Construcción de normas locales para la técnica Rorschach : Sistema Comprehensivo

Se describe el camino recorrido por los temas de investigación abordados por el equipo desde 1995 hasta 2008, camino en el cual se sitúa el Proyecto de construcción de normas para la técnica Rorschach, Sistema Comprehensivo(1999-2004) El Objetivo se origina en la actual gran difusión internacional y en nuestro país, del Sistema Comprehensivo de Exner (1974) para la Técnica Rorschach, lo que planteó la necesidad de contar con normas de nuestro contexto cultural para analizar e interpretar los resultados. Luego de destinar un año completo a la capacitación del equipo en el Sistema Comprehensivo y de obtener mediante información del INDEC (Instituto Nacional de Estadísticas y Censos) la distribución de los rangos de género y edad demográficamente representativos de la población, se obtuvo la muestra de 506 casos, estratificados según rangos de edad de 18-25 años; 26-35 años; 36-45 años; 46 a 55 años y 56 a 65 años, En la muestra normativa se excluyeron todos los casos que estuvieran o hubieran estado en tratamiento psicoterapéutico o psiquiátrico. Se describe el proyecto y comentan resultados

Biomagnetostratigraphy of ODP Leg 189 sites

Late Cretaceous (Maastrichtian)-Quaternary summary biostratigraphies are presented for Ocean Drilling Program (ODP) Leg 189 Sites 1168 (West Tasmanian Margin), 1170 and 1171 (South Tasman Rise), and 1172 (East Tasman Plateau). The age models are calibrated to magnetostratigraphy and integrate both calcareous (planktonic foraminifers and nannofossils) and siliceous (diatoms and radiolarians) microfossil groups with organic walled microfossils (organic walled dinoflagellate cysts, or dinocysts). We also incorporate benthic oxygen isotope stratigraphies into the upper Quaternary parts of the age models for further control. The purpose of this paper is to provide a summary age-depth model for all deep-penetrating sites of Leg 189 incorporating updated shipboard biostratigraphic data with new information obtained during the 3 yr since the cruise. In this respect we provide a report of work to November 2003, not a final synthesis of the biomagnetostratigraphy of Leg 189, yet we present the most complete integrated age model for these sites at this time. Detailed information of the stratigraphy of individual fossil groups, paleomagnetism, and isotope data are presented elsewhere. Ongoing efforts aim toward further integration of age information for Leg 189 sites and will include an attempt to correlate zonation schemes for all the major microfossil groups and detailed correlation between all sites.

Brain-wide slowing of spontaneous alpha rhythms in mild cognitive impairment

The neurophysiological changes associated with Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI) include an increase in low frequency activity, as measured with electroencephalography or magnetoencephalography (MEG). A relevant property of spectral measures is the alpha peak, which corresponds to the dominant alpha rhythm. Here we studied the spatial distribution of MEG resting state alpha peak frequency and amplitude values in a sample of 27 MCI patients and 24 age-matched healthy controls. Power spectra were reconstructed in source space with linearly constrained minimum variance beamformer. Then, 88 Regions of Interest (ROIs) were defined and an alpha peak per ROI and subject was identified. Statistical analyses were performed at every ROI, accounting for age, sex and educational level. Peak frequency was significantly decreased (p < 0.05) in MCIs in many posterior ROIs. The average peak frequency over all ROIs was 9.68 ± 0.71 Hz for controls and 9.05 ± 0.90 Hz for MCIs and the average normalized amplitude was (2.57 ± 0.59)·10−2 for controls and (2.70 ± 0.49)·10−2 for MCIs. Age and gender were also found to play a role in the alpha peak, since its frequency was higher in females than in males in posterior ROIs and correlated negatively with age in frontal ROIs. Furthermore, we examined the dependence of peak parameters with hippocampal volume, which is a commonly used marker of early structural AD-related damage. Peak frequency was positively correlated with hippocampal volume in many posterior ROIs. Overall, these findings indicate a pathological alpha slowing in MCI.

Perception of the sport events held in a permanent facility: the case of the Madrid Sports Palace

The aims of this study were to analyse perceptions regarding the sporting events held in the Madrid Sports Palace and to analyse whether those perceptions vary by age or gender. One hundred and ninetyfive residents answered the Ntloko and Swart (2008) questionnaire. The dimensions most highly rated were economic benefits (3.9±0.8), the event as a regional showcase (3.6±0.7), and the event as entertainment (3.4±0.6). However, the respondents did not agree with the negative environmental impact (2.0±0.8). Men rated the use of public money (z=2.4; pmenor que.05) and the regional showcase (z=2.0 pmenor que.05) more positively than women. Finally, women rated the increase in prices (z=2.0; pmenor que.05) more highly than men. The age groups differed significantly only regarding the promotion of community pride. Seniors and middle-aged adults rated it more positively than young adults (?2(2)=9.9; pmenor que.01). The fact that in an urban sports facility regular sporting events take place on a regular basis means that there are diverse perceptions, though mainly positive, and those perceptions differ from the perceptions about mega events that take place once in a life time at temporary sports facilities.

La coordinación motriz en la Adolescencia y su relación con el IMC, hábitos de práctica y motivación en E.F: Estudio transversal y longitudinal

En las últimas décadas, ha aumentado el interés de la investigación sobre el desarrollo de la coordinación motriz en la adolescencia por ser una etapa sensible, crítica y crucial para la adquisición de hábitos y conductas saludables de vida. Estos estudios han mostrado que la adquisición de unos niveles óptimos de coordinación y competencia motriz van a ser determinantes para el bienestar del adolescente y van a estar relacionados e influidos por otras dimensiones del desarrollo de la persona. Recientes investigaciones han sacado a la luz datos alarmantes sobre el aumento de problemas de coordinación motriz en la población infantil y adolescente (Cantell, Smyth y Ahonen, 1994; Gómez, 2004; Ruiz, Graupera, Gutiérrez y Miyahara, 2003; Sudgen y Chambers, 2005) donde abrocharse los botones de una camisa o correr de forma armónica puede ser todo un mundo lleno de dificultades y consecuencias sobre otras dimensiones del desarrollo (Ramón-Otero y Ruiz, 2015). Estos problemas han sido tratados por investigadores como una “dificultad oculta” (Gómez, Ruiz y Mata, 2006), cuya manifestación está presente en las actividades de la vida cotidiana, en contextos deportivos, en juegos y/o en la clase de Educación Física (Ruiz, 2004). La preocupación por estas dificultades se ha extendido a nivel internacional, creando todo un campo de investigación que estudia el diagnóstico de éstos problemas, conocido bajo las siglas DCD (Developmental Coordination Disorder). El presente estudio se centra en la etapa adolescente, periodo de transición entre la etapa infantil y adulta, caracterizada por numerosos cambios biológicos, cognitivos y socioemocionales (Santrock, 2005), que van a determinar la adaptación con el entorno (Gallahue, Ozmun y Goodway, 2011; Gómez, Ruiz, y Mata, 2006). El propósito principal del estudio es analizar el desarrollo de la coordinación motriz en la etapa adolescente investigando las diferencias de género y de edad en relación con variables psicosociales, los hábitos de práctica y las variables antropométricas. El diseño de la investigación se estructura en dos estudios. El primero de ellos, de carácter transversal, analizó una muestra representativa de 1.966 adolescentes de 1º a 4º de la ESO. El segundo, de naturaleza longitudinal, utilizó un grupo de 89 adolescentes del estudio transversal los cuales fueron estudiados durante 4 años, desde los 12 a los 15 años. Los mismos instrumentos fueron utilizados en ambos estudios: el Test Sportcomp para la evaluación de la coordinación motriz, el test AMPET4 para valorar la motivación de logro para el aprendizaje en Educación Física, el inventario HBSC para conocer los hábitos saludables sobre la práctica de actividad física y, por ultimo, se utilizó un estadiómetro para obtener el peso y la altura y así calcular el índice de masa corporal (IMC). La toma de datos del Estudio Transversal se realizó en 2 cursos académicos (2011/12 - 2012/13), en la cual se requirieron 3 sesiones coincidiendo con la clase de Educación Física. En la primera sesión, se evaluó la coordinación motriz. En la segunda se aplicaron los cuestionarios (AMPET4 y HBSC) y, en la última sesión se midió el peso y la altura en un espacio reservado al estadiómetro. El análisis de datos fue descriptivo y diferencial de cada una de las variables estudiadas: motoras, psicosociales, de hábitos de práctica de actividad física y antropométricas. Asimismo, se llevaron a cabo pruebas de análisis univariante y multivariante, calculando el valor-p y las pruebas de efecto. Respecto al Estudio Longitudinal, la toma de datos se llevó cabo durante 4 años desde el 2011 al 2014. La evaluación de la coordinación motriz se realizó en cada uno de los 4 años. Sin embargo, los 2 cuestionarios y las medidas antropométricas fueron evaluadas en el primer y cuarto año. Los análisis de datos fueron descriptivos y comparativos entre las variables analizadas. En el caso de la coordinación motriz, se realizaron las pruebas de medidas repetidas y, en el caso de las demás variables analizadas, se realizaron Prueba T para muestras relacionadas. Los resultados globales mostraron que el índice motor en el Estudio Transversal fue progresivo en el conjunto de chicos. Sin embargo, en las chicas, el rendimiento se estabiliza a partir de los 13 años. En el caso del Estudio Longitudinal, este índice se estabiliza en los 3 primeros años y a la edad de los 14, es cuando comienzan a acusarse las diferencias de género. En el caso de los hombres el rendimiento mejora y, por el contrario, en las mujeres empeora. En el Estudio Transversal, el análisis de varianza mostraron diferencias en función de la edad [F(7, 1958) = 220.70, p < .001; η2 = .101], del género [F(7, 1958) = 29.76, p < .001; η2 = .044], así como en la interacción entre ambos [F(7, 1958)= 11.90, p < .001; η2 = .018]. Únicamente aparecieron diferencias significativas con la edad en todos los grupos de hombres, excepto entre 14 y 15 años. En el Longitudinal, los contrastes multivariados mostraron que no hubo diferencias sgnificativas en el tiempo [F(3,85) = .05, p = .987, η2= .002] mostrando un nivel de coordinación estable a lo largo de los años, aunque existieron diferencias entre chicos y chicas [F(3,85) = 4.64 p = .005] con un tamaño de efecto destacable (η2 = .141). En cuanto a la motivación de logro para prender en Educación Física, en ambos estudios, los chicos fueron los que obtuvieron puntuaciones más elevadas en todas las dimensiones positivas del test (compromiso de aprendizaje, competencia autopercibida y comparada). Sin embargo, en la dimensión negativa del test, la referida a la ansiedad y al agobio ante el fracaso, fueron las chicas las que puntuaron más alto. En el Estudio Transversal, los resultados mostraron diferencias significativas en todas las dimensiones del AMPET4 en función del nivel de coordinación motriz: compromiso con el aprendizaje [F(2, 1644) = 8.66, p < .001; η2 = .010], competencia autopercibida [F(2, 1644) = 50.94, p < .001; η2 = .048], competencia comparada [F(2, 1644) = 41.56, p < .001, η2 = .020] y ansiedad [F(2, 1644) = 16.67, p < .001, η2 = .058]. En este sentido, los grupos de mejor nivel de coordinación motriz, fueron los que mayor puntuación obtuvieron en las dimensiones positivas y los que menor, en la negativa. En el Estudio Longitudinal, también se encontraron diferencias entre el primer y cuarto año de estudio en todas las dimensiones, excepto en competencia motriz autopercibida. Estas diferencias se tradujeron en una disminución en las 3 variables significativas del primer al cuarto año. Respecto al inventario HBSC, en el Estudio Longitudinal, la prueba T mostró únicamente la existencia de diferencias significativas entre el primer y cuarto año en 2 de los 11 ítems: percepción de la forma física (p = .006) y percepción de la salud (p = .047), los cuales disminuyeron en el intervalo de tiempo del estudio. En el Transversal, las diferencias se observaron en función del género (p < .001) y de la edad (p < .001). Asimismo, se mostraron diferencias significativas en todos los ítems respecto al nivel de coordinación motriz, excepto en 2 de ellos: frecuencia tiempo libre con los amigos fuera del colegio (p = .580) y facilidad para hacer amigos en el centro escolar (p = .098). Por último, en las variables antropométricas, los resultados del Estudio Transversal y Longitudinal coinciden tanto en la estatura como en el peso, apuntando, que en ambos estudios, se produce un aumento progresivo tanto en chicos como en chicas a medida que se avanza en edad. Concretamente en el Transversal, estas diferencias en la edad se encuentran en todos los grupos en ambos géneros, excepto en el conjunto de chicas entre los 14 y los 15 años. Asimismo, ambos estudios coincidieron en que tanto las ganancias en cm y kg, como las puntuaciones medias, fueron mayores en los chicos que en las chicas. Respecto al IMC, los 2 estudios coincidieron en que la evolución es paralela, y tal y como apuntan los resultados del Transversal, no se encontraron diferencias ni en la edad (p = 792) ni en el género (p = 284). No obstante, el Longitudinal apuntó únicamente diferencias significativas entre el primer y cuarto año en el conjunto de los hombres [t(41) = -4.01, p < .001]. Finalmente, y en relación con los niveles de coordinación motriz, hubo diferencias significativas en relación con el IMC (p = .012), mostrando como el grupo de peso normal coincide con puntuaciones óptimas de coordinación motriz. A modo de conclusiones, el presente estudio revela cómo la adquisición de un nivel de coordinación óptimo va a ser fundamental para el desarrollo psicosocial, para el desarrollo de hábitos saludables de práctica y para mantener un IMC dentro de la normalidad para el género y la edad. De esta manera, el desarrollo de la coordinación motriz será un aspecto fundamental para lograr un estado de bienestar físico y mental, y unos hábitos favorables para la práctica de actividad física. ABSTRACT In the past couple of decades, adolescence stage in motor coordination gained significant interest in research especially due to its sensitive and critical importance to achieving a healthy life style. These studies observed how to acquire optimum levels of coordination and motor competence, which proved crucial to the quality of the adolescent stage in addition to being influenced by other dimensions of development for each individual. Recent research shed light to an alarming set of data, which showed increased motor coordination problems in children and adolescents (Cantell, Smyth & Ahonen, 1994; Gómez, 2004; Ruiz, Graupera, Gutierrez & Miyahara, 2003; Sugden & Chambers, 2005). For instance, even to the extent that buttoning a shirt or running in a harmonic form can lead to a whole set of consequences and difficulties on the development stage. Researchers have addressed such problems in various studies such as “dificultad oculta” (Gomez, Ruiz & Mata, 2006), which literally translates as “hidden trouble”. The studies are evidently present in the activities of daily life, sporting contexts, games and/or Physical Education (Ruiz, 2004). Concern about these difficulties spread internationally, creating a whole framework research studying the diagnosis of these problems, known under the acronym DCD (Developmental Coordination Disorder). The study focuses on the adolescent stage, transition period between childhood and adulthood characterized by numerous biological, cognitive and socio-emotional changes (Santrock, 2005), which interestingly determines an individual´s adaptation to the environment (Gallahue, Ozmun & Goodway, 2011; Gomez, Ruiz & Mata, 2006). The main purpose of the study is to analyse the development of motor coordination in the adolescent stage investigating gender differences and age in relation to psychological variables, physical activity habits and anthropometric variables. The research design is structured in two studies. The first (transversal nature), analyses a representative sample of 1,966 adolescents from 1st to 4th of Secondary Education School. The second (longitudinal nature) used a group of 89 teenagers from cross-sectional study, which were studied for four years, from 12 to 15 years. The same instruments were used in both studies, namely; “Sportcomp Test” used to evaluate of motor coordination; “AMPET4 Test” which assesses the motivational achievement of learning Physical Education; “HBSC Inventory” to find out the healthy habits gained from physical activities; And finally a “stadiometer” was used to obtain the weight and height and thus calculate the body mass index (BMI). The data collection of the cross-sectional Study was conducted in two academic years (2011/12 - 2012/13), in which 3 sessions coinciding with the Physical Education level are required. In the first session, motor coordination was evaluated; questionnaires were applied in the second session (AMPET4 and HBSC); and in the last session the weight and height were measured in a reserved space for the “stadiometer”. Notably, data analysis was descriptive and differential in each of the variable studies: motor, psychological, practical and anthropometric habits of physical activity. Thus the tests were conducted in a univariate and multivariate analysis, calculating the p-value and effect tests. Regarding the Longitudinal Study, data collection was carried out during four years from 2011 to 2014 inclusively. The assessment of motor coordination was performed on each of the four years, however, the 2 questionnaires and anthropometric measures were evaluated in the first and fourth year. Data analyses were also descriptive and comparative among the variables that were put to the test. In the case of motor coordination tests, they were done on repeated measures, whilst, in the case of other variables analysed, they were accomplished through T Tests under comparable samples. The overall results showed that the engine Motor Index in Study 1 was progressive in all male gender studies, however in the females the performance remained constant after reaching 13 years of age. For the Longitudinal Study, this index is stabilized in the first 3 years and at the age of 14 is when the gender differences take place. In the case of males, the performance improves, however, in females worsens. The cross-sectional Study, analysis of variance showed differences in terms of age [F(7, 1958) = 220.70, p < .001; η2 = .101], gender [F(7, 1958) = 29.76, p <.001; η2 = .044], as well as their interaction [F(7, 1958) = 11.90, p <.001; η2 = .018]. They only show significant differences in respect to age in the male set sample, in all groups except between 14 and 15 years old. In the Longitudinal, the multivariate contrasts showed no significant differences in time [F(3,85) = 0.05, p = 0.987, η2 = 0.002] showing a stable level of coordination over the years, but if there were differences between both genders [F(3,85) = 4.64, p = .005] it took place with a noteworthy effect size (η2 = .141). In regards, to the Motivational Achievement for learning Physical Education, in both studies the male sample administered obtained higher scores on all the positive dimensions of the test (commitment to learning, self-assessed competence, and comparable competence). However, on the negative assessment side, namely, anxiety and fear of failure, the female sample scored higher than the male one. In Study 1, the multivariate analysis showed significant differences between the psychosocial dimensions and levels of motor coordination with moderate to significant effect [Lambada de Wilks = .931, F(8, 3282) = 14.99; p = <0.001; η2 = .035]. By the same token, the groups with the best level of motor coordination were the highest scoring ones in the positive dimensions, whilst the lower performing ones, performed better in the negative dimension. In the longitudinal study, there is also differences were also found between the first and fourth years of study in all dimensions, except in self-perceived motor competition. These differences resulted in a significant decrease in the 3 variables from first to fourth year. Regarding, the “HBSC Inventory”, the T test in the longitudinal study showed uniquely the existence of significant differences between the first and fourth year in 2 of the 11 items: perception of physical fitness (p = .006) and perceived health (p = 047), which diminished in the interval time of the study. In the Cross-sectional study, the se differences were also observed in gender (p < .001) and age (p < .001). Similarly, they showed significant differences in all items in respect to the motor coordination level, except in 2 of them; frequency of free time with friends outside of school (p = .580) and the ease to make friends at the educational centre (p = 098). And last but not least, the anthropometric variables, both the results of the Transversal and Longitudinal Study matched both height and weight, pointing out that in both studies a gradual increase in both genders, as they grow older. Notably in the Cross-sectional, these differences in age are found in all groups in both genders, except for the set of girls between 14 and 15 years. Thus both studies concluded that both gains in cm and kg and the mean scores were higher amongst males compared to females. Regarding BMI, the 2 studies concluded that the evolution is parallel, and as pointed cross-sectional study there isn’t differences found in age (p = 792) or in gender (p = 284). However, the Longitudinal study uniquely shows significant difference between the first and fourth year for male set sample [t (41) = -4.01, p < .001]. Finally, in relation to levels of motor coordination, there were significant differences in relation to BMI (p = .012), showing how the “normal weight group” matches the optimal scores of motor coordination. In conclusion, this study reveals how the acquisition of an optimal level of coordination is vital for psychological development, to develop and practice healthy habits, and to maintain a BMI within the normal range for age and gender. Therefore, the development of motor coordination is fundamental to achieving a state of physical and mental wellbeing, and preferable habits to pursuing physical activity.

Evidence for a genetic basis for hyperandrogenemia in polycystic ovary syndrome

Our preliminary family studies have suggested that some female first-degree relatives of women with polycystic ovary syndrome (PCOS) have hyperandrogenemia per se. It was our hypothesis that this may be a genetic trait and thus could represent a phenotype suitable for linkage analysis. To investigate this hypothesis, we examined 115 sisters of 80 probands with PCOS from unrelated families. PCOS was diagnosed by the combination of elevated serum androgen levels and ≤6 menses per year with the exclusion of secondary causes. The sisters were compared with 70 healthy age- and weight-comparable control women with regular menses, no clinical evidence of hyperandrogenemia, and normal glucose tolerance. Twenty-two percent of the sisters fulfilled diagnostic criteria for PCOS. In addition, 24% of the sisters had hyperandrogenemia and regular menstrual cycles. Circulating testosterone (T) and nonsex hormone-binding globulin-bound testosterone (uT) levels in both of these groups of sisters were significantly increased compared with unaffected sisters and control women (P < 0.0001 for both T and uT). Probands, sisters with PCOS, and hyperandrogenemic sisters had elevated serum luteinizing hormone levels compared with control women. We conclude that there is familial aggregation of hyperandrogenemia (with or without oligomenorrhea) in PCOS kindreds. In affected sisters, only one-half have oligomenorrhea and hyperandrogenemia characteristic of PCOS, whereas the remaining one-half have hyperandrogenemia per se. This familial aggregation of hyperandrogenemia in PCOS kindreds suggests that it is a genetic trait. We propose that hyperandrogenemia be used to assign affected status in linkage studies designed to identify PCOS genes.

Isoform-specific effects of human apolipoprotein E on brain function revealed in ApoE knockout mice: Increased susceptibility of females

Apolipoprotein E (apoE) mediates the redistribution of lipids among cells and is expressed at highest levels in brain and liver. Human apoE exists in three major isoforms encoded by distinct alleles (ɛ2, ɛ3, and ɛ4). Compared with APOE ɛ2 and ɛ3, APOE ɛ4 increases the risk of cognitive impairments, lowers the age of onset of Alzheimer’s disease (AD), and decreases the response to AD treatments. Besides age, inheritance of the APOE ɛ4 allele is the most important known risk factor for the development of sporadic AD, the most common form of this illness. Although numerous hypotheses have been advanced, it remains unclear how APOE ɛ4 might affect cognition and increase AD risk. To assess the effects of distinct human apoE isoforms on the brain, we have used the neuron-specific enolase (NSE) promoter to express human apoE3 or apoE4 at similar levels in neurons of transgenic mice lacking endogenous mouse apoE. Compared with NSE-apoE3 mice and wild-type controls, NSE-apoE4 mice showed impairments in learning a water maze task and in vertical exploratory behavior that increased with age and were seen primarily in females. These findings demonstrate that human apoE isoforms have differential effects on brain function in vivo and that the susceptibility to apoE4-induced deficits is critically influenced by age and gender. These results could be pertinent to cognitive impairments observed in human APOE ɛ4 carriers. NSE-apoE mice and similar models may facilitate the preclinical assessment of treatments for apoE-related cognitive deficits.

An impairment in sniffing contributes to the olfactory impairment in Parkinson's disease

Although the presence of an olfactory impairment in Parkinson's disease (PD) has been recognized for 25 years, its cause remains unclear. Here we suggest a contributing factor to this impairment, namely, that PD impairs active sniffing of odorants. We tested 10 men and 10 women with clinically typical PD, and 20 age- and gender-matched healthy controls, in four olfactory tasks: (i) the University of Pennsylvania smell identification test; (ii and iii) detection threshold tests for the odorants vanillin and propionic acid; and (iv) a two-alternative forced-choice detection paradigm during which sniff parameters (airflow peak rate, mean rate, volume, and duration) were recorded with a pneomatotachograph-coupled spirometer. An additional experiment tested the effect of intentionally increasing sniff vigor on olfactory performance in 20 additional patients. PD patients were significantly impaired in olfactory identification (P < 0.0001) and detection (P < 0.007). As predicted, PD patients were also significantly impaired at sniffing, demonstrating significantly reduced sniff airflow rate (P < 0.01) and volume (P < 0.002). Furthermore, a patient's ability to sniff predicted his or her performance on olfactory tasks, i.e., the more poorly patients sniffed, the worse their performance on olfaction tests (P < 0.009). Finally, increasing sniff vigor improved olfactory performance in those patients whose baseline performance had been poorest (P < 0.05). These findings implicate a sniffing impairment as a component of the olfactory impairment in PD and further depict sniffing as an important component of human olfaction.

Chronic stress alters the immune response to influenza virus vaccine in older adults.

To determine whether a chronic stressor (caregiving for a spouse with a progressive dementia) is associated with an impaired immune response to influenza virus vaccination, we compared 32 caregivers' vaccine responses with those of 32 sex-, age-, and socioeconomically matched control subjects. Caregivers showed a poorer antibody response following vaccination relative to control subjects as assessed by two independent methods, ELISA and hemagglutination inhibition. Caregivers also had lower levels of in vitro virus-specific-induced interleukin 2 levels and interleukin 1beta; interleukin 6 did not differ between groups. These data demonstrate that down-regulation of the immune response to influenza virus vaccination is associated with a chronic stressor in the elderly. These results could have implications for vulnerability to infection among older adults.

Valutazione della risposta immunitaria cellulare e fenotipizzazione linfocitaria nel suino in corso di infezione naturale da virus della PRRS (“Porcine Reproductive and Respiratory Syndrome”) e dopo stimolazione di PBMC (“Peripheral Blood Mononuclear Cells”) in vitro con Peptide Killer (KP)

SUMMARY The Porcine Reproductive and Respiratory Syndrome (PRRS) virus is one of the most spread pathogens in swine herds all over the world and responsible for a reproductive and respiratory syndrome that causes severe heath and economical problems. This virus emerged in late 1980’s but although about 30 years have passed by, the knowledge about some essential facets related to the features of the virus (pathogenesis, immune response, and epidemiology) seems to be still incomplete. Taking into account that the development of modern vaccines is based on how innate and acquire immunity react, a more and more thorough knowledge on the immune system is needed, in terms of molecular modulation/regulation of the inflammatory and immune response upon PRRSV infection. The present doctoral thesis, which is divided into 3 different studies, is aimed to increase the knowledge about the interaction between the immune system and the PRRS virus upon natural infection. The objective of the first study entitled “Coordinated immune response of memory and cytotoxic T cells together with IFN-γ secreting cells after porcine reproductive and respiratory syndrome virus (PRRSV) natural infection in conventional pigs” was to evaluate the activation and modulation of the immune response in pigs naturally infected by PRRSV compared to an uninfected control group. The course of viremia was evaluated by PCR, the antibody titres by ELISA, the number of IFN-γ secreting cells (IFN- SC) by an ELISPOT assay and the immunophenotyping of some lymphocyte subsets (cytotoxic cells, memory T lymphocytes and cytotoxic T lymphocytes) by flow cytometry. The results showed that the activation of the cell-mediated immune response against PRRSV is delayed upon infection and that however the levels of IFN-γ SC and lymphocyte subsets subsequently increase over time. Furthermore, it was observed that the course of the different immune cell subsets is time-associated with the levels of PRRSV-specific IFN-γ SC and this can be interpreted based on the functional role that such lymphocyte subsets could have in the specific production/secretion of the immunostimulatory cytokine IFN-γ. In addition, these data support the hypothesis that the age of the animals upon the onset of infection or the diverse immunobiological features of the field isolate, as typically hypothesized during PRRSV infection, are critical conditions able to influence the qualitative and quantitative course of the cell-mediated immune response during PRRSV natural infection. The second study entitled “Immune response to PCV2 vaccination in PRRSV viremic piglets” was aimed to evaluate whether PRRSV could interfere with the activation of the immune response to PCV2 vaccination in pigs. In this trial, 200 pigs were divided into 2 groups: PCV2-vaccinated (at 4 weeks of age) and PCV2-unvaccinated (control group). Some piglets of both groups got infected by PRRSV, as determined by PRRSV viremia detection, so that 4 groups were defined as follows: PCV2 vaccinated - PRRSV viremic PCV2 vaccinated - PRRSV non viremic PCV2 unvaccinated - PRRSV viremic PCV2 unvaccinated - PRRSV non viremic The following parameters were evaluated in the 4 groups: number of PCV2-specific IFN-γ secreting cells, antibody titres by ELISA and IPMA. Based on the immunological data analysis, it can be deduced that: 1) The low levels of antibodies against PCV2 in the PCV2-vaccinated – PRRSV-viremic group at vaccination (4 weeks of age) could be related to a reduced colostrum intake influenced by PRRSV viremia. 2) Independently of the viremia status, serological data of the PCV2-vaccinated group by ELISA and IPMA does not show statistically different differences. Consequently, it can be be stated that, under the conditions of the study, PRRSV does not interfere with the antibody response induced by the PCV2 vaccine. 3) The cell-mediated immune response in terms of number of PCV2-specific IFN-γ secreting cells in the PCV2-vaccinated – PRRSV-viremic group seems to be compromised, as demonstrated by the reduction of the number of IFN-γ secreting cells after PCV2 vaccination, compared to the PCV2-vaccinated – PRRSV-non-viremic group. The data highlight and further support the inhibitory role of PRRSV on the development and activation of the immune response and highlight how a natural infection at early age can negatively influence the immune response to other pathogens/antigens. The third study entitled “Phenotypic modulation of porcine CD14+ monocytes, natural killer/natural killer T cells and CD8αβ+ T cell subsets by an antibody-derived killer peptide (KP)” was aimed to determine whether and how the killer peptide (KP) could modulate the immune response in terms of activation of specific lymphocyte subsets. This is a preliminary approach also aimed to subsequently evaluate such KP with a potential antivural role or as adjuvant. In this work, pig peripheral blood mononuclear cells (PBMC) were stimulated with three KP concentrations (10, 20 and 40 g/ml) for three time points (24, 48 and 72 hours). TIME POINTS (hours) KP CONCENTRATIONS (g/ml) 24 0-10-20-40 48 0-10-20-40 72 0-10-20-40 By using flow cytometry, the qualitative and quantitative modulation of the following immune subsets was evaluated upon KP stimulation: monocytes, natural killer (NK) cells, natural killer T (NKT) cells, and CD4+ and CD8α/β+ T lymphocyte subsets. Based on the data, it can be deduced that: 1) KP promotes a dose-dependent activation of monocytes, particularly after 24 hours of stimulation, by inducing a monocyte phenotypic and maturation shift mainly involved in sustaining the innate/inflammatory response. 2) KP induces a strong dose-dependent modulation of NK and NKT cells, characterized by an intense increase of the NKT cell fraction compared to NK cells, both subsets involved in the antibody-dependent cell cytotoxicity (ADCC). The increase is observed especially after 24 hours of stimulation. 3) KP promotes a significant activation of the cytotoxic T lymphocyte subset (CTL). 4) KP can modulate both the T helper and T cytotoxic phenotype, by inducing T helper cells to acquire the CD8α thus becoming doube positive cells (CD4+CD8+) and by inducing CTL (CD4-CD8+high) to acquire the double positive phenotype (CD4+CD8α+high). Therefore, KP may induce several effects on different immune cell subsets. For this reason, further research is needed aimed at characterizing each “effect” of KP and thus identifying the best use of the decapeptide for vaccination practice, therapeutic purposes or as vaccine adjuvant. RIASSUNTO Il virus della PRRS (Porcine Reproductive Respiratory Syndrome) è uno dei più diffusi agenti patogeni negli allevamenti suini di tutto il mondo, responsabile di una sindrome riproduttiva e respiratoria causa di gravi danni ad impatto sanitario ed economico. Questo virus è emerso attorno alla fine degli anni ’80 ma nonostante siano passati circa una trentina di anni, le conoscenze su alcuni punti essenziali che riguardano le caratteristiche del virus (patogenesi, risposta immunitaria, epidemiologia) appaiono ancora spesso incomplete. Considerando che lo sviluppo dei vaccini moderni è basato sui principi dell’immunità innata e acquisita è essenziale una sempre più completa conoscenza del sistema immunitario inteso come modulazione/regolazione molecolare della risposta infiammatoria e immunitaria in corso di tale infezione. Questo lavoro di tesi, suddiviso in tre diversi studi, ha l’intento di contribuire all’aumento delle informazioni riguardo l’interazione del sistema immunitario, con il virus della PRRS in condizioni di infezione naturale. L’obbiettivo del primo studio, intitolato “Associazione di cellule memoria, cellule citotossiche e cellule secernenti IFN- nella risposta immunitaria in corso di infezione naturale da Virus della Sindrome Riproduttiva e Respiratoria del Suino (PRRSV)” è stato di valutare l’attivazione e la modulazione della risposta immunitaria in suini naturalmente infetti da PRRSV rispetto ad un gruppo controllo non infetto. I parametri valutati sono stati la viremia mediante PCR, il titolo anticorpale mediante ELISA, il numero di cellule secernenti IFN- (IFN- SC) mediante tecnica ELISPOT e la fenotipizzazione di alcune sottopopolazioni linfocitarie (Cellule citotossiche, linfociti T memoria e linfociti T citotossici) mediante citofluorimetria a flusso. Dai risultati ottenuti è stato possibile osservare che l’attivazione della risposta immunitaria cellulo-mediata verso PRRSV appare ritardata durante l’infezione e che l’andamento, in termini di IFN- SC e dei cambiamenti delle sottopopolazioni linfocitarie, mostra comunque degli incrementi seppur successivi nel tempo. E’ stato inoltre osservato che gli andamenti delle diverse sottopopolazioni immunitarie cellulari appaiono temporalmente associati ai livelli di IFN- SC PRRSV-specifiche e ciò potrebbe essere interpretato sulla base del ruolo funzionale che tali sottopopolazioni linfocitarie potrebbero avere nella produzione/secrezione specifica della citochina immunoattivatrice IFN-. Questi dati inoltre supportano l’ipotesi che l’età degli animali alla comparsa dell’infezione o, come tipicamente ipotizzato nell’infezione da PRRSV, le differenti caratteristiche immunobiologiche dell’isolato di campo, sia condizioni critiche nell’ influenzare l’andamento qualitativo e quantitativo della risposta cellulo-mediata durante l’infezione naturale da PRRSV. Il secondo studio, dal titolo “Valutazione della risposta immunitaria nei confronti di una vaccinazione contro PCV2 in suini riscontrati PRRSV viremici e non viremici alla vaccinazione” ha avuto lo scopo di valutare se il virus della PRRS potesse andare ad interferire sull’attivazione della risposta immunitaria indotta da vaccinazione contro PCV2 nel suino. In questo lavoro sono stati arruolati 200 animali divisi in due gruppi, PCV2 Vaccinato (a 4 settimane di età) e PCV2 Non Vaccinato (controllo negativo). Alcuni suinetti di entrambi i gruppi, si sono naturalmente infettati con PRRSV, come determinato con l’analisi della viremia da PRRSV, per cui è stato possibile creare quattro sottogruppi, rispettivamente: PCV2 vaccinato - PRRSV viremico PCV2 vaccinato - PRRSV non viremico PCV2 non vaccinato - PRRSV viremico PCV2 non vaccinato - PRRSV non viremico Su questi quattro sottogruppi sono stati valutati i seguenti parametri: numero di cellule secernenti IFN- PCV2 specifiche, ed i titoli anticorpali mediante tecniche ELISA ed IPMA. Dall’analisi dei dati immunologici derivati dalle suddette tecniche è stato possibile dedurre che:  I bassi valori anticorpali nei confronti di PCV2 del gruppo Vaccinato PCV2-PRRSV viremico già al periodo della vaccinazione (4 settimane di età) potrebbero essere messi in relazione ad una ridotta assunzione di colostro legata allo stato di viremia da PRRSV  Indipendentemente dallo stato viremico, i dati sierologici del gruppo vaccinato PCV2 provenienti sia da ELISA sia da IPMA non mostrano differenze statisticamente significative. Di conseguenza è possibile affermare che in questo caso PRRSV non interferisce con la risposta anticorpale promossa dal vaccino PCV2.  La risposta immunitaria cellulo-mediata, intesa come numero di cellule secernenti IFN- PCV2 specifiche nel gruppo PCV2 vaccinato PRRS viremico sembra essere compromessa, come viene infatti dimostrato dalla diminuzione del numero di cellule secernenti IFN- dopo la vaccinazione contro PCV2, comparata con il gruppo PCV2 vaccinato- non viremico. I dati evidenziano ed ulteriormente sostengono il ruolo inibitorio del virus della PRRSV sullo sviluppo ed attivazione della risposta immunitaria e come un infezione naturale ad età precoci possa influenzare negativamente la risposta immunitaria ad altri patogeni/antigeni. Il terzo studio, intitolato “Modulazione fenotipica di: monociti CD14+, cellule natural killer (NK), T natural killer (NKT) e sottopopolazioni linfocitarie T CD4+ e CD8+ durante stimolazione con killer peptide (KP) nella specie suina” ha avuto come scopo quello di stabilire se e come il Peptide Killer (KP) potesse modulare la risposta immunitaria in termini di attivazione di specifiche sottopopolazioni linfocitarie. Si tratta di un approccio preliminare anche ai fini di successivamente valutare tale KP in un potenziale ruolo antivirale o come adiuvante. In questo lavoro, periferal blood mononuclear cells (PBMC) suine sono state stimolate con KP a tre diverse concentrazioni (10, 20 e 40 g/ml) per tre diversi tempi (24, 48 e 72 ore). TEMPI DI STIMOLAZIONE (ore) CONCENTRAZIONE DI KP (g/ml) 24 0-10-20-40 48 0-10-20-40 72 0-10-20-40 Mediante la citometria a flusso è stato dunque possibile analizzare il comportamento qualitativo e quantitativo di alcune sottopopolazioni linfocitarie sotto lo stimolo del KP, tra cui: monociti, cellule Natural Killer (NK), cellule T Natural Killer (NKT) e linfociti T CD4 e CD8+. Dai dati ottenuti è stato possibile dedurre che: 1) KP promuove un’attivazione dei monociti dose-dipendente in particolare dopo 24 ore di stimolazione, inducendo uno “shift” fenotipico e di maturazione monocitaria maggiormente coinvolto nel sostegno della risposta innata/infiammatoria. 2) KP induce una forte modulazione dose-dipendente di cellule NK e NKT con un forte aumento della frazione delle cellule NKT rispetto alle NK, sottopopolazioni entrambe coinvolte nella citotossicità cellulare mediata da anticorpi (ADCC). L’aumento è riscontrabile soprattutto dopo 24 ore di stimolazione. 3) KP promuove una significativa attivazione della sottopopolazione del linfociti T citotossici (CTL). 4) Per quanto riguarda la marcatura CD4+/CD8+ è stato dimostrato che KP ha la capacità di modulare sia il fenotipo T helper che T citotossico, inducendo le cellule T helper ad acquisire CD8 diventando quindi doppio positive (CD4+CD8+) ed inducendo il fenotipo CTL (CD4-CD8+high) ad acquisire il fenotipo doppio positivo (CD4+CD8α+high). Molti dunque potrebbero essere gli effetti che il decapeptide KP potrebbe esercitare sulle diverse sottopopolazioni del sistema immunitario, per questo motivo va evidenziata la necessità di impostare e attuare nuove ricerche che portino alla caratterizzazione di ciascuna “abilità” di KP e che conducano successivamente alla scoperta del migliore utilizzo che si possa fare del decapeptide sia dal punto di vista vaccinale, terapeutico oppure sotto forma di adiuvante vaccinale.

Caracterização anatomopatológica, microbiológica e parasitológica de ratos Wistar (Rattus norvegicus) em diferentes idades

Os ratos Wistar são amplamente empregados como modelo animal na pesquisa biomédica e o controle sanitário dos biotérios é essencial para garantir a qualidade dos experimentos. O objetivo do estudo foi a caracterização do estado sanitário da colônia de ratos Wistar em sistema de criação convencional e para tanto determinar as bactérias, fungos, virus e parasitos, bem como caracterizar as lesões anatomopatológicas do sistema respiratório. Foram utilizados 273 ratos (N), machos (M) e fêmeas (F), das faixas etárias 4, 8, 12, 16 a 20 semanas e entre 12 a 18 meses, para as determinações de peso e condição corpórea (N=273, 140M, 133F); avaliação bacteriológica de orofaringe, mucosa intestinal e lavado traqueobrônquico (N=40, 20M, 20F); determinação de anticorpos para vírus e bactérias (N=20, 10M, 10F); exame parasitológico (N=60, 30M, 30F); identificação molecular de Mycoplasma pulmonis em amostras de pulmão (N=25, 15M, 10F), e caracterização anatomopatológica da cavidade nasal, orofaringe, laringe, traqueia e pulmão (N=106, 53M, 53F). Foram realizadas ainda avaliações microbiológicas das salas dos ratos em três períodos com isolamento de Micrococcus spp., Staphylococcus spp., Bacillus spp., Aspergillus spp. e Penicillium spp. O peso se mostrou homogêneo dentro da faixa etária e gênero, com apenas sete animais magros (2,56%) e nove em sobrepeso (3,30%). Não foram isoladas bactérias patogênicas na orofaringe, mucosa intestinal e lavado traqueobrônquico por cultivo. Mycoplasma pulmonis foi determinado em 72% das amostras pulmonares e em 100% dos soros testados. Em 35% foram detectados anticorpos para Reovirus tipo III e em 100% para bacilos associados ao epitélio respiratório ciliado. Syphacia muris foi diagnosticada em 91,67%, Eimeria spp. em 3,33% e Entamoeba muris em 1,67%. Lesões relacionadas a infecção por agentes exógenos foram observadas em cavidade nasal e na orofaringe, laringe e traqueia a partir da 4 semanas de idade e, em pulmão desde as 12 semanas, com aumento de frequência de ocorrência e do grau de progressão, com o avançar da idade, nos vários segmentos estudados. Concluímos que a caracterização do estado sanitário dos ratos permite conhecer as particularidades do modelo biológico utilizado e compor base de dados para auxiliar no desenho e na interpretação experimental dos pesquisadores, além de garantir uma base para o programa de monitorização sanitária de biotérios em condições similares

Estudo de alterações estruturais cerebrais em pacientes com esquizofrenia crônica e de primeiro episódio através de imagens por ressonância magnética com morfometria baseada no voxel

Introdução: Embora alterações estruturais cerebrais na esquizofrenia venham sendo repetidamente demonstradas em estudos de ressonância magnética (RM), ainda permanece incerto se tais alterações são estáticas ou progressivas. Enquanto estudos longitudinais são tradicionalmente utilizados na avaliação da questão da progressão, estudos transversais de neuroimagem comparando diretamente pacientes com esquizofrenia crônica e de primeiro episódio a controles saudáveis têm sido bastante raros até o presente. Com o recente interesse em meganálises combinando dados multicêntricos de RM visando-se a maior poder estatístico, o presente estudo multicêntrico de morfometria baseada no voxel (VBM) foi realizado para avaliar os padrões de alterações estruturais cerebrais segundo os diferentes estágios da doença, bem como para avaliar quais (se alguma) dessas alterações se correlacionariam especificamente a moderadores clínicos potenciais, tais como exposição cumulativa a antipsicóticos, tempo de doença e gravidade da doença. Métodos: Selecionou-se uma ampla amostra de pacientes com esquizofrenia (161, sendo 99 crônicos e 62 de primeiro episódio) e controles (151) a partir de quatro estudos prévios de RM (1,5T) realizados na mesma região do Brasil. O processamento e análise das imagens foi realizado usando-se o software Statistical Parametric Mapping (SPM8) com emprego do algoritmo DARTEL (diffeomorphic anatomical registration through exponentiated Lie algebra). Os efeitos de grupo sobre os volumes regionais de substância cinzenta (SC) foram analisados através de comparações voxel-a-voxel por análises de covariância em modelos lineares gerais, inserindo-se, em todas as análises, o volume total de SC, protocolo do scanner, idade e sexo como variáveis de confusão. Por fim, foram realizadas análises de correlação entre os aludidos moderadores clínicos potenciais e os volumes cerebrais globais e regionais. Resultados: Os pacientes com esquizofrenia de primeiro episódio apresentaram reduções volumétricas sutis em comparação aos controles, em um circuito neural circunscrito e identificável apenas em análises SVC (small volume correction) [p < 0.05, com correção family-wise error (FWE)], incluindo a ínsula, estruturas têmporo-límbicas e corpo estriado. Os pacientes crônicos, por outro lado, apresentaram um padrão de alterações extensas comparativamente aos controles, envolvendo os córtices frontais orbitais, superiores e inferiores bilateralmente, córtex frontal médio direito, ambos os córtices cingulados anteriores, ambas as ínsulas, e os córtices temporais superior e médio direitos (p < 0.05, análises whole-brain com correção FWE). Foram encontradas correlações negativas significantes entre exposição cumulativa a antipsicóticos e volumes globais de SC e substância branca nos pacientes com esquizofrenia, embora as correlações com reduções regionais não tenham sido significantes. Detectaram-se, ainda, correlações negativas significantes entre tempo de doença e volumes regionais relativos da ínsula esquerda, córtex cingulado anterior direito e córtices pré-frontais dorsolaterais nas análises SVC para os grupos conjuntos (esquizofrenia crônica e de primeiro episódio). Conclusão: Os achados supracitados indicam que: a) as alterações estruturais associadas com o diagnóstico de esquizofrenia são mais disseminadas na forma crônica em comparação à de primeiro episódio; b) reduções volumétricas regionais em áreas específicas do cérebro podem variar em função do tempo de doença; c) a exposição cumulativa a antipsicóticos associou-se a alterações volumétricas globais, e não regionais

The First Century of Right to Arms Litigation

This Article examines state court cases involving the right to arms, during the first century following ratification of the Amendment in 1791. This is not the first article to survey some of those cases. This Article includes additional cases, and details the procedural postures and facts, not only the holdings. The Article closely examines how the Supreme Court integrated the nineteenth century arms cases into Heller and McDonald to shape modern Second Amendment law. Part I briefly explains two English cases which greatly influenced American legal understandings. Semayne’s Case is the foundation of “castle doctrine” — the right to home security which includes the right of armed self-defense in the home. Sir John Knight’s Case fortified the tradition of the right to bear arms, providing that the person must bear arms in a non-terrifying manner. Part II examines American antebellum cases; these are the cases to which Heller looked for guidance on the meaning of the Second Amendment. Part III looks at cases from Reconstruction and the early years of Jim Crow, through 1891. As with the antebellum cases, the large majority of post-war cases are from the Southeast, which during the nineteenth century was the region most ardent for gun control. The heart of gun control country was Tennessee and Arkansas; courts there resisted some infringements of the right to arms, but eventually gave up. Heller and McDonald did not look to the Jim Crow cases as constructive precedents on the Second Amendment.

Development of a Household Pharmaceutical Waste Collection Program for Atlanta, Georgia: An Analysis of Risk Factors and Public Awareness with a Comprehensive Collection Plan

Decades of mixed messages from three federal agencies left many Americans unaware of the hazards associated with the indiscriminate disposal of unwanted or expired medicines. For this Capstone project, a systematic review of state and federal regulations was undertaken to determine how these laws obstruct household pharmaceutical waste collection. In addition, a survey of 654 Atlanta residents was conducted to evaluate unwanted medicine disposal habits, awareness of pharmaceutical compounds being detected in drinking water, surface, and ground waters, and willingness to participate in a household pharmaceutical waste collection program. Survey responses were tabulated to provide overall results and by age group, gender, and race. A household pharmaceutical waste collection plan was developed for the city and included as an appendix.

Autopercepción del bienestar del cuidador familiar del adulto mayor y características sociodemográficas

Introducción: La autopercepción del bienestar dimensional se relaciona con características de cuidadoras. Objetivo: Establecer asociación de autopercepción en dimensiones de bienestar y características de cuidadores. Método: Estudio descriptivo, analítico y correlacional. Muestra 300 cuidadores. Matamoros Tamaulipas, México. Cuestionarios: Datos Sociodemográficos, Índice Barthel, Calidad Vida: dimensiones física, psicológica, social; y espiritual, éste con alpha de Cronbach 0.69. Pruebas chi-cuadrada y coeficiente correlación de Pearson. Resultados: Características mayoría mujeres, 42 años, casadas, hija, alfabetizadas, labores hogar, baja escolaridad, sin trabajo o ingresos limitados. Autopercepción con significancia en bienestar general, alfabetización y parentesco; dimensiones física, edad y género; psicológica, escolaridad; social, parentesco y espiritual alfabetización, situación laboral, ocupación y estado civil. Discusión: Características vulneran a cuidadoras a efectos adversos del cuidado y determinan mayor percepción de carga que altera su bienestar dimensional.