What are the origins of growing microbial resistance? Both Lamarck and Darwin were right.

INTRODUCTION: Microorganisms of clinical importance frequently develop resistance to drug therapy, now a growing problem. The experience with Mycobacterium tuberculosis is a representative example of increasing multi-drug resistance. To avoid reaching a crisis in which patients could be left without adequate treatment, a new strategy is needed. Anti-microbial therapy has historically targeted the mechanisms rather than origin of drug resistance, thus allowing microorganisms to adapt and survive. AREAS COVERED: This contribution analyses the historical development (1943-2020) of the evolution of multi-drug resistance by M. tuberculosis strains in light of Darwin's and Lamarck's theories of evolution. EXPERT OPINION: Regarding the molecular origin of microbial drug resistance, genetic mutations and epigenetic modifications are known to participate. The analysis of the history of drug resistance by M. tuberculosis evidences a gradual development of resistance to some antibiotics, undoubtedly due to random mutations together with natural selection based on environmental pressures (e.g., antibiotics), representing Darwin's idea. More rapid adaptation of M. tuberculosis to new antibiotic treatments has also occurred, probably because of heritable acquired characteristics, evidencing Lamarck's proposal. Therefore, microbial infections should be treated with an antibiotic producing null or low mutagenic activity along with a resistance inhibitor, preferably in a single medication.

Prolonged slow expiration technique improves recovery from acute bronchiolitis in infants: FIBARRIX randomized controlled trial.

OBJECTIVE:: To examine the effect of prolonged slow expiration respiratory physiotherapy treatment on the acute bronchiolitis severity scale and O2 saturation at short-time and at medical discharge in infants and the hospital stay. DESIGN:: Randomized controlled trial. SETTING:: Infants' unit of university hospital. PARTICIPANTS:: Infants with acute bronchiolitis ( N = 80). INTERVENTION:: Infants were randomized into respiratory treatment (RT) with prolonged slow expiration or treatment as usual (control) for one-week period. MAIN OUTCOME MEASURES:: The primary outcomes were Acute Bronchiolitis Severity Scale score and O2 saturation, recorded shortly after each intervention during the stay and at medical discharge, and the hospital stay. RESULTS:: The RT had a significantly lower Acute Bronchiolitis Severity Scale 10-minute after the first intervention (mean difference -1.7 points, 95% confidence interval (CI) -3.0 to -0.38), 2 hours after (-2.0 points, 95% CI -3.2 to -0.86) and the last day before medical discharge (-1.3 points, 95% CI -2.1 to 0.51). No changes were detected in O2 saturation. The survival analysis of time at medical discharge showed decrease in the average number of days to achieve an Acute Bronchiolitis Severity Scale of less than 2 points (RT: 2.6 days, 95% CI 2.1-3.1; Control: 4.4 days, 95% CI 3.6-5.1). CONCLUSION:: A prolonged slow expiration physiotherapy reduces Acute Bronchiolitis Severity Scale scores and does not change O2 saturation. Infants in RT group stay less days in hospital than infants in control group and no adverse events were detected.

Relaciones de equivalencia de estímulos y relaciones de equivalencia-equivalencia: efectos de la estructura de entrenamiento / Stimulus Equivalence Relations and Equivalence-Equivalence Relations: Effects of the Training Structure

The influence of training structure on the formation of equivalence relations and equivalence-equivalence relations was assessed. Three groups learned conditional relations using different training structures: Many to One, One to Many and Linear Series. The results showed a training structure effect on the percentage of correct responses in the equivalence relations test. However, this effect was not observed on the test of equivalence-equivalence relations. These results show that training structure has effects on the formation of equivalence relations, but it has no influence on equivalence-equivalence relations. These findings are analyzed according to the requirements for the formation of equivalence-equivalence relations (AU)

En el presente estudio se investiga la influencia de la estructura de entrenamiento en la formación de relaciones de equivalencia y de “equivalencia-equivalencia”. Se estudiaron tres grupos de sujetos los cuales fueron entrenados con las estructuras: Muchos a Uno, Uno a Muchos o Serie Lineal para las relaciones condicionales. Se verificó el efecto de estructura de entrenamiento sobre la variable porcentaje de aciertos en el test de relaciones de equivalencia. Sin embargo, este fenómeno no se replicó en el test de relaciones de equivalencia-equivalencia. Los resultados indican que la estructura de entrenamiento influye cuando se forman relaciones de equivalencia, pero no cuando se forman relaciones de equivalencia-equivalencia. Se analizan los hallazgos considerando los requisitos para la formación de relaciones de equivalencia-equivalencia (AU)

An ERP study of structural anomalies in native and semantic free artificial grammar: evidence for shared processing mechanisms.

Artificial grammars have been widely applied to the study of sequential learning in language, but few studies have directly compared the neural correlates of artificial and native grammar processing. In this study, we examined Event Related Potentials (ERPs) elicited by structural anomalies in semantic-free artificial grammar sequences and sentences in the subjects' native language (Spanish). Although ERPs differed during early stages, we observed similar posterior negativities (N400) and P600 effects in a late stage. We interpret these results as evidence of at least partially shared neural mechanisms for processing of language and artificial grammars. We suggest that in both the natural and artificial grammars, the N400 and P600 components we observed can be explained as the result of unfulfilled predictions about incoming stimuli.

On the learnability of frequent and infrequent word orders: an artificial language learning study.

Most languages have a basic or "canonical" word order, which determines the relative positions of the subject (S), the verb (V), and the object (O) in a typical declarative sentence. The frequency of occurrence of the six possible word orders among world languages is not distributed uniformly. While SVO and SOV represent around 85% of world languages, orders like VSO (9%) or OSV (0.5%) are much less frequent or extremely rare. One possible explanation for this asymmetry is that biological and cognitive constraints for structured sequence processing make some word orders easier to be processed than others. Therefore, the high frequency of these word orders would be related to their higher learnability. The aim of the present study was to compare the learnability of different word orders between groups of adult subjects. Four artificial languages with different word orders were trained: two frequent (SVO, SOV) and two infrequent (VSO, OSV). In a test stage, subjects were asked to discriminate between new correct sentences and syntax or semantic violations. Higher performance rates and faster responses were observed for more frequent word orders. The results support the hypothesis that more frequent word orders are more easily learned.

Expectancy modulates a late positive ERP in an artificial grammar task.

A wide range of studies have found late positive ERP components in response to anomalies during processing of structured sequences. In language studies, this component is named Syntactic Positive Shift (SPS) or P600. It is characterized by an increase in potential peaking around 600 ms after the appearance of the syntactic anomaly and has a centroparietal topography. Similar late positive components were found more recently in non-linguistic contexts. These results have led to the hypothesis that these components index the detection of anomalies in rule-governed sequences, or the access to abstract rule representations, regardless of the nature of the stimuli. Additionally, there is evidence showing that the SPS/P600 is sensitive to probability manipulations, which affect the subjects' expectancy of the stimuli. Our aim in the present work was to address the hypothesis that the late positive component is modulated by the subject's expectancy of the stimuli. To do so, we employed an artificial grammar learning task, and controlled the frequency of presentation to different kind of sequences during training. Results showed that certain sequence types elicited a late positive component which was modulated by different factors in two distinct time windows. In an earlier window, the component was higher for sequences which had a low or null probability of occurrence during training, while in a later window, the component was higher for incorrect than correct sequences. Furthermore, this late window effect was absent in those subjects whose performance was not significantly above chance. Two possible explanations for this effect are suggested.

Neural set point for the control of arterial pressure: role of the nucleus tractus solitarius.

BACKGROUND: Physiological experiments have shown that the mean arterial blood pressure (MAP) can not be regulated after chemo and cardiopulmonary receptor denervation. Neuro-physiological information suggests that the nucleus tractus solitarius (NTS) is the only structure that receives information from its rostral neural nuclei and from the cardiovascular receptors and projects to nuclei that regulate the circulatory variables. METHODS: From a control theory perspective, to answer if the cardiovascular regulation has a set point, we should find out whether in the cardiovascular control there is something equivalent to a comparator evaluating the error signal (between the rostral projections to the NTS and the feedback inputs). The NTS would function as a comparator if: a) its lesion suppresses cardiovascular regulation; b) the negative feedback loop still responds normally to perturbations (such as mechanical or electrical) after cutting the rostral afferent fibers to the NTS; c) perturbation of rostral neural structures (RNS) to the NTS modifies the set point without changing the dynamics of the elicited response; and d) cardiovascular responses to perturbations on neural structures within the negative feedback loop compensate for much faster than perturbations on the NTS rostral structures. RESULTS: From the control theory framework, experimental evidence found currently in the literature plus experimental results from our group was put together showing that the above-mentioned conditions (to show that the NTS functions as a comparator) are satisfied. CONCLUSIONS: Physiological experiments suggest that long-term blood pressure is regulated by the nervous system. The NTS functions as a comparator (evaluating the error signal) between its RNS and the cardiovascular receptor afferents and projects to nuclei that regulate the circulatory variables. The mean arterial pressure (MAP) is regulated by the feedback of chemo and cardiopulmonary receptors and the baroreflex would stabilize the short term pressure value to the prevailing carotid MAP. The discharge rates of rostral neural projections to the NTS would function as the set point of the closed and open loops of cardiovascular control. No doubt, then, the RNS play a functional role not only under steady-state conditions, but also in different behaviors and pathologies.

Efectos del desarrollo en la memoria de trabajo y el aprendizaje de categorías en niños / Developmet effects on working memory and category learning in children

Se han reportado diferencias relacionadas con la edad en el desempeño de diversas tareas dependientes del lóbulo frontal, incluyendo tareas de memoria de trabajo (Luciana and Nelson, 1998; Luna et al. 2001; Bunge et al., 2002). Se han encontrado también efectos de edad y género sobre la memoria de trabajo en niños (Vuontela et. al, 2003). Además, el aprendizaje de categorías ha sido asociado con la actividad del lóbulo frontal (Dickins, 2000; Schlund 2007). El presente trabajo investigó los efectos de la edad y el género sobre la memoria de trabajo y el aprendizaje de categorías en niños de 8 a 13 años. Se encontraron efectos de edad y género sobre la memoria de trabajo, y en la tarea de aprendizaje de categorías sólo se observaron efectos de la edad. Los resultados sugieren que el desempeño de memoria de trabajo podría estar asociado con la velocidad de procesamiento en el aprendizaje de categorías.

Age-related differences have been reported in the performance of several frontal lobe-dependent tasks, including working memory (Luciana and Nelson, 1998; Luna et al. 2001; Bunge et al., 2002). Effects of age and gender on working memory have been found in children (Vuontela et. al, 2003). On the other hand, category learning has also been associated with frontal lobe activity (Dickins, 2000; Schlund 2007). The present study addressed the effects of age and gender on working memory and category learning, in 8-13 year old children. Age and gender effects were found on the working memory task, and age effects only were observed on category learning. The results suggest that working memory performance might be associated with processing speed in the category learning task.

Event-related potential correlates of perceptual and functional categories: comparison between stimuli matching by identity and equivalence.

Event-related potentials (ERPs) correlates of two test criteria of an abstract category task were dissociated. In a stimulus equivalence task, 10 subjects observed pairs of figures presented serially in three conditions: reflexivity (generalized identity), equivalence (arbitrary derived relations from a previous training), and unrelated pairs. They were instructed to decide whether the second item in a pair matched or mismatched the first one. Participants' performance in reflexivity matching tests was faster and more accurate than in equivalence matching or mismatching responses. In the three conditions, an occipital P2, a frontal N2 and a parietal P3 ERP component were elicited. The earlier components P2 and N2 exhibited reflexivity matching effects, while the later component (P3) exhibited the only equivalence matching effect. In addition, the subtracted ERP components from unrelated minus identity and unrelated minus equivalence trials were computed within two time windows: 150-250ms (dN300) and 350-450ms (dN400). While both dN300 waves were not significantly different, the comparison of both dN400 waves showed statistical differences. Correlates of partially perceptual (but contextually abstract) concepts are elicited earlier than those of pure abstract concepts. These ERPs correlates of stimulus equivalence relation tests of semantic categories are in concordance with the behavioral data.

Potenciales cerebrales relacionados con categorización lógica en humanos: estudio descriptivo y planteos experimentales / Brain potentiales associated with logic categorization in humans: descriptive study and experimental issues

El presente trabajo investiga desde un abordaje “biocomportamental” aspectos electroneurofisiológicos correlativos al aprendizaje de categorías lógicas en sujetos humanos sanos. Se empleó la técnica de potenciales relacionados a eventos (PREs) para registrar la actividad electrofisiológica de los sujetos durante la realización de una tarea de relaciones de equivalencia (Sidman, 1982). Como resultado, pudo observarse la siguiente sucesión temporal relacionada con los estímulos de comparación: un potencial visual temprano en la región occipital, luego un componente negativo en la región frontal y otro positivo tardío parietal. Finalmente, en sincronía con las respuestas, se obtuvo un componente negativo lateralizado en la región central. Se discute el significado funcional de los potenciales identificados, y se propone como planteo experimental examinar la correspondencia temporal de los distintos componentes PREs entre sí y con el tiempo de respuesta, como dispositivo experimental para el estudio de aspectos funcionales y estructurales del comportamiento complejo en humanos.

Evaluación de algunos factores que pudieron influir en el incremento de la fiebre porcina clásica en el Estado de México, México, durante 1997 / Evaluation of some factors influencing the increment of classical swine fever in athe State of Mexico during 1997

El área de control de la fiebre porcina clásica se encuentra localizada en la parte central y sur de México. Se continúa con la vacunación de los animales y se han seguido presentando casos de la enfermedad. El número de brotes se incrementó durante 1997, siendo 87 por ciento en explotaciones de traspatio. Con el propósito de determinar algunos de los factores que contribuyeron al incremento de los brotes en 1997, se hicieron encuestas en 424 explotaciones de traspatio de cuatro municipios, cuatro mercados o tianguis de animales, cuatro rastros municipales y 16 granjas de ciclo completo de la zona poniente del Estado de México, México, que se encuentra dentro del área de control. En las explotaciones de traspatio, en promedio, 25 por ciento de los cerdos fueron vacunados y en el muestreo serológico 43 por ciento tenían anticuerpos. En promedio 37 por ciento de los cerdos eran vendidos y remplazados cada tres meses. De las granjas de ciclo completo, en 12 por ciento no vacunaban a los animales. En los tianguis, un promedio de 40 por ciento de los cerdos comercializados provenían de la zona en erradicación y 60 por ciento de la zona en control. En los cuatro rastros encuestados, los veterinarios oficiales informaron el decomiso de animales con lesiones sugerentes de fiebre porcina clásica. Se concluyó que los factores que contribuyeron al incremento del número de brotes en 1997 en la población de traspatio, fueron el elevado número de animales susceptibles que estaban entrando al área de control y eran mezclados con otros cerdos en los tianguis, su gran movilidad y bajo nivel de inmunidad, y cerdos enfermos y virémicos eran mandados al rastro por lo que los vehículos y choferes se pudieron contaminar en los rastros y acarrear el virus a las explotaciones porcinas.

El estrés del equipo de salud: presentación de un programa interdisciplinario de salud ocupacional / Health staff stress: interdisciplinary program on occupational health

El objetivo de este trabajo es describir los pasos seguidos para la elaboración de protocolos confiables que provean información fehaciente acerca del nivel general de estrés en una población bien acotada desde una visión trans e interdisciplinaria. Se presenta la información obtenida a partir de un protocolo elaborado por el Equipo de Investigación del Programa de Salud Ocupacional (IBYME-CONICET-UBA) y que fuera administrado a los miembros (médicos y enfermeras) del Equipo de Salud del Departamento de Urgencias del Hospital General de Agudos Juan A. Fernández de la Ciudad de Buenos Aires. La técnica utilizada, solitando a los propios actores del problema que enuncien los estímulos estresantes, parece ser adecuada para este tipo de programa. Se observaron diferencias en cuanto al área de origen del suceso más estresante entre médicos y enfermeras. La percepción de modificabilidad de dicho suceso es mayor en médicos que en enfermeras

El estrés del equipo de salud: presentación de un programa interdisciplinario de salud ocupacional / Health staff stress: interdisciplinary program on occupational health

El objetivo de este trabajo es describir los pasos seguidos para la elaboración de protocolos confiables que provean información fehaciente acerca del nivel general de estrés en una población bien acotada desde una visión trans e interdisciplinaria. Se presenta la información obtenida a partir de un protocolo elaborado por el Equipo de Investigación del Programa de Salud Ocupacional (IBYME-CONICET-UBA) y que fuera administrado a los miembros (médicos y enfermeras) del Equipo de Salud del Departamento de Urgencias del Hospital General de Agudos Juan A. Fernández de la Ciudad de Buenos Aires. La técnica utilizada, solitando a los propios actores del problema que enuncien los estímulos estresantes, parece ser adecuada para este tipo de programa. Se observaron diferencias en cuanto al área de origen del suceso más estresante entre médicos y enfermeras. La percepción de modificabilidad de dicho suceso es mayor en médicos que en enfermeras (AU)

Efecto de la falta de predicción sobre el status social de ratas / Effect of unpredictability about the social status of rats

Se analizó el efecto que la estimulación aversiva predecible e impredecible provoca sobre el rango social en ratas. Se formaron parejas de ratas Sprague Dawley macho adultas y se procedió a evaluar y caracterizar el rango jerárquico de cada miembro del par. Para ello, se registró la prioridad y desplazamientos de los animales para acceder a una fuente limitada de agua. Una vez verificado el rango de cada individuo, se procedió a someter a los animales dominantes de cada pareja a una sesión de 100 shocks eléctricos no escapables, en donde mitad de los animales lo recibieron a intervalos constantes y la otra a intervalos variables. Posteriormente, se volvió a analizar la jerarquía. Los resultados mostraron que la aplicación de descargas a intervalos variables (descargas no predecibles) provocaron una caída del status de los dominantes, mientras que la misma cantidad de descargas presentadas a intervalos fijos no produjo cambios en la jerarquía de los dominantes.

Anormalidades eléctricas cerebrales asociadas a trastornos conductuales en ratas con exposición prolongada a diferentes dosis de plomo / Electrical brain abnormalities associated with behavioral disorders in rats with different doses prolonged exposure to lead

Se describen alteraciones de aprendizaje por exposición al plomo en animales y en humanos. En el presente trabajo se estudian pruebas conductuales (open-field y aprendizaje de evitación pasiva) conjuntamente con registros electroneurofisiológicos (electroencefalograma y potenciales relacionados con eventos) en ratas expuestas a diferentes dosis de plomo. Se comprueban diferencias significativas en las pruebas conductuales entre controles y animales expuestos al plomo. Además, las alteraciones electroneurofisiológicas presentan correlaciones significativas con los nivels de plomo tisular. Se concluye que las variables electroneurofisiológicas consideradas pueden ser indicadores indirectos de mecanismos celulares y neuroquimicos subyacentes a los defectos cognitivos.

Relaciones entre asimetrías interhemisféricas de la actividad eléctrica cerebral, frecuencia cardíaca y factores de personalidad / Relations between interhemispheric asymmetry of brain electrical activity, heart rate and personality factors

Las asimetrías de amplitud interhemisféricas de la actividad alfa EEG se presentan normalmente en un elevado número de sujetos normales, tanto en condiciones de reposo mental como ante la presentación de estímulos y la realización de tareas que implican habilidades cognitivas. Numerosos estudios investigaron la relación de estas asimetrías con preferencia manual y con diferencias individuales en capacidades cognitivas. También fueron comprobadas asimetrías asociadas a estados emocionales. El presente trabajo estudia las relaciones entre factores de personalidad y rasgos de personalidad que predisponen a estados de ansiedad y asimetría alfa EEG en sujetos normales. Fueron estudiados 55 voluntarios normales a quienes se efectuaron una evaluación psicológica y registro EEG en sesiones separadas. Se comprobaron correlaciones significativas en la asimetría alfa EEG y factores de personalidad de Eysenck (1977), Tobal y Cano Vindel (1984). Estos hallazgos sugieren que el grado de activación tónica lateralizada en un hemisferio cerebral podría predisponer a estilos de afrontamiento ante estresores.

Evaluación de factores de riesgo en el desarrollo cognitivo en infantes: un modelo de protocolo / Evaluation of risk factors in congnitive development in infants: a protocol model

No hay duda que el rendimiento cognitivo de un individuo en edad escolar depende tanto de factores biológicos como no biológicos. La evaluación confiable y precoz de dichos factores para la instrumentación de acciones preventivas eficaces, constituye un objetivo que contempla necesidades de orden clínico, educacional y social. Esto requiere la implementación de técnicas de diagnóstico neuropsicológico en infantes, así como la evaluación de todos los factores determinantes de riesgo cognitivo en los mismos. Aquí presentamos una sistematización de la información relevante de los factores que participan en el desarrollo cognitivo. Esto permitirá establecer criterios de riesgo en estudios poblacionales y complementar el cuadro de riesgo de casos clínicos específicos

Prazosin and stress effect on tumoral growth of 7.12-Dimethylbenz[A]anthracene-induced rat mammary tumors

Repeated isolation stress and prazosin effect were evaluated in 7,12-dimetylbenz [A] anthracene (DMBA) mammary tumors. Tumor volume was significantly lower in stressed than in control animals from 10 to 52 days considering day 1 the moment when tumors became palpable and treament began. Control Prazosin (0.5 mg/Kg) rats showed diminished tumor volume after 40 days. Stress Prazosin curve was similar to stress alone. The proportion of progressing tumors in control was significantly higher than in stressed groups, regardless of Prazosin administration. Body weight gain was similar in every group throughout the experiment. Behavioral studies were performed when stress effect was no longer evident. Grooming and the number of fecal boli were similar in all groups, as well as prolactin serum levels, suggesting that habituation took place. No significant differences were observed between groups for estrogen receptors. However, a greater concentration of progesterone receptors was found in Stressed rats, compared to all other groups. We conclude that the decrease of tumor volume provoked by stress could not be reversed by the alpha 1-adrenergic antagonist prazosin. Then, it appears that the main effect of stress is not mediated by the alpha 1-adrenergic receptors. Higher progesterone receptors in stressed rats could explain the differences observed.

Prazosin and stress effect on tumoral growth of 7.12-Dimethylbenz[A]anthracene-induced rat mammary tumors

Repeated isolation stress and prazosin effect were evaluated in 7,12-dimetylbenz [A] anthracene (DMBA) mammary tumors. Tumor volume was significantly lower in stressed than in control animals from 10 to 52 days considering day 1 the moment when tumors became palpable and treament began. Control Prazosin (0.5 mg/Kg) rats showed diminished tumor volume after 40 days. Stress Prazosin curve was similar to stress alone. The proportion of progressing tumors in control was significantly higher than in stressed groups, regardless of Prazosin administration. Body weight gain was similar in every group throughout the experiment. Behavioral studies were performed when stress effect was no longer evident. Grooming and the number of fecal boli were similar in all groups, as well as prolactin serum levels, suggesting that habituation took place. No significant differences were observed between groups for estrogen receptors. However, a greater concentration of progesterone receptors was found in Stressed rats, compared to all other groups. We conclude that the decrease of tumor volume provoked by stress could not be reversed by the alpha 1-adrenergic antagonist prazosin. Then, it appears that the main effect of stress is not mediated by the alpha 1-adrenergic receptors. Higher progesterone receptors in stressed rats could explain the differences observed. (AU)