Chronic Exposure to High Fat Diet Affects the Synaptic Transmission That Regulates the Dopamine Release in the Nucleus Accumbens of Adolescent Male Rats.

Obesity is a pandemic caused by many factors, including a chronic excess in hypercaloric and high-palatable food intake. In addition, the global prevalence of obesity has increased in all age categories, such as children, adolescents, and adults. However, at the neurobiological level, how neural circuits regulate the hedonic consumption of food intake and how the reward circuit is modified under hypercaloric diet consumption are still being unraveled. We aimed to determine the molecular and functional changes of dopaminergic and glutamatergic modulation of nucleus accumbens (NAcc) in male rats exposed to chronic consumption of a high-fat diet (HFD). Male Sprague-Dawley rats were fed a chow diet or HFD from postnatal day (PND) 21 to 62, increasing obesity markers. In addition, in HFD rats, the frequency but not amplitude of the spontaneous excitatory postsynaptic current is increased in NAcc medium spiny neurons (MSNs). Moreover, only MSNs expressing dopamine (DA) receptor type 2 (D2) increase the amplitude and glutamate release in response to amphetamine, downregulating the indirect pathway. Furthermore, NAcc gene expression of inflammasome components is increased by chronic exposure to HFD. At the neurochemical level, DOPAC content and tonic dopamine (DA) release are reduced in NAcc, while phasic DA release is increased in HFD-fed rats. In conclusion, our model of childhood and adolescent obesity functionally affects the NAcc, a brain nucleus involved in the hedonic control of feeding, which might trigger addictive-like behaviors for obesogenic foods and, through positive feedback, maintain the obese phenotype.

Dissociable Neural Information Dynamics of Perceptual Integration and Differentiation during Bistable Perception.

At any given moment, we experience a perceptual scene as a single whole and yet we may distinguish a variety of objects within it. This phenomenon instantiates two properties of conscious perception: integration and differentiation. Integration is the property of experiencing a collection of objects as a unitary percept and differentiation is the property of experiencing these objects as distinct from each other. Here, we evaluated the neural information dynamics underlying integration and differentiation of perceptual contents during bistable perception. Participants listened to a sequence of tones (auditory bistable stimuli) experienced either as a single stream (perceptual integration) or as two parallel streams (perceptual differentiation) of sounds. We computed neurophysiological indices of information integration and information differentiation with electroencephalographic and intracranial recordings. When perceptual alternations were endogenously driven, the integrated percept was associated with an increase in neural information integration and a decrease in neural differentiation across frontoparietal regions, whereas the opposite pattern was observed for the differentiated percept. However, when perception was exogenously driven by a change in the sound stream (no bistability), neural oscillatory power distinguished between percepts but information measures did not. We demonstrate that perceptual integration and differentiation can be mapped to theoretically motivated neural information signatures, suggesting a direct relationship between phenomenology and neurophysiology.

Expression and function of TLR4- induced B1R bradykinin receptor on cardiac fibroblasts.

Cardiac fibroblasts (CF) are key cells for maintaining extracellular matrix (ECM) protein homeostasis in the heart, and for cardiac repair through CF-to-cardiac myofibroblast (CMF) differentiation. Additionally, CF play an important role in the inflammatory process after cardiac injury, and they express Toll like receptor 4 (TLR4), B1 and B2 bradykinin receptors (B1R and B2R) which are important in the inflammatory response. B1R and B2R are induced by proinflammatory cytokines and their activation by bradykinin (BK: B2R agonist) or des-arg-kallidin (DAKD: B1R agonist), induces NO and PGI2 production which is key for reducing collagen I levels. However, whether TLR4 activation regulates bradykinin receptor expression remains unknown. CF were isolated from human, neonatal rat and adult mouse heart. B1R mRNA expression was evaluated by qRT-PCR, whereas B1R, collagen, COX-2 and iNOS protein levels were evaluated by Western Blot. NO and PGI2 were evaluated by commercial kits. We report here that in CF, TLR4 activation increased B1R mRNA and protein levels, as well as COX-2 and iNOS levels. B1R mRNA levels were also induced by interleukin-1α via its cognate receptor IL-1R1. In LPS-pretreated CF the DAKD treatment induced higher responses with respect to those observed in non LPS-pretreated CF, increasing PGI2 secretion and NO production; and reducing collagen I protein levels in CF. In conclusion, no significant response to DAKD was observed (due to very low expression of B1R in CF) - but pre-activation of TLR4 in CF, conditions that significantly enhanced B1R expression, led to an additional response of DAKD.

Spectral signatures of reorganised brain networks in disorders of consciousness.

Theoretical advances in the science of consciousness have proposed that it is concomitant with balanced cortical integration and differentiation, enabled by efficient networks of information transfer across multiple scales. Here, we apply graph theory to compare key signatures of such networks in high-density electroencephalographic data from 32 patients with chronic disorders of consciousness, against normative data from healthy controls. Based on connectivity within canonical frequency bands, we found that patient networks had reduced local and global efficiency, and fewer hubs in the alpha band. We devised a novel topographical metric, termed modular span, which showed that the alpha network modules in patients were also spatially circumscribed, lacking the structured long-distance interactions commonly observed in the healthy controls. Importantly however, these differences between graph-theoretic metrics were partially reversed in delta and theta band networks, which were also significantly more similar to each other in patients than controls. Going further, we found that metrics of alpha network efficiency also correlated with the degree of behavioural awareness. Intriguingly, some patients in behaviourally unresponsive vegetative states who demonstrated evidence of covert awareness with functional neuroimaging stood out from this trend: they had alpha networks that were remarkably well preserved and similar to those observed in the controls. Taken together, our findings inform current understanding of disorders of consciousness by highlighting the distinctive brain networks that characterise them. In the significant minority of vegetative patients who follow commands in neuroimaging tests, they point to putative network mechanisms that could support cognitive function and consciousness despite profound behavioural impairment.

Glucagon Increases Retinal Rod Bipolar Cell Inhibition Through a D1 Dopamine Receptor-Dependent Pathway That Is Altered After Lens-Defocus Treatment in Mice.

Purpose: Members of the secretin/glucagon family have diverse roles in retinal physiological and pathological conditions. Out of them, glucagon has been associated with eye growth regulation and image defocus signaling in the eye, both processes central in myopia induction. On the other hand, dopamine is perhaps the most studied molecule in myopia and has been proposed as fundamental in myopia pathogenesis. However, glucagonergic activity in the mammalian retina and its possible link with dopaminergic signaling remain unknown. Methods: To corroborate whether glucagon and dopamine participate together in the modulation of synaptic activity in the retina, inhibitory post-synaptic currents were measured in rod bipolar cells from retinal slices of wild type and negative lens-exposed mice, using whole cell patch-clamp recordings and selective pharmacology. Results: Glucagon produced an increase of inhibitory post-synaptic current frequency in rod bipolar cells, which was also dependent on dopaminergic activity, as it was abolished by dopamine type 1 receptor antagonism and under scotopic conditions. The effect was also abolished after 3-week negative lens-exposure but could be recovered using dopamine type 1 receptor agonism. Conclusions: Altogether, these results support a possible neuromodulatory role of glucagon in the retina of mammals as part of a dopaminergic activity-dependent synaptic pathway that is affected under myopia-inducing conditions.

Early-Life Exposure to Non-Absorbable Broad-Spectrum Antibiotics Affects the Dopamine Mesocorticolimbic Pathway of Adult Rats in a Sex-Dependent Manner.

Gut microbiota with a stable, rich, and diverse composition is associated with adequate postnatal brain development. Colonization of the infant's gut begins at birth when parturition exposes the newborn to a set of maternal bacteria, increasing richness and diversity until one to two first years of age when a microbiota composition is stable until old age. Conversely, alterations in gut microbiota by diet, stress, infection, and antibiotic exposure have been associated with several pathologies, including metabolic and neuropsychiatric diseases such as obesity, anxiety, depression, and drug addiction, among others. However, the consequences of early-life exposure to antibiotics (ELEA) on the dopamine (DA) mesocorticolimbic circuit are poorly studied. In this context, we administered oral non-absorbable broad-spectrum antibiotics to pregnant Sprague-Dawley dams during the perinatal period (from embryonic day 18 until postnatal day 7) and investigated their adult offspring (postnatal day 60) to assess methylphenidate-induced conditioned place preference (CPP) and locomotor activity, DA release, DA and 3,4-dihydroxyphenylacetic acid (DOPAC) content in ventral tegmental area (VTA), and expression of key proteins within the mesocorticolimbic system. Our results show that ELEA affect the rats conduct by increasing drug-seeking behavior and locomotor activity induced by methylphenidate of males and females, respectively, while reducing dopamine striatal release and VTA content of DOPAC in females. In addition, antibiotics increased protein levels of DA type 1 receptor in prefrontal cortex and VTA of female rats, and tyrosine hydroxylase in VTA of adult male and female rats. Altogether, these results suggest that ELEA alters the development of the microbiota-gut-brain axis affecting the reward system and the response to abuse drugs in adulthood.

Altered Grooming Syntax and Amphetamine-Induced Dopamine Release in EAAT3 Overexpressing Mice.

The excitatory amino acid transporter EAAT3 plays an important role in the neuronal uptake of glutamate regulating the activation of glutamate receptors. Polymorphisms in the gene-encoding EAAT3 have been associated with obsessive-compulsive disorder (OCD), although the mechanisms underlying this relationship are still unknown. We recently reported that mice with increased EAAT3 expression in forebrain neurons (EAAT3 g lo /CMKII) display behavioral and synaptic features relevant to OCD, including increased grooming, higher anxiety-like behavior and altered cortico-striatal synaptic function. The dopamine neurotransmitter system is implicated in ritualistic behaviors. Indeed, dopaminergic neurons express EAAT3, and mice lacking EAAT3 exhibit decreased dopamine release and decreased expression of the dopamine D1 receptor. Moreover, EAAT3 plays a role on the effect of the psychostimulant amphetamine. As such, we sought to determine if the OCD-like behavior in EAAT3 g lo /CMKII mice is accompanied by altered nigro-striatal dopaminergic transmission. The aim of this study was to analyze dopamine transmission both in basal conditions and after an acute challenge of amphetamine, using behavioral, neurochemical, molecular, and cellular approaches. We found that in basal conditions, EAAT3 g lo /CMKII mice performed more grooming events and that they remained in phase 1 of the grooming chain syntax compared with control littermates. Administration of amphetamine increased the number of grooming events in control mice, while EAAT3 g lo /CMKII mice remain unaffected. Interestingly, the grooming syntax of amphetamine-control mice resembled that of EAAT3 g lo /CMKII mice in basal conditions. Using in vivo microdialysis, we found decreased basal dopamine levels in EAAT3 g lo /CMKII compared with control mice. Unexpectedly, we found that after acute amphetamine, EAAT3 g lo /CMKII mice had a higher release of dopamine compared with that of control mice, suggesting that EAAT3 overexpression leads to increased dopamine releasability. To determine postsynaptic effect of EAAT3 overexpression over dopamine transmission, we performed Western blot analysis of dopaminergic proteins and found that EAAT3 g lo /CMKII mice have higher expression of D2 receptors, suggesting a higher inhibition of the indirect striatal pathway. Together, the data indicate that EAAT3 overexpression impacts on dopamine transmission, making dopamine neurons more sensitive to the effect of amphetamine and leading to a disbalance between the direct and indirect striatal pathways that favors the performance of repetitive behaviors.

Mechanical Behavior of Plaster Composites Based on Rubber Particles from End-of-Life Tires Reinforced with Carbon Fibers.

The principal objective of this research project is the disposal of end-of-life tire rubber waste and its incorporation in gypsum composites. As a continuation of previous projects, which established a reduction in the mechanical properties of the resulting products, the behavior of these composites is analyzed with the incorporation of carbon fibers. The density, Shore C hardness, flexural strength, compressive strength, dynamic modulus of elasticity, strength-strain curves, toughness and resistance values and microstructure of the material are studied and compared. The results obtained show a significant increase in the mechanical tensile strength of all of the samples containing fibers. The moduli of elasticity results show a decrease in rigidity and increase in toughness and resistance of the material produced by incorporating the fibers. An optimum dosage of a water/gypsum ratio of 0.6 and incorporation of 1.5% carbon fibers is proposed. This lightweight material, which offers a high mechanical performance, features characteristics which are suitable for large prefabricated building elements in the form of panels or boards.

Escala de desarrollo armónico (EDA): Una propuesta para la evaluación clínica del desarrollo infantil desde la Teoría de Sistemas / Harmonic Development Scale (SHD): A proposal for the clinical evaluation of child development from Systems Theory

El objetivo de este trabajo es presentar la Escala de Desarrollo Armónico ­EDA­ como una propuesta innovadora para llevar a cabo la prevención de los trastornos del desarrollo infantil. La escala se construyó para observar el ascenso del paisaje epigenético individual desde el paradigma de los sistemas dinámicos. Para lograrlo, se han estudiado parámetros que pueden explicar la evolución del sistema ­índice de armonía y cociente de desarrollo estable­, un mecanismo del cambio ­tirón cognitivo­ y fuerzas moldeadoras ­velocidad y cristalización­, siguiendo el principio de «armonía¼ para alcanzar el máximo desarrollo potencial. La estructura de la escala es adecuada para funcionar como un test adaptativo informatizado, por lo que resulta accesible, fácil de usar y puede validarse siguiendo la metodología de respuesta al ítem ­TRI­. Las cualidades «orgánicas¼ de la EDA permiten un funcionamiento interactivo a través de Internet ­www.maternal.eu­.

The objective of this work is to present the Scale of Harmonic Development ­SHD­ as an innovative proposal to carry out the prevention of childhood development disorders. The scale was built to observe the individual epigenetic landscape ascent from the dynamic system paradigm. To achieve this, several parameters have been studied, those which that can explain the system's evolution ­harmonic index and stable development quotient­, a change mechanism ­cognitive pull­ and shaping forces ­speed and crystallization ­, following the «harmony¼ principle to achieve the desired potential. The scales structure is suitable to work as a computerized adaptive test, therefore it being accessible, easy to use and it can be validated through the item response theory ­IRT­. The «organic¼ qualities of the SHD allow an interactive operation through Internet ­www.maternal.eu­.

Neurophenomenology revisited: second-person methods for the study of human consciousness.

In the study of consciousness, neurophenomenology was originally established as a novel research program attempting to reconcile two apparently irreconcilable methodologies in psychology: qualitative and quantitative methods. Its potential relies on Francisco Varela's idea of reciprocal constraints, in which first-person accounts and neurophysiological data mutually inform each other. However, since its first conceptualization, neurophenomenology has encountered methodological problems. These problems have emerged mainly because of the difficulty of obtaining and analyzing subjective reports in a systematic manner. However, more recently, several interview techniques for describing subjective accounts have been developed, collectively known as "second-person methods." Second-person methods refer to interview techniques that solicit both verbal and non-verbal information from participants in order to obtain systematic and detailed subjective reports. Here, we examine the potential for employing second-person methodologies in the neurophenomenological study of consciousness and we propose three practical ideas for developing a second-person neurophenomenological method. Thus, we first describe second-person methodologies available in the literature for analyzing subjective reports, identifying specific constraints on the status of the first-, second- and third- person methods. Second, we analyze two experimental studies that explicitly incorporate second-person methods for traversing the "gap" between phenomenology and neuroscience. Third, we analyze the challenges that second-person accounts face in establishing an objective methodology for comparing results across different participants and interviewers: this is the "validation" problem. Finally, we synthesize the common aspects of the interview methods described above. In conclusion, our arguments emphasize that second-person methods represent a powerful approach for closing the gap between the experiential and the neurobiological levels of description in the study of human consciousness.

Serial position effects in social transmission of food preference.

The serial position effect in Long-Evans rats was evaluated in two experiments. In Experiment 1, the effect in a group for which an interstimulus interval (ISI) was introduced between items in a list of demonstrators was compared with that in a group without an ISI. With an ISI, a recency effect was produced. In Experiment 2, a serial position effect group was compared with four groups in which either the distinctiveness or the context of the middle item was changed, relative to the items on either side of it. A von Restorff effect was produced when a rat from a different strain was used as a demonstrator in Position 2. The results for Experiment 1 are discussed in relation to interstimulus effects in monkeys and those for Experiment 2 with respect to changes in the physical properties of middle items.

El uso de cefadroxilo en sinusitis infantil / Cefadroxil use un children sinusitis

Se revisan 47 casos de sinusitis en niños, confirmados radiológicamente, en los cuales se utilizó cefadroxilo como terapia antimicrobiana por un lapso de 2 a 4 semanas, dependiendo de la evolución clínica y radiológica del proceso infeccioso. Se consideró curada la sinusitis cuando los controles radiológicos así lo confirmaban y no cuando los sintomas desaparecian

Niños con sinusitis bacteriología / Children with sinusitis bacteriology

El presente trabajo está basado en el estudio bacteriológico, realizado en el laboratorio de microbiología del Centro Médico de Caracas de las muestras tomadas a través de punción maxilar por fosa canina en niños que no han respondido a la terapia antimicrobiana convencional y que ameritan un procedimiento quirúrgico como adenoidectomía, adenoidotonsilectomía y/o miringotomía bajo anestesia general por resistencia al tratamiento médico indicado o tienen una obstrucción respiratoria documentada radiológicamente. Mediante este procedimiento, no sólo se beneficia el niño de la identificación del germen patógeno, sino, que como se realiza conjuntamente un lavado de la cavidad sinusal, mejora de su problema infeccioso

Desaparición de la imagen radiográfica de un macroprolactinoma con bromocriptina / Radiographic image description, of a macroprolactinoma with bromocriptine

Se informa a una paciente con síndrome de amenorrea galactorrea ocasionado por un macroadenoma hipofisario secretor de prolactina (PRL), el cual fue tratado médicamente con 5 mg/día de bromocriptina, normalizándose las cifras de PRL a las seis semanas y reapareciendo la menstruación a las ocho semanas de tratamiento. Después de 20 meses de tratamiento, se realizó un segundo estudio tomográfico de la hipófisis el cual fue normal. Se revisan las controversias en el manejo de los macroprolactinomas y se propone el manejo médico con agonistas dopaminérgicos como el tratamiento electivo para estas pacientes

Timpanoplastia tipo I en niños / Tympanoplasty in children type I

Esta serie evalúa el resultado de la timpanoplastia tipo I en niños menores de 17 años. Sólo se incluyen pacientes con perforación de la membrana timpánica, excluyéndose portadores de colesteatoma o daño de la cadena osicular. Se evaluaron retrospectivamente las historias de 66 pacientes, analizando el impacto de variables como la edad y la asociación de enfermedades como hiperplasia adenoidea, rinitis alérgica y labiopaladar hendido en los resultados tanto anatómicos como funcionales. Encontramos un 88 por ciento de éxito de toma del injerto, con un 73 por ciento de cierre del GAP aire-hueso menor de 20 db. No apreciamos relación del éxito del injerto, con enfermedades como hiperplasia adenoidea o rinitis alérgica. Concluimos que la timpanoplasia tipo I en niños, tiene resultados similares a los encontrados en los adultos

Cura de atresia del conducto auditivo externo: experiencia en el Hospital San Juan de Dios / Cure of atresia of the external auditory canal: experience in the Hopital San Juan de Dios

Se presentan los resultados obtenidos en 16 intevenciones para corrección de atresia del conducto auditivo externo, realizadas por el autor en el Hospital San Juan de Dios entre los años 1989 a 1995. De los casos, 14 fueron correcciones primarias y de exploraciones en segundo tiempo. Se consideraron las variaciones edad quirúrgica, sexo, presencia de colesteatoma, audiometría tonal pre y post quirúrgicas, hallazgos operatorios y complicaciones. De los datos obtenidos se concluye que el procedimiento realizado, en manos entrenadas, es seguro y aporta resultados predecibles. La adecuada evaluación preoperatoria de los pacientes permite conocer el pronóstico de la intervención.