Mesenchymal stem cells regulate airway contractile tissue remodeling in murine experimental asthma.

BACKGROUND: Mesenchymal stem cells may offer therapeutic potential for asthma due to their immunomodulatory properties and host tolerability, yet prior evidence suggests that bloodborne progenitor cells may participate in airway remodeling. Here, we tested whether mesenchymal stem cells administered as anti-inflammatory therapy may favor airway remodeling and therefore be detrimental. METHODS: Adipose tissue-derived mesenchymal stem cells were retrovirally transduced to express green fluorescent protein and intravenously injected into mice with established experimental asthma induced by repeat intranasal house dust mite extract. Controls were house dust mite-instilled animals receiving intravenous vehicle or phosphate-buffered saline-instilled animals receiving mesenchymal stem cells. Data on lung function, airway inflammation, and remodeling were collected at 72 h after injection or after 2 weeks of additional intranasal challenge. RESULTS: The mesenchymal stem cells homed to the lungs and rapidly downregulated airway inflammation in association with raised T-helper-1 lung cytokines, but such effect declined under sustained allergen challenge despite a persistent presence of mesenchymal stem cells. Conversely, airway hyperresponsiveness and contractile tissue underwent a late reduction regardless of continuous pathogenic stimuli and inflammatory rebound. Tracking of green fluorescent protein did not show mesenchymal stem cell integration or differentiation in airway wall tissues. CONCLUSIONS: Therapeutic mesenchymal stem cell infusion in murine experimental asthma is free of unwanted pro-remodeling effects and ameliorates airway hyper-responsiveness and contractile tissue remodeling. These outcomes support furthering the development of mesenchymal stem cell-based asthma therapies, although caution and solid preclinical data building are warranted.

Construct validity of the Trail Making Test: role of task-switching, working memory, inhibition/interference control, and visuomotor abilities.

The aim of this study was to clarify which cognitive mechanisms underlie Trail Making Test (TMT) direct and derived scores. A comprehensive review of the literature on the topic was carried out to clarify which cognitive factors had been related to TMT performance. Following the review, we explored the relative contribution from working memory, inhibition/interference control, task-switching ability, and visuomotor speed to TMT performance. Forty-one healthy old subjects participated in the study and performed a battery of neuropsychological tests including the TMT, the Digit Symbol subtest [Wechsler Adult Intelligence Scale (Third Version) (WAIS-III)], a Finger Tapping Test, the Digits Forward and Backward subtests (WAIS-III), Stroop Test, and a task-switching paradigm inspired in the Wisconsin Card Sorting Test. Correlation and regression analyses were used in order to clarify the joint and unique contributions from different cognitive factors to the prediction of TMT scores. The results suggest that TMT-A requires mainly visuoperceptual abilities, TMT-B reflects primarily working memory and secondarily task-switching ability, while B-A minimizes visuoperceptual and working memory demands, providing a relatively pure indicator of executive control abilities.

[Organic personality disorder: conceptual review and research strategies]. / El trastorno orgánico de la personalidad: análisis conceptual y estrategias para la investigación.

The historical review of "psychiatric personality disorders" reveals the lack of convergence of those disorders with the organic personality disorder (OPD). Only the psychopathy concept has been used as a psychopathological phenotype for one of the groups of OPD, the so-called "pseudopsychopaths". These patients have been described from the beginning of the XXth century under the heading of "frontal lobe syndrome". It was only with the development of the psychiatric nosologies, towards the middle of the XXth century, that the term "organic personality disorder" started to be used. The accumulation of knowledge about the different prefrontal areas and the development of neuropsychological models that try to explain social behavior have opened new ways of understanding this syndrome. The orbitofrontal cortex has been identified as one of the key structures in behavioral and emotional regulation. Recognition of emotions in voices and faces, empathy, appreciation of humor, tasks that show "theory of mind" are some of the dimensions included in the examination of the non-cognitive functions of the prefrontal cortex

El trastorno orgánico de la personalidad: análisis conceptual y estrategias para la investigación / Organic personality disorder: conceptual review and research strategies

La revisión histórica del concepto de trastorno de la personalidad en psiquiatría pone de manifiesto que dicha categoría no converge ni da pie al concepto actual de trastorno orgánico de la personalidad (TOP); solamente el concepto de psicopatía sirve de viñeta fenomenológica que será utilizada para la descripción de algunos de los TOP como «seudopsicopáticos». Estos pacientes han sido descritos desde principios del siglo XX bajo el paraguas del síndrome del lóbulo frontal; a mediados del siglo XX, con el desarrollo de las nosologías psiquiátricas se adoptó el término trastorno orgánico de la personalidad para caracterizarlos. El fraccionamiento de la corteza prefrontal y el desarrollo de modelos neuropsicológicos que tratan de explicar la conducta social han abierto nuevas posibilidades de exploración y comprensión de esta patología. La distinción anatomofuncional entre corteza ventral y corteza dorsolateral señala a la primera como responsable de la modulación emocional y conductual. La evaluación del reconocimiento de emociones en voces y caras, de la empatía, del sentido del humor y de la «teoría de la mente» son algunas de las nuevas herramientas de que disponemos para explorar las funciones no cognitivas de la corteza prefrontal

The historical review of «psychiatric personality disorders » reveals the lack of convergence of those disorders with the organic personality disorder (OPD). Only the psychopathy concept has been used as a psychopathological phenotype for one of the groups of OPD, the socalled «pseudopsychopaths». These patients have been described from the beginning of the XXth century under the heading of «frontal lobe syndrome». It was only with the development of the psychiatric nosologies, towards the middle of the XXth century, that the term «organic personality disorder» started to be used. The accumulation of knowledge about the different prefrontal areas and the development of neuropsychological models that try to explain social behavior have opened new ways of understanding this syndrome. The orbitofrontal cortex has been identified as one of the key structures in behavioral and emotional regulation. Recognition of emotions in voices and faces, empathy, appreciation of humor, tasks that show «theory of mind» are some of the dimensions included in the examination of the non-cognitive functions of the prefrontal cortex

Trail Making Test in traumatic brain injury, schizophrenia, and normal ageing: sample comparisons and normative data.

The Trail Making Test (TMT) has been a useful assessment tool to investigate executive function. Several studies have recently improved the existing TMT norms by mean of large samples of healthy individuals stratified by a number of demographic variables from different populations. In contrast, criticisms have been raised about the utility of norms from healthy samples to detect changes across time in clinical samples where TMT performance used to be altered. In addition, few studies have compared groups of patients with deficits in TMT performance, making it difficult to decide whether a single set of norms is sufficient to assess different clinical populations. We provide normative data from three large samples of patients with traumatic brain injury (TBI) (n=90), schizophrenia spectrum disorders (n=127), and healthy Spanish speakers (n=223). Differences between healthy participants and patients in all TMT direct (TMT-A, TMT-B) and derived (B-A, B:A, B-A/A) scores were found. TMT performance was poorer in TBI patients than in schizophrenia patients except for the B:A and B-A/A scores, suggesting a similar underlying executive deficit. Normal ageing impaired both direct and derived TMT indices, as revealed by lower scores in the healthy elderly group (55-80 years old) as compared with young (16-24) and middle-aged (25-54) healthy participants. Three different sets of norms stratified by age, education, or both are presented for clinical use. Recommendations on TMT scores are made for future research.