significantly, SEC functions are modulated by P-TEFb.

  16. Super elongation complex promotes early HIV transcription and its function is modulated by P-TEFb

    PubMed Central

    Kuzmina, Alona; Krasnopolsky, Simona; Taube, Ran

    2017-01-01

    ABSTRACT Early work on the control of transcription of the human immunodeficiency virus (HIV) laid the foundation for our current knowledge of how RNA Polymerase II is released from promoter-proximal pausing sites and transcription elongation is enhanced. The viral Tat activator recruits Positive Transcription Elongation Factor b (P-TEFb) and Super Elongation Complex (SEC) that jointly drive transcription elongation. While substantial progress in understanding the role of SEC in HIV gene transcription elongation has been obtained, defining of the mechanisms that govern SEC functions is still limited, and the role of SEC in controlling HIV transcription in the absence of Tat is less clear. Here we revisit the contribution of SEC in early steps of HIV gene transcription. In the absence of Tat, the AF4/FMR2 Family member 4 (AFF4) of SEC efficiently activates HIV transcription, while gene activation by its homolog AFF1 is substantially lower. Differential recruitment to the HIV promoter and association with Human Polymerase-Associated Factor complex (PAFc) play key role in this functional distinction between AFF4 and AFF1. Moreover, while depletion of cyclin T1 expression has subtle effects on HIV gene transcription in the absence of Tat, knockout (KO) of AFF1, AFF4, or both proteins slightly repress this early step of viral transcription. Upon Tat expression, HIV transcription reaches optimal levels despite KO of AFF1 or AFF4 expression. However, double AFF1/AFF4 KO completely diminishes Tat trans-activation. Significantly, our results show that P-TEFb phosphorylates AFF4 and modulates SEC assembly, AFF1/4 dimerization and recruitment to the viral promoter. We conclude that SEC promotes both early steps of HIV transcription in the absence of Tat, as well as elongation of transcription, when Tat is expressed. Significantly, SEC functions are modulated by P-TEFb. PMID:28340332

  17. Executive Function in Very Preterm Children at Early School Age

    ERIC Educational Resources Information Center

    Aarnoudse-Moens, Cornelieke S. H.; Smidts, Diana P.; Oosterlaan, Jaap; Duivenvoorden, Hugo J.; Weisglas-Kuperus, Nynke

    2009-01-01

    We examined whether very preterm ([less than or equal to] 30 weeks gestation) children at early school age have impairments in executive function (EF) independent of IQ and processing speed, and whether demographic and neonatal risk factors were associated with EF impairments. A consecutive sample of 50 children (27 boys and 23 girls) born very…

  18. Socioeconomic Status and Functional Brain Development--Associations in Early Infancy

    ERIC Educational Resources Information Center

    Tomalski, Przemyslaw; Moore, Derek G.; Ribeiro, Helena; Axelsson, Emma L.; Murphy, Elizabeth; Karmiloff-Smith, Annette; Johnson, Mark H.; Kushnerenko, Elena

    2013-01-01

    Socioeconomic status (SES) impacts on both structural and functional brain development in childhood, but how early its effects can be demonstrated is unknown. In this study we measured resting baseline EEG activity in the gamma frequency range in awake 6-9-month-olds from areas of East London with high socioeconomic deprivation. Between-subject…

  19. Early post-stroke cognition in stroke rehabilitation patients predicts functional outcome at 13 months.

    PubMed

    Wagle, Jørgen; Farner, Lasse; Flekkøy, Kjell; Bruun Wyller, Torgeir; Sandvik, Leiv; Fure, Brynjar; Stensrød, Brynhild; Engedal, Knut

    2011-01-01

    To identify prognostic factors associated with functional outcome at 13 months in a sample of stroke rehabilitation patients. Specifically, we hypothesized that cognitive functioning early after stroke would predict long-term functional outcome independently of other factors. 163 stroke rehabilitation patients underwent a structured neuropsychological examination 2-3 weeks after hospital admittance, and their functional status was subsequently evaluated 13 months later with the modified Rankin Scale (mRS) as outcome measure. Three predictive models were built using linear regression analyses: a biological model (sociodemographics, apolipoprotein E genotype, prestroke vascular factors, lesion characteristics and neurological stroke-related impairment); a functional model (pre- and early post-stroke cognitive functioning, personal and instrumental activities of daily living, ADL, and depressive symptoms), and a combined model (including significant variables, with p value <0.05, from the biological and functional models). A combined model of 4 variables best predicted long-term functional outcome with explained variance of 49%: neurological impairment (National Institute of Health Stroke Scale; β = 0.402, p < 0.001), age (β = 0.233, p = 0.001), post-stroke cognitive functioning (Repeatable Battery of Neuropsychological Status, RBANS; β = -0.248, p = 0.001) and prestroke personal ADL (Barthel Index; β = -0.217, p = 0.002). Further linear regression analyses of which RBANS indexes and subtests best predicted long-term functional outcome showed that Coding (β = -0.484, p < 0.001) and Figure Copy (β = -0.233, p = 0.002) raw scores at baseline explained 42% of the variance in mRS scores at follow-up. Early post-stroke cognitive functioning as measured by the RBANS is a significant and independent predictor of long-term functional post-stroke outcome. Copyright © 2011 S. Karger AG, Basel.

  20. In utero and early childhood exposure to arsenic decreases lung function in children

    PubMed Central

    Recio-Vega, Rogelio; Gonzalez-Cortes, Tania; Olivas-Calderon, Edgar; Lantz, R. Clark; Gandolfi, A. Jay; Gonzalez-De Alba, Cesar

    2016-01-01

    Background The lung is a target organ for adverse health outcomes following exposure to arsenic. Several studies have reported a high prevalence of respiratory symptoms and diseases in subjects highly exposed to arsenic through drinking water, however, most studies to date has been performed in exposed adults, with little information on respiratory effects in children. The objective of the study was to evaluate the association between urinary levels of arsenic and its metabolites with lung function in children exposed in utero and in early childhood to high arsenic levels through drinking water. Methods A total of 358 healthy children were included in our study. Individual exposure was assessed based on urinary concentration of inorganic arsenic. Lung function was assessed by spirometry. Results Participants were exposed since pregnancy until early childhood to an average water As concentration of 152.13 μg/L. The mean urinary arsenic level registered in the studied subjects was 141.2 μg/L and only 16.7% had a urinary concentration below the national concern level. Forced vital capacity was significantly decreased in the studied population and it was negatively associated with the percent of inorganic arsenic. More than 57% of the subjects had a restrictive spirometric pattern. The urinary As level was higher in those children with restrictive lung patterns when compared with the levels registered in subjects with normal spirometric patterns. Conclusion Exposure to arsenic through drinking water during in utero and early life was associated with a decrease in FVC and with a restrictive spirometric pattern in the children evaluated. PMID:25131850

  1. Alterations in Sociability and Functional Brain Connectivity Caused by Early-Life Seizures is Reversed by Bumetanide

    PubMed Central

    Holmes, Gregory L.; Tian, Chengju; Hernan, Amanda E.; Flynn, Sean; Camp, Devon; Barry, Jeremy

    2015-01-01

    There is a well-described association between infantile epilepsy and pervasive cognitive and behavioral deficits, including a high incidence of autism spectrum disorders. Despite the robustness of the relationship between early-life seizures and the development of autism, the pathophysiological mechanism by which this occurs has not been explored. As a result of increasing evidence that autism is a disorder of brain connectivity we hypothesized that early-life seizures would interrupt normal brain connectivity during brain maturation and result in an autistic phenotype. Normal rat pups underwent recurrent flurothyl-induced seizures from postnatal (P) day 5-14 and then tested, along with controls, for developmental alterations of development brain oscillatory activity from P18-25. Specifically we wished to understand how normal changes in rhythmicity in and between brain regions change as a function of age and if this rhythmicity is altered or interrupted by early life seizures. In rat pups with early-life seizures, field recordings from dorsal and ventral hippocampus and prefrontal cortex demonstrated marked increase in coherence as well as a decrease in voltage correlation at all bandwidths compared to controls while there were minimal differences in total power and relative power spectral densities. Rats with early-life seizures had resulting impairment in the sociability and social novelty tests but demonstrated no evidence of increased activity or generalized anxiety as measured in the open field. In addition, rats with early-life seizures had lower seizure thresholds than controls, indicating long-standing alterations in the excitatory/inhibition balance. Bumetanide, a pharmacological agent that blocks the activity of NKCC1 and induces a significant shift of ECl toward more hyperpolarized values, administration at the time of the seizures precluded the subsequent abnormalities in coherence and voltage correlation and resulted in normal sociability and seizure

  2. Development and Application of a Tendon Prosthesis for Early Functional Restoration of the Hand.

    DTIC Science & Technology

    1975-09-01

    F’A-AOk 322 JEFFERSON MEDICAL COLL PHILADELPHIA PA F/B 6/5 DEVELOPMENT AND APPLICATION OF A TENDON PROSTHESIS FOR EARLY FU--ETC(U) SEP 75 J M HUNTER...LEVEL INVENTORY DEELOPKWTI AND APPLICATION OF A TENDON PROSTHESIS FOR EARLY FUNCTIOKAL RESTORATION OF THE RAND BIDETICATION DISTRIBUTION STATEMENT A...AND RETURN TO DTIC-DDA-2 FORM DOCUMENT PROCESSING SHEETCToc 79 0 AD DEVELOPNDT AND APPLICATION OF A TENDOR PROSTHESIS FOR EARLY FUNCTIONAL

  3. Do Children's Executive Functions Account for Associations Between Early Autonomy-Supportive Parenting and Achievement Through High School?

    PubMed

    Bindman, Samantha W; Pomerantz, Eva M; Roisman, Glenn I

    2015-08-01

    This study evaluated whether the positive association between early autonomy-supportive parenting and children's subsequent achievement is mediated by children's executive functions. Using observations of mothers' parenting from the NICHD Study of Early Child Care and Youth Development ( N = 1,306), analyses revealed that mothers' autonomy support over the first 3 years of life predicted enhanced executive functions (i.e., inhibition, delay of gratification, and sustained attention) during the year prior to kindergarten and academic achievement in elementary and high school even when mothers' warmth and cognitive stimulation, as well as other factors (e.g., children's early general cognitive skills and mothers' educational attainment) were covaried. Mediation analyses demonstrated that over and above other attributes (e.g., temperament), children's executive functions partially accounted for the association between early autonomy-supportive parenting and children's subsequent achievement.

  4. Gut microbial functional maturation and succession during human early life.

    PubMed

    Cerdó, Tomás; Ruiz, Alicia; Acuña, Inmaculada; Jáuregui, Ruy; Jehmlich, Nico; Haange, Sven-Bastian; von Bergen, Martin; Suárez, Antonio; Campoy, Cristina

    2018-04-24

    The evolutional trajectory of gut microbial colonization from birth has been shown to prime for health later in life. Here, we combined cultivation-independent 16S rRNA gene sequencing and metaproteomics to investigate the functional maturation of gut microbiota in faecal samples from full-term healthy infants collected at 6 and 18 months of age. Phylogenetic analysis of the metaproteomes showed that Bifidobacterium provided the highest number of distinct protein groups. Considerable divergences between taxa abundance and protein phylogeny were observed at all taxonomic ranks. Age had a profound effect on early microbiota where compositional and functional diversity of less dissimilar communities increased with time. Comparisons of the relative abundances of proteins revealed the transition of taxon-associated saccharolytic and fermentation strategies from milk and mucin-derived monosaccharide catabolism feeding acetate/propanoate synthesis to complex food-derived hexoses fuelling butanoate production. Furthermore, co-occurrence network analysis uncovered two anti-correlated modules of functional taxa. A low-connected Bifidobacteriaceae-centred guild of facultative anaerobes was succeeded by a rich club of obligate anaerobes densely interconnected around Lachnospiraceae, underpinning their pivotal roles in microbial ecosystem assemblies. Our findings establish a framework to visualize whole microbial community metabolism and ecosystem succession dynamics, proposing opportunities for microbiota-targeted health-promoting strategies early in life. © 2018 Society for Applied Microbiology and John Wiley & Sons Ltd.

  5. Early Functional Deficit and Microglial Disturbances in a Mouse Model of Amyotrophic Lateral Sclerosis

    PubMed Central

    Rabano, Miriam; Vivanco, Maria d M; Perrin, Florence Evelyne

    2012-01-01

    Background Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by selective motoneurons degeneration. There is today no clear-cut pathogenesis sequence nor any treatment. However growing evidences are in favor of the involvement, besides neurons, of several partners such as glia and muscles. To better characterize the time course of pathological events in an animal model that recapitulates human ALS symptoms, we investigated functional and cellular characteristics of hSOD1G93A mice. Methods and Findings We have evaluated locomotor function of hSOD1G93A mice through dynamic walking patterns and spontaneous motor activity analysis. We detected early functional deficits that redefine symptoms onset at 60 days of age, i.e. 20 days earlier than previously described. Moreover, sequential combination of these approaches allows monitoring of motor activity up to disease end stage. To tentatively correlate early functional deficit with cellular alterations we have used flow cytometry and immunohistochemistry approaches to characterize neuromuscular junctions, astrocytes and microglia. We show that (1) decrease in neuromuscular junction's number correlates with motor impairment, (2) astrocytes number is not altered at pre- and early-symptomatic ages but intraspinal repartition is modified at symptoms onset, and (3) microglia modifications precede disease onset. At pre-symptomatic age, we show a decrease in microglia number whereas at onset of the disease two distinct microglia sub-populations emerge. Conclusions In conclusion, precise motor analysis updates the onset of the disease in hSOD1G93A mice and allows locomotor monitoring until the end stage of the disease. Early functional deficits coincide with alterations of neuromuscular junctions. Importantly, we identify different sets of changes in microglia before disease onset as well as at early-symptomatic stage. This finding not only brings a new sequence of cellular events in the natural

  6. Cognitive function of children with cystic fibrosis: deleterious effect of early malnutrition.

    PubMed

    Koscik, Rebecca L; Farrell, Philip M; Kosorok, Michael R; Zaremba, Kathleen M; Laxova, Anita; Lai, Hui-Chuan; Douglas, Jeff A; Rock, Michael J; Splaingard, Mark L

    2004-06-01

    Patients who have cystic fibrosis (CF) and experience delayed diagnosis by traditional methods have greater nutritional insult compared with peers diagnosed via neonatal screening. The objective of this study was to evaluate cognitive function in children with CF and the influence of both early diagnosis through neonatal screening and the potential effect of early malnutrition. Cognitive assessment data were obtained for 89 CF patients (aged 7.3-17 years) during routine clinic visits. Patients had been enrolled in either the screened (N = 42) or traditional diagnosis (control) group (N = 47) of the Wisconsin CF Neonatal Screening Project. The Test of Cognitive Skills, Second Edition was administered to generate the Cognitive Skills Index (CSI) and cognitive factor scores (Verbal, Nonverbal, and Memory). Cognitive scores in the overall study population were similar to normative data (CSI mean [standard deviation]: 102.5 [16.6]; 95% confidence interval: 99.1-105.9). The mean (standard deviation) CSI scores for the screened and control groups were 104.4 (14.4) and 99.8 (18.5), respectively. Significantly lower cognitive scores correlated with indicators of malnutrition and unfavorable family factors such as single parents, lower socioeconomic status, and less parental education. Our analyses revealed lower cognitive scores in patients with low plasma alpha-tocopherol (alpha-T) levels at diagnosis. In addition, patients in the control group who also had vitamin E deficiency at diagnosis (alpha-T < 300 microg/dl) showed significantly lower CSI scores in comparison with alpha-T-sufficient control subjects and both deficient and sufficient alpha-T subsets of screened patients. Results suggest that prevention of prolonged malnutrition by early diagnosis and nutritional therapy, particularly minimizing the duration of vitamin E deficiency, is associated with better cognitive functioning in children with CF.

  7. Mental health functioning (SF-36) and intentions to retire early among ageing municipal employees: the Helsinki Health Study.

    PubMed

    Harkonmäki, Karoliina; Lahelma, Eero; Martikainen, Pekka; Rahkonen, Ossi; Silventoinen, Karri

    2006-01-01

    To examine the associations of mental health functioning with intentions to retire early among ageing municipal employees. Cross-sectional survey data (n = 7,765) from the Helsinki Health Study in 2000, 2001, and 2002 were used. Intentions to retire early were sought with a question: "Have you considered retiring before normal retirement age?" The dependent variable was divided into three categories: 1 = no intentions to retire early; 2 = weak intentions; 3 = strong intentions. Mental health functioning was measured by the Short Form 36 (SF-36) mental component summary (MCS). Other variables included age, sex, physical health functioning (SF-36), limiting longstanding illness, socioeconomic status, and spouse's employment status. Multinomial regression analysis was used to examine the association of mental health functioning with intentions to retire early. Employees with the poorest mental health functioning were much more likely to report strong intentions to retire early (OR 6.09, 95% CI 4.97-7.47) than those with the best mental health functioning. Adjustments for physical health, socioeconomic status, and spouse's employment status did not substantially affect this association. The findings highlight the importance of mental health for intentions to retire early. Strategies aimed at keeping people at work for longer should emphasize the importance of mental well-being and the prevention of poor mental health. More evidence is needed on why mental problems among ageing baby-boomer employees are giving rise to increasing social consequences, although the overall prevalence of mental problems has not increased.

  8. Early Ambulation Decreases Length of Hospital Stay, Perioperative Complications and Improves Functional Outcomes in Elderly Patients Undergoing Surgery for Correction of Adult Degenerative Scoliosis.

    PubMed

    Adogwa, Owoicho; Elsamadicy, Aladine A; Fialkoff, Jared; Cheng, Joseph; Karikari, Isaac O; Bagley, Carlos

    2017-09-15

    Ambispective cohort review. To examine the effects of early mobilization on patient outcomes, complications profile, and 30-day readmission rates. Prolonged immobilization after surgery can result in functional decline and an increased risk of hospital-associated complications. We conducted an ambispective study of 125 elderly patients (>65 years) undergoing elective spinal surgery for correction of adult degenerative scoliosis. We identified all unplanned readmissions within 30 days of discharge. Unplanned readmissions were defined to have occurred as a result of either a surgical or a nonsurgical complication. "Days of immobility" was defined as the number of days until a patient moved out of bed beyond a chair. Patients in the top and bottom quartiles were dichotomized into "early ambulators" and "late ambulators", respectively. Early ambulators were ambulatory within 24 hours of surgery, whereas late ambulators were ambulatory at a minimum of 48 hours after surgery. Complication rates, duration of hospital stay, and 30-day readmission rates were compared between early ambulators and late ambulators. Baseline characteristics were similar between both cohorts. Compared with patients with a longer duration of immobility (i.e., late ambulators), the prevalence of at least one perioperative complication was significantly lower in the early ambulators cohort (30% vs. 54%, P = 0.06). The length of inhospital stay was 34% shorter in the early ambulators cohort (5.33 days vs. 8.11 days, P = 0.01). Functional independence was superior in the early ambulators cohort, with the majority of patients discharged directly home after surgery compared with late ambulators (71.2% vs. 22.0%, P = 0.01). Early ambulation after surgery significantly reduces the incidence of perioperative complications, shortens duration of inhospital stay, and contributes to improved perioperative functional status in elderly patients. Even a delay of 24 hours to ambulation is

  9. The Angular Correlation Function of Galaxies from Early Sloan Digital Sky Survey Data

    NASA Astrophysics Data System (ADS)

    Connolly, Andrew J.; Scranton, Ryan; Johnston, David; Dodelson, Scott; Eisenstein, Daniel J.; Frieman, Joshua A.; Gunn, James E.; Hui, Lam; Jain, Bhuvnesh; Kent, Stephen; Loveday, Jon; Nichol, Robert C.; O'Connell, Liam; Postman, Marc; Scoccimarro, Roman; Sheth, Ravi K.; Stebbins, Albert; Strauss, Michael A.; Szalay, Alexander S.; Szapudi, István; Tegmark, Max; Vogeley, Michael S.; Zehavi, Idit; Annis, James; Bahcall, Neta; Brinkmann, J.; Csabai, István; Doi, Mamoru; Fukugita, Masataka; Hennessy, G. S.; Hindsley, Robert; Ichikawa, Takashi; Ivezić, Željko; Kim, Rita S. J.; Knapp, Gillian R.; Kunszt, Peter; Lamb, D. Q.; Lee, Brian C.; Lupton, Robert H.; McKay, Timothy A.; Munn, Jeff; Peoples, John; Pier, Jeff; Rockosi, Constance; Schlegel, David; Stoughton, Christopher; Tucker, Douglas L.; Yanny, Brian; York, Donald G.

    2002-11-01

    The Sloan Digital Sky Survey is one of the first multicolor photometric and spectroscopic surveys designed to measure the statistical properties of galaxies within the local universe. In this paper we present some of the initial results on the angular two-point correlation function measured from the early SDSS galaxy data. The form of the correlation function, over the magnitude interval 18results from existing wide-field, photographic-based surveys and narrower CCD galaxy surveys. On scales between 1' and 1° the correlation function is well described by a power law with an exponent of ~-0.7. The amplitude of the correlation function, within this angular interval, decreases with fainter magnitudes in good agreement with analysis from existing galaxy surveys. There is a characteristic break in the correlation function on scales of approximately 1°-2°. On small scales, θ<1', the SDSS correlation function does not appear to be consistent with the power-law form fitted to the 1'<θ<0.5d data. With a data set that is less than 2% of the full SDSS survey area, we have obtained high-precision measurements of the power-law angular correlation function on angular scales 1'<θ<1deg, which are robust to systematic uncertainties. Because of the limited area and the highly correlated nature of the error covariance matrix, these initial results do not yet provide a definitive characterization of departures from the power-law form at smaller and larger angles. In the near future, however, the area of the SDSS imaging survey will be sufficient to allow detailed analysis of the small- and large-scale regimes, measurements of higher order correlations, and studies of angular clustering as a function of redshift and galaxy type.

  10. Disruption of Hox9,10,11 function results in cellular level lineage infidelity in the kidney.

    PubMed

    Drake, Keri A; Adam, Mike; Mahoney, Robert; Potter, S Steven

    2018-04-20

    Hox genes are important regulators of development. The 39 mammalian Hox genes have considerable functional overlap, greatly confounding their study. In this report, we generated mice with multiple combinations of paralogous and flanking Abd-B Hox gene mutations to investigate functional redundancies in kidney development. The resulting mice developed a number of kidney abnormalities, including hypoplasia, agenesis, and severe cysts, with distinct Hox functions observed in early metanephric kidney formation and nephron progenitor maintenance. Most surprising, however, was that extensive removal of Hox shared function in these kidneys resulted in cellular level lineage infidelity. Strikingly, mutant nephron tubules consisted of intermixed cells with proximal tubule, loop of Henle, and collecting duct identities, with some single cells expressing markers associated with more than one nephron segment. These results indicate that Hox genes are required for proper lineage selection/maintenance and full repression of genes involved in cell fate restriction in the developing kidney.

  11. Do Children's Executive Functions Account for Associations Between Early Autonomy-Supportive Parenting and Achievement Through High School?

    PubMed Central

    Bindman, Samantha W.; Pomerantz, Eva M.; Roisman, Glenn I.

    2015-01-01

    This study evaluated whether the positive association between early autonomy-supportive parenting and children's subsequent achievement is mediated by children's executive functions. Using observations of mothers’ parenting from the NICHD Study of Early Child Care and Youth Development (N = 1,306), analyses revealed that mothers’ autonomy support over the first 3 years of life predicted enhanced executive functions (i.e., inhibition, delay of gratification, and sustained attention) during the year prior to kindergarten and academic achievement in elementary and high school even when mothers’ warmth and cognitive stimulation, as well as other factors (e.g., children's early general cognitive skills and mothers’ educational attainment) were covaried. Mediation analyses demonstrated that over and above other attributes (e.g., temperament), children's executive functions partially accounted for the association between early autonomy-supportive parenting and children's subsequent achievement. PMID:26366009

  12. Deoxyribonucleic Acid Replication and Expression of Early and Late Bacteriophage Functions in Bacillus subtilis

    PubMed Central

    Pène, Jacques J.; Marmur, Julius

    1967-01-01

    The role of deoxyribonucleic acid (DNA) replication in the control of the synthesis of deoxycytidylate (dCMP) deaminase and lysozyme in Bacillus subtilis infected with bacteriophage 2C has been studied. These phage-induced enzymes are synthesized at different times during the latent period. It was shown by actinomycin inhibition that the formation of the late enzyme (lysozyme) required messenger ribonucleic acid (mRNA) synthesized de novo after the initiation of translation of mRNA which specifies the early function (dCMP deaminase). The inhibition of phage DNA synthesis by mitomycin C prevented the synthesis of lysozyme only when added before the onset of phage DNA replication, but it did not affect the synthesis or action of dCMP deaminase when added at any time during the latent period. Treatment of infected cells with mitomycin C after phage DNA synthesis had reached 8 to 10% of its maximal rate resulted in the production of normal amounts of lysozyme. These observations suggest that mRNA specifying early enzymes can be transcribed from parental (and probably also from progeny) DNA, whereas late functional messengers can be transcribed only after the formation of progeny DNA. PMID:4990039

  13. Imaging frontostriatal function in ultra-high-risk, early, and chronic schizophrenia during executive processing.

    PubMed

    Morey, Rajendra A; Inan, Seniha; Mitchell, Teresa V; Perkins, Diana O; Lieberman, Jeffrey A; Belger, Aysenil

    2005-03-01

    Individuals experiencing prodromal symptoms of schizophrenia (ultra-high-risk group) demonstrate impaired performance on tasks of executive function, attention, and working memory. The neurobiological underpinnings of such executive deficits in ultra-high-risk individuals remains unclear. We assessed frontal and striatal functions during a visual oddball continuous performance task, in ultra-high-risk, early, and chronic schizophrenic patients with the use of functional magnetic resonance imaging. Cross-sectional case-control design. Community; outpatient clinic. Patients Fifty-two individuals (control, n = 16; ultra-high risk, n = 10; early, n = 15; chronic, n = 11) from a referred clinical sample and age- and sex-matched control volunteers underwent scanning. Percentage of active voxels and percentage signal change calculated for the anterior cingulate gyrus (ACG), middle frontal gyrus (MFG), inferior frontal gyrus (IFG), basal ganglia, and thalamus. Performance on the visual oddball task was measured with percentage of hits and d' (a measure based on the hit rate and the false-alarm rate). The ultra-high-risk group showed significantly smaller differential activation between task-relevant and task-irrelevant stimuli in the frontal regions (ACG, IFG, MFG) than the control group. Frontostriatal activation associated with target stimuli in the early and chronic groups was significantly lower than the control group, while the ultra-high-risk group showed a trend toward the early group. Our findings suggest that prefrontal function begins to decline before the onset of syndromally defined illness and hence may represent a vulnerability marker in assessing the risk of developing psychotic disorders among ultra-high-risk individuals.

  14. Effects of Antiretroviral Therapy on Autonomic Function in Early HIV Infection: A Preliminary Report

    PubMed Central

    Chow, Dominic; Kocher, Morgan; Shikuma, Cecilia; Parikh, Nisha; Grandinetti, Andrew; Nakamoto, Beau; Seto, Todd; Low, Phillip

    2012-01-01

    Background: A prospective study was conducted in human immunodeficiency virus (HIV)-infected patients as they undergo alterations in their antiretroviral therapy (ART) to determine the effect of ART on autonomic function. Methods: HIV-infected subjects who were either 1) naïve to ART and initiating ART, or 2) receiving ART and in HIV virologic failure for at least 4 months and were about to switch ART were enrolled in this study. Autonomic function assessment (cardiovagal, adrenergic, and sudomotor tests) was performed prior to and 4 months after initiating the new ART. Changes in clinical autonomic symptoms and virologic assessment were assessed. Results: Twelve subjects completed the study: 92% male; median age (Q1, Q3) was 41.0 (28.0, 48.2) years; and 50% White/Non-Hispanic. Seventy-five percent were ART naïve while 25% were failing their ART regimen. The median CD4 count was 336.5 (245.3, 372.3) cells/mm3. All subjects achieved an undetectable HIV viral load by the 4-month follow-up visit. The majority of naïve subjects were started on an ART regimen of tenofovir / emtricitabine / efavirenz. There were no significant differences in autonomic function assessment, as measured by cardiovagal, adrenergic, and sudomotor tests, with regards to ART initiation. Conclusion: This is the first study to examine the effects of initiating ART on autonomic function in early HIV infection. This study found no appreciable differences of ART on the autonomic nervous system when ART is initiated early in the course of HIV disease. ART may not contribute to short-term changes in autonomic function. PMID:22859899

  15. Effect of Early Referral to Specialist in Dementia on Institutionalization and Functional Decline: Findings from a Population-Based Study.

    PubMed

    Pimouguet, Clément; Le-Goff, Mélanie; Rizzuto, Debora; Berr, Claudine; Leffondré, Karen; Pérès, Karine; Dartigues, Jean FranÇois; Helmer, Catherine

    2016-01-01

    Although early diagnosis has been hypothesized to benefit both patients and caregivers, until now studies evaluating the effect of early dementia diagnosis are lacking. To investigate the influence of early specialist referral for dementia on the risk of institutionalization and functional decline in Activity of Daily Living (ADL). Incident dementia cases were screened in a prospective population-based cohort, the Three-City Study, and initial specialist consultation for cognitive complaint was assessed at dementia diagnosis. Proportional hazard regression and illness-death models were used to test the association between specialist referral and, respectively, institutionalization and functional decline. Only one third of the incident individuals with dementia had consulted a specialist for cognitive problems early (36%). After adjustment on potential confounders (including cognitive and functional decline) and competing risk of death, participants who had consulted a specialist early in the disease course presented a higher rate of being institutionalized than those who did not (Hazard Ratio = 2.00, 95% Confidence Interval (CI): 1.09- 3.64). But early specialist referral was not associated with further functional decline (HR = 1.09, 95% CI: 0.71- 1.67). Early specialist referral in dementia is associated with increased risk of institutionalization but not with functional decline in ADL. These findings suggest that early care referral in dementia may be a marker of concern for patients and/or caregivers; subsequent medical and social care could be suboptimal or inappropriate to allow patients to stay longer at home.

  16. Reduction of Interhemispheric Functional Brain Connectivity in Early Blindness: A Resting-State fMRI Study

    PubMed Central

    2017-01-01

    Objective The purpose of this study was to investigate the resting-state interhemispheric functional connectivity in early blindness by using voxel-mirrored homotopic connectivity (VMHC). Materials and Methods Sixteen early blind patients (EB group) and sixteen age- and gender-matched sighted control volunteers (SC group) were recruited in this study. We used VMHC to identify brain areas with significant differences in functional connectivity between different groups and used voxel-based morphometry (VBM) to calculate the individual gray matter volume (GMV). Results VMHC analysis showed a significantly lower connectivity in primary visual cortex, visual association cortex, and somatosensory association cortex in EB group compared to sighted controls. Additionally, VBM analysis revealed that GMV was reduced in the left lateral calcarine cortices in EB group compared to sighted controls, while it was increased in the left lateral middle occipital gyri. Statistical analysis showed the duration of blindness negatively correlated with VMHC in the bilateral middle frontal gyri, middle temporal gyri, and inferior temporal gyri. Conclusions Our findings help elucidate the pathophysiological mechanisms of EB. The interhemispheric functional connectivity was impaired in EB patients. Additionally, the middle frontal gyri, middle temporal gyri, and inferior temporal gyri may be potential target regions for rehabilitation. PMID:28656145

  17. The role of thyroid hormone in trophoblast function, early pregnancy maintenance, and fetal neurodevelopment.

    PubMed

    Ohara, Noriyuki; Tsujino, Taro; Maruo, Takeshi

    2004-11-01

    To review the literature on the roles of thyroid hormone in trophoblast function, early pregnancy maintenance, and fetal neurodevelopment. MEDLINE was searched for English-language papers published from 1971 to 2003, using the key words "brain," "hypothyroidism," "placenta," "pregnancy," "threatened abortion," "thyroid hormone," "thyroid hormone receptor," "thyroid hormone replacement therapy," "thyroid hormone-responsive gene," and "trophoblast." Transplacental transfer of thyroid hormone occurs before the onset of fetal thyroid hormone secretion. Thyroid hormone receptors and iodothyronine deiodinases are present in the placenta and the fetal central nervous system early in pregnancy, and thyroid hormone plays a crucial role both in trophoblast function and fetal neurodevelopment. Maternal hypothyroxinemia is associated with a high rate of spontaneous abortion and long-term neuropsychological deficits in children born of hypothyroid mothers. Maternal iodine deficiency also causes a wide spectrum of neuropsychological disorders in children, ranging from subclinical deficits in cognitive motor and auditory functions to hypothyroid-induced cognitive impairment in infants. However, these conditions are preventable when iodine supplementation is initiated before the second trimester. Although thyroid hormone replacement therapy is effective for reducing the adverse effects complicated by maternal hypothyroidism, the appropriate dose of thyroid hormone is mandatory in protecting the early stage of pregnancy. Close monitoring of maternal thyroid hormone status and ensuring adequate maternal thyroid hormone levels in early pregnancy are of great importance to prevent miscarriage and neuropsychological deficits in infants.

  18. Early Feasibility Study of a Transcatheter Tricuspid Valve Annuloplasty: SCOUT Trial 30-Day Results.

    PubMed

    Hahn, Rebecca T; Meduri, Christopher U; Davidson, Charles J; Lim, Scott; Nazif, Tamim M; Ricciardi, Mark J; Rajagopal, Vivek; Ailawadi, Gorav; Vannan, Mani A; Thomas, James D; Fowler, Dale; Rich, Stuart; Martin, Randy; Ong, Geraldine; Groothuis, Adam; Kodali, Susheel

    2017-04-11

    The SCOUT (Percutaneous Tricuspid Valve Annuloplasty System for Symptomatic Chronic Functional Tricuspid Regurgitation) trial is a prospective, single-arm, multicenter, early feasibility study of a novel transcatheter device to plicate the tricuspid annulus (TA) and reduce tricuspid regurgitation (TR). This study tested the feasibility and safety of a novel transcatheter device and assessed its early performance and functional outcomes. Between November 2015 and June 2016, 15 patients with New York Heart Association (NYHA) functional class ≥II and moderate or greater functional TR were enrolled. Primary performance and safety endpoint outcomes were technically successful at 30 days with no reintervention. Echocardiographic measurements (TA diameter, effective regurgitant orifice area [EROA], left ventricular stroke volume [LVSV]) and quality-of-life (QoL) measurements (NYHA functional class, Minnesota Living with Heart Failure Questionnaire [MLHFQ], and 6-min walk test [6MWT]) were performed at baseline and 30 days. All patients (mean 73.2 ± 6.9 years of age, 87% female) underwent successful device implantation with no deaths, strokes, bleeding, tamponade, or valve reintervention. Technical success rate at 30 days was 80%, with 3 single-pledget annular detachments without reintervention. In the remaining 12 patients, there were significant reductions in TA (12.3 ± 3.1 cm 2 to 11.3 ± 2.7 cm 2 , respectively; p = 0.019) and EROA (0.51 ± 0.18 cm 2 vs. 0.32 ± 0.18 cm 2 , respectively; p = 0.020), with significant increase in LVSV (63.6 ± 17.9 ml vs. 71.5 ± 25.7 ml, respectively; p = 0.021). In the intention-to-treat cohort, there were significant improvements in NYHA functional class (≥1 class, p = 0.001), MLHFQ (47.4 ± 17.6 to 20.9 ± 14.8; p < 0.001), and 6MWT (245.2 ± 110.1 to 298.0 m ± 107.6 m; p = 0.008). The 30-day results of the SCOUT trial confirmed the safety of the novel transcatheter device, which reduced TA and EROA, increased LVSV

  19. Caloric restriction preserves memory and reduces anxiety of aging mice with early enhancement of neurovascular functions.

    PubMed

    Parikh, Ishita; Guo, Janet; Chuang, Kai-Hsiang; Zhong, Yu; Rempe, Ralf G; Hoffman, Jared D; Armstrong, Rachel; Bauer, Björn; Hartz, Anika M S; Lin, Ai-Ling

    2016-11-08

    Neurovascular integrity plays an important role in protecting cognitive and mental health in aging. Lifestyle interventions that sustain neurovascular integrity may thus be critical on preserving brain functions in aging and reducing the risk for age-related neurodegenerative disorders. Here we show that caloric restriction (CR) had an early effect on neurovascular enhancements, and played a critical role in preserving vascular, cognitive and mental health in aging. In particular, we found that CR significantly enhanced cerebral blood flow (CBF) and blood-brain barrier function in young mice at 5-6 months of age. The neurovascular enhancements were associated with reduced mammalian target of rapamycin expression, elevated endothelial nitric oxide synthase signaling, and increased ketone bodies utilization. With age, CR decelerated the rate of decline in CBF. The preserved CBF in hippocampus and frontal cortex were highly correlated with preserved memory and learning, and reduced anxiety, of the aging mice treated with CR (18-20 months of age). Our results suggest that dietary intervention started in the early stage (e.g., young adults) may benefit cognitive and mental reserve in aging. Understanding nutritional effects on neurovascular functions may have profound implications in human brain aging and age-related neurodegenerative disorders.

  20. Early life linguistic ability, late life cognitive function, and neuropathology: findings from the Nun Study.

    PubMed

    Riley, Kathryn P; Snowdon, David A; Desrosiers, Mark F; Markesbery, William R

    2005-03-01

    The relationships between early life variables, cognitive function, and neuropathology were examined in participants in the Nun Study who were between the ages of 75 and 95. Our early life variable was idea density, which is a measure of linguistic ability, derived from autobiographies written at a mean age of 22 years. Six discrete categories of cognitive function, including mild cognitive impairments, were evaluated, using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) battery of cognitive tests. Neuropathologic data included Braak staging, neurofibrillary tangle and senile plaque counts, brain weight, degree of cerebral atrophy, severity of atherosclerosis, and the presence of brain infarcts. Early-life idea density was significantly related to the categories of late-life cognitive function, including mild cognitive impairments: low idea density was associated with greater impairment. Low idea density also was significantly associated with lower brain weight, higher degree of cerebral atrophy, more severe neurofibrillary pathology, and the likelihood of meeting neuropathologic criteria for Alzheimer's disease.

  1. Modulation of early functional recovery of Achilles tendon to bone unit after transection by BPC 157 and methylprednisolone.

    PubMed

    Krivic, A; Majerovic, M; Jelic, I; Seiwerth, S; Sikiric, P

    2008-05-01

    In the presented study we compared the effect of stable peptide BPC 157 and methylprednisolone on early functional recovery after Achilles tendon to bone transection in a rat model before collagen healing started. Surgical transection of the right Achilles tendon to bone area was performed in seventy two Wistar Albino male rats. Healing Achilles tendon edges were harvested at days 1-4 following the transection. Using Achilles functional index (AFI), myeloperoxidase activity, histological inflammatory cell influx and vascular index early functional recovery was evaluated. Agents (stable peptide BPC 157 10 microg methylprednisolone 5 mg, normal saline 5 ml) were given alone (/kg b.w., intraperitoneally, once daily, first 30 min after surgery, last 24 h before analysis). Control group received normal saline 5 ml/kg. BPC 157 improved functional recovery (AFI values increased at all time points, p <0.05) by anti-inflammatory (decreased myeloperoxidase (MPO) activity and histological inflammatory cell influx, p <0.05) and increased new blood vessel formation (increased vascular index, p <0.05). Methyprednisolone decreased MPO activity and histological inflammatory cell influx, (p <0.05) but also decreased new blood vessel formation and did not affect early functional recovery. Stable peptide BPC 157 with combined anti-inflammatory action and induction of early new blood vessel formation facilitates early functional recovery in Achilles tendon to bone healing.

  2. ASSOCIATION BETWEEN VISUAL FUNCTION AND SUBRETINAL DRUSENOID DEPOSITS IN NORMAL AND EARLY AGE-RELATED MACULAR DEGENERATION EYES.

    PubMed

    Neely, David; Zarubina, Anna V; Clark, Mark E; Huisingh, Carrie E; Jackson, Gregory R; Zhang, Yuhua; McGwin, Gerald; Curcio, Christine A; Owsley, Cynthia

    2017-07-01

    To examine the association between subretinal drusenoid deposits (SDDs) identified by multimodal retinal imaging and visual function in older eyes with normal macular health or in the earliest phases of age-related macular degeneration (AMD). Age-related macular degeneration status for each eye was defined according to the Age-Related Eye Disease Study (AREDS) 9-step classification system (normal = Step 1, early AMD = Steps 2-4) based on color fundus photographs. Visual functions measured were best-corrected photopic visual acuity, contrast and light sensitivity, mesopic visual acuity, low-luminance deficit, and rod-mediated dark adaptation. Subretinal drusenoid deposits were identified through multimodal imaging (color fundus photographs, infrared reflectance and fundus autofluorescence images, and spectral domain optical coherence tomography). The sample included 1,202 eyes (958 eyes with normal health and 244 eyes with early AMD). In normal eyes, SDDs were not associated with any visual function evaluated. In eyes with early AMD, dark adaptation was markedly delayed in eyes with SDDs versus no SDD (a 4-minute delay on average), P = 0.0213. However, this association diminished after age adjustment, P = 0.2645. Other visual functions in early AMD eyes were not associated with SDDs. In a study specifically focused on eyes in normal macular health and in the earliest phases of AMD, early AMD eyes with SDDs have slower dark adaptation, largely attributable to the older ages of eyes with SDD; they did not exhibit deficits in other visual functions. Subretinal drusenoid deposits in older eyes in normal macular health are not associated with any visual functions evaluated.

  3. Parental Substance Abuse As an Early Traumatic Event. Preliminary Findings on Neuropsychological and Personality Functioning in Young Drug Addicts Exposed to Drugs Early

    PubMed Central

    Parolin, Micol; Simonelli, Alessandra; Mapelli, Daniela; Sacco, Marianna; Cristofalo, Patrizia

    2016-01-01

    Parental substance use is a major risk factor for child development, heightening the risk of drug problems in adolescence and young adulthood, and exposing offspring to several types of traumatic events. First, prenatal drug exposure can be considered a form of trauma itself, with subtle but long-lasting sequelae at the neuro-behavioral level. Second, parents' addiction often entails a childrearing environment characterized by poor parenting skills, disadvantaged contexts and adverse childhood experiences (ACEs), leading to dysfunctional outcomes. Young adults born from/raised by parents with drug problems and diagnosed with a Substance Used Disorder (SUD) themselves might display a particularly severe condition in terms of cognitive deficits and impaired personality function. This preliminary study aims to investigate the role of early exposure to drugs as a traumatic event, capable of affecting the psychological status of young drug addicts. In particular, it intends to examine the neuropsychological functioning and personality profile of young adults with severe SUDs who were exposed to drugs early in their family context. The research involved three groups, each consisting of 15 young adults (aged 18–24): a group of inpatients diagnosed with SUDs and exposed to drugs early, a comparison group of non-exposed inpatients and a group of non-exposed youth without SUDs. A neuropsychological battery (Esame Neuropsicologico Breve-2), an assessment procedure for personality disorders (Shedler-Westen Assessment Procedure-200) and the Symptom CheckList-90-Revised were administered. According to present preliminary results, young drug addicts exposed to drugs during their developmental age were characterized by elevated rates of neuropsychological impairments, especially at the expense of attentive and executive functions (EF); personality disorders were also common but did not differentiate them from non-exposed youth with SUDs. Alternative multi-focused prevention and

  4. The typical developmental trajectory of social and executive functions in late adolescence and early adulthood.

    PubMed

    Taylor, Sophie Jane; Barker, Lynne Ann; Heavey, Lisa; McHale, Sue

    2013-07-01

    Executive functions and social cognition develop through childhood into adolescence and early adulthood and are important for adaptive goal-oriented behavior (Apperly, Samson, & Humphreys, 2009; Blakemore & Choudhury, 2006). These functions are attributed to frontal networks known to undergo protracted maturation into early adulthood (Barker, Andrade, Morton, Romanowski, & Bowles, 2010; Lebel, Walker, Leemans, Phillips, & Beaulieu, 2008), although social cognition functions are also associated with widely distributed networks. Previously, nonlinear development has been reported around puberty on an emotion match-to-sample task (McGivern, Andersen, Byrd, Mutter, & Reilly, 2002) and for IQ in midadolescence (Ramsden et al., 2011). However, there are currently little data on the typical development of social and executive functions in late adolescence and early adulthood. In a cross-sectional design, 98 participants completed tests of social cognition and executive function, Wechsler Abbreviated Scale of Intelligence (Wechsler, 1999), Positive and Negative Affect Schedule (Watson, Clark, & Tellegen, 1988), Hospital Anxiety and Depression Scale (Zigmond & Snaith, 1983), and measures of pubertal development and demographics at ages 17, 18, and 19. Nonlinear age differences for letter fluency and concept formation executive functions were found, with a trough in functional ability in 18-year-olds compared with other groups. There were no age group differences on social cognition measures. Gender accounted for differences on 1 scale of concept formation, 1 dynamic social interaction scale, and 2 empathy scales. The clinical, developmental, and educational implications of these findings are discussed.

  5. Executive Function in Early Childhood: Longitudinal Measurement Invariance and Developmental Change

    ERIC Educational Resources Information Center

    Willoughby, Michael T.; Wirth, R. J.; Blair, Clancy B.

    2012-01-01

    This study tested the longitudinal measurement invariance and developmental changes of a newly developed battery of executive function (EF) tasks for use in early childhood. The battery was administered in the Family Life Project--a prospective longitudinal study (N = 1,292) of families who were oversampled from low-income and African American…

  6. [Screening interview for early detection of high-functioning autism spectrum disorders].

    PubMed

    Hoffmann, Wiebke; Heinzel-Gutenbrunner, Monika; Becker, Katja; Kamp-Becker, Inge

    2015-05-01

    Various different questionnaires are available for the screening of autism spectrum disorders (ASD). These screening instruments show high sensitivity and are able to identify a large number of individuals with ASD, but they lack the specificity to differentiate individuals with ASD from those children and adolescents with other complex neurobehavioural disorders (such as attention-deficit/hyperactivity disorder, emotional disorders, and others), especially for those without intellectual disabilities. The present study evaluates the data of 309 individuals (153 with high-functioning ASD, 156 with other psychiatric disorders, IQ > 70) to find out whether selected items of the ADI-R can be used for an economic and sensitive screening of high-functioning ASD. The results show that 8 items of the ADI-R can be used to discriminate high-functioning ASD and other psychiatric disorders. A cutoff of 5 led to a sensitivity of 0.93 and a cutoff of 6 to a specificity of 0.74. The combination of early onset, serious abnormalities in social contact with stereotyped or compulsive-ritualized behaviour or interests can be detected with few interview questions for screening of ASD. Nevertheless, a more detailed and specific assessment in an expert setting should follow the screening process.

  7. Early results from Magsat. [studies of near-earth magnetic fields

    NASA Technical Reports Server (NTRS)

    Langel, R. A.; Estes, R. H.; Mayhew, M. A.

    1981-01-01

    Papers presented at the May 27, 1981 meeting of the American Geophysical Union concerning early results from the Magsat satellite program, which was designed to study the near-earth magnetic fields originating in the core and lithosphere, are discussed. The satellite was launched on October 30, 1979 into a sun-synchronous (twilight) orbit, and re-entered the atmosphere on June 11, 1980. Instruments carried included a cesium vapor magnetometer to measure field magnitudes, a fluxgate magnetometer to measure field components and an optical system to measure fluxgate magnetometer orientation. Early results concerned spherical harmonic models, fields due to ionospheric and magnetospheric currents, the identification and interpretation of fields from lithospheric sources. The preliminary results confirm the possibility of separating the measured field into core, crustal and external components, and represent significant developments in analytical techniques in main-field modelling and the physics of the field sources.

  8. A continued role for signaling functions in the early evolution of feathers.

    PubMed

    Ruxton, Graeme D; Persons Iv, W Scott; Currie, Philip J

    2017-03-01

    Persons and Currie (2015) argued against either flight, thermoregulation, or signaling as a functional benefit driving the earliest evolution of feathers; rather, they favored simple feathers having an initial tactile sensory function, which changed to a thermoregulatory function as density increased. Here, we explore the relative merits of early simple feathers that may have originated as tactile sensors progressing instead toward a signaling, rather than (or in addition to) a thermoregulatory function. We suggest that signaling could act in concert with a sensory function more naturally than could thermoregulation. As such, the dismissal of a possible signaling function and the presumption that an initial sensory function led directly to a thermoregulatory function (implicit in the title "bristles before down") are premature. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

  9. Cognitive functioning in healthy aging: the role of reserve and lifestyle factors early in life.

    PubMed

    Fritsch, Thomas; McClendon, McKee J; Smyth, Kathleen A; Lerner, Alan J; Friedland, Robert P; Larsen, Janet D

    2007-06-01

    According to the reserve perspective on cognitive aging, individuals are born with or can develop resources that help them resist normal and disease-related cognitive changes that occur in aging. The reserve perspective is becoming more sophisticated, but gaps in knowledge persist. In the present research, we considered three understudied questions about reserve: Is reserve primarily static (unchangeable) throughout the life course or dynamic (changeable, in terms of increases or decreases)? Can reserve be increased at any point in life, or are there optimal time periods--such as early life, midlife, or late life--to increase it? Does participation in different types of leisure and occupational activities in early life and midlife have different effects depending on specific domains of late-life cognitive functioning? Here we link early cognitive and activity data--gathered from archival sources--with cognitive data from older adults to examine these issues. 349 participants, all mid-1940s graduates of the same high school, underwent telephone cognitive screening. All participants provided access to adolescent IQ scores; we determined activity levels from yearbooks. We used path analysis to evaluate the complex relationships between early life, midlife, and late-life variables. Adolescent IQ had strong direct effects on global cognitive functioning, episodic memory, verbal fluency, and processing speed. Participants' high school mental activities had direct effects on verbal fluency, but physical and social activities did not predict any cognitive measure. Education had direct effects on global cognitive functioning, episodic memory, and, most strongly, processing speed, but other midlife factors (notably, occupational demands) were not significant predictors of late-life cognition. There were weak indirect effects of adolescent IQ on global cognitive functioning, episodic memory, and processing speed, working through high school mental activities and education

  10. Alterations of functional connectivities from early to middle adulthood: Clues from multivariate pattern analysis of resting-state fMRI data.

    PubMed

    Tian, Lixia; Ma, Lin; Wang, Linlin

    2016-04-01

    In contrast to extended research interests in the maturation and aging of human brain, alterations of brain structure and function from early to middle adulthood have been much less studied. The aim of the present study was to investigate the extent and pattern of the alterations of functional interactions between brain regions from early to middle adulthood. We carried out the study by multivariate pattern analysis of resting-state fMRI (RS-fMRI) data of 63 adults aged 18 to 45 years. Specifically, using elastic net, we performed brain age estimation and age-group classification (young adults aged 18-28 years vs. middle-aged adults aged 35-45 years) based on the resting-state functional connectivities (RSFCs) between 160 regions of interest (ROIs) evaluated on the RS-fMRI data of each subject. The results indicate that the estimated brain ages were significantly correlated with the chronological age (R=0.78, MAE=4.81), and a classification rate of 94.44% and area under the receiver operating characteristic curve (AUC) of 0.99 were obtained when classifying the young and middle-aged adults. These results provide strong evidence that functional interactions between brain regions undergo notable alterations from early to middle adulthood. By analyzing the RSFCs that contribute to brain age estimation/age-group classification, we found that a majority of the RSFCs were inter-network, and we speculate that inter-network RSFCs might mature late but age early as compared to intra-network ones. In addition, the strengthening/weakening of the RSFCs associated with the left/right hemispheric ROIs, the weakening of cortico-cerebellar RSFCs and the strengthening of the RSFCs between the default mode network and other networks contributed much to both brain age estimation and age-group classification. All these alterations might reflect that aging of brain function is already in progress in middle adulthood. Overall, the present study indicated that the RSFCs undergo notable

  11. Intrauterine and early postnatal exposure to outdoor air pollution and lung function at preschool age.

    PubMed

    Morales, Eva; Garcia-Esteban, Raquel; de la Cruz, Oscar Asensio; Basterrechea, Mikel; Lertxundi, Aitana; de Dicastillo, Maria D Martinez López; Zabaleta, Carlos; Sunyer, Jordi

    2015-01-01

    Effects of prenatal and postnatal exposure to air pollution on lung function at preschool age remain unexplored. We examined the association of exposure to air pollution during specific trimesters of pregnancy and postnatal life with lung function in preschoolers. Lung function was assessed with spirometry in preschoolers aged 4.5 years (n=620) participating in the INfancia y Medio Ambiente (INMA) cohort. Temporally adjusted land use regression (LUR) models were applied to estimate individual residential exposures to benzene and nitrogen dioxide (NO₂) during specific trimesters of pregnancy and early postnatal life (the first year of life). Recent and current (1 year and 1 week before lung function testing, respectively) exposures to NO₂ and nitrogen oxides (NOx) were also assessed. Exposure to higher levels of benzene and NO₂ during pregnancy was associated with reduced lung function. FEV1 estimates for an IQR increase in exposures during the second trimester of pregnancy were -18.4 mL, 95% CI -34.8 to -2.1 for benzene and -28.0 mL, 95% CI -52.9 to -3.2 for NO₂. Relative risk (RR) of low lung function (<80% of predicted FEV1) for an IQR increase in benzene and NO₂ during the second trimester of pregnancy were 1.22, 95% CI 1.02 to 1.46 and 1.30, 95% CI 0.97 to 1.76, respectively. Associations for early postnatal, recent and current exposures were not statistically significant. Stronger associations appeared among allergic children and those of lower social class. Prenatal exposure to residential traffic-related air pollution may result in long-term lung function deficits at preschool age. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  12. Language processing and executive functions in early treated adults with phenylketonuria (PKU).

    PubMed

    De Felice, Sara; Romani, Cristina; Geberhiwot, Tarekegn; MacDonald, Anita; Palermo, Liana

    We provide an in-depth analysis of language functions in early-treated adults with phenylketonuria (AwPKUs, N = 15-33), as compared to age- and education-matched controls (N = 24-32; N varying across tasks), through: a. narrative production (the Cinderella story), b. language pragmatics comprehension (humour, metaphors, inferred meaning), c. prosody discrimination d. lexical inhibitory control and planning (Blocked Cyclic Naming; Hayling Sentence Completion Test, Burgess & Shallice, 1997). AwPKUs exhibited intact basic language processing (lexical retrieval, phonology/articulation, sentence construction). Instead, deficits emerged in planning and reasoning abilities. Compared to controls, AwPKUs were: less informative in narrative production (lower rate of Correct Information Units); slower in metaphorical understanding and inferred meaning; less accurate in focused lexical-search (Hayling test). These results suggest that i) executive deficits in PKU cannot be explained by an accumulation of lower-order deficits and/or general speed impairments, ii) executive functions engage dedicated neurophysiological resources, rather than simply being an emergent property of lower-level systems.

  13. Comparison of Neuropsychological Functioning Between Adults With Early- and Late-Onset DSM-5 ADHD.

    PubMed

    Lin, Yu-Ju; Gau, Susan Shur-Fen

    2017-09-01

    We aimed to compare the visually dependent neuropsychological functioning among adults with Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5) ADHD who recalled symptom onset by and after age 7 and non-ADHD controls. We divided the participants, aged 17 to 40 years, into three groups-(a) ADHD, onset <7 years (early-onset, n = 142); (b) ADHD, onset between 7 and <12 years (late-onset, n = 41); (c) non-ADHD controls ( n = 148)-and compared their neuropsychological functioning, measured by the Cambridge Neuropsychological Testing Automated Battery. Both ADHD groups had deficits in attention and signal detectability, spatial working memory, and short-term spatial memory, but only the early-onset group showed deficits in alertness, set-shifting, and planning after controlling for age, sex, and psychiatric comorbidities. There was no statistical difference between the two ADHD groups in neuropsychological functioning. DSM-5 criteria for diagnosing adult ADHD are not too lax regarding neuropsychological functioning.

  14. Executive Function in Adolescence: Associations with Child and Family Risk Factors and Self-Regulation in Early Childhood.

    PubMed

    Berthelsen, Donna; Hayes, Nicole; White, Sonia L J; Williams, Kate E

    2017-01-01

    Executive functions are important higher-order cognitive skills for goal-directed thought and action. These capacities contribute to successful school achievement and lifelong wellbeing. The importance of executive functions to children's education begins in early childhood and continues throughout development. This study explores contributions of child and family factors in early childhood to the development of executive function in adolescence. Analyses draw on data from the nationally representative study, Growing up in Australia: The Longitudinal Study of Australian Children . Participants are 4819 children in the Kindergarten Cohort who were recruited at age 4-5 years. Path analyses were employed to examine contributions of early childhood factors, including family socio-economic position (SEP), parenting behaviors, maternal mental health, and a child behavioral risk index, to the development of executive function in adolescence. The influence of children's early self-regulatory behaviors (attentional regulation at 4-5 years and approaches to learning at 6-7 years) were also taken into account. A composite score for the outcome measure of executive function was constructed from scores on three Cogstate computerized tasks for assessing cognition and measured visual attention, visual working memory, and spatial problem-solving. Covariates included child gender, age at assessment of executive function, Aboriginal and Torres Strait Islander status, speaking a language other than English at home, and child's receptive vocabulary skills. There were significant indirect effects involving child and family risk factors measured at 4-5 years on executive function at age 14-15 years, mediated by measures of self-regulatory behavior. Child behavioral risk, family SEP and parenting behaviors (anger, warmth, and consistency) were associated with attentional regulation at 4-5 years which, in turn, was significantly associated with approaches to learning at 6-7 years. Both

  15. Early Functional Connectome Integrity and 1-Year Recovery in Comatose Survivors of Cardiac Arrest.

    PubMed

    Sair, Haris I; Hannawi, Yousef; Li, Shanshan; Kornbluth, Joshua; Demertzi, Athena; Di Perri, Carol; Chabanne, Russell; Jean, Betty; Benali, Habib; Perlbarg, Vincent; Pekar, James; Luyt, Charles-Edouard; Galanaud, Damien; Velly, Lionel; Puybasset, Louis; Laureys, Steven; Caffo, Brian; Stevens, Robert D

    2018-04-01

    Purpose To assess whether early brain functional connectivity is associated with functional recovery 1 year after cardiac arrest (CA). Materials and Methods Enrolled in this prospective multicenter cohort were 46 patients who were comatose after CA. Principal outcome was cerebral performance category at 12 months, with favorable outcome (FO) defined as cerebral performance category 1 or 2. All participants underwent multiparametric structural and functional magnetic resonance (MR) imaging less than 4 weeks after CA. Within- and between-network connectivity was measured in dorsal attention network (DAN), default-mode network (DMN), salience network (SN), and executive control network (ECN) by using seed-based analysis of resting-state functional MR imaging data. Structural changes identified with fluid-attenuated inversion recovery and diffusion-weighted imaging sequences were analyzed by using validated morphologic scales. The association between connectivity measures, structural changes, and the principal outcome was explored with multivariable modeling. Results Patients underwent MR imaging a mean 12.6 days ± 5.6 (standard deviation) after CA. At 12 months, 11 patients had an FO. Patients with FO had higher within-DMN connectivity and greater anticorrelation between SN and DMN and between SN and ECN compared with patients with unfavorable outcome, an effect that was maintained after multivariable adjustment. Anticorrelation of SN-DMN predicted outcomes with higher accuracy than fluid-attenuated inversion recovery or diffusion-weighted imaging scores (area under the receiver operating characteristic curves, respectively, 0.88, 0.74, and 0.71). Conclusion MR imaging-based measures of cerebral functional network connectivity obtained in the acute phase of CA were independently associated with FO at 1 year, warranting validation as early markers of long-term recovery potential in patients with anoxic-ischemic encephalopathy. © RSNA, 2017.

  16. Percutaneous device closure of atrial septal defect results in very early and sustained changes of right and left heart function.

    PubMed

    Monfredi, Oliver; Luckie, Matthew; Mirjafari, Hoda; Willard, Terence; Buckley, Helen; Griffiths, Linda; Clarke, Bernard; Mahadevan, Vaikom S

    2013-08-20

    To investigate the echocardiographic effects of percutaneous closure of secundum atrial septal defect (ASD) in adults and assess which pre-closure parameters predict good response to closure. ASD is a common congenital heart disease often undiscovered until adulthood. ASD closure has been revolutionized by the use of percutaneous devices. The effects of these procedures on echocardiographic parameters are not well characterized. Patients undergoing percutaneous device closure of ASD between June 2007 and June 2009 had 3 sequential echocardiograms reviewed: pre-procedure, immediate post-procedure (24 hours) and 6-8 weeks post-procedure. Significant changes from baseline were investigated using paired t-test/1-way ANOVA. Pearson correlation (2-tailed) tests were used to categorize patients as 'good responders' to closure in terms of selected parameters. 129 echocardiograms in 43 consecutive patients were included. Remodeling of both ventricles occurred immediately following ASD closure and was sustained. Right ventricular (RV) diameter in diastole decreased by 13.5% and 19.3% compared to baseline at 24 hours and 6-8 weeks post-closure, respectively (p<0.05); Left ventricular (LV) diameter in diastole increased by 8.5% and 15.6%, respectively (p<0.05). Functional parameters of the RV also demonstrated early and sustained decreases (TAPSE decreased by 8.3% and 17% compared to baseline at 24 hours and 6-8 weeks post-closure, respectively (p<0.05)). Smaller RV baseline diameter appeared to predict good response to closure. Percutaneous ASD closure has immediate, sustained benefits on multiple echocardiographic parameters. Good responders have smaller RV at baseline, suggesting early closure is preferable. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  17. Neurocognitive predictors of remission of symptoms and social and role functioning in the early course of first-episode schizophrenia.

    PubMed

    Torgalsbøen, Anne-Kari; Mohn, Christine; Rishovd Rund, Bjørn

    2014-04-30

    In a Norwegian ongoing longitudinal study, we investigate the neurocognitive development in first-episode schizophrenia patients, and the influence of neurocognition on remission and real life functioning. In the present study, results from the early course of illness are reported. The sample includes 28 schizophrenia spectrum patients and 28 pairwise matched healthy controls. The patients were recruited from mental health service institutions and data on psychosocial functioning, remission and neurocognition were obtained through a clinical interview, an inventory on social and role functioning, operational criteria of remission, and a standardized neurocognitive test battery, the MATRICS Consensus Cognitive Battery (MCCB). Large effect size differences between patients and controls were observed at baseline on every cognitive domain, as well as statistically significant improvements on overall cognitive function at follow-up for the patient group. A remission rate of 61% was found. The neurocognitive baseline measure of Attention significantly predicted remission status at follow-up, whereas Attention and Working Memory at baseline predicted levels of social and role functioning. In the early course of the illness, more than half of the group of first-episode patients were in remission, and neurocognitive functions are significantly associated with both remission of symptoms and social and role functioning. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  18. Relationship between macular pigment and visual function in subjects with early age-related macular degeneration.

    PubMed

    Akuffo, Kwadwo Owusu; Nolan, John M; Peto, Tunde; Stack, Jim; Leung, Irene; Corcoran, Laura; Beatty, Stephen

    2017-02-01

    To investigate the relationship between macular pigment (MP) and visual function in subjects with early age-related macular degeneration (AMD). 121 subjects with early AMD enrolled as part of the Central Retinal Enrichment Supplementation Trial (CREST; ISRCTN13894787) were assessed using a range of psychophysical measures of visual function, including best corrected visual acuity (BCVA), letter contrast sensitivity (CS), mesopic and photopic CS, mesopic and photopic glare disability (GD), photostress recovery time (PRT), reading performance and subjective visual function, using the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25). MP was measured using customised heterochromatic flicker photometry. Letter CS, mesopic and photopic CS, photopic GD and mean reading speed were each significantly (p<0.05) associated with MP across a range of retinal eccentricities, and these statistically significant relationships persisted after controlling for age, sex and cataract grade. BCVA, NEI VFQ-25 score, PRT and mesopic GD were unrelated to MP after controlling for age, sex and cataract grade (p>0.05, for all). MP relates positively to many measures of visual function in unsupplemented subjects with early AMD. The CREST trial will investigate whether enrichment of MP influences visual function among those afflicted with this condition. ISRCTN13894787. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  19. Linguistic ability in early life and cognitive function and Alzheimer's disease in late life. Findings from the Nun Study.

    PubMed

    Snowdon, D A; Kemper, S J; Mortimer, J A; Greiner, L H; Wekstein, D R; Markesbery, W R

    1996-02-21

    To determine if linguistic ability in early life is associated with cognitive function and Alzheimer's disease in late life. Two measures of linguistic ability in early life, idea density and grammatical complexity, were derived from autobiographies written at a mean age of 22 years. Approximately 58 years later, the women who wrote these autobiographies participated in an assessment of cognitive function, and those who subsequently died were evaluated neuropathologically. Convents in the United States participating in the Nun Study; primarily convents in the Milwaukee, Wis, area. Cognitive function was investigated in 93 participants who were aged 75 to 95 years at the time of their assessments, and Alzheimer's disease was investigated in the 14 participants who died at 79 to 96 years of age. Seven neuropsychological tests and neuropathologically confirmed Alzheimer's disease. Low idea density and low grammatical complexity in autobiographies written in early life were associated with low cognitive test scores in late life. Low idea density in early life had stronger and more consistent associations with poor cognitive function than did low grammatical complexity. Among the 14 sisters who died, neuropathologically confirmed Alzheimer's disease was present in all of those with low idea density in early life and in none of those with high idea density. Low linguistic ability in early life was a strong predictor of poor cognitive function and Alzheimer's disease in late life.

  20. Atypical Lexical/Semantic Processing in High-Functioning Autism Spectrum Disorders without Early Language Delay

    ERIC Educational Resources Information Center

    Kamio, Yoko; Robins, Diana; Kelley, Elizabeth; Swainson, Brook; Fein, Deborah

    2007-01-01

    Although autism is associated with impaired language functions, the nature of semantic processing in high-functioning pervasive developmental disorders (HFPDD) without a history of early language delay has been debated. In this study, we aimed to examine whether the automatic lexical/semantic aspect of language is impaired or intact in these…

  1. Ecological variation in South American geophagine cichlids arose during an early burst of adaptive morphological and functional evolution

    PubMed Central

    Arbour, Jessica Hilary; López-Fernández, Hernán

    2013-01-01

    Diversity and disparity are unequally distributed both phylogenetically and geographically. This uneven distribution may be owing to differences in diversification rates between clades resulting from processes such as adaptive radiation. We examined the rate and distribution of evolution in feeding biomechanics in the extremely diverse and continentally distributed South American geophagine cichlids. Evolutionary patterns in multivariate functional morphospace were examined using a phylomorphospace approach, disparity-through-time analyses and by comparing Brownian motion (BM) and adaptive peak evolutionary models using maximum likelihood. The most species-rich and functionally disparate clade (CAS) expanded more efficiently in morphospace and evolved more rapidly compared with both BM expectations and its sister clade (GGD). Members of the CAS clade also exhibited an early burst in functional evolution that corresponds to the development of modern ecological roles and may have been related to the colonization of a novel adaptive peak characterized by fast oral jaw mechanics. Furthermore, reduced ecological opportunity following this early burst may have restricted functional evolution in the GGD clade, which is less species-rich and more ecologically specialized. Patterns of evolution in ecologically important functional traits are consistent with a pattern of adaptive radiation within the most diverse clade of Geophagini. PMID:23740780

  2. Can Parents' Involvement in Children's Education Offset the Effects of Early Insensitivity on Academic Functioning?

    ERIC Educational Resources Information Center

    Monti, Jennifer D.; Pomerantz, Eva M.; Roisman, Glenn I.

    2014-01-01

    Data from the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development (N = 1,312) were analyzed to examine whether the adverse effects of early insensitive parenting on children's academic functioning can be offset by parents' later involvement in children's education. Observations of mothers' early…

  3. The interplay of early-life stress, nutrition, and immune activation programs adult hippocampal structure and function

    PubMed Central

    Hoeijmakers, Lianne; Lucassen, Paul J.; Korosi, Aniko

    2015-01-01

    Early-life adversity increases the vulnerability to develop psychopathologies and cognitive decline later in life. This association is supported by clinical and preclinical studies. Remarkably, experiences of stress during this sensitive period, in the form of abuse or neglect but also early malnutrition or an early immune challenge elicit very similar long-term effects on brain structure and function. During early-life, both exogenous factors like nutrition and maternal care, as well as endogenous modulators, including stress hormones and mediator of immunological activity affect brain development. The interplay of these key elements and their underlying molecular mechanisms are not fully understood. We discuss here the hypothesis that exposure to early-life adversity (specifically stress, under/malnutrition and infection) leads to life-long alterations in hippocampal-related cognitive functions, at least partly via changes in hippocampal neurogenesis. We further discuss how these different key elements of the early-life environment interact and affect one another and suggest that it is a synergistic action of these elements that shapes cognition throughout life. Finally, we consider different intervention studies aiming to prevent these early-life adversity induced consequences. The emerging evidence for the intriguing interplay of stress, nutrition, and immune activity in the early-life programming calls for a more in depth understanding of the interaction of these elements and the underlying mechanisms. This knowledge will help to develop intervention strategies that will converge on a more complete set of changes induced by early-life adversity. PMID:25620909

  4. Early results from the ultra heavy cosmic ray experiment

    NASA Technical Reports Server (NTRS)

    Osullivan, D.; Thompson, A.; Bosch, J.; Keegan, R.; Wenzel, K.-P.; Jansen, F.; Domingo, C.

    1995-01-01

    Data extraction and analysis of the LDEF Ultra Heavy Cosmic Ray Experiment is continuing. Almost twice the pre LDEF world sample has been investigated and some details of the charge spectrum in the region from Z approximately 70 up to and including the actinides are presented. The early results indicate r process enhancement over solar system source abundances.

  5. Motivational deficits in early schizophrenia: prevalent, persistent, and key determinants of functional outcome.

    PubMed

    Fervaha, Gagan; Foussias, George; Agid, Ofer; Remington, Gary

    2015-08-01

    Negative symptoms, in particular motivational deficits, are reported as impediments to functional recovery in patients with schizophrenia. This study examined the prevalence of motivational deficits in patients early in the illness, and the impact these deficits have on community functioning. Patients with schizophrenia between the ages of 18 and 35years, and within 5years of initiating antipsychotic treatment were included in the present investigation (N=166). The impact of motivation and cognition on concurrent and longitudinal functioning was evaluated. Motivational impairments were found in more than 75% of participants, and were not associated with receipt of social support. These deficits served as the most robust and reliable predictor of functional outcome, while neurocognition demonstrated significantly weaker associations with outcome. When considered together, motivational deficits demonstrated a reliable link with concurrent and longitudinal functioning, with cognition not offering any independent predictive value. Moreover, motivation was found to mediate the relationship between cognition and outcome. Changes in motivation were linked to changes in functioning; however, this was not the case for changes in cognitive performance. Motivation emerged as a significant predictor of functioning even after selected demographic and clinical characteristics (e.g., positive symptoms) were accounted for. These data indicate that motivational deficits are prevalent in patients with schizophrenia, even in the early stages of the illness, and these deficits stand as one of the most robust barriers to people with schizophrenia achieving functional recovery. Greater understanding of the mechanisms underlying these deficits is critical to effective treatment innovation. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Early-life sugar consumption has long-term negative effects on memory function in male rats.

    PubMed

    Noble, Emily E; Hsu, Ted M; Liang, Joanna; Kanoski, Scott E

    2017-09-25

    Added dietary sugars contribute substantially to the diet of children and adolescents in the USA, and recent evidence suggests that consuming sugar-sweetened beverages (SSBs) during early life has deleterious effects on hippocampal-dependent memory function. Here, we test whether the effects of early-life sugar consumption on hippocampal function persist into adulthood when access to sugar is restricted to the juvenile/adolescent phase of development. Male rats were given ad libitum access to an 11% weight-by-volume sugar solution (made with high fructose corn syrup-55) throughout the adolescent phase of development (post-natal day (PN) 26-56). The control group received a second bottle of water instead, and both groups received ad libitum standard laboratory chow and water access throughout the study. At PN 56 sugar solutions were removed and at PN 175 rats were subjected to behavioral testing for hippocampal-dependent episodic contextual memory in the novel object in context (NOIC) task, for anxiety-like behavior in the Zero maze, and were given an intraperitoneal glucose tolerance test. Early-life exposure to SSBs conferred long-lasting impairments in hippocampal-dependent memory function later in life- yet had no effect on body weight, anxiety-like behavior, or glucose tolerance. A second experiment demonstrated that NOIC performance was impaired at PN 175 even when SSB access was limited to 2 hours daily from PN 26-56. Our data suggest that even modest SSB consumption throughout early life may have long-term negative consequences on memory function during adulthood.

  7. Targeted deletion of p97 (VCP/CDC48) in mouse results in early embryonic lethality.

    PubMed

    Müller, J M M; Deinhardt, K; Rosewell, I; Warren, G; Shima, D T

    2007-03-09

    The highly conserved AAA ATPase p97 (VCP/CDC48) has well-established roles in cell cycle progression, proteasome degradation and membrane dynamics. Gene disruption in Saccromyces cerevisiae, Drosophila melanogaster and Trypanosoma brucei demonstrated that p97 is essential in unicellular and multicellular organisms. To explore the requirement for p97 in mammalian cell function and embryogenesis, we disrupted the p97 locus by gene targeting. Heterozygous p97+/- mice were indistinguishable from their wild-type littermates, whereas homozygous mutants did not survive to birth and died at a peri-implantation stage. These results show that p97 is an essential gene for early mouse development.

  8. Caloric restriction preserves memory and reduces anxiety of aging mice with early enhancement of neurovascular functions

    PubMed Central

    Parikh, Ishita; Guo, Janet; Chuang, Kai-Hsiang; Zhong, Yu; Rempe, Ralf G.; Hoffman, Jared D.; Armstrong, Rachel; Bauer, Björn; Hartz, Anika M.S.; Lin, Ai-Ling

    2016-01-01

    Neurovascular integrity plays an important role in protecting cognitive and mental health in aging. Lifestyle interventions that sustain neurovascular integrity may thus be critical on preserving brain functions in aging and reducing the risk for age-related neurodegenerative disorders. Here we show that caloric restriction (CR) had an early effect on neurovascular enhancements, and played a critical role in preserving vascular, cognitive and mental health in aging. In particular, we found that CR significantly enhanced cerebral blood flow (CBF) and blood-brain barrier function in young mice at 5-6 months of age. The neurovascular enhancements were associated with reduced mammalian target of rapamycin expression, elevated endothelial nitric oxide synthase signaling, and increased ketone bodies utilization. With age, CR decelerated the rate of decline in CBF. The preserved CBF in hippocampus and frontal cortex were highly correlated with preserved memory and learning, and reduced anxiety, of the aging mice treated with CR (18-20 months of age). Our results suggest that dietary intervention started in the early stage (e.g., young adults) may benefit cognitive and mental reserve in aging. Understanding nutritional effects on neurovascular functions may have profound implications in human brain aging and age-related neurodegenerative disorders. PMID:27829242

  9. Early Pregnancy Diabetes Screening and Diagnosis: Prevalence, Rates of Abnormal Test Results, and Associated Factors.

    PubMed

    Mission, John F; Catov, Janet; Deihl, Tiffany E; Feghali, Maisa; Scifres, Christina

    2017-11-01

    To evaluate the prevalence of early diabetes screening in pregnancy, rates of abnormal diabetes test results before 24 weeks of gestation, and factors associated with early diabetes screening. This was a retrospective cohort study of all singleton deliveries from 2012 to 2014 among diverse clinical practices at a large academic medical center. We assessed rates of early (less than 24 weeks of gestation) and routine (at or beyond 24 weeks of gestation) diabetes screening, with abnormal test results defined using the Carpenter-Coustan criteria, a 50-g glucose challenge test result greater than 200 mg/dL, or a hemoglobin A1C level greater than 6.5%. Univariate and multivariate analyses were used to evaluate clinical and demographic determinants of screening and diagnosis. Overall, 1,420 of 11,331 (12.5%) women underwent early screening. Increasing body mass index (BMI) category, race, public insurance, history of gestational diabetes mellitus, a family history of diabetes, and chronic hypertension were associated with early screening. Early screening rates rose with increasing BMI category, but only 268 of 551 (48.6%) of women with class III obesity underwent early screening. Among those screened early, 2.0% of normal-weight women, 4.0% of overweight women, 4.2% of class I obese women, 3.8% of class II obese women, and 9.0% of class III obese women had abnormal early test results (P<.001). Early diabetes screening is used inconsistently, and many women with risk factors do not undergo early screening. A significant proportion of women with class III obesity will test positive for gestational diabetes mellitus before 24 weeks of gestation, and studies are urgently needed to assess the effect of early diabetes screening and diagnosis on perinatal outcomes in high-risk women.

  10. Biochemical, histological and behavioural aspects of visual function during early development of rainbow trout

    USGS Publications Warehouse

    Carvalho, Paulo S. M.; Noltie, Douglas B.; Tillitt, D.E.

    2004-01-01

    Retinal structure and concentration of retinoids involved in phototransduction changed during early development of rainbow trout Oncorhynchus mykiss, correlating with improvements in visual function. A test chamber was used to evaluate the presence of optokinetic or optomotor responses and to assess the functionality of the integrated cellular, physiological and biochemical components of the visual system. The results indicated that in rainbow trout optomotor responses start at 10 days post-hatch, and demonstrated for the first time that increases in acuity, sensitivity to low light as well as in motion detection abilities occur from this stage until exogenous feeding starts. The structure of retinal cells such as cone ellipsoids increased in length as photopic visual acuity improved, and rod densities increased concurrently with improvements in scotopic thresholds (2.2 log10 units). An increase in the concentrations of the chromophore all-trans-retinal correlated with improvements of all behavioural measures of visual function during the same developmental phase. ?? 2004 The Fisheries Society of the British Isles.

  11. Team functioning as a predictor of patient outcomes in early medical home implementation.

    PubMed

    Wu, Frances M; Rubenstein, Lisa V; Yoon, Jean

    New models of patient-centered primary care such as the patient-centered medical home (PCMH) depend on high levels of interdisciplinary primary care team functioning to achieve improved outcomes. A few studies have qualitatively assessed barriers and facilitators to optimal team functioning; however, we know of no prior study that assesses PCMH team functioning in relationship to patient health outcomes. The aim of the study was to assess the relationships between primary care team functioning, patients' use of acute care, and mortality. Retrospective longitudinal cohort analysis of patient outcomes measured at two time points (2012 and 2013) after PCMH implementation began in Veterans Health Administration practices. Multilevel models examined practice-level measures of team functioning in relationship to patient outcomes (all-cause and ambulatory care-sensitive condition-related hospitalizations, emergency department visits, and mortality). We controlled for practice-level factors likely to affect team functioning, including leadership support, provider and staff burnout, and staffing sufficiency, as well as for individual patient characteristics. We also tested the model among a subgroup of vulnerable patients (homeless, mentally ill, or with dementia). In adjusted analyses, higher team functioning was associated with lower mortality (OR = 0.92, p = .04) among all patients and with fewer all-cause admissions (incidence rate ratio [IRR] = 0.90, p < 0.01), ambulatory care-sensitive condition-related admissions (IRR = 0.91, p = .04), and emergency department visits (IRR = 0.91, p = .03) in the vulnerable patient subgroup. These early findings give support for the importance of team functioning within PCMH models for achieving improved patient outcomes. A focus on team functioning is important especially in the early implementation of team-based primary care models.

  12. Early-Life Exposure to Perfluoroalkyl Substances and Childhood Metabolic Function.

    PubMed

    Fleisch, Abby F; Rifas-Shiman, Sheryl L; Mora, Ana M; Calafat, Antonia M; Ye, Xiaoyun; Luttmann-Gibson, Heike; Gillman, Matthew W; Oken, Emily; Sagiv, Sharon K

    2017-03-01

    Perfluoroalkyl substances (PFASs) are synthetic chemicals that may persist in the environment and in humans. There is a possible association between early-life PFAS exposure and metabolic dysfunction in later life, but data are limited. We studied 665 mother-child pairs in Project Viva, a Boston, Massachusetts-area cohort recruited 1999-2002. We quantified concentrations of PFASs [perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoate (PFNA), perfluorohexane sulfonate (PFHxS), and perfluorodecanoate (PFDeA)] in maternal plasma collected at the first prenatal visit (median, 9.6 weeks gestation) and in child plasma from the mid-childhood research visit (median, 7.7 years). We assessed leptin, adiponectin, and homeostatic model assessment of insulin resistance (HOMA-IR) in mid-childhood. We fit covariate-adjusted linear regression models and conducted stratified analyses by child sex. Children with higher PFAS concentrations had lower HOMA-IR [e.g., -10.1% (95% CI: -17.3, -2.3) per interquartile range increment in PFOA]. This inverse association between child PFAS and HOMA-IR was more pronounced in females [e.g., PFOA: -15.6% (95% CI: -25.4, -4.6) vs. -6.1% (95% CI: -16.2, 5.2) for males]. Child PFAS plasma concentrations were not associated with leptin or adiponectin. Prenatal PFAS plasma concentrations were not associated with leptin, adiponectin, or HOMA-IR in offspring. We found no evidence for an adverse effect of early-life PFAS exposure on metabolic function in mid-childhood. In fact, children with higher PFAS concentrations had lower insulin resistance. Citation: Fleisch AF, Rifas-Shiman SL, Mora AM, Calafat AM, Ye X, Luttmann-Gibson H, Gillman MW, Oken E, Sagiv SK. 2017. Early-life exposure to perfluoroalkyl substances and childhood metabolic function. Environ Health Perspect 125:481-487; http://dx.doi.org/10.1289/EHP303.

  13. An Early Years Toolbox for Assessing Early Executive Function, Language, Self-Regulation, and Social Development: Validity, Reliability, and Preliminary Norms

    ERIC Educational Resources Information Center

    Howard, Steven J.; Melhuish, Edward

    2017-01-01

    Several methods of assessing executive function (EF), self-regulation, language development, and social development in young children have been developed over previous decades. Yet new technologies make available methods of assessment not previously considered. In resolving conceptual and pragmatic limitations of existing tools, the Early Years…

  14. Modified Da Chengqi granules improvement in immune function in early severe acute pancreatitis patients.

    PubMed

    Jiang, D-L; Yang, J; Jiang, S-Y; Yuan, F-L; Gu, Y-L; Li, J-P; Pei, Z-J

    2016-06-24

    We investigated the role of modified Da Chengqi granules in improving immune function in early severe acute pancreatitis patients. Early severe acute pancreatitis patients who agreed to receive combined treatment of traditional Chinese and Western medicine were randomly assigned to the experimental or control group. All subjects received conventional therapy to support organ function. The experimental group also received modified Da Chengqi granules. Cytokine (interleukin-6, interleukin-10, and tumor necrosis factor-α) levels, immunological markers (HLA-DR, Treg, and Th1/Th2), urinary lactulose/mannitol ratio, and endotoxin levels were measured at 1, 3, 7, and 14 days after hospital admission. The total mortality rate was 11.69% (9/77), which was significantly lower in the experimental group [4.88% (2/41)] than in the control group [19.44% (7/36); χ(2) = 3.940, P < 0.05]. Serum interleukin-6, interleukin-10, tumor necrosis factor-α and endotoxin levels and the lactulose/mannitol ratio were significantly lower on day 7 and day 14 than on day 1 in experimental and control groups (P < 0.01). Immunological indices were significantly lower in the experimental group than in the control group on day 14 (all P < 0.01 or 0.05). HLA-DR-positive cell ratio gradually increased over 14 days in experimental and control groups (P < 0.01 vs day 1), but was higher in the experimental group than in the control group by day 14 (P < 0.05). Notably, Treg cell prevalence and Th1/Th2 cell ratio deteriorated within 7 days in both groups (P < 0.01 vs day 1), but then returned to day 1 levels (P < 0.01 or 0.05 vs day 1). Significant differences in Treg levels and Th1/Th2 cell ratio between experimental and control groups were observed on day 14 (P < 0.01). These results show that modified Da Chengqi granules can improve immune function in early severe acute pancreatitis patients.

  15. Function of the two Xenopus smad4s in early frog development.

    PubMed

    Chang, Chenbei; Brivanlou, Ali H; Harland, Richard M

    2006-10-13

    Signals from the transforming growth factor beta family members are transmitted in the cell through specific receptor-activated Smads and a common partner Smad4. Two Smad4 genes (alpha and beta/10, or smad4 and smad4.2) have been isolated from Xenopus, and conflicting data are reported for Smad4beta/10 actions in mesodermal and neural induction. To further understand the functions of the Smad4s in early frog development, we analyzed their activities in detail. We report that Smad10 is a mutant form of Smad4beta that harbors a missense mutation of a conserved arginine to histidine in the MH1 domain. The mutation results in enhanced association of Smad10 with the nuclear transcription corepressor Ski and leads to its neural inducing activity through inhibition of bone morphogenetic protein (BMP) signaling. In contrast to Smad10, both Smad4alpha and Smad4beta enhanced BMP signals in ectodermal explants. Using antisense morpholino oligonucleotides (MOs) to knockdown endogenous Smad4 protein levels, we discovered that Smad4beta was required for both activin- and BMP-mediated mesodermal induction in animal caps, whereas Smad4alpha affected only the BMP signals. Neither Smad4 was involved directly in neural induction. Expression of Smad4beta-MO in early frog embryos resulted in reduction of mesodermal markers and defects in axial structures, which were rescued by either Smad4alpha or Smad4beta. Smad4alpha-MO induced only minor deficiency at late stages. As Smad4beta, but not Smad4alpha, is expressed at high levels maternally and during early gastrulation, our data suggest that although Smad4alpha and Smad4beta may have similar activities, they are differentially utilized during frog embryogenesis, with only Smad4beta being essential for mesoderm induction.

  16. Executive Function in Adolescence: Associations with Child and Family Risk Factors and Self-Regulation in Early Childhood

    PubMed Central

    Berthelsen, Donna; Hayes, Nicole; White, Sonia L. J.; Williams, Kate E.

    2017-01-01

    Executive functions are important higher-order cognitive skills for goal-directed thought and action. These capacities contribute to successful school achievement and lifelong wellbeing. The importance of executive functions to children’s education begins in early childhood and continues throughout development. This study explores contributions of child and family factors in early childhood to the development of executive function in adolescence. Analyses draw on data from the nationally representative study, Growing up in Australia: The Longitudinal Study of Australian Children. Participants are 4819 children in the Kindergarten Cohort who were recruited at age 4–5 years. Path analyses were employed to examine contributions of early childhood factors, including family socio-economic position (SEP), parenting behaviors, maternal mental health, and a child behavioral risk index, to the development of executive function in adolescence. The influence of children’s early self-regulatory behaviors (attentional regulation at 4–5 years and approaches to learning at 6–7 years) were also taken into account. A composite score for the outcome measure of executive function was constructed from scores on three Cogstate computerized tasks for assessing cognition and measured visual attention, visual working memory, and spatial problem-solving. Covariates included child gender, age at assessment of executive function, Aboriginal and Torres Strait Islander status, speaking a language other than English at home, and child’s receptive vocabulary skills. There were significant indirect effects involving child and family risk factors measured at 4–5 years on executive function at age 14–15 years, mediated by measures of self-regulatory behavior. Child behavioral risk, family SEP and parenting behaviors (anger, warmth, and consistency) were associated with attentional regulation at 4–5 years which, in turn, was significantly associated with approaches to learning at 6

  17. Technology-based functional assessment in early childhood intervention: a pilot study.

    PubMed

    Khetani, Mary A; McManus, Beth M; Arestad, Kristen; Richardson, Zachary; Charlifue-Smith, Renee; Rosenberg, Cordelia; Rigau, Briana

    2018-01-01

    Electronic patient-reported outcomes (e-PROs) may provide valid and feasible options for obtaining family input on their child's functioning for care planning and outcome monitoring, but they have not been adopted into early intervention (EI). The purpose of this pilot study was to evaluate the feasibility of implementing technology-based functional assessment into EI practice and to examine child, family, service, and environmental correlates of caregiver-reported child functioning in the home. In a cross-sectional design, eight individual EI providers participated in a 90-min technology-based functional assessment training to recruit participants and a 60-min semi-structured focus group post data collection. Participants completed the Young Children's Participation and Environment Measure (YC-PEM) home section online and Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT) via iPad. Participants' EI service use data were obtained from administrative records. A total of 37 caregivers of children between 6 and 35 months old (mean age = 19.4, SD = 7.7) enrolled, a rate of 44% (37/84) in 2.5 months. Providers suggested expanding staff training, gathering data during scheduled evaluations, and providing caregivers and providers with access to assessment summaries. Caregivers wanted their child's participation to change in 56% of home activities. Lower caregiver education and higher EI intensity were related to less child involvement in home activities. Implementing technology-based functional assessment is feasible with modifications, and these data can be useful for highlighting child, family, and EI service correlates of caregiver-reported child functioning that merit further study. Feasibility results informed protocol modifications related to EI provider training, timing of data collection, and management of EI service use data extraction, as preparation for a subsequent scale-up study that is underway.

  18. Early life stress determines the effects of glucocorticoids and stress on hippocampal function: Electrophysiological and behavioral evidence respectively.

    PubMed

    Pillai, Anup G; Arp, Marit; Velzing, Els; Lesuis, Sylvie L; Schmidt, Mathias V; Holsboer, Florian; Joëls, Marian; Krugers, Harm J

    2018-05-01

    Exposure to early-life adversity may program brain function to prepare individuals for adaptation to matching environmental contexts. In this study we tested this hypothesis in more detail by examining the effects of early-life stress - induced by raising offspring with limited nesting and bedding material from postnatal days 2-9 - in various behavioral tasks and on synaptic function in adult mice. Early-life stress impaired adult performance in the hippocampal dependent low-arousing object-in-context recognition memory task. This effect was absent when animals were exposed to a single stressor before training. Early-life stress did not alter high-arousing context and auditory fear conditioning. Early-life stress-induced behavioral modifications were not associated with alterations in the dendritic architecture of hippocampal CA1 pyramidal neurons or principal neurons of the basolateral amygdala. However, early-life stress reduced the ratio of NMDA to AMPA receptor-mediated excitatory postsynaptic currents and glutamate release probability specifically in hippocampal CA1 neurons, but not in the basolateral amygdala. These ex vivo effects in the hippocampus were abolished by acute glucocorticoid treatment. Our findings support that early-life stress can hamper object-in-context learning via pre- and postsynaptic mechanisms that affect hippocampal function but these effects are counteracted by acute stress or elevated glucocorticoid levels. Copyright © 2018. Published by Elsevier Ltd.

  19. Altered functional connectivity in early Alzheimer's disease: a resting-state fMRI study.

    PubMed

    Wang, Kun; Liang, Meng; Wang, Liang; Tian, Lixia; Zhang, Xinqing; Li, Kuncheng; Jiang, Tianzi

    2007-10-01

    Previous studies have led to the proposal that patients with Alzheimer's disease (AD) may have disturbed functional connectivity between different brain regions. Furthermore, recent resting-state functional magnetic resonance imaging (fMRI) studies have also shown that low-frequency (<0.08 Hz) fluctuations (LFF) of the blood oxygenation level-dependent signals were abnormal in several brain areas of AD patients. However, few studies have investigated disturbed LFF connectivity in AD patients. By using resting-state fMRI, this study sought to investigate the abnormal functional connectivities throughout the entire brain of early AD patients, and analyze the global distribution of these abnormalities. For this purpose, the authors divided the whole brain into 116 regions and identified abnormal connectivities by comparing the correlation coefficients of each pair. Compared with healthy controls, AD patients had decreased positive correlations between the prefrontal and parietal lobes, but increased positive correlations within the prefrontal lobe, parietal lobe, and occipital lobe. The AD patients also had decreased negative correlations (closer to zero) between two intrinsically anti-correlated networks that had previously been found in the resting brain. By using resting-state fMRI, our results supported previous studies that have reported an anterior-posterior disconnection phenomenon and increased within-lobe functional connectivity in AD patients. In addition, the results also suggest that AD may disturb the correlation/anti-correlation effect in the two intrinsically anti-correlated networks. Wiley-Liss, Inc.

  20. Executive function impairment in early-treated PKU subjects with normal mental development.

    PubMed

    Leuzzi, V; Pansini, M; Sechi, E; Chiarotti, F; Carducci, Cl; Levi, G; Antonozzi, I

    2004-01-01

    Executive functions were studied in 14 early and continuously treated PKU subjects (age 10.8 years, range 8-13) in comparison with controls matched for IQ, sex, age and socioeconomic status. Brain MRI examination was normal in all PKU patients. Neuropsychological evaluation included Wisconsin Card Sorting Test, Rey-Osterreith Complex Figure Test, Elithorn's Perceptual Maze Test, Weigl's Sorting Test, Tower of London, Visual Search and Motor Motor Learning Test. Whatever the IQ, PKU subjects performed worse than controls in tests exploring executive functions. Subgrouping the PKU subjects according to the quality of dietary control for the entire follow-up period (using 400 micromol/L as cut-off value for blood phenylalanine (Phe) concentration) showed that patients with worse dietary control performed more poorly than both the PKU group with the best dietary control and the control group. However, a mild impairment of executive functions was still found in PKU patients with a good dietary control (Phe <400 micromol/L) compared to controls. Concerning the PKU group as a whole, no linear correlation was found between neuropsychological performance and historical and concurrent biochemical parameters. We conclude that (a) PKU patients, even when treated early, rigorously and continuously, show an impairment of frontal lobe functions; (b) a protracted exposure to moderately high levels of Phe can affect frontal lobe functions independently of the possible effect of the same exposure on IQ; (c) in order to reduce the risk of frontal lobe dysfunction, the target of dietary therapy should be to maintain blood Phe concentration below 400 micromol/L.

  1. Manipulation under anaesthetic for frozen shoulder using Codman's paradox: a safe and early return of function.

    PubMed

    Tsvieli, Oren; Atoun, Ehud; Consigliere, Paolo; Polyzois, Ioannis; Walecka, Joanna; Pradhan, Rajib; Ippolito, Giorgio; Rath, Ehud; Levy, Ofer

    2018-02-01

    Although previously frozen shoulder was thought to resolve by two to three years, recent studies demonstrated the symptoms can remain for much longer. Manipulation under anaesthetic (MUA) has been shown to be successful in relieving pain and restoring function. Yet, concerns have been raised regarding its safety and the risks of complications. We utilise Codman's paradox to manipulate the shoulder, avoiding rotational torque on the humerus. The aim of our study was to asses shoulder function in the early post MUA period. Two hundred twelve consecutive patients (224 shoulders) (mean age 52.4 years) underwent MUA using Codman's paradox for frozen shoulder as sole procedure between 2005 and 2013. All were evaluated clinically, preoperatively and postoperatively, at three weeks and three months, for Constant score (CS), pain, range of motion (ROM), patient satisfaction and subjective shoulder value (SSV). At three weeks and three months, a significant improvement was found in CS from 30.7 to 66 and 70 respectively. Forward elevation improved from 91° to 154° and 160 °, abduction from 69° to 150° and 156 °, internal rotation from 12° to 62° and 66 °, and external rotation from 10° to 46° and 50 °. Pain score improved from 4.4/15 to 9.6/15 and 10.4/15, SSV improved from 1.5/10 to 6.5/10 and 6.7/10. (p<0.001). Use of Codman's paradox provides a safe and efficient way to perform MUA for frozen shoulder. It results in dramatic early improvement in ROM, functional outcomes and high satisfaction, as early as three weeks post-operatively.

  2. Early Morning Functional Impairments in Stimulant-Treated Children with Attention-Deficit/Hyperactivity Disorder Versus Controls: Impact on the Family

    PubMed Central

    Schachar, Russell J.; Barkley, Russell A.; Nullmeier, Rick; Sallee, F. Randy

    2017-01-01

    Abstract Objective: Children with attention-deficit/hyperactivity disorder (ADHD) frequently manifest early morning functional (EMF) impairments before school. We conducted a quantitative research survey to assess the impact of these EMF impairments on the family unit (caregiver, spouse/partner, and siblings). Study Design: We developed an online survey questionnaire to collect data from 300 primary caregivers of children with ADHD and 50 primary caregivers of children who did not have ADHD. Results: Although the ADHD children we surveyed were currently treated with stable doses of stimulants as their primary ADHD medication for at least 3 months, their parents reported high levels of EMF impairments in the child, which had a substantial negative effect on the emotional well-being of parents, on parents' functioning during the early morning routine, and on the level of conflict with siblings. The impact of EMF impairments on family functioning was mediated by the severity of the index child's impairments. Conclusions: EMF impairments exert a pervasive and significantly negative emotional and functional burden on not only the primary caregiver but also on the spouse/partner and siblings. This work suggests that adequate ADHD symptom control during the early morning period may be an unmet need for school-age children with ADHD being treated with stimulants. More work is needed to confirm this finding and determine the degree to which symptom control at other times of day is also an unmet need. PMID:28394175

  3. Extraperitoneoscopic transcapsular adenomectomy: complications and functional results after at least 1 year of followup.

    PubMed

    Porpiglia, Francesco; Fiori, Cristian; Cavallone, Barbara; Morra, Ivano; Bertolo, Riccardo; Scarpa, Roberto Mario

    2011-05-01

    Laparoscopic simple prostatectomy has been proposed to treat large glands. To date groups have investigated the feasibility and perioperative results of laparoscopic simple prostatectomy but to our knowledge no study has focused on its complications and functional results at longer followup. We investigated complications and functional results in patients with a large prostate who were treated with laparoscopic simple prostatectomy and had at least 1 year of followup. From our prospectively maintained database we extracted data on 78 patients treated with laparoscopic simple prostatectomy at our institution who had at least 1 year of reported followup. Demographics, perioperative results, early and late complications, and functional results were evaluated. Followup was planned at 1, 3, 6 and 12 months, and every 6 months thereafter. Mean followup was 30 months. Grade III complications were recorded in 2 cases and late complications were reported in 4 (5%). Statistically significant differences were observed in the International Prostate Symptom Score, the International Prostate Symptom Score quality of life index and maximum urine flow when comparing preoperative and postoperative results. No significant differences were recorded in maximum urine flow or the International Prostate Symptom Score quality of life index during followup. Results suggest that laparoscopic simple prostatectomy is safe and effective even after a significant period, as indicated by the low complication rate and positive, stable functional results found during followup. In our opinion laparoscopic simple prostatectomy can be offered to patients as a valid treatment option for a large prostate at advanced laparoscopic centers. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  4. [Early functional hemispherectomy in hemimegalencephaly associated to refractory epilepsy].

    PubMed

    Fonseca, Luiz Fernando; Melo, Renato Pacheco de; Cukiert, Arthur; Burattini, Jose Augusto; Mariani, Pedro Paulo; Brandão, Ródio; Ceda, Lauro; Baldauf, Cristine Mella; Argentoni, Meire; Forster, Cássio; Baise, Carla

    2004-12-01

    Hemimegalencephaly (HME) is a rare congenital brain malformation of unknown etiology. Patients with HME can present with an early onset epileptic syndrome which is often refractory to medical treatment and associated to impaired neurological development. Functional hemispherectomy (FH) has proven to be a valuable treatment alternative in patients with refractory epilepsy in this setting. Very few children operated under the age of 6 months and bearing HME and catastrophic epilepsy (CE) have been described in the literature. This study reports on 2 kids younger than 6 months with HME and CE submitted to FH with good clinical outcome.

  5. A Strategy for Embedding Functional Motor and Early Numeracy Skill Instruction into Physical Education Activities

    ERIC Educational Resources Information Center

    Whinnery, Stacie B.; Whinnery, Keith W.; Eddins, Daisy

    2016-01-01

    This article addresses the challenges educators face when attempting to find a balance between both functional and academic skill instruction for students with severe, multiple disabilities including motor impairments. The authors describe a strategy that employs embedded instruction of early numeracy and functional motor skills during physical…

  6. Final visual acuity results in the early treatment for retinopathy of prematurity study.

    PubMed

    Good, William V; Hardy, Robert J; Dobson, Velma; Palmer, Earl A; Phelps, Dale L; Tung, Betty; Redford, Maryann

    2010-06-01

    To compare visual acuity at 6 years of age in eyes that received early treatment for high-risk prethreshold retinopathy of prematurity (ROP) with conventionally managed eyes. Infants with symmetrical, high-risk prethreshold ROP (n = 317) had one eye randomized to earlier treatment at high-risk prethreshold disease and the other eye managed conventionally, treated if ROP progressed to threshold severity. For asymmetric cases (n = 84), the high-risk prethreshold eye was randomized to either early treatment or conventional management. The main outcome measure was ETDRS visual acuity measured at 6 years of age by masked testers. Retinal structure was assessed as a secondary outcome. Analysis of all subjects with high-risk prethreshold ROP showed no statistically significant benefit for early treatment (24.3% vs 28.6% [corrected] unfavorable outcome; P = .15). Analysis of 6-year visual acuity results according to the Type 1 and 2 clinical algorithm showed a benefit for Type 1 eyes (25.1% vs 32.8%; P = .02) treated early but not Type 2 eyes (23.6% vs 19.4%; P = .37). Early-treated eyes showed a significantly better structural outcome compared with conventionally managed eyes (8.9% vs 15.2% unfavorable outcome; P < .001), with no greater risk of ocular complications. Early treatment for Type 1 high-risk prethreshold eyes improved visual acuity outcomes at 6 years of age. Early treatment for Type 2 high-risk prethreshold eyes did not. Application to Clinical Practice Type 1 eyes, not Type 2 eyes, should be treated early. These results are particularly important considering that 52% of Type 2 high-risk prethreshold eyes underwent regression of ROP without requiring treatment. Trial Registration clinicaltrials.gov Identifier: NCT00027222.

  7. Adult outcomes as a function of an early childhood educational program: an Abecedarian Project follow-up.

    PubMed

    Campbell, Frances A; Pungello, Elizabeth P; Burchinal, Margaret; Kainz, Kirsten; Pan, Yi; Wasik, Barbara H; Barbarin, Oscar A; Sparling, Joseph J; Ramey, Craig T

    2012-07-01

    Adult (age 30) educational, economic, and social-emotional adjustment outcomes were investigated for participants in the Abecedarian Project, a randomized controlled trial of early childhood education for children from low-income families. Of the original 111 infants enrolled (98% African American), 101 took part in the age 30 follow-up. Primary indicators of educational level, economic status, and social adjustment were examined as a function of early childhood treatment. Treated individuals attained significantly more years of education, but income-to-needs ratios and criminal involvement did not vary significantly as a function of early treatment. A number of other indicators were described for each domain. Overall, the findings provide strong evidence for educational benefits, mixed evidence for economic benefits, and little evidence for treatment-related social adjustment outcomes. Implications for public policy are discussed.

  8. Towards developing drought impact functions to advance drought monitoring and early warning

    NASA Astrophysics Data System (ADS)

    Bachmair, Sophie; Stahl, Kerstin; Hannaford, Jamie; Svoboda, Mark

    2015-04-01

    In natural hazard analysis, damage functions (also referred to as vulnerability or susceptibility functions) relate hazard intensity to the negative effects of the hazard event, often expressed as damage ratio or monetary loss. While damage functions for floods and seismic hazards have gained considerable attention, there is little knowledge on how drought intensity translates into ecological and socioeconomic impacts. One reason for this is the multifaceted nature of drought affecting different domains of the hydrological cycle and different sectors of human activity (for example, recognizing meteorological - agricultural - hydrological - socioeconomic drought) leading to a wide range of drought impacts. Moreover, drought impacts are often non-structural and hard to quantify or monetarize (e.g. impaired navigability of streams, bans on domestic water use, increased mortality of aquatic species). Knowledge on the relationship between drought intensity and drought impacts, i.e. negative environmental, economic or social effects experienced under drought conditions, however, is vital to identify critical thresholds for drought impact occurrence. Such information may help to improve drought monitoring and early warning (M&EW), one goal of the international DrIVER project (Drought Impacts: Vulnerability thresholds in monitoring and Early-warning Research). The aim of this study is to test the feasibility of designing "drought impact functions" for case study areas in Europe (Germany and UK) and the United States to derive thresholds meaningful for drought impact occurrence; to account for the multidimensionality of drought impacts, we use the broader term "drought impact function" over "damage function". First steps towards developing empirical drought impact functions are (1) to identify meaningful indicators characterizing the hazard intensity (e.g. indicators expressing a precipitation or streamflow deficit), (2) to identify suitable variables representing impacts

  9. Results of an early hearing detection program.

    PubMed

    Borkoski Barreiro, Silvia A; Falcón González, Juan C; Bueno Yanes, Jorge; Pérez Bermúdez, José L; López Cano, Zoraida; Ramos Macías, Ángel

    2013-01-01

    Neonatal hearing loss is a public health problem that meets the requirements for submission to universal screening. Our objective was to analyse the results of the early hearing detection and intervention program implemented at our centre between January 2007 and December 2010. We studied 26,717 newborns during the period mentioned, using transient otoacoustic emissions (TOAEs) for the screening. The diagnostic phase was carried out at the hearing loss department. In our area, there were 27,935 births between January 2007 and December 2010. The screening was performed on 26,717 children. Of these, 24,173 had positive TOAEs, 1,040 had no TOAEs and 1,504 presented TOAEs in 1 ear with absence of TOAEs in the contralateral ear. Risk factors associated with hearing loss were found in 4,674 infants. In a second phase of the program, TOAEs were given to 5,156 children, of whom 4,626 had positive otoacoustic emissions in both ears, 323 had no TOAEs in 1 ear and 207 failed this second phase. Of all children studied, 3.8% were referred to auditory brainstem response (ABR) testing and 26 children entered the cochlear implant program. The program reached coverage of 95.64%. The early hearing detection and intervention program at our hospital is suitable for our environment, reaching 95.64% of coverage. We consider the relationship between effectiveness and efficiency to be positive. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  10. Thresholds in forest bird occurrence as a function of the amount of early-seral broadleaf forest at landscape scales

    USGS Publications Warehouse

    Betts, M.G.; Hagar, J.C.; Rivers, J.W.; Alexander, J.D.; McGarigal, K.; McComb, B.C.

    2010-01-01

    Recent declines in broadleaf-dominated, early-seral forest globally as a function of intensive forest management and/or fire suppression have raised concern about the viability of populations dependent on such forest types. However, quantitative information about the strength and direction of species associations with broadleaf cover at landscape scales are rare. Uncovering such habitat relationships is essential for understanding the demography of species and in developing sound conservation strategies. It is particularly important to detect points in habitat reduction where rates of population decline may accelerate or the likelihood of species occurrence drops rapidly (i.e., thresholds). Here, we use a large avian point-count data set (N = 4375) from southwestern and northwestern Oregon along with segmented logistic regression to test for thresholds in forest bird occurrence as a function of broadleaf forest and early-seral broadleaf forest at local (150-m radius) and landscape (500–2000-m radius) scales. All 12 bird species examined showed positive responses to either broadleaf forest in general, and/or early-seral broadleaf forest. However, regional variation in species response to these conditions was high. We found considerable evidence for landscape thresholds in bird species occurrence as a function of broadleaf cover; threshold models received substantially greater support than linear models for eight of 12 species. Landscape thresholds in broadleaf forest ranged broadly from 1.35% to 24.55% mean canopy cover. Early-seral broadleaf thresholds tended to be much lower (0.22–1.87%). We found a strong negative relationship between the strength of species association with early-seral broadleaf forest and 42-year bird population trends; species most associated with this forest type have declined at the greatest rates. Taken together, these results provide the first support for the hypothesis that reductions in broadleaf-dominated early-seral forest due to

  11. Is Early-onset in Major Depression a Predictor of Specific Clinical Features with More Impaired Social Function?

    PubMed Central

    Liu, Yan-Hong; Chen, Lin; Su, Yun-Ai; Fang, Yi-Ru; Srisurapanont, Manit; Hong, Jin Pyo; Hatim, Ahmad; Chua, Hong Choon; Bautista, Dianne; Si, Tian-Mei

    2015-01-01

    Background: Early-onset major depressive disorder (MDD) (EOD) is often particularly malignant due to its special clinical features, accompanying impaired social function, protracted recovery time, and frequent recurrence. This study aimed to observe the effects of age onset on clinical characteristics and social function in MDD patients in Asia. Methods: In total, 547 out-patients aged 18–65 years who were from 13 study sites in five Asian countries were included. These patients had MDD diagnose according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria. Clinical features and social function were assessed using Symptom Checklist-90-revised (SCL-90-R) and Sheehan Disability Scale (SDS). Quality of life was assessed by a 36-item Short-form Health Survey (SF-36). Analyses were performed using a continuous or dichotomous (cut-off: 30 years) age-of-onset indicator. Results: Early-onset MDD (EOD, <30 years) was associated with longer illness (P = 0.003), unmarried status (P < 0.001), higher neuroticism (P ≤ 0.002) based on the SCL-90-R, and more limited social function and mental health (P = 0.006, P = 0.007) based on the SF-36 and SDS. The impairment of social function and clinical severity were more prominent at in-patients with younger onset ages. Special clinical features and more impaired social function and quality of life were associated with EOD, as in western studies. Conclusions: EOD often follows higher levels of neuroticism. Age of onset of MDD may be a predictor of clinical features and impaired social function, allowing earlier diagnosis and treatment. PMID:25758278

  12. The longitudinal development of social and executive functions in late adolescence and early adulthood

    PubMed Central

    Taylor, Sophie J.; Barker, Lynne A.; Heavey, Lisa; McHale, Sue

    2015-01-01

    Our earlier work suggests that, executive functions and social cognition show protracted development into late adolescence and early adulthood (Taylor et al., 2013). However, it remains unknown whether these functions develop linearly or non-linearly corresponding to dynamic changes to white matter density at these age ranges. Executive functions are particularly in demand during the transition to independence and autonomy associated with this age range (Ahmed and Miller, 2011). Previous research examining executive function (Romine and Reynolds, 2005) and social cognition (Dumontheil et al., 2010a) in late adolescence has utilized a cross sectional design. The current study employed a longitudinal design with 58 participants aged 17, 18, and 19 years completing social cognition and executive function tasks, Wechsler Abbreviated Scale of Intelligence (Wechsler, 1999), Positive and Negative Affect Schedule (Watson et al., 1988), and Hospital Anxiety and Depression Scale (Zigmond and Snaith, 1983) at Time 1 with follow up testing 12–16 months later. Inhibition, rule detection, strategy generation and planning executive functions and emotion recognition with dynamic stimuli showed longitudinal development between time points. Self-report empathy and emotion recognition functions using visual static and auditory stimuli were stable by age 17 whereas concept formation declined between time points. The protracted development of some functions may reflect continued brain maturation into late adolescence and early adulthood including synaptic pruning (Sowell et al., 2001) and changes to functional connectivity (Stevens et al., 2007) and/or environmental change. Clinical implications, such as assessing the effectiveness of rehabilitation following Head Injury, are discussed. PMID:26441579

  13. The Contribution of Executive Function to Source Memory Development in Early Childhood

    ERIC Educational Resources Information Center

    Rajan, Vinaya; Cuevas, Kimberly; Bell, Martha Ann

    2014-01-01

    Age-related differences in episodic memory judgments assessing recall of fact information and the source of this information were examined. The role of executive function (EF) in supporting early episodic memory ability was also explored. Four- and 6-year-old children were taught 10 novel facts from two different sources (experimenter or puppet),…

  14. Impairment in Proverb Interpretation as an Executive Function Deficit in Patients with Amnestic Mild Cognitive Impairment and Early Alzheimer's Disease

    PubMed Central

    Leyhe, Thomas; Saur, Ralf; Eschweiler, Gerhard W.; Milian, Monika

    2011-01-01

    Background/Aims Proverb interpretation is assumed to reflect executive functions. We hypothesized that proverb interpretation is impaired in patients with amnestic mild cognitive impairment (aMCI) diagnosed as single-domain impairment by common neuropsychological testing. Methods We compared performance in a proverb interpretation test in single-domain aMCI patients and patients with early Alzheimer's disease (EAD). Results The groups with aMCI and EAD performed significantly worse than healthy controls. Both patient groups gave concrete answers with a similar frequency. However, patients with EAD tended to give senseless answers more frequently. Conclusions Our data suggest that in patients diagnosed as single-domain aMCI, deterioration of executive functions is detectable with subtle and appropriate neuropsychological testing. Implementation of these procedures may improve the early prediction of AD. PMID:22163233

  15. Typologies of family functioning and children's adjustment during the early school years.

    PubMed

    Sturge-Apple, Melissa L; Davies, Patrick T; Cummings, E Mark

    2010-01-01

    Guided by family systems theory, the present study sought to identify patterns of family functioning from observational assessments of interparental, parent-child, and triadic contexts. In addition, it charted the implications for patterns of family functioning for children's developmental trajectories of adjustment in the school context across the early school years. Two-hundred thirty-four kindergarten children (129 girls and 105 boys; mean age = 6.0 years, SD = 0.50 at Wave 1) and their parents participated in this multimethod, 3-year longitudinal investigation. As expected, latent class analyses extracted 3 primary typologies of functioning including: (a) cohesive, (b) enmeshed, and (c) disengaged families. Furthermore, family patterns were differentially associated with children's maladaptive adjustment trajectories in the school context. The findings highlight the developmental utility of incorporating pattern-based approaches to family functioning.

  16. Relationship among blood indicators of lipomobilization and hepatic function during early lactation in high-yielding dairy cows.

    PubMed

    González, Felix Diaz; Muiño, Rodrigo; Pereira, Víctor; Campos, Rómulo; Benedito, José Luis

    2011-09-01

    Blood indicators are used as a tool to diagnose metabolic disorders. The present work was conducted to study the relationships among blood indicators of lipomobilization and hepatic function in high-yielding dairy cows. Two groups of Holstein cows were studied: 27 early lactation cows and 14 mid lactation cows from four different herds with similar husbandry characteristics in Galicia, Spain. Blood samples were obtained to measure beta-hydroxybutyrate (BHB), non-esterified fatty acids (NEFA), triglycerides (TG), and the activity of aspartate transaminase (AST) and gamma-glutamyl transferase. Cows in early lactation had higher levels of BHB and NEFA than mid lactation cows. High lipomobilization (NEFA > 400 µmol/L) was detected in 67% and 7% of early lactation and mid lactation cows, respectively, while subclinical ketosis (BHB > 1.2 mmol/L) was detected in 41% and 28% of the early lactation and lactation cows, respectively. TG concentrations were low in all cows suffering subclinical ketosis and in 61% of the cows with high lipomobilization. During early lactation, 30% of cows suffered hepatic lipidosis as detected by levels of AST. Compromised hepatic function was observed in early lactation cows as shown by lower concentrations of glucose, total protein, and urea.

  17. Optimization of CRISPR/Cas9 genome editing for loss-of-function in the early chick embryo.

    PubMed

    Gandhi, Shashank; Piacentino, Michael L; Vieceli, Felipe M; Bronner, Marianne E

    2017-12-01

    The advent of CRISPR/Cas9 has made genome editing possible in virtually any organism, including those not previously amenable to genetic manipulations. Here, we present an optimization of CRISPR/Cas9 for application to early avian embryos with improved efficiency via a three-fold strategy. First, we employed Cas9 protein flanked with two nuclear localization signal sequences for improved nuclear localization. Second, we used a modified guide RNA (gRNA) scaffold that obviates premature termination of transcription and unstable Cas9-gRNA interactions. Third, we used a chick-specific U6 promoter that yields 4-fold higher gRNA expression than the previously utilized human U6. For rapid screening of gRNAs for in vivo applications, we also generated a chicken fibroblast cell line that constitutively expresses Cas9. As proof of principle, we performed electroporation-based loss-of-function studies in the early chick embryo to knock out Pax7 and Sox10, key transcription factors with known functions in neural crest development. The results show that CRISPR/Cas9-mediated deletion causes loss of their respective proteins and transcripts, as well as predicted downstream targets. Taken together, the results reveal the utility of this optimized CRISPR/Cas9 method for targeted gene knockout in chicken embryos in a manner that is reproducible, robust and specific. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. [Evaluation and analysis of monitoring and early warning functions of the occupational disease reporting system in China].

    PubMed

    Zhu, Xiaojun; Li, Tao; Liu, Mengxuan

    2015-06-01

    To evaluate the monitoring and early warning functions of the occupational disease reporting system right now in China, and to analyze their influencing factors. An improved audit tool (ODIT) was used to score the monitoring and early warning functions with a total score of 10. The nine indices were completeness of information on the reporting form, coverage of the reporting system, accessibility of criteria or guidelines for diagnosis, education and training for physicians, completeness of the reporting system, statistical methods, investigation of special cases, release of monitoring information, and release of early warning information. According to the evaluation, the occupational disease reporting system in China had a score of 5.5 in monitoring existing occupational diseases with a low score for release of monitoring information; the reporting system had a score of 6.5 in early warning of newly occurring occupational diseases with low scores for education and training for physicians as well as completeness of the reporting system. The occupational disease reporting system in China still does not have full function in monitoring and early warning. It is the education and participation of physicians from general hospitals in the diagnosis and treatment of occupational diseases and suspected occupational diseases that need to be enhanced. In addition, the problem of monitoring the incidence of occupational diseases needs to be solved as soon as possible.

  19. Performance on innate behaviour during early development as a function of stress level.

    PubMed

    Ryu, Soojin; De Marco, Rodrigo J

    2017-08-10

    What is the relationship between the level of acute stress and performance on innate behaviour? The diversity of innate behaviours and lack of sufficient data gathered under the same experimental conditions leave this question unresolved. While evidence points to an inverted-U shaped relationship between the level of acute stress and various measures of learning and memory function, it is unknown the extent to which such a non-linear function applies to performance on innate behaviour, which develops without example or practice under natural circumstances. The fundamental prediction of this view is that moderate stress levels will improve performance, while higher levels will not. Testing this proposition has been difficult because it entails an overall effect that must be invariant to the nature of the stressor, the behaviour under scrutiny and the stimulus that drives it. Here, we report new experimental results showing that developing zebrafish (Danio rerio) under moderate but not higher levels of stress improved their performance on instinctive activities driven by visual, hydrodynamic and thermal inputs. Our findings reveal, for the first time, the existence of an inverted-U shaped performance function according to stress level during early development in a series of innate behaviours.

  20. Examination of the Positive and Negative Syndrome Scale factor structure and longitudinal relationships with functioning in early psychosis.

    PubMed

    Best, Michael W; Grossman, Michael; Oyewumi, L Kola; Bowie, Christopher R

    2016-04-01

    We examined the factor structure of the Positive and Negative Syndrome Scale (PANSS) in early-episode psychosis and its relationships with functioning at baseline and follow-up. A total of 240 consecutive admissions to an early intervention in psychosis clinic were assessed at intake to the program with the PANSS, Global Assessment of Functioning (GAF) and Social and Occupational Functioning Assessment Scale (SOFAS). Seventy individuals were reassessed at follow-up. A maximum likelihood factor analysis was conducted on baseline PANSS scores and the ability of each factor to predict baseline and follow-up GAF and SOFAS was examined. A five-factor model with varimax rotation was the best fit to our data and was largely congruent with factors found previously. The negative symptom factor was the best predictor of GAF and SOFAS at baseline and follow-up. Negative symptoms are the best symptomatic predictor of functioning in individuals with early psychosis and are an important treatment target to improve recovery. © 2014 Wiley Publishing Asia Pty Ltd.

  1. Early detection of endothelial injury and dysfunction in conjunction with correction of hemodynamic maladjustment can effectively restore renal function in type 2 diabetic nephropathy.

    PubMed

    Futrakul, Narisa; Butthep, Punnee; Vongthavarawat, Varaphon; Futrakul, Prasit; Sirisalipoch, Sasitorn; Chaivatanarat, Tawatchai; Suwanwalaikorn, Sompongse

    2006-01-01

    This paper was aimed to investigate (1) the early marker of endothelial injury in type 2 diabetes, (2) the intrarenal hemodynamics and renal function, and (3) the therapeutic strategy aiming to restore renal function. Fifty patients (35 normoalbuminuric and 15 albuminuric type 2 diabetes) were examined. Blood was collected for determination of circulating vascular endothelial cells (CEC) and the serum was prepared for determination of transforming growth factor beta (TGFbeta), ratio of CEC/TGFbeta, and soluble vascular cell adhesion molecule. Intrarenal hemodynamics and renal function were also assessed. The results showed that increased number of circulating EC, elevated TGFbeta and depleted ratio of CEC/TGFbeta were significantly observed. Intrarenal hemodynamic study revealed a hemodynamic maladjustment characterized by preferential constriction of the efferent arteriole, intraglomerular hypertension and reduction in peritubular capillary flow. It was concluded that early marker of endothelial injury is reflected by increasing number of CEC. Such markers correlate with the glomerular endothelial dysfunction associated with hemodynamic maladjustment. Early detection of endothelial injury and appropriate correction of hemodynamic maladjustment by multidrug vasodilators can effectively restore renal function in type 2 diabetic nephropathy.

  2. Associations of SF-36 mental health functioning and work and family related factors with intentions to retire early among employees.

    PubMed

    Harkonmäki, K; Rahkonen, O; Martikainen, P; Silventoinen, K; Lahelma, E

    2006-08-01

    To examine the associations of mental health functioning (SF-36) and work and family related psychosocial factors with intentions to retire early. Cross sectional survey data (n = 5037) from the Helsinki Health Study occupational cohort in 2001 and 2002 were used. Intentions to retire early were inquired with a question: "Have you considered retiring before normal retirement age?" Mental health functioning was measured by the Short Form 36 (SF-36) mental component summary (MCS). Work and family related psychosocial factors included job demands and job control, procedural and relational justice, conflicts between work and family, and social network size. Multinomial regression models were used to analyse the data. Poor mental health functioning, unfavourable psychosocial working conditions, and conflicts between work and family were individually related to intentions to retire early. After adjustments for all work and family related factors the odds ratio for low mental health functioning was halved (from OR = 6.05 to 3.67), but nevertheless the association between poor mental health functioning and strong intentions to retire early remained strong. These findings highlight not only the importance of low mental health and unfavourable working conditions but also the simultaneous impact of conflicts between work and family to employees' intentions to retire early.

  3. Executive Function Skills, Early Mathematics, and Vocabulary in Head Start Preschool Children

    ERIC Educational Resources Information Center

    Harvey, Hattie A.; Miller, Gloria E.

    2017-01-01

    Research Findings: The contribution of 3 executive function skills (shifting, inhibitory control, and working memory) and their relation to early mathematical skills was investigated with preschoolers attending 6 Head Start centers. Ninety-two children ranging in age from 3 years, 1 month, to 4 years, 11 months, who were native English or Spanish…

  4. Functioning of Social Skills from Middle Childhood to Early Adolescence in Hungary

    ERIC Educational Resources Information Center

    Zsolnai, Anikó; Kasik, László

    2014-01-01

    The aim of this cross-sectional study was to describe the social skills that crucially affect children's social behaviour in the school. Our objective was to gather information about the functioning of social skills from middle childhood to early adolescence. The sample consisted of 7-, 9-, and 11-year-old Hungarian students (N = 1398). Based on…

  5. Later Life Changes in Hippocampal Neurogenesis and Behavioral Functions After Low-Dose Prenatal Irradiation at Early Organogenesis Stage

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

    Ganapathi, Ramya; Manda, Kailash, E-mail: kailashmanda@gmail.com

    Purpose: To investigate long-term changes in behavioral functions of mice after exposure to low-dose prenatal radiation at an early organogenesis stage. Methods and Materials: Pregnant C57BL/6J mice were irradiated (20 cGy) at postcoitus day 5.5. The male and female offspring were subjected to different behavioral assays for affective, motor, and cognitive functions at 3, 6, and 12 months of age. Behavioral functions were further correlated with the population of CA1 and CA3 pyramidal neurons and immature neurons in hippocampal dentate gyrus. Results: Prenatally exposed mice of different age groups showed a sex-specific pattern of sustained changes in behavioral functions. Male mice showed significantmore » changes in anxiety-like phenotypes, learning, and long-term memory at age 3 months. At 6 months of age such behavioral functions were recovered to a normal level but could not be sustained at age 12 months. Female mice showed an appreciable recovery in almost all behavioral functions at 12 months. Patterns of change in learning and long-term memory were comparable to the population of CA1 and CA3 pyramidal neurons and doublecortin-positive neurons in hippocampus. Conclusion: Our finding suggests that prenatal (early organogenesis stage) irradiation even at a lower dose level (20 cGy) is sufficient to cause potential changes in neurobehavioral function at later stages of life. Male mice showed relatively higher vulnerability to radiation-induced neurobehavioral changes as compared with female.« less

  6. Results of a Coordinated Specialty Care Program for Early Psychosis and Predictors of Outcomes.

    PubMed

    Nossel, Ilana; Wall, Melanie M; Scodes, Jennifer; Marino, Leslie A; Zilkha, Sacha; Bello, Iruma; Malinovsky, Igor; Lee, Rufina; Radigan, Marleen; Smith, Thomas E; Sederer, Lloyd; Gu, Gyojeong; Dixon, Lisa

    2018-05-15

    This study prospectively evaluated outcomes of OnTrackNY, a statewide coordinated specialty care (CSC) program for treatment of early psychosis in community settings, as well as predictors of outcomes. The sample included 325 individuals ages 16-30 with recent-onset nonaffective psychosis who were enrolled in OnTrackNY and who had at least one three-month follow-up. Clinicians provided data at baseline and quarterly up to one year. Domains assessed included demographic and clinical characteristics, social and occupational functioning, medications, suicidality and violence, hospitalization, and time to intervention. Primary outcomes included the symptoms, occupational functioning, and social functioning scales of the Global Assessment of Functioning (GAF), as adapted by the U.S. Department of Veterans Affairs Mental Illness Research, Education and Clinical Center; education and employment status; and psychiatric hospitalization rate. Education and employment rates increased from 40% to 80% by six months, hospitalization rates decreased from 70% to 10% by three months, and improvement in GAF scores continued for 12 months. Female gender, non-Hispanic white race-ethnicity, and more education at baseline predicted better education and employment status at follow-up. Individuals with early psychosis receiving CSC achieved significant improvements in education and employment and experienced a decrease in hospitalization rate. Demographic variables and baseline education predicted education and employment outcomes. CSC teams should make particular effort to support the occupational goals of individuals at increased risk of not engaging in work or school, including male participants and participants from racial and ethnic minority groups.

  7. Early colonization of functional groups of microbes in the infant gut.

    PubMed

    Pham, Van T; Lacroix, Christophe; Braegger, Christian P; Chassard, Christophe

    2016-07-01

    The colonization of the infant gut is crucial for early life development. Although the composition and diversity of the infant gut microbiota (GM) has been well described at a taxonomic level, functional aspects of this ecosystem remain unexplored. In the infant gut, lactate is produced by a number of bacteria and plays an important role in the trophic chain of the fermentation process. However, little is known about the lactate-utilizing bacteria (LUB) community in infants and their impact on gut health. By combining culture-based and molecular methods, we intensively studied LUB in fecal samples of 40 healthy infants on both taxonomic and functional levels. We demonstrated metabolic cross-feeding of lactate and identified keystone species specified for lactate utilization. The interactions of such species and their metabolic outcome could have direct impacts on infant health, either beneficial (production of short chain fatty acids) or detrimental (accumulation of hydrogen or hydrogen sulfide). We identified mode of delivery as a strong determinant for lactate-producing and -utilizing bacteria levels. These findings present the early establishment of GM with a novel perspective and emphasize the importance of lactate utilization in infancy. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

  8. Effects of early-life adversity on immune function are mediated by prenatal environment: Role of prenatal alcohol exposure.

    PubMed

    Raineki, Charlis; Bodnar, Tamara S; Holman, Parker J; Baglot, Samantha L; Lan, Ni; Weinberg, Joanne

    2017-11-01

    The contribution of the early postnatal environment to the pervasive effects of prenatal alcohol exposure (PAE) is poorly understood. Moreover, PAE often carries increased risk of exposure to adversity/stress during early life. Dysregulation of immune function may play a role in how pre- and/or postnatal adversity/stress alters brain development. Here, we combine two animal models to examine whether PAE differentially increases vulnerability to immune dysregulation in response to early-life adversity. PAE and control litters were exposed to either limited bedding (postnatal day [PN] 8-12) to model early-life adversity or normal bedding, and maternal behavior and pup vocalizations were recorded. Peripheral (serum) and central (amygdala) immune (cytokines and C-reactive protein - CRP) responses of PAE animals to early-life adversity were evaluated at PN12. Insufficient bedding increased negative maternal behavior in both groups. Early-life adversity increased vocalization in all animals; however, PAE pups vocalized less than controls. Early-life adversity reduced serum TNF-α, KC/GRO, and IL-10 levels in control but not PAE animals. PAE increased serum CRP, and levels were even higher in pups exposed to adversity. Finally, PAE reduced KC/GRO and increased IL-10 levels in the amygdala. Our results indicate that PAE alters immune system development and both behavioral and immune responses to early-life adversity, which could have subsequent consequences for brain development and later life health. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Functional connectivity measures after psilocybin inform a novel hypothesis of early psychosis.

    PubMed

    Carhart-Harris, Robin L; Leech, Robert; Erritzoe, David; Williams, Tim M; Stone, James M; Evans, John; Sharp, David J; Feilding, Amanda; Wise, Richard G; Nutt, David J

    2013-11-01

    Psilocybin is a classic psychedelic and a candidate drug model of psychosis. This study measured the effects of psilocybin on resting-state network and thalamocortical functional connectivity (FC) using functional magnetic resonance imaging (fMRI). Fifteen healthy volunteers received intravenous infusions of psilocybin and placebo in 2 task-free resting-state scans. Primary analyses focused on changes in FC between the default-mode- (DMN) and task-positive network (TPN). Spontaneous activity in the DMN is orthogonal to spontaneous activity in the TPN, and it is well known that these networks support very different functions (ie, the DMN supports introspection, whereas the TPN supports externally focused attention). Here, independent components and seed-based FC analyses revealed increased DMN-TPN FC and so decreased DMN-TPN orthogonality after psilocybin. Increased DMN-TPN FC has been found in psychosis and meditatory states, which share some phenomenological similarities with the psychedelic state. Increased DMN-TPN FC has also been observed in sedation, as has decreased thalamocortical FC, but here we found preserved thalamocortical FC after psilocybin. Thus, we propose that thalamocortical FC may be related to arousal, whereas DMN-TPN FC is related to the separateness of internally and externally focused states. We suggest that this orthogonality is compromised in early psychosis, explaining similarities between its phenomenology and that of the psychedelic state and supporting the utility of psilocybin as a model of early psychosis.

  10. Air pollution and diastolic function in elderly women - Results from the SALIA study cohort.

    PubMed

    Ohlwein, Simone; Klümper, Claudia; Vossoughi, Mohammad; Sugiri, Dorothea; Stolz, Sabine; Vierkötter, Andrea; Schikowski, Tamara; Kara, Kaffer; Germing, Alfried; Quass, Ulrich; Krämer, Ursula; Hoffmann, Barbara

    2016-07-01

    Studies linking particulate matter (PM) with heart failure (HF) show inconsistent results. However, the association of air pollution with diastolic function, an important determinant of heart failure, has not been studied yet and is addressed in the presented study. 402 women (69-79 years) of the clinical follow-up (2007-2010) of the ongoing population-based prospective SALIA (Study on the influence of Air pollution on Lung function, Inflammation and Ageing) cohort were examined using Doppler echocardiography: Of the 291 women with preserved ejection fraction, the ratio of peak early diastolic filling velocity and peak early diastolic mitral annulus velocity (E/E') was collected in 264 and left atrial volume index (LAVI) in 262 women. Residential long-term air pollution exposure (nitrogen oxides, size-fractioned PM) was modeled at baseline and at follow-up, applying land use regression models. We used linear regression to model the cross-sectional associations of air pollutants per interquartile range (IQR) with different measures of diastolic function, adjusting for personal risk factors. Median concentrations of annual NOx, NO2, PM2.5, and PM10 at follow-up were 37.7, 25.9, 17.4 and 26.4μg/m(3), respectively. In the fully adjusted models, LAVI was associated with an IQR increase in PM2.5 (1.05 [0.99; 1.12]) and NOx (1.04 [1.00; 1.09]) at follow-up, and with NOx and NO2 (both 1.05 [1.00; 1.11]) at baseline. None of the pollutants were clearly associated with E/E'. In this analysis of elderly women, we found suggestive evidence for an association of air pollution with impaired diastolic function. Copyright © 2016. Published by Elsevier GmbH.

  11. Do child's psychosocial functioning, and parent and family characteristics predict early alcohol use? The TRAILS Study.

    PubMed

    Visser, Leenke; de Winter, Andrea F; Vollebergh, Wilma A M; Verhulst, Frank C; Reijneveld, Sijmen A

    2015-02-01

    Given the negative consequences of early alcohol use for health and social functioning, it is essential to detect children at risk of early drinking. The aim of this study is to determine predictors of early alcohol use that can easily be detected in Preventive Child Healthcare (PCH). We obtained data from the first two waves on 1261 Dutch adolescents who participated in TRAILS (TRacking Adolescents' Individual Lives Survey) at ages 10-14 years and from the PCH records regarding ages 4-10 years. Early adolescence alcohol use (age 10-14 years) was defined as alcohol use at least once at ages 10-12 years (wave 1) and at least once in the previous 4 weeks at ages 12-14 years (wave 2). Predictors of early alcohol use concerned parent and teacher reports at wave 1 and PCH registrations, regarding the child's psychosocial functioning, and parental and socio-demographic characteristics. A total of 17.2% of the adolescents reported early alcohol use. Predictors of early alcohol use were teacher-reported aggressive behaviour [odds ratios (OR); 95% confidence interval (CI): 1.86; 1.11-3.11], being a boy (OR 1.80, 95%-CI 1.31-2.56), being a non-immigrant (OR 2.31, 95%CI 1.05-5.09), and low and middle educational level of the father (OR 1.71, 95%CI 1.12-2.62 and OR 1.77, 95%CI 1.16-2.70, respectively), mutually adjusted. A limited set of factors was predictive for early alcohol use. Use of this set may improve the detection of early adolescence alcohol use in PCH. © The Author 2014. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

  12. Cost-effectiveness of early versus delayed functional restoration for chronic disabling occupational musculoskeletal disorders.

    PubMed

    Theodore, Brian R; Mayer, Tom G; Gatchel, Robert J

    2015-06-01

    Despite extensive evidence for the treatment effectiveness of interdisciplinary functional restoration (FR) for chronic disabling occupational musculoskeletal disorders (CDOMD), there is little documentation on the cost-effectiveness of early rehabilitation using FR. A total of 1,119 CDOMD patients were classified according to duration of disability on FR entry, corresponding to early rehabilitation (ER: 4-8 months of disability, N = 373), intermediate duration (ID: 9-18 months, N = 373), and delayed rehabilitation (DR: >18 months, N = 373). Groups were matched on sex, age, ethnicity, and injured musculoskeletal region. One-year post-rehabilitation outcomes included return-to-work, work retention and healthcare utilization. Economic analyses included a cost-effectiveness analysis of the FR program, and estimation of the total cost-of-illness. At 1-year post-rehabilitation, all groups were comparable on return-to-work (overall 88%), work retention (overall 80%), and additional healthcare utilization (overall, 2.2% of patients received re-operations/new surgeries, 2 visits to new healthcare provider). Savings of up to 64% in medical costs, and up to 80% in disability benefits and productivity losses was associated with the ER group. The cost of rehabilitation was also up to 56% lower when administered early. Overall, ER resulted in estimated cost savings of up to 72% (or almost $170,000 per claim). Duration of disability does not negatively impact objective work or healthcare utilization outcomes following interdisciplinary FR. However, early rehabilitation is more likely to be a cost-effective solution compared to cases that progress >8 months and receiving FR as a treatment of "last resort".

  13. Do Children's Executive Functions Account for Associations between Early Autonomy-Supportive Parenting and Achievement through High School?

    ERIC Educational Resources Information Center

    Bindman, Samantha W.; Pomerantz, Eva M.; Roisman, Glenn I.

    2015-01-01

    This study evaluated whether the positive association between early autonomy-supportive parenting and children's subsequent achievement is mediated by children's executive functions. Using observations of mothers' parenting from the National Institute of Child Health and Human Development (NICHD) Study of Early Child Care and Youth Development (N…

  14. ESCRT-I function is required for Tyrp1 transport from early endosomes to the melanosome limiting membrane

    PubMed Central

    Truschel, Steven T.; Simoes, Sabrina; Setty, Subba Rao Gangi; Harper, Dawn C.; Tenza, Danièle; Thomas, Penelope C.; Herman, Kathryn E.; Sackett, Sara D.; Cowan, David C.; Theos, Alexander C.; Raposo, Graça; Marks, Michael S.

    2009-01-01

    Melanosomes are lysosome-related organelles that coexist with lysosomes within melanocytes. The pathways by which melanosomal proteins are diverted from endocytic organelles toward melanosomes are incompletely defined. In melanocytes from mouse models of Hermansky-Pudlak syndrome (HPS) that lack BLOC-1, melanosomal proteins such as Tyrp1 accumulate in early endosomes. Whether this accumulation represents an anomalous pathway or an arrested normal intermediate in melanosome protein trafficking is not clear. Here we show that early endosomes are requisite intermediates in the trafficking of Tyrp1 from the Golgi to late stage melanosomes in normal melanocytic cells. Kinetic analyses show that very little newly synthesized Tyrp1 traverses the cell surface and that internalized Tyrp1 is inefficiently sorted to melanosomes. Nevertheless, nearly all Tyrp1 traverses early endosomes since it becomes trapped within enlarged, modified endosomes upon overexpression of Hrs. Although Tyrp1 localization is not affected by Hrs depletion, depletion of the ESCRT-I component, Tsg101, or inhibition of ESCRT function by dominant negative approaches results in a dramatic redistribution of Tyrp1 to aberrant endosomal membranes that are largely distinct from those harboring traditional ESCRT-dependent, ubiquitylated cargoes such as MART-1. The lysosomal protein content of some of these membranes and the lack of Tyrp1 recycling to the plasma membrane in Tsg101-depleted cells suggests that ESCRT-I functions downstream of BLOC-1. Our data delineate a novel pathway for Tyrp1 trafficking and illustrate a requirement for ESCRT-I function in controlling protein sorting from vacuolar endosomes to the limiting membrane of a lysosome-related organelle. PMID:19624486

  15. Dietary Sodium Modulation of Aldosterone Activation and Renal Function During the Progression of Experimental Heart Failure Miller: Dietary Sodium and Early Heart Failure

    PubMed Central

    Miller, Wayne L.; Borgeson, Daniel D.; Grantham, J. Aaron; Luchner, Andreas; Redfield, Margaret M.; Burnett, John C.

    2015-01-01

    Aims Aldosterone activation is central to the sodium-fluid retention that marks the progression of heart failure (HF). The actions of dietary sodium restriction, a mainstay in HF management, on cardiorenal and neuroendocrine adaptations during the progression of HF are poorly understood. The study aim was to assess the role of dietary sodium during the progression of experimental HF. Methods and Results Experimental HF was produced in a canine model by rapid right ventricular pacing which evolves from early mild HF to overt, severe HF. Dogs were fed one of three diets: 1) high sodium [250 mEq (5.8 grams) per day, n=6]; 2) standard sodium [58 mEq (1.3 grams) per day, n=6]; and 3) sodium restriction [11 mEq (0.25 grams) per day, n=6]. During the 38 day study hemodynamics, renal function, renin activity (PRA), and aldosterone were measured. Changes in hemodynamics at 38 days were similar in all three groups, as were changes in renal function. Aldosterone activation was demonstrated in all three groups, however, dietary sodium restriction, in contrast to high sodium, resulted in early (10 days) activation of PRA and aldosterone. High sodium demonstrated significant suppression of aldosterone activation over the course of HF progression. Conclusions Excessive dietary sodium restriction particularly in early stage HF results in early aldosterone activation, while normal and excess sodium intake are associated with delayed or suppressed activation. These findings warrant evaluation in humans to determine if dietary sodium manipulation, particularly during early stage HF, may have a significant impact on neuroendocrine disease progression. PMID:25823360

  16. Early loosening of a press-fit cup with ceramic-on-ceramic articulation: our early results.

    PubMed

    Haverkamp, Daniël; Westerbos, Stijn; Campo, Martin M; Boonstra, Ritsert H; Rob Albers, G H; van der Vis, Harm M

    2013-12-01

    In this study, we present the short-term results of the Selexys TH+ cup with the Ceramys inlay which is a press-fit cup with a ceramic-on-ceramic articulation. (Mathys, Bettlach, Switzerland). We compared the results with a retrospective-matched control group with a Delta PF cup (Lima, Udine, Italy), which is also a press-fit cup with a ceramic-on-ceramic articulation. 257 elective hip arthroplasties with the Selexys TH+ cup in 250 patients placed in 2009 and 2010 were analyzed and compared with a control group retrospective analysis of the uncemented Delta PF cup (Lima, Udine, Italy) placed in 2007 and 2008 in 208 patients (222 hips). Surgical technique and surgeons were identical in both groups. During a follow-up period of 3-21 months, 19 aseptic loosenings (7.4 %) were found for the Selexys TH+ cup. The survival plotted by a Kaplan-Meier curve shows a 1-year survival of 87.4 %. The Lima Delta PF cup showed a 1-year survival of 99.5 %. Failure analysis showed no clear explanation for this early loosening. The Selexys TH+ cup combined with the Ceramys ceramic-on-ceramic inlay coupling show an unacceptable high early revision rate. Therefore, we advice against using this combination.

  17. Functional Topography of Early Periventricular Brain Lesions in Relation to Cytoarchitectonic Probabilistic Maps

    ERIC Educational Resources Information Center

    Staudt, Martin; Ticini, Luca F.; Grodd, Wolfgang; Krageloh-Mann, Ingeborg; Karnath, Hans-Otto

    2008-01-01

    Early periventricular brain lesions can not only cause cerebral palsy, but can also induce a reorganization of language. Here, we asked whether these different functional consequences can be attributed to topographically distinct portions of the periventricular white matter damage. Eight patients with pre- and perinatally acquired left-sided…

  18. Primary cortical folding in the human newborn: an early marker of later functional development.

    PubMed

    Dubois, J; Benders, M; Borradori-Tolsa, C; Cachia, A; Lazeyras, F; Ha-Vinh Leuchter, R; Sizonenko, S V; Warfield, S K; Mangin, J F; Hüppi, P S

    2008-08-01

    In the human brain, the morphology of cortical gyri and sulci is complex and variable among individuals, and it may reflect pathological functioning with specific abnormalities observed in certain developmental and neuropsychiatric disorders. Since cortical folding occurs early during brain development, these structural abnormalities might be present long before the appearance of functional symptoms. So far, the precise mechanisms responsible for such alteration in the convolution pattern during intra-uterine or post-natal development are still poorly understood. Here we compared anatomical and functional brain development in vivo among 45 premature newborns who experienced different intra-uterine environments: 22 normal singletons, 12 twins and 11 newborns with intrauterine growth restriction (IUGR). Using magnetic resonance imaging (MRI) and dedicated post-processing tools, we investigated early disturbances in cortical formation at birth, over the developmental period critical for the emergence of convolutions (26-36 weeks of gestational age), and defined early 'endophenotypes' of sulcal development. We demonstrated that twins have a delayed but harmonious maturation, with reduced surface and sulcation index compared to singletons, whereas the gyrification of IUGR newborns is discordant to the normal developmental trajectory, with a more pronounced reduction of surface in relation to the sulcation index compared to normal newborns. Furthermore, we showed that these structural measurements of the brain at birth are predictors of infants' outcome at term equivalent age, for MRI-based cerebral volumes and neurobehavioural development evaluated with the assessment of preterm infant's behaviour (APIB).

  19. Relationship among blood indicators of lipomobilization and hepatic function during early lactation in high-yielding dairy cows

    PubMed Central

    Muiño, Rodrigo; Pereira, Víctor; Campos, Rómulo; Benedito, José Luis

    2011-01-01

    Blood indicators are used as a tool to diagnose metabolic disorders. The present work was conducted to study the relationships among blood indicators of lipomobilization and hepatic function in high-yielding dairy cows. Two groups of Holstein cows were studied: 27 early lactation cows and 14 mid lactation cows from four different herds with similar husbandry characteristics in Galicia, Spain. Blood samples were obtained to measure beta-hydroxybutyrate (BHB), non-esterified fatty acids (NEFA), triglycerides (TG), and the activity of aspartate transaminase (AST) and gamma-glutamyl transferase. Cows in early lactation had higher levels of BHB and NEFA than mid lactation cows. High lipomobilization (NEFA > 400 µmol/L) was detected in 67% and 7% of early lactation and mid lactation cows, respectively, while subclinical ketosis (BHB > 1.2 mmol/L) was detected in 41% and 28% of the early lactation and lactation cows, respectively. TG concentrations were low in all cows suffering subclinical ketosis and in 61% of the cows with high lipomobilization. During early lactation, 30% of cows suffered hepatic lipidosis as detected by levels of AST. Compromised hepatic function was observed in early lactation cows as shown by lower concentrations of glucose, total protein, and urea. PMID:21897097

  20. Early-Life Socioeconomic Status and Adult Physiological Functioning: A Life Course Examination of Biosocial Mechanisms.

    PubMed

    Yang, Yang Claire; Gerken, Karen; Schorpp, Kristen; Boen, Courtney; Harris, Kathleen Mullan

    2017-01-01

    A growing literature has demonstrated a link between early-life socioeconomic conditions and adult health at a singular point in life. No research exists, however, that specifies the life course patterns of socioeconomic status (SES) in relation to the underlying biological processes that determine health. Using an innovative life course research design consisting of four nationally representative longitudinal datasets that collectively cover the human life span from early adolescence to old age (Add Health, MIDUS, NSHAP, and HRS), we address this scientific gap and assess how SES pathways from childhood into adulthood are associated with biophysiological outcomes in different adult life stages. For each dataset, we constructed standardized composite measures of early-life SES and adult SES and harmonized biophysiological measurements of immune and metabolic functioning. We found that the relative importance of early-life SES and adult SES varied across young, mid, and late adulthood, such that early-life SES sets a life course trajectory of socioeconomic well-being and operates through adult SES to influence health as adults age. We also documented evidence of the detrimental health effects of downward mobility and persistent socioeconomic disadvantage. These findings are the first to specify the life course patterns of SES that matter for underlying biophysiological functioning in different stages of adulthood. The study thus contributes new knowledge critical for improving population health by identifying the particular points in the life course at which interventions might be most effective in preventing disease and premature mortality.

  1. Functional neuroanatomical associations of working memory in early-onset Alzheimer's disease.

    PubMed

    Kobylecki, Christopher; Haense, Cathleen; Harris, Jennifer M; Stopford, Cheryl L; Segobin, Shailendra H; Jones, Matthew; Richardson, Anna M T; Gerhard, Alexander; Anton-Rodriguez, José; Thompson, Jennifer C; Herholz, Karl; Snowden, Julie S

    2018-01-01

    To characterize metabolic correlates of working memory impairment in clinically defined subtypes of early-onset Alzheimer's disease. Established models of working memory suggest a key role for frontal lobe function, yet the association in Alzheimer's disease between working memory impairment and visuospatial and language symptoms suggests that temporoparietal neocortical dysfunction may be responsible. Twenty-four patients with predominantly early-onset Alzheimer's disease were clinically classified into groups with predominantly amnestic, multidomain or visual deficits. Patients underwent neuropsychological evaluation focused on the domains of episodic and working memory, T1-weighted magnetic resonance imaging and brain fluorodeoxyglucose positron emission tomography. Fluorodeoxyglucose positron emission tomography data were analysed by using a region-of-interest approach. Patients with multidomain and visual presentations performed more poorly on tests of working memory compared with amnestic Alzheimer's disease. Working memory performance correlated with glucose metabolism in left-sided temporoparietal, but not frontal neocortex. Carriers of the apolipoprotein E4 gene showed poorer episodic memory and better working memory performance compared with noncarriers. Our findings support the hypothesis that working memory changes in early-onset Alzheimer's disease are related to temporoparietal rather than frontal hypometabolism and show dissociation from episodic memory performance. They further support the concept of subtypes of Alzheimer's disease with distinct cognitive profiles due to prominent neocortical dysfunction early in the disease course. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  2. Functional and physical abilities in the early continuum of cognitive decline.

    PubMed

    Shin, Joon-Ho; Lim, Jae-Young; Kim, Ki Woong; Kim, Suyoung; Lee, Jaebong; Paik, Nam-Jong

    2015-01-01

    The early cognitive continuum has been emphasized recently. We sought to characterize the functional and physical aspects of the cognitive continuum in subjects with no cognitive impairment (NCI), subjective cognitive impairment (SCI), nonamnestic (NA-MCI), and amnestic mild cognitive impairment (A-MCI). Furthermore, we identified the potential diagnostic utility of specific functional tasks. A total of 702 participants, aged ≥65 years and defined as NCI, SCI, NA-MCI, and A-MCI according to the original Petersen criteria, were included. They completed the Korean basic (K-ADL) and Instrumental Activities of Daily Living Scales (K-IADL) and the Performance-Oriented Mobility Assessment (POMA). Significant differences were observed between the different cognitive status groups in three items and total scores on the K-ADL, six items and total scores on the K-IADL and POMA. Controlling for confounding factors revealed that subjects from the A-MCI group performed poorly at bathing, shopping, handling money, and the sum of assorted functional items. These findings demonstrated the declining feature of functional and physical performance according to the cognitive continuum, with A-MCI being discriminative with respect to specific functional tasks as compared to milder cognitive statuses. © 2014 S. Karger AG, Basel.

  3. Feminizing genitoplasty in adult transsexuals: early and long-term surgical results.

    PubMed

    Goddard, Jonathan C; Vickery, Richard M; Qureshi, Assad; Summerton, Duncan J; Khoosal, Deenesh; Terry, Tim R

    2007-09-01

    median follow up was 36 (9-96) months. Overall, 63 (98%) had a sensate neoclitoris, with 31 (48%) able to achieve orgasm; nine (14%) were hypersensitive. Vaginal depth was considered adequate by 38 (61%) and 14 (23%) had or were having regular intercourse. Vaginal hair growth troubled 18 (29%), four (6%) had a vaginal prolapse and two (3%) had vaginal necrosis. Urinary problems were reported by 19 (27%) patients, of these 18 (26%) required revision surgery, 14 (20%) complained of urinary spraying, 18 (26%) had an upward directed stream and 16 (23%) had urethral stenosis. The patients deemed the cosmetic result acceptable in 53 (76%) cases and 56 (80%) said the surgery met with their expectations. This is largest series of early results after male to female FG. Complications are common after this complex surgery and long-term follow-up is difficult, as patients tend to re-locate at the start of their 'new life' after FG. There were good overall cosmetic and functional results, with a sustained high patient satisfaction.

  4. Visual Function Metrics in Early and Intermediate Dry Age-related Macular Degeneration for Use as Clinical Trial Endpoints.

    PubMed

    Cocce, Kimberly J; Stinnett, Sandra S; Luhmann, Ulrich F O; Vajzovic, Lejla; Horne, Anupama; Schuman, Stefanie G; Toth, Cynthia A; Cousins, Scott W; Lad, Eleonora M

    2018-05-01

    To evaluate and quantify visual function metrics to be used as endpoints of age-related macular degeneration (AMD) stages and visual acuity (VA) loss in patients with early and intermediate AMD. Cross-sectional analysis of baseline data from a prospective study. One hundred and one patients were enrolled at Duke Eye Center: 80 patients with early AMD (Age-Related Eye Disease Study [AREDS] stage 2 [n = 33] and intermediate stage 3 [n = 47]) and 21 age-matched, normal controls. A dilated retinal examination, macular pigment optical density measurements, and several functional assessments (best-corrected visual acuity, macular integrity assessment mesopic microperimety, dark adaptometry, low-luminance visual acuity [LLVA] [standard using a log 2.0 neutral density filter and computerized method], and cone contrast test [CCT]) were performed. Low-luminance deficit (LLD) was defined as the difference in numbers of letters read at standard vs low luminance. Group comparisons were performed to evaluate differences between the control and the early and intermediate AMD groups using 2-sided significance tests. Functional measures that significantly distinguished between normal and intermediate AMD were standard and computerized (0.5 cd/m 2 ) LLVA, percent reduced threshold and average threshold on microperimetry, CCTs, and rod intercept on dark adaptation (P < .05). The intermediate group demonstrated deficits in microperimetry reduced threshhold, computerized LLD2, and dark adaptation (P < .05) relative to early AMD. Our study suggests that LLVA, microperimetry, CCT, and dark adaptation may serve as functional measures differentiating early-to-intermediate stages of dry AMD. Copyright © 2018 Elsevier Inc. All rights reserved.

  5. Caregiver Ratings of Long-term Executive Dysfunction and Attention Problems After Early Childhood Traumatic Brain Injury: Family Functioning Is Important

    PubMed Central

    Kurowski, Brad G.; Taylor, H. Gerry; Yeates, Keith Owen; Walz, Nicolay C.; Stancin, Terry; Wade, Shari L.

    2013-01-01

    Objective To evaluate the relationship of family and parenting factors to long-term executive dysfunction and attention problems after early childhood traumatic brain injury (TBI). We hypothesized that the magnitude of executive dysfunction and attention problems would be moderated by family and parenting factors. Design A multicenter, prospective cohort study that included an orthopedic injury (OI) reference group. Setting Three tertiary academic children’s hospital medical centers and one general medical center. Participants Children, ages 3–7 years, hospitalized for OI, moderate TBI, or severe TBI. Methods and Outcome Measurements Parental ratings of family functioning and parenting styles were obtained 18 months after the injury occurred. The main outcome measurements, which were parental ratings of children’s executive function and attention, were performed at least 24 months after the injury occurred (mean, 39 months; range, 25–63 months). Analysis Group comparisons were conducted with use of t-tests, χ2 analysis, analysis of variance, and Pearson and Spearman correlations. Regression analysis was used to examine associations of the outcomes with family functioning and parenting styles and to test moderating effects of these factors on group differences. Results Participants with severe TBI demonstrated increased executive dysfunction and attention problems compared with those who sustained moderate TBI or OI. Lower levels of family dysfunction were associated with better executive function and attention across groups but did not moderate group differences. However, attention deficits after severe TBI were exacerbated under conditions of more permissive parenting relative to attention deficits after OIs. Conclusions Executive function and attention problems persisted on a long-term basis (>24 months) after early childhood TBI, and positive global family functioning and nonpermissive parenting were associated with better outcomes. Better

  6. Early impaired β-cell function in chinese women with polycystic ovary syndrome.

    PubMed

    Tao, Tao; Li, Shengxian; Zhao, Aimin; Mao, Xiuyin; Liu, Wei

    2012-01-01

    The pathogenic factors that account for the development of diabetes condition in Chinese women with polycystic ovary syndrome (PCOS) remain elusive. To clarify the pathogenic features by evaluating the levels of insulin sensitivity and β cell function in these women with PCOS, either separately or by using of a disposition indexes (DIs). Cross-sectional study involving 137 Chinese women with PCOS and 123 normal women were examined by anthropometry, lipid profile, sex hormone, high-sensitivity C reactive protein, oral glucose tolerance tests and insulin tolerance tests. After controlling for BMI status, the Matsuda Index was significantly lower in women with PCOS in comparison to those of normal women (p<0.000). The early phase of insulin secretion (insulinogenic index) remained significantly lower in lean women with PCOS(LP) than those of both lean and obese women of control group (p=0.007, and p = 0.01, respectively). The mean HOMA-F values were significantly lower (p =0.045) in obese women with PCOS (OP) than those of BMI-matched women. Further, all DIs derived from non-fasting state indexes in women with PCOS were significantly lower than those of BMI-matched control women (p<0.001 for all). Lastly, DIs derived from fasting states indexes in OP were significantly lower than those of LP. Early impaired β cell function was detected in both LP and OP. However, more serious primary defect in insulin action was detected in LP compared to OP. These findings imply that early screening and intervention for PCOS would be therapeutic for Chinese women.

  7. Tracking early decline in cognitive function in older individuals at risk for Alzheimer's disease dementia: the Alzheimer's Disease Cooperative Study Cognitive Function Instrument

    PubMed Central

    Amariglio, Rebecca E.; Donohue, Michael C.; Marshall, Gad A.; Rentz, Dorene M.; Salmon, David P.; Ferris, Steven H.; Karantzoulis, Stella; Aisen, Paul S.; Sperling, Reisa A.

    2015-01-01

    Importance Several large-scale Alzheimer's disease (AD) secondary prevention trials have begun to target individuals at the preclinical stage. The success of these trials depends on validated outcome measures that are sensitive to early clinical progression in individuals who are initially asymptomatic. Objective To investigate the utility of the Cognitive Function Instrument (CFI) to track early changes in cognitive function in older individuals without clinical impairment at baseline. Design, Setting, and Participants Longitudinal study over the course of 48 months at participating Alzheimer's Disease Cooperative Study (ADCS) sites. The study included 468 healthy older individuals (Clinical Dementia Rating Scale [CDR] Global = 0, above cut-off on modified Mini-Mental State Exam and Free and Cued Selective Reminding Test) (mean age= 79.4 years ±3.6). All subjects and their study partners completed the Self and Partner CFI annually. Subjects also underwent concurrent annual neuropsychological assessment and apolipoprotein E (APOE) genotyping. Main outcomes and measures Comparison of CFI scores between clinical progressors (Clinical Dementia Rating Scale [CDR] ≥ 0.5) and non-progressors (CDR remained = 0), as well as between APOE ε4 carriers and non-carriers were performed. Correlations of change between the CFI and neuropsychological performance were assessed longitudinally. Results At 48 months, group differences between clinical progressors and non-progressors were significant for CFI Self, CFI Partner, and CFI Self+Partner total scores. At month 48, APOE ε4 carriers showed greater progression than non-carriers on CFI Partner and CFI Self+Partner scores. Both CFI Self and CFI Partner scores were associated with longitudinal cognitive decline, although findings suggest self report may be more accurate early in the process, whereas accuracy of partner report improves when there is progression to cognitive impairment. Conclusions and Relevance Demonstrating

  8. Prospective Single-Arm, Multi-Center Trial of a Patient-Specific Interpositional Knee Implant: Early Clinical Results

    PubMed Central

    Koeck, F.X; Luring, C; Goetz, J; Handel, M; Tingart, M; Grifka, J; Beckmann, J

    2011-01-01

    Background: The treatment of unicompartmental arthritis in younger patients is challenging. The aim of this study is to report final safety and efficacy analysis results for the iForma patient–specific interpositional device, which is designed for the treatment of isolated medial or lateral compartment arthritis of the knee. Methods: From June 2005 to June 2008 78 subjects (42 men, 36 women) received an iForma implant. The mean age was 53 years, the mean Body Mass Index 29.0. We surveyed the WOMAC scores, the visual analog pain scale and the Knee Society Scores. Results: The mean follow up was 16.4 months. The mean WOMAC knee scores increased from 48.3 before surgery to 71.3 after 24 months. A reduction in pain was achieved for all five pain measures using a standard visual analog scale (VAS). Knee Society Knee Score improved from 39.2 before to 61.9 24 month after surgery. The Knee Society Function Scores improved form preoperative 64.5 to 82.5 2 years postoperative. The preoperative range of motion could be restored. The overall revision rate was 24%. 15 implants were removed early, 4 knees were revised without implant removal. Conclusion: Within narrow indication of patients with unicompartmental disease, the iForma device can provide improvement in knee function and reduction in pain, however, with a significant higher risk of early revision compared to traditional arthroplasty. Respecting this limitation it may be an alternative option for arthritic patients with unicompartmental disease who have contraindications to High Tibial Osteotomy or are too young for knee replacement; the iForma device further has the distinct advantage of time and cost saving compared to those procedures. PMID:21552462

  9. The Eole experiment - Early results and current objectives.

    NASA Technical Reports Server (NTRS)

    Morel, P.; Bandeen, W.

    1973-01-01

    The Eole experiment with 480 constant level balloons released in the Southern Hemisphere is described. Each balloon, floating freely at approximately the 200-mb level, is a precise tracer of the horizontal motion of air masses, the accuracy of which is limited only by the laminated structure of the stratospheric flow, within an rms uncertainty of 1.5 m/sec. The balloons were found after 2 months to distribute at random over the whole hemisphere outside the tropics, irrespective of their original launching site. Early results of Eulerian and Lagrangian averages of the Eole wind data are given for describing the mean 200-mb zonal and meridional circulations.

  10. Multiple populations within globular clusters in Early-type galaxies Exploring their effect on stellar initial mass function estimates

    NASA Astrophysics Data System (ADS)

    Chantereau, W.; Usher, C.; Bastian, N.

    2018-05-01

    It is now well-established that most (if not all) ancient globular clusters host multiple populations, that are characterised by distinct chemical features such as helium abundance variations along with N-C and Na-O anti-correlations, at fixed [Fe/H]. These very distinct chemical features are similar to what is found in the centres of the massive early-type galaxies and may influence measurements of the global properties of the galaxies. Additionally, recent results have suggested that M/L variations found in the centres of massive early-type galaxies might be due to a bottom-heavy stellar initial mass function. We present an analysis of the effects of globular cluster-like multiple populations on the integrated properties of early-type galaxies. In particular, we focus on spectral features in the integrated optical spectrum and the global mass-to-light ratio that have been used to infer variations in the stellar initial mass function. To achieve this we develop appropriate stellar population synthesis models and take into account, for the first time, an initial-final mass relation which takes into consideration a varying He abundance. We conclude that while the multiple populations may be present in massive early-type galaxies, they are likely not responsible for the observed variations in the mass-to-light ratio and IMF sensitive line strengths. Finally, we estimate the fraction of stars with multiple populations chemistry that come from disrupted globular clusters within massive ellipticals and find that they may explain some of the observed chemical patterns in the centres of these galaxies.

  11. Early-onset lymphoproliferation and autoimmunity caused by germline STAT3 gain-of-function mutations

    PubMed Central

    Vogel, Tiphanie P.; Forbes, Lisa; Ma, Chi A.; Stray-Pedersen, Asbjørg; Niemela, Julie E.; Lyons, Jonathan J.; Engelhardt, Karin R.; Zhang, Yu; Topcagic, Nermina; Roberson, Elisha D. O.; Matthews, Helen; Verbsky, James W.; Dasu, Trivikram; Vargas-Hernandez, Alexander; Varghese, Nidhy; McClain, Kenneth L.; Karam, Lina B.; Nahmod, Karen; Makedonas, George; Mace, Emily M.; Sorte, Hanne S.; Perminow, Gøri; Rao, V. Koneti; O’Connell, Michael P.; Price, Susan; Su, Helen C.; Butrick, Morgan; McElwee, Joshua; Hughes, Jason D.; Willet, Joseph; Swan, David; Xu, Yaobo; Santibanez-Koref, Mauro; Slowik, Voytek; Dinwiddie, Darrell L.; Ciaccio, Christina E.; Saunders, Carol J.; Septer, Seth; Kingsmore, Stephen F.; White, Andrew J.; Cant, Andrew J.; Hambleton, Sophie

    2015-01-01

    Germline loss-of-function mutations in the transcription factor signal transducer and activator of transcription 3 (STAT3) cause immunodeficiency, whereas somatic gain-of-function mutations in STAT3 are associated with large granular lymphocytic leukemic, myelodysplastic syndrome, and aplastic anemia. Recently, germline mutations in STAT3 have also been associated with autoimmune disease. Here, we report on 13 individuals from 10 families with lymphoproliferation and early-onset solid-organ autoimmunity associated with 9 different germline heterozygous mutations in STAT3. Patients exhibited a variety of clinical features, with most having lymphadenopathy, autoimmune cytopenias, multiorgan autoimmunity (lung, gastrointestinal, hepatic, and/or endocrine dysfunction), infections, and short stature. Functional analyses demonstrate that these mutations confer a gain-of-function in STAT3 leading to secondary defects in STAT5 and STAT1 phosphorylation and the regulatory T-cell compartment. Treatment targeting a cytokine pathway that signals through STAT3 led to clinical improvement in 1 patient, suggesting a potential therapeutic option for such patients. These results suggest that there is a broad range of autoimmunity caused by germline STAT3 gain-of-function mutations, and that hematologic autoimmunity is a major component of this newly described disorder. Some patients for this study were enrolled in a trial registered at www.clinicaltrials.gov as #NCT00001350. PMID:25359994

  12. CALIPSO Overview and Early Results

    NASA Astrophysics Data System (ADS)

    McCormick, M. P.

    2008-05-01

    The CALIPSO spacecraft was co-manifested with the CloudSat spacecraft and launched by a Boeing Delta~II rocket from Vandenberg Air Force Base, California on April~28,~2006. CALIPSO is the acronym for Cloud Aerosol Lidar and Infrared Pathfinder Satellite Observations. CALIOP (Cloud-Aerosol Lidar with Orthogonal Polarization) is a three-channel lidar on board that uses a Nd:YAG laser emitting pulses at 1064 and 532~nm. The receiver uses a 1-meter diameter telescope and photomultipliers in the two 532~nm channels; one for parallel-polarized backscatter, and the other for perpendicular-polarized backscatter. The 1064~nm channel uses an APD for measuring the total backscatter at this wavelength. CALIPSO is in a near-circular sunsynchronous polar 705-km orbit with a 1:30~PM ascending node, and is flying in formation with CloudSat, Aura, Aqua and PARASOL. CALIPSO and CloudSat are flying 15~seconds apart in the formation. This talk will present an overview of the CALIPSO mission and details of CALIOP and the rest of the payload. It will show typical results from measurements of clouds, details on cirrus cloud statistics for the first year of data, a characterization of Polar Stratospheric Clouds over the Artic and Antarctic during local winters and early springs, and some general atmospheric events like hurricanes and aerosols from minor volcanic eruptions, desert dust events, and smoke from fires and their transport. The presentation will end with a look toward the future of spaceborne lidars.

  13. How emotional abilities modulate the influence of early life stress on hippocampal functioning.

    PubMed

    Aust, Sabine; Alkan Härtwig, Elif; Koelsch, Stefan; Heekeren, Hauke R; Heuser, Isabella; Bajbouj, Malek

    2014-07-01

    Early life stress (ELS) is known to have considerable influence on brain development, mental health and affective functioning. Previous investigations have shown that alexithymia, a prevalent personality trait associated with difficulties experiencing and verbalizing emotions, is particularly related to ELS. The aim of the present study was to investigate how neural correlates of emotional experiences in alexithymia are altered in the presence and absence of ELS. Therefore, 50 healthy individuals with different levels of alexithymia were matched regarding ELS and investigated with respect to neural correlates of audio-visually induced emotional experiences via functional magnetic resonance imaging. The main finding was that ELS modulated hippocampal responses to pleasant (>neutral) stimuli in high-alexithymic individuals, whereas there was no such modulation in low-alexithymic individuals matched for ELS. Behavioral and psychophysiological results followed a similar pattern. When considered independent of ELS, alexithymia was associated with decreased responses in insula (pleasant > neutral) and temporal pole (unpleasant > neutral). Our results show that the influence of ELS on emotional brain responses seems to be modulated by an individual's degree of alexithymia. Potentially, protective and adverse effects of emotional abilities on brain responses to emotional experiences are discussed. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  14. Predictors of Behavioral Regulation in Kindergarten: Household Chaos, Parenting, and Early Executive Functions

    ERIC Educational Resources Information Center

    Vernon-Feagans, Lynne; Garrett-Peters, Patricia; Willoughby, Michael

    2016-01-01

    Behavioral regulation is an important school readiness skill that has been linked to early executive function (EF) and later success in learning and school achievement. Although poverty and related risks, as well as negative parenting, have been associated with poorer EF and behavioral regulation, chaotic home environments may also play a role in…

  15. Functional Recovery in Major Depressive Disorder: Providing Early Optimal Treatment for the Individual Patient

    PubMed Central

    Katzman, Martin A; Habert, Jeffrey; McIntosh, Diane; MacQueen, Glenda M; Milev, Roumen V; McIntyre, Roger S; Blier, Pierre

    2018-01-01

    Abstract Major depressive disorder is an often chronic and recurring illness. Left untreated, major depressive disorder may result in progressive alterations in brain morphometry and circuit function. Recent findings, however, suggest that pharmacotherapy may halt and possibly reverse those effects. These findings, together with evidence that a delay in treatment is associated with poorer clinical outcomes, underscore the urgency of rapidly treating depression to full recovery. Early optimized treatment, using measurement-based care and customizing treatment to the individual patient, may afford the best possible outcomes for each patient. The aim of this article is to present recommendations for using a patient-centered approach to rapidly provide optimal pharmacological treatment to patients with major depressive disorder. Offering major depressive disorder treatment determined by individual patient characteristics (e.g., predominant symptoms, medical history, comorbidities), patient preferences and expectations, and, critically, their own definition of wellness provides the best opportunity for full functional recovery. PMID:29024974

  16. Functional Recovery in Major Depressive Disorder: Providing Early Optimal Treatment for the Individual Patient.

    PubMed

    Oluboka, Oloruntoba J; Katzman, Martin A; Habert, Jeffrey; McIntosh, Diane; MacQueen, Glenda M; Milev, Roumen V; McIntyre, Roger S; Blier, Pierre

    2018-02-01

    Major depressive disorder is an often chronic and recurring illness. Left untreated, major depressive disorder may result in progressive alterations in brain morphometry and circuit function. Recent findings, however, suggest that pharmacotherapy may halt and possibly reverse those effects. These findings, together with evidence that a delay in treatment is associated with poorer clinical outcomes, underscore the urgency of rapidly treating depression to full recovery. Early optimized treatment, using measurement-based care and customizing treatment to the individual patient, may afford the best possible outcomes for each patient. The aim of this article is to present recommendations for using a patient-centered approach to rapidly provide optimal pharmacological treatment to patients with major depressive disorder. Offering major depressive disorder treatment determined by individual patient characteristics (e.g., predominant symptoms, medical history, comorbidities), patient preferences and expectations, and, critically, their own definition of wellness provides the best opportunity for full functional recovery. © The Author(s) 2017. Published by Oxford University Press on behalf of CINP.

  17. Periconceptional Folic Acid Supplementation Benefit to Development of Early Sensory-Motor Function through Increase DNA Methylation in Rat Offspring

    PubMed Central

    Li, Wen; Li, Zhenshu; Li, Shou; Wang, Xinyan; Wilson, John X.; Huang, Guowei

    2018-01-01

    Periconceptional maternal folate levels may alter DNA methylation patterns and health outcomes in offspring. We hypothesized that maternal folic acid supplementation alters fetal neural development through DNA methylation in the fetal brain. Twenty-eight rats were randomly assigned to four groups: three groups of the female rats were fed folate-normal, folate-deficient or folate-supplemented diets from seven days before mating to delivery. In another group, folic acid supplementation diet short-period group was fed a folate-normal diet, except for 10 days (begin mating) when this group was fed a folate-supplemented diet. After delivery, the diets were changed to folate-normal diet for all four groups. The cliff avoidance and forelimb grip tests were used to assess sensory motor function of rat offspring. The results indicate that maternal folic acid supplementation improved the early development of sensory-motor function in offspring. Maternal folic acid supplementation increased the methylation potential, global DNA methylation (5-mC) and DNA methyltransferase expression and activity in the brains of the offspring. In conclusion, maternal folic acid supplementation increases DNA methylation pattern in offspring brain and improves the early development of sensory-motor function. PMID:29494536

  18. Functional Connectivity Measures After Psilocybin Inform a Novel Hypothesis of Early Psychosis

    PubMed Central

    Carhart-Harris, Robin L.

    2013-01-01

    Psilocybin is a classic psychedelic and a candidate drug model of psychosis. This study measured the effects of psilocybin on resting-state network and thalamocortical functional connectivity (FC) using functional magnetic resonance imaging (fMRI). Fifteen healthy volunteers received intravenous infusions of psilocybin and placebo in 2 task-free resting-state scans. Primary analyses focused on changes in FC between the default-mode- (DMN) and task-positive network (TPN). Spontaneous activity in the DMN is orthogonal to spontaneous activity in the TPN, and it is well known that these networks support very different functions (ie, the DMN supports introspection, whereas the TPN supports externally focused attention). Here, independent components and seed-based FC analyses revealed increased DMN-TPN FC and so decreased DMN-TPN orthogonality after psilocybin. Increased DMN-TPN FC has been found in psychosis and meditatory states, which share some phenomenological similarities with the psychedelic state. Increased DMN-TPN FC has also been observed in sedation, as has decreased thalamocortical FC, but here we found preserved thalamocortical FC after psilocybin. Thus, we propose that thalamocortical FC may be related to arousal, whereas DMN-TPN FC is related to the separateness of internally and externally focused states. We suggest that this orthogonality is compromised in early psychosis, explaining similarities between its phenomenology and that of the psychedelic state and supporting the utility of psilocybin as a model of early psychosis. PMID:23044373

  19. Early functional and morphological brain disturbances in late-onset intrauterine growth restriction.

    PubMed

    Starčević, Mirta; Predojević, Maja; Butorac, Dražan; Tumbri, Jasna; Konjevoda, Paško; Kadić, Aida Salihagić

    2016-02-01

    To determine whether the brain disturbances develop in late-onset intrauterine growth restriction (IUGR) before blood flow redistribution towards the fetal brain (detected by Doppler measurements in the middle cerebral artery and umbilical artery). Further, to evaluate predictive values of Doppler arterial indices and umbilical cord blood gases and pH for early functional and/or morphological brain disturbances in late-onset IUGR. This cohort study included 60 singleton term pregnancies with placental insufficiency caused late-onset IUGR (IUGR occurring after 34 gestational weeks). Umbilical artery resistance index (URI), middle cerebral artery resistance index (CRI), and cerebroumbilical (C/U) ratio (CRI/URI) were monitored once weekly. Umbilical blood cord samples (arterial and venous) were collected for the analysis of pO2, pCO2 and pH. Morphological neurological outcome was evaluated by cranial ultrasound (cUS), whereas functional neurological outcome by Amiel-Tison Neurological Assessment at Term (ATNAT). 50 fetuses had C/U ratio>1, and 10 had C/U ratio≤1; among these 10 fetuses, 9 had abnormal neonatal cUS findings and all 10 had non-optimal ATNAT. However, the total number of abnormal neurological findings was much higher. 32 neonates had abnormal cUS (53.37%), and 42 (70.00%) had non-optimal ATNAT. Furthermore, Doppler indices had higher predictive validity for early brain disturbances than umbilical cord blood gases and pH. C/U ratio had the highest predictive validity with threshold for adverse neurological outcome at value 1.13 (ROC analysis), i.e., 1.18 (party machine learning algorithm). Adverse neurological outcome at average values of C/U ratios>1 confirmed that early functional and/or structural brain disturbances in late-onset IUGR develop even before activation of fetal cardiovascular compensatory mechanisms, i.e., before Doppler signs of blood flow redistribution between the fetal brain and the placenta. Copyright © 2015 Elsevier Ireland Ltd

  20. A continuum of executive function deficits in early subcortical vascular cognitive impairment: A systematic review and meta-analysis.

    PubMed

    Sudo, Felipe Kenji; Amado, Patricia; Alves, Gilberto Sousa; Laks, Jerson; Engelhardt, Eliasz

    2017-01-01

    Subcortical Vascular Cognitive Impairment (SVCI) is a clinical continuum of vascular-related cognitive impairment, including Vascular Mild Cognitive Impairment (VaMCI) and Vascular Dementia. Deficits in Executive Function (EF) are hallmarks of the disorder, but the best methods to assess this function have yet to be determined. The insidious and almost predictable course of SVCI and the multidimensional concept of EF suggest that a temporal dissociation of impairments in EF domains exists early in the disorder. This study aims to review and analyze data from the literature about performance of VaMCI patients on the most used EF tests through a meta-analytic approach. Medline, Web of Knowledge and PsycINFO were searched, using the terms: "vascular mild cognitive impairment" OR "vascular cognitive impairment no dementia" OR "vascular mild neurocognitive disorder" AND "dysexecutive" OR "executive function". Meta-analyses were conducted for each of the selected tests, using random-effect models. Systematic review showed major discrepancies among the results of the studies included. Meta-analyses evidenced poorer performance on the Trail-Making Test part B and the Stroop color test by VaMCI patients compared to controls. A continuum of EF impairments has been proposed in SVCI. Early deficits appear to occur in cognitive flexibility and inhibitory control.

  1. From Perception to Metacognition: Auditory and Olfactory Functions in Early Blind, Late Blind, and Sighted Individuals

    PubMed Central

    Cornell Kärnekull, Stina; Arshamian, Artin; Nilsson, Mats E.; Larsson, Maria

    2016-01-01

    Although evidence is mixed, studies have shown that blind individuals perform better than sighted at specific auditory, tactile, and chemosensory tasks. However, few studies have assessed blind and sighted individuals across different sensory modalities in the same study. We tested early blind (n = 15), late blind (n = 15), and sighted (n = 30) participants with analogous olfactory and auditory tests in absolute threshold, discrimination, identification, episodic recognition, and metacognitive ability. Although the multivariate analysis of variance (MANOVA) showed no overall effect of blindness and no interaction with modality, follow-up between-group contrasts indicated a blind-over-sighted advantage in auditory episodic recognition, that was most pronounced in early blind individuals. In contrast to the auditory modality, there was no empirical support for compensatory effects in any of the olfactory tasks. There was no conclusive evidence for group differences in metacognitive ability to predict episodic recognition performance. Taken together, the results showed no evidence of an overall superior performance in blind relative sighted individuals across olfactory and auditory functions, although early blind individuals exceled in episodic auditory recognition memory. This observation may be related to an experience-induced increase in auditory attentional capacity. PMID:27729884

  2. [Restoring of the speech functions in patients with aphasia in the early rehabilitation period of ischemic stroke].

    PubMed

    Kotov, S V; Belova, Yu A; Shcherbakova, M M; Chervinskaya, A D; Isakova, E V; Volchenkova, T V

    To study the efficacy of combined therapy including daily sessions and two 10-day injections of the drug cellex in patients with aphasia in the early rehabilitation period of ischemic stroke (II). Forty patients in the early rehabilitation period of II in the basin of the left middle cerebral artery with moderate to severe aphasia were studied. Twenty patients received combined therapy, including daily sessions with a speech therapist-aphasiologist within 10 days using the improved method, then a self-study using educational materials and two 10-day injections of cellex. Other 20 patients received only speech therapy. To assess the efficacy of therapy, the automated "Program of examination of patients with aphasia", Goodglass-Kaplan scale, modified Rankin scale were used. There was a significant improvement of speech functions, communicative abilities and functional recovery (p<0.01) in patients of both groups. However, a significantly greater level of rehabilitation (p<0.05) was noted in patients treated with combined therapy included two courses of cellex. The results allow to recommend the inclusion of cellex in the complex rehabilitation of patients with post-stroke speech disorders.

  3. Characterizing Tumor Heterogeneity With Functional Imaging and Quantifying High-Risk Tumor Volume for Early Prediction of Treatment Outcome: Cervical Cancer as a Model

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

    Mayr, Nina A., E-mail: Nina.Mayr@osumc.edu; Huang Zhibin; Wang, Jian Z.

    2012-07-01

    Purpose: Treatment response in cancer has been monitored by measuring anatomic tumor volume (ATV) at various times without considering the inherent functional tumor heterogeneity known to critically influence ultimate treatment outcome: primary tumor control and survival. This study applied dynamic contrast-enhanced (DCE) functional MRI to characterize tumors' heterogeneous subregions with low DCE values, at risk for treatment failure, and to quantify the functional risk volume (FRV) for personalized early prediction of treatment outcome. Methods and Materials: DCE-MRI was performed in 102 stage IB{sub 2}-IVA cervical cancer patients to assess tumor perfusion heterogeneity before and during radiation/chemotherapy. FRV represents the totalmore » volume of tumor voxels with critically low DCE signal intensity (<2.1 compared with precontrast image, determined by previous receiver operator characteristic analysis). FRVs were correlated with treatment outcome (follow-up: 0.2-9.4, mean 6.8 years) and compared with ATVs (Mann-Whitney, Kaplan-Meier, and multivariate analyses). Results: Before and during therapy at 2-2.5 and 4-5 weeks of RT, FRVs >20, >13, and >5 cm{sup 3}, respectively, significantly predicted unfavorable 6-year primary tumor control (p = 0.003, 7.3 Multiplication-Sign 10{sup -8}, 2.0 Multiplication-Sign 10{sup -8}) and disease-specific survival (p = 1.9 Multiplication-Sign 10{sup -4}, 2.1 Multiplication-Sign 10{sup -6}, 2.5 Multiplication-Sign 10{sup -7}, respectively). The FRVs were superior to the ATVs as early predictors of outcome, and the differentiating power of FRVs increased during treatment. Discussion: Our preliminary results suggest that functional tumor heterogeneity can be characterized by DCE-MRI to quantify FRV for predicting ultimate long-term treatment outcome. FRV is a novel functional imaging heterogeneity parameter, superior to ATV, and can be clinically translated for personalized early outcome prediction before or as early as 2

  4. Early adaption to the antarctic environment at dome C: consequences on stress-sensitive innate immune functions.

    PubMed

    Feuerecker, Matthias; Crucian, Brian; Salam, Alex P; Rybka, Ales; Kaufmann, Ines; Moreels, Marjan; Quintens, Roel; Schelling, Gustav; Thiel, Manfred; Baatout, Sarah; Sams, Clarence; Choukèr, Alexander

    2014-09-01

    Abstract Feuerecker, Matthias, Brian Crucian, Alex P. Salam, Ales Rybka, Ines Kaufmann, Marjan Moreels, Roel Quintens, Gustav Schelling, Manfred Thiel, Sarah Baatout, Clarence Sams, and Alexander Choukèr. Early adaption in the Antarctic environment at Dome C: Consequences on stress-sensitive innate immune functions. High Alt Med Biol 15:341-348, 2014.-Purpose/Aims: Medical reports of Antarctic expeditions indicate that health is affected under these extreme conditions. The present study at CONCORDIA-Station (Dome C, 3233 m) seeks to investigate the early consequences of confinement and hypobaric hypoxia on the human organism. Nine healthy male participants were included in this study. Data collection occurred before traveling to Antarctica (baseline), and at 1 week and 1 month upon arrival. Investigated parameters included basic physiological variables, psychological stress tests, cell blood count, stress hormones, and markers of innate immune functions in resting and stimulated immune cells. By testing for the hydrogen peroxide (H2O2) production of stimulated polymorphonuclear leukocytes (PMNs), the effects of the hypoxia-adenosine-sensitive immune modulatory pathways were examined. As compared to baseline data, reduced oxygen saturation, hemoconcentration, and an increase of secreted catecholamines was observed, whereas no psychological stress was seen. Upon stimulation, the activity of PMNs and L-selectin shedding was mitigated after 1 week. Endogenous adenosine concentration was elevated during the early phase. In summary, living conditions at high altitude influence the innate immune system's response. After 1 month, some of the early effects on the human organism were restored. As this early adaptation is not related to psychological stress, the changes observed are likely to be induced by environmental stressors, especially hypoxia. As hypoxia is triggering ATP-catabolism, leading to elevated endogenous adenosine concentrations, this and the increased

  5. Early graft function and carboxyhemoglobin level in liver transplanted patients.

    PubMed

    Ali, Yasser; Negmi, H; Elmasry, N; Sadek, M; Riaz, A; Al Ouffi, H; Khalaf, H

    2007-10-01

    Heme-Oxygenase-1 catalyzes hemoglobin into bilirubin, iron, and carbon monoxide, a well known vasodilator. Heme-Oxygenase-1 expression and carbon monoxide production as measured by blood carboxyhemoglobin levels, increase in end stage liver disease patients. We hypothesized that there may be a correlation between carboxyhemoglobin level and early graft function in patients undergoing liver transplant surgeries. In a descriptive retrospective study, 39 patients who underwent liver transplantation between the year 2005 and 2006 at KFSH&RC, are included in the study. All patients received general anesthesia with isoflurane in 50% oxygen and air. Levels of oxyhemoglobin, carboxyhemoglobin and methemoglobin concentration in percentage were recorded at preoperative time, anhepatic phase, end of surgery, ICU admission and 24 hr after surgery. The level of lactic acid, prothrombin time (PT), partial thrombin time (PTT), serum total bilirubin and ammonia were also recorded at ICU admission and 24 hr after surgery. The numbers of blood units transfused were recorded. 39 patients were included in the study with 13/39 for living donor liver transplant (LDLT) compared to 26/39 patients scheduled for deceased donor liver transplant (DDLT). The mean age was 35.9 +/- 16.9 years while the mean body weight was 60.3 +/- 20.9 Kg. Female to male ratio was 21/18. The median packed red blood cell (PRBC) units was 4 (Rang 0-40). There was a significant increase in carboxyhemoglobin level during the anhepatic phase, end of surgery and on ICU admission compared with preoperative value (p<0.005). However, there was insignificant changes in methemoglobin level and significant decrease in oxyhemoglobin levels throughout the study period compared to the preoperative value (p<0.005). The changes in carboxyhemoglobin level on ICU admission and 24 hrs postoperatively were positively correlated with the changes in serum total bilirubin and prothrombin time (R = 0.35, 0.382, 0.325 and 0

  6. Cognition, social cognition and functional disability in early-stage schizophrenia: A study from southern India.

    PubMed

    Kurtz, Matthew M; Gopal, Subhashini; John, Sujit; Thara, R

    2018-04-24

    In high-income countries a wealth of studies has revealed cognitive and social cognitive deficits in schizophrenia and a close relationship of these deficits to psychosocial functioning. Studies examining these illness features in middle and low-income countries are rare, particularly in early-stage samples. Sixty adult participants within 5 years of diagnosis with schizophrenia and 53 matched, healthy control were assessed with the MATRICS Consensus Cognitive Battery and the PEAT emotion identification task at study entry, and the WHODAS functioning scale one year later. Deficits on cognitive instruments ranged from d = 0.64-1.04 and were consistent with those reported in Western samples. Negative symptoms were linked to function longitudinally. Deficits in social cognitive skills and longitudinal links between cognition and functioning were not evident. These findings suggest a highly consistent magnitude of neurocognitive deficits in people with schizophrenia across widely varying cultures, but with limited evidence of social cognitive skill deficits using Western-based instruments. There was little evidence of a relationship between cognition and psychosocial disability in people with early-stage schizophrenia in this sample. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Dietary glutamine supplementation affects macrophage function, hematopoiesis and nutritional status in early weaned mice.

    PubMed

    Rogero, Marcelo Macedo; Borelli, Primavera; Vinolo, Marco Aurélio Ramirez; Fock, Ricardo Ambrósio; de Oliveira Pires, Ivanir Santana; Tirapegui, Julio

    2008-06-01

    To investigate the effect that early weaning associated with the ingestion of either a glutamine-free or supplemented diet has on the functioning of peritoneal macrophages, hematopoiesis and nutritional status of mice. Swiss Webster mice were early weaned on their 14th day of life and distributed to two groups, being fed either a glutamine-free diet (-GLN) or a glutamine-supplemented diet (+GLN). Animals belonging to a control group (CON) were weaned on their 21st day of life. The -GLN and +GLN groups had a lower lean body mass, carcass protein and ash content, plasma glutamine concentration and lymphocyte counts both in the peripheral blood and bone marrow when compared to the CON group (P<0.05). Dietary supplementation with glutamine reversed both the lower concentrations of protein and DNA in the muscle and liver, as well as the reduced capacity of spreading and synthesizing nitric oxide, hydrogen peroxide, TNF-alpha, IL-1 beta and IL-6 in cultures of peritoneal macrophages obtained from the -GLN group (P<0.05). These data indicate that the ingestion of glutamine modulates the function of peritoneal macrophages in early weaned mice. However, a glutamine-supplemented diet cannot substitute maternal milk in respect to immunological and metabolic parameters.

  8. Associations between early life adversity and executive function in children adopted internationally from orphanages

    PubMed Central

    Hostinar, Camelia E.; Stellern, Sarah A.; Schaefer, Catherine; Carlson, Stephanie M.; Gunnar, Megan R.

    2012-01-01

    Executive function (EF) abilities are increasingly recognized as an important protective factor for children experiencing adversity, promoting better stress and emotion regulation as well as social and academic adjustment. We provide evidence that early life adversity is associated with significant reductions in EF performance on a developmentally sensitive battery of laboratory EF tasks that measured cognitive flexibility, working memory, and inhibitory control. Animal models also suggest that early adversity has a negative impact on the development of prefrontal cortex-based cognitive functions. In this study, we report EF performance 1 y after adoption in 2.5- to 4-y-old children who had experienced institutional care in orphanages overseas compared with a group of age-matched nonadopted children. To our knowledge, this is the youngest age and the soonest after adoption that reduced EF performance has been shown using laboratory measures in this population. EF reductions in performance were significant above and beyond differences in intelligence quotient. Within the adopted sample, current EF was associated with measures of early deprivation after controlling for intelligence quotient, with less time spent in the birth family before placement in an institution and lower quality of physical/social care in institutions predicting poorer performance on the EF battery. PMID:23047689

  9. Associations between early life adversity and executive function in children adopted internationally from orphanages.

    PubMed

    Hostinar, Camelia E; Stellern, Sarah A; Schaefer, Catherine; Carlson, Stephanie M; Gunnar, Megan R

    2012-10-16

    Executive function (EF) abilities are increasingly recognized as an important protective factor for children experiencing adversity, promoting better stress and emotion regulation as well as social and academic adjustment. We provide evidence that early life adversity is associated with significant reductions in EF performance on a developmentally sensitive battery of laboratory EF tasks that measured cognitive flexibility, working memory, and inhibitory control. Animal models also suggest that early adversity has a negative impact on the development of prefrontal cortex-based cognitive functions. In this study, we report EF performance 1 y after adoption in 2.5- to 4-y-old children who had experienced institutional care in orphanages overseas compared with a group of age-matched nonadopted children. To our knowledge, this is the youngest age and the soonest after adoption that reduced EF performance has been shown using laboratory measures in this population. EF reductions in performance were significant above and beyond differences in intelligence quotient. Within the adopted sample, current EF was associated with measures of early deprivation after controlling for intelligence quotient, with less time spent in the birth family before placement in an institution and lower quality of physical/social care in institutions predicting poorer performance on the EF battery.

  10. Precursors of social emotional functioning among full-term and preterm infants at 12 months: Early infant withdrawal behavior and symptoms of maternal depression.

    PubMed

    Moe, Vibeke; Braarud, Hanne Cecilie; Wentzel-Larsen, Tore; Slinning, Kari; Vannebo, Unni Tranaas; Guedeney, Antoine; Heimann, Mikael; Rostad, Anne Margrethe; Smith, Lars

    2016-08-01

    This study forms part of a longitudinal investigation of early infant social withdrawal, maternal symptoms of depression and later child social emotional functioning. The sample consisted of a group of full-term infants (N=238) and their mothers, and a group of moderately premature infants (N=64) and their mothers. At 3 months, the infants were observed with the Alarm Distress Baby Scale (ADBB) and the mothers completed the Edinburgh Postnatal Depression Scale (EPDS). At 12 months, the mothers filled out questionnaires about the infants' social emotional functioning (Infant Toddler Social Emotional Assessment and the Ages and Stages Questionnaire-Social Emotional). At 3 months, as we have previously shown, the premature infants had exhibited more withdrawal behavior and their mothers reported elevated maternal depressive symptoms as compared with the full-born group. At 12 months the mothers of the premature infants reported more child internalizing behavior. These data suggest that infant withdrawal behavior as well as maternal depressive mood may serve as sensitive indices of early risk status. Further, the results suggest that early maternal depressive symptoms are a salient predictor of later child social emotional functioning. However, neither early infant withdrawal behavior, nor gestational age, did significantly predict social emotional outcome at 12 months. It should be noted that the differences in strength of the relations between ADBB and EPDS, respectively, to the outcome at 12 months was modest. An implication of the study is that clinicians should be aware of the complex interplay between early infant withdrawal and signs of maternal postpartum depression in planning ports of entry for early intervention. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Can reactivity to stress and family environment explain memory and executive function performance in early and middle childhood?

    PubMed

    Piccolo, Luciane da Rosa; Salles, Jerusa Fumagalli de; Falceto, Olga Garcia; Fernandes, Carmen Luiza; Grassi-Oliveira, Rodrigo

    2016-01-01

    According to the literature, children's overall reactivity to stress is associated with their socioeconomic status and family environment. In turn, it has been shown that reactivity to stress is associated with cognitive performance. However, few studies have systematically tested these three constructs together. To investigate the relationship between family environment, salivary cortisol measurements and children's memory and executive function performance. Salivary cortisol levels of 70 children aged 9 or 10 years were measured before and after performing tasks designed to assess memory and executive functions. Questionnaires on socioeconomic issues, family environment and maternal psychopathologies were administered to participants' families during the children's early childhood and again when they reached school age. Data were analyzed by calculating correlations between variables and conducting hierarchical regression. High cortisol levels were associated with poorer working memory and worse performance in tasks involving executive functions, and were also associated with high scores for maternal psychopathology (during early childhood and school age) and family dysfunction. Family environment variables and changes in cortisol levels explain around 20% of the variance in performance of cognitive tasks. Family functioning and maternal psychopathology in early and middle childhood and children's stress levels were associated with children's working memory and executive functioning.

  12. Specific Early Number Skills Mediate the Association between Executive Functioning Skills and Mathematics Achievement

    ERIC Educational Resources Information Center

    Fuhs, Mary Wagner; Hornburg, Caroline Byrd; McNeil, Nicole M.

    2016-01-01

    A growing literature reports significant associations between children's executive functioning skills and their mathematics achievement. The purpose of this study was to examine if specific early number skills, such as quantity discrimination, number line estimation, number sets identification, fast counting, and number word comprehension, mediate…

  13. Early on-orbit calibration results from Aqua MODIS

    NASA Astrophysics Data System (ADS)

    Xiong, Xiaoxiong; Barnes, William L.

    2003-04-01

    Aqua MODIS, also known as the MODIS Flight Model 1 (FM1), was launched on May 4, 2002. It opened its nadir aperture door (NAD) on June 24, 2002, beginning its Earth observing mission. In this paper, we present early results from Aqua MODIS on-orbit calibration and characterization and assess the instrument's overall performance. MODIS has 36 spectral bands located on four focal plane assemblies (FPAs). Bands 1-19, and 26 with wavelengths from 0.412 to 2.1 microns are the reflective solar bands (RSB) that are calibrated on-orbit by a solar diffuser (SD). The degradation of the SD is tracked using a solar diffuser stability monitor (SDSM). The bands 20-25, and 27-36 with wavelengths from 3.75 to 14.5 microns are the thermal emissive bands (TEB) that are calibrated on-orbit by a blackbody (BB). Early results indicate that the on-orbit performance has been in good agreement with the predications determined from pre-launch measurements. Except for band 21, the low gain fire band, band 6, known to have some inoperable detectors from pre-launch characterization, and one noisy detector in band 36, all of the detectors' noise characterizations are within their specifications. Examples of the sensor's short-term and limited long-term responses in both TEB and RSB will be provided to illustrate the sensor's on-orbit stability. In addition, we will show some of the improvements that Aqua MODIS made over its predecessor, Terra MODIS (Protoflight Model - PFM), such as removal of the optical leak into the long-wave infrared (LWIR) photoconductive (PC) bands and reduction of electronic crosstalk and out-of-band (OOB) thermal leak into the short-wave infrared (SWIR) bands.

  14. NOSE laparoscopic gastrectomies for early gastric cancer may reduce morbidity and hospital stay: early results from a prospective nonrandomized study.

    PubMed

    Hüscher, Cristiano G S; Lirici, Marco Maria; Ponzano, Cecilia

    2017-04-01

    Natural orifice specimen extraction - NOSE laparoscopy is a promising technique that avoids mini-laparotomy, possibly reducing postoperative pain, wound infections and hospital stay. Recent systematic reviews have shown that postoperative morbidity associated with laparoscopically assisted gastrectomies is similar to that after open gastrectomies. More specifically, there is no difference in wound infection rate. The study objective was to evaluate whether postoperative morbidity and hospital stay may be reduced by transoral specimen extraction after laparoscopically assisted gastrectomy for early gastric cancer (EGC). A prospective, nonrandomized study was carried out starting in August 2012. Data from all patients operated on during the first year, with minimum 18 months follow-up, were collected to assess feasibility, oncologic results, postoperative morbidity, hospital stay and functional results. Overall, 14 patients were included and followed-up. After gastric resection, a 3 cm opening was created on the gastric stump, and the specimen, divided into three segments stitched one to each other, was sutured to the gastric tube and retrieved through the mouth. Postoperative morbidity was 7.14% (1/14): one case of pneumonia. No wound infection occurred. The mean postoperative hospital stay was 4.7 ± 1.0 days. NOSE laparoscopic subtotal gastrectomy is feasible and safe, with similar oncologic results as LAG, but decreased morbidity and hospital stay.

  15. Early effects of cranial irradiation on hypothalamic-pituitary function

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

    Lam, K.S.; Tse, V.K.; Wang, C.

    1987-03-01

    Hypothalamic-pituitary function was studied in 31 patients before and after cranial irradiation for nasopharyngeal carcinoma. The estimated radiotherapy (RT) doses to the hypothalamus and pituitary were 3979 +/- 78 (+/- SD) and 6167 +/- 122 centiGrays, respectively. All patients had normal pituitary function before RT. One year after RT, there was a significant decrease in the integrated serum GH response to insulin-induced hypoglycemia. In the male patients, basal serum FSH significantly increased, while basal serum LH and testosterone did not change. Moreover, in response to LHRH, the integrated FSH response was increased while that of LH was decreased. Such discordantmore » changes in FSH and LH may be explained by a defect in LHRH pulsatile release involving predominantly a decrease in pulse frequency. The peak serum TSH response to TRH became delayed in 28 patients, suggesting a defect in TRH release. Twenty-one patients were reassessed 2 yr after RT. Their mean basal serum T4 and plasma cortisol levels had significantly decreased. Hyperprolactinemia associated with oligomenorrhoea was found in 3 women. Further impairment in the secretion of GH, FSH, LH, TSH, and ACTH had occurred, and 4 patients had hypopituitarism. Thus, progressive impairment in hypothalamic-pituitary function occurs after cranial irradiation and can be demonstrated as early as 1 yr after RT.« less

  16. Mediated Pathways from Maternal Depression and Early Parenting to Children's Executive Function and Externalizing Behaviour Problems

    ERIC Educational Resources Information Center

    Baker, Claire; Kuhn, Laura

    2018-01-01

    Structural equation models were used to examine pathways from maternal depression and early parenting to children's executive function (EF) and externalizing behaviours in the first nationally representative study to obtain direct assessments of children's kindergarten EF skills (i.e., the Early Childhood Longitudinal Study Kindergarten Class of…

  17. Primary Cortical Folding in the Human Newborn: An Early Marker of Later Functional Development

    ERIC Educational Resources Information Center

    Dubois, J.; Benders, M.; Borradori-Tolsa, C.; Cachia, A.; Lazeyras, F.; Leuchter, R. Ha-Vinh; Sizonenko, S. V.; Warfield, S. K.; Mangin, J. F.; Huppi, P. S.

    2008-01-01

    In the human brain, the morphology of cortical gyri and sulci is complex and variable among individuals, and it may reflect pathological functioning with specific abnormalities observed in certain developmental and neuropsychiatric disorders. Since cortical folding occurs early during brain development, these structural abnormalities might be…

  18. From External Regulation to Self-Regulation: Early Parenting Precursors of Young Children's Executive Functioning

    ERIC Educational Resources Information Center

    Bernier, Annie; Carlson, Stephanie M.; Whipple, Natasha

    2010-01-01

    In keeping with proposals emphasizing the role of early experience in infant brain development, this study investigated the prospective links between quality of parent-infant interactions and subsequent child executive functioning (EF), including working memory, impulse control, and set shifting. Maternal sensitivity, mind-mindedness and autonomy…

  19. Early Results from NICER Observations of Accreting Neutron Stars

    NASA Astrophysics Data System (ADS)

    Chakrabarty, Deepto; Ozel, Feryal; Arzoumanian, Zaven; Gendreau, Keith C.; Bult, Peter; Cackett, Ed; Chenevez, Jerome; Fabian, Andy; Guillot, Sebastien; Guver, Tolga; Homan, Jeroen; Keek, Laurens; Lamb, Frederick; Ludlam, Renee; Mahmoodifar, Simin; Markwardt, Craig B.; Miller, Jon M.; Psaltis, Dimitrios; Strohmayer, Tod E.; Wilson-Hodge, Colleen A.; Wolff, Michael T.

    2018-01-01

    The Neutron Star Interior Composition Explorer (NICER) offers significant new capabilities for the study of accreting neuton stars relative to previous X-ray missions including large effective area, low background, and greatly improved low-energy response. The NICER Burst and Accretion Working Group has designed a 2 Ms observation program to study a number of phenomena in accreting neutron stars including type-I X-ray bursts, superbursts, accretion-powered pulsations, quasi-periodic oscillations, and accretion disk reflection spectra. We present some early results from the first six months of the NICER mission.

  20. The reorganization of functional architecture in the early-stages of Parkinson's disease.

    PubMed

    Tuovinen, Noora; Seppi, Klaus; de Pasquale, Francesco; Müller, Christoph; Nocker, Michael; Schocke, Michael; Gizewski, Elke R; Kremser, Christian; Wenning, Gregor K; Poewe, Werner; Djamshidian, Atbin; Scherfler, Christoph; Seki, Morinobu

    2018-05-01

    The study aim was to identify longitudinal abnormalities of functional connectivity and its relation with motor disability in early to moderately advanced stages of Parkinson's disease patients. 3.0T structural and resting-state functional MRI was performed in healthy subjects (n = 16) and Parkinson's disease patients (n = 16) with mean disease duration of 2.2 ± 1.2 years at baseline with a clinical follow-up of 1.5 ± 0.3 years. Resting-state fMRI analysis included region-to-region connectivity in correlation with UPDRS-III scores and computation of Global Efficiency and Degree Centrality. At baseline, patients' connectivity increased between the cerebellum and somatomotor network, and decreased between motor regions (Rolandic operculum, precentral gyrus, supplementary motor area, postcentral gyrus) and cingulate connectivity. At 1.5 years follow-up, connectivity remained altered in the same regions identified at baseline. The cerebellum showed additional hyperconnectivity within itself and to the caudate nucleus, thalamus and amygdala compared to controls. These differences correlated with UPDRS-III scores. Seed-based connectivity revealed increased involvement of the default mode network with precentral gyrus in patients at follow-up investigation. Resting-state fMRI identified marked disturbances of the overall architecture of connectivity in Parkinson's disease. The noted alterations in cortical motor areas were associated with cerebellar hyperconnectivity in early to moderately advanced stages of Parkinson's disease suggesting ongoing attempts of recovery and compensatory mechanism for affected functions. The potential to identify connectivity alterations in regions related to both motor and attentional functions requires further evaluation as an objective marker to monitor disease progression, and medical, as well as surgical interventions. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. Early-life adversity programs emotional functions and the neuroendocrine stress system: the contribution of nutrition, metabolic hormones and epigenetic mechanisms.

    PubMed

    Yam, Kit-Yi; Naninck, Eva F G; Schmidt, Mathias V; Lucassen, Paul J; Korosi, Aniko

    2015-01-01

    Clinical and pre-clinical studies have shown that early-life adversities, such as abuse or neglect, can increase the vulnerability to develop psychopathologies and cognitive decline later in life. Remarkably, the lasting consequences of stress during this sensitive period on the hypothalamic-pituitary-adrenal axis and emotional function closely resemble the long-term effects of early malnutrition and suggest a possible common pathway mediating these effects. During early-life, brain development is affected by both exogenous factors, like nutrition and maternal care as well as by endogenous modulators including stress hormones. These elements, while mostly considered for their independent actions, clearly do not act alone but rather in a synergistic manner. In order to better understand how the programming by early-life stress takes place, it is important to gain further insight into the exact interplay of these key elements, the possible common pathways as well as the underlying molecular mechanisms that mediate their effects. We here review evidence that exposure to both early-life stress and early-life under-/malnutrition similarly lead to life-long alterations on the neuroendocrine stress system and modify emotional functions. We further discuss how the different key elements of the early-life environment interact and affect one another and next suggest a possible role for the early-life adversity induced alterations in metabolic hormones and nutrient availability in shaping later stress responses and emotional function throughout life, possibly via epigenetic mechanisms. Such knowledge will help to develop intervention strategies, which gives the advantage of viewing the synergistic action of a more complete set of changes induced by early-life adversity.

  2. Asynchronous (segmental early) relaxation impairs left ventricular filling in patients with coronary artery disease and normal systolic function.

    PubMed

    Vanoverschelde, J L; Wijns, W; Michel, X; Cosyns, J; Detry, J M

    1991-11-01

    Asynchronous segmental early relaxation, defined as a localized early segmental outward motion of the left ventricular endocardium during isovolumetric relaxation, has been associated with an altered left ventricular relaxation rate. To determine whether asynchronous segmental early relaxation also results in impaired left ventricular filling, early diastolic ventricular wall motion and Doppler-derived left ventricular filling indexes were examined in 25 patients with documented coronary artery disease and normal systolic function. Patients were further classified into two groups according to the presence (n = 15, group 1) or absence (n = 10, group 2) of asynchronous early relaxation at left ventriculography. A third group of 10 age-matched normal subjects served as a control group. No differences were observed between the two patient groups with coronary artery disease with respect to age, gender distribution, heart rate, left ventricular systolic and diastolic pressures or extent and severity of coronary artery disease. No differences in transmitral filling dynamics were observed between group 2 patients and age-matched control subjects. Conversely, group 1 patients had significantly lower peak early filling velocities (44 +/- 11 vs. 58 +/- 11 cm/s, p less than 0.01), larger atrial filling fraction (45 +/- 4% vs. 38 +/- 4%, p less than 0.001), lower ratio of early to late transmitral filling velocities (0.6 +/- 0.08 vs. 0.99 +/- 0.18, p less than 0.001) and a longer isovolumetric relaxation period (114 +/- 12 vs. 90 +/- 6 ms, p less than 0.001) compared with group 2 patients and control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Early changes in somatosensory function in spinal pain: a systematic review and meta-analysis.

    PubMed

    Marcuzzi, Anna; Dean, Catherine M; Wrigley, Paul J; Hush, Julia M

    2015-02-01

    Alterations in sensory processing have been demonstrated in chronic low back and neck pain. However, it has not been yet systematically summarized how early these changes occur in spinal pain. This systematic review examines the available literature measuring somatosensory function in acute (<6 weeks) and subacute (6-12 weeks) spinal pain. The protocol for this review has been registered on the International Prospective Register of Systematic Reviews (PROSPERO). An electronic search of 4 databases was conducted to retrieve studies assessing somatosensory function by quantitative sensory testing in adults with spinal pain of up to 12 weeks duration. Two reviewers independently screened the studies and assessed the risk of bias. Studies were grouped according to spinal pain condition (whiplash injury, idiopathic neck pain, and nonspecific low back pain), and, where possible, meta-analyses were performed for comparable results. Fifteen studies were included. Sources of bias included lack of assessor blinding, unclear sampling methods, and lack of control for confounders. We found that: (1) there is consistent evidence for thermal and widespread mechanical pain hypersensitivity in the acute stage of whiplash, (2) there is no evidence for pain hypersensitivity in the acute and subacute stage of idiopathic neck pain, although the body of evidence is small, and (3) hyperalgesia and spinal cord hyperexcitability have been detected in early stages of nonspecific low back pain, although evidence about widespread effects are conflicting. Future longitudinal research using multiple sensory modalities and standardized testing may reveal the involvement of somatosensory changes in the development and maintenance of chronic pain.

  4. P4-ATPase Requirement for AP-1/Clathrin Function in Protein Transport from the trans-Golgi Network and Early Endosomes

    PubMed Central

    Liu, Ke; Surendhran, Kavitha; Nothwehr, Steven F.

    2008-01-01

    Drs2p is a resident type 4 P-type ATPase (P4-ATPase) and potential phospholipid translocase of the trans-Golgi network (TGN) where it has been implicated in clathrin function. However, precise protein transport pathways requiring Drs2p and how it contributes to clathrin-coated vesicle budding remain unclear. Here we show a functional codependence between Drs2p and the AP-1 clathrin adaptor in protein sorting at the TGN and early endosomes of Saccharomyces cerevisiae. Genetic criteria indicate that Drs2p and AP-1 operate in the same pathway and that AP-1 requires Drs2p for function. In addition, we show that loss of AP-1 markedly increases Drs2p trafficking to the plasma membrane, but does not perturb retrieval of Drs2p from the early endosome back to the TGN. Thus AP-1 is required at the TGN to sort Drs2p out of the exocytic pathway, presumably for delivery to the early endosome. Moreover, a conditional allele that inactivates Drs2p phospholipid translocase (flippase) activity disrupts its own transport in this AP-1 pathway. Drs2p physically interacts with AP-1; however, AP-1 and clathrin are both recruited normally to the TGN in drs2Δ cells. These results imply that Drs2p acts independently of coat recruitment to facilitate AP-1/clathrin-coated vesicle budding from the TGN. PMID:18508916

  5. TECHNIQUES FOR COMBINED PROCUREMENT OF HEARTS AND KIDNEYS WITH SATISFACTORY EARLY FUNCTION OF RENAL ALLOGRAFTS

    PubMed Central

    Shaw, Byers W.; Rosenthal, J. Thomas; Griffith, Bartley F.; Haresty, Robert L.; Broznik, Brian; Hakala, Thomas; Bahnson, Henry T.; Starzl, Thomas E.

    2009-01-01

    SUMMARY Methods for combination of donor nephrectomy with donor cardiectomy are outlined. The satisfactory early function of 29 of 34 transplanted kidneys harvested with these techniques supports their wider application and should encourage their wider acceptance. PMID:6351307

  6. Hospitalisation with otitis media in early childhood and cognitive function in young adult life: a prevalence study among Danish conscripts

    PubMed Central

    2013-01-01

    Background Otitis media (OM) is a very common condition in children and occurs during years that are critical to the development of learning, literacy, and math skills. Therefore, among a large cohort of Danish conscripts, we aimed to examine the association between hospitalisation with OM in early childhood and cognitive function and educational level in early adulthood. Methods We conducted a population-based prevalence study using linked data from healthcare databases and conscription records of Danish men born between 1977 and 1983. We identified all hospitalisations with OM before 8 years of age. Cognitive function was measured by the Boerge Prien validated group intelligence test (Danish Børge Prien Prøve, BPP). We adjusted for potential confounders with and without stratification by hearing impairment. Furthermore, we examined the association between hospitalisation with OM and the prevalence of having achieved a General Certificate of Secondary Education (GCSE), stratified by quartiles of BPP scores. Results Of the 18 412 eligible conscripts aged 18–25 years, 1000 (5.5%) had been hospitalised with OM before age 8. Compared with conscripts without such a record, the adjusted prevalence ratio (PR) for a BPP score in the bottom quartile was 1.20 (95% confidence interval [CI]: 1.09–1.33). There was no major difference in the proportion of men with a GCSE and those without among those hospitalised with OM in early childhood. For men in the bottom and upper quartiles of BPP scores, the PRs for early childhood hospitalisation with OM were 0.89 (95% CI: 0.59–1.33) and 0.96 (95% CI, 0.88–1.05), respectively. Among men with severe hearing impairment, the proportion with a BPP score in the bottom quartile did not differ between those with and without an OM hospitalisation [PR = 1.01 (95% CI: 0.78–1.34)]. Conclusions Overall, we found that hospitalisation with OM in early childhood was associated with a slightly lower cognitive function in early

  7. Closing the achievement gap through modification of neurocognitive and neuroendocrine function: results from a cluster randomized controlled trial of an innovative approach to the education of children in kindergarten.

    PubMed

    Blair, Clancy; Raver, C Cybele

    2014-01-01

    Effective early education is essential for academic achievement and positive life outcomes, particularly for children in poverty. Advances in neuroscience suggest that a focus on self-regulation in education can enhance children's engagement in learning and establish beneficial academic trajectories in the early elementary grades. Here, we experimentally evaluate an innovative approach to the education of children in kindergarten that embeds support for self-regulation, particularly executive functions, into literacy, mathematics, and science learning activities. Results from a cluster randomized controlled trial involving 29 schools, 79 classrooms, and 759 children indicated positive effects on executive functions, reasoning ability, the control of attention, and levels of salivary cortisol and alpha amylase. Results also demonstrated improvements in reading, vocabulary, and mathematics at the end of kindergarten that increased into the first grade. A number of effects were specific to high-poverty schools, suggesting that a focus on executive functions and associated aspects of self-regulation in early elementary education holds promise for closing the achievement gap.

  8. Closing the Achievement Gap through Modification of Neurocognitive and Neuroendocrine Function: Results from a Cluster Randomized Controlled Trial of an Innovative Approach to the Education of Children in Kindergarten

    PubMed Central

    Blair, Clancy; Raver, C. Cybele

    2014-01-01

    Effective early education is essential for academic achievement and positive life outcomes, particularly for children in poverty. Advances in neuroscience suggest that a focus on self-regulation in education can enhance children’s engagement in learning and establish beneficial academic trajectories in the early elementary grades. Here, we experimentally evaluate an innovative approach to the education of children in kindergarten that embeds support for self-regulation, particularly executive functions, into literacy, mathematics, and science learning activities. Results from a cluster randomized controlled trial involving 29 schools, 79 classrooms, and 759 children indicated positive effects on executive functions, reasoning ability, the control of attention, and levels of salivary cortisol and alpha amylase. Results also demonstrated improvements in reading, vocabulary, and mathematics at the end of kindergarten that increased into the first grade. A number of effects were specific to high-poverty schools, suggesting that a focus on executive functions and associated aspects of self-regulation in early elementary education holds promise for closing the achievement gap. PMID:25389751

  9. Early, middle, or late administration of zoledronate alleviates spontaneous nociceptive behavior and restores functional outcomes in a mouse model of CFA-induced arthritis.

    PubMed

    Morado-Urbina, Carlos Eduardo; Alvarado-Vázquez, Perla Abigail; Montiel-Ruiz, Rosa Mariana; Acosta-González, Rosa Issel; Castañeda-Corral, Gabriela; Jiménez-Andrade, Juan Miguel

    2014-11-01

    This study was performed to evaluate whether early, middle, or late treatment of zoledronate, an approved bisphosphonate that blocks bone resorption, can reduce nociceptive behaviors in a mouse arthritis model. Arthritis was produced by repeated intra-articular knee injections of complete Freund's adjuvant (CFA). A dose-response curve with zoledronate (3, 30, 100, and 300 μg/kg, i.p., day 4 to day 25, twice weekly for 3 weeks) was performed, and the most effective dose of zoledronate (100 μg/kg, i.p.) was initially administered at different times of disease progression: day 4 (early), day 15 (middle), or day 21 (late) and continued until day 25 after the first CFA injection. Flinching of the injected extremity (spontaneous nociceptive behavior), vertical rearings and horizontal activity (functional outcomes), and knee edema were assessed. Zoledronate improved both functional outcomes and reduced flinching behavior. At day 25, the effect of zoledronate on flinching behavior and vertical rearings was greater in magnitude when it was given early or middle rather than late in the treatment regimen. Chronic zoledronate did not reduce knee edema in CFA-injected mice nor functional outcomes in naïve mice by itself. These results suggest that zoledronate may have a positive effect on arthritis-induced nociception and functional disabilities. © 2014 Wiley Periodicals, Inc.

  10. Early changes in somatosensory function in spinal pain: protocol for a systematic review.

    PubMed

    Marcuzzi, Anna; Dean, Catherine M; Hush, Julia M

    2013-10-02

    Back and neck pain are common conditions that have a high burden of disease. Changes in somatosensory function in the periphery, the spinal cord and the brain have been well documented at the time when these conditions have become chronic. It is unknown, however, how early these changes occur, what the timecourse is of sensory dysfunction and what the specific nature of these changes are in the first 12 weeks after onset of pain. In this paper, we describe the protocol for a systematic review of the literature on somatosensory dysfunction in the first 12 weeks after pain onset. We will conduct a comprehensive search for articles indexed in the databases Ovid MEDLINE, Ovid Embase, Ovid PsycINFO and Cochrane Central Register of Controlled Trial (CENTRAL) from their inception to August 2013 that report on any aspect of somatosensory function in acute or subacute neck or back pain. Two independent reviewers will screen studies for eligibility, assess risk of bias and extract relevant data. Results will be tabulated and a narrative synthesis of the results conducted. Currently, there is a gap in our knowledge about the timing of somatosensory changes in back and neck pain. The systematic review outlined in this protocol aims to address this knowledge gap and inform developments in diagnostic tools and pain mechanism-based treatments. Our protocol has been registered on PROSPERO, CRD42013005113.

  11. The role of early life nutrition in programming of reproductive function.

    PubMed

    Chadio, S; Kotsampasi, B

    2014-02-01

    Accumulating evidence suggest that the concept of programming can also be applied to reproductive development and function, representing an ever expanding research area. Recently issues such as peri- or even preconceptional nutrition, transgenerational effects and underlying mechanisms have received considerable attention. The present chapter presents the existed evidence and reviews the available data from numerous animal and human studies on the effects of early life nutritional environment on adult reproductive function. Specific outcomes depend on the severity, duration and stage of development when nutritional perturbations are imposed, while sex-specific effects are also manifested. Apart from undernutrition, effects of relative overnutrition as well as the complex interactions between pre- and postnatal nutrition is of high importance, especially in the context of our days obesity epidemic. Mechanisms underlying reproductive programming are yet unclear, but may include a role for epigenetic modifications. Epigenetic modulation of critical genes involved in the control of reproductive function and potential intergenerational effects represent an exciting area of interdisciplinary research toward the development of new nutritional approaches during pre- and postnatal periods to ensure reproductive health in later life.

  12. A continuum of executive function deficits in early subcortical vascular cognitive impairment: A systematic review and meta-analysis

    PubMed Central

    Sudo, Felipe Kenji; Amado, Patricia; Alves, Gilberto Sousa; Laks, Jerson; Engelhardt, Eliasz

    2017-01-01

    ABSTRACT. Background. Subcortical Vascular Cognitive Impairment (SVCI) is a clinical continuum of vascular-related cognitive impairment, including Vascular Mild Cognitive Impairment (VaMCI) and Vascular Dementia. Deficits in Executive Function (EF) are hallmarks of the disorder, but the best methods to assess this function have yet to be determined. The insidious and almost predictable course of SVCI and the multidimensional concept of EF suggest that a temporal dissociation of impairments in EF domains exists early in the disorder. Objective: This study aims to review and analyze data from the literature about performance of VaMCI patients on the most used EF tests through a meta-analytic approach. Methods: Medline, Web of Knowledge and PsycINFO were searched, using the terms: “vascular mild cognitive impairment” OR “vascular cognitive impairment no dementia” OR “vascular mild neurocognitive disorder” AND “dysexecutive” OR “executive function”. Meta-analyses were conducted for each of the selected tests, using random-effect models. Results: Systematic review showed major discrepancies among the results of the studies included. Meta-analyses evidenced poorer performance on the Trail-Making Test part B and the Stroop color test by VaMCI patients compared to controls. Conclusion: A continuum of EF impairments has been proposed in SVCI. Early deficits appear to occur in cognitive flexibility and inhibitory control. PMID:29354217

  13. Raw milk consumption and other early-life farm exposures and adult pulmonary function in the Agricultural Lung Health Study.

    PubMed

    Wyss, Annah B; House, John S; Hoppin, Jane A; Richards, Marie; Hankinson, John L; Long, Stuart; Henneberger, Paul K; Beane Freeman, Laura E; Sandler, Dale P; O'Connell, Elizabeth Long; Cummings, Christie Barker; Umbach, David M; London, Stephanie J

    2018-03-01

    Literature suggests that early exposure to the farming environment protects against atopy and asthma; few studies have examined pulmonary function. We evaluated associations between early-life farming exposures and pulmonary function in 3061 adults (mean age=63) from a US farming population using linear regression. Childhood raw milk consumption was associated with higher FEV 1 (β=49.5 mL, 95% CI 2.8 to 96.1 mL, p=0.04) and FVC (β=66.2 mL, 95% CI 13.2 to 119.1 mL, p=0.01). We did not find appreciable associations with other early-life farming exposures. We report a novel association between raw milk consumption and higher pulmonary function that lasts into older adulthood. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  14. Predicting Acceptance and Popularity in Early Adolescence as a Function of Hearing Status, Gender, and Educational Setting

    ERIC Educational Resources Information Center

    Wolters, Nina; Knoors, Harry E. T.; Cillessen, Antonius H. N.; Verhoeven, Ludo

    2011-01-01

    This study examined associations of communicative skills, social behavior, and personality with acceptance and popularity as a function of hearing status, gender, and educational setting. Participants were 87 deaf and 672 hearing early adolescents of 52 6th grade classrooms in mainstream and special education. Acceptance varied as a function of…

  15. Early Results from the NASA Orbiting Carbon Observatory-2 (OCO-2)

    NASA Astrophysics Data System (ADS)

    Crisp, David; Eldering, Annmarie

    2015-04-01

    The Orbiting Carbon Observatory-2 (OCO-2) is NASA's first satellite designed to collect the measurements needed to estimate the column-averaged carbon dioxide (CO2) dry air mole fraction, XCO2, with the sensitivity, accuracy, and resolution needed to characterize the CO2 sources and sinks on regional scales over the globe. OCO-2 was successfully launched from Vandenberg Air Force Base in California on July 2, 2014 and joined the 705-km Afternoon Constellation (A-Train) on August 3, 2014. The three-channel imaging grating spectrometer was then cooled to its operating temperatures and a comprehensive series of characterization and calibration activities were initiated. Since early October 2014, the observatory has been routinely collecting almost 1 million soundings over the sunlit hemisphere each day. Early cloud screening results indicate that 15-30% of these measurements may be sufficiently cloud free to yield precise estimates of XCO2. Initial deliveries of calibrated, geo-located OCO-2 spectra to the NASA Goddard Earth Science Data and Information Services Center (GES DISC) began on December 30, 2014. Preliminary estimates of XCO2 retrieved from these data are currently being validated against observations from the Total Carbon Column Observing Network (TCCON) and other standards. Routine deliveries XCO2 and other products, including surface pressure and chlorophyll fluorescence, to the GES DISC are expected to begin before the end of March, 2015. This presentation will summarize the status of the OCO-2 mission and the coverage, resolution, and accuracy of its early results.

  16. Emotional Reactivity and Regulation in Infancy Interact to Predict Executive Functioning in Early Childhood

    ERIC Educational Resources Information Center

    Ursache, Alexandra; Blair, Clancy; Stifter, Cynthia; Voegtline, Kristin

    2013-01-01

    The relation of observed emotional reactivity and regulation in infancy to executive function in early childhood was examined in a prospective longitudinal sample of 1,292 children from predominantly low-income and rural communities. Children participated in a fear eliciting task at ages 7, 15, and 24 months and completed an executive function…

  17. Dissociable changes in functional network topology underlie early category learning and development of automaticity

    PubMed Central

    Soto, Fabian A.; Bassett, Danielle S.; Ashby, F. Gregory

    2016-01-01

    Recent work has shown that multimodal association areas–including frontal, temporal and parietal cortex–are focal points of functional network reconfiguration during human learning and performance of cognitive tasks. On the other hand, neurocomputational theories of category learning suggest that the basal ganglia and related subcortical structures are focal points of functional network reconfiguration during early learning of some categorization tasks, but become less so with the development of automatic categorization performance. Using a combination of network science and multilevel regression, we explore how changes in the connectivity of small brain regions can predict behavioral changes during training in a visual categorization task. We find that initial category learning, as indexed by changes in accuracy, is predicted by increasingly efficient integrative processing in subcortical areas, with higher functional specialization, more efficient integration across modules, but a lower cost in terms of redundancy of information processing. The development of automaticity, as indexed by changes in the speed of correct responses, was predicted by lower clustering (particularly in subcortical areas), higher strength (highest in cortical areas) and higher betweenness centrality. By combining neurocomputational theories and network scientific methods, these results synthesize the dissociative roles of multimodal association areas and subcortical structures in the development of automaticity during category learning. PMID:27453156

  18. Systematic review of early surgery for chronic pancreatitis: impact on pain, pancreatic function, and re-intervention.

    PubMed

    Yang, Catherine J; Bliss, Lindsay A; Schapira, Emily F; Freedman, Steven D; Ng, Sing Chau; Windsor, John A; Tseng, Jennifer F

    2014-10-01

    Surgical intervention has traditionally been reserved as the last management option for pain in chronic pancreatitis. Recently, there has been a call for surgery to be offered earlier in the disease process. The objectives of this review were to evaluate the effect of early surgery on postoperative pain, pancreatic function, and re-intervention rates in chronic pancreatitis. A systematic literature search through EMBASE, Cochrane Review, and PubMed from January 1950 to January 2014 was conducted. Citations found in relevant papers are hand-searched. Data which could be pooled were analyzed using Revman (v5.2). Risk of bias analysis was conducted. Of the 2,886 potentially eligible studies identified, 11 studies met the inclusion criteria. There was large heterogeneity in the study designs, and studies were conducted over a lengthy time span. Seven studies examined pain, three studies examined pancreatic function, and three studies examined rates of re-intervention. Meta-analysis of the three studies with comparative raw data regarding complete pain relief showed that early surgery was associated with an increased likelihood of complete postoperative pain relief (RR = 1.67, 95% CI 1.09-2.56, p = 0.02). Early surgery was also associated with reduced risk of pancreatic insufficiency and low re-intervention rates. Data from this study supports considering early surgery for pain management in patients with chronic pancreatitis, with the potential of a reduced risk of pancreatic insufficiency and the need for further intervention. Further prospective randomized studies are warranted comparing early surgery against conservative step-up approaches.

  19. Early radiological and functional outcomes for a cementless press-fit design modular femoral stem revision system.

    PubMed

    Hancock, Douglas S; Sharplin, Paul K; Larsen, Peter D; Phillips, Fredrick Ts

    2018-05-01

    To assess early radiological and functional outcomes of revision hip surgery with a cementless press-fit design femoral stem. A retrospective review of 48 consecutive revision total hip replacements using the RECLAIM revision hip system, between October 2012 and August 2015. Radiographic assessment was undertaken with serial anteroposterior (AP) X-rays of the pelvis. Risk factors for subsidence were evaluated. Prospective clinical follow up was performed on 21 patients to assess functional outcomes. Mean stem subsidence was 1.1 mm (95% confidence interval[CI]: 0.63-1.57). Median follow up of 12 months. An inverse relationship was observed between level of subsidence and femoral stem diameter r = -0.45, p = 0.001. Subsidence at the time of follow-up assessment was correlated with initial subsidence (correlation coefficient rho 0.69, p = 0.001). The mean Merle d'Aubigne score at the latest follow up was 14.2 (range 8-17). The mean OHS was 34.1 (range 15-48). Early radiological and functional outcomes for the RECLAIM revision system showed very low levels of subsidence and good functional outcomes. There was an association with smaller diameter femoral stems and greater levels of subsidence.

  20. Feasibility of Undertaking Off-Site Infant Eye-Tracking Assessments of Neuro-Cognitive Functioning in Early-Intervention Centres

    ERIC Educational Resources Information Center

    Ballieux, Haiko; Tomalski, Przemyslaw; Kushnerneko, Elena; Johnson, Mark H.; Karmiloff-Smith, Annette; Moore, Derek G.

    2016-01-01

    Recent work suggests that differences in functional brain development are already identifiable in 6- to 9-month-old infants from low socio-economic status (SES) backgrounds. Investigation of early SES-related differences in neuro-cognitive functioning requires the recruitment of large and diverse samples of infants, yet it is often difficult to…

  1. Early diagnosis in glaucoma.

    PubMed

    Garway-Heath, David F

    2008-01-01

    This chapter reviews the evidence for the clinical application of vision function tests and imaging devices to identify early glaucoma, and sets out a scheme for the appropriate use and interpretation of test results in screening/case-finding and clinic settings. In early glaucoma, signs may be equivocal and the diagnosis is often uncertain. Either structural damage or vision function loss may be the first sign of glaucoma; neither one is consistently apparent before the other. Quantitative tests of visual function and measurements of optic-nerve head and retinal nerve fiber layer anatomy are useful to either raise or lower the probability that glaucoma is present. The posttest probability for glaucoma may be calculated from the pretest probability and the likelihood ratio of the diagnostic criterion, and the output of several diagnostic devices may be combined to achieve a final probability. However, clinicians need to understand how these diagnostic devices make their measurements, so that the validity of each test result can be adequately assessed. Only then should the result be used, together with the patient history and clinical examination, to derive a diagnosis.

  2. Systematic variation of the stellar initial mass function in early-type galaxies.

    PubMed

    Cappellari, Michele; McDermid, Richard M; Alatalo, Katherine; Blitz, Leo; Bois, Maxime; Bournaud, Frédéric; Bureau, M; Crocker, Alison F; Davies, Roger L; Davis, Timothy A; de Zeeuw, P T; Duc, Pierre-Alain; Emsellem, Eric; Khochfar, Sadegh; Krajnović, Davor; Kuntschner, Harald; Lablanche, Pierre-Yves; Morganti, Raffaella; Naab, Thorsten; Oosterloo, Tom; Sarzi, Marc; Scott, Nicholas; Serra, Paolo; Weijmans, Anne-Marie; Young, Lisa M

    2012-04-25

    Much of our knowledge of galaxies comes from analysing the radiation emitted by their stars, which depends on the present number of each type of star in the galaxy. The present number depends on the stellar initial mass function (IMF), which describes the distribution of stellar masses when the population formed, and knowledge of it is critical to almost every aspect of galaxy evolution. More than 50 years after the first IMF determination, no consensus has emerged on whether it is universal among different types of galaxies. Previous studies indicated that the IMF and the dark matter fraction in galaxy centres cannot both be universal, but they could not convincingly discriminate between the two possibilities. Only recently were indications found that massive elliptical galaxies may not have the same IMF as the Milky Way. Here we report a study of the two-dimensional stellar kinematics for the large representative ATLAS(3D) sample of nearby early-type galaxies spanning two orders of magnitude in stellar mass, using detailed dynamical models. We find a strong systematic variation in IMF in early-type galaxies as a function of their stellar mass-to-light ratios, producing differences of a factor of up to three in galactic stellar mass. This implies that a galaxy's IMF depends intimately on the galaxy's formation history.

  3. FUNCTIONAL OUTCOMES OF HIP ARTHROSCOPY IN AN ACTIVE DUTY MILITARY POPULATION UTILIZING A CRITERION-BASED EARLY WEIGHT BEARING PROGRESSION

    PubMed Central

    Jacobs, Jeremy M.; Evanson, J. Richard; Pniewski, Josh; Dickston, Michelle L.; Mueller, Terry; Bojescul, John A.

    2017-01-01

    Introduction Hip arthroscopy allows surgeons to address intra-articular pathology of the hip while avoiding more invasive open surgical dislocation. However the post-operative rehabilitation protocols have varied greatly in the literature, with many having prolonged periods of limited motion and weight bearing. Purpose The purpose of this study was to describe a criterion-based early weight bearing protocol following hip arthroscopy and investigate functional outcomes in the subjects who were active duty military. Methods Active duty personnel undergoing hip arthroscopy for symptomatic femoroacetabular impingement were prospectively assessed in a controlled environment for the ability to incorporate early postoperative weight-bearing with the following criteria: no increased pain complaint with weight bearing and normalized gait pattern. Modified Harris Hip (HHS) and Hip Outcome score (HOS) were performed preoperatively and at six months post-op. Participants were progressed with a standard hip arthroscopy protocol. Hip flexion was limited to not exceed 90 degrees for the first three weeks post-op, with progression back to running beginning at three months. Final discharge was dependent upon the ability to run two miles at military specified pace and do a single leg broad jump within six inches of the contralateral leg without an increase in pain. Results Eleven participants met inclusion criteria over the study period. Crutch use was discontinued at an average of five days following surgery based on established weight bearing criteria. Only one participant required continued crutch use at 15 days. Participants’ functional outcome was improved postoperatively, as demonstrated by significant increases in HOS and HHS. At the six month follow up, eight of 11 participants were able to take and complete a full Army Physical Fitness Test. Conclusions Following completion of the early weight bearing rehabilitation protocol, 81% of participants were able to progress to

  4. Family Risks and Protective Factors: Pathways to Early Head Start Toddlers' Social-Emotional Functioning

    ERIC Educational Resources Information Center

    Vick Whittaker, Jessica E.; Harden, Brenda Jones; See, Heather M.; Meisch, Allison D.; Westbrook, T'Pring R.

    2011-01-01

    Early Head Start children may be more likely to exhibit difficulties with social-emotional functioning due to the high-risk environments in which they live. However, positive parenting may serve as a protective factor against the influence of risk on children's outcomes. The current study examines the effects of contextual and proximal risks on…

  5. During early to mid adolescence, moderate to vigorous physical activity is associated with restoring sleep, psychological functioning, mental toughness and male gender.

    PubMed

    Brand, Serge; Kalak, Nadeem; Gerber, Markus; Clough, Peter J; Lemola, Sakari; Sadeghi Bahmani, Dena; Pühse, Uwe; Holsboer-Trachsler, Edith

    2017-03-01

    Numerous studies showed that regular physical activity (PA) is associated with both favourable and restorative sleep and improved psychological functioning (PF). However, there is little research on the topic covering the early to mid-adolescence period. Moreover, curiosity and exploratory behaviour (CEB) and mental toughness (MT) as a result of PA remains thus far uninvestigated, as do possible gender differences. The aim of the present study was to explore the associations between PA, subjective sleep (sS), PF, CEB, and MT during early to mid-adolescence. A total of 1361 participants (mean age = 13.37 years; range: 11-16 years; 51.2% female) took part in the study. They completed questionnaires covering PA, sS, PF, CEB, and MT. Greater PA was related to improved PF, better sS, and increased CEB and MT. Compared to male participants, females reported less PA, poorer sS, and had lower PF and MT scores. The present pattern of results suggests that during early and mid-adolescence greater PA was associated with more favourable sS and better PF, including CEB and MT, and that female participants reported lower scores in PA, sS, and PF. Accordingly, if PA has a favourable impact on sleep and psychological functioning, then data suggest that sports participation should be more tailored to increase motivation among female adolescents.

  6. Nanoparticle-facilitated functional and molecular imaging for the early detection of cancer

    PubMed Central

    Sivasubramanian, Maharajan; Hsia, Yu; Lo, Leu-Wei

    2014-01-01

    Cancer detection in its early stages is imperative for effective cancer treatment and patient survival. In recent years, biomedical imaging techniques, such as magnetic resonance imaging, computed tomography and ultrasound have been greatly developed and have served pivotal roles in clinical cancer management. Molecular imaging (MI) is a non-invasive imaging technique that monitors biological processes at the cellular and sub-cellular levels. To achieve these goals, MI uses targeted imaging agents that can bind targets of interest with high specificity and report on associated abnormalities, a task that cannot be performed by conventional imaging techniques. In this respect, MI holds great promise as a potential therapeutic tool for the early diagnosis of cancer. Nevertheless, the clinical applications of targeted imaging agents are limited due to their inability to overcome biological barriers inside the body. The use of nanoparticles has made it possible to overcome these limitations. Hence, nanoparticles have been the subject of a great deal of recent studies. Therefore, developing nanoparticle-based imaging agents that can target tumors via active or passive targeting mechanisms is desirable. This review focuses on the applications of various functionalized nanoparticle-based imaging agents used in MI for the early detection of cancer. PMID:25988156

  7. Lung Function in Rural Guatemalan Women Before and After a Chimney Stove Intervention to Reduce Wood Smoke Exposure: Results From the Randomized Exposure Study of Pollution Indoors and Respiratory Effects and Chronic Respiratory Effects of Early Childhood Exposure to Respirable Particulate Matter Study.

    PubMed

    Guarnieri, Michael; Diaz, Esperanza; Pope, Daniel; Eisen, Ellen A; Mann, Jennifer; Smith, Kirk R; Smith-Sivertsen, Tone; Bruce, Nigel G; Balmes, John R

    2015-11-01

    COPD is the third most frequent cause of death globally, with much of this burden attributable to household biomass smoke exposure in developing countries. As biomass smoke exposure is also associated with cardiovascular disease, lower respiratory infection, lung cancer, and cataracts, it presents an important target for public health intervention. Lung function in Guatemalan women exposed to wood smoke from open fires was measured throughout the Randomized Exposure Study of Pollution Indoors and Respiratory Effects (RESPIRE) stove intervention trial and continued during the Chronic Respiratory Effects of Early Childhood Exposure to Respirable Particulate Matter (CRECER) cohort study. In RESPIRE, early stove households received a chimney woodstove at the beginning of the 18-month trial, and delayed stove households received a stove at trial completion. Personal exposure to wood smoke was assessed with exhaled breath carbon monoxide (CO) and personal CO tubes. Change in lung function between intervention groups and as a function of wood smoke exposure was assessed using random effects models. Of 306 women participating in both studies, acceptable spirometry was collected in 129 early stove and 136 delayed stove households (n = 265), with a mean follow-up of 5.6 years. Despite reduced wood smoke exposures in early stove households, there were no significant differences in any of the measured spirometric variables during the study period (FEV1, FVC, FEV1/FVC ratio, and annual change) after adjustment for confounding. In these young Guatemalan women, there was no association between lung function and early randomization to a chimney stove or personal wood smoke exposure. Future stove intervention trials should incorporate cleaner stoves, longer follow-up, or potentially susceptible groups to identify meaningful differences in lung function.

  8. Riociguat in patients with chronic thromboembolic pulmonary hypertension: results from an early access study.

    PubMed

    McLaughlin, Vallerie V; Jansa, Pavel; Nielsen-Kudsk, Jens E; Halank, Michael; Simonneau, Gérald; Grünig, Ekkehard; Ulrich, Silvia; Rosenkranz, Stephan; Gómez Sánchez, Miguel A; Pulido, Tomás; Pepke-Zaba, Joanna; Barberá, Joan Albert; Hoeper, Marius M; Vachiéry, Jean-Luc; Lang, Irene; Carvalho, Francine; Meier, Christian; Mueller, Katharina; Nikkho, Sylvia; D'Armini, Andrea M

    2017-12-28

    Following positive results from the Phase III CHEST-1 study in patients with inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH), the Phase IIIb CTEPH early access study (EAS) was designed to assess the safety and tolerability of riociguat in real-world clinical practice, as well as to provide patients with early access to riociguat before launch. Riociguat is approved for the treatment of inoperable and persistent/recurrent CTEPH. We performed an open-label, uncontrolled, single-arm, early access study in which 300 adult patients with inoperable or persistent/recurrent CTEPH received riociguat adjusted from 1 mg three times daily (tid) to a maximum of 2.5 mg tid. Patients switching from unsatisfactory prior pulmonary arterial hypertension (PAH)-targeted therapy (n = 84) underwent a washout period of at least 3 days before initiating riociguat. The primary aim was to assess the safety and tolerability of riociguat, with World Health Organization functional class and 6-min walking distance (6MWD) as exploratory efficacy endpoints. In total, 262 patients (87%) completed study treatment and entered the safety follow-up (median treatment duration 47 weeks). Adverse events were reported in 273 patients (91%). The most frequently reported serious adverse events were syncope (6%), right ventricular failure (3%), and pneumonia (2%). There were five deaths, none of which was considered related to study medication. The safety and tolerability of riociguat was similar in patients switched from other PAH-targeted therapies and those who were treatment naïve. In patients with data available, mean ± standard deviation 6MWD had increased by 33 ± 42 m at Week 12 with no clinically relevant differences between the switched and treatment-naïve subgroups. Riociguat was well tolerated in patients with CTEPH who were treatment naïve, and in those who were switched from other PAH-targeted therapies. No new safety signals were

  9. Cardiac and peripheral adjustments induced by early exercise training intervention were associated with autonomic improvement in infarcted rats: role in functional capacity and mortality.

    PubMed

    Jorge, Luciana; Rodrigues, Bruno; Rosa, Kaleizu Teodoro; Malfitano, Christiane; Loureiro, Tatiana Carolina Alba; Medeiros, Alessandra; Curi, Rui; Brum, Patricia Chakur; Lacchini, Silvia; Montano, Nicola; De Angelis, Kátia; Irigoyen, Maria-Cláudia

    2011-04-01

    To test the effects of early exercise training (ET) on left ventricular (LV) and autonomic functions, haemodynamics, tissues blood flows (BFs), maximal oxygen consumption (VO(2) max), and mortality after myocardial infarction (MI) in rats. Male Wistar rats were divided into: control (C), sedentary-infarcted (SI), and trained-infarcted (TI). One week after MI, TI group underwent an ET protocol (90 days, 50-70% VO(2) max). Left ventricular function was evaluated non-invasively and invasively. Baroreflex sensitivity, heart rate variability, and pulse interval were measured. Cardiac output (CO) and regional BFs were determined using coloured microspheres. Infarcted area was reduced in TI (19 ± 6%) compared with SI (34 ± 5%) after ET. Exercise training improved the LV and autonomic functions, the CO and regional BF changes induced by MI, as well as increased SERCA2 expression and mRNA vascular endothelial growth factor levels. These changes brought about by ET resulted in mortality rate reduction in the TI (13%) group compared with the SI (54%) group. Early aerobic ET reduced cardiac and peripheral dysfunctions and preserved cardiovascular autonomic control after MI in trained rats. Consequently, these ET-induced changes resulted in improved functional capacity and survival after MI.

  10. Effect of early and late rehabilitation onset in a chronic rat model of ischemic stroke- assessment of motor cortex signaling and gait functionality over time.

    PubMed

    Nielsen, Rasmus K; Samson, Katrine L; Simonsen, Daniel; Jensen, Winnie

    2013-11-01

    The aim of the present study was to investigate the effects of ischemic stroke and onset of subsequent rehabilitation of gait function in rats. Nine male Sprague-Dawley rats were instrumented with a 16-channel intracortical (IC) electrode array. An ischemic stroke was induced within the hindlimb area of the left motor cortex. The rehabilitation consisted of a repetitive training paradigm over 28 days, initiated on day one ("Early-onset", 5 rats) and on day seven, ("Late-onset", 4 rats). Data were obtained from IC microstimulation tests, treadmill walking tests, and beam walking tests. Results revealed an expansion of the hindlimb representation within the motor cortex area and an increased amount of cortical firing rate modulation for the "Early-onset" group but not for the "Late-onset" group. Kinematic data revealed a significant change for both intervention groups. However, this difference was larger for the "Early-onset" group. Results from the beam walking test showed functional performance deficits following stroke which returned to pre-stroke level after the rehabilitative training. The results from the present study indicate the existence of a critical time period following stroke where onset of rehabilitative training may be more effective and related to a higher degree of true recovery.

  11. Elevated alanine aminotransferase (ALT) in the deceased donor: impact on early post-transplant liver allograft function.

    PubMed

    Mangus, Richard S; Fridell, Jonathan A; Kubal, Chandrashekhar A; Davis, Jason P; Tector, A Joseph

    2015-02-01

    Serum alanine aminotransferase (ALT) levels are frequently elevated with liver injury and such elevations are common in deceased organ donors. The impact of this injury on early liver allograft function has not been well described. This study analyses the immediate function and 1-year graft and patient survival for liver allografts stratified by peak serum ALT levels in the deceased donor. The on-site organ procurement records for 1348 consecutive deceased liver donors were reviewed (2001–2011). Serum ALT was categorized into three study groups: normal/mild elevation, 0–499 μ/L; moderate elevation, 500–999 μ/L (>10× upper limit of normal) and severe elevation, ≥1000 μ/L (>20× upper limit of normal). Outcomes included early graft function and graft loss, and 1-year graft and patient survival. Distribution of subjects included: normal/mild, 1259 (93%); moderate, 34 (3%) and severe, 55 (4%). Risk of 30-day graft loss for the three study groups was: 72 (6%), 3 (9%) and 3 (6%) (P = 0.74). Graft and patient survival at 1 year for the three groups was: normal/mild, 1031 (87%), 1048 (88%); moderate, 31 (91%), 31 (91%) and severe, 43 (88%), 44 (90%) (P = 0.71, 0.79). Cox proportional hazards modelling of survival while controlling for donor age and recipient model for end-stage liver disease score (MELD) demonstrates no statistically significant difference among the three study groups. This study demonstrates clinical equivalence in early graft function and 1-year graft and patient survival for donor livers with varying peak levels of serum ALT. These donor allografts may, therefore, be utilized successfully.

  12. Do Economic Recessions During Early and Mid-Adulthood Influence Cognitive Function in Older Age?

    PubMed Central

    Leist, Anja K.; Hessel, Philipp; Avendano, Mauricio

    2014-01-01

    Background Fluctuations in the national economy shape labour market opportunities and outcomes, which in turn may influence the accumulation of cognitive reserve. This study examines whether economic recessions experienced in early and mid-adulthood are associated with later-life cognitive function. Method Data came from 12,020 respondents in 11 countries participating in the Survey of Health, Ageing and Retirement in Europe (SHARE). Cognitive assessments in 2004/5 and 2006/7 were linked to complete work histories retrospectively collected in 2008/9, and to historical annual data on fluctuations in Gross Domestic Product (GDP) per capita for each country. Controlling for confounders, we assessed whether recessions experienced at ages 25-34, 35-44 and 45-49 were associated with cognitive function at ages 50-74. Results Among men, each additional recession at ages 45-49 was associated with worse cognitive function at ages 50-74 (b = -0.06, Confidence Interval [CI] -0.11, -0.01). Among women, each additional recession at ages 25-44 was associated with worse cognitive function at ages 50-74 (b25-34 = -0.03, CI -0.04, -0.01; b35-44= -0.02, CI -0.04, -0.00). Among men, recessions at ages 45-49 influenced risk of being laid-off, whereas among women, recessions at ages 25-44 led to working part-time and higher likelihood of downward occupational mobility, which were all predictors of worse later-life cognitive function. Conclusions Recessions at ages 45-49 among men and 25-44 among women are associated with later-life cognitive function, possibly via more unfavourable labour market trajectories. If replicated in future studies, findings may indicate that policies that ameliorate the impact of recessions on labour market outcomes may promote later-life cognitive function. PMID:24258197

  13. A Functional Neuroimaging Study of Sound Localization: Visual Cortex Activity Predicts Performance in Early-Blind Individuals

    PubMed Central

    Gougoux, Frédéric; Zatorre, Robert J; Lassonde, Maryse; Voss, Patrice

    2005-01-01

    Blind individuals often demonstrate enhanced nonvisual perceptual abilities. However, the neural substrate that underlies this improved performance remains to be fully understood. An earlier behavioral study demonstrated that some early-blind people localize sounds more accurately than sighted controls using monaural cues. In order to investigate the neural basis of these behavioral differences in humans, we carried out functional imaging studies using positron emission tomography and a speaker array that permitted pseudo-free-field presentations within the scanner. During binaural sound localization, a sighted control group showed decreased cerebral blood flow in the occipital lobe, which was not seen in early-blind individuals. During monaural sound localization (one ear plugged), the subgroup of early-blind subjects who were behaviorally superior at sound localization displayed two activation foci in the occipital cortex. This effect was not seen in blind persons who did not have superior monaural sound localization abilities, nor in sighted individuals. The degree of activation of one of these foci was strongly correlated with sound localization accuracy across the entire group of blind subjects. The results show that those blind persons who perform better than sighted persons recruit occipital areas to carry out auditory localization under monaural conditions. We therefore conclude that computations carried out in the occipital cortex specifically underlie the enhanced capacity to use monaural cues. Our findings shed light not only on intermodal compensatory mechanisms, but also on individual differences in these mechanisms and on inhibitory patterns that differ between sighted individuals and those deprived of vision early in life. PMID:15678166

  14. Early functional impairment of sensory-motor connectivity in a mouse model of spinal muscular atrophy

    PubMed Central

    Mentis, George Z.; Blivis, Dvir; Liu, Wenfang; Drobac, Estelle; Crowder, Melissa E.; Kong, Lingling; Alvarez, Francisco J.; Sumner, Charlotte J.; O'Donovan, Michael J.

    2011-01-01

    SUMMARY To define alterations of neuronal connectivity that occur during motor neuron degeneration, we characterized the function and structure of spinal circuitry in spinal muscular atrophy (SMA) model mice. SMA motor neurons show reduced proprioceptive reflexes that correlate with decreased number and function of synapses on motor neuron somata and proximal dendrites. These abnormalities occur at an early stage of disease in motor neurons innervating proximal hindlimb muscles and medial motor neurons innervating axial muscles, but only at end-stage disease in motor neurons innervating distal hindlimb muscles. Motor neuron loss follows afferent synapse loss with the same temporal and topographical pattern. Trichostatin A, which improves motor behavior and survival of SMA mice, partially restores spinal reflexes illustrating the reversibility of these synaptic defects. De-afferentation of motor neurons is an early event in SMA and may be a primary cause of motor dysfunction that is amenable to therapeutic intervention. PMID:21315257

  15. In utero and early childhood exposure to arsenic decreases lung function in children.

    PubMed

    Recio-Vega, Rogelio; Gonzalez-Cortes, Tania; Olivas-Calderon, Edgar; Lantz, R Clark; Gandolfi, A Jay; Gonzalez-De Alba, Cesar

    2015-04-01

    The lung is a target organ for adverse health outcomes following exposure to As. Several studies have reported a high prevalence of respiratory symptoms and diseases in subjects highly exposed to As through drinking water; however, most studies to date has been performed in exposed adults, with little information on respiratory effects in children. The objective of the study was to evaluate the association between urinary levels of As and its metabolites with lung function in children exposed in utero and in early childhood to high As levels through drinking water. A total of 358 healthy children were included in our study. Individual exposure was assessed based on urinary concentration of inorganic As. Lung function was assessed by spirometry. Participants were exposed since pregnancy until early childhood to an average water As concentration of 152.13 µg l⁻¹. The mean urinary As level registered in the studied subjects was 141.2 µg l⁻¹ and only 16.7% had a urinary concentration below the national concern level. Forced vital capacity was significantly decreased in the studied population and it was negatively associated with the percentage of inorganic As. More than 57% of the subjects had a restrictive spirometric pattern. The urinary As level was higher in those children with restrictive lung patterns when compared with the levels registered in subjects with normal spirometric patterns. Exposure to As through drinking water during in utero and early life was associated with a decrease in forced vital capacity and with a restrictive spirometric pattern in the children evaluated. Copyright © 2014 John Wiley & Sons, Ltd.

  16. Early Functional Treatment of Proximal Phalanx Fractures in Children: A Case Series Study.

    PubMed

    Bohr, Stefan; Mammadli, Toghrul

    2018-05-23

    The objective of this study was to assess proper indications a nonsurgical treatment regime for pediatric fractures of the proximal phalanx based on principles of early functional treatment. A case series (evidence level 4) of 30 pediatric patients with fractures of the proximal phalanx were treated nonsurgically using protective dynamic splinting techniques and fiberglass casting material. Assessments were performed clinically and by x-ray within 4 to 8 weeks of commencement of treatment. Outcome measures included Disabilities of the Arm, Shoulder, and Hand score questionnaire as well as fingertip palm distance (cm) and dynamic pain interval assessments. All fractures healed without any clinically apparent bony deformities. Disabilities of the Arm, Shoulder, and Hand scores were of 25.17 ± 5.29 (mean ± SD), which indicated good functional results usually within 2 weeks of removal of dynamic splints. Fingertip palm distance measurements at endpoints were of 0.17 ± 0.27 cm (mean ± SD), which indicated an almost free range of finger motion. Absence of pain perception under active finger motion (dynamic pain interval) was noted at 14.10 ± 6.79 days (mean ± SD). Well-established criteria for surgical treatment of phalangeal fractures exist. However, in our experience, a majority of pediatric fractures of the proximal phalanx can be safely treated nonsurgically with dynamic splinting along with shorter intervals of immobilization of the affected fingers and faster restoration of overall hand function compared to surgical treatment.

  17. Cognitive advantages and disadvantages in early and late bilinguals.

    PubMed

    Pelham, Sabra D; Abrams, Lise

    2014-03-01

    Previous research has documented advantages and disadvantages of early bilinguals, defined as learning a 2nd language by school age and using both languages since that time. Relative to monolinguals, early bilinguals manifest deficits in lexical access but benefits in executive function. We investigated whether becoming bilingual after childhood (late bilinguals) can produce the cognitive advantages and disadvantages typical of early bilinguals. Participants were 30 monolingual English speakers, 30 late English-Spanish bilinguals, and 30 early Spanish-English bilinguals who completed a picture naming task (lexical access) and an attentional network task (executive function). Late and early bilinguals manifested equivalent cognitive effects in both tasks, demonstrating lexical access deficits and executive function benefits. These findings provide support for the hypothesis that cognitive effects associated with bilingualism arise as the result of proficient, habitual use of 2 languages and not of developmental changes associated with becoming bilingual during childhood.

  18. Early changes in somatosensory function in spinal pain: protocol for a systematic review

    PubMed Central

    2013-01-01

    Background Back and neck pain are common conditions that have a high burden of disease. Changes in somatosensory function in the periphery, the spinal cord and the brain have been well documented at the time when these conditions have become chronic. It is unknown, however, how early these changes occur, what the timecourse is of sensory dysfunction and what the specific nature of these changes are in the first 12 weeks after onset of pain. In this paper, we describe the protocol for a systematic review of the literature on somatosensory dysfunction in the first 12 weeks after pain onset. Methods and design We will conduct a comprehensive search for articles indexed in the databases Ovid MEDLINE, Ovid Embase, Ovid PsycINFO and Cochrane Central Register of Controlled Trial (CENTRAL) from their inception to August 2013 that report on any aspect of somatosensory function in acute or subacute neck or back pain. Two independent reviewers will screen studies for eligibility, assess risk of bias and extract relevant data. Results will be tabulated and a narrative synthesis of the results conducted. Discussion Currently, there is a gap in our knowledge about the timing of somatosensory changes in back and neck pain. The systematic review outlined in this protocol aims to address this knowledge gap and inform developments in diagnostic tools and pain mechanism-based treatments. Trial Registration Our protocol has been registered on PROSPERO, CRD42013005113. PMID:24088219

  19. Modification of visual function by early visual experience.

    PubMed

    Blakemore, C

    1976-07-01

    Physiological experiments, involving recording from the visual cortex in young kittens and monkeys, have given new insight into human developmental disorders. In the visual cortex of normal cats and monkeys most neurones are selectively sensitive to the orientation of moving edges and they receive very similar signals from both eyes. Even in very young kittens without visual experience, most neurones are binocularly driven and a small proportion of them are genuinely orientation selective. There is no passive maturation of the system in the absence of visual experience, but even very brief exposure to patterned images produces rapid emergence of the adult organization. These results are compared to observations on humans who have "recovered" from early blindness. Covering one eye in a kitten or a monkey, during a sensitive period early in life, produces a virtually complete loss of input from that eye in the cortex. These results can be correlated with the production of "stimulus deprivation amblyopia" in infants who have had one eye patched. Induction of a strabismus causes a loss of binocularity in the visual cortex, and in humans it leads to a loss of stereoscopic vision and binocular fusion. Exposing kittens to lines of one orientation modifies the preferred orientations of cortical cells and there is an analogous "meridional amblyopia" in astigmatic humans. The existence of a sensitive period in human vision is discussed, as well as the possibility of designing remedial and preventive treatments for human developmental disorders.

  20. Emergence and early survival of early versus late seral species in Great Basin restoration in two different soil types

    Treesearch

    Shauna M. Uselman; Keirith A. Snyder; Elizabeth A. Leger; Sara E. Duke

    2015-01-01

    Comparing emergence and survival probabilities, early seral natives generally outperformed late seral natives when growing with exotics and had earlier emergence timing, although results differed among functional groups and soil types. In contrast, survival probabilities did not differ between the early and late seral mixes when growing without exotics. Within each...

  1. Western gulf culture-density study-early results

    Treesearch

    Mohd S. Rahman; Michael G. Messina; Richard F. Fisher; Alan B. Wilson; Nick Chappell; Conner Fristoe; Larry Anderson

    2006-01-01

    The Western Gulf Culture-Density Study is a collaborative research effort between Texas A&M University and five forest products companies to examine the effects of early silvicultural treatment intensity and a wide range of both densities and soil types on performance of loblolly pine. The study tests 2 silvicultural intensities, 5 planting densities (200 to 1,200...

  2. A hierarchical competing systems model of the emergence and early development of executive function

    PubMed Central

    Marcovitch, Stuart; Zelazo, Philip David

    2010-01-01

    The hierarchical competing systems model (HCSM) provides a framework for understanding the emergence and early development of executive function – the cognitive processes underlying the conscious control of behavior – in the context of search for hidden objects. According to this model, behavior is determined by the joint influence of a developmentally invariant habit system and a conscious representational system that becomes increasingly influential as children develop. This article describes a computational formalization of the HCSM, reviews behavioral and computational research consistent with the model, and suggests directions for future research on the development of executive function. PMID:19120405

  3. Initiation of ART during Early Acute HIV Infection Preserves Mucosal Th17 Function and Reverses HIV-Related Immune Activation

    PubMed Central

    Schuetz, Alexandra; Deleage, Claire; Sereti, Irini; Rerknimitr, Rungsun; Phanuphak, Nittaya; Phuang-Ngern, Yuwadee; Estes, Jacob D.; Sandler, Netanya G.; Sukhumvittaya, Suchada; Marovich, Mary; Jongrakthaitae, Surat; Akapirat, Siriwat; Fletscher, James L. K.; Kroon, Eugene; Dewar, Robin; Trichavaroj, Rapee; Chomchey, Nitiya; Douek, Daniel C.; O′Connell, Robert J.; Ngauy, Viseth; Robb, Merlin L.; Phanuphak, Praphan; Michael, Nelson L.; Excler, Jean-Louis; Kim, Jerome H.; de Souza, Mark S.; Ananworanich, Jintanat

    2014-01-01

    Mucosal Th17 cells play an important role in maintaining gut epithelium integrity and thus prevent microbial translocation. Chronic HIV infection is characterized by mucosal Th17 cell depletion, microbial translocation and subsequent immune-activation, which remain elevated despite antiretroviral therapy (ART) correlating with increased mortality. However, when Th17 depletion occurs following HIV infection is unknown. We analyzed mucosal Th17 cells in 42 acute HIV infection (AHI) subjects (Fiebig (F) stage I-V) with a median duration of infection of 16 days and the short-term impact of early initiation of ART. Th17 cells were defined as IL-17+ CD4+ T cells and their function was assessed by the co-expression of IL-22, IL-2 and IFNγ. While intact during FI/II, depletion of mucosal Th17 cell numbers and function was observed during FIII correlating with local and systemic markers of immune-activation. ART initiated at FI/II prevented loss of Th17 cell numbers and function, while initiation at FIII restored Th17 cell numbers but not their polyfunctionality. Furthermore, early initiation of ART in FI/II fully reversed the initially observed mucosal and systemic immune-activation. In contrast, patients treated later during AHI maintained elevated mucosal and systemic CD8+ T-cell activation post initiation of ART. These data support a loss of Th17 cells at early stages of acute HIV infection, and highlight that studies of ART initiation during early AHI should be further explored to assess the underlying mechanism of mucosal Th17 function preservation. PMID:25503054

  4. Longitudinal Changes in Sexual Functioning as Women Transition Through Menopause: Results from the Study of Women’s Health Across the Nation (SWAN)

    PubMed Central

    Avis, Nancy E.; Brockwell, Sarah; Randolph, John F.; Shen, Shunhua; Cain, Virginia S.; Ory, Marcia; Greendale, Gail A.

    2009-01-01

    Objective Sexual functioning is an important component of women’s lives. The extent to which the menopause transition is associated with decreased sexual functioning remains inconclusive. This study seeks to determine if advancing through the menopause transition is associated with changes in sexual functioning. Design A prospective, longitudinal cohort study of women aged 42–52 at baseline recruited at 7 US sites (N=3302) in the Study of Women’s Health Across the Nation (SWAN). Cohort eligible women had an intact uterus, at least one ovary, were not currently using exogenous hormones, were either pre- or early perimenopausal, and self-identified as one of the study’s designated racial/ethnic groups. Data from the baseline interview and six annual follow-up visits are reported. Outcomes are self-reported ratings of importance of sex; frequency of sexual desire, arousal, masturbation, sexual intercourse, and pain during intercourse; degree of emotional satisfaction and physical pleasure. Results Adjusting for baseline age, chronological aging, and relevant social, health, and psychological parameters, the odds of reporting vaginal or pelvic pain increased and desire decreased by late perimenopause. Masturbation increased at early perimenopause, but declined during postmenopause. Menopausal transition was unrelated to other outcomes. Health, psychological functioning, and importance of sex were related to all sexual function outcomes. Age, race/ethnicity, marital status, change in relationship, and vaginal dryness were also associated with sexual functioning. Conclusions Pain during sexual intercourse increases and sexual desire decreases over the menopausal transition. Masturbation increases during the early transition, but then declines in postmenopause. Adjusting for other factors, the menopausal transition was not independently associated with reports of the importance of sex, sexual arousal, frequency of sexual intercourse, emotional satisfaction with

  5. Novel Mahalanobis-based feature selection improves one-class classification of early hepatocellular carcinoma.

    PubMed

    Thomaz, Ricardo de Lima; Carneiro, Pedro Cunha; Bonin, João Eliton; Macedo, Túlio Augusto Alves; Patrocinio, Ana Claudia; Soares, Alcimar Barbosa

    2018-05-01

    Detection of early hepatocellular carcinoma (HCC) is responsible for increasing survival rates in up to 40%. One-class classifiers can be used for modeling early HCC in multidetector computed tomography (MDCT), but demand the specific knowledge pertaining to the set of features that best describes the target class. Although the literature outlines several features for characterizing liver lesions, it is unclear which is most relevant for describing early HCC. In this paper, we introduce an unconstrained GA feature selection algorithm based on a multi-objective Mahalanobis fitness function to improve the classification performance for early HCC. We compared our approach to a constrained Mahalanobis function and two other unconstrained functions using Welch's t-test and Gaussian Data Descriptors. The performance of each fitness function was evaluated by cross-validating a one-class SVM. The results show that the proposed multi-objective Mahalanobis fitness function is capable of significantly reducing data dimensionality (96.4%) and improving one-class classification of early HCC (0.84 AUC). Furthermore, the results provide strong evidence that intensity features extracted at the arterial to portal and arterial to equilibrium phases are important for classifying early HCC.

  6. Grating visual acuity results in the early treatment for retinopathy of prematurity study.

    PubMed

    Dobson, Velma; Quinn, Graham E; Summers, C Gail; Hardy, Robert J; Tung, Betty; Good, William V

    2011-07-01

    To compare grating (resolution) visual acuity at 6 years of age in eyes that received early treatment (ET) for high-risk prethreshold retinopathy of prematurity (ROP) with that in eyes that underwent conventional management (CM). In a randomized clinical trial, infants with bilateral, high-risk prethreshold ROP (n = 317) had one eye undergo ET and the other eye undergo CM, with treatment only if ROP progressed to threshold severity. For asymmetric cases (n = 84), the high-risk prethreshold eye was randomized to ET or CM. Grating visual acuity measured at 6 years of age by masked testers using Teller acuity cards. Monocular grating acuity results were obtained from 317 of 370 surviving children (85.6%). Analysis of grating acuity results for all study participants with high-risk prethreshold ROP showed no statistically significant overall benefit of ET (18.1% vs 22.8% unfavorable outcomes; P = .08). When the 6-year grating acuity results were analyzed according to a clinical algorithm (high-risk types 1 and 2 prethreshold ROP), a benefit was seen in type 1 eyes (16.4% vs 25.2%; P = .004) undergoing ET, but not in type 2 eyes (21.3% vs 15.9%; P = .29). Early treatment of eyes with type 1 ROP improves grating acuity outcomes, but ET for eyes with type 2 ROP does not. APPLICATION TO CLINICAL MEDICINE: Type 1 eyes should be treated early; however, based on acuity results at 6 years of age, type 2 eyes should be cautiously monitored for progression to type 1 ROP. Trial Registration clinicaltrials.gov Identifier: NCT00027222.

  7. Effects of maltreatment and parental schizophrenia spectrum disorders on early childhood social-emotional functioning: a population record linkage study.

    PubMed

    Matheson, S L; Kariuki, M; Green, M J; Dean, K; Harris, F; Tzoumakis, S; Tarren-Sweeney, M; Brinkman, S; Chilvers, M; Sprague, T; Carr, V J; Laurens, K R

    2017-12-01

    Childhood maltreatment and a family history of a schizophrenia spectrum disorder (SSD) are each associated with social-emotional dysfunction in childhood. Both are also strong risk factors for adult SSDs, and social-emotional dysfunction in childhood may be an antecedent of these disorders. We used data from a large Australian population cohort to determine the independent and moderating effects of maltreatment and parental SSDs on early childhood social-emotional functioning. The New South Wales Child Development Study combines intergenerational multi-agency data using record linkage methods. Multiple measures of social-emotional functioning (social competency, prosocial/helping behaviour, anxious/fearful behaviour; aggressive behaviour, and hyperactivity/inattention) on 69 116 kindergarten children (age ~5 years) were linked with government records of child maltreatment and parental presentations to health services for SSD. Multivariable analyses investigated the association between maltreatment and social-emotional functioning, adjusting for demographic variables and parental SSD history, in the population sample and in sub-cohorts exposed and not exposed to parental SSD history. We also examined the association of parental SSD history and social-emotional functioning, adjusting for demographic variables and maltreatment. Medium-sized associations were identified between maltreatment and poor social competency, aggressive behaviour and hyperactivity/inattention; small associations were revealed between maltreatment and poor prosocial/helping and anxious/fearful behaviours. These associations did not differ greatly when adjusted for parental SSD, and were greater in magnitude among children with no history of parental SSD. Small associations between parental SSD and poor social-emotional functioning remained after adjusting for demographic variables and maltreatment. Childhood maltreatment and history of parental SSD are associated independently with poor early

  8. Regional Coronary Endothelial Function is Closely Related to Local Early Coronary Atherosclerosis in Patients with Mild Coronary Artery Disease: A Pilot Study

    PubMed Central

    Hays, Allison G.; Kelle, Sebastian; Hirsch, Glenn A.; Soleimanifard, Sahar; Yu, Jing; Agarwal, Harsh K.; Gerstenblith, Gary; Schär, Michael; Stuber, Matthias; Weiss, Robert G.

    2012-01-01

    Background Coronary endothelial function (endoFx) is abnormal in patients with established coronary artery disease (CAD) and was recently shown by MRI to relate to the severity of luminal stenosis. Recent advances in MRI now allow the non-invasive assessment of both anatomic and functional (endoFx) changes that previously required invasive studies. We tested the hypothesis that abnormal coronary endoFx is related to measures of early atherosclerosis such as increased coronary wall thickness (CWT). Methods and Results Seventeen arteries in fourteen healthy adults and seventeen arteries in fourteen patients with non-obstructive CAD were studied. To measure endoFx, coronary MRI was performed before and during isometric handgrip exercise, an endothelial-dependent stressor and changes in coronary cross-sectional area (CSA) and flow were measured. Black blood imaging was performed to quantify CWT and other indices of arterial remodeling. The mean stress-induced change in CSA was significantly higher in healthy adults (13.5%±12.8%, mean±SD, n=17) than in those with mildly diseased arteries (-2.2±6.8%, p<0.0001, n=17). Mean CWT was lower in healthy subjects (0.9±0.2mm) than in CAD patients (1.4±0.3mm, p<0.0001). In contrast to healthy subjects, stress-induced changes in CSA, a measure of coronary endoFx, correlated inversely with CWT in CAD patients (r= -0.73, p=0.0008). Conclusions There is an inverse relationship between coronary endothelial function and local CWT in CAD patients but not in healthy adults. These findings demonstrate that local endothelial-dependent functional changes are related to the extent of early anatomic atherosclerosis in mildly diseased arteries. This combined MRI approach enables the anatomic and functional investigation of early coronary disease. PMID:22492483

  9. Functionality of empirical model-based predictive analytics for the early detection of hemodynamic instabilty.

    PubMed

    Summers, Richard L; Pipke, Matt; Wegerich, Stephan; Conkright, Gary; Isom, Kristen C

    2014-01-01

    Background. Monitoring cardiovascular hemodynamics in the modern clinical setting is a major challenge. Increasing amounts of physiologic data must be analyzed and interpreted in the context of the individual patient’s pathology and inherent biologic variability. Certain data-driven analytical methods are currently being explored for smart monitoring of data streams from patients as a first tier automated detection system for clinical deterioration. As a prelude to human clinical trials, an empirical multivariate machine learning method called Similarity-Based Modeling (“SBM”), was tested in an In Silico experiment using data generated with the aid of a detailed computer simulator of human physiology (Quantitative Circulatory Physiology or “QCP”) which contains complex control systems with realistic integrated feedback loops. Methods. SBM is a kernel-based, multivariate machine learning method that that uses monitored clinical information to generate an empirical model of a patient’s physiologic state. This platform allows for the use of predictive analytic techniques to identify early changes in a patient’s condition that are indicative of a state of deterioration or instability. The integrity of the technique was tested through an In Silico experiment using QCP in which the output of computer simulations of a slowly evolving cardiac tamponade resulted in progressive state of cardiovascular decompensation. Simulator outputs for the variables under consideration were generated at a 2-min data rate (0.083Hz) with the tamponade introduced at a point 420 minutes into the simulation sequence. The functionality of the SBM predictive analytics methodology to identify clinical deterioration was compared to the thresholds used by conventional monitoring methods. Results. The SBM modeling method was found to closely track the normal physiologic variation as simulated by QCP. With the slow development of the tamponade, the SBM model are seen to disagree while the

  10. Combined small-molecule inhibition accelerates the derivation of functional, early-born, cortical neurons from human pluripotent stem cells

    PubMed Central

    Qi, Yuchen; Zhang, Xin-Jun; Renier, Nicolas; Wu, Zhuhao; Atkin, Talia; Sun, Ziyi; Ozair, M. Zeeshan; Tchieu, Jason; Zimmer, Bastian; Fattahi, Faranak; Ganat, Yosif; Azevedo, Ricardo; Zeltner, Nadja; Brivanlou, Ali H.; Karayiorgou, Maria; Gogos, Joseph; Tomishima, Mark; Tessier-Lavigne, Marc; Shi, Song-Hai; Studer, Lorenz

    2017-01-01

    Considerable progress has been made in converting human pluripotent stem cells (hPSCs) into functional neurons. However, the protracted timing of human neuron specification and functional maturation remains a key challenge that hampers the routine application of hPSC-derived lineages in disease modeling and regenerative medicine. Using a combinatorial small-molecule screen, we previously identified conditions for the rapid differentiation of hPSCs into peripheral sensory neurons. Here we generalize the approach to central nervous system (CNS) fates by developing a small-molecule approach for accelerated induction of early-born cortical neurons. Combinatorial application of 6 pathway inhibitors induces post-mitotic cortical neurons with functional electrophysiological properties by day 16 of differentiation, in the absence of glial cell co-culture. The resulting neurons, transplanted at 8 days of differentiation into the postnatal mouse cortex, are functional and establish long-distance projections, as shown using iDISCO whole brain imaging. Accelerated differentiation into cortical neuron fates should facilitate hPSC-based strategies for disease modeling and cell therapy in CNS disorders. PMID:28112759

  11. The impact of early-onset cannabis use on functional brain correlates of working memory.

    PubMed

    Becker, Benjamin; Wagner, Daniel; Gouzoulis-Mayfrank, Euphrosyne; Spuentrup, Elmar; Daumann, Jörg

    2010-08-16

    Cannabis is the most commonly used illicit drug. Prevalence rates are particularly high among adolescents. Neuropsychological studies have identified cannabis-associated memory deficits, particularly linked to an early onset of use. However, it remains unclear, whether the age of onset accounts for altered cortical activation patterns usually observed in cannabis users. Functional magnetic resonance imaging was used to examine cortical activation during verbal working memory challenge in (1) early-onset (onset before the age of sixteen; n=26) and (2) late-onset cannabis users (age at onset at least sixteen; n=17). Early-onset users showed increased activation in the left superior parietal lobe. Correlational analyses confirmed the association between an earlier start of use and increased activity. Contrariwise neither cumulative dose, frequency nor time since last use was significantly associated with cortical activity. Our findings suggest that an early start of cannabis use is associated with increased cortical activation in adult cannabis users, possibly reflecting suboptimal cortical efficiency during cognitive challenge. The maturing brain might be more vulnerable to the harmful effects of cannabis use. However, due to a lack of a non-using control group we cannot exclude alternative interpretations. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  12. Decidualization and angiogenesis in early pregnancy: unravelling the functions of DC and NK cells.

    PubMed

    Blois, Sandra M; Klapp, Burghard F; Barrientos, Gabriela

    2011-03-01

    Differentiation of endometrial stromal cells and formation of new maternal blood vessels at the time of embryo implantation are critical for the establishment and maintenance of gestation. The regulatory functions of decidual leukocytes during early pregnancy, particularly dendritic cells (DC) and NK cells, may be important not only for the generation of maternal immunological tolerance but also in the regulation of stromal cell differentiation and the vascular responses associated with the implantation process. However, the specific contributions of DC and NK cells during implantation are still difficult to dissect mainly due to reciprocal regulatory interactions established between them within the decidualizing microenvironment. The present review article discusses current evidence on the regulatory pathways driving decidualization in mice, suggesting that NK cells promote uterine vascular modifications that assist decidual growth but DC directly control stromal cell proliferation, angiogenesis and the homing and maturation of NK cell precursors in the pregnant uterus. Thus, successful implantation appears to result from an interplay between cellular components of the decidualizing endometrium involving immunoregulatory and pro-angiogenic functions of DC and NK cells. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  13. Interactions between Callous Unemotional Behaviors and Executive Function in Early Childhood Predict later Aggression and Lower Peer-liking in Late-childhood.

    PubMed

    Waller, Rebecca; Hyde, Luke W; Baskin-Sommers, Arielle R; Olson, Sheryl L

    2017-04-01

    Callous unemotional (CU) behaviors are linked to aggression, behavior problems, and difficulties in peer relationships in children and adolescents. However, few studies have examined whether early childhood CU behaviors predict aggression or peer-rejection during late-childhood or potential moderation of this relationship by executive function. The current study examined whether the interaction of CU behaviors and executive function in early childhood predicted different forms of aggression in late-childhood, including proactive, reactive, and relational aggression, as well as how much children were liked by their peers. Data from cross-informant reports and multiple observational tasks were collected from a high-risk sample (N = 240; female = 118) at ages 3 and 10 years old. Parent reports of CU behaviors at age 3 predicted teacher reports of reactive, proactive, and relational aggression, as well as lower peer-liking at age 10. Moderation analysis showed that specifically at high levels of CU behaviors and low levels of observed executive function, children were reported by teachers as showing greater reactive and proactive aggression, and were less-liked by peers. Findings demonstrate that early childhood CU behaviors and executive function have unique main and interactive effects on both later aggression and lower peer-liking even when taking into account stability in behavior problems over time. By elucidating how CU behaviors and deficits in executive function potentiate each other during early childhood, we can better characterize the emergence of severe and persistent behavior and interpersonal difficulties across development.

  14. Early histological and functional effects of chronic copper exposure in rat liver.

    PubMed

    Cisternas, Felipe A; Tapia, Gladys; Arredondo, Miguel; Cartier-Ugarte, Denise; Romanque, Pamela; Sierralta, Walter D; Vial, María T; Videla, Luis A; Araya, Magdalena

    2005-10-01

    Cu is an essential trace element capable of producing toxic effects in animals and man when ingested acutely or chronically in excess. Although chronic Cu exposure is increasingly recognized as a public health issue, its early effects remain largely unknown. We approached the significance of a moderate chronic Cu load in young rats to correlate early hepatic histopathological changes with functional alterations of liver cells. For this purpose, supplementation with 1,200 ppm of Cu in rat food for 16 weeks was chosen. In these conditions, Cu load elicited a significant decrease in growth curves. There were mild light microscopy alterations in Cu-treated rats, although increasing intracellular Cu storage was correlated with longer Cu exposure both by histological and biochemical measurements. Ultrastructural alterations included lysosomal inclusions as well as mitochondrial and nuclear changes. Liver perfusion studies revealed higher rates of basal O(2) consumption and colloidal carbon-induced O(2) uptake in Cu-treated rats, with enhanced carbon-induced O(2)/carbon uptake ratios and NF-kappaB DNA binding activity. These changes were time-dependent and returned to control values after 12 or 16 weeks. It is concluded that subchronic Cu loading in young rats induces early hepatic morphological changes, with enhancement in Küpffer cell-dependent respiratory burst activity and NF-kappaB DNA binding, cellular responses that may prevent or alleviate the hepatotoxicity of the metal.

  15. Analog "neuronal" networks in early vision.

    PubMed Central

    Koch, C; Marroquin, J; Yuille, A

    1986-01-01

    Many problems in early vision can be formulated in terms of minimizing a cost function. Examples are shape from shading, edge detection, motion analysis, structure from motion, and surface interpolation. As shown by Poggio and Koch [Poggio, T. & Koch, C. (1985) Proc. R. Soc. London, Ser. B 226, 303-323], quadratic variational problems, an important subset of early vision tasks, can be "solved" by linear, analog electrical, or chemical networks. However, in the presence of discontinuities, the cost function is nonquadratic, raising the question of designing efficient algorithms for computing the optimal solution. Recently, Hopfield and Tank [Hopfield, J. J. & Tank, D. W. (1985) Biol. Cybern. 52, 141-152] have shown that networks of nonlinear analog "neurons" can be effective in computing the solution of optimization problems. We show how these networks can be generalized to solve the nonconvex energy functionals of early vision. We illustrate this approach by implementing a specific analog network, solving the problem of reconstructing a smooth surface from sparse data while preserving its discontinuities. These results suggest a novel computational strategy for solving early vision problems in both biological and real-time artificial vision systems. PMID:3459172

  16. Functional weight-bearing mobilization after Achilles tendon rupture enhances early healing response: a single-blinded randomized controlled trial.

    PubMed

    Valkering, Kars P; Aufwerber, Susanna; Ranuccio, Francesco; Lunini, Enricomaria; Edman, Gunnar; Ackermann, Paul W

    2017-06-01

    Functional weight-bearing mobilization may improve repair of Achilles tendon rupture (ATR), but the underlying mechanisms and outcome were unknown. We hypothesized that functional weight-bearing mobilization by means of increased metabolism could improve both early and long-term healing. In this prospective randomized controlled trial, patients with acute ATR were randomized to either direct post-operative functional weight-bearing mobilization (n = 27) in an orthosis or to non-weight-bearing (n = 29) plaster cast immobilization. During the first two post-operative weeks, 15°-30° of plantar flexion was allowed and encouraged in the functional weight-bearing mobilization group. At 2 weeks, patients in the non-weight-bearing cast immobilization group received a stiff orthosis, while the functional weight-bearing mobilization group continued with increased range of motion. At 6 weeks, all patients discontinued immobilization. At 2 weeks, healing metabolites and markers of procollagen type I (PINP) and III (PIIINP) were examined using microdialysis. At 6 and 12 months, functional outcome using heel-rise test was assessed. Healing tendons of both groups exhibited increased levels of metabolites glutamate, lactate, pyruvate, and of PIIINP (all p < 0.05). Patients in functional weight-bearing mobilization group demonstrated significantly higher concentrations of glutamate compared to the non-weight-bearing cast immobilization group (p = 0.045).The upregulated glutamate levels were significantly correlated with the concentrations of PINP (r = 0.5, p = 0.002) as well as with improved functional outcome at 6 months (r = 0.4; p = 0.014). Heel-rise tests at 6 and 12 months did not display any differences between the two groups. Functional weight-bearing mobilization enhanced the early healing response of ATR. In addition, early ankle range of motion was improved without the risk of Achilles tendon elongation and without altering long-term functional

  17. Contributions of Modern Measurement Theory to Measuring Executive Function in Early Childhood: An Empirical Demonstration

    ERIC Educational Resources Information Center

    Willoughby, Michael T.; Wirth, R. J.; Blair, Clancy B.

    2011-01-01

    This study demonstrates the merits of evaluating a newly developed battery of executive function tasks, designed for use in early childhood, from the perspective of item response theory (IRT). The battery was included in the 48-month assessment of the Family Life Project, a prospective longitudinal study of 1292 children oversampled from…

  18. Naturalistic Observations of Schoolyard Social Participation: Marker Variables for Socio-Emotional Functioning in Early Adolescence

    ERIC Educational Resources Information Center

    Coplan, Robert J.; Ooi, Laura L.; Rose-Krasnor, Linda

    2015-01-01

    The goal of this study was to examine links between observed social participation in the schoolyard and indices of socio-emotional functioning in early adolescence. Participants were children (N = 290) aged 9 to 12 years. Social participation (e.g., solitary play, dyadic interaction, group interaction) was assessed in the schoolyard during recess…

  19. Parental Family Stress during Pregnancy and Cognitive Functioning in Early Childhood: The Generation R Study

    ERIC Educational Resources Information Center

    Henrichs, Jens; Schenk, Jacqueline J.; Kok, Rianne; Ftitache, Bouchra; Schmidt, Henk G.; Hofman, Albert; Jaddoe, Vincent W. V.; Verhulst, Frank C.; Tiemeier, Henning

    2011-01-01

    We investigated whether parental family stress during pregnancy is associated with cognitive functioning in early childhood in a population-based cohort (n = 3139). Family stress was assessed using the Family Assessment Device at the 20th week of pregnancy and was reported by mothers and fathers. Mothers completed the MacArthur Communicative…

  20. Demographic and Familial Predictors of Early Executive Function Development: Contribution of a Person-Centered Perspective

    ERIC Educational Resources Information Center

    Rhoades, Brittany L.; Greenberg, Mark T.; Lanza, Stephanie T.; Blair, Clancy

    2011-01-01

    Executive function (EF) skills are integral components of young children's growing competence, but little is known about the role of early family context and experiences in their development. We examined how demographic and familial risks during infancy predicted EF competence at 36 months of age in a large, predominantly low-income sample of…

  1. The development of executive function and language skills in the early school years.

    PubMed

    Gooch, Debbie; Thompson, Paul; Nash, Hannah M; Snowling, Margaret J; Hulme, Charles

    2016-02-01

    The developmental relationships between executive functions (EF) and early language skills are unclear. This study explores the longitudinal relationships between children's early EF and language skills in a sample of children with a wide range of language abilities including children at risk of dyslexia. In addition, we investigated whether these skills independently predict children's attention/behaviour skills. Data are presented from 243 children at four time points. Children were selected for being at risk of reading difficulties either because of a family history of dyslexia (FR; N = 90) or because of concerns regarding their language development (LI; N = 79) or as typically developing controls (TD; N = 74). The children completed tasks to assess their executive function and language skills at ages 4, 5 and 6 years. At 6 (T4) and 7 years (T5) parents and teachers rated the children's attention/behaviour skills. There was a strong concurrent relationship between language and EF at each assessment. Longitudinal analyses indicated a considerable degree of stability in children's language and EF skills: the influence of language on later EF skills (and vice versa) was weak and not significant in the current sample. Children's EF, but not language, skills at T3 predicted attention/behaviour ratings at T4/T5. There is a strong concurrent association between language and EF skills during the preschool and early school years, when children with language impairment show persistent EF deficits. Latent variables measuring language and EF show high longitudinal stability with little evidence of significant or strong reciprocal influences between these constructs. EF, but not language, skills predict later ratings of children's attention and behaviour. © 2015 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.

  2. Functional requirements regarding medical registries--preliminary results.

    PubMed

    Oberbichler, Stefan; Hörbst, Alexander

    2013-01-01

    The term medical registry is used to reference tools and processes to support clinical or epidemiologic research or provide a data basis for decisions regarding health care policies. In spite of this wide range of applications the term registry and the functional requirements which a registry should support are not clearly defined. This work presents preliminary results of a literature review to discover functional requirements which form a registry. To extract these requirements a set of peer reviewed articles was collected. These set of articles was screened by using methods from qualitative research. Up to now most discovered functional requirements focus on data quality (e. g. prevent transcription error by conducting automatic domain checks).

  3. Adenoviral bcl-2 transfer improves survival and early graft function after ischemia and reperfusion in rat liver transplantation.

    PubMed

    Rentsch, Markus; Kienle, Klaus; Mueller, Thomas; Vogel, Mandy; Jauch, Karl Walter; Püllmann, Kerstin; Obed, Aiman; Schlitt, Hans J; Beham, Alexander

    2005-11-27

    Primary graft dysfunction due to ischemia and reperfusion injury represents a major problem in liver transplantation. The related cell stress may induce apoptosis, which can be suppressed by bcl-2. The purpose of the study was to investigate the effect of adenoviral bcl-2 gene transfer on early graft function and survival in rat liver transplantation. An adenoviral construct that transfers bcl-2 under the control of a tetracycline inducible promoter was generated (advTetOn bcl-2) and used with a second adenovirus that transfers the repressor protein (advCMV Rep). Forty-eight hours before explantation, donor rats were treated with advTetOn bcl-2/ advCMV Rep (n=7) and doxycyclin, with the control adenoviral construct advCMV GFP (n=8) or with doxycyclin alone (n=8). Liver transplantation was performed following 16 hours of cold storage (UW). Bcl-2 expression and intrahepatic apoptosis was assessed. Bile flow was monitored 90 min posttransplantation. The endpoint for survival was 7 days. Bcl-2 was expressed in hepatocytes and sinusoidal lining cells. This was associated with a significant reduction of apoptotic sinusoidal lining cells and hepatocytes after 24 hours and 7 days. Bile production was significantly higher following bcl-2 pretreatment. Furthermore, bcl-2 transfer resulted in significantly improved survival (100% vs. 50% both control groups). Adenoviral bcl-2 transfer results in protein expression in hepatocytes and sinusoidal lining cells resulting in early graft function and survival enhancement after prolonged ischemia and reperfusion injury. The inhibition of apoptosis in the context of liver transplantation might be a reasonable approach in the treatment of graft dysfunction.

  4. Long-term effects of early life exposure to environmental estrogens on ovarian function: Role of epigenetics

    PubMed Central

    Cruz, Gonzalo; Foster, Warren; Paredes, Alfonso; Yi, Kun Don; Uzumcu, Mehmet

    2014-01-01

    Estrogens play an important role in development and function of the brain and reproductive tract. Accordingly, it is thought that developmental exposure to environmental estrogens can disrupt neural and reproductive tract development potentially resulting in long-term alterations in neurobehavior and reproductive function. Many chemicals have been shown to have estrogenic activity whereas others affect estrogen production and turnover resulting in disruption of estrogen signaling pathways. However, these mechanisms and the concentrations required to induce these effects cannot account for the myriad adverse effects of environmental toxicants on estrogen sensitive target tissues. Hence, alternative mechanisms are thought to underlie the adverse effects documented in experimental animal models and thus could be important to human health. In this review, the epigenetic regulation of gene expression is explored as a potential target of environmental toxicants including estrogenic chemicals. We suggest that toxicant-induced changes in epigenetic signatures are important mechanisms underlying disruption of ovarian follicular development. In addition, we discuss how exposure to environmental estrogens during early life can alter gene expression through effects on epigenetic control potentially leading to permanent changes in ovarian physiology. PMID:25040227

  5. Long-term effects of early-life exposure to environmental oestrogens on ovarian function: role of epigenetics.

    PubMed

    Cruz, G; Foster, W; Paredes, A; Yi, K D; Uzumcu, M

    2014-09-01

    Oestrogens play an important role in development and function of the brain and reproductive tract. Accordingly, it is considered that developmental exposure to environmental oestrogens can disrupt neural and reproductive tract development, potentially resulting in long-term alterations in neurobehaviour and reproductive function. Many chemicals have been shown to have oestrogenic activity, whereas others affect oestrogen production and turnover, resulting in the disruption of oestrogen signalling pathways. However, these mechanisms and the concentrations required to induce these effects cannot account for the myriad adverse effects of environmental toxicants on oestrogen-sensitive target tissues. Hence, alternative mechanisms are assumed to underlie the adverse effects documented in experimental animal models and thus could be important to human health. In this review, the epigenetic regulation of gene expression is explored as a potential target of environmental toxicants including oestrogenic chemicals. We suggest that toxicant-induced changes in epigenetic signatures are important mechanisms underlying the disruption of ovarian follicular development. In addition, we discuss how exposure to environmental oestrogens during early life can alter gene expression through effects on epigenetic control potentially leading to permanent changes in ovarian physiology. © 2014 British Society for Neuroendocrinology.

  6. Prognostic Importance of Early Worsening Renal Function Following Initiation of Angiotensin Converting Enzyme Inhibitor Therapy in Patients with Cardiac Dysfunction

    PubMed Central

    Testani, Jeffrey M.; Kimmel, Stephen E.; Dries, Daniel L.; Coca, Steven G.

    2011-01-01

    Background Worsening renal function (WRF) in the setting of heart failure has been associated with increased mortality. However, it is unclear if this decreased survival is a direct result of the reduction in glomerular filtration rate (GFR) or if the mechanism underlying the deterioration in GFR is driving prognosis. Given that WRF in the setting of angiotensin converting enzyme inhibitor (ACE-I) initiation is likely mechanistically distinct from spontaneously occurring WRF, we sought to investigate the relative early WRF associated mortality rates in subjects randomized to ACE-I or placebo. Methods and Results Subjects in the Studies Of Left Ventricular Dysfunction limited data set were studied (6,377 patients). The interaction between early WRF (decrease in estimated GFR ≥20% at 14 days), randomization to enalapril, and mortality was the primary endpoint. In the overall population, early WRF was associated with increased mortality (adjusted HR=1.2, 95% CI 1.0–1.4, p=0.037). When analysis was restricted to the placebo group, this association strengthened (adjusted HR=1.4, 95% CI 1.1–1.8, p=0.004). However, in the enalapril group, early WRF had no adverse prognostic significance (adjusted HR=1.0, 95% CI 0.8–1.3, p=1.0, p interaction=0.09). In patients that continued study drug despite early WRF, a survival advantage remained with enalapril therapy (adjusted HR=0.66, 95% CI 0.5–0.9, p=0.018). Conclusions These data support the notion that the mechanism underlying WRF is important in determining its prognostic significance. Specifically, early WRF in the setting of ACE-I initiation appears to represent a benign event which is not associated with a loss of benefit from continued ACE-I therapy. PMID:21903907

  7. Nonsurgical treatment and early return to activity leads to improved Achilles tendon fatigue mechanics and functional outcomes during early healing in an animal model

    PubMed Central

    Freedman, BR; Gordon, JA; Bhatt, PB; Pardes, AM; Thomas, SJ; Sarver, JJ; Riggin, CN; Tucker, JJ; Williams, AW; Zanes, RC; Hast, MW; Farber, DC; Silbernagel, KG; Soslowsky, LJ

    2016-01-01

    Achilles tendon ruptures are common and devastating injuries; however, an optimized treatment and rehabilitation protocol has yet to be defined. Therefore, the objective of this study was to investigate the effects of surgical repair and return to activity on joint function and Achilles tendon properties after 3-weeks of healing. Sprague Dawley rats (N=100) received unilateral blunt transection of their Achilles tendon. Animals were then randomized into repaired or non-repaired treatments, and further randomized into groups that returned to activity after 1-week (RTA1) or after 3-weeks (RTA3) of limb casting in plantarflexion. Limb function, passive joint mechanics, and tendon properties (mechanical, organizational using high frequency ultrasound, histological, and compositional) were evaluated. Results showed that both treatment and return to activity collectively affected limb function, passive joint mechanics, and tendon properties. Functionally, RTA1 animals had increased dorsiflexion ROM and weight bearing of the injured limb compared to RTA3 animals 3-weeks post injury. Such functional improvements in RTA1 tendons were evidenced in their mechanical fatigue properties and increased cross sectional area compared to RTA3 tendons. When RTA1 was coupled with nonsurgical treatment, superior fatigue properties were achieved compared to repaired tendons. No differences in cell shape, cellularity, GAG, collagen type I, or TGF-β staining were identified between groups, but collagen type III was elevated in RTA3 repaired tendons. The larger tissue area and increased fatigue resistance created in RTA1 tendons may prove critical for optimized outcomes in early Achilles tendon healing following complete rupture. PMID:27038306

  8. Perceived reciprocity in social exchange and health functioning in early old age: prospective findings from the GAZEL study.

    PubMed

    Wahrendorf, Morten; Ribet, Celine; Zins, Marie; Goldberg, Marcel; Siegrist, Johannes

    2010-05-01

    To assess prospectively the effects of perceived non-reciprocity of exchange in three different types of social engagement on health functioning in early old age. In the frame of the prospective French GAZEL cohort study, data on reciprocity in three types of role-related social engagement (principal regular activity in everyday life, marital role relationship, trusting relationships in civic life) were collected from 8679 men and 2742 women (mean age: 60.4 years) in 2005. Two years later, health functioning was assessed using the SF-36 mental and physical component scores, as well as self-perceived health. Multivariate regressions were calculated, controlling for important confounders including baseline self-perceived health. Consistent effects of perceived non-reciprocity in all three types of social exchange on mental and physical health functioning were observed. After adjustment for relevant confounders including baseline self-perceived, health effects were attenuated, but largely remained significant. Findings underline the importance of the quality of social exchange (reciprocity vs. non-reciprocity) for health functioning in early old age.

  9. Executive functions in early childhood: the role of maternal and paternal parenting practices.

    PubMed

    Lucassen, Nicole; Kok, Rianne; Bakermans-Kranenburg, Marian J; Van Ijzendoorn, Marinus H; Jaddoe, Vincent W V; Hofman, Albert; Verhulst, Frank C; Lambregtse-Van den Berg, Mijke P; Tiemeier, Henning

    2015-11-01

    We investigated the association between mothers' and fathers' harsh parenting and sensitive parenting practices and child's executive functions (EF) in early childhood in 607 families. We focused on three broad dimensions of child EF: Emergent metacognition, inhibitory self-control, and flexibility measured with the parent-reported Behavior Rating Inventory of Executive Function-Preschool Version. Less sensitive parenting of the mother and harsher parenting of the father were related to lower scores of emergent metacognition and inhibitory self-control. Parenting was not associated with child flexibility. This study extends previous research on the association between parenting and EF by the focus on the role of the father and demonstrates independent effects of mother and father on child EF. © 2015 The British Psychological Society.

  10. Functional Fitness Testing Results Following Long-Duration ISS Missions.

    PubMed

    Laughlin, Mitzi S; Guilliams, Mark E; Nieschwitz, Bruce A; Hoellen, David

    2015-12-01

    Long-duration spaceflight missions lead to the loss of muscle strength and endurance. Significant reduction in muscle function can be hazardous when returning from spaceflight. To document these losses, NASA developed medical requirements that include measures of functional strength and endurance. Results from this Functional Fitness Test (FFT) battery are also used to evaluate the effectiveness of in-flight exercise countermeasures. The purpose of this paper is to document results from the FFT and correlate this information with performance of in-flight exercise on board the International Space Station. The FFT evaluates muscular strength and endurance, flexibility, and agility and includes the following eight measures: sit and reach, cone agility, push-ups, pull-ups, sliding crunches, bench press, leg press, and hand grip dynamometry. Pre- to postflight functional fitness measurements were analyzed using dependent t-tests and correlation analyses were used to evaluate the relationship between functional fitness measurements and in-flight exercise workouts. Significant differences were noted post space flight with the sit and reach, cone agility, leg press, and hand grip measurements while other test scores were not significantly altered. The relationships between functional fitness and in-flight exercise measurements showed minimal to moderate correlations for most in-flight exercise training variables. The change in FFT results can be partially explained by in-flight exercise performance. Although there are losses documented in the FFT results, it is important to realize that the crewmembers are successfully performing activities of daily living and are considered functional for normal activities upon return to Earth.

  11. Identification of genetic variants predictive of early onset pancreatic cancer through a population science analysis of functional genomic datasets

    PubMed Central

    Chen, Jinyun; Wu, Xifeng; Huang, Yujing; Chen, Wei; Brand, Randall E.; Killary, Ann M.; Sen, Subrata; Frazier, Marsha L.

    2016-01-01

    Biomarkers are critically needed for the early detection of pancreatic cancer (PC) are urgently needed. Our purpose was to identify a panel of genetic variants that, combined, can predict increased risk for early-onset PC and thereby identify individuals who should begin screening at an early age. Previously, we identified genes using a functional genomic approach that were aberrantly expressed in early pathways to PC tumorigenesis. We now report the discovery of single nucleotide polymorphisms (SNPs) in these genes associated with early age at diagnosis of PC using a two-phase study design. In silico and bioinformatics tools were used to examine functional relevance of the identified SNPs. Eight SNPs were consistently associated with age at diagnosis in the discovery phase, validation phase and pooled analysis. Further analysis of the joint effects of these 8 SNPs showed that, compared to participants carrying none of these unfavorable genotypes (median age at PC diagnosis 70 years), those carrying 1–2, 3–4, or 5 or more unfavorable genotypes had median ages at diagnosis of 64, 63, and 62 years, respectively (P = 3.0E–04). A gene-dosage effect was observed, with age at diagnosis inversely related to number of unfavorable genotypes (Ptrend = 1.0E–04). Using bioinformatics tools, we found that all of the 8 SNPs were predicted to play functional roles in the disruption of transcription factor and/or enhancer binding sites and most of them were expression quantitative trait loci (eQTL) of the target genes. The panel of genetic markers identified may serve as susceptibility markers for earlier PC diagnosis. PMID:27486767

  12. Functional disability and health-related quality of life in South Africans with early rheumatoid arthritis.

    PubMed

    Hodkinson, B; Musenge, E; Ally, M; Meyer, P W A; Anderson, R; Tikly, M

    2012-10-01

    The severity and predictors of functional disability and health-related quality of life (HRQoL) in a cohort of South Africans with early rheumatoid arthritis (RA) were investigated. Changes in the Health Assessment Questionnaire Disability Index (HAQ) and the 36-Item Short Form Health Survey (SF-36) following 12 months of traditional disease-modifying anti-rheumatic drugs (DMARDs) were studied in previously DMARD-naïve adults with disease duration ≤ 2 years. The majority of the 171 patients were female (82%), Black Africans (89%) with a mean (SD) symptom duration of 11.6 (7.0) months. In the 134 patients seen at 12 months, there were significant improvements in the HAQ and all domains of the SF-36 but 92 (69%) still had substantial functional disability (HAQ > 0.5) and 89 (66%) had suboptimal mental health [SF-36 mental composite score (MCS) < 66.6]. Multivariate analysis showed that female sex (p = 0.05) and high baseline HAQ score (p < 0.01) predicted substantial functional disability at 12 months. Unemployment (p = 0.03), high baseline pain (p = 0.02), and HAQ score (p = 0.04) predicted suboptimal mental health, with a trend towards a low level of schooling being significant (p = 0.08). Early RA has a broad impact on HRQoL in indigent South Africans, with a large proportion of patients still showing substantial functional disability and suboptimal mental health despite 12 months of DMARD therapy. Further research is needed to establish the role of interventions including psychosocial support, rehabilitation programmes, and biological therapy to improve physical function and HRQoL in this population.

  13. The EOLE experiment: Early results and current objectives

    NASA Technical Reports Server (NTRS)

    Morel, P.; Bandeen, W. R.

    1972-01-01

    The EOLE experiment with 480 constant level balloons released in the Southern Hemisphere is described. Each balloon floating freely at approximately the 200 mb level, is a precise tracer of the horizontal motion of air masses, the accuracy of which is limited only by the laminated structure of the stratospheric flow, within an RMS uncertainty of 1.5 m/sec. The balloons were found after 2 months to distribute at random over the whole hemisphere outside the tropics, irrespective of their original launching site. Early results of Eulerian and Lagrangian averages of the EOLE wind data are given for describing the mean 200 mb zonal and meridional circulations. The effect of the small scale eddies of two-dimensional turbulence has been studied with respect to the relative eddy diffusion of pairs of balloons and the relative dispersion of triangular clusters. New estimates of the RMS divergence of the 200 mb flow are given, together with their scale dependence which was found to be a logarithmic law.

  14. Early-life nutritional effects on the female reproductive system.

    PubMed

    Chan, K A; Tsoulis, M W; Sloboda, D M

    2015-02-01

    There is now considerable epidemiological and experimental evidence indicating that early-life environmental conditions, including nutrition, affect subsequent development in later life. These conditions induce highly integrated responses in endocrine-related homeostasis, resulting in persistent changes in the developmental trajectory producing an altered adult phenotype. Early-life events trigger processes that prepare the individual for particular circumstances that are anticipated in the postnatal environment. However, where the intrauterine and postnatal environments differ markedly, such modifications to the developmental trajectory may prove maladaptive in later life. Reproductive maturation and function are similarly influenced by early-life events. This should not be surprising, because the primordial follicle pool is established early in life and is thus vulnerable to early-life events. Results of clinical and experimental studies have indicated that early-life adversity is associated with a decline in ovarian follicular reserve, changes in ovulation rates, and altered age at onset of puberty. However, the underlying mechanisms regulating the relationship between the early-life developmental environment and postnatal reproductive development and function are unclear. This review examines the evidence linking early-life nutrition and effects on the female reproductive system, bringing together clinical observations in humans and experimental data from targeted animal models. © 2015 Society for Endocrinology.

  15. Effect of prenatal and postnatal malnutrition on intellectual functioning in early school-aged children in rural western China

    PubMed Central

    Li, Chao; Zhu, Ni; Zeng, Lingxia; Dang, Shaonong; Zhou, Jing; Yan, Hong

    2016-01-01

    Abstract The aim of this study was to evaluate the effect of prenatal and postnatal malnutrition on the intellectual functioning of early school-aged children. We followed the offspring of women who had participated in a trial of prenatal supplementation with different combinations of micronutrients and who remained resident in the study field. We measured their intellectual functioning using the Wechsler intelligence scale for children (WISC-IV). Height-for-age, weight-for-age, and body mass index (BMI)-for-age were used as anthropometric nutritional status indices. Four of the 5 composite scores derived from the WISC-IV, except for working memory index (WMI), were significantly lower in low birth weight children after adjusting for confounds. All 5 composite scores, including full-scale intelligence quotient (FSIQ), verbal comprehension index (VCI), WMI, perceptual reasoning index (PRI), and processing speed index (PSI) were significant lower in stunted and underweight children. The differences in the means of WISC-IV test scores were greatest between stunted and nonstunted children. The means for FSIQ, VCI, WMI, PRI, and PSI were as follows: 5.88 (95% confidence interval [CI]: 2.84–8.92), 5.08 (95% CI: 1.12–8.41), 4.71 (95% CI: 1.78–7.66), 6.13 (95% CI: 2.83–9.44), and 5.81 (95% CI: 2.61–9.00). These means were lower in stunted children after adjusting for confounds. Our results suggest the important influences of low birth weight and postnatal malnutrition (stunting, low body weight) on intellectual functioning in early school-aged children. PMID:27495020

  16. Effect of prenatal and postnatal malnutrition on intellectual functioning in early school-aged children in rural western China.

    PubMed

    Li, Chao; Zhu, Ni; Zeng, Lingxia; Dang, Shaonong; Zhou, Jing; Yan, Hong

    2016-08-01

    The aim of this study was to evaluate the effect of prenatal and postnatal malnutrition on the intellectual functioning of early school-aged children. We followed the offspring of women who had participated in a trial of prenatal supplementation with different combinations of micronutrients and who remained resident in the study field. We measured their intellectual functioning using the Wechsler intelligence scale for children (WISC-IV). Height-for-age, weight-for-age, and body mass index (BMI)-for-age were used as anthropometric nutritional status indices. Four of the 5 composite scores derived from the WISC-IV, except for working memory index (WMI), were significantly lower in low birth weight children after adjusting for confounds. All 5 composite scores, including full-scale intelligence quotient (FSIQ), verbal comprehension index (VCI), WMI, perceptual reasoning index (PRI), and processing speed index (PSI) were significant lower in stunted and underweight children. The differences in the means of WISC-IV test scores were greatest between stunted and nonstunted children. The means for FSIQ, VCI, WMI, PRI, and PSI were as follows: 5.88 (95% confidence interval [CI]: 2.84-8.92), 5.08 (95% CI: 1.12-8.41), 4.71 (95% CI: 1.78-7.66), 6.13 (95% CI: 2.83-9.44), and 5.81 (95% CI: 2.61-9.00). These means were lower in stunted children after adjusting for confounds. Our results suggest the important influences of low birth weight and postnatal malnutrition (stunting, low body weight) on intellectual functioning in early school-aged children.

  17. Early Morning Functional Impairments in Stimulant-Treated Children with Attention-Deficit/Hyperactivity Disorder Versus Controls: Impact on the Family.

    PubMed

    Faraone, Stephen V; Schachar, Russell J; Barkley, Russell A; Nullmeier, Rick; Sallee, F Randy

    2017-10-01

    Children with attention-deficit/hyperactivity disorder (ADHD) frequently manifest early morning functional (EMF) impairments before school. We conducted a quantitative research survey to assess the impact of these EMF impairments on the family unit (caregiver, spouse/partner, and siblings). We developed an online survey questionnaire to collect data from 300 primary caregivers of children with ADHD and 50 primary caregivers of children who did not have ADHD. Although the ADHD children we surveyed were currently treated with stable doses of stimulants as their primary ADHD medication for at least 3 months, their parents reported high levels of EMF impairments in the child, which had a substantial negative effect on the emotional well-being of parents, on parents' functioning during the early morning routine, and on the level of conflict with siblings. The impact of EMF impairments on family functioning was mediated by the severity of the index child's impairments. EMF impairments exert a pervasive and significantly negative emotional and functional burden on not only the primary caregiver but also on the spouse/partner and siblings. This work suggests that adequate ADHD symptom control during the early morning period may be an unmet need for school-age children with ADHD being treated with stimulants. More work is needed to confirm this finding and determine the degree to which symptom control at other times of day is also an unmet need.

  18. Changes in cognitive function in women with HIV infection and early life stress.

    PubMed

    Spies, Georgina; Fennema-Notestine, Christine; Cherner, Mariana; Seedat, Soraya

    2017-01-01

    HIV is frequently associated with deficits in brain function, including memory, psychomotor speed, executive function and attention. Early life stress (ELS) has also been shown to have a direct influence on neurocognitive performance. However, little is known about the combined impact of ELS and HIV on neurocognitive function over time. The aim of the present study was to follow a cohort of affected women, allowing us to assess the effects of HIV and childhood trauma on cognition and the change in cognition over time. A battery of neurocognitive tests was administered to 117 women at baseline and then a year later. The sample included a total of 67 HIV + and 50 HIV - women, 71 with ELS and 46 without ELS. Controlling for age, education and antiretroviral therapy (ART) at baseline and 12-month follow-up, raw scores were compared across groups using a repeated-measures analysis of covariance. More women were on ART at follow-up compared to baseline. Results revealed a significant combined HIV and childhood trauma effect over time on the Wisconsin Card Sorting Test (p = .003) and Category Fluency Test (p = .006). A significant individual HIV effect over time was evident on the WAIS-III Digit Symbol Test (p = .03) and the Controlled Oral Word Association Test (p = .003). Findings suggest better performance in abstract reasoning, speed of information processing and verbal fluency over time. While all groups showed improvements that may correspond to practice effects, effects of HIV and childhood trauma remained evident at 12-month follow-up despite greater ART uptake and improved HIV disease status. This is the first study to assess the combined impact of HIV and trauma on neurocognitive function over time in an all-female cohort with more advanced disease.

  19. Reorganization of Functional Networks in Verbal Working Memory Circuitry in Early Midlife: The Impact of Sex and Menopausal Status.

    PubMed

    Jacobs, Emily G; Weiss, Blair; Makris, Nikos; Whitfield-Gabrieli, Sue; Buka, Stephen L; Klibanski, Anne; Goldstein, Jill M

    2017-05-01

    Converging preclinical and human evidence indicates that the decline in ovarian estradiol production during the menopausal transition may play a mechanistic role in the neuronal changes that occur early in the aging process. Here, we present findings from a population-based fMRI study characterizing regional and network-level differences in working memory (WM) circuitry in midlife men and women (N = 142; age range 46-53), as a function of sex and reproductive stage. Reproductive histories and hormonal evaluations were used to determine menopausal status. Participants performed a verbal WM task during fMRI scanning. Results revealed robust differences in task-evoked responses in dorsolateral prefrontal cortex and hippocampus as a function of women's reproductive stage, despite minimal variance in chronological age. Sex differences in regional activity and functional connectivity that were pronounced between men and premenopausal women were diminished for postmenopausal women. Critically, analyzing data without regard to sex or reproductive status obscured group differences in the circuit-level neural strategies associated with successful working memory performance. These findings underscore the importance of reproductive age and hormonal status, over and above chronological age, for understanding sex differences in the aging of memory circuitry. Further, these findings suggest that early changes in working memory circuitry are evident decades before the age range typically targeted in cognitive aging studies. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  20. The Epidermal Growth Factor Receptor Critically Regulates Endometrial Function during Early Pregnancy

    PubMed Central

    Large, Michael J.; Wetendorf, Margeaux; Lanz, Rainer B.; Hartig, Sean M.; Creighton, Chad J.; Mancini, Michael A.; Kovanci, Ertug; Lee, Kuo-Fen; Threadgill, David W.; Lydon, John P.; Jeong, Jae-Wook; DeMayo, Francesco J.

    2014-01-01

    Infertility and adverse gynecological outcomes such as preeclampsia and miscarriage represent significant female reproductive health concerns. The spatiotemporal expression of growth factors indicates that they play an important role in pregnancy. The goal of this study is to define the role of the ERBB family of growth factor receptors in endometrial function. Using conditional ablation in mice and siRNA in primary human endometrial stromal cells, we identified the epidermal growth factor receptor (Egfr) to be critical for endometrial function during early pregnancy. While ablation of Her2 or Erbb3 led to only a modest reduction in litter size, mice lacking Egfr expression are severely subfertile. Pregnancy demise occurred shortly after blastocyst implantation due to defects in decidualization including decreased proliferation, cell survival, differentiation and target gene expression. To place Egfr in a genetic regulatory hierarchy, transcriptome analyses was used to compare the gene signatures from mice with conditional ablation of Egfr, wingless-related MMTV integration site 4 (Wnt4) or boneless morphogenic protein 2 (Bmp2); revealing that not only are Bmp2 and Wnt4 key downstream effectors of Egfr, but they also regulate distinct physiological functions. In primary human endometrial stromal cells, marker gene expression, a novel high content image-based approach and phosphokinase array analysis were used to demonstrate that EGFR is a critical regulator of human decidualization. Furthermore, inhibition of EGFR signaling intermediaries WNK1 and AKT1S1, members identified in the kinase array and previously unreported to play a role in the endometrium, also attenuate decidualization. These results demonstrate that EGFR plays an integral role in establishing the cellular context necessary for successful pregnancy via the activation of intricate signaling and transcriptional networks, thereby providing valuable insight into potential therapeutic targets. PMID

  1. Early intake of long-chain polyunsaturated fatty acids preserves brain structure and function in diet-induced obesity.

    PubMed

    Arnoldussen, Ilse A C; Zerbi, Valerio; Wiesmann, Maximilian; Noordman, Rikko H J; Bolijn, Simone; Mutsaers, Martina P C; Dederen, Pieter J W C; Kleemann, Robert; Kooistra, Teake; van Tol, Eric A F; Gross, Gabriele; Schoemaker, Marieke H; Heerschap, Arend; Wielinga, Peter Y; Kiliaan, Amanda J

    2016-04-01

    Worldwide, the incidence of obesity is increasing at an alarming rate, and the number of children with obesity is especially worrisome. These developments raise concerns about the physical, psychosocial and cognitive consequences of obesity. It was shown that early dietary intake of arachidonic acid (ARA) and docosahexaenoic acid (DHA) can reduce the detrimental effects of later obesogenic feeding on lipid metabolism and adipogenesis in an animal model of mild obesity. In the present study, the effects of early dietary ARA and DHA on cognition and brain structure were examined in mildly obesogenic ApoE*3Leiden mouse model. We used cognitive tests and neuroimaging during early and later life. During their early development after weaning (4-13weeks of age), mice were fed a chow diet or ARA and DHA diet for 8 weeks and then switched to a high-fat and high-carbohydrate (HFHC) diet for 12weeks (14-26weeks of age). An HFHC-diet led to increased energy storage in white adipose tissue, increased cholesterol levels, decreased triglycerides levels, increased cerebral blood flow and decreased functional connectivity between brain regions as well as cerebrovascular and gray matter integrity. ARA and DHA intake reduced the HFHC-diet-induced increase in body weight, attenuated plasma triglycerides levels and improved cerebrovasculature, gray matter integrity and functional connectivity in later life. In conclusion, an HFHC diet causes adverse structural brain and metabolic adaptations, most of which can be averted by dietary ARA and DHA intake early in life supporting metabolic flexibility and cerebral integrity later in life. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Adolescent cannabis use, change in neurocognitive function, and high-school graduation: A longitudinal study from early adolescence to young adulthood

    PubMed Central

    CASTELLANOS-RYAN, NATALIE; PINGAULT, JEAN-BAPTISTE; PARENT, SOPHIE; VITARO, FRANK; TREMBLAY, RICHARD E.; SÉGUIN, JEAN R.

    2017-01-01

    The main objective of this prospective longitudinal study was to investigate bidirectional associations between adolescent cannabis use (CU) and neurocognitive performance in a community sample of 294 young men from ages 13 to 20 years. The results showed that in early adolescence, and prior to initiation to CU, poor short-term and working memory, but high verbal IQ, were associated with earlier age of onset of CU. In turn, age of CU onset and CU frequency across adolescence were associated with (a) specific neurocognitive decline in verbal IQ and executive function tasks tapping trial and error learning and reward processing by early adulthood and (b) lower rates of high-school graduation. The association between CU onset and change in neurocognitive function, however, was found to be accounted for by CU frequency. Whereas the link between CU frequency across adolescence and change in verbal IQ was explained (mediated) by high school graduation, the link between CU frequency and tasks tapping trial and error learning were independent from high school graduation, concurrent cannabis and other substance use, adolescent alcohol use, and externalizing behaviors. Findings support prevention efforts aimed at delaying onset and reducing frequency of CU. PMID:28031069

  3. Adolescent cannabis use, change in neurocognitive function, and high-school graduation: A longitudinal study from early adolescence to young adulthood.

    PubMed

    Castellanos-Ryan, Natalie; Pingault, Jean-Baptiste; Parent, Sophie; Vitaro, Frank; Tremblay, Richard E; Séguin, Jean R

    2017-10-01

    The main objective of this prospective longitudinal study was to investigate bidirectional associations between adolescent cannabis use (CU) and neurocognitive performance in a community sample of 294 young men from ages 13 to 20 years. The results showed that in early adolescence, and prior to initiation to CU, poor short-term and working memory, but high verbal IQ, were associated with earlier age of onset of CU. In turn, age of CU onset and CU frequency across adolescence were associated with (a) specific neurocognitive decline in verbal IQ and executive function tasks tapping trial and error learning and reward processing by early adulthood and (b) lower rates of high-school graduation. The association between CU onset and change in neurocognitive function, however, was found to be accounted for by CU frequency. Whereas the link between CU frequency across adolescence and change in verbal IQ was explained (mediated) by high school graduation, the link between CU frequency and tasks tapping trial and error learning were independent from high school graduation, concurrent cannabis and other substance use, adolescent alcohol use, and externalizing behaviors. Findings support prevention efforts aimed at delaying onset and reducing frequency of CU.

  4. Brain regions and functional interactions supporting early word recognition in the face of input variability.

    PubMed

    Benavides-Varela, Silvia; Siugzdaite, Roma; Gómez, David Maximiliano; Macagno, Francesco; Cattarossi, Luigi; Mehler, Jacques

    2017-07-18

    Perception and cognition in infants have been traditionally investigated using habituation paradigms, assuming that babies' memories in laboratory contexts are best constructed after numerous repetitions of the very same stimulus in the absence of interference. A crucial, yet open, question regards how babies deal with stimuli experienced in a fashion similar to everyday learning situations-namely, in the presence of interfering stimuli. To address this question, we used functional near-infrared spectroscopy to test 40 healthy newborns on their ability to encode words presented in concomitance with other words. The results evidenced a habituation-like hemodynamic response during encoding in the left-frontal region, which was associated with a progressive decrement of the functional connections between this region and the left-temporal, right-temporal, and right-parietal regions. In a recognition test phase, a characteristic neural signature of recognition recruited first the right-frontal region and subsequently the right-parietal ones. Connections originating from the right-temporal regions to these areas emerged when newborns listened to the familiar word in the test phase. These findings suggest a neural specialization at birth characterized by the lateralization of memory functions: the interplay between temporal and left-frontal regions during encoding and between temporo-parietal and right-frontal regions during recognition of speech sounds. Most critically, the results show that newborns are capable of retaining the sound of specific words despite hearing other stimuli during encoding. Thus, habituation designs that include various items may be as effective for studying early memory as repeated presentation of a single word.

  5. Do postoperative platelet-rich plasma injections accelerate early tendon healing and functional recovery after arthroscopic supraspinatus repair? A randomized controlled trial.

    PubMed

    Wang, Allan; McCann, Philip; Colliver, Jess; Koh, Eamon; Ackland, Timothy; Joss, Brendan; Zheng, Minghao; Breidahl, Bill

    2015-06-01

    Tendon-bone healing after rotator cuff repair directly correlates with a successful outcome. Biological therapies that elevate local growth-factor concentrations may potentiate healing after surgery. To ascertain whether postoperative and repeated application of platelet-rich plasma (PRP) to the tendon repair site improves early tendon healing and enhances early functional recovery after double-row arthroscopic supraspinatus repair. Randomized controlled trial; Level of evidence, 1. A total of 60 patients underwent arthroscopic double-row supraspinatus tendon repair. After randomization, half the patients received 2 ultrasound-guided injections of PRP to the repair site at postoperative days 7 and 14. Early structural healing was assessed with MRI at 16 weeks, and cuff appearances were graded according to the Sugaya classification. Functional scores were recorded with the Oxford Shoulder Score; Quick Disability of the Arm, Shoulder and Hand; visual analog scale for pain; and Short Form-12 quality-of-life score both preoperatively and at postoperative weeks 6, 12, and 16; isokinetic strength and active range of motion were measured at 16 weeks. PRP treatment did not improve early functional recovery, range of motion, or strength or influence pain scores at any time point after arthroscopic supraspinatus repair. There was no difference in structural integrity of the supraspinatus repair on MRI between the PRP group (0% full-thickness retear; 23% partial tear; 77% intact) and the control group (7% full-thickness retear; 23% partial tear; 70% intact) at 16 weeks postoperatively (P = .35). After arthroscopic supraspinatus tendon repair, image-guided PRP treatment on 2 occasions does not improve early tendon-bone healing or functional recovery. © 2015 The Author(s).

  6. CD4+ T cells are required to contain early extrathoracic TB dissemination and sustain multi-effector functions of CD8+ T and CD3− lymphocytes

    PubMed Central

    Yao, Shuyu; Huang, Dan; Chen, Crystal Y.; Halliday, Lisa; Wang, Richard C.; Chen, Zheng W.

    2014-01-01

    The possibility that CD4+ T cells can act as “innate-like” cells to contain very-early M. tuberculosis (Mtb) dissemination and function as master helpers to sustain multiple effector functions of CD8+ T cells and CD3-negative lymphocytes during development of adaptive immunity against primary tuberculosis(TB) has not been demonstrated. We showed that pulmonary Mtb infection of CD4-depleted macaques surprisingly led to very-early extrathoracic Mtb dissemination, whereas CD4 deficiency clearly resulted in rapid TB progression. CD4 depletion during Mtb infection revealed the ability of CD8+ T cells to compensate and rapidly differentiate to Th17-like/Th1-like, and cytotoxic-like effectors, but these effector functions were subsequently unsustainable due to CD4 deficiency. While CD3-negative non-T lymphocytes in presence of CD4+ T cells developed predominant Th22-like and NK-like (perforin production) responses to Mtb infection, CD4 depletion abrogated these Th22-/NK-like effector functions and favored IL-17 production by CD3-negative lymphocytes. CD4-depleted macaques exhibited no or few pulmonary T effector cells constitutively producing IFN-γ, TNFα, IL-17, IL-22, and perforin at the endpoint of more severe TB, but presented pulmonary IL-4+ T effectors. TB granulomas in CD4-depleted macaques contained fewer IL-22+ and perforin+ cells despite presence of IL-17+ and IL-4+ cells. These results implicate previously-unknown “innate-like” ability of CD4+ T cells to contain extrathoracic Mtb dissemination at very early stage. Data also suggest that CD4+ T cells are required to sustain multiple effector functions of CD8+ T cells and CD3-negative lymphocytes and to prevent rapid TB progression during Mtb infection of nonhuman primates. PMID:24489088

  7. Social Factors in the Development of Early Executive Functioning: A Closer Look at the Caregiving Environment

    ERIC Educational Resources Information Center

    Bernier, Annie; Carlson, Stephanie M.; Deschenes, Marie; Matte-Gagne, Celia

    2012-01-01

    This study investigated prospective links between quality of the early caregiving environment and children's subsequent executive functioning (EF). Sixty-two families were met on five occasions, allowing for assessment of maternal interactive behavior, paternal interactive behavior, and child attachment security between 1 and 2 years of age, and…

  8. Decursin inhibits vasculogenesis in early tumor progression by suppression of endothelial progenitor cell differentiation and function.

    PubMed

    Jung, Seok Yun; Choi, Jin Hwa; Kwon, Sang-Mo; Masuda, Haruchika; Asahara, Takayuki; Lee, You-Mie

    2012-05-01

    Endothelial progenitor cells (EPCs) contribute to the tumor vasculature during tumor progression. Decursin isolated from the herb Angelica gigas is known to possess potent anti-inflammatory activities. Recently, we reported that decursin is a novel candidate for an angiogenesis inhibitor [Jung et al., 2009]. In this study, we investigated whether decursin regulates EPC differentiation and function to inhibit tumor vasculogenesis. We isolated AC133+ cells from human cord blood and decursin significantly decreased the number of EPC colony forming units of human cord blood-derived AC133+ cells that produce functional EPC progenies. Decursin dose-dependently decreased the cell number of EPC committing cells as demonstrated by EPC expansion studies. Decursin inhibited EPC differentiation from progenitor cells into spindle-shaped EPC colonies. Additionally, decursin inhibited proliferation and migration of early EPCs isolated from mouse bone marrow. Furthermore, decursin suppressed expression of angiopoietin-2, angiopoietin receptor Tie-2, Flk-1 (vascular endothelial growth factor receptor-2), and endothelial nitric oxide synthase in mouse BM derived EPCs in a dose-dependent manner. Decursin suppressed tube formation ability of EPCs in collaboration with HUVEC. Decursin (4 mg/kg) inhibited tumor-induced mobilization of circulating EPCs (CD34 + /VEGFR-2+ cells) from bone marrow and early incorporation of Dil-Ac-LDL-labeled or green fluorescent protein (GFP)+ EPCs into neovessels of xenograft Lewis lung carcinoma tumors in wild-type- or bone-marrow-transplanted mice. Accordingly, decursin attenuated EPC-derived endothelial cells in neovessels of Lewis lung carcinoma tumor masses grown in mice. Together, decursin likely affects EPC differentiation and function, thereby inhibiting tumor vasculogenesis in early tumorigenesis. Copyright © 2012 Wiley Periodicals, Inc.

  9. [Early results of proximal femoral fractures treated with FENIX modular hemiarthroplasty].

    PubMed

    Görski, Radosław; Górecki, Andrzej; Olszewski, Paweł; Biedrzycki, Jerzy; Skowronek, Paweł

    2010-01-01

    The article discusses preliminary clinical results in patients with proximal femoral fractures treated with hemiarthroplasty using a FENIX implant. The study group comprised 41 subjects aged 69 to 97 (median age 82.3 year). The follow-up study provided data on 26 subjects (63.4%), among which 15 attended the check-up, 5 subjects refused to visit at the Department and 6 subjects were reported as deceased. Median follow-up period amounted to 6.8 month (1 to 22 months). General hospitalization-related complications occurred in 8 patients (19.5%). During hospitalization no deaths occurred, in the deceased group 3 patients died within 12 months after surgery, while another 3 died after the twelve-month postoperative period (median of 13.3%). According to Merle d'Aubigne-Postel score favorable long-term results were observed in 9 patients (59.9%), 13 patients regained the level of motor function similar to the functional ability prior to fracture. The need to postpone the surgery due to general health status and impaired pre-operative motor function are significant negative prognostic factors. The results obtained were compared with previous efficacy studies on femoral fracture treatment using an Austin-Moore implant. Functional ability and self-reliance was higher in the FENIX group. FENIX arthroplasty effectively helps patients regain self-reliance and motor function thanks to its modular characteristics and anatmoical construction.

  10. Early stages of functional diversification in the Rab GTPase gene family revealed by genomic and localization studies in Paramecium species

    PubMed Central

    Bright, Lydia J.; Gout, Jean-Francois; Lynch, Michael

    2017-01-01

    New gene functions arise within existing gene families as a result of gene duplication and subsequent diversification. To gain insight into the steps that led to the functional diversification of paralogues, we tracked duplicate retention patterns, expression-level divergence, and subcellular markers of functional diversification in the Rab GTPase gene family in three Paramecium aurelia species. After whole-genome duplication, Rab GTPase duplicates are more highly retained than other genes in the genome but appear to be diverging more rapidly in expression levels, consistent with early steps in functional diversification. However, by localizing specific Rab proteins in Paramecium cells, we found that paralogues from the two most recent whole-genome duplications had virtually identical localization patterns, and that less closely related paralogues showed evidence of both conservation and diversification. The functionally conserved paralogues appear to target to compartments associated with both endocytic and phagocytic recycling functions, confirming evolutionary and functional links between the two pathways in a divergent eukaryotic lineage. Because the functionally diversifying paralogues are still closely related to and derived from a clade of functionally conserved Rab11 genes, we were able to pinpoint three specific amino acid residues that may be driving the change in the localization and thus the function in these proteins. PMID:28251922

  11. Virtual multiple errands test (VMET): a virtual reality-based tool to detect early executive functions deficit in Parkinson’s disease

    PubMed Central

    Cipresso, Pietro; Albani, Giovanni; Serino, Silvia; Pedroli, Elisa; Pallavicini, Federica; Mauro, Alessandro; Riva, Giuseppe

    2014-01-01

    Introduction: Several recent studies have pointed out that early impairment of executive functions (EFs) in Parkinson’s Disease (PD) may be a crucial marker to detect patients at risk for developing dementia. The main objective of this study was to compare the performances of PD patients with mild cognitive impairment (PD-MCI) with PD patients with normal cognition (PD-NC) and a control group (CG) using a traditional assessment of EFs and the Virtual Multiple Errands Test (VMET), a virtual reality (VR)-based tool. In order to understand which subcomponents of EFs are early impaired, this experimental study aimed to investigate specifically which instrument best discriminates among these three groups. Materials and methods: The study included three groups of 15 individuals each (for a total of 45 participants): 15 PD-NC; 15 PD-MCI, and 15 cognitively healthy individuals (CG). To assess the global neuropsychological functioning and the EFs, several tests (including the Mini Mental State Examination (MMSE), Clock Drawing Test, and Tower of London test) were administered to the participants. The VMET was used for a more ecologically valid neuropsychological evaluation of EFs. Results: Findings revealed significant differences in the VMET scores between the PD-NC patients vs. the controls. In particular, patients made more errors in the tasks of the VMET, and showed a poorer ability to use effective strategies to complete the tasks. This VMET result seems to be more sensitive in the early detection of executive deficits because these two groups did not differ in the traditional assessment of EFs (neuropsychological battery). Conclusion: This study offers initial evidence that a more ecologically valid evaluation of EFs is more likely to lead to detection of subtle executive deficits. PMID:25538578

  12. Early diagnosis of asthma in young children by using non-invasive biomarkers of airway inflammation and early lung function measurements: study protocol of a case-control study

    PubMed Central

    van de Kant, Kim DG; Klaassen, Ester MM; Jöbsis, Quirijn; Nijhuis, Annedien J; van Schayck, Onno CP; Dompeling, Edward

    2009-01-01

    Background Asthma is the most common chronic disease in childhood, characterized by chronic airway inflammation. There are problems with the diagnosis of asthma in young children since the majority of the children with recurrent asthma-like symptoms is symptom free at 6 years, and does not have asthma. With the conventional diagnostic tools it is not possible to differentiate between preschool children with transient symptoms and children with asthma. The analysis of biomarkers of airway inflammation in exhaled breath is a non-invasive and promising technique to diagnose asthma and monitor inflammation in young children. Moreover, relatively new lung function tests (airway resistance using the interrupter technique) have become available for young children. The primary objective of the ADEM study (Asthma DEtection and Monitoring study), is to develop a non-invasive instrument for an early asthma diagnosis in young children, using exhaled inflammatory markers and early lung function measurements. In addition, aetiological factors, including gene polymorphisms and gene expression profiles, in relation to the development of asthma are studied. Methods/design A prospective case-control study is started in 200 children with recurrent respiratory symptoms and 50 control subjects without respiratory symptoms. At 6 years, a definite diagnosis of asthma is made (primary outcome measure) on basis of lung function assessments and current respiratory symptoms ('golden standard'). From inclusion until the definite asthma diagnosis, repeated measurements of lung function tests and inflammatory markers in exhaled breath (condensate), blood and faeces are performed. The study is registered and ethically approved. Discussion This article describes the study protocol of the ADEM study. The new diagnostic techniques applied in this study could make an early diagnosis of asthma possible. An early and reliable asthma diagnosis at 2–3 years will have consequences for the management of

  13. Does an early onset and continuous chain of rehabilitation improve the long-term functional outcome of patients with severe traumatic brain injury?

    PubMed

    Andelic, Nada; Bautz-Holter, Erik; Ronning, Pal; Olafsen, Kjell; Sigurdardottir, Solrun; Schanke, Anne-Kristine; Sveen, Unni; Tornas, Sveinung; Sandhaug, Maria; Roe, Cecilie

    2012-01-01

    There are currently no international guidelines regarding treatment in the early rehabilitation phase for persons with severe traumatic brain injury (TBI), and only a few studies have investigated the effect of integrating rehabilitation into acute TBI care. The aim of the study was to evaluate whether a continuous chain of rehabilitation that begins with the acute phase could improve the functional outcome of severe TBI patients, compared to a broken chain of rehabilitation that starts in the sub-acute phase of TBI. A total of 61 surviving patients with severe TBI were included in a quasi-experimental study conducted at the Level I trauma center in Eastern Norway. In the study, 31 patients were in the early rehabilitation group (Group A) and 30 patients were in the delayed rehabilitation group (Group B). The functional outcomes were assessed 12 months post-injury with the Glasgow Outcome Scale Extended (GOSE) and the Disability Rating Scale (DRS). A favorable outcome (GOSE 6-8) occurred in 71% of the patients from Group A versus 37% in Group B (p=0.007). The DRS score was significantly better in Group A (p=0.03). The ordinal logistic regression analysis was used to quantify the relationship between the type of rehabilitation chain and the GOSE. A better GOSE outcome was found in patients from Group A (unadjusted OR 3.25 and adjusted OR 2.78, respectively). These results support the hypothesis that better functional outcome occurs in patients who receive early onset and a continuous chain of rehabilitation.

  14. Early Parenting and the Development of Externalizing Behavior Problems: Longitudinal Mediation Through Children's Executive Function.

    PubMed

    Sulik, Michael J; Blair, Clancy; Mills-Koonce, Roger; Berry, Daniel; Greenberg, Mark

    2015-01-01

    Path analysis was used to investigate the longitudinal associations among parenting and children's executive function and externalizing behavior problems from 36 to 90 months of age in the Family Life Project (N = 1,115), a study of child development in the context of rural poverty. While controlling for stability in the constructs, semistructured observations of parenting prospectively predicted performance on a battery of executive function tasks and primary caregivers' reports of externalizing behavior. Furthermore, the association between early parenting and later externalizing behavior was longitudinally mediated by executive function, providing support for a process model in which sensitive parenting promotes children's self-regulation, which in turn reduces children's externalizing behavior. © 2015 The Authors. Child Development © 2015 Society for Research in Child Development, Inc.

  15. Early clinical results of a high-flexion, posterior-stabilized, mobile-bearing total knee arthroplasty: a US investigational device exemption trial.

    PubMed

    Scuderi, Giles R; Hedden, David R; Maltry, John A; Traina, Steven M; Sheinkop, Mitchell B; Hartzband, Mark A

    2012-03-01

    Between May 2001 and June 2004, 388 total knee arthroplasty cases were enrolled in a prospective, randomized, multicenter investigational device exemption trial. Patients received either the investigational high-flexion mobile-bearing knee or a fixed-bearing control. At 2 to 4 years of follow-up, results in 293 patients with degenerative joint disease were compared using Knee Society Assessment and Function scores, radiographic results, complications analysis, and survival estimates. The mobile-bearing and fixed-bearing groups demonstrated similar, significant improvement over preoperative assessments in Knee Scores, maximum flexion, and range of motion. One mobile-bearing arthroplasty required revision. Radiographic results were unremarkable, and implant-related complications were rare in both groups. At this early follow-up, the investigational high-flexion mobile-bearing knee and its fixed-bearing counterpart demonstrated comparable, effective performance. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Early poststroke rehabilitation using a robotic tilt-table stepper and functional electrical stimulation.

    PubMed

    Kuznetsov, Alexey N; Rybalko, Natalia V; Daminov, Vadim D; Luft, Andreas R

    2013-01-01

    Background. Stroke frequently leaves survivors with hemiparesis. To prevent persistent deficits, rehabilitation may be more effective if started early. Early training is often limited because of orthostatic reactions. Tilt-table stepping robots and functional electrical stimulation (FES) may prevent these reactions. Objective. This controlled convenience sample study compares safety and feasibility of robotic tilt-table training plus FES (ROBO-FES) and robotic tilt-table training (ROBO) against tilt-table training alone (control). A preliminary assessment of efficacy is performed. Methods. Hemiparetic ischemic stroke survivors (age 58.3 ± 1.2 years, 4.6 ± 1.2 days after stroke) were assigned to 30 days of ROBO-FES (n = 38), ROBO (n = 35), or control (n = 31) in addition to conventional physical therapy. Impedance cardiography and transcranial doppler sonography were performed before, during, and after training. Hemiparesis was assessed using the British Medical Research Council (MRC) strength scale. Results. No serious adverse events occurred; 8 patients in the tilt-table group prematurely quit the study because of orthostatic reactions. Blood pressure and CBFV dipped <10% during robot training. In 52% of controls mean arterial pressure decreased by ≥20%. ROBO-FES increased leg strength by 1.97 ± 0.88 points, ROBO by 1.50 ± 0.85 more than control (1.03 ± 0.61, P < 0.05). CBFV increased in both robotic groups more than in controls (P < 0.05). Conclusions. Robotic tilt-table exercise with or without FES is safe and may be more effective in improving leg strength and cerebral blood flow than tilt table alone.

  17. Early Poststroke Rehabilitation Using a Robotic Tilt-Table Stepper and Functional Electrical Stimulation

    PubMed Central

    Kuznetsov, Alexey N.; Rybalko, Natalia V.; Daminov, Vadim D.; Luft, Andreas R.

    2013-01-01

    Background. Stroke frequently leaves survivors with hemiparesis. To prevent persistent deficits, rehabilitation may be more effective if started early. Early training is often limited because of orthostatic reactions. Tilt-table stepping robots and functional electrical stimulation (FES) may prevent these reactions. Objective. This controlled convenience sample study compares safety and feasibility of robotic tilt-table training plus FES (ROBO-FES) and robotic tilt-table training (ROBO) against tilt-table training alone (control). A preliminary assessment of efficacy is performed. Methods. Hemiparetic ischemic stroke survivors (age 58.3 ± 1.2 years, 4.6 ± 1.2 days after stroke) were assigned to 30 days of ROBO-FES (n = 38), ROBO (n = 35), or control (n = 31) in addition to conventional physical therapy. Impedance cardiography and transcranial doppler sonography were performed before, during, and after training. Hemiparesis was assessed using the British Medical Research Council (MRC) strength scale. Results. No serious adverse events occurred; 8 patients in the tilt-table group prematurely quit the study because of orthostatic reactions. Blood pressure and CBFV dipped <10% during robot training. In 52% of controls mean arterial pressure decreased by ≥20%. ROBO-FES increased leg strength by 1.97 ± 0.88 points, ROBO by 1.50 ± 0.85 more than control (1.03 ± 0.61, P < 0.05). CBFV increased in both robotic groups more than in controls (P < 0.05). Conclusions. Robotic tilt-table exercise with or without FES is safe and may be more effective in improving leg strength and cerebral blood flow than tilt table alone. PMID:23691432

  18. Associations of early childhood adversities with mental disorders, psychological functioning, and suitability for psychotherapy in adulthood.

    PubMed

    Heinonen, Erkki; Knekt, Paul; Härkänen, Tommi; Virtala, Esa; Lindfors, Olavi

    2018-06-01

    Childhood adversities frequently precede adulthood depression and anxiety. Yet, how they impact needed treatment duration, type or focus in these common disorders, is unclear. For developing more individualized and precise interventions, we investigated whether specific early adversities associate with patients' distinct psychiatric problems, psychological vulnerabilities, and suitability for psychotherapy. A total of 221 depressed and anxious adult outpatients (excluding psychotic, severe personality, bipolar, and substance abuse disorders) referred from community, student, occupational, and private healthcare services filled the Childhood Family Atmosphere Questionnaire (CFAQ). They also filled self-reports on interpersonal behavior and problems, perceived competence, dispositional optimism, sense of coherence, defenses, and psychiatric history. Clinicians assessed the patients' symptomatology, personality, object relations, cognitive performance, and psychotherapy suitability. Regression analyses were conducted. Childhood adversities predicted both worse current psychological functioning (e.g., interpersonal problems), and better clinician-rated capacities for benefiting from psychotherapy (e.g. self-reflection, capacity for interaction). Parental problems had the most numerous negative associations to psychological functioning. Best capacities for psychotherapy were predicted by recollected family unhappiness. Associations with psychiatric criteria were, however, largely non-significant. In conclusion, for psychosocial treatment planning, patients' early adversities may indicate both vulnerability and resources. As childhood adversities are frequent among treatment-seekers, further studies examining how early adversities predict psychotherapy outcome are needed. Copyright © 2018. Published by Elsevier B.V.

  19. Using e-Coaching to Support an Early Intervention Provider's Implementation of a Functional Assessment-Based Intervention

    ERIC Educational Resources Information Center

    Fettig, Angel; Barton, Erin E.; Carter, Alice S.; Eisenhower, Abbey S.

    2016-01-01

    This study examined the effects of e-coaching on the implementation of a functional assessment-based intervention delivered by an early intervention provider in reducing challenging behaviors during home visits. A multiple baseline design across behavior support plan components was used with a provider-child dyad. The e-coaching intervention…

  20. Asking for Action or Information? Crosslinguistic Comparison of Interrogative Functions in Early Child Cantonese and Mandarin

    ERIC Educational Resources Information Center

    Li, Hui; Wong, Eileen Chin Mei; Tse, Shek Kam; Leung, Shing On; Ye, Qianling

    2015-01-01

    Request for information (RfI) is believed to be the universally dominant function of young children's questioning, whereas request for action (RfA) has been reported to be the leading interrogative form used in early child Cantonese. The possibility of crosslinguistic variability prompts further research and comparison with additional languages.…

  1. Early Response of Soil Properties and Function to Riparian Rainforest Restoration

    PubMed Central

    Gageler, Rose; Bonner, Mark; Kirchhof, Gunnar; Amos, Mark; Robinson, Nicole; Schmidt, Susanne; Shoo, Luke P.

    2014-01-01

    Reforestation of riparian zones is increasingly practiced in many regions for purposes of biodiversity conservation, bank stabilisation, and improvement in water quality. This is in spite of the actual benefits of reforestation for recovering underlying soil properties and function remaining poorly understood. Here we compare remnant riparian rainforest, pasture and reforestation plantings aged 2–20 years in an Australian subtropical catchment on ferrosols to determine the extent to which reforestation restores key soil properties. Of the nine soil attributes measured (total nitrogen, nitrate and ammonium concentrations, net nitrification and ammonification rates, organic carbon, bulk density, fine root biomass and water infiltration rates), only infiltration rates were significantly lower in pasture than remnant riparian rainforest. Within reforestation plantings, bulk density decreased up to 1.4-fold and infiltration rates increased up to 60-fold with time post-reforestation. Our results suggest that the main outcome of belowground processes of early reforestation is the recovery of the soils' physical structure, with potential beneficial ecosystem services including reduced runoff, erosion and associated sediment and nutrient loads in waterways. We also demonstrate differential impacts of two commonly planted tree species on a subset of soil properties suggesting that preferential planting of select species could accelerate progress on specific restoration objectives. PMID:25117589

  2. Early response of soil properties and function to riparian rainforest restoration.

    PubMed

    Gageler, Rose; Bonner, Mark; Kirchhof, Gunnar; Amos, Mark; Robinson, Nicole; Schmidt, Susanne; Shoo, Luke P

    2014-01-01

    Reforestation of riparian zones is increasingly practiced in many regions for purposes of biodiversity conservation, bank stabilisation, and improvement in water quality. This is in spite of the actual benefits of reforestation for recovering underlying soil properties and function remaining poorly understood. Here we compare remnant riparian rainforest, pasture and reforestation plantings aged 2-20 years in an Australian subtropical catchment on ferrosols to determine the extent to which reforestation restores key soil properties. Of the nine soil attributes measured (total nitrogen, nitrate and ammonium concentrations, net nitrification and ammonification rates, organic carbon, bulk density, fine root biomass and water infiltration rates), only infiltration rates were significantly lower in pasture than remnant riparian rainforest. Within reforestation plantings, bulk density decreased up to 1.4-fold and infiltration rates increased up to 60-fold with time post-reforestation. Our results suggest that the main outcome of belowground processes of early reforestation is the recovery of the soils' physical structure, with potential beneficial ecosystem services including reduced runoff, erosion and associated sediment and nutrient loads in waterways. We also demonstrate differential impacts of two commonly planted tree species on a subset of soil properties suggesting that preferential planting of select species could accelerate progress on specific restoration objectives.

  3. Preoperative determinant of early postoperative renal function following radical cystectomy and intestinal urinary diversion.

    PubMed

    Gondo, Tatsuo; Ohno, Yoshio; Nakashima, Jun; Hashimoto, Takeshi; Nakagami, Yoshihiro; Tachibana, Masaaki

    2017-02-01

    To identify preoperative factors correlated with postoperative early renal function in patients who had undergone radical cystectomy (RC) and intestinal urinary diversion. We retrospectively identified 201 consecutive bladder cancer patients without distant metastasis who had undergone RC at our institution between 2003 and 2012. The estimated glomerular filtration rate (eGFR) was calculated using the modified Chronic Kidney Disease Epidemiology equation before RC and 3 months following RC. Univariate and stepwise multiple linear regression analyses were applied to estimate postoperative renal function and to identify significant preoperative predictors of postoperative renal function. Patients who had undergone intestinal urinary diversion and were available for the collection of follow-up data (n = 164) were eligible for the present study. Median preoperative and postoperative eGFRs were 69.7 (interquartile range [IQR] 56.3-78.0) and 70.7 (IQR 57.3-78.1), respectively. In univariate analyses, age, preoperative proteinuria, thickness of abdominal subcutaneous fat tissue (TSF), preoperative serum creatinine level, preoperative eGFR, and urinary diversion type were significantly associated with postoperative eGFR. In a stepwise multiple linear regression analysis, preoperative eGFR, age, and TSF were significant factors for predicting postoperative eGFR (p < 0.001, p = 0.02, and p = 0.046, respectively). The estimated postoperative eGFRs correlated well with the actual postoperative eGFRs (r = 0.65, p < 0.001). Preoperative eGFR, age, and TSF were independent preoperative factors for determining postoperative renal function in patients who had undergone RC and intestinal urinary diversion. These results may be used for patient counseling before surgery, including the planning of perioperative chemotherapy administration.

  4. Early liraglutide treatment is better in glucose control, β-cell function improvement and mass preservation in db/db mice.

    PubMed

    Shao, Yimin; Yuan, Geheng; Feng, Yan; Zhang, Junqing; Guo, Xiaohui

    2014-02-01

    Glucagon-like peptide-1 (GLP-1) has been proved to have effects of anti-hyperglycemia and β-cell preservation. However, it is still unclear whether there are differences between early and late GLP-1 intervention in type 2 diabetes mellitus (T2DM). We divided the mice into 5 groups: early treated group (n=7, 8-week old, fasting glucose>10mmol/l), late treated group (n=7, 10-week old, fasting glucose>20mmol/l), early control group (n=7), late control group (n=7) and wild type group (n=7). Treated group was injected with liraglutide (a GLP-1 analog) 300μg/kg bid for 4 weeks, while control group was given saline at the same time. The results showed that compared with control group, food intake and body weight gain were reduced in both early and late treated group (p<0.05), and there was no significance between the two treated groups. Early liraglutide intervention showed better improvements in glucose control, acute insulin response to glucose (AIRg) and disposition index (before vs. after treatment, AIRg 1.01±0.53 vs. 2.98±0.63, disposition index 10.81±0.89 vs. 27.4±2.15) than late intervention (AIRg 0.99±0.02 vs. 1.41±0.32, disposition index 3.47±0.38 vs. 6.43±1.62, p=0.001). The histopathology of the pancreas showed the estimated β-cell mass (BCM) was increased more in early treated group than that in late one (0.03 vs. 0.01g). Expressions of the proliferation related genes PDX-1, MafA and GLP-1 receptor (GLP-1R) in early treated group were 1.81, 2.57 and 1.59 times as much as that in late treated group. In conclusion, early liraglutide intervention was better in glucose control, β-cell function improvement and β-cell mass preservation. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Can targeted early intervention improve functional recovery in psychosis? A historical control evaluation of the effectiveness of different models of early intervention service provision in Norfolk 1998-2007.

    PubMed

    Fowler, David; Hodgekins, Jo; Howells, Lawrence; Millward, Melanie; Ivins, Annabel; Taylor, Gavin; Hackmann, Corinna; Hill, Katherine; Bishop, Nick; Macmillan, Iain

    2009-11-01

    This paper assesses the impact of different models of early intervention (EI) service provision on functional recovery and inpatient hospital admission. The study compares the outcome of a comprehensive EI team with a partial model (community mental health team (CMHT) plus specialist support) and traditional care (generic CMHT) over a 10-year period. The design is in comparison with historical control. The study compares the functional recovery outcomes of three cohorts from the same geographical area over the period 1998-2007. The primary outcomes were partial and full functional recovery defined with respect to readily identifiable UK benefit system thresholds and psychiatric inpatient admission days at 1 and 2 years post-referral. Only 15% of individuals made a full or partial functional recovery at 2 years under the care of a traditional generic CMHT in 1998. In 2007, 52% of the cases were making a full or partial functional recovery under the care of the comprehensive EI team. A large reduction in inpatient admissions was associated with the EI strategy. The implementation of comprehensive EI teams can have a major impact in improving functional recovery outcomes in psychosis and reducing inpatient admissions. Partial implementation using limited funding of specialist workers in collaboration with traditional care appeared to have a more limited effect on these recovery dimensions. The implementation of targeted EI in psychosis strategies can result in substantive functional benefits. © 2009 The Authors. Journal compilation © 2009 Blackwell Publishing Asia Pty Ltd.

  6. Shaping Early Reorganization of Neural Networks Promotes Motor Function after Stroke

    PubMed Central

    Volz, L. J.; Rehme, A. K.; Michely, J.; Nettekoven, C.; Eickhoff, S. B.; Fink, G. R.; Grefkes, C.

    2016-01-01

    Neural plasticity is a major factor driving cortical reorganization after stroke. We here tested whether repetitively enhancing motor cortex plasticity by means of intermittent theta-burst stimulation (iTBS) prior to physiotherapy might promote recovery of function early after stroke. Functional magnetic resonance imaging (fMRI) was used to elucidate underlying neural mechanisms. Twenty-six hospitalized, first-ever stroke patients (time since stroke: 1–16 days) with hand motor deficits were enrolled in a sham-controlled design and pseudo-randomized into 2 groups. iTBS was administered prior to physiotherapy on 5 consecutive days either over ipsilesional primary motor cortex (M1-stimulation group) or parieto-occipital vertex (control-stimulation group). Hand motor function, cortical excitability, and resting-state fMRI were assessed 1 day prior to the first stimulation and 1 day after the last stimulation. Recovery of grip strength was significantly stronger in the M1-stimulation compared to the control-stimulation group. Higher levels of motor network connectivity were associated with better motor outcome. Consistently, control-stimulated patients featured a decrease in intra- and interhemispheric connectivity of the motor network, which was absent in the M1-stimulation group. Hence, adding iTBS to prime physiotherapy in recovering stroke patients seems to interfere with motor network degradation, possibly reflecting alleviation of post-stroke diaschisis. PMID:26980614

  7. Functional ankle instability as a risk factor for osteoarthritis: using T2-mapping to analyze early cartilage degeneration in the ankle joint of young athletes.

    PubMed

    Golditz, T; Steib, S; Pfeifer, K; Uder, M; Gelse, K; Janka, R; Hennig, F F; Welsch, G H

    2014-10-01

    The aim of this study was to investigate, using T2-mapping, the impact of functional instability in the ankle joint on the development of early cartilage damage. Ethical approval for this study was provided. Thirty-six volunteers from the university sports program were divided into three groups according to their ankle status: functional ankle instability (FAI, initial ankle sprain with residual instability); ankle sprain Copers (initial sprain, without residual instability); and controls (without a history of ankle injuries). Quantitative T2-mapping magnetic resonance imaging (MRI) was performed at the beginning ('early-unloading') and at the end ('late-unloading') of the MR-examination, with a mean time span of 27 min. Zonal region-of-interest T2-mapping was performed on the talar and tibial cartilage in the deep and superficial layers. The inter-group comparisons of T2-values were analyzed using paired and unpaired t-tests. Statistical analysis of variance was performed. T2-values showed significant to highly significant differences in 11 of 12 regions throughout the groups. In early-unloading, the FAI-group showed a significant increase in quantitative T2-values in the medial, talar regions (P = 0.008, P = 0.027), whereas the Coper-group showed this enhancement in the central-lateral regions (P = 0.05). Especially the comparison of early-loading to late-unloading values revealed significantly decreasing T2-values over time laterally and significantly increasing T2-values medially in the FAI-group, which were not present in the Coper- or control-group. Functional instability causes unbalanced loading in the ankle joint, resulting in cartilage alterations as assessed by quantitative T2-mapping. This approach can visualize and localize early cartilage abnormalities, possibly enabling specific treatment options to prevent osteoarthritis in young athletes. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  8. Early cessation of pressure garment therapy results in scar contraction and thickening.

    PubMed

    DeBruler, Danielle M; Zbinden, Jacob C; Baumann, Molly E; Blackstone, Britani N; Malara, Megan M; Bailey, J Kevin; Supp, Dorothy M; Powell, Heather M

    2018-01-01

    Pressure garment therapy is often prescribed to improve scar properties following full-thickness burn injuries. Pressure garment therapy is generally recommended for long periods of time following injury (1-2 years), though it is plagued by extremely low patient compliance. The goal of this study was to examine the effects of early cessation of pressure garment therapy on scar properties. Full-thickness burn injuries were created along the dorsum of red Duroc pigs. The burn eschar was excised and wound sites autografted with split-thickness skin. Scars were treated with pressure garments within 1 week of injury and pressure was maintained for either 29 weeks (continuous pressure) or for 17 weeks followed by cessation of pressure for an additional 12 weeks (pressure released); scars receiving no treatment served as controls. Scars that underwent pressure garment therapy were significantly smoother and less contracted with decreased scar height compared to control scars at 17 weeks. These benefits were maintained in the continuous pressure group until week 29. In the pressure released group, grafts significantly contracted and became more raised, harder and rougher after the therapy was discontinued. Pressure cessation also resulted in large changes in collagen fiber orientation and increases in collagen fiber thickness. The results suggest that pressure garment therapy effectively improves scar properties following severe burn injury; however, early cessation of the therapy results in substantial loss of these improvements.

  9. FRONTIER FIELDS: HIGH-REDSHIFT PREDICTIONS AND EARLY RESULTS

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

    Coe, Dan; Bradley, Larry; Zitrin, Adi, E-mail: DCoe@STScI.edu

    2015-02-20

    The Frontier Fields program is obtaining deep Hubble and Spitzer Space Telescope images of new ''blank'' fields and nearby fields gravitationally lensed by massive galaxy clusters. The Hubble images of the lensed fields are revealing nJy sources (AB mag > 31), the faintest galaxies yet observed. The full program will transform our understanding of galaxy evolution in the first 600 million years (z > 9). Previous programs have yielded a dozen or so z > 9 candidates, including perhaps fewer than expected in the Ultra Deep Field and more than expected in shallower Hubble images. In this paper, we present high-redshift (z >more » 6) number count predictions for the Frontier Fields and candidates in three of the first Hubble images. We show the full Frontier Fields program may yield up to ∼70 z > 9 candidates (∼6 per field). We base this estimate on an extrapolation of luminosity functions observed between 4 < z < 8 and gravitational lensing models submitted by the community. However, in the first two deep infrared Hubble images obtained to date, we find z ∼ 8 candidates but no strong candidates at z > 9. We defer quantitative analysis of the z > 9 deficit (including detection completeness estimates) to future work including additional data. At these redshifts, cosmic variance (field-to-field variation) is expected to be significant (greater than ±50%) and include clustering of early galaxies formed in overdensities. The full Frontier Fields program will significantly mitigate this uncertainty by observing six independent sightlines each with a lensing cluster and nearby blank field.« less

  10. Results of paleomagnetic study of Early Proterozoic rocks in the Baikal Range of the Siberian craton

    NASA Astrophysics Data System (ADS)

    Vodovozov, V. Yu.; Didenko, A. N.; Gladkochub, D. P.; Mazukabzov, A. M.; Donskaya, T. V.

    2007-10-01

    This paper presents paleomagnetic results obtained from the study of Early Proterozoic rocks in the Baikal Range of the Siberian craton, namely, the 1850 1880-Ma volcanicalstic rocks of the Akitkanskian series of the North Baikal volcanic-plutonic belt) and 1674-Ma basic dikes of the Chaya complex within the massif. The data of this work are used to reconstruct the development of the Siberian craton structure in the Early Precambrian. The projections of the inferred paleomagnetic directions onto a sphere form S (southern) and W (western) groups of vectors of characteristic magnetization components. The S group consists of three clusters representing primary magnetization components belonging to different time levels of the end of the Early Proterozoic. The W group is represented by directions associated with a metachronous magnetization probably acquired during the Riphean. Four paleomagnetic poles are obtained. Two of them that can be regarded as key poles correspond to time levels of 1875 and 1670 Ma (the Early Proterozoic). The two other poles can be used for a detailed reconstruction of the Proterozoic segment of the Siberian apparent polar wander path. The data presented in the paper indicate that the formation of the southern Siberian craton structure was accomplished at the end of the Early Proterozoic, which resulted in a synchronous motion of different blocks composing the southern flank of the craton (in particular, the Sharyzhalgai and Baikal Ranges).

  11. Functional Results-Oriented Healthcare Leadership: A Novel Leadership Model

    PubMed Central

    Al-Touby, Salem Said

    2012-01-01

    This article modifies the traditional functional leadership model to accommodate contemporary needs in healthcare leadership based on two findings. First, the article argues that it is important that the ideal healthcare leadership emphasizes the outcomes of the patient care more than processes and structures used to deliver such care; and secondly, that the leadership must strive to attain effectiveness of their care provision and not merely targeting the attractive option of efficient operations. Based on these premises, the paper reviews the traditional Functional Leadership Model and the three elements that define the type of leadership an organization has namely, the tasks, the individuals, and the team. The article argues that concentrating on any one of these elements is not ideal and proposes adding a new element to the model to construct a novel Functional Result-Oriented healthcare leadership model. The recommended Functional-Results Oriented leadership model embosses the results element on top of the other three elements so that every effort on healthcare leadership is directed towards attaining excellent patient outcomes. PMID:22496933

  12. Functional results-oriented healthcare leadership: a novel leadership model.

    PubMed

    Al-Touby, Salem Said

    2012-03-01

    This article modifies the traditional functional leadership model to accommodate contemporary needs in healthcare leadership based on two findings. First, the article argues that it is important that the ideal healthcare leadership emphasizes the outcomes of the patient care more than processes and structures used to deliver such care; and secondly, that the leadership must strive to attain effectiveness of their care provision and not merely targeting the attractive option of efficient operations. Based on these premises, the paper reviews the traditional Functional Leadership Model and the three elements that define the type of leadership an organization has namely, the tasks, the individuals, and the team. The article argues that concentrating on any one of these elements is not ideal and proposes adding a new element to the model to construct a novel Functional Result-Oriented healthcare leadership model. The recommended Functional-Results Oriented leadership model embosses the results element on top of the other three elements so that every effort on healthcare leadership is directed towards attaining excellent patient outcomes.

  13. Prefrontal gray matter morphology mediates the association between serum anticholinergicity and cognitive functioning in early course schizophrenia.

    PubMed

    Wojtalik, Jessica A; Eack, Shaun M; Pollock, Bruce G; Keshavan, Matcheri S

    2012-11-30

    Antipsychotic and other medications used in the treatment of schizophrenia place a burden on the cholinergic subsystems of the brain, which have been associated with increased cognitive impairment in the disorder. This study sought to examine the neurobiologic correlates of the association between serum anticholinergic activity (SAA) and cognitive impairments in early schizophrenia. Neurocognitive performance on measures of memory and executive function, structural magnetic resonance imaging (MRI) scans, and SAA assays were collected from 47 early course, stabilized outpatients with schizophrenia or schizoaffective disorder. Voxel-based morphometry analyses employing general linear models, adjusting for demographic and illness-related confounds, were used to investigate the associations between SAA, gray matter morphology, and neurocognitive impairment. SAA was related to working memory and executive function impairments. Higher SAA was significantly associated with lower gray matter density in broad regions of the frontal and medial-temporal lobes, including the dorsolateral prefrontal cortex (DLPFC), hippocampus, and striatum. Lower gray matter volume in the left DLPFC was found to significantly mediate the association between SAA and working memory impairment. Disease- and/or medication-related cholinergic dysfunction may be associated with brain volume abnormalities in early course schizophrenia, which may account for the association between SAA and cognitive dysfunction in the disorder. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  14. Early reduced myocardial diastolic function in children and adolescents with type 1 diabetes mellitus a population-based study.

    PubMed

    Brunvand, Leif; Fugelseth, Drude; Stensaeth, Knut Håkon; Dahl-Jørgensen, Knut; Margeirsdottir, Hanna Dis

    2016-05-25

    Reduced diastolic myocardial function is an early sign of diabetic cardiomyopathy. The aim of this study was to test the hypothesis that children and adolescents with type 1 diabetes mellitus (T1D), but without other known complications, have early reduced diastolic myocardial function diagnosed with echocardiographic color tissue Doppler imaging (cTDI). cTDI examination was carried out in 173 T1D patients and 62 age-matched controls. The T1D-patients were 8-18 years old with (mean (SD)) diabetes duration of 5.6 (3.4) years and HbA1c of 8.4 (1.3). All were treated with either insulin pumps or 4-6 daily insulin injections. cTDI early (E') and late (A') peak diastolic velocities and systolic peak velocity were measured from the lateral, septal, anterior and posterior mitral annulus and from the lateral tricuspidal annulus. Myocardial diastolic function was reduced in the T1D-patients with higher peak A'-velocity and lower E'/A'-ratio in all registrations. Overall mean (SD) mitral E'/A'-ratio was 2.3 (0.5) in T1D and 2.7 (0.6) in the controls (p < 0001). The overall mitral E'/A'-ratio was negative associated with blood pressure (BP) and body mass index (BMI). Stratifying all participants into three groups according to BMI (<25, 25-75, >75 centile, respectively), the T1D had lower E'/A'-values in all stratified groups, except for in the highest BMI-group where both T1D and controls had the lowest E'/A'-ratio. Systolic function did not differ in any of the measurements. There were no associations with sex, diabetes duration, carotid artery intima-media-thickness, vessel elasticity or HbA1c. Diabetic children and adolescents using modern intensive insulin treatment had echocardiographic signs of reduced diastolic myocardial function despite short duration of disease. The reduced function was associated with higher BP and higher BMI.

  15. Virtual multiple errands test (VMET): a virtual reality-based tool to detect early executive functions deficit in Parkinson's disease.

    PubMed

    Cipresso, Pietro; Albani, Giovanni; Serino, Silvia; Pedroli, Elisa; Pallavicini, Federica; Mauro, Alessandro; Riva, Giuseppe

    2014-01-01

    Several recent studies have pointed out that early impairment of executive functions (EFs) in Parkinson's Disease (PD) may be a crucial marker to detect patients at risk for developing dementia. The main objective of this study was to compare the performances of PD patients with mild cognitive impairment (PD-MCI) with PD patients with normal cognition (PD-NC) and a control group (CG) using a traditional assessment of EFs and the Virtual Multiple Errands Test (VMET), a virtual reality (VR)-based tool. In order to understand which subcomponents of EFs are early impaired, this experimental study aimed to investigate specifically which instrument best discriminates among these three groups. The study included three groups of 15 individuals each (for a total of 45 participants): 15 PD-NC; 15 PD-MCI, and 15 cognitively healthy individuals (CG). To assess the global neuropsychological functioning and the EFs, several tests (including the Mini Mental State Examination (MMSE), Clock Drawing Test, and Tower of London test) were administered to the participants. The VMET was used for a more ecologically valid neuropsychological evaluation of EFs. Findings revealed significant differences in the VMET scores between the PD-NC patients vs. the controls. In particular, patients made more errors in the tasks of the VMET, and showed a poorer ability to use effective strategies to complete the tasks. This VMET result seems to be more sensitive in the early detection of executive deficits because these two groups did not differ in the traditional assessment of EFs (neuropsychological battery). This study offers initial evidence that a more ecologically valid evaluation of EFs is more likely to lead to detection of subtle executive deficits.

  16. A population-based prospective cohort study examining the influence of early-life respiratory tract infections on school-age lung function and asthma.

    PubMed

    van Meel, Evelien R; den Dekker, Herman T; Elbert, Niels J; Jansen, Pauline W; Moll, Henriëtte A; Reiss, Irwin K; de Jongste, Johan C; Jaddoe, Vincent W V; Duijts, Liesbeth

    2018-02-01

    Early-life respiratory tract infections could affect airway obstruction and increase asthma risk in later life. However, results from previous studies are inconsistent. We examined the associations of early-life respiratory tract infections with lung function and asthma in school-aged children. This study among 5197 children born between April 2002 and January 2006 was embedded in a population-based prospective cohort study. Information on physician-attended upper and lower respiratory tract infections until age 6 years (categorised into ≤ 3 and >3-6 years) was obtained by annual questionnaires. Spirometry measures and physician-diagnosed asthma were assessed at age 10 years. Upper respiratory tract infections were not associated with adverse respiratory outcomes. Compared with children without lower respiratory tract infections ≤3 years, children with lower respiratory tract infections ≤3 years had a lower FEV 1 , FVC, FEV 1 :FVC and forced expiratory flow at 75% of FVC (FEF 75 ) (Z-score (95% CI): ranging from -0.22 (-0.31 to -0.12) to -0.12 (-0.21 to -0.03)) and an increased risk of asthma (OR (95% CI): 1.79 (1.19 to 2.59)). Children with lower respiratory tract infections >3-6 years had an increased risk of asthma (3.53 (2.37 to 5.17)) only. Results were not mediated by antibiotic or paracetamol use and not modified by inhalant allergic sensitisation. Cross-lagged modelling showed that results were not bidirectional and independent of preschool wheezing patterns. Early-life lower respiratory tract infections ≤3 years are most consistently associated with lower lung function and increased risk of asthma in school-aged children. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  17. Early Executive Function and Mathematics Relations: Correlation Does Not Ensure Concordance.

    PubMed

    Mazzocco, Michèle M M; Chan, Jenny Yun-Chen; Bock, Allison M

    2017-01-01

    In this chapter, we address one potentially overlooked component of the relation between executive function (EF) skills and early mathematics, a relation for which there is widespread empirical support. Evidence for this relation has, thus far, been largely correlational. Here we emphasize that because positive correlations do not guarantee concordance among all members of a sample or population, a small but meaningful number of children may either fare well in mathematics despite poor EF skills, or may have strong EF skills despite weak mathematics skills. We propose that attention to different profiles of discordance for EF and mathematics may help identify individualized learning needs for students at risk for mathematics difficulties and disabilities. © 2017 Elsevier Inc. All rights reserved.

  18. The prosocial functions of early social emotions: the case of guilt.

    PubMed

    Vaish, Amrisha

    2018-04-01

    To safeguard human cooperation, it is vital that when cooperative relationships break down, they are repaired. This requirement is met by the social emotion of guilt, at two levels: the experience of guilt motivates transgressors to repair the damage they have caused, and transgressors' displays of guilt appease victims and bystanders and elicit cooperation toward the transgressor. I review recent evidence that guilt functions in both of these ways from early in development. The experience of guilt motivates reparative behavior in children 2-3 years of age, and transgressors' displays of guilt appease and elicit cooperation in children 4-5 years of age. Thus, over the first few years of ontogeny, guilt becomes an important mechanism for upholding cooperation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Managing Student Behavior with Class-Wide Function-Related Intervention Teams: An Observational Study in Early Elementary Classrooms

    ERIC Educational Resources Information Center

    Caldarella, Paul; Williams, Leslie; Hansen, Blake D.; Wills, Howard

    2015-01-01

    Comprehensive evidence-based interventions are needed to help early childhood educators manage challenging student behaviors. One such intervention, class-wide function-related intervention teams (CW-FIT), is a multi-tiered behavioral intervention program based on positive behavior support principles, including four main elements: (a) teaching…

  20. A prospective cohort study among new Chinese coal miners: the early pattern of lung function change.

    PubMed

    Wang, M-L; Wu, Z-E; Du, Q-G; Petsonk, E L; Peng, K-L; Li, Y-D; Li, S-K; Han, G-H; Atffield, M D

    2005-11-01

    To investigate the early pattern of longitudinal change in forced expiratory volume in 1 second (FEV1) among new Chinese coal miners, and the relation between coal mine dust exposure and the decline of lung function. The early pattern of lung function changes in 317 newly hired Chinese underground coal miners was compared to 132 referents. This three year prospective cohort study involved a pre-employment and 15 follow up health surveys, including a questionnaire and spirometry tests. Twice a month, total and respirable dust area sampling was done. The authors used a two stage analysis and a linear mixed effects model approach to analyse the longitudinal spirometry data, and to investigate the changes in FEV1 over time, controlling for age, height, pack years of smoking, mean respirable dust concentration, the room temperature during testing, and the groupxtime interaction terms. FEV1 change over time in new miners is non-linear. New miners experience initial rapid FEV1 declines, primarily during the first year of mining, little change during the second year, and partial recovery during the third year. Both linear and quadratic time trends in FEV1 change are highly significant. Smoking miners lost more FEV1 than non-smokers. Referents, all age less than 20 years, showed continued lung growth, whereas the miners who were under age 20 exhibited a decline in FEV1. Dust and smoking affect lung function in young, newly hired Chinese coal miners. FEV1 change over the first three years of employment is non-linear. The findings have implications for both methods and interpretation of medical screening in coal mining and other dusty work: during the first several years of employment more frequent testing may be desirable, and caution is required in interpreting early FEV1 declines.

  1. Early functional outcome of a modified Brostrom-Gould surgery using bioabsorbable suture anchor for chronic lateral ankle instability.

    PubMed

    Shahrulazua, A; Ariff Sukimin, M S; Tengku Muzaffar, T M; Yusof, M I

    2010-03-01

    The purpose of this study was to evaluate the early functional outcome following the use of a bioabsorbable suture anchor to simplify the repair of injured lateral ankle structures as a variation of an established technique known as the Brostrom-Gould procedure. This was a prospective study of 30 ankles with chronic lateral instability that underwent a modified Brostrom-Gould surgery using a bioabsorbable suture anchor, performed by a single surgeon. A total of 29 patients, aged 15 to 52 (mean is 33) years, were enrolled in the study. The follow-up period ranged from three to six (mean is four) months. The function of the patients' ankles was scored using the Kaikkonen Functional Scale, both preoperatively and postoperatively. Preoperatively, all ankles had poor scores (less than 50). Postoperatively, 28 ankles showed excellent scores and two ankles showed good scores, while none obtained a fair or poor score. The difference in the overall means between the postoperative and preoperative scores was statistically significant (p-value is 0.001). Post surgery, 24 ankles had no symptoms, while six had only mild ankle tightness with extreme inversion movement at the last review. All patients were able to walk normally, and 29 ankles regained their normal running capability. There was marked improvement in the ability to descend stairs, to rise on heels and toes, to perform a single-limb stance, and in range of motions of the ankle dorsiflexion as well as in ankle laxity. The modified Brostrom-Gould procedure using a bioabsorbable suture anchor allowed for early ankle rehabilitation and offered a reproducible and excellent early functional outcome with minimal complications.

  2. Adverse effects of meglumine diatrizoate on renal function in the early post-transplant period.

    PubMed

    Light, J A; Perloff, L J; Etheredge, E E; Hill, G; Spees, E K

    1975-11-01

    Thirty-four renal transplant recipients received drip infusion urograms from 2-24 days post-transplantation. Twenty-two patients exhibited changes in renal function within 1-4 days of the urogram that were indistinguishable from allograft rejection: a tender, swollen kidney, elevation of serum creatinine, oliguria, decreased urine sodium concentration, weight gain, and hypertension. Two patients developed acute tubular necrosis and required hemodialysis, but renal function in the remaining 20 patients improved after therapy for "graft rejection" with i.v. methyprednisolone sodium succinnate. Kidneys from older-age donors that were functioning suboptimally and kidneys which exhibited subsequent clinical allograft rejection were more at risk for contrast media toxicity. This suggests that occult vascular lesions may have been present in the allograft which were exacerbated when exposed to the irritant vascular effects of contrast media, producing a mild, reversible toxic nephritis. However, several kidneys with normal function and several kidneys which never exhibited rejection activity were also adversely affected by exposure to contrast media. It appears these agents should be used cautiously, if at all, in the early post-transplant period.

  3. The early and midterm function of decellularized aortic valve allografts.

    PubMed

    da Costa, Francisco D A; Costa, Ana Claudia B A; Prestes, Roberta; Domanski, Ana Carolina; Balbi, Eduardo Mendel; Ferreira, Andreia D A; Lopes, Sergio Veiga

    2010-12-01

    This study evaluates the early and midterm results of decellularized aortic valve allografts (DAVA) as an aortic valve replacement. Between October 2005 and February 2010, 41 patients, 28 of whom were male, with a median age of 34 years (range, 0.1 to 71), had aortic valve replacement with DAVA. Decellularization was obtained with a 0.1% sodium dodecyl sulfate solution. Postoperative evaluation was performed with serial echocardiograms, magnetic resonance imaging, and multislice computed tomography studies to evaluate valve hemodynamics, allograft conduit dimensions, and calcification scores. There were 3 early deaths and 1 late death, with a mean follow-up of 19 months (range, 1 to 53). There was 1 reoperation due to a failed mitral valve repair. By echocardiography in all patients, the median immediate postoperative peak gradient was 7 mm Hg (range, 1 to 26 mm Hg), and at last follow-up it was 4 mm Hg (range, 1 to 16 mm Hg); valvular regurgitation was graded as none or trivial in all but 1 patient, who had a regurgitation graded as mild to moderate. By magnetic resonance imaging (n = 4), mean root dimensions were stable at the annulus (24 mm), sinus of Valsalva (33 mm), and sinotubular junction (28 mm). By computed tomography (n = 22), there was only discrete conduit calcification (median calcium score 63 Hounsfield units [HU]; range, 0 to 894 HU) to 3 years of follow-up. Conduit biopsy in the patient who underwent reoperation demonstrated well-preserved wall structure, absence of calcification, and limited in vivo host repopulation. The early and midterm results with DAVA demonstrated stable structural integrity, low rate of calcification, and adequate hemodynamics. Although longer periods of observation are necessary, DAVA appears to be a promising alternative for aortic valve replacement in selected patients. Copyright © 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  4. Early Parenting and the Development of Externalizing Behavior Problems: Longitudinal Mediation through Children’s Executive Function

    PubMed Central

    Sulik, Michael J.; Blair, Clancy; Mills-Koonce, Roger; Berry, Daniel; Greenberg, Mark

    2015-01-01

    Path analysis was used to investigate the longitudinal associations among parenting and children’s executive function and externalizing behavior problems from 36 to 90 months of age in the Family Life Project (N = 1,115), a study of child development in the context of rural poverty. While controlling for stability in the constructs, semi-structured observations of parenting prospectively predicted performance on a battery of executive function tasks and primary caregivers’ reports of externalizing behavior. Furthermore, the association between early parenting and later externalizing behavior was longitudinally mediated by executive function, providing support for a process model in which sensitive parenting promotes children’s self-regulation, which in turn reduces children’s externalizing behavior. PMID:26082032

  5. POSNA Quality Safety Value Initiative: From Vision to Implementation to Early Results.

    PubMed

    Waters, Peter M; Flynn, John M

    2015-01-01

    The POSNA Quality, Safety and Value Initiative (QSVI) formally started with POSNA board approval in early 2011. The initial vision statement was: "To lead in defining our members' value based clinical care. To partner with hospital based and orthopedic organizational efforts to guarantee safe, high quality outcomes for our patients. To communicate our initiatives and results cooperatively with payer, credentialing, and compliance organizations to improve pediatric orthopedic care in North America."

  6. The Associations among Preschool Children's Growth in Early Reading, Executive Function, and Invented Spelling Skills

    ERIC Educational Resources Information Center

    Zhang, Chenyi; Bingham, Gary E.; Quinn, Margaret F.

    2017-01-01

    The purpose of the present study was to examine associations among children's emergent literacy (early reading), language, executive function (EF), and invented spelling skills across prekindergarten. Participants included 123, primarily African American, 4-year-old children enrolled in a variety of prekindergarten settings. In addition to…

  7. Establishing Early Functional Perfusion and Structure in Tissue Engineered Cardiac Constructs

    PubMed Central

    Wang, Bo; Patnaik, Sourav S.; Brazile, Bryn; Butler, J. Ryan; Claude, Andrew; Zhang, Ge; Guan, Jianjun; Hong, Yi; Liao, Jun

    2016-01-01

    Myocardial infarction (MI) causes massive heart muscle death and remains a leading cause of death in the world. Cardiac tissue engineering aims to replace the infarcted tissues with functional engineered heart muscles or revitalize the infarcted heart by delivering cells, bioactive factors, and/or biomaterials. One major challenge of cardiac tissue engineering and regeneration is the establishment of functional perfusion and structure to achieve timely angiogenesis and effective vascularization, which are essential to the survival of thick implants and the integration of repaired tissue with host heart. In this paper, we review four major approaches to promoting angiogenesis and vascularization in cardiac tissue engineering and regeneration: delivery of pro-angiogenic factors/molecules, direct cell implantation/cell sheet grafting, fabrication of prevascularized cardiac constructs, and the use of bioreactors to promote angiogenesis and vascularization. We further provide a detailed review and discussion on the early perfusion design in nature-derived biomaterials, synthetic biodegradable polymers, tissue-derived acellular scaffolds/whole hearts, and hydrogel derived from extracellular matrix. A better understanding of the current approaches and their advantages, limitations, and hurdles could be useful for developing better materials for future clinical applications. PMID:27480586

  8. Establishing Early Functional Perfusion and Structure in Tissue Engineered Cardiac Constructs.

    PubMed

    Wang, Bo; Patnaik, Sourav S; Brazile, Bryn; Butler, J Ryan; Claude, Andrew; Zhang, Ge; Guan, Jianjun; Hong, Yi; Liao, Jun

    2015-01-01

    Myocardial infarction (MI) causes massive heart muscle death and remains a leading cause of death in the world. Cardiac tissue engineering aims to replace the infarcted tissues with functional engineered heart muscles or revitalize the infarcted heart by delivering cells, bioactive factors, and/or biomaterials. One major challenge of cardiac tissue engineering and regeneration is the establishment of functional perfusion and structure to achieve timely angiogenesis and effective vascularization, which are essential to the survival of thick implants and the integration of repaired tissue with host heart. In this paper, we review four major approaches to promoting angiogenesis and vascularization in cardiac tissue engineering and regeneration: delivery of pro-angiogenic factors/molecules, direct cell implantation/cell sheet grafting, fabrication of prevascularized cardiac constructs, and the use of bioreactors to promote angiogenesis and vascularization. We further provide a detailed review and discussion on the early perfusion design in nature-derived biomaterials, synthetic biodegradable polymers, tissue-derived acellular scaffolds/whole hearts, and hydrogel derived from extracellular matrix. A better understanding of the current approaches and their advantages, limitations, and hurdles could be useful for developing better materials for future clinical applications.

  9. Pulmonary function, respiratory symptoms, and dust exposures among workers engaged in early manufacturing processes of tea: a cohort study.

    PubMed

    Shieh, Tzong-Shiun; Chung, Jui-Jung; Wang, Chung-Jing; Tsai, Perng-Jy; Kuo, Yau-Chang; Guo, How-Ran

    2012-02-13

    To evaluate pulmonary function and respiratory symptoms in workers engaged in the early manufacturing processes of tea and to identify the associated factors, we conducted a study in a tea production area in Taiwan. We recruited tea workers who engaged in the early manufacturing process in the Mountain Ali area in Taiwan and a comparison group of local office workers who were matched for age, gender, and smoking habits. We performed questionnaire interviews, pulmonary function tests, skin prick tests, and measurement of specific IgE for tea on the participants and assessed tea dust exposures in the tea factories. The 91 participating tea workers had higher prevalence of respiratory symptoms than the comparison group (32 participants). Among tea workers, ball-rolling workers had the highest prevalence of symptoms and the highest exposures of inhalable dusts. At baseline, tea workers had similar pulmonary functions as the comparison group, but compared to the other tea workers ball-rolling workers had a lower ratio of the 1-second forced expiratory volume to forced vital capacity (FEV1/FVC) and a lower maximal mid-expiratory flow rate expressed as% of the predicted value--MMF (%pred). A total of 58 tea workers participated in the on-site investigation and the cross-shift lung function measurements. We found ball-rolling yielded the highest inhalable dust level, panning yielded the highest respirable dust level, and withering yielded the lowest levels of both dusts. Ball-rolling also yielded the highest coarse fraction (defined as inhalable dusts minus respirable dusts), which represented exposures from nose to tracheobronchial tract. During the shift, we observed significant declines in pulmonary function, especially in ball-rolling workers. Multiple regressions showed that age, height, work tasks, coarse fraction, and number of months working in tea manufacturing each year were independent predictors of certain pulmonary function parameters in tea workers. Tea

  10. Hygiene and other early childhood influences on the subsequent function of the immune system.

    PubMed

    Rook, Graham A W; Lowry, Christopher A; Raison, Charles L

    2015-08-18

    The immune system influences brain development and function. Hygiene and other early childhood influences impact the subsequent function of the immune system during adulthood, with consequences for vulnerability to neurodevelopmental and psychiatric disorders. Inflammatory events during pregnancy can act directly to cause developmental problems in the central nervous system (CNS) that have been implicated in schizophrenia and autism. The immune system also acts indirectly by "farming" the intestinal microbiota, which then influences brain development and function via the multiple pathways that constitute the gut-brain axis. The gut microbiota also regulates the immune system. Regulation of the immune system is crucial because inflammatory states in pregnancy need to be limited, and throughout life inflammation needs to be terminated completely when not required; for example, persistently raised levels of background inflammation during adulthood (in the presence or absence of a clinically apparent inflammatory stimulus) correlate with an increased risk of depression. A number of factors in the perinatal period, notably immigration from rural low-income to rich developed settings, caesarean delivery, breastfeeding and antibiotic abuse have profound effects on the microbiota and on immunoregulation during early life that persist into adulthood. Many aspects of the modern western environment deprive the infant of the immunoregulatory organisms with which humans co-evolved, while encouraging exposure to non-immunoregulatory organisms, associated with more recently evolved "crowd" infections. Finally, there are complex interactions between perinatal psychosocial stressors, the microbiota, and the immune system that have significant additional effects on both physical and psychiatric wellbeing in subsequent adulthood. This article is part of a Special Issue entitled Neuroimmunology in Health And Disease. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights

  11. Cancer-specific self-efficacy and psychosocial and functional adaptation to early stage breast cancer.

    PubMed

    Manne, Sharon L; Ostroff, Jamie S; Norton, Tina R; Fox, Kevin; Grana, Generosa; Goldstein, Lori

    2006-04-01

    Although self-efficacy is considered a key psychological resource in adapting to chronic physical illness, this construct has received less attention among individuals coping with cancer. To examine changes in cancer self-efficacy over time among women with early stage breast cancer and associations between task-specific domains of self-efficacy and specific psychological, relationship, and functional outcomes. Ninety-five women diagnosed with early stage breast cancer completed surveys postsurgery and 1 year later. Cancer-related self-efficacy was relatively stable over 1 year, with only 2 domains of efficacy-(a) Activity Management and (b) Self-Satisfaction-evidencing significant increases over the 1-year time period. Cross-sectional findings were relatively consistent with predictions and suggested that specific domains of self-efficacy were more strongly related to relevant domains of adaptation. Longitudinal findings were not as consistent with the domain-specificity hypothesis but did suggest several predictive associations between self-efficacy and outcomes. Personal Management self-efficacy was associated with higher relationship satisfaction, higher Communication Self-Efficacy was associated with less functional impairment, and higher Affective Management self-efficacy was associated with higher self-esteem 1 year later. Specific domains of cancer-related self-efficacy are most closely related to relevant areas of adaptation when considered cross-sectionally, but further study is needed to clarify the nature of these relationships over time.

  12. Evolution of human brain functions: the functional structure of human consciousness.

    PubMed

    Cloninger, C Robert

    2009-11-01

    The functional structure of self-aware consciousness in human beings is described based on the evolution of human brain functions. Prior work on heritable temperament and character traits is extended to account for the quantum-like and holographic properties (i.e. parts elicit wholes) of self-aware consciousness. Cladistic analysis is used to identify the succession of ancestors leading to human beings. The functional capacities that emerge along this lineage of ancestors are described. The ecological context in which each cladogenesis occurred is described to illustrate the shifting balance of evolution as a complex adaptive system. Comparative neuroanatomy is reviewed to identify the brain structures and networks that emerged coincident with the emergent brain functions. Individual differences in human temperament traits were well developed in the common ancestor shared by reptiles and humans. Neocortical development in mammals proceeded in five major transitions: from early reptiles to early mammals, early primates, simians, early Homo, and modern Homo sapiens. These transitions provide the foundation for human self-awareness related to sexuality, materiality, emotionality, intellectuality, and spirituality, respectively. The functional structure of human self-aware consciousness is concerned with the regulation of five planes of being: sexuality, materiality, emotionality, intellectuality, and spirituality. Each plane elaborates neocortical functions organized around one of the five special senses. The interactions among these five planes gives rise to a 5 x 5 matrix of subplanes, which are functions that coarsely describe the focus of neocortical regulation. Each of these 25 neocortical functions regulates each of five basic motives or drives that can be measured as temperaments or basic emotions related to fear, anger, disgust, surprise, and happiness/sadness. The resulting 5 x 5 x 5 matrix of human characteristics provides a general and testable model of the

  13. Impact of Early Life Adversity on Reward Processing in Young Adults: EEG-fMRI Results from a Prospective Study over 25 Years

    PubMed Central

    Boecker, Regina; Holz, Nathalie E.; Buchmann, Arlette F.; Blomeyer, Dorothea; Plichta, Michael M.; Wolf, Isabella; Baumeister, Sarah; Meyer-Lindenberg, Andreas; Banaschewski, Tobias

    2014-01-01

    Several lines of evidence have implicated the mesolimbic dopamine reward pathway in altered brain function resulting from exposure to early adversity. The present study examined the impact of early life adversity on different stages of neuronal reward processing later in life and their association with a related behavioral phenotype, i.e. attention deficit/hyperactivity disorder (ADHD). 162 healthy young adults (mean age = 24.4 years; 58% female) from an epidemiological cohort study followed since birth participated in a simultaneous EEG-fMRI study using a monetary incentive delay task. Early life adversity according to an early family adversity index (EFA) and lifetime ADHD symptoms were assessed using standardized parent interviews conducted at the offspring's age of 3 months and between 2 and 15 years, respectively. fMRI region-of-interest analysis revealed a significant effect of EFA during reward anticipation in reward-related areas (i.e. ventral striatum, putamen, thalamus), indicating decreased activation when EFA increased. EEG analysis demonstrated a similar effect for the contingent negative variation (CNV), with the CNV decreasing with the level of EFA. In contrast, during reward delivery, activation of the bilateral insula, right pallidum and bilateral putamen increased with EFA. There was a significant association of lifetime ADHD symptoms with lower activation in the left ventral striatum during reward anticipation and higher activation in the right insula during reward delivery. The present findings indicate a differential long-term impact of early life adversity on reward processing, implicating hyporesponsiveness during reward anticipation and hyperresponsiveness when receiving a reward. Moreover, a similar activation pattern related to lifetime ADHD suggests that the impact of early life stress on ADHD may possibly be mediated by a dysfunctional reward pathway. PMID:25118701

  14. Nonsurgical treatment and early return to activity leads to improved Achilles tendon fatigue mechanics and functional outcomes during early healing in an animal model.

    PubMed

    Freedman, Benjamin R; Gordon, Joshua A; Bhatt, Pankti R; Pardes, Adam M; Thomas, Stephen J; Sarver, Joseph J; Riggin, Corinne N; Tucker, Jennica J; Williams, Alexis W; Zanes, Robert C; Hast, Michael W; Farber, Daniel C; Silbernagel, Karin G; Soslowsky, Louis J

    2016-12-01

    Achilles tendon ruptures are common and devastating injuries; however, an optimized treatment and rehabilitation protocol has yet to be defined. Therefore, the objective of this study was to investigate the effects of surgical repair and return to activity on joint function and Achilles tendon properties after 3 weeks of healing. Sprague-Dawley rats (N = 100) received unilateral blunt transection of their Achilles tendon. Animals were then randomized into repaired or non-repaired treatments, and further randomized into groups that returned to activity after 1 week (RTA1) or after 3 weeks (RTA3) of limb casting in plantarflexion. Limb function, passive joint mechanics, and tendon properties (mechanical, organizational using high frequency ultrasound, histological, and compositional) were evaluated. Results showed that both treatment and return to activity collectively affected limb function, passive joint mechanics, and tendon properties. Functionally, RTA1 animals had increased dorsiflexion ROM and weight bearing of the injured limb compared to RTA3 animals 3-weeks post-injury. Such functional improvements in RTA1 tendons were evidenced in their mechanical fatigue properties and increased cross sectional area compared to RTA3 tendons. When RTA1 was coupled with nonsurgical treatment, superior fatigue properties were achieved compared to repaired tendons. No differences in cell shape, cellularity, GAG, collagen type I, or TGF-β staining were identified between groups, but collagen type III was elevated in RTA3 repaired tendons. The larger tissue area and increased fatigue resistance created in RTA1 tendons may prove critical for optimized outcomes in early Achilles tendon healing following complete rupture. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2172-2180, 2016. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  15. Early cessation of pressure garment therapy results in scar contraction and thickening

    PubMed Central

    DeBruler, Danielle M.; Zbinden, Jacob C.; Baumann, Molly E.; Blackstone, Britani N.; Malara, Megan M.; Bailey, J. Kevin

    2018-01-01

    Pressure garment therapy is often prescribed to improve scar properties following full-thickness burn injuries. Pressure garment therapy is generally recommended for long periods of time following injury (1–2 years), though it is plagued by extremely low patient compliance. The goal of this study was to examine the effects of early cessation of pressure garment therapy on scar properties. Full-thickness burn injuries were created along the dorsum of red Duroc pigs. The burn eschar was excised and wound sites autografted with split-thickness skin. Scars were treated with pressure garments within 1 week of injury and pressure was maintained for either 29 weeks (continuous pressure) or for 17 weeks followed by cessation of pressure for an additional 12 weeks (pressure released); scars receiving no treatment served as controls. Scars that underwent pressure garment therapy were significantly smoother and less contracted with decreased scar height compared to control scars at 17 weeks. These benefits were maintained in the continuous pressure group until week 29. In the pressure released group, grafts significantly contracted and became more raised, harder and rougher after the therapy was discontinued. Pressure cessation also resulted in large changes in collagen fiber orientation and increases in collagen fiber thickness. The results suggest that pressure garment therapy effectively improves scar properties following severe burn injury; however, early cessation of the therapy results in substantial loss of these improvements. PMID:29897933

  16. Rotigotine Effects on Early Morning Motor Function and Sleep in Parkinson's Disease: A Double-Blind, Randomized, pLacebo-Controlled Study (RECOVER)

    PubMed Central

    Trenkwalder, Claudia; Kies, Bryan; Rudzinska, Monika; Fine, Jennifer; Nikl, Janos; Honczarenko, Krystyna; Dioszeghy, Peter; Hill, Dennis; Anderson, Tim; Myllyla, Vilho; Kassubek, Jan; Steiger, Malcolm; Zucconi, Marco; Tolosa, Eduardo; Poewe, Werner; Surmann, Erwin; Whitesides, John; Boroojerdi, Babak; Chaudhuri, Kallol Ray

    2011-01-01

    In a multinational, double-blind, placebo-controlled trial (NCT00474058), 287 subjects with Parkinson's disease (PD) and unsatisfactory early-morning motor symptom control were randomized 2:1 to receive rotigotine (2–16 mg/24 hr [n = 190]) or placebo (n = 97). Treatment was titrated to optimal dose over 1–8 weeks with subsequent dose maintenance for 4 weeks. Early-morning motor function and nocturnal sleep disturbance were assessed as coprimary efficacy endpoints using the Unified Parkinson's Disease Rating Scale (UPDRS) Part III (Motor Examination) measured in the early morning prior to any medication intake and the modified Parkinson's Disease Sleep Scale (PDSS-2) (mean change from baseline to end of maintenance [EOM], last observation carried forward). At EOM, mean UPDRS Part III score had decreased by −7.0 points with rotigotine (from a baseline of 29.6 [standard deviation (SD) 12.3] and by −3.9 points with placebo (baseline 32.0 [13.3]). Mean PDSS-2 total score had decreased by −5.9 points with rotigotine (from a baseline of 19.3 [SD 9.3]) and by −1.9 points with placebo (baseline 20.5 [10.4]). This represented a significantly greater improvement with rotigotine compared with placebo on both the UPDRS Part III (treatment difference: −3.55 [95% confidence interval (CI) −5.37, −1.73]; P = 0.0002) and PDSS-2 (treatment difference: −4.26 [95% CI −6.08, −2.45]; P < 0.0001). The most frequently reported adverse events were nausea (placebo, 9%; rotigotine, 21%), application site reactions (placebo, 4%; rotigotine, 15%), and dizziness (placebo, 6%; rotigotine 10%). Twenty-four-hour transdermal delivery of rotigotine to PD patients with early-morning motor dysfunction resulted in significant benefits in control of both motor function and nocturnal sleep disturbances. © 2010 Movement Disorder Society PMID:21322021

  17. Early arthroscopic release in stiff shoulder

    PubMed Central

    Sabat, Dhananjaya; Kumar, Vinod

    2008-01-01

    Purpose: To evaluate the results of early arthroscopic release in the patients of stiff shoulder Methods: Twenty patients of stiff shoulder, who had symptoms for at least three months and failed to improve with steroid injections and physical therapy of 6 weeks duration, underwent arthroscopic release. The average time between onset of symptoms and the time of surgery was 4 months and 2 weeks. The functional outcome was evaluated using ASES and Constant and Murley scoring systems. Results: All the patients showed significant improvement in the range of motion and relief of pain by end of three months following the procedure. At 12 months, mean improvement in ASES score is 38 points and Constant and Murley score is 4O.5 points. All patients returned to work by 3-5 months (average -4.5 months). Conclusion: Early arthroscopic release showed promising results with reliable increase in range of motion, early relief of symptoms and consequent early return to work. So it is highly recommended in properly selected patients. Level of evidence: Level IV PMID:20300309

  18. A progressive 5-week exercise therapy program leads to significant improvement in knee function early after anterior cruciate ligament injury.

    PubMed

    Eitzen, Ingrid; Moksnes, Håvard; Snyder-Mackler, Lynn; Risberg, May Arna

    2010-11-01

    Prospective cohort study without a control group. Firstly, to present our 5-week progressive exercise therapy program in the early stage after anterior cruciate ligament (ACL) injury. Secondly, to evaluate changes in knee function after completion of the program for patients with ACL injury in general and also when classified as potential copers or noncopers, and, finally, to examine potential adverse events. Few studies concerning early-stage ACL rehabilitation protocols exist. Consequently, little is known about the tolerance for, and outcomes from, short-term exercise therapy programs in the early stage after injury. One-hundred patients were included in a 5-week progressive exercise therapy program, within 3 months after injury. Knee function before and after completion of the program was evaluated from isokinetic quadriceps and hamstrings muscle strength tests, 4 single-leg hop tests, 2 different self-assessment questionnaires, and a global rating of knee function. A 2-way mixed-model analysis of variance was conducted to evaluate changes from pretest to posttest for the limb symmetry index for muscle strength and single-leg hop tests, and the change in scores for the patient-reported questionnaires. In addition, absolute values and the standardized response mean for muscle strength and single-leg hop tests were calculated at pretest and posttest for the injured and uninjured limb. Adverse events during the 5-week period were recorded. The progressive 5-week exercise therapy program led to significant improvements (P<.05) in knee function from pretest to posttest both for patients classified as potential copers and noncopers. Standardized response mean values for changes in muscle strength and single-leg hop performance from pretest to posttest for the injured limb were moderate to strong (0.49-0.84), indicating the observed improvements to be clinically relevant. Adverse events occurred in 3.9% of the patients. Short-term progressive exercise therapy programs

  19. Uric acid lowering to prevent kidney function loss in diabetes: the preventing early renal function loss (PERL) allopurinol study.

    PubMed

    Maahs, David M; Caramori, Luiza; Cherney, David Z I; Galecki, Andrzej T; Gao, Chuanyun; Jalal, Diana; Perkins, Bruce A; Pop-Busui, Rodica; Rossing, Peter; Mauer, Michael; Doria, Alessandro

    2013-08-01

    Diabetic kidney disease causes significant morbidity and mortality among people with type 1 diabetes (T1D). Intensive glucose and blood pressure control have thus far failed to adequately curb this problem and therefore a major need for novel treatment approaches exists. Multiple observations link serum uric acid levels to kidney disease development and progression in diabetes and strongly argue that uric acid lowering should be tested as one such novel intervention. A pilot of such a trial, using allopurinol, is currently being conducted by the Preventing Early Renal Function Loss (PERL) Consortium. Although the PERL trial targets T1D individuals at highest risk of kidney function decline, the use of allopurinol as a renoprotective agent may also be relevant to a larger segment of the population with diabetes. As allopurinol is inexpensive and safe, it could be cost-effective even for relatively low-risk patients, pending the completion of appropriate trials at earlier stages.

  20. The stressful (and not so stressful) nature of language brokering: identifying when brokering functions as a cultural stressor for Latino immigrant children in early adolescence.

    PubMed

    Kam, Jennifer A; Lazarevic, Vanja

    2014-12-01

    Language brokering remains prevalent among immigrant families, but it is widely assumed that brokering functions as a cultural stressor, resulting in adverse health outcomes for immigrant youth. Few studies, however, have tested this assumption, particularly while using longitudinal data and capturing multiple dimensions of brokering. Thus, this study examined how depressive symptoms and family-based acculturation stress mediated the relationships between various aspects of brokering (i.e., frequency of brokering, positive and negative feelings about brokering, brokering norms, and brokering efficacy) and alcohol, cigarette, and marijuana use and other risky behaviors. Using longitudinal survey data from 234 Latino early adolescents in 6th-8th grades (M age  = 12.4 years; Females = 46.2 %), brokering for parents indirectly affected alcohol and marijuana use through family-based acculturation stress; however, these significant indirect effects became non-significant when taking into account negative brokering feelings and brokering as a burden on one's time. Feeling positively or efficacious about brokering or having pro-brokering norms did not directly predict any adverse mental and behavioral health outcomes. Moderation analyses, however, revealed that brokering for parents did not seem to function as a stressor when Latino early adolescents were high in brokering efficacy (e.g., feeling confident in one's ability to broker) or descriptive brokering norms (e.g., perceiving one's peers as brokering often). By contrast, when Latino early adolescents perceived brokering as a burden, brokering for parents functioned as a stressor, placing Latino early adolescents at risk for family-based acculturation stress, and in turn, alcohol and marijuana use. Such findings point to the complexity of brokering.

  1. How has early testicular cancer affected your life? A study of sexual function in men attending active surveillance for stage one testicular cancer.

    PubMed

    Brand, Sue; Williams, Hilary; Braybrooke, Jeremy

    2015-06-01

    Testicular cancer is the most common cancer in young men, it is frequently diagnosed at key times in relationship formation. In early stage disease the vast majority of tumours will be cured by surgery alone with patients being offered active surveillance rather than adjuvant therapies. To date, research has not evaluated how surveillance alone impacts on sexual function. The aim of this quantitative longitudinal study was to ascertain the sexual function of men with stage one disease at 3 and 12 months post diagnosis and to compare with normative data. Additional data was collected on the information men sought regarding sexual function and media they used to access this. This study shows that men's sexual function is altered at diagnosis and improves by 3 months. At 12 months, whilst not statistically significant, sexual function improves but not to the same level as normative data comparison. Men appear to find verbal information useful at 3 months, however men appear to be seeking written and online information at 12 months. The intricacies of sexual function together with the low number of participants may have been best met with a qualitative approach. However, the information data indicates the importance of further research into the effects of early stage testicular cancer on sexual function. Therefore, further qualitative research is recommended to explore the effects of early stage testicular cancer in relation to sexual function. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Shifts in color discrimination during early pregnancy.

    PubMed

    Orbán, Levente L; Dastur, Farhad N

    2012-05-25

    The present study explores two hypotheses: a) women during early pregnancy should experience increased color discrimination ability, and b) women during early pregnancy should experience shifts in subjective preference away from images of foods that appear either unripe or spoiled. Both of these hypotheses derive from an adaptive view of pregnancy sickness that proposes the function of pregnancy sickness is to decrease the likelihood of ingestion of foods with toxins or teratogens. Changes to color discrimination could be part of a network of perceptual and physiological defenses (e.g., changes to olfaction, nausea, vomiting) that support such a function. Participants included 13 pregnant women and 18 non-pregnant women. Pregnant women scored significantly higher than non-pregnant controls on the Farnsworth-Munsell (FM) 100 Hue Test, an objective test of color discrimination, although no difference was found between groups in preferences for food images at different stages of ripeness or spoilage. These results are the first indication that changes to color discrimination may occur during early pregnancy, and is consistent with the view that pregnancy sickness may function as an adaptive defense mechanism.

  3. Clinical and Biochemical Characteristics of Brain-Dead Donors as Predictors of Early- and Long-Term Renal Function After Transplant.

    PubMed

    Kwiatkowska, Ewa; Domański, Leszek; Bober, Joanna; Safranow, Krzysztof; Pawlik, Andrzej; Ciechanowski, Kazimierz; Wiśniewska, Magda; Kędzierska, Karolina

    2017-08-01

    Organs from brain-dead donors are the main source of allografts for transplant. Comparisons between living-donor and brain-dead donor kidneys show that the latter are more likely to demonstrate delayed graft function and lower long-term survival. This study aimed to assess the effects of various clinical and biochemical factors of donors on early- and long-term renal function after transplant. We analyzed data from kidney recipients treated between 2006 and 2008 who received organs from brain-dead donors. Data from 54 donors and 89 recipients were analyzed. No relation was observed between donor sodium concentration and the presence of delayed graft function. Donor height was positively correlated with creatinine clearance in recipients in the 1 to 3 months after renal transplant. Donor diastolic blood pressure was negatively correlated with estimated glomerular filtration rate throughout the observation period. Donor age was negatively correlated with the allograft recipient's estimated glomerular filtration rate throughout 4 years of observation. Donor estimated glomerular filtration rate was positively correlated with that of the recipient throughout 3 years of observation. The results of this study indicate that various factors associated with allograft donors may influence graft function.

  4. Early impact of robot-assisted partial nephrectomy on renal function as assessed by renal scintigraphy.

    PubMed

    Luciani, Lorenzo G; Chiodini, Stefano; Donner, Davide; Cai, Tommaso; Vattovani, Valentino; Tiscione, Daniele; Giusti, Guido; Proietti, Silvia; Chierichetti, Franca; Malossini, Gianni

    2016-06-01

    To measure the early impact of robot-assisted partial nephrectomy (RAPN) on renal function as assessed by renal scan (Tc 99m-DTPA), addressing the issue of risk factors for ischemic damage to the kidney. All patients undergoing RAPN for cT1 renal masses between June 2013 and May 2014 were included in this prospective study. Renal function as expressed by glomerular filtration rate (GFR) was assessed by Technetium 99m-diethylenetriaminepentaacetic acid (Tc 99m-DTPA) renal scan preoperatively and postoperatively at 1 month in every patient. A multivariable analysis was used for the determination of independent factors predictive of GFR decrease of the operated kidney. Overall, 32 patients underwent RAPN in the time interval. Median tumor size, blood loss, and ischemia time were 4 cm, 200 mL, and 24 min, respectively. Two grade III complications occurred (postoperative bleeding in the renal fossa, urinoma). The GFR of the operated kidney decreased significantly from 51.7 ± 15.1 mL/min per 1.73 m(2) preoperatively to 40, 12 ± 12.4 mL/min per 1.73 m(2) 1 month postoperatively (p = 0.001) with a decrease of 22.4 %. On multivariable analysis, only tumor size (p = 0.05) was a predictor of GFR decrease of the operated kidney. Robotic-assisted partial nephrectomy had a detectable impact on early renal function in a series of relatively large tumors and prevailing intermediate nephrometric risk. A mean decrease of 22 % of GFR as assessed by renal scan in the operated kidney was found at 1 month postoperatively. In multivariable analysis, tumor size only was a significant predictor of renal function loss.

  5. A study of structural and functional connectivity in early Alzheimer's disease using rest fMRI and diffusion tensor imaging.

    PubMed

    Balachandar, R; John, J P; Saini, J; Kumar, K J; Joshi, H; Sadanand, S; Aiyappan, S; Sivakumar, P T; Loganathan, S; Varghese, M; Bharath, S

    2015-05-01

    Alzheimer's disease (AD) is a progressive neurodegenerative condition where in early diagnosis and interventions are key policy priorities in dementia services and research. We studied the functional and structural connectivity in mild AD to determine the nature of connectivity changes that coexist with neurocognitive deficits in the early stages of AD. Fifteen mild AD subjects and 15 cognitively healthy controls (CHc) matched for age and gender, underwent detailed neurocognitive assessment and magnetic resonance imaging (MRI) of resting state functional MRI (rs-fMRI) and diffusion tensor imaging (DTI). Rest fMRI was analyzed using dual regression approach and DTI by voxel wise statistics. Patients with mild AD had significantly lower functional connectivity (FC) within the default mode network and increased FC within the executive network. The mild AD group scored significantly lower in all domains of cognition compared with CHc. But fractional anisotropy did not significantly (p < 0.05) differ between the groups. Resting state functional connectivity alterations are noted during initial stages of cognitive decline in AD, even when there are no significant white matter microstructural changes. Copyright © 2014 John Wiley & Sons, Ltd.

  6. Individual differences in early adolescents' latent trait cortisol (LTC): Relation to early adversity.

    PubMed

    Stroud, Catherine B; Chen, Frances R; Doane, Leah D; Granger, Douglas A

    2016-09-01

    Substantial evidence suggests that youth who experience early adversity exhibit alterations in hypothalamic pituitary adrenal (HPA) axis functioning, thereby increasing risk for negative health outcomes. However, few studies have explored whether early adversity alters enduring trait indicators of HPA axis activity. Using objective contextual stress interviews with adolescents and their mothers to assess early adversity, we examined the cumulative impact of nine types of early adversity on early adolescents girls' latent trait cortisol (LTC). Adolescents (n = 122; M age = 12.39 years) provided salivary cortisol samples three times a day (waking, 30 min post-waking, and bedtime) over 3 days. Latent state-trait modeling indicated that the waking and 30 min post-waking samples contributed to a LTC factor. Moreover, greater early adversity was associated with a lower LTC level. Implications of LTC for future research examining the impact of early adversity on HPA axis functioning are discussed. © 2016 Wiley Periodicals, Inc. Dev Psychobiol 58:700-713, 2016. © 2016 Wiley Periodicals, Inc.

  7. Enhancing Recognition of High Quality, Functional IEP Goals: A Training Activity for Early Childhood Special Education Staff

    ERIC Educational Resources Information Center

    Lucas, Anne; Gillaspy, Kathi; Peters, Mary Louise; Hurth, Joicey

    2014-01-01

    This training activity was created to support participants' understanding of the criteria needed to develop and write high quality, participation-based Individualized Education Program (IEP) goals. The term "functional" is often used to describe what goals ought to be, yet many Early Childhood Special Education (ECSE) staff (e.g.,…

  8. Functional asymmetries in early learning during right, left, and bimanual performance in right-handed subjects.

    PubMed

    Aznárez-Sanado, Maite; Fernández-Seara, Maria A; Loayza, Francis R; Pastor, Maria A

    2013-03-01

    To elucidate differences in activity and connectivity during early learning due to the performing hand. Twenty right-handed subjects were recruited. The neural correlates of explicit visuospatial learning executed with the right, the left hand, and bimanually were investigated using functional magnetic resonance imaging. Connectivity analyses were carried out using the psychophysiological interactions model, considering right and left anterior putamen as index regions. A common neural network was found for the three tasks during learning. Main activity increases were located in posterior cingulate cortex, supplementary motor area, parietal cortex, anterior putamen, and cerebellum (IV-V), whereas activity decrements were observed in prefrontal regions. However, the left hand task showed a greater recruitment of left hippocampal areas when compared with the other tasks. In addition, enhanced connectivity between the right anterior putamen and motor cortical and cerebellar regions was found for the left hand when compared with the right hand task. An additional recruitment of brain regions and increased striato-cortical and striato-cerebellar functional connections is needed when early learning is performed with the nondominant hand. In addition, access to brain resources during learning may be directed by the dominant hand in the bimanual task. Copyright © 2012 Wiley Periodicals, Inc.

  9. Caregiver ratings of long-term executive dysfunction and attention problems after early childhood traumatic brain injury: family functioning is important.

    PubMed

    Kurowski, Brad G; Taylor, H Gerry; Yeates, Keith Owen; Walz, Nicolay C; Stancin, Terry; Wade, Shari L

    2011-09-01

    To evaluate the relationship of family and parenting factors to long-term executive dysfunction and attention problems after early childhood traumatic brain injury (TBI). We hypothesized that the magnitude of executive dysfunction and attention problems would be moderated by family and parenting factors. A multicenter, prospective cohort study that included an orthopedic injury (OI) reference group. Three tertiary academic children's hospital medical centers and one general medical center. Children, ages 3-7 years, hospitalized for OI, moderate TBI, or severe TBI. METHODS AND OUTCOME MEASUREMENTS: Parental ratings of family functioning and parenting styles were obtained 18 months after the injury occurred. The main outcome measurements, which were parental ratings of children's executive function and attention, were performed at least 24 months after the injury occurred (mean, 39 months; range, 25-63 months). Group comparisons were conducted with use of t-tests, χ(2) analysis, analysis of variance, and Pearson and Spearman correlations. Regression analysis was used to examine associations of the outcomes with family functioning and parenting styles and to test moderating effects of these factors on group differences. Participants with severe TBI demonstrated increased executive dysfunction and attention problems compared with those who sustained moderate TBI or OI. Lower levels of family dysfunction were associated with better executive function and attention across groups but did not moderate group differences. However, attention deficits after severe TBI were exacerbated under conditions of more permissive parenting relative to attention deficits after OIs. Executive function and attention problems persisted on a long-term basis (>24 months) after early childhood TBI, and positive global family functioning and nonpermissive parenting were associated with better outcomes. Better characterization of the optimal family environment for recovery from early childhood

  10. The selection system of silviculture in spruce-fir stands - procedures, early results, and comparisons with unmanaged stands

    Treesearch

    Robert M. Frank; Barton M. Blum

    1978-01-01

    Early results after 20 years of record keeping indicate that spruce-fir stands will respond to the selection system of silviculture. Stand quality is improved, species composition can be altered, diameter-class distribution approaches a stated goal, stand density is controlled, and yields are increased. Selection silviculture in spruce-fir can now be compared to early...

  11. Effectiveness and feasibility of early physical rehabilitation programs for geriatric hospitalized patients: a systematic review

    PubMed Central

    2013-01-01

    Background Old adults admitted to the hospital are at severe risk of functional loss during hospitalization. Early in-hospital physical rehabilitation programs appear to prevent functional loss in geriatric patients. The first aim of this review was to investigate the effect of early physical rehabilitation programs on physical functioning among geriatric patients acutely admitted to the hospital. The second aim was to evaluate the feasibility of early physical rehabilitation programs. Methods Two searches, one for physical functioning and one for feasibility, were conducted in PubMed, CINAHL, and EMBASE. Additional studies were identified through reference and citation tracking. To be included articles had to report on in-hospital early physical rehabilitation of patients aged 65 years and older with an outcome measure of physical functioning. Studies were excluded when the treatment was performed on specialized units other than geriatric units. Randomized controlled trials were included to examine the effect of early physical rehabilitation on physical functioning, length of stay and discharge destination. To investigate feasibility also non randomized controlled trials were added. Results Fifteen articles, reporting on 13 studies, described the effect on physical functioning. The early physical rehabilitation programs were classified in multidisciplinary programs with an exercise component and usual care with an exercise component. Multidisciplinary programs focussed more on facilitating discharge home and independent ADL, whereas exercise programs aimed at improving functional outcomes. At time of discharge patients who had participated in a multidisciplinary program or exercise program improved more on physical functional tests and were less likely to be discharged to a nursing home compared to patients receiving only usual care. In addition, multidisciplinary programs reduced the length of hospital stay significantly. Follow-up interventions improved

  12. The Association Between Childhood Emotional Functioning and Adulthood Inflammation Is Modified by Early-Life Socioeconomic Status

    PubMed Central

    Appleton, Allison A.; McCormick, Marie C.; Loucks, Eric B.; Buka, Stephen L.; Koenen, Karestan C.; Kubzansky, Laura D.

    2013-01-01

    Objective Identifying interrelationships among childhood social disadvantage, emotional functioning and adult health may help illustrate how health disparities may become embedded early in life, yet few have considered how these factors are associated. We examined whether the association of child emotional functioning and adult health risk was modified by child socioeconomic status (CSES), or whether child emotional functioning mediated the association of CSES and adult health risk. Method We studied 430 adult offspring (mean age 42 years) of Collaborative Perinatal Project participants, a cohort of pregnant women enrolled in 1959–1966 (Broman, Nichols, & Kennedy, 1975; Niswander & Gordon, 1972). Child emotional functioning was assessed by psychologist ratings at age 7 and included inappropriate self regulation (ISR) and distress proneness. CSES measures included parental education, household income, and parental occupation. Adult health risk was measured by the inflammatory marker C-reactive protein (CRP). Hypotheses were tested with multiple linear regression. Effect modification was evaluated via interaction terms and stratification of fully adjusted models by CSES. Mediation by child emotional functioning was evaluated via coefficient changes. Results There was no evidence that child emotional functioning mediated the association of CSES and CRP. Significant interactions were observed for ISR and low income (b = 1.67, SE = 0.70, p < .05), and distress proneness and low (b = 3.14, SE = 1.47, p < .05) and middle (b = 3.52, SE = 1.46, p < .05) income. Stratified models indicated that associations of child emotion with CRP varied significantly by level of parental education, household income and occupation. Conclusion The highest levels of adult inflammation were observed among those with childhood emotional problems who were also exposed to low socioeconomic status as children. This study suggests adulthood disparities in CRP may have developmental origins in

  13. Effects of stress in early life on immune functions in rats with asthma and the effects of music therapy.

    PubMed

    Lu, Yanxia; Liu, Meng; Shi, Shousen; Jiang, Hong; Yang, Lejin; Liu, Xin; Zhang, Qian; Pan, Fang

    2010-06-01

    Although studies have shown that psychological stress has detrimental effects on bronchial asthma, there are few objective data on whether early-life stress, as early postnatal psychosocial environment, has a long-lasting effect on adult asthma and the potential pathophysiologic mechanism. This study aims to examine the effects on immune function and hypothalamic-pituitary-adrenal (HPA) axis responses in adult asthmatic rats that experienced stress in early life and the potential ameliorative effects of music therapy on these parameters. Forty male Wistar rat pups were randomly assigned to the asthma group, the adulthood-stressed asthma group, the childhood-stressed asthma group, the music group, and the control group. Restraint stress and Mozart's Sonata K.448 were applied to ovalbumin (OVA)-induced asthmatic rats to establish psychological stress and music therapy models. The levels of serum corticosterone were examined in both childhood after stress and adulthood after OVA challenge. Immune indicators in blood, lung, and brain tissues were measured after the last OVA challenge. Stress in both childhood and adulthood resulted in increases in leukocyte and eosinophil numbers and serum interleukin (IL)-4 levels. The adulthood-stressed group demonstrated increased corticosterone levels after challenge, whereas the childhood-stressed group showed increased corticosterone concentration in childhood but decreased level in adulthood. Central IL-1beta exhibited a similar tendency. Music group rats showed reduced serum IL-4 and corticosterone. Stress in childhood and adulthood resulted in different HPA axis responsiveness in the exacerbation of markers of asthma. These data provide the first evidence of the long-term normalizing effects of music on asthmatic rats.

  14. Stability and Change in Executive Function Abilities from Late Adolescence to Early Adulthood: A Longitudinal Twin Study

    ERIC Educational Resources Information Center

    Friedman, Naomi P.; Miyake, Akira; Altamirano, Lee J.; Corley, Robin P.; Young, Susan E.; Rhea, Sally Ann; Hewitt, John K.

    2016-01-01

    Executive functions (EFs)--the higher level cognitive abilities that enable us to control our own thoughts and actions--continue to develop into early adulthood, yet no longitudinal study has examined their stability during the important life transition from late adolescence to young adulthood. In this twin study (total N = 840 individuals from…

  15. Prognostic importance of early worsening renal function after initiation of angiotensin-converting enzyme inhibitor therapy in patients with cardiac dysfunction.

    PubMed

    Testani, Jeffrey M; Kimmel, Stephen E; Dries, Daniel L; Coca, Steven G

    2011-11-01

    Worsening renal function (WRF) in the setting of heart failure has been associated with increased mortality. However, it is unclear if this decreased survival is a direct result of the reduction in glomerular filtration rate (GFR) or if the mechanism underlying the deterioration in GFR is driving prognosis. Given that WRF in the setting of angiotensin-converting enzyme inhibitor (ACE-I) initiation is likely mechanistically distinct from spontaneously occurring WRF, we investigated the relative early WRF-associated mortality rates in subjects randomized to ACE-I or placebo. Subjects in the Studies Of Left Ventricular Dysfunction (SOLVD) limited data set (n=6337) were studied. The interaction between early WRF (decrease in estimated GFR ≥20% at 14 days), randomization to enalapril, and mortality was the primary end point. In the overall population, early WRF was associated with increased mortality (adjusted hazard ratio [HR], 1.2; 95% CI, 1.0-1.4; P=0.037). When analysis was restricted to the placebo group, this association strengthened (adjusted HR, 1.4; 95% CI, 1.1-1.8; P=0.004). However, in the enalapril group, early WRF had no adverse prognostic significance (adjusted HR, 1.0; 95% CI, 0.8-1.3; P=1.0; P=0.09 for the interaction). In patients who continued to receive study drug despite early WRF, a survival advantage remained with enalapril therapy (adjusted HR, 0.66; 95% CI, 0.5-0.9; P=0.018). These data support the notion that the mechanism underlying WRF is important in determining its prognostic significance. Specifically, early WRF in the setting of ACE-I initiation appears to represent a benign event that is not associated with a loss of benefit from continued ACE-I therapy.

  16. Effective treatment of haemorrhoids: early complication and late results after 150 consecutive stapled haemorrhoidectomies.

    PubMed

    Bove, Aldo; Bongarzoni, Giuseppe; Palone, Gino; Chiarini, Stella; Calisesi, Enrico Maria; Corbellini, Luciano

    2009-01-01

    Haemorrhoidectomy according to Longo potentially reduces post-operative pain and allows an early return to work. The aim of this study was to evaluate the efficacy of the technique, the early and especially late complications, and recurrences, in 150 patients. Between January 2005 and December 2006, we performed 150 consecutive haemorrhoidectomies with the Longo technique: 82 for third degree haemorrhoids and 68 for fourth degree haemorrhoids. The mean age of patients was 42 years. Every patient had a pre-operative proctoscopy and endoscopy KIT PPH01 (Ethicon Endo Surgery) was used. We evaluated the length of the operation, the post-operative pain, the early and late complications, and the recurrence of the disease. The mean follow up was 52 months (range 36-72). There was no mortality. The mean length of the operation was 25 minutes with a range of 15 to 45 minutes. Pain, evaluated using the V.A.S. scale, was very light in 114 patients (V.A.S. 2,1) and light in 36 (V.A.S. 3.2). Only 11 (7.5%) patients took painkillers, on demand, for a week after discharge from hospital and 2 patients (1,3%) for more than one month. Early complications (6.6%) were: 5 bleeding (2 after seven days), 4 acute urinary retentions, 1 external haemorrhoid thrombosis and 1 haematoma of the rectus wall. Mean Hospital stay was 2.1 days. Late complications (10%) were: 5 "faecal urgency" which disappeared after six months, 6 moderate asymptomatic strictures, and 4 persistent skin tags. There were 8 recurrences (5.1%), 2 for haemorrhoids of grade 3 e 6 for haemorrhoids of grade 4. All the recurrences appeared within the first 24 months. The stapled procedure according to Longo is an effective treatment for haemorrhoids. The results for postoperative pain and early return to work are very good. However, special care for haemostasis is essential in order to avoid bleeding. An effective surgical technique prevents late complications, but results after long term follow up show a not insignificant

  17. Detection of early changes in renal function using 99mTc-MAG3 imaging in a murine model of ischemia-reperfusion injury

    PubMed Central

    Roberts, John; Chen, Bo; Curtis, Lisa M.; Agarwal, Anupam; Sanders, Paul W.; Zinn, Kurt R.

    2012-01-01

    Accurate determination of renal function in mice is a major impediment to the use of murine models in acute kidney injury. The purpose of this study was to determine whether early changes in renal function could be detected using dynamic gamma camera imaging in a mouse model of ischemia-reperfusion (I/R) injury. C57BL/6 mice (n = 5/group) underwent a right nephrectomy, followed by either 30 min of I/R injury or sham surgery of the remaining kidney. Dynamic renal studies (21 min, 10 s/frame) were conducted before surgery (baseline) and at 5, 24, and 48 h by injection of 99mTc-mercaptoacetyltriglycine (MAG3; ~1.0 mCi/mouse) via the tail vein. The percentage of injected dose (%ID) in the kidney was calculated for each 10-s interval after MAG3 injection, using standard region of interest analyses. A defect in renal function in I/R-treated mice was detected as early as 5 h after surgery compared with sham-treated mice, identified by the increased %ID (at peak) in the I/R-treated kidneys at 100 s (P < 0.01) that remained significantly higher than sham-treated mice for the duration of the scan until 600 s (P < 0.05). At 48 h, the renal scan demonstrated functional renal recovery of the I/R mice and was comparable to sham-treated mice. Our study shows that using dynamic imaging, renal dysfunction can be detected and quantified reliably as early as 5 h after I/R insult, allowing for evaluation of early treatment interventions. PMID:17634403

  18. Evaluation of renal allografts function early after transplantation using intravoxel incoherent motion and arterial spin labeling MRI.

    PubMed

    Ren, Tao; Wen, Cheng-Long; Chen, Li-Hua; Xie, Shuang-Shuang; Cheng, Yue; Fu, Ying-Xin; Oesingmann, Niels; de Oliveira, Andre; Zuo, Pan-Li; Yin, Jian-Zhong; Xia, Shuang; Shen, Wen

    2016-09-01

    To evaluate renal allografts function early after transplantation using intravoxel incoherent motion (IVIM) and arterial spin labeling (ASL) MRI. This prospective study was approved by the local ethics committee, and written informed consent was obtained from all participants. A total of 82 participants with 62 renal allograft recipients (2-4weeks after kidney transplantation) and 20 volunteers were enrolled to be scanned using IVIM and ASL MRI on a 3.0T MR scanner. Recipients were divided into two groups with either normal or impaired function according to the estimated glomerular filtration rate (eGFR) with a threshold of 60ml/min/1.73m(2). The apparent diffusion coefficient (ADC) of pure diffusion (ADCslow), the ADC of pseudodiffusion (ADCfast), perfusion fraction (PF), and renal blood flow (RBF) of cortex were compared among three groups. The correlation of ADCslow, ADCfast, PF and RBF with eGFR was evaluated. The receiver operating characteristic (ROC) curve and binary logistic regression analyses were performed to assess the diagnostic efficiency of using IVIM and ASL parameters to discriminate allografts with impaired function from normal function. P<0.05 was considered statistically significant. In allografts with normal function, no significant difference of mean cortical ADCslow, ADCfast, and PF was found compared with healthy controls (P>0.05). Cortical RBF in allografts with normal function was statistically lower than that of healthy controls (P<0.001). Mean cortical ADCslow, ADCfast, PF and RBF were lower for allografts with impaired function than that with normal function (P<0.05). Mean cortical ADCslow, ADCfast, PF and RBF showed a positive correlation with eGFR (all P<0.01) for recipients. The combination of IVIM and ASL MRI showed a higher area under the ROC curve (AUC) (0.865) than that of ASL MRI alone (P=0.02). Combined IVIM and ASL MRI can better evaluate the diffusion and perfusion properties for allografts early after kidney transplantation

  19. Migration characteristics and early clinical results of the NANOS® short-stem hip arthroplasty.

    PubMed

    Kaipel, Martin; Grabowiecki, Phillip; Sinz, Katrina; Farr, Sebastian; Sinz, Günter

    2015-05-01

    Femoral short stems promise essential advantages in total hip arthroplasty. Up to now, only short- and midterm clinical studies exist. Data on early stem migration that could predict later aseptic loosening at an early stage are rare. The purpose of this study was to assess migration patterns and clinical outcome 2 years after hip replacement by a metaphyseal anchored cementless short stem. Migration data and clinical results were prospectively assessed in 49 patients. Clinical outcome was measured using the Harris Hip Score (HHS). Migration analyses were performed using the computer-assisted Einzel-Bild-Roentgen-Analyse (EBRA) system. At 2 years after surgery, none of the implants needed revision, and HHS increased from 47.9 up to 98.1. Of 49 patients, 5 (10%) showed increased vertical stem migration (1.5 mm/2a) that might predict late aseptic loosening. Of 49 stems, 44 (90%) showed stable migration patterns indicating a beneficial long-term outcome. Results of this study confirm the excellent clinical data of previous works. Migration patterns strongly suggest that short-stem arthroplasty is not only an innovative but also a reliable strategy in total hip replacement.

  20. Functional Analysis and Treatment of Problem Behavior in Early Education Classrooms

    ERIC Educational Resources Information Center

    Greer, Brian D.; Neidert, Pamela L.; Dozier, Claudia L.; Payne, Steven W.; Zonneveld, Kimberley L. M.; Harper, Amy M.

    2013-01-01

    We conducted functional analyses (FA) with 4 typically developing preschool children during ongoing classroom activities and evaluated treatments that were based on FA results. Results of each child's FA suggested social-positive reinforcement functions, and differential reinforcement of alternative behavior plus time-out was effective in…

  1. PHOTOMETRIC PROPERTIES AND LUMINOSITY FUNCTION OF NEARBY MASSIVE EARLY-TYPE GALAXIES

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

    He, Y. Q.; Xia, X. Y.; Hao, C. N.

    We perform photometric analyses of a bright early-type galaxy sample with 2949 galaxies (M{sub r} < -22.5 mag) in the redshift range of 0.05-0.15, drawn from the Sloan Digital Sky Survey (SDSS) DR7 with morphological classification from Galaxy Zoo 1. We measure the Petrosian and isophotal magnitudes, as well as the corresponding half-light radius for each galaxy. We find that for the brightest galaxies (M{sub r} < -23 mag), our Petrosian magnitudes and isophotal magnitudes to 25 mag arcsec{sup -2} and 1% of the sky brightness are on average 0.16 mag, 0.20 mag, and 0.26 mag brighter than the SDSSmore » Petrosian values, respectively. In the first case, the underestimations are caused by overestimations in the sky background by the SDSS PHOTO algorithm, while the latter two are also due to deeper photometry. Similarly, the typical half-light radii (r{sub 50}) measured by the SDSS algorithm are smaller than our measurements. As a result, the bright end of the r-band luminosity function is found to decline more slowly than previous works. Our measured luminosity densities at the bright end are more than one order of magnitude higher than those of Blanton et al., and the stellar mass densities at M{sub *} {approx} 5 Multiplication-Sign 10{sup 11} M{sub Sun} and M{sub *} {approx} 10{sup 12} M{sub Sun} are a few tenths and a factor of a few higher than those of Bernardi et al. These results may significantly alleviate the tension in the assembly of massive galaxies between observations and predictions of the hierarchical structure formation model.« less

  2. Impairment in proverb interpretation as an executive function deficit in patients with amnestic mild cognitive impairment and early Alzheimer's disease.

    PubMed

    Leyhe, Thomas; Saur, Ralf; Eschweiler, Gerhard W; Milian, Monika

    2011-01-01

    Proverb interpretation is assumed to reflect executive functions. We hypothesized that proverb interpretation is impaired in patients with amnestic mild cognitive impairment (aMCI) diagnosed as single-domain impairment by common neuropsychological testing. We compared performance in a proverb interpretation test in single-domain aMCI patients and patients with early Alzheimer's disease (EAD). The groups with aMCI and EAD performed significantly worse than healthy controls. Both patient groups gave concrete answers with a similar frequency. However, patients with EAD tended to give senseless answers more frequently. Our data suggest that in patients diagnosed as single-domain aMCI, deterioration of executive functions is detectable with subtle and appropriate neuropsychological testing. Implementation of these procedures may improve the early prediction of AD.

  3. The Use of Cryotherapy for Papilloma and Early Laryngeal Cancers: Long-term Results.

    PubMed

    Benninger, Michael S; Derakhshan, Adeeb; Milstein, Claudio F

    2015-07-01

    Retrospective chart review. To determine the efficacy of adjuvant cryotherapy in the treatment of early glottic cancer and laryngeal papillomatosis. The use of cryotherapy in conjunction with traditional modalities has recently been proposed to improve voice outcomes in patients with early laryngeal cancer as compared to pretreatment conditions. This study investigates its utility in improving oncological outcomes and decreasing recurrences of laryngeal papillomatosis. Patients with either early glottic cancer or laryngeal papillomatosis that received cryotherapy as part of their surgical regimen were investigated. All patients were seen at a large tertiary care center within a 10-year window. Demographic data were collected and all postoperative notes were reviewed. Recurrences of the laryngeal cancer were noted, as was the duration of time between successive papillomatosis operations. The charts of 54 glottic cancer and 29 papillomatosis patients that received cryotherapy were reviewed. One patient from the papillomatosis cohort was excluded from statistical analysis due to lack of follow-up. Overall, 16 (30%) of the laryngeal cancer patient experienced a malignant recurrence. The overall 5-year survival of these patients was 98% and the 5-year disease-free survival was 74%. The use of adjuvant cryotherapy in the treatment of laryngeal papillomatosis extended the duration of time between surgeries by an average of 79 days (P=.23). The use of adjuvant cryotherapy in the treatment of early glottic cancer does not improve the rate of carcinoma recurrences. Additionally, cryotherapy does not result in a statistically significant increase in the duration of disease-free period for laryngeal papillomatosis patients, although the observed increase may be clinically important. © The Author(s) 2015.

  4. Merger-driven evolution of the effective stellar initial mass function of massive early-type galaxies

    NASA Astrophysics Data System (ADS)

    Sonnenfeld, Alessandro; Nipoti, Carlo; Treu, Tommaso

    2017-02-01

    The stellar initial mass function (IMF) of early-type galaxies is the combination of the IMF of the stellar population formed in situ and that of accreted stellar populations. Using as an observable the effective IMF αIMF, defined as the ratio between the true stellar mass of a galaxy and the stellar mass inferred assuming a Salpeter IMF, we present a theoretical model for its evolution as a result of dry mergers. We use a simple dry-merger evolution model, based on cosmological N-body simulations, together with empirically motivated prescriptions for the IMF to make predictions on how the effective IMF of massive early-type galaxies changes from z = 2 to z = 0. We find that the IMF normalization of individual galaxies becomes lighter with time. At fixed velocity dispersion, αIMF is predicted to be constant with redshift. Current dynamical constraints on the evolution of the IMF are in slight tension with this prediction, even though systematic uncertainties, including the effect of radial gradients in the IMF, prevent a conclusive statement. The correlation of αIMF with stellar mass becomes shallower with time, while the correlation between αIMF and velocity dispersion is mostly preserved by dry mergers. We also find that dry mergers can mix the dependence of the IMF on stellar mass and velocity dispersion, making it challenging to infer, from z = 0 observations of global galactic properties, what is the quantity that is originally coupled with the IMF.

  5. Functional Characterization of Cnidarian HCN Channels Points to an Early Evolution of Ih.

    PubMed

    Baker, Emma C; Layden, Michael J; van Rossum, Damian B; Kamel, Bishoy; Medina, Monica; Simpson, Eboni; Jegla, Timothy

    2015-01-01

    HCN channels play a unique role in bilaterian physiology as the only hyperpolarization-gated cation channels. Their voltage-gating is regulated by cyclic nucleotides and phosphatidylinositol 4,5-bisphosphate (PIP2). Activation of HCN channels provides the depolarizing current in response to hyperpolarization that is critical for intrinsic rhythmicity in neurons and the sinoatrial node. Additionally, HCN channels regulate dendritic excitability in a wide variety of neurons. Little is known about the early functional evolution of HCN channels, but the presence of HCN sequences in basal metazoan phyla and choanoflagellates, a protozoan sister group to the metazoans, indicate that the gene family predates metazoan emergence. We functionally characterized two HCN channel orthologs from Nematostella vectensis (Cnidaria, Anthozoa) to determine which properties of HCN channels were established prior to the emergence of bilaterians. We find Nematostella HCN channels share all the major functional features of bilaterian HCNs, including reversed voltage-dependence, activation by cAMP and PIP2, and block by extracellular Cs+. Thus bilaterian-like HCN channels were already present in the common parahoxozoan ancestor of bilaterians and cnidarians, at a time when the functional diversity of voltage-gated K+ channels was rapidly expanding. NvHCN1 and NvHCN2 are expressed broadly in planulae and in both the endoderm and ectoderm of juvenile polyps.

  6. Cognitive load effects on early visual perceptual processing.

    PubMed

    Liu, Ping; Forte, Jason; Sewell, David; Carter, Olivia

    2018-05-01

    Contrast-based early visual processing has largely been considered to involve autonomous processes that do not need the support of cognitive resources. However, as spatial attention is known to modulate early visual perceptual processing, we explored whether cognitive load could similarly impact contrast-based perception. We used a dual-task paradigm to assess the impact of a concurrent working memory task on the performance of three different early visual tasks. The results from Experiment 1 suggest that cognitive load can modulate early visual processing. No effects of cognitive load were seen in Experiments 2 or 3. Together, the findings provide evidence that under some circumstances cognitive load effects can penetrate the early stages of visual processing and that higher cognitive function and early perceptual processing may not be as independent as was once thought.

  7. Early results from NASA's SnowEx campaign

    NASA Astrophysics Data System (ADS)

    Kim, Edward; Gatebe, Charles; Hall, Dorothy; Misakonis, Amy; Elder, Kelly; Marshall, Hans Peter; Hiemstra, Chris; Brucker, Ludovic; Crawford, Chris; Kang, Do Hyuk; De Marco, Eugenia; Beckley, Matt; Entin, Jared

    2017-04-01

    SnowEx is a multi-year airborne snow campaign with the primary goal of addressing the question: How much water is stored in Earth's terrestrial snow-covered regions? Year 1 (2016-17) focuses on the distribution of snow-water equivalent (SWE) and the snow energy balance in a forested environment. The year 1 primary site is Grand Mesa and the secondary site is the Senator Beck Basin, both in western, Colorado, USA. Ten core sensors on four core aircraft will make observations using a broad suite of airborne sensors including active and passive microwave, and active and passive optical/infrared sensing techniques to determine the sensitivity and accuracy of these potential satellite remote sensing techniques, along with models, to measure snow under a range of forest conditions. SnowEx also includes an extensive range of ground truth measurements—in-situ samples, snow pits, ground based remote sensing measurements, and sophisticated new techniques. A detailed description of the data collected will be given and some early results will be presented. Seasonal snow cover is the largest single component of the cryosphere in areal extent (covering an average of 46M km2 of Earth's surface (31 % of land areas) each year). This seasonal snow has major societal impacts in the areas of water resources, natural hazards (floods and droughts), water security, and weather and climate. The only practical way to estimate the quantity of snow on a consistent global basis is through satellites. Yet, current space-based techniques underestimate storage of snow water equivalent (SWE) by as much as 50%, and model-based estimates can differ greatly vs. estimates based on remotely-sensed observations. At peak coverage, as much as half of snow-covered terrestrial areas involve forested areas, so quantifying the challenge represented by forests is important to plan any future snow mission. Single-sensor approaches may work for certain snow types and certain conditions, but not for others

  8. Education and Executive Function Mediate Engagement in Advance Care Planning in Early Cognitive Impairment.

    PubMed

    Tay, Sze Yan; Davison, John; Jin, Ng Chong; Yap, Philip Lin Kiat

    2015-11-01

    Advance care planning (ACP) is an important component to holistic care for people with early cognitive impairment (ECI) who are generally still mentally capable of making rational decisions. This study explores the willingness of people with ECI to engage in ACP and how clinical and behavioral variables shape their decisions. Ninety-eight persons with ECI (mild cognitive impairment or early dementia, Clinical Dementia Rating = 0.5/1.0) and assessed to have adequate insight (Clinical Insight Rating Scale) underwent an ACP information session. They were assessed on their knowledge of dementia (Knowledge of Alzheimer Disease) and willingness to engage in ACP, and were interviewed on their beliefs and attitudes toward ACP (Perceived Barriers and Benefits Scale to ACP). Univariate analysis and logistic regression identified factors that predicted persons willing or unwilling to engage in ACP based on their responses to the perceived barriers and benefits of ACP as well as sociodemographic and clinical variables. Fifty-two persons (54%) were keen on ACP. On univariate analysis, persons with better executive function [Frontal Assessment Battery (FAB)] (t = -3.63, P < .0001), were more educated (t = -2.11, P = .038) and had lower barriers to ACP (t = 2.47, P = .015), particularly less "passive coping" (t = 2.83, P = .006), were more keen on ACP. Logistic regression revealed that the combined predictive model comprising FAB, education, and passive coping as a whole reliably differentiated those unwilling to engage in ACP from those who were willing (χ(2) = 18.995, P = .001 with df = 4). Wald criterion showed that FAB (P = .016) and passive coping (P = .023) contributed most to prediction. Better education and executive function predict willingness to engage in ACP, and these factors are instrumental in a person's ability to acquire knowledge and process information. Initiating ACP discussions early, increasing efforts at education, and providing tailored information are

  9. Racial differences in kidney function among individuals with obesity and metabolic syndrome: results from the Kidney Early Evaluation Program (KEEP).

    PubMed

    Bomback, Andrew S; Kshirsagar, Abhijit V; Whaley-Connell, Adam T; Chen, Shu-Cheng; Li, Suying; Klemmer, Philip J; McCullough, Peter A; Bakris, George L

    2010-03-01

    Obesity and metabolic syndrome may differ by race. For participants in the National Kidney Foundation's Kidney Early Evaluation Program (KEEP), we examined whether African American and white participants with obesity and metabolic syndrome differ regarding albuminuria, estimated glomerular filtration rate (eGFR), anemia, and bone/mineral metabolism derangements in chronic kidney disease (CKD). 3 study cohorts were assembled: (1) eligible African American and white KEEP participants with body mass index > or = 30 kg/m(2), (2) a subgroup meeting criteria for metabolic syndrome, and (3) a subgroup with eGFR < 60 mL/min/1.73 m(2) and laboratory measurements for hemoglobin, parathyroid hormone, calcium, and phosphorus. Patient characteristics and kidney function assessments were compared and tested using chi(2) (categorical variables) and t test (continuous variables). Univariate and multivariate logistic regression analyses were performed to evaluate associations of race with kidney disease measures. Of 37,107 obese participants, 48% were African American and 52% were white. Whites were more likely to have metabolic syndrome components (hypertension, 87.1% vs 84.8%; dyslipidemia, 81.6% vs 66.7%; diabetes, 42.7% vs 34.9%) and more profoundly decreased eGFR than African Americans (CKD stages 3-5 prevalence, 23.6% vs 13.0%; P < 0.001). African Americans were more likely to have abnormal urinary albumin excretion (microalbuminuria, 12.5% vs 10.2%; OR, 1.60 [95% CI, 1.45-1.76]; macroalbuminuria, 1.3% vs 1.2%; OR, 1.61 [95% CI, 1.23-2.12]) and CKD stages 1-2 (10.3% vs 7.1%; OR, 1.54 [95% CI, 1.38-1.72]). For participants with CKD stages 3-5, anemia prevalence was 32.4% in African Americans and 14.1% in whites; corresponding values for secondary hyperparathyroidism were 66.2% and 46.6%, respectively. Obesity and metabolic syndrome may be heterogeneous disease states in African Americans and whites, possibly explaining differences in long-term kidney and cardiovascular

  10. Early-life perturbations in glucocorticoid activity impacts on the structure, function and molecular composition of the adult zebrafish (Danio rerio) heart

    PubMed Central

    Wilson, K.S.; Baily, J.; Tucker, C.S.; Matrone, G.; Vass, S.; Moran, C.; Chapman, K.E.; Mullins, J.J.; Kenyon, C.; Hadoke, P.W.F.; Denvir, M.A.

    2015-01-01

    Background Transient early-life perturbations in glucocorticoids (GC) are linked with cardiovascular disease risk in later life. Here the impact of early life manipulations of GC on adult heart structure, function and gene expression were assessed. Methods and results Zebrafish embryos were incubated in dexamethasone (Dex) or injected with targeted glucocorticoid receptor (GR) morpholino knockdown (GR Mo) over the first 120 h post fertilisation (hpf); surviving embryos (>90%) were maintained until adulthood under normal conditions. Cardiac function, heart histology and cardiac genes were assessed in embryonic (120 hpf) and adult (120 days post fertilisation (dpf)) hearts. GR Mo embryos (120 hpf) had smaller hearts with fewer cardiomyocytes, less mature striation pattern, reduced cardiac function and reduced levels of vmhc and igf mRNA compared with controls. GR Mo adult hearts were smaller with diminished trabecular network pattern, reduced expression of vmhc and altered echocardiographic Doppler flow compared to controls. Dex embryos had larger hearts at 120 hpf (Dex 107.2 ± 3.1 vs. controls 90.2 ± 1.1 μm, p < 0.001) with a more mature trabecular network and larger cardiomyocytes (1.62 ± 0.13 cells/μm vs control 2.18 ± 0.13 cells/μm, p < 0.05) and enhanced cardiac performance compared to controls. Adult hearts were larger (1.02 ± 0.07 μg/mg vs controls 0.63 ± 0.06 μg/mg, p = 0.0007), had increased vmhc and gr mRNA levels. Conclusion Perturbations in GR activity during embryonic development results in short and long-term alterations in the heart. PMID:26219824

  11. Study of the mesosphere using wide-field twilight polarization measurements: Early results beyond the polar circle

    NASA Astrophysics Data System (ADS)

    Ugolnikov, O. S.; Kozelov, B. V.

    2016-07-01

    This paper discusses the results of early measurements of temperature and dust in the mesosphere on the basis of wide-field twilight sky polarimetry, which began in 2015 in Apatity (North of Russia, 67.6° N, 33.4° E) using the original entire-sky camera. These measurements have been performed for the first time beyond the Polar Circle in the winter and early spring period. The general polarization properties of the twilight sky and the procedure for identifying single scattering are described. The key results of the study include the Boltzmann temperature values at altitudes higher than 70 km and the conclusion on a weak effect of dust on scattering properties of the mesosphere during this period.

  12. Early-onset growth hormone deficiency results in diastolic dysfunction in adult-life and is prevented by growth hormone supplementation.

    PubMed

    Groban, L; Lin, M; Kassik, K A; Ingram, R L; Sonntag, W E

    2011-04-01

    The primary goal of growth hormone (GH) replacement is to promote linear growth in children with growth hormone deficiency (GHD). GH and insulin-like growth factor-1 (IGF-1) are also known to have roles in cardiac development and as modulators of myocardial structure and function in the adult heart. However, little is known about cardiac diastolic function in young adults with childhood onset GH deficiency in which GH treatment was discontinued following puberty. The aim of the study was to evaluate the effects of long standing GHD and peri-pubertal or continuous GH replacement therapy on diastolic function in the adult dwarf rat. The dwarf rat, which possesses a mutation in a transcription factor necessary for development of the somatotroph, does not exhibit the normal peri-pubertal rise in GH around day 28 and was used to model childhood or early-onset GHD (EOGHD). In another group of male dwarfs, GH replacement therapy was initiated at 4 weeks of age when GH pulsatility normally begins. Ten weeks after initiation of injections, GH-treated dwarf rats were divided into 2 groups; continued treatment with GH for 12 weeks (GH-replete) or treatment with saline for 12 weeks. This latter group models GH supplementation during adolescence with GHD beginning in adulthood (adult-onset GHD; AOGHD). Saline-treated heterozygous (HZ) rats were used as age-matched controls. At 26 weeks of age, cardiac function was assessed using invasive or noninvasive (conventional and tissue Doppler) indices of myocardial contractility and lusitropy. Systolic function, as determined by echocardiography, was similar among groups. Compared with HZ rats and GH-replete dwarfs, the EOGHD group exhibited significant reductions in myocardial relaxation and increases in left ventricular filling pressure, indicative of moderate diastolic dysfunction. This was further associated with a decrease in the cardiac content of sarcoplasmic reticulum Ca(2+) ATPase (SERCA2), one of the important cardiac calcium

  13. Are There Long-Term Effects of Early Child Care?

    ERIC Educational Resources Information Center

    Belsky, Jay; Vandell, Deborah Lowe; Burchinal, Margaret; Clarke-Stewart, K. Alison; McCartney, Kathleen; Owen, Margaret Tresch

    2007-01-01

    Effects of early child care on children's functioning from 4 1/2 years through the end of 6th grade (M age=12.0 years) were examined in the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development (n=1,364). The results indicated that although parenting was a stronger and more consistent predictor of…

  14. The impact of premorbid adjustment, neurocognition, and depression on social and role functioning in patients in an early psychosis treatment program.

    PubMed

    Minor, Kyle S; Friedman-Yakoobian, Michelle; Leung, Y Jude; Meyer, Eric C; Zimmet, Suzanna V; Caplan, Brina; Monteleone, Thomas; Bryant, Caitlin; Guyer, Margaret; Keshavan, Matcheri S; Seidman, Larry J

    2015-05-01

    Functional impairments are debilitating concomitants of psychotic disorders and are present early in the illness course and, commonly, prior to psychosis onset. The factors affecting social and role functioning in early psychosis (EP) following treatment are unclear. We evaluated whether six months of participation in the PREP(R), Boston, EP treatment program, part of a public-academic community mental health center, was related to improvements in social and role functioning and whether premorbid adjustment in adolescence, baseline neurocognition, and depression symptoms predicted functional improvement. The Global Functioning Social and Role scales, MATRICS neurocognitive battery, and Calgary Depression Scale were assessed at baseline and six months during naturalistic treatment, while premorbid adjustment was measured at baseline. All participants were psychotic disorder patients in PREP(R) (n = 46 with social functioning and 47 with role functioning measures at both time points). Large improvements were observed in role functioning (d = 0.84) and medium to large improvements were observed in social functioning (d = 0.70). Models consisting of adolescent premorbid adjustment and change in depression symptoms predicted social and role functioning change, whereas neuropsychological functioning did not. Substantial improvements in social and role functioning were observed among this sample participating in a recovery-based EP program. The impact of clinical factors on social and role functioning was highlighted. Further studies of premorbid adjustment in adolescence and the treatment of depression in EP programs in controlled treatment trials are needed to confirm these findings. © The Royal Australian and New Zealand College of Psychiatrists 2015.

  15. Hyperspectral recognition of processing tomato early blight based on GA and SVM

    NASA Astrophysics Data System (ADS)

    Yin, Xiaojun; Zhao, SiFeng

    2013-03-01

    Processing tomato early blight seriously affect the yield and quality of its.Determine the leaves spectrum of different disease severity level of processing tomato early blight.We take the sensitive bands of processing tomato early blight as support vector machine input vector.Through the genetic algorithm(GA) to optimize the parameters of SVM, We could recognize different disease severity level of processing tomato early blight.The result show:the sensitive bands of different disease severity levels of processing tomato early blight is 628-643nm and 689-692nm.The sensitive bands are as the GA and SVM input vector.We get the best penalty parameters is 0.129 and kernel function parameters is 3.479.We make classification training and testing by polynomial nuclear,radial basis function nuclear,Sigmoid nuclear.The best classification model is the radial basis function nuclear of SVM. Training accuracy is 84.615%,Testing accuracy is 80.681%.It is combined GA and SVM to achieve multi-classification of processing tomato early blight.It is provided the technical support of prediction processing tomato early blight occurrence, development and diffusion rule in large areas.

  16. External-environmental and internal-health early life predictors of adolescent development.

    PubMed

    Hartman, Sarah; Li, Zhi; Nettle, Daniel; Belsky, Jay

    2017-12-01

    A wealth of evidence documents associations between various aspects of the rearing environment and later development. Two evolutionary-inspired models advance explanations for why and how such early experiences shape later functioning: (a) the external-prediction model, which highlights the role of the early environment (e.g., parenting) in regulating children's development, and (b) the internal-prediction model, which emphasizes internal state (i.e., health) as the critical regulator. Thus, by using data from the NICHD Study of Early Child Care and Youth Development, the current project draws from both models by investigating whether the effect of the early environment on later adolescent functioning is subject to an indirect effect by internal-health variables. Results showed a significant indirect effect of internal health on the relation between the early environment and adolescent behavior. Specifically, early environmental adversity during the first 5 years of life predicted lower quality health during childhood, which then led to problematic adolescent functioning and earlier age of menarche for girls. In addition, for girls, early adversity predicted lower quality health that forecasted earlier age of menarche leading to increased adolescent risk taking. The discussion highlights the importance of integrating both internal and external models to further understand the developmental processes that effect adolescent behavior.

  17. Early results of a prospective study on the pyrolytic carbon (pyrocarbon) Amandys® for osteoarthritis of the wrist

    PubMed Central

    Daruwalla, ZJ; Davies, KL; Shafighian, A; Gillham, NR

    2012-01-01

    INTRODUCTION The preliminary results of a pyrocarbon interpositional radiocarpal implant in a small cohort of patients were reviewed. As it is currently only a limited release product, we describe to potential users early complications and negative outcomes. METHODS Patients were assessed using pain levels, ranges of motion, grip strength, type of and time to return to work as well as pre-operative and post-operative DASH (Disabilities of the Arm, Shoulder and Hand) scores. Radiographs were taken and patient satisfaction was recorded. RESULTS All six patients were contacted. One was not satisfied. Three had reduced motion. None experienced squeaking. There were no immediate or late post-operative complications. There was one early volar displacement of an implant. CONCLUSIONS Although our early results are somewhat encouraging, further and longer studies are warranted before supporting the use of this particular pyrocarbon implant as a primary procedure. PMID:23031769

  18. Early Calibration Results of CYGNSS Mission

    NASA Astrophysics Data System (ADS)

    Balasubramaniam, R.; Ruf, C. S.; McKague, D. S.; Clarizia, M. P.; Gleason, S.

    2017-12-01

    The first of its kind, GNSS-R complete orbital mission, CYGNSS was successfully launched on Dec 15 2016. The goal of this mission is to accurately forecast the intensification of tropical cyclones by modelling its inner core. The 8 micro observatories of CYGNSS carry a passive instrument called Delay Doppler Mapping Instrument (DDMI). The DDMIs form a 2D representation called the Delay-Doppler Map (DDM) of the forward scattered power signal. Each DDMI outputs 4 DDMs per second which are compressed and sent to the ground resulting in a total of 32 sea-surface measurements produced by the CYGNSS constellation per second. These are subsequently used in the Level-2 wind retrieval algorithm to extract wind speed information. In this paper, we perform calibration and validation of CYGNSS measurements for accurate extraction of wind speed information. The calibration stage involves identification and correction for dependence of the CYGNSS observables namely Normalised Bistatic Radar Cross Section and Leading Edge Slope of the Integrated Delay Waveform over instrument parameters, geometry etc. The validation stage involves training of the Geophysical Model Function over a multitude of ground truth sources during the Atlantic hurricane season and also refined validation of high wind speed data products.

  19. Longitudinal changes in sexual functioning as women transition through menopause: results from the Study of Women's Health Across the Nation.

    PubMed

    Avis, Nancy E; Brockwell, Sarah; Randolph, John F; Shen, Shunhua; Cain, Virginia S; Ory, Marcia; Greendale, Gail A

    2009-01-01

    Sexual functioning is an important component of women's lives. The extent to which the menopausal transition is associated with decreased sexual functioning remains inconclusive. This study seeks to determine if advancing through the menopausal transition is associated with changes in sexual functioning. This was a prospective, longitudinal cohort study of women aged 42 to 52 years at baseline recruited at seven US sites (N = 3,302) in the Study of Women's Health Across the Nation (SWAN). Cohort-eligible women had an intact uterus, had at least one ovary, were not currently using exogenous hormones, were either premenopausal or early perimenopausal, and self-identified as one of the study's designated racial/ethnic groups. Data from the baseline interview and six annual follow-up visits are reported. Outcomes are self-reported ratings of importance of sex; frequency of sexual desire, arousal, masturbation, sexual intercourse, and pain during intercourse; and degree of emotional satisfaction and physical pleasure. With adjustment for baseline age, chronological aging, and relevant social, health, and psychological parameters, the odds of reporting vaginal or pelvic pain increased and desire decreased by late perimenopause. Masturbation increased at early perimenopause but declined during postmenopause. The menopausal transition was unrelated to other outcomes. Health, psychological functioning, and importance of sex were related to all sexual function outcomes. Age, race/ethnicity, marital status, change in relationship, and vaginal dryness were also associated with sexual functioning. Pain during sexual intercourse increases and sexual desire decreases over the menopausal transition. Masturbation increases during the early transition, but then declines in postmenopause. With adjustment for other factors, the menopausal transition was not independently associated with reports of the importance of sex, sexual arousal, frequency of sexual intercourse, emotional

  20. False Positive Functional Analysis Results as a Contributor of Treatment Failure during Functional Communication Training

    ERIC Educational Resources Information Center

    Mann, Amanda J.; Mueller, Michael M.

    2009-01-01

    Research has shown that functional analysis results are beneficial for treatment selection because they identify reinforcers for severe behavior that can then be used to reinforce replacement behaviors either differentially or noncontingently. Theoretically then, if a reinforcer is identified in a functional analysis erroneously, a well researched…

  1. Radiological study of the secondary reduction effect of early functional exercise on displaced intra-articular calcaneal fractures after internal compression fixation.

    PubMed

    Chen, Wei; Liu, Bo; Lv, Hongzhi; Su, Yanling; Chen, Xiao; Zhu, Yanbin; Du, Chenguang; Zhang, Xiaolin; Zhang, Yingze

    2017-09-01

    Early post-operative exercise and weight-bearing activities are found to improve the functional recovery of patients with displaced intra-articular calcaneal fractures (DIACFs). We hypothesized that early functional exercise after surgery might have a secondary reduction effect on the subtalar joint, in particular the smaller fracture fragments that were not fixed firmly. A prospective study was conducted to verify this hypothesis. From December 2012 to September 2013, patients with unilateral DIACFs were enrolled and received a treatment consisting of percutaneous leverage and minimally invasive fixation. After surgery, patients in the study group started exercising on days two to three, using partial weight bearing starting week three, and full weight bearing starting week 12. Patients in the control group followed a conventional post-operative protocol of partial weight bearing after week six and full weight bearing after the bone healed. Computed tomography (CT) scanning was performed at post-operative day one, week four, week eight, and week 12 to reconstruct coronal, sagittal, and axial images, on which the maximal residual displacements of the fractures were measured. Function was evaluated using the American Orthopaedic Foot and Ankle Society (AOFAS) scoring scale at the 12th post-operative month. Twenty-eight patients in the study group and 32 in the control group were followed up for more than 12 months; their data were collected and used for the final analysis. Repeated-measures analysis of variance (ANOVA) of the maximal residual displacements of the fracture measured on CT images revealed significant differences between the study and the control groups. There were interaction effects between group and time point. Except for the first time point, the differences between the groups at all studied time points were significant. In the study group, the differences between all studied time points were significant. Strong correlations were observed between

  2. Morphological and functional abnormalities of salience network in the early-stage of paranoid schizophrenia.

    PubMed

    Pu, Weidan; Li, Li; Zhang, Huiran; Ouyang, Xuan; Liu, Haihong; Zhao, Jingping; Li, Lingjiang; Xue, Zhimin; Xu, Ke; Tang, Haibo; Shan, Baoci; Liu, Zhening; Wang, Fei

    2012-10-01

    A salience network (SN), mainly composed of the anterior insula (AI) and anterior cingulate cortex (ACC), has been suggested to play an important role in salience attribution which has been proposed as central to the pathology of paranoid schizophrenia. The role of this SN in the pathophysiology of paranoid schizophrenia, however, still remains unclear. In the present study, voxel-based morphometry and resting-state functional connectivity analyses were combined to identify morphological and functional abnormalities in the proposed SN in the early-stage of paranoid schizophrenia (ESPS). Voxel-based morphometry and resting-state functional connectivity analyses were applied to 90 ESPS patients and 90 age- and sex-matched healthy controls (HC). Correlation analyses were performed to examine the relationships between various clinical variables and both gray matter morphology and functional connectivity within the SN in ESPS. Compared to the HC group, the ESPS group showed significantly reduced gray matter volume (GMV) in both bilateral AI and ACC. Moreover, significantly reduced functional connectivity within the SN sub-networks was identified in the ESPS group. These convergent morphological and functional deficits in SN were significantly associated with hallucinations. Additionally, illness duration correlated with reduced GMV in the left AI in ESPS. In conclusion, these findings provide convergent evidence for the morphological and functional abnormalities of the SN in ESPS. Moreover, the association of illness duration with the reduced GMV in the left AI suggests that the SN and the AI, in particular, may manifest progressive morphological changes that are especially important in the emergence of ESPS. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. Identification and functional analysis of long non-coding RNAs in human and mouse early embryos based on single-cell transcriptome data

    PubMed Central

    Qiu, Jia-jun; Ren, Zhao-rui; Yan, Jing-bin

    2016-01-01

    Epigenetics regulations have an important role in fertilization and proper embryonic development, and several human diseases are associated with epigenetic modification disorders, such as Rett syndrome, Beckwith-Wiedemann syndrome and Angelman syndrome. However, the dynamics and functions of long non-coding RNAs (lncRNAs), one type of epigenetic regulators, in human pre-implantation development have not yet been demonstrated. In this study, a comprehensive analysis of human and mouse early-stage embryonic lncRNAs was performed based on public single-cell RNA sequencing data. Expression profile analysis revealed that lncRNAs are expressed in a developmental stage–specific manner during human early-stage embryonic development, whereas a more temporal-specific expression pattern was identified in mouse embryos. Weighted gene co-expression network analysis suggested that lncRNAs involved in human early-stage embryonic development are associated with several important functions and processes, such as oocyte maturation, zygotic genome activation and mitochondrial functions. We also found that the network of lncRNAs involved in zygotic genome activation was highly preservative between human and mouse embryos, whereas in other stages no strong correlation between human and mouse embryo was observed. This study provides insight into the molecular mechanism underlying lncRNA involvement in human pre-implantation embryonic development. PMID:27542205

  4. Trajectories of functional limitation in early rheumatoid arthritis and their association with mortality.

    PubMed

    Norton, Sam; Sacker, Amanda; Dixey, Josh; Done, John; Williams, Peter; Young, Adam

    2013-11-01

    This study aimed to identify subgroups with distinct trajectories of functional (HAQ) progression over 10 years following diagnosis of RA and identify baseline characteristics associated with the trajectories and their prognostic value for mortality. Between 1986 and 1998, 1460 patients with RA symptoms <2 years and prior to disease-modifying treatment (DMARDs) were recruited to an inception cohort (Early RA Study). Standard clinical, functional and laboratory assessments were performed at presentation and annually. Deaths were tracked by the National Health Service Central Register. Growth mixture modelling was used to identify distinct trajectories of HAQ score progression and survival analysis employed to compare all-cause mortality across the trajectory classes. Four HAQ score progression classes were identified: moderate increasing (46%), low stable (6%), moderate stable (28%) and high stable (20%). Only the moderate-increasing class exhibited an accelerated decline in function over normal ageing. Compared with the moderate-increasing class, individuals with high-stable HAQ scores were more likely to be female, have more severe disease and other coexistent conditions. Low-stable class patients were more likely to be male and report less pain. The high-stable class had increased risk of mortality compared with the moderate-increasing class after adjusting for potential confounding factors, whereas low-stable and moderate-stable classes were at reduced mortality risk. The effect of RA on function is set within the first few years and is affected by comorbidity. Identifying distinct groups of patients may help to target those at greater risk of poor functional outcome and mortality.

  5. Early experience and results of bone graft enriched with autologous platelet gel for recalcitrant nonunions of lower extremity.

    PubMed

    Chiang, Chao-Ching; Su, Chen-Yao; Huang, Ching-Kuei; Chen, Wei-Ming; Chen, Tain-Hsiung; Tzeng, Yun-Hsuan

    2007-09-01

    Refractory nonunions of the tibia or femur are physically and mentally devastating conditions for the patients, and the treatment is challenging for orthopedic surgeons. The goal of this study was to assess the feasibility and outcome of surgical treatment in recalcitrant nonunions of a lower extremity with bone graft enriched with autologous platelet gel (APG). Twelve patients with four femoral and eight tibial atrophic nonunions after multiple prior procedures were included. All of them were treated with the bone grafting procedures with autograft complex enriched with APG. They were evaluated with radiographs, bone mineral density for bony healing process, and the Short-Form 36 Health Survey for functional outcome. Of the 12 patients, 11 healed at an average of 19.7 weeks after the first attempt and 1 healed after the second attempt at 21 weeks. The bone mineral density continued to increase steadily from early healing to the remodeling phase. Functional status was greatly improved at an average follow-up of 32.4 months. The results of this preliminary study implied the possible potential of bone graft enriched with APG in the treatment of recalcitrant nonunions of the lower extremity. More research is necessary to clarify its role in augmentation of bone graft to enhance healing of nonunion.

  6. How does social functioning in the early stages of psychosis relate to depression and social anxiety?

    PubMed

    Chudleigh, Catherine; Naismith, Sharon L; Blaszczynski, Alex; Hermens, Daniel F; Hodge, M Antoinette Redoblado; Hickie, Ian B

    2011-08-01

    The study aims to compare social functioning in young people considered to be at risk of psychosis with those meeting criteria for first episode psychosis (FEP) and controls, and to determine the association between social functioning and positive and negative symptoms, depressive symptoms, and social anxiety. This study examined social functioning in 20 individuals at risk of psychosis, 20 FEP patients and 20 healthy controls. Social functioning was measured using the Social Functioning Scale and World Health Organization Disability Assessment Scale. Psychiatric variables were also measured using the Comprehensive Assessment of At-Risk Mental States, the Brief Psychiatric Rating Scale, the Brief Social Phobia Scale, and the Depression Anxiety and Stress Scale. At-risk individuals had comparable social deficits to the FEP group, and both patient groups had significantly poorer social functioning than controls. Importantly, social functioning was most strongly associated with depressive and social anxiety symptoms and to a lesser extent with positive symptoms. However, negative symptoms did not appear to relate to social functioning. Social functioning impairments precede the onset of full-threshold psychosis and may therefore be a significant marker for the illness. Additionally, associated psychiatric symptoms such as depression and social anxiety may provide an avenue for early interventions of social functioning deficits in psychosis. © 2011 Blackwell Publishing Asia Pty Ltd.

  7. Functional Dicer Is Necessary for Appropriate Specification of Radial Glia during Early Development of Mouse Telencephalon

    PubMed Central

    Nowakowski, Tomasz Jan; Mysiak, Karolina Sandra; Pratt, Thomas; Price, David Jonathan

    2011-01-01

    Early telencephalic development involves transformation of neuroepithelial stem cells into radial glia, which are themselves neuronal progenitors, around the time when the tissue begins to generate postmitotic neurons. To achieve this transformation, radial precursors express a specific combination of proteins. We investigate the hypothesis that micro RNAs regulate the ability of the early telencephalic progenitors to establish radial glia. We ablate functional Dicer, which is required for the generation of mature micro RNAs, by conditionally mutating the Dicer1 gene in the early embryonic telencephalon and analyse the molecular specification of radial glia as well as their progeny, namely postmitotic neurons and basal progenitors. Conditional mutation of Dicer1 from the telencephalon at around embryonic day 8 does not prevent morphological development of radial glia, but their expression of Nestin, Sox9, and ErbB2 is abnormally low. The population of basal progenitors, which are generated by the radial glia, is disorganised and expanded in Dicer1-/- dorsal telencephalon. While the proportion of cells expressing markers of postmitotic neurons is unchanged, their laminar organisation in the telencephalic wall is disrupted suggesting a defect in radial glial guided migration. We found that the laminar disruption could not be accounted for by a reduction of the population of Cajal Retzius neurons. Together, our data suggest novel roles for micro RNAs during early development of progenitor cells in the embryonic telencephalon. PMID:21826226

  8. Functional dicer is necessary for appropriate specification of radial glia during early development of mouse telencephalon.

    PubMed

    Nowakowski, Tomasz Jan; Mysiak, Karolina Sandra; Pratt, Thomas; Price, David Jonathan

    2011-01-01

    Early telencephalic development involves transformation of neuroepithelial stem cells into radial glia, which are themselves neuronal progenitors, around the time when the tissue begins to generate postmitotic neurons. To achieve this transformation, radial precursors express a specific combination of proteins. We investigate the hypothesis that micro RNAs regulate the ability of the early telencephalic progenitors to establish radial glia. We ablate functional Dicer, which is required for the generation of mature micro RNAs, by conditionally mutating the Dicer1 gene in the early embryonic telencephalon and analyse the molecular specification of radial glia as well as their progeny, namely postmitotic neurons and basal progenitors. Conditional mutation of Dicer1 from the telencephalon at around embryonic day 8 does not prevent morphological development of radial glia, but their expression of Nestin, Sox9, and ErbB2 is abnormally low. The population of basal progenitors, which are generated by the radial glia, is disorganised and expanded in Dicer1⁻/⁻ dorsal telencephalon. While the proportion of cells expressing markers of postmitotic neurons is unchanged, their laminar organisation in the telencephalic wall is disrupted suggesting a defect in radial glial guided migration. We found that the laminar disruption could not be accounted for by a reduction of the population of Cajal Retzius neurons. Together, our data suggest novel roles for micro RNAs during early development of progenitor cells in the embryonic telencephalon.

  9. Increased efficacy of VX-809 in different cellular systems results from an early stabilization effect of F508del-CFTR.

    PubMed

    Farinha, Carlos M; Sousa, Marisa; Canato, Sara; Schmidt, André; Uliyakina, Inna; Amaral, Margarida D

    2015-08-01

    Cystic fibrosis (CF), the most common recessive autosomal disease among Caucasians, is caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR) protein. The most common mutation, F508del, leads to CFTR impaired plasma membrane trafficking. Therapies modulating CFTR basic defect are emerging, such as VX-809, a corrector of F508del-CFTR traffic which just succeeded in a Phase III clinical trial. We recently showed that VX-809 is additive to two other correctors (VRT-325 and compound 4a). Here, we aimed to determine whether the differential rescuing by these compounds results from cell-specific factors or rather from distinct effects at the early biogenesis and/or processing. The rescuing efficiencies of the above three correctors were first compared in different cellular models (primary respiratory cells, cystic fibrosis bronchial epithelial and baby hamster kidney [BHK] cell lines) by functional approaches: micro-Ussing chamber and iodide efflux. Next, biochemical methods (metabolic labeling, pulse-chase and immunoprecipitation) were used to determine their impact on CFTR biogenesis / processing. Functional analyses revealed that VX-809 has the greatest rescuing efficacy and that the relative efficiencies of the three compounds are essentially maintained in all three cellular models tested. Nevertheless, biochemical data show that VX-809 significantly stabilizes F508del-CFTR immature form, an effect that is not observed for C3 nor C4. VX-809 and C3 also significantly increase accumulation of immature CFTR. Our data suggest that VX-809 increases the stability of F508del-CFTR immature form at an early phase of its biogenesis, thus explaining its increased efficacy when inducing its rescue.

  10. Increased efficacy of VX-809 in different cellular systems results from an early stabilization effect of F508del-CFTR

    PubMed Central

    Farinha, Carlos M; Sousa, Marisa; Canato, Sara; Schmidt, André; Uliyakina, Inna; Amaral, Margarida D

    2015-01-01

    Cystic fibrosis (CF), the most common recessive autosomal disease among Caucasians, is caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR) protein. The most common mutation, F508del, leads to CFTR impaired plasma membrane trafficking. Therapies modulating CFTR basic defect are emerging, such as VX-809, a corrector of F508del-CFTR traffic which just succeeded in a Phase III clinical trial. We recently showed that VX-809 is additive to two other correctors (VRT-325 and compound 4a). Here, we aimed to determine whether the differential rescuing by these compounds results from cell-specific factors or rather from distinct effects at the early biogenesis and/or processing. The rescuing efficiencies of the above three correctors were first compared in different cellular models (primary respiratory cells, cystic fibrosis bronchial epithelial and baby hamster kidney [BHK] cell lines) by functional approaches: micro-Ussing chamber and iodide efflux. Next, biochemical methods (metabolic labeling, pulse-chase and immunoprecipitation) were used to determine their impact on CFTR biogenesis / processing. Functional analyses revealed that VX-809 has the greatest rescuing efficacy and that the relative efficiencies of the three compounds are essentially maintained in all three cellular models tested. Nevertheless, biochemical data show that VX-809 significantly stabilizes F508del-CFTR immature form, an effect that is not observed for C3 nor C4. VX-809 and C3 also significantly increase accumulation of immature CFTR. Our data suggest that VX-809 increases the stability of F508del-CFTR immature form at an early phase of its biogenesis, thus explaining its increased efficacy when inducing its rescue. PMID:26171232

  11. Pelvic floor morphometry and function in women with and without puborectalis avulsion in the early postpartum period.

    PubMed

    Cyr, Marie-Pierre; Kruger, Jennifer; Wong, Vivien; Dumoulin, Chantale; Girard, Isabelle; Morin, Mélanie

    2017-03-01

    Pelvic floor muscles are subject to considerable stretching during vaginal birth. In 13-36% of women, stretching results in avulsion injury whereby the puborectalis muscle disconnects from its insertion points on the pubis bone. Until now, few studies have investigated the effect of this lesion on pelvic floor muscles in the early postpartum period. The primary aim of this study was to compare pelvic floor muscle morphometry and function in primiparous women with and without puborectalis avulsion in the early postpartum period. Our secondary objective was to compare the 2 groups for pelvic floor disorders and impact on quality of life. In all, 52 primiparous women diagnosed with (n = 22) or without (n = 30) puborectalis avulsion injury were assessed at 3 months postpartum. Pelvic floor muscle morphometry was evaluated with 3-/4-dimensional transperineal ultrasound at rest, maximal contraction, and Valsalva maneuver. Different parameters were measured in the midsagittal and axial planes: bladder neck position, levator plate angle, anorectal angle, and levator hiatus dimensions. The dynamometric speculum was used to assess pelvic floor muscle function including: passive properties (passive forces and stiffness) during dynamic stretches, maximal strength, speed of contraction, and endurance. Pelvic floor disorder-related symptoms (eg, urinary incontinence, vaginal and bowel symptoms) and impact on quality of life were evaluated with the International Consultation on Incontinence Questionnaire and the Pelvic Floor Impact Questionnaire-Short Form. Pelvic Organ Prolapse Quantification was also assessed. In comparison to women without avulsion, women with avulsion presented an enlarged hiatus area at rest, maximal contraction, and Valsalva maneuver (P ≤ .013) and all other ultrasound parameters were found to be significantly altered during maximal contraction (P ≤ .014). They showed lower passive forces at maximal and 20-mm vaginal apertures as well as lower

  12. A case of functional growth hormone deficiency and early growth retardation in a child with IFT172 mutations.

    PubMed

    Lucas-Herald, Angela K; Kinning, Esther; Iida, Aritoshi; Wang, Zheng; Miyake, Noriko; Ikegawa, Shiro; McNeilly, Jane; Ahmed, S Faisal

    2015-04-01

    Ciliopathies are a group of rare conditions that present through a wide range of manifestations. Given the relative common occurrence of defects of the GH/IGF-I axis in children with short stature and growth retardation, the association between ciliopathies and these defects needs further attention. Our patient is a boy who was born at term and noted to have early growth retardation and weight gain within the first 18 months of life. Biochemical tests demonstrated low IGF-I but a normal peak GH on stimulation and an adequate increase in IGF-I on administration of recombinant human growth hormone (rhGH). A magnetic resonance imaging scan revealed pituitary hypoplasia and an ectopic posterior pituitary. His growth responded well to rhGH therapy. Subsequently he also developed a retinopathy of his rods and cones, metaphyseal dysplasia, and hypertension with renal failure requiring renal replacement therapy. Whole-exome sequencing demonstrated compound heterozygous mutations of IFT172, thus consistent with a ciliopathy. This is the first reported case of a child with a mutation in IFT172 who presented with growth retardation in early childhood and was initially managed as a case of functional GH deficiency that responded to rhGH therapy. This case highlights the importance of ciliary function in pituitary development and the link between early onset growth failure and ciliopathies.

  13. Early application of an intermittent pneumatic compression device is safe and results in proximal arteriovenous fistula enlargement.

    PubMed

    Desai, Sanjay; Mitra, Amit; Arkans, Ed; Singh, Tej M

    2018-05-01

    Delays in arteriovenous fistula maturation can cause care delays and increased costs. Increased distention pressure and intermittent wall shear stress may dilate veins based on prior research. Early use of non-invasive devices may help assist clinical arteriovenous fistula dilation. This was an Institutional Review Board approved study. After arteriovenous fistula creation, a novel, intermittent pneumatic compression device (Fist Assist ® ) was applied 15 cm proximal to arteriovenous fistula enabling 60 mmHg of cyclic compression for 6 h daily for 30 days. Among the patients who completed 1 month follow-up, 30 (n = 30) arteriovenous fistula patients were in the study arm to test vein dilation with Fist Assist. Controls (n = 16) used a sham device. Vein size was measured and recorded at baseline and after 30 days by duplex measurement. Clinical results (percentage increase) were recorded and tested for significance. No patients experienced thrombosis or adverse effects. Patient compliance and satisfaction was high. After 1 month, the mean percentage increase in vein diameter in the Fist Assist treatment group was significantly larger (p = 0.026) than controls in the first 5 mm segment of the fistula after the anastomosis. All fistulas treated with Fist Assist are still functional with no reported thrombosis or extravasations. Early application of an intermittent pneumatic compression device may assist in arteriovenous fistula dilation and are safe. Non-invasive devices like Fist Assist may have clinical utility to help fistulae development and decrease costs as they may eventually assist maturation.

  14. Probing the early development of visual working memory capacity with functional near-infrared spectroscopy

    PubMed Central

    Buss, Aaron T.; Fox, Nicholas; Boas, David A.; Spencer, John P.

    2013-01-01

    Visual working memory (VWM) is a core cognitive system with a highly limited capacity. The present study is the first to examine VWM capacity limits in early development using functional neuroimaging. We recorded optical neuroimaging data while 3- and 4-year-olds completed a change detection task where they detected changes in the shapes of objects after a brief delay. Near-infrared sources and detectors were placed over the following 10–20 positions: F3 and F5 in left frontal cortex, F4 and F6 in right frontal cortex, P3 and P5 in left parietal cortex, and P4 and P6 in right parietal cortex. The first question was whether we would see robust task-specific activation of the frontal-parietal network identified in the adult fMRI literature. This was indeed the case: three left frontal channels and 11 of 12 parietal channels showed a statistically robust difference between the concentration of oxygenated and deoxygenated hemoglobin following the presentation of the sample array. Moreover, four channels in the left hemisphere near P3, P5, and F5 showed a robust increase as the working memory load increased from 1–3 items. Notably, the hemodynamic response did not asymptote at 1–2 items as expected from previous fMRI studies with adults. Finally, 4-year-olds showed a more robust parietal response relative to 3-year-olds, and an increasing sensitivity to the memory load manipulation. These results demonstrate that fNIRS is an effective tool to study the neural processes that underlie the early development of VWM capacity. PMID:23707803

  15. Probing the early development of visual working memory capacity with functional near-infrared spectroscopy.

    PubMed

    Buss, Aaron T; Fox, Nicholas; Boas, David A; Spencer, John P

    2014-01-15

    Visual working memory (VWM) is a core cognitive system with a highly limited capacity. The present study is the first to examine VWM capacity limits in early development using functional neuroimaging. We recorded optical neuroimaging data while 3- and 4-year-olds completed a change detection task where they detected changes in the shapes of objects after a brief delay. Near-infrared sources and detectors were placed over the following 10-20 positions: F3 and F5 in left frontal cortex, F4 and F6 in right frontal cortex, P3 and P5 in left parietal cortex, and P4 and P6 in right parietal cortex. The first question was whether we would see robust task-specific activation of the frontal-parietal network identified in the adult fMRI literature. This was indeed the case: three left frontal channels and 11 of 12 parietal channels showed a statistically robust difference between the concentration of oxygenated and deoxygenated hemoglobin following the presentation of the sample array. Moreover, four channels in the left hemisphere near P3, P5, and F5 showed a robust increase as the working memory load increased from 1 to 3 items. Notably, the hemodynamic response did not asymptote at 1-2 items as expected from previous fMRI studies with adults. Finally, 4-year-olds showed a more robust parietal response relative to 3-year-olds, and an increasing sensitivity to the memory load manipulation. These results demonstrate that fNIRS is an effective tool to study the neural processes that underlie the early development of VWM capacity. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Early stages of functional diversification in the Rab GTPase gene family revealed by genomic and localization studies in Paramecium species.

    PubMed

    Bright, Lydia J; Gout, Jean-Francois; Lynch, Michael

    2017-04-15

    New gene functions arise within existing gene families as a result of gene duplication and subsequent diversification. To gain insight into the steps that led to the functional diversification of paralogues, we tracked duplicate retention patterns, expression-level divergence, and subcellular markers of functional diversification in the Rab GTPase gene family in three Paramecium aurelia species. After whole-genome duplication, Rab GTPase duplicates are more highly retained than other genes in the genome but appear to be diverging more rapidly in expression levels, consistent with early steps in functional diversification. However, by localizing specific Rab proteins in Paramecium cells, we found that paralogues from the two most recent whole-genome duplications had virtually identical localization patterns, and that less closely related paralogues showed evidence of both conservation and diversification. The functionally conserved paralogues appear to target to compartments associated with both endocytic and phagocytic recycling functions, confirming evolutionary and functional links between the two pathways in a divergent eukaryotic lineage. Because the functionally diversifying paralogues are still closely related to and derived from a clade of functionally conserved Rab11 genes, we were able to pinpoint three specific amino acid residues that may be driving the change in the localization and thus the function in these proteins. © 2017 Bright et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  17. Vitamin D, the placenta and early pregnancy: effects on trophoblast function.

    PubMed

    Ganguly, Ankana; Tamblyn, Jennifer A; Finn-Sell, Sarah; Chan, Shiao-Y; Westwood, Melissa; Gupta, Janesh; Kilby, Mark D; Gross, Stephane R; Hewison, Martin

    2018-02-01

    Pregnancy is associated with significant changes in vitamin D metabolism, notably increased maternal serum levels of active vitamin D, 1,25-dihydroxyvitamin (1,25(OH) 2 D). This appears to be due primarily to increased renal activity of the enzyme 25-hydroxyvitamin D-1α-hydroxylase (CYP27B1) that catalyzes synthesis of 1,25(OH) 2 D, but CYP27B1 expression is also prominent in both the maternal decidua and fetal trophoblast components of the placenta. The precise function of placental synthesis of 1,25(OH) 2 D remains unclear, but is likely to involve localized tissue-specific responses with both decidua and trophoblast also expressing the vitamin D receptor (VDR) for 1,25(OH) 2 D. We have previously described immunomodulatory responses to 1,25(OH) 2 D by diverse populations of VDR-expressing cells within the decidua. The aim of the current review is to detail the role of vitamin D in pregnancy from a trophoblast perspective, with particular emphasis on the potential role of 1,25(OH) 2 D as a regulator of trophoblast invasion in early pregnancy. Vitamin D deficiency is common in pregnant women, and a wide range of studies have linked low vitamin D status to adverse events in pregnancy. To date, most of these studies have focused on adverse events later in pregnancy, but the current review will explore the potential impact of vitamin D on early pregnancy, and how this may influence implantation and miscarriage. © 2018 Society for Endocrinology.

  18. Social-cognitive functioning and social skills in patients with early treated phenylketonuria: a PKU-COBESO study.

    PubMed

    Jahja, Rianne; van Spronsen, Francjan J; de Sonneville, Leo M J; van der Meere, Jaap J; Bosch, Annet M; Hollak, Carla E M; Rubio-Gozalbo, M Estela; Brouwers, Martijn C G J; Hofstede, Floris C; de Vries, Maaike C; Janssen, Mirian C H; van der Ploeg, Ans T; Langendonk, Janneke G; Huijbregts, Stephan C J

    2016-05-01

    Early treatment of phenylketonuria (ET-PKU) prevents mental retardation, but many patients still show cognitive and mood problems. In this study, it was investigated whether ET-PKU-patients have specific phenylalanine (Phe-)related problems with respect to social-cognitive functioning and social skills. Ninety five PKU-patients (mean age 21.6 ± 10.2 years) and 95 healthy controls (mean age 19.6 ± 8.7 years) were compared on performance of computerized and paper-and-pencil tasks measuring social-cognitive abilities and on parent- and self-reported social skills, using multivariate analyses of variance, and controlling for general cognitive ability (IQ-estimate). Further comparisons were made between patients using tetrahydrobiopterin (BH4, N = 30) and patients not using BH4. Associations with Phe-levels on the day of testing, during childhood, during adolescence and throughout life were examined. PKU-patients showed poorer social-cognitive functioning and reportedly had poorer social skills than controls (regardless of general cognitive abilities). Quality of social-cognitive functioning was negatively related to recent Phe-levels and Phe-levels between 8 and 12 years for adolescents with PKU. Quality of social skills was negatively related to lifetime phenylalanine levels in adult patients, and specifically to Phe-levels between 0 and 7, and between 8 and 12 years. There were no differences with respect to social outcome measures between the BH4 and non-BH4 groups. PKU-patients have Phe-related difficulties with social-cognitive functioning and social skills. Problems seem to be more evident among adolescents and adults with PKU. High Phe-levels during childhood and early adolescence seem to be of greater influence than current and recent Phe-levels for these patients.

  19. Early sepsis does not stimulate reactive oxygen species production and does not reduce cardiac function despite an increased inflammation status.

    PubMed

    Léger, Thibault; Charrier, Alice; Moreau, Clarisse; Hininger-Favier, Isabelle; Mourmoura, Evangelia; Rigaudière, Jean-Paul; Pitois, Elodie; Bouvier, Damien; Sapin, Vincent; Pereira, Bruno; Azarnoush, Kasra; Demaison, Luc

    2017-07-01

    If it is sustained for several days, sepsis can trigger severe abnormalities of cardiac function which leads to death in 50% of cases. This probably occurs through activation of toll-like receptor-9 by bacterial lipopolysaccharides and overproduction of proinflammatory cytokines such as TNF- α and IL-1 β In contrast, early sepsis is characterized by the development of tachycardia. This study aimed at determining the early changes in the cardiac function during sepsis and at finding the mechanism responsible for the observed changes. Sixty male Wistar rats were randomly assigned to two groups, the first one being made septic by cecal ligation and puncture (sepsis group) and the second one being subjected to the same surgery without cecal ligation and puncture (sham-operated group). The cardiac function was assessed in vivo and ex vivo in standard conditions. Several parameters involved in the oxidative stress and inflammation were determined in the plasma and heart. As evidenced by the plasma level of TNF- α and gene expression of IL-1 β and TNF- α in the heart, inflammation was developed in the sepsis group. The cardiac function was also slightly stimulated by sepsis in the in vivo and ex vivo situations. This was associated with unchanged levels of oxidative stress, but several parameters indicated a lower cardiac production of reactive oxygen species in the septic group. In conclusion, despite the development of inflammation, early sepsis did not increase reactive oxygen species production and did not reduce myocardial function. The depressant effect of TNF- α and IL-1 β on the cardiac function is known to occur at very high concentrations. The influence of low- to moderate-grade inflammation on the myocardial mechanical behavior must thus be revisited. © 2017 French National Institute of Agronomical Research (INRA). Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  20. The effects of early-life stress on dopamine system function in adolescent female rats.

    PubMed

    Majcher-Maślanka, Iwona; Solarz, Anna; Wędzony, Krzysztof; Chocyk, Agnieszka

    2017-04-01

    During adolescence, many neural systems, including the dopamine system, undergo essential remodeling and maturation. It is well known that early-life stress (ELS) increases the risk for many psychopathologies during adolescence and adulthood. It is hypothesized that ELS interferes with the maturation of the dopamine system. There is a sex bias in the prevalence of stress-related mental disorders. Information regarding the effects of ELS on brain functioning in females is very limited. In the current study, maternal separation (MS) procedures were carried out to study the effects of ELS on dopamine system functioning in adolescent female rats. Our study showed that MS increased the density of tyrosine hydroxylase immunoreactive fibers in the prelimbic cortex (PLC) and nucleus accumbens (Acb). These changes were accompanied by a decrease in the level of D5 receptor mRNA and an increase in D2 receptor mRNA expression in the PLC of MS females. Conversely, D1 and D5 receptor mRNA levels were augmented in the caudate putamen (CPu), while the expression of the D3 dopamine receptor transcript was reduced in MS females. Additionally, in the Acb, MS elicited a decrease in D2 receptor mRNA expression. At the behavioral level, MS increased apomorphine-induced locomotion; however, it did not change locomotor responses to selective D1/D5 receptor agonist and attenuated D2/D3 receptor agonist-triggered locomotion. Moreover, MS decreased D1/D5 receptor agonist-induced grooming behavior. These results indicate that ELS disrupts dopamine receptor function in the PLC and basal ganglia during adolescence in females and may predispose them to psychopathologies during adolescence and adulthood. Copyright © 2017 ISDN. Published by Elsevier Ltd. All rights reserved.

  1. Dual function of CD70 in viral infection: modulator of early cytokine responses and activator of adaptive responses1

    PubMed Central

    Allam, Atef; Swiecki, Melissa; Vermi, William; Ashwell, Jonathan D.; Colonna, Marco

    2014-01-01

    The role of the tumor necrosis factor family member CD70 in adaptive T cell responses has been intensively studied but its function in innate responses is still under investigation. Here we show that CD70 inhibits the early innate response to murine cytomegalovirus (MCMV) but is essential for the optimal generation of virus-specific CD8 T cells. CD70-/- mice reacted to MCMV infection with a robust type I interferon and proinflammatory cytokine response. This response was sufficient for initial control of MCMV, although at later time points, CD70-/- mice became more susceptible to MCMV infection. The heightened cytokine response during the early phase of MCMV infection in CD70-/- mice was paralleled by a reduction in regulatory T cells (Treg). Treg from naïve CD70-/- mice were not as efficient at suppressing T cell proliferation compared to Treg from naïve WT mice and depletion of Treg during MCMV infection in Foxp3-DTR mice or in WT mice recapitulated the phenotype observed in CD70-/- mice. Our study demonstrates that while CD70 is required for the activation of the antiviral adaptive response, it has a regulatory role in early cytokine responses to viruses such as MCMV, possibly through maintenance of Treg survival and function. PMID:24913981

  2. A novel mixed phospholipid functionalized monolithic column for early screening of drug induced phospholipidosis risk.

    PubMed

    Zhao, XiangLong; Chen, WeiJia; Liu, ZhengHua; Guo, JiaLiang; Zhou, ZhengYin; Crommen, Jacques; Moaddel, Ruin; Jiang, ZhengJin

    2014-11-07

    Drug-induced phospholipidosis (PLD) is characterized by the excessive accumulation of phospholipids, resulting in multilamellar vesicle structure within lysosomes. In the present study, a novel mixed phospholipid functionalized monolithic column was developed for the first time through a facile one-step co-polymerization approach. The phospholipid composition of the monolith can be adjusted quantitatively and accurately to mimic the mixed phospholipid environment of different biomembranes on a solid matrix. The mixed phospholipid functionalized monolith as a promising immobilized artificial membrane technique was used to study drug-phospholipid interaction. Scanning electron microscopy, elemental analysis, FT-IR spectra, ζ-potential analysis and micro-HPLC were carried out to characterize the physicochemical properties and separation performance of the monolith. Mechanism studies revealed that both hydrophobic and electrostatic interactions play an important role in the retention of analytes. The ratio of their contributions to retention can be easily manipulated by adjusting the composition of the mixed phospholipids, in order to better mimic the interaction between drugs and cell membrane. The obtained mixed phospholipid functionalized monolithic columns were applied to the screening of drug-induced PLD potency. Data from 79 drugs on the market demonstrated that the chromatographic hydrophobicity index referring to the mixed phospholipid functionalized monolith at pH 7.4 (CHI IAM7.4) for the selected drugs were highly correlated with the drug-induced PLD potency data obtained from other in vivo or in vitro assays. Moreover, the effect of the acidic phospholipid phosphatidylserine proportion on prediction accuracy was also investigated. The monolith containing 20% phosphatidylserine and 80% phosphatidylcholine exhibited the best prediction ability for the drug-induced PLD potency of the tested compounds. This research has led to the successful development of a

  3. Early life environmental and pharmacological stressors result in persistent dysregulations of the serotonergic system

    PubMed Central

    Wong, Peiyan; Sze, Ying; Gray, Laura Jane; Chang, Cecilia Chin Roei; Cai, Shiwei; Zhang, Xiaodong

    2015-01-01

    Dysregulations in the brain serotonergic system and exposure to environmental stressors have been implicated in the development of major depressive disorder. Here, we investigate the interactions between the stress and serotonergic systems by characterizing the behavioral and biochemical effects of chronic stress applied during early-life or adulthood in wild type (WT) mice and mice with deficient tryptophan hydroxylase 2 (TPH2) function. We showed that chronic mild stress applied in adulthood did not affect the behaviors and serotonin levels of WT and TPH2 knock-in (KI) mice. Whereas, maternal separation (MS) stress increased anxiety- and depressive-like behaviors of WT mice, with no detectable behavioral changes in TPH2 KI mice. Biochemically, we found that MS WT mice had reduced brain serotonin levels, which was attributed to increased expression of monoamine oxidase A (MAO A). The increased MAO A expression was detected in MS WT mice at 4 weeks old and adulthood. No change in TPH2 expression was detected. To determine whether a pharmacological stressor, dexamethasone (Dex), will result in similar biochemical results obtained from MS, we used an in vitro system, SH-SY5Y cells, and found that Dex treatment resulted in increased MAO A expression levels. We then treated WT mice with Dex for 5 days, either during postnatal days 7–11 or adulthood. Both groups of Dex treated WT mice had reduced basal corticosterone and glucocorticoid receptors expression levels. However, only Dex treatment during PND7–11 resulted in reduced serotonin levels and increased MAO A expression. Just as with MS WT mice, TPH2 expression in PND7–11 Dex-treated WT mice was unaffected. Taken together, our findings suggest that both environmental and pharmacological stressors affect the expression of MAO A, and not TPH2, when applied during the critical postnatal period. This leads to long-lasting perturbations in the serotonergic system, and results in anxiety- and depressive

  4. Optimal methotrexate dose is associated with better clinical outcomes than non-optimal dose in daily practice: results from the ESPOIR early arthritis cohort.

    PubMed

    Gaujoux-Viala, Cécile; Rincheval, Nathalie; Dougados, Maxime; Combe, Bernard; Fautrel, Bruno

    2017-12-01

    Although methotrexate (MTX) is the consensual first-line disease-modifying antirheumatic drug (DMARD) for rheumatoid arthritis (RA), substantial heterogeneity remains with its prescription and dosage, which are often not optimal. To evaluate the symptomatic and structural impact of optimal MTX dose in patients with early RA in daily clinical practice over 2 years. Patients included in the early arthritis ESPOIR cohort who fulfilled the ACR-EULAR (American College of Rheumatology/European League against Rheumatism) criteria for RA and received MTX as a first DMARD were assessed. Optimal MTX dose was defined as ≥10 mg/week during the first 3 months, with escalation to ≥20 mg/week or 0.3 mg/kg/week at 6 months without Disease Activity Score in 28 joints remission. Symptomatic and structural efficacy with and without optimal MTX dose was assessed by generalised logistic regression with adjustment for appropriate variables. Within the first year of follow-up, 314 patients (53%) with RA received MTX as a first DMARD (mean dose 12.2±3.8 mg/week). Only 26.4% (n=76) had optimal MTX dose. After adjustment, optimal versus non-optimal MTX dose was more efficient in achieving ACR-EULAR remission at 1 year (OR 4.28 (95% CI 1.86 to 9.86)) and normal functioning (Health Assessment Questionnaire ≤0.5; OR at 1 year 4.36 (95% CI 2.03 to 9.39)), with no effect on radiological progression. Results were similar during the second year. Optimal MTX dose is more efficacious than non-optimal dose for remission and function in early arthritis in daily practice, with no impact on radiological progression over 2 years. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  5. A Test of Three Alternative Hypotheses regarding the Effects of Early Delinquency on Adolescent Psychosocial Functioning and Substance Involvement

    ERIC Educational Resources Information Center

    Mason, W. Alex; Hitchings, Julia E.; McMahon, Robert J.; Spoth, Richard L.

    2007-01-01

    This study compared alternative hypotheses (from general deviance, life course, and developmental psychopathology perspectives) regarding the effects of early adolescent delinquency on psychosocial functioning in family, school, and peer contexts, and on alcohol use. Analyses also examined parent-child negative affective quality, prosocial school…

  6. Effects of Aerobic Exercise Applied Early After Coronary Artery Bypass Grafting on Pulmonary Function, Respiratory Muscle Strength, and Functional Capacity: A Randomized Controlled Trial.

    PubMed

    Borges, Daniel L; Silva, Mayara Gabrielle; Silva, Luan Nascimento; Fortes, João Vyctor; Costa, Erika Thalita; Assunção, Rebeca Pessoa; Lima, Carlos Magno; da Silva Nina, Vinícius José; Bernardo-Filho, Mário; Caputo, Danúbia Sá

    2016-09-01

    Physical activity is beneficial in several clinical situations and recommended for patients with ischemic heart disease, as well as for those undergoing cardiac surgery. In a randomized controlled trial, 34 patients underwent coronary artery bypass grafting. A randomized control group (n = 15) submitted to conventional physiotherapy. The intervention group (n = 19) received the same protocol plus additional aerobic exercise with cycle ergometer. Pulmonary function by spirometry, respiratory muscle strength by manovacuometry, and functional capacity through 6-minute walking test was assessed before surgery and at hospital discharge. There was significant reduction in pulmonary function in both groups. In both groups, inspiratory muscle strength was maintained while expiratory muscle strength significantly decreased. Functional capacity was maintained in the intervention group (364.5 [324.5 to 428] vs. 348 [300.7 to 413.7] meters, P = .06), but it decreased significantly in control group patients (320 [288.5 to 393.0] vs. 292 [237.0 to 336.0] meters, P = .01). A significant difference in functional capacity was also found in intergroup analyses at hospital discharge (P = .03). Aerobic exercise applied early on coronary artery bypass grafting patients may promote maintenance of functional capacity, with no impact on pulmonary function and respiratory muscle strength when compared with conventional physiotherapy.

  7. Early aphasia rehabilitation is associated with functional reactivation of the left inferior frontal gyrus: a pilot study.

    PubMed

    Mattioli, Flavia; Ambrosi, Claudia; Mascaro, Lorella; Scarpazza, Cristina; Pasquali, Patrizia; Frugoni, Marina; Magoni, Mauro; Biagi, Laura; Gasparotti, Roberto

    2014-02-01

    Early poststroke aphasia rehabilitation effects and their functional MRI (fMRI) correlates were investigated in a pilot, controlled longitudinal study. Twelve patients with mild/moderate aphasia (8 Broca, 3 anomic, and 1 Wernicke) were randomly assigned to daily language rehabilitation for 2 weeks (starting 2.2 [mean] days poststroke) or no rehabilitation. The Aachen Aphasia Test and fMRI recorded during an auditory comprehension task were performed at 3 time intervals: mean 2.2 (T1), 16.2 (T2), and 190 (T3) days poststroke. Groups did not differ in terms of age, education, aphasia severity, lesions volume, baseline fMRI activations, and in task performance during fMRI across examinations. Rehabilitated patients significantly improved in naming and written language tasks (P<0.05) compared with no rehabilitation group both at T2 and T3. Functional activity at T1 was reduced in language-related cortical areas (right and left inferior frontal gyrus and middle temporal gyrus, right inferior parietal lobule and superior temporal gyrus) in patients compared with controls. T2 and T3 follow-ups revealed a cortical activation increase, with significantly greater activation in the left hemisphere areas in rehabilitated patients at T2 and T3, and a time×treatment effect at T2 in the left inferior Broca area after rehabilitation. Left inferior frontal gyrus activation at T2 significantly correlated with naming improvement. Early poststroke aphasia treatment is useful, has durable effects, and may lead to early enhanced recruitment of brain areas, particularly the left inferior frontal gyrus, which persists in the chronic phase.

  8. FUNCTIONAL OUTCOMES OF HIP ARTHROSCOPY IN AN ACTIVE DUTY MILITARY POPULATION UTILIZING A CRITERION-BASED EARLY WEIGHT BEARING PROGRESSION.

    PubMed

    Shaw, K Aaron; Jacobs, Jeremy M; Evanson, J Richard; Pniewski, Josh; Dickston, Michelle L; Mueller, Terry; Bojescul, John A

    2017-10-01

    Hip arthroscopy allows surgeons to address intra-articular pathology of the hip while avoiding more invasive open surgical dislocation. However the post-operative rehabilitation protocols have varied greatly in the literature, with many having prolonged periods of limited motion and weight bearing. The purpose of this study was to describe a criterion-based early weight bearing protocol following hip arthroscopy and investigate functional outcomes in the subjects who were active duty military. Active duty personnel undergoing hip arthroscopy for symptomatic femoroacetabular impingement were prospectively assessed in a controlled environment for the ability to incorporate early postoperative weight-bearing with the following criteria: no increased pain complaint with weight bearing and normalized gait pattern. Modified Harris Hip (HHS) and Hip Outcome score (HOS) were performed preoperatively and at six months post-op. Participants were progressed with a standard hip arthroscopy protocol. Hip flexion was limited to not exceed 90 degrees for the first three weeks post-op, with progression back to running beginning at three months. Final discharge was dependent upon the ability to run two miles at military specified pace and do a single leg broad jump within six inches of the contralateral leg without an increase in pain. Eleven participants met inclusion criteria over the study period. Crutch use was discontinued at an average of five days following surgery based on established weight bearing criteria. Only one participant required continued crutch use at 15 days. Participants' functional outcome was improved postoperatively, as demonstrated by significant increases in HOS and HHS. At the six month follow up, eight of 11 participants were able to take and complete a full Army Physical Fitness Test. Following completion of the early weight bearing rehabilitation protocol, 81% of participants were able to progress to full weight bearing by four days post

  9. Early results of Latitude primary total elbow replacement with a minimum follow-up of 2 years.

    PubMed

    Mehta, Saurabh S; Watts, Adam C; Talwalkar, Sumedh C; Birch, Ann; Nuttall, David; Trail, Ian A

    2017-10-01

    The aim of this study was to present outcomes of primary Latitude total elbow replacement (TER) with a minimum follow-up of 2 years. A retrospective cohort study was undertaken with prospective outcome data collection for the latest outcome. Included were 63 consecutive primary Latitude TERs in 58 patients performed during a period of 5 years at a specialist orthopedic hospital. The mean age of the patients was 62 years (33-85 years). Five primary TERs (4 patients) were lost to follow-up. The primary diagnosis was rheumatoid arthritis in 49, osteoarthritis in 8, and trauma in 6 elbows. The mean flexion-extension arc was 75° preoperatively and 97° postoperatively. Mean postoperative Elbex pain score was 19/100, and function score was 37/100. Mean postoperative scores were 42/100 for the Quick Disabilities of the Arm, Shoulder, and Hand and 38/50 for the elbow-specific American Shoulder and Elbow Surgeons assessment. Four patients died of unrelated causes, and 8 of 63 underwent further surgical intervention, including explantation and conversion from unlinked to linked implant. On radiographic review of 41 surviving TERs, aseptic radiologic loosening was observed of the humeral component in 4 elbows and of the ulnar component in 9. Seven elbows had no radial component, and of the remaining 34 elbows, 16 (47%) had signs of loosening of the radial implant. Complications included 1 heterotopic ossification, 1 olecranon fracture, and 3 further procedures for ulnar nerve entrapment. The results indicate that the early outcome of Latitude TER is comparable to that of other prostheses. There is concern about early radiologic loosening of the radial component. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  10. Limitation of myocardial infarct size and preservation of left ventricular function by early administration of APSAC in myocardial infarction.

    PubMed

    Bassand, J P; Machecourt, J; Cassagnes, J; Lusson, J R; Borel, E; Schiele, F

    1989-07-05

    In cases of acute myocardial infarction (MI), it has been shown that preserving left ventricular function and limiting infarct size with early reperfusion of the occluded artery by means of a thrombolytic agent could eventually result in a reduced mortality rate. The aim of the APSIM study (anisoylated plasminogen streptokinase activator complex [APSAC] dans l'infarctus du Myocarde) was to demonstrate that early administration of APSAC in patients with recent acute MI could limit the infarct size and preserve left ventricular systolic function. In all, 231 patients with a first acute MI were randomly allocated to either APSAC (30 U over 5 minutes) or to conventional heparin therapy (5,000 IU in bolus injection) within 5 hours of the onset of symptoms. Of these patients, 112 received APSAC and 119 received heparin within a mean period of 188 +/- 62 minutes after the onset of symptoms. The patency rate of the infarct-related artery was 77% in the APSAC group and 36% in the heparin group (p less than 0.001). Left ventricular ejection fraction determined from contrast angiography was significantly higher in the APSAC than in the heparin group. This was true for the entire population (0.53 +/- 0.13 vs 0.47 +/- 0.13, p = 0.002) as well as for the subgroups of anterior and inferior wall infarctions (0.47 +/- 0.13 vs 0.4 +/- 0.16, p = 0.004 and 0.56 +/- 0.11 vs 0.51 +/- 0.09, p = 0.02). At 3 weeks, the difference remained significant for patients with anterior MI.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. Behavioral and anatomical consequences of early versus late symbol training in macaques.

    PubMed

    Srihasam, Krishna; Mandeville, Joseph B; Morocz, Istvan A; Sullivan, Kevin J; Livingstone, Margaret S

    2012-02-09

    Distinct brain regions, reproducible from one person to the next, are specialized for processing different kinds of human expertise, such as face recognition and reading. Here, we explore the relationship between age of learning, learning ability, and specialized brain structures. Specifically, we ask whether the existence of reproducible cortical domains necessarily means that certain abilities are innate, or innately easily learned, or whether reproducible domains can be formed, or refined, by interactions between genetic programs and common early experience. Functional MRI showed that intensive early, but not late, experience caused the formation of category-selective regions in macaque temporal lobe for stimuli never naturally encountered by monkeys. And behaviorally, early training produced more fluent processing of these stimuli than the same training in adults. One explanation for these results is that in higher cortical areas, as in early sensory areas, experience drives functional clustering and functional clustering determines how that information is processed. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. Applying cognitive training to target executive functions during early development.

    PubMed

    Wass, Sam V

    2015-01-01

    Developmental psychopathology is increasingly recognizing the importance of distinguishing causal processes (i.e., the mechanisms that cause a disease) from developmental outcomes (i.e., the symptoms of the disorder as it is eventually diagnosed). Targeting causal processes early in disordered development may be more effective than waiting until outcomes are established and then trying to reverse the pathogenic process. In this review, I evaluate evidence suggesting that neural and behavioral plasticity may be greatest at very early stages of development. I also describe correlational evidence suggesting that, across a number of conditions, early emerging individual differences in attentional control and working memory may play a role in mediating later-developing differences in academic and other forms of learning. I review the currently small number of studies that applied direct and indirect cognitive training targeted at young individuals and discuss methodological challenges associated with targeting this age group. I also discuss a number of ways in which early, targeted cognitive training may be used to help us understand the developmental mechanisms subserving typical and atypical cognitive development.

  13. Applying cognitive training to target executive functions during early development

    PubMed Central

    Wass, Sam V.

    2015-01-01

    Developmental psychopathology is increasingly recognizing the importance of distinguishing causal processes (i.e., the mechanisms that cause a disease) from developmental outcomes (i.e., the symptoms of the disorder as it is eventually diagnosed). Targeting causal processes early in disordered development may be more effective than waiting until outcomes are established and then trying to reverse the pathogenic process. In this review, I evaluate evidence suggesting that neural and behavioral plasticity may be greatest at very early stages of development. I also describe correlational evidence suggesting that, across a number of conditions, early emerging individual differences in attentional control and working memory may play a role in mediating later-developing differences in academic and other forms of learning. I review the currently small number of studies that applied direct and indirect cognitive training targeted at young individuals and discuss methodological challenges associated with targeting this age group. I also discuss a number of ways in which early, targeted cognitive training may be used to help us understand the developmental mechanisms subserving typical and atypical cognitive development. PMID:24511910

  14. Functionalized nanoparticles provide early cardioprotection after acute myocardial infarction.

    PubMed

    Chang, Ming-Yao; Yang, Yu-Jen; Chang, Chih-Han; Tang, Alan C L; Liao, Wei-Yin; Cheng, Fong-Yu; Yeh, Chen-Sheng; Lai, James J; Stayton, Patrick S; Hsieh, Patrick C H

    2013-09-10

    Recent developments in nanotechnology have created considerable potential toward diagnosis and cancer therapy. In contrast, the use of nanotechnology in tissue repair or regeneration remains largely unexplored. We hypothesized that intramyocardial injection of insulin-like growth factor (IGF)-1-complexed poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (PLGA-IGF-1 NPs) increases IGF-1 retention, induces Akt phosphorylation, and provides early cardioprotection after acute myocardial infarction (MI). We synthesized 3 different sizes of PLGA particles (60 nm, 200 nm, and 1 μm) which were complexed with IGF-1 using electrostatic force to preserve the biological function of IGF-1. Afterward, we injected PLGA-IGF-1 NPs in the heart after MI directly. Compared with the other two larger particles, the 60 nm-sized PLGA-IGF-1 NPs carried more IGF-1 and induced more Akt phosphorylation in cultured cardiomyocytes. PLGA-IGF-1 NPs also prolonged Akt activation in cardiomyocytes up to 24h and prevented cardiomyocyte apoptosis induced by doxorubicin in a dose-dependent manner. In vivo, PLGA-IGF-1 NP treatment significantly retained more IGF-1 in the myocardium than the IGF-1 alone treatment at 2, 6, 8, and 24 h. Akt phosphorylation was detected in cardiomyocytes 24h post-MI only in hearts receiving PLGA-IGF-1 NP treatment, but not in hearts receiving injection of PBS, IGF-1 or PLGA NPs. Importantly, a single intramyocardial injection of PLGA-IGF-1 NPs was sufficient to prevent cardiomyocyte apoptosis (P<0.001), reduce infarct size (P<0.05), and improve left ventricle ejection fraction (P<0.01) 21 days after experimental MI in mice. Our results not only demonstrate the potential of nanoparticle-based technology as a new approach to treating MI, but also have significant implications for translation of this technology into clinical therapy for ischemic cardiovascular diseases. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. A New Observation Technique Applied to Early/Fast VLF Scattering Events

    NASA Astrophysics Data System (ADS)

    Kotovsky, D. A.; Moore, R. C.

    2012-12-01

    Early/fast very low frequency (VLF, 3-30 kHz) events are understood to result from ionospheric conductivity changes associated with lightning. Early/fast amplitude and phase perturbations have been observed coincidentally with various optical observations of transient luminous events (TLEs), including elves, sprites, and sprite halos, each of which can have temporal characteristics consistent with those of early/fast VLF events. It is yet unresolved, however, whether a specific type of TLE is directly related to the ionospheric conductivity changes responsible for the typical early/fast event. In this paper, we present spread spectrum VLF scattering observations of early/fast events. The spread spectrum analysis technique determines the amplitude and phase of a subionospherically propagating VLF signal as a function of time during the early/fast event and as a function of frequency across the 200 Hz bandwidth of the VLF transmission. VLF scattering observations, each identified with causative lightning logged by the National Lightning Detection Network (NLDN), are compared with the predictions of the Long-Wave Propagation Capability (LWPC) code, a three-dimensional earth-ionosphere waveguide propagation and scattering model. Theoretical predictions for VLF scattering from ionization changes associated with elves are compared with those associated with sprite halos, and each are compared with experimental observations. Results indicate that the observed frequency dependence of VLF scattering during early/fast events results from the combination of scattering source properties and Earth-ionosphere waveguide propagation effects. Observations are more consistent with the modeled amplitude perturbations associated with sprite halos than those with elves.

  16. A functional requirement for astroglia in promoting blood vessel development in the early postnatal brain.

    PubMed

    Ma, Shang; Kwon, Hyo Jun; Huang, Zhen

    2012-01-01

    Astroglia are a major cell type in the brain and play a key role in many aspects of brain development and function. In the adult brain, astrocytes are known to intimately ensheath blood vessels and actively coordinate local neural activity and blood flow. During development of the neural retina, blood vessel growth follows a meshwork of astrocytic processes. Several genes have also been implicated in retinal astrocytes for regulating vessel development. This suggests a role of astrocytes in promoting angiogenesis throughout the central nervous system. To determine the roles that astrocytes may play during brain angiogenesis, we employ genetic approaches to inhibit astrogliogenesis during perinatal corticogenesis and examine its effects on brain vessel development. We find that conditional deletion from glial progenitors of orc3, a gene required for DNA replication, dramatically reduces glial progenitor cell number in the subventricular zone and astrocytes in the early postnatal cerebral cortex. This, in turn, results in severe reductions in both the density and branching frequency of cortical blood vessels. Consistent with a delayed growth but not regression of vessels, we find neither significant net decreases in vessel density between different stages after normalizing for cortical expansion nor obvious apoptosis of endothelial cells in these mutants. Furthermore, concomitant with loss of astroglial interactions, we find increased endothelial cell proliferation, enlarged vessel luminal size as well as enhanced cytoskeletal gene expression in pericytes, which suggests compensatory changes in vascular cells. Lastly, we find that blood vessel morphology in mutant cortices recovers substantially at later stages, following astrogliosis. These results thus implicate a functional requirement for astroglia in promoting blood vessel growth during brain development.

  17. Functional analysis and treatment of problem behavior in early education classrooms.

    PubMed

    Greer, Brian D; Neidert, Pamela L; Dozier, Claudia L; Payne, Steven W; Zonneveld, Kimberley L M; Harper, Amy M

    2013-01-01

    We conducted functional analyses (FA) with 4 typically developing preschool children during ongoing classroom activities and evaluated treatments that were based on FA results. Results of each child's FA suggested social-positive reinforcement functions, and differential reinforcement of alternative behavior plus time-out was effective in decreasing problem behavior and increasing appropriate behavior. We discuss the utility of classroom-based FAs and potential compromises to experimental control. © Society for the Experimental Analysis of Behavior.

  18. Evaluation of right ventricular function in early period following transcatheter closure of atrial septal defect.

    PubMed

    Ağaç, Mustafa Tarık; Akyüz, Ali Rıza; Acar, Zeydin; Akdemir, Ramazan; Korkmaz, Levent; Kırış, Abdülkadir; Erkuş, Emre; Erkan, Hakan; Celik, Sükrü

    2012-03-01

    There is limited data on alterations in novel right ventricular (RV) function indices like tricuspid annular plane systolic excursion (TAPSE) and tricuspid annular systolic velocity (TASV) after transcatheter atrial septal defect (ASD) closure. We aimed to evaluate RV function by echocardiography (ECG) with these novel indices in early period in patients with secundum-type ASD that was closed percutaneously. Patients were enrolled to study if they had secundum-type ASD that was suitable for percutaneous closure. Patient population consisted of 4 men and 16 women. Echocardiography was performed before and 1 month after closure. Mean age was 37 ± 16. Mean diameter of ASD and total atrial septum length measured by ECG were 19 ± 6 mm and 49 ± 7 mm, respectively. Mean diameter of defect in transesophageal echocardiography was 20 ± 6 mm. Stretched mean diameter in catheterization was 23 ± 6 mm. One month after closure, there were statistically significant decreases in RV end-diastolic diameters (43.3 ± 10.7 mm vs. 34.9 ± 5.5 mm; P < 0.001), RV/left ventricular (LV) end-diastolic diameter ratio (1.1 ± 0.3 vs. 0.87 ± 0.1; P < 0.001), TASV (16.9 ± 3.2 cm/sec vs. 14.3 ± 3.3 cm/sec; P < 0.05), early diastolic tricuspid annular velocity (15.3 ± 3.1 cm/sec vs. 13.4 ± 2.4 cm/sec P <0.05), late diastolic tricuspid annular velocity (16.2 ± 5.4 cm/sec vs. 14.3 ± 6.3 cm/sec; P < 0.05), and TAPSE (29.9 ± 6.2 mm vs. 22.4 ± 7.4 mm; P < 0.001). LV end-diastolic diameter (38.0 ± 6.9 mm and 40.0 ± 4.5 P < 0.05) was increased, whereas there was no change in LV ejection fraction. Closure of ASD by using Amplatzer devices led to decrease in right heart chamber size, tissue Doppler-derived tricuspid annular velocities and TAPSE in early period. © 2011, Wiley Periodicals, Inc.

  19. Lipid raft disarrangement as a result of neuropathological progresses: a novel strategy for early diagnosis?

    PubMed

    Marin, R; Rojo, J A; Fabelo, N; Fernandez, C E; Diaz, M

    2013-08-15

    Lipid rafts are the preferential site of numerous membrane signaling proteins which are involved in neuronal functioning and survival. These proteins are organized in multiprotein complexes, or signalosomes, in close contact with lipid classes particularly represented in lipid rafts (i.e. cholesterol, sphingolipids and saturated fatty acids), which may contribute to physiological responses leading to neuroprotection. Increasing evidence indicates that alteration of lipid composition in raft structures as a consequence of neuropathologies, such as Alzheimer's disease (AD) and Parkinson's disease (PD), causes a dramatic increase in lipid raft order. These phenomena may correlate with perturbation of signalosome activities, likely contributing to neurodegenerative progression. Interestingly, significant disruption of stable raft microenvironments has been already observed in the first stages of either AD or PD, suggesting that these alterations may represent early events in the neuropathological development. In this regard, the search for biochemical markers, such as specific metabolic products altered in the brain at the first steps of the disease, presently represents an important challenge for early diagnostic strategies. Alterations of these biomarkers may be reflected in either plasma or cerebrospinal fluid, thus representing a potential strategy to predict an accurate diagnosis. We propose that pathologically-linked lipid raft markers may be interesting candidates to be explored at this level, although it has not been studied so far to what extent alteration of different signalosome components may be reflected in peripheral fluids. In this mini-review, we will discuss on relevant aspects of lipid rafts that contribute to the modulation of neuropathological events related to AD and PD. An interesting hypothesis is that anomalies on raft biomarkers measured at peripheral fluids might mirror the lipid raft pathology observed in early stages of AD and PD. Copyright

  20. Assessment of renal perfusion with contrast-enhanced ultrasound: Preliminary results in early diabetic nephropathies.

    PubMed

    Dong, Yi; Wang, Wen-Ping; Lin, Pan; Fan, Peili; Mao, Feng

    2016-01-01

    We performed a prospective study to evaluate the value of contrast-enhanced ultrasound (CEUS) in quantitative evaluation of renal cortex perfusion in patients suspected of early diabetic nephropathies (DN), with the estimated GFR (MDRD equation) as the gold standard. The study protocol was approved by the hospital review board; each patient gave written informed consent. Our study included 46 cases (21 males and 25 females, mean age 55.6 ± 4.14 years) of clinical confirmed early DN patients. After intravenous bolus injection of 1 ml sulfur hexafluoride microbubbles of ultrasound contrast agent, real time CEUS of renal cortex was performed successively using a 2-5 MHz convex probe. Time-intensity curves (TICs) and quantitative indexes were created with Qlab software. Receiver operating characteristic (ROC) curves were used to predict the diagnostic criteria of CEUS quantitative indexes, and their diagnostic efficiencies were compared with resistance index (RI) and peak systolic velocity (PSV) of renal segmental arteries by chi square test. Our control group included forty-five healthy volunteers. Difference was considered statistically significant with P <  0.05. Changes of area under curve (AUC), derived peak intensity (DPI) were statistically significant (P <  0.05). DPI less than 12 and AUC greater than 1400 had high utility in DN, with 71.7% and 67.3% sensitivity, 77.8% and 80.0% specificity. These results were significantly better than those obtained with RI and PSV which had no significant difference in early stage of DN (P > 0.05). CEUS might be helpful to improve early diagnosis of DN by quantitative analyses. AUC and DPI might be valuable quantitative indexes.