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Hoy en día la mediación es considerada como un medio para alcanzar la solución de los problemas, siempre y cuando sean susceptibles de poder medirlos, por ello el presente artículo de investigación se centra en un análisis sobre la obligatoriedad de la mediación en los procesos judiciales en materia de familia, niñez y adolescencia, esto con la finalidad de no involucrar en el litigio al niño, niña y adolescente, y más aún cuando son procesos de tenencia, régimen de visitas; producto de una separación o divorcio en los cuales dicha crisis matrimonial o relación de pareja no terminó de la mejor manera; y, por otra parte, descongestionar las causas procesales en las Unidades Judiciales de Familia, Mujer, Niñez y Adolescencia, y de esta manera se cumpla con los principios procesales de celeridad y debida diligencia. De igual forma, se describirá que en el derecho comparado de Chile y Argentina, procede una demanda cuando se ha agotado dicho proceso en los centros de mediación autorizados. Para ello se recurre al método analítico, científico, hermenéutico y de derecho comparado.

Increased adenosine A2A receptor (A2AR) expression and activation underlies a higher incidence of spontaneous calcium release in atrial fibrillation (AF). Adenosine A3 receptors (A3R) could counteract excessive A2AR activation, but their functional role in the atrium remains elusive, and we therefore aimed to address the impact of A3Rs on intracellular calcium homeostasis. For this purpose, we analyzed right atrial samples or myocytes from 53 patients without AF, using quantitative PCR, patch-clamp technique, immunofluorescent labeling or confocal calcium imaging. A3R mRNA accounted for 9% and A2AR mRNA for 32%. At baseline, A3R inhibition increased the transient inward current (ITI) frequency from 0.28 to 0.81 events/min (p < 0.05). Simultaneous stimulation of A2ARs and A3Rs increased the calcium spark frequency seven-fold (p < 0.001) and the ITI frequency from 0.14 to 0.64 events/min (p < 0.05). Subsequent A3R inhibition caused a strong additional increase in the ITI frequency (to 2.04 events/min; p < 0.01) and increased phosphorylation at s2808 1.7-fold (p < 0.001). These pharmacological treatments had no significant effects on L-type calcium current density or sarcoplasmic reticulum calcium load. In conclusion, A3Rs are expressed and blunt spontaneous calcium release at baseline and upon A2AR-stimulation in human atrial myocytes, pointing to A3R activation as a means to attenuate physiological and pathological elevations of spontaneous calcium release events.

The classical terms agonists and antagonists for G protein coupled receptors (GPCRs) have often become misleading. Even the biased agonism concept does not describe all the possibilities already demonstrated for GPCRs. The cannabinoid CB receptor (CBR) emerged as a promising target for a variety of diseases. Reasons for such huge potential are centered around the way drugs sit in the orthosteric and/or exosites of the receptor. On the one hand, a given drug in a specific CBR conformation leads to a signaling cascade that differs qualitatively and/or quantitatively from that triggered by another drug. On the other hand, a given drug may lead to different signaling outputs in two different tissues (or cell contexts) in which the conformation of the receptor is affected by allosteric effects derived from interactions with other proteins or with membrane lipids. This highlights the pharmacological complexity of this receptor and the need to further unravel the binding mode of CBR ligands in order to fine-tune signaling effects and therapeutic propositions.

Evidence-Based Practice (EBP) is a cost-effective approach for improving the quality of clinical care and implementing only well-tested evidence. Health professions, especially physiotherapy, must embrace EBP principles. This paper presents normative data from the Spanish physiotherapist population using the Health-Sciences Evidence-Based Practice questionnaire and explores EBP clusters/profiles of professionals in practice. An intentional sample of 419 practicing physiotherapists was recruited from the Spanish Professional Council of Physiotherapy. Participants completed a cross-sectional online survey with 60 Likert items (scale 1–10) measuring 5 dimensions: 1) Beliefs and attitudes, 2) Results from literature, 3) Professional practice, 4) Assessment of results, and 5) Barriers and Facilitators. The protocol also included sociodemographic, training, and practice-related contrast variables. Normative data were estimated and tabulated for each dimension and then a K-means clustering procedure was implemented using the contrast variables. Results for normative data showed, in descending order, the following 50th percentile values for the five EBP factors: Beliefs and attitudes (8.25), Professional practice (8.00), Assessment of results (7.42), Results from literature (6.71), and EBP Barriers and Facilitators (5.17); all expressed on a scale of 1 to 10. Academic degree, EBP training level, and work time shared in healthcare activity, research, or teaching activity were all statistically significant for discriminating EBP dimension scores. Finally, six different clusters showed that when EBP level is low, the scores in all dimensions are equally low, and vice-versa. The EBP dimensions "Beliefs and attitudes", "Professional practice", and "Evaluation of results" obtained better normative scores overall than "Search for bibliographic evidence and its inclusion in practice" and especially "Perception of EBP barriers", which had the worst score. Normative data are useful f

Using a previously unexplored, efficient, and versatile multicomponent method, we herein report the rapid generation of novel potent and subtype-selective DRD2 biased partial agonists. This strategy exemplifies the search for diverse and previously unexplored moieties for the secondary/allosteric pharmacophore of the common phenyl-piperazine scaffold. The pharmacological characterization of the new compound series led to the identification of several ligands with excellent DRD2 affinity and subtype selectivity and remarkable functional selectivity for either the cAMP (22a and 24d) or the beta-arrestin (27a and 29c) signaling pathways. These results were further interpreted on the basis of molecular models of these ligands in complex with the recent DRD2 crystal structures, highlighting the critical role of the secondary/allosteric pharmacophore in modulating the functional selectivity profile.

Altres ajuts: This work was partially supported by the AARFD-17-503612 grant from the US Alzheimer's Association., (1) Background. N-methyl d-aspartate (NMDA) ionotropic glutamate receptor (NMDAR), which is one of the main targets to combat Alzheimer's disease (AD), is expressed in both neurons and glial cells. The aim of this paper was to assess whether the adenosine A2A receptor (A2AR), which is a target in neurodegeneration, may affect NMDAR functionality. (2) Methods. Immuno-histo/cytochemical, biophysical, biochemical and signaling assays were performed in a heterologous cell expression system and in primary cultures of neurons and microglia (resting and activated) from control and the APPSw,Ind transgenic mice. (3) Results. On the one hand, NMDA and A2A receptors were able to physically interact forming complexes, mainly in microglia. Furthermore, the amount of complexes was markedly enhanced in activated microglia. On the other hand, the interaction resulted in a novel functional entity that displayed a cross-antagonism, that could be useful to prevent the exacerbation of NMDAR function by using A2AR antagonists. Interestingly, the amount of complexes was markedly higher in the hippocampal cells from the APPSw,Ind than from the control mice. In neurons, the number of complexes was lesser, probably due to NMDAR not interacting with the A2AR. However, the activation of the A2AR receptors resulted in higher NMDAR functionality in neurons, probably by indirect mechanisms. (4) Conclusions. A2AR antagonists such as istradefylline, which is already approved for Parkinson's disease (Nouriast® in Japan and Nourianz® in the US), have potential to afford neuroprotection in AD in a synergistic-like fashion. i.e., via both neurons and microglia.

Angiotensin-converting enzyme 2 (ACE2) is a membrane peptidase and a component of the renin-angiotensin system (RAS) that has been found in cells of all organs, including the lungs. While ACE2 has been identified as the receptor for severe acute respiratory syndrome (SARS) coronaviruses, the mechanism underlying cell entry remains unknown. Human immunodeficiency virus infects target cells via CXC chemokine receptor 4 (CXCR4)-mediated endocytosis. Furthermore, CXCR4 interacts with dipeptidyl peptidase-4 (CD26/DPPIV), an enzyme that cleaves CXCL12/SDF-1, which is the chemokine that activates this receptor. By analogy, we hypothesized that ACE2 might also be capable of interactions with RAS-associated G-protein coupled receptors. Using resonance energy transfer and cAMP and mitogen-activated protein kinase signaling assays, we found that human ACE2 interacts with RAS-related receptors, namely the angiotensin II type 1 receptor (AT1R), the angiotensin II type 2 receptor (AT2R), and the MAS1 oncogene receptor (MasR). Although these interactions led to various alterations of signal transduction, but, more importantly, ligand binding to AT1R resulted in the downregulation of ACE2 cell surface expression, while ligand binding to AT2R, but not to MasR, resulted in upregulation of ACE2 cell surface expression. Proximity ligation assays performed in situ revealed macromolecular complexes containing ACE2 and AT1R, AT2R or MasR in adult but not fetal mouse lung tissue. These findings highlight the relevance of RAS in SARS-CoV-2 infection and the role of ACE2-containing complexes as potential therapeutic targets

This study was conducted in the district of Curuguaty-Paraguay in the period 2017/18 to evaluate the effects of different population densities on sesame cultivation’s agronomic characteristics using the Escoba Blanca variety (Sesamum indicum L.). The experimental design used was randomized complete blocks with 6 treatments; 60, 80, 100, 120, 140 and 160 plants per m2 with 4 repetitions. The average height of plants was 263.80 cm without significant statistical differences between treatments. With 100 plants per m2, 458 capsules were obtained, and it was different from the treatment with 140 plants per m2. The highest number of branches and best productivity was observed with 100 plants per m2. With 140 plants per m2 it was observed that the weight of a thousand grains reached 3,06 g and was different from the treatment with 160 plants per m, Con el objetivo de evaluar los efectos de diferentes densidades poblacionales sobre las características agronómicas del cultivo de sésamo (Sesamum indicum L.), se realizó este estudio en el distrito de Curuguaty-Paraguay en el periodo 2017/18, utilizando la variedad Escoba blanca. El diseño experimental usado fue el de bloques completos al azar con 6 tratamientos: 60, 80, 100, 120, 140 y 160 plantas por m2 con 4 repeticiones. La altura media de plantas fue de 263,80 cm sin diferencias estadísticas significativas entre tratamientos. Con 100 plantas por m2 se obtuvieron 458 cápsulas y fue diferente al tratamiento con 140 plantas por m2. El mayor número de ramos y mejor rendimiento se logró con 100 plantas por m2. Con 140 plantas por m2 se observó que el peso de mil granos llegó a 3,06 g y fue diferente al tratamiento con 160 plantas por m2

The combination of aging populations with the obesity pandemic results in an alarming rise in non-communicable diseases. Here, we show that the enigmatic adenosine A2B receptor (A2B) is abundantly expressed in skeletal muscle (SKM) as well as brown adipose tissue (BAT) and might be targeted to counteract age-related muscle atrophy (sarcopenia) as well as obesity. Mice with SKM-specific deletion of A2B exhibited sarcopenia, diminished muscle strength, and reduced energy expenditure (EE), whereas pharmacological A2B activation counteracted these processes. Adipose tissue-specific ablation of A2B exacerbated age-related processes and reduced BAT EE, whereas A2B stimulation ameliorated obesity. In humans, A2B expression correlated with EE in SKM, BAT activity, and abundance of thermogenic adipocytes in white fat. Moreover, A2B agonist treatment increased EE from human adipocytes, myocytes, and muscle explants. Mechanistically, A2B forms heterodimers required for adenosine signaling. Overall, adenosine/A2B signaling links muscle and BAT and has both anti-aging and anti-obesity potential.

Single chemical entities with potential to simultaneously interact with two binding sites are emerging strategies in medicinal chemistry. We have designed, synthesized and functionally characterized the first bitopic ligands for the CB2 receptor. These compounds selectively target CB2 versus CB1 receptors. Their binding mode was studied by molecular dynamic simulations and site¿directed mutagenesis.

Hypothalamic neurons show sex differences in neuritogenesis, female neurons have longer axons and higher levels of the neuritogenic factor neurogenin 3 (Ngn3) than male neurons in vitro. Moreover, the effect of 17-ß-estradiol (E2) on axonal growth and Ngn3 expression is only found in male-derived neurons. To investigate whether sex chromosomes regulate these early sex differences in neuritogenesis by regulating the E2 effect on Ngn3, we evaluated the growth and differentiation of hypothalamic neurons derived from the "four core genotypes" mouse model, in which the factors of "gonadal sex" and "sex chromosome complement" are dissociated. We showed that sex differences in neurite outgrowth are determined by sex chromosome complement (XX > XY). Moreover, E2 increased the mRNA expression of Ngn3 and axonal length only in XY neurons. ER¿/ß expressions are regulated by sex chromosome complement; however, E2-effect on Ngn3 expression in XY neurons was only fully reproduced by PPT, a specific ligand of ER¿, and prevented by MPP, a specific antagonist of ER¿. Together our data indicate that sex chromosomes regulate early development of hypothalamic neurons by orchestrating not only sex differences in neuritogenesis, but also regulating the effect of E2 on Ngn3 expression through activation of ER¿ in hypothalamic neurons.

Despite ancient knowledge on cocaine appetite-suppressant action, the molecular basis of such fact remains unknown. Addiction/eating disorders (e.g., binge eating, anorexia, bulimia) share a central control involving reward circuits. However, we here show that the sigma-1 receptor (σ R) mediates cocaine anorectic effects by interacting in neurons with growth/hormone/secretagogue (ghrelin) receptors. Cocaine increases colocalization of σ R and GHS-R1a at the cell surface. Moreover, in transfected HEK-293T and neuroblastoma SH-SY5Y cells, and in primary neuronal cultures, pretreatment with cocaine or a σ R agonist inhibited ghrelin-mediated signaling, in a similar manner as the GHS-R1a antagonist YIL-781. Results were similar in G protein-dependent (cAMP accumulation and calcium release) and in partly dependent or independent (ERK1/2 phosphorylation and label-free) assays. We provide solid evidence for direct interaction between receptors and the functional consequences, as well as a reliable structural model of the macromolecular σ R-GHS-R1a complex, which arises as a key piece in the puzzle of the events linking cocaine consumption and appetitive/consummatory behaviors.

The aim of this work is the development of an animation of a hexapod robot in virtual reality environments through the use of Unity software. The movement of the robot is 18 degrees of freedom, which are based on servo motors that are controlled by the use of a microcontroller; It also shows the processes necessary to transfer the 3D design of the hexapod robot made in the use of CAD (Computer Aided Design) software to a virtual reality environment without losing the physical characteristics of the original design. Finally, the results obtained from the simulation of movement and responses of the hexapod robot to disturbances such as roughness of the floor, uneven ground and gravity among others are presented; allowing a correct evaluation to possible designs of robots before being elaborated., El presente artículo muestra el desarrollo y ejecución de una animación de un robot hexápodo en entornos de realidad virtual mediante el uso del software Unity. El movimiento del robot es de 18 grados de libertad, los cuales están basados en servo motores que se controlan por medio del uso de un micro controlador; además se muestran los procesos necesarios para transferir el diseño 3D del robot hexápodo realizado a partir de un software CAD (Diseño asistido por computador) a un entorno de realidad virtual sin que las características físicas del diseño original se pierdan. Finalmente, se presentan los resultados obtenidos de la simulación de movimiento y respuestas del robot hexápodo a perturbaciones como rugosidad del piso, suelo irregular, gravedad entre otras; permitiendo una correcta evaluación a posibles diseños de robots antes de ser elaborados.

Background: Appropriate use of antimicrobials is essential to improve outcomes in sepsis. The aim of this study was to determine whether the use of a rapid molecular blood test - SeptiFast (SF) reduces the antibiotic consumption through early de-escalation in patients with nosocomial sepsis compared with conventional blood cultures (BCs). Methods: This was a prospective, randomized, superiority, controlled trial conducted at Sao Paulo Heart Institute in the period October 2012-May 2016. Adult patients admitted to the hospital for at least 48 h with a diagnosis of nosocomial sepsis underwent microorganism identification by both SF test and BCs. Patients randomized into the intervention group received antibiotic therapy adjustment according to the results of SF. Patients randomized into the control group received standard antibiotic adjustment according to the results of BCs. The primary endpoint was antimicrobial consumption during the first 14 days after randomization. Results: A total of 200 patients were included (100 in each group). The intention to treat analysis found no significant differences in median antibiotic consumption. In the subgroup of patients with positive SF and blood cultures (19 and 25 respectively), we found a statistically significant reduction in the median antimicrobial consumption which was 1429 (1071-2000) days of therapy (DOT)/1000 patients-day in the intervention group and 1889 (1357-2563) DOT/1000 patients-day in the control group (p = 0.017), in the median time of antimicrobial de-escalation (8 versus 54 h - p < 0.001), in the duration of antimicrobial therapy (p = 0.039) and in anti-gram-positive antimicrobial costs (p = 0.002). Microorganism identification was possible in 24.5% of patients (45/184) by SF and 21.2% (39/184) by BC (p = 0.45). Conclusion: This randomized clinical trial showed that the use of a rapid molecular-based pathogen identification test does not reduce the median antibiotic consumption in nosocomial sepsis. Howev, SCOPUS: ar.j, info:eu-repo/semantics/published

La compra de tiquetes aéreos por internet es la operación de adquisición virtual más frecuente de los colombianos -- Sin embargo, estos consumidores poseen mayor vulnerabilidad derivada de la falta de información y la dificultad misma de tratar con la multiplicidad de tarifas para un mismo trayecto -- El derecho de retracto es la facultad que le permite a estos compradores a distancia evitar perder los recursos invertidos en un vuelo que, independientemente de su causa, no desean realizar -- Se abordará la figura partiendo de los principios de protección del pasajero aéreo, sus diferencias con los mandatos de salvaguarda al consumidor establecidos en el Estatuto del Consumidor, las reglas sobre derechos de los pasajeros y el análisis específico del derecho de retracto consagrado en nuestra normativa, así como los debates académicos con relación a su concepto y similitud con otras figuras del derecho privado -- Posteriormente evaluaremos la eficacia normativa de esta facultad del consumidor aéreo en nuestro contexto, The purchase of airline tickets online is the most frequent virtual acquisition operation for Colombians -- However, these consumers have greater vulnerability derived from the lack of information and the difficulty of dealing with the multiplicity of rates for the same journey -- The right of withdrawal is the faculty that allows these remote buyers to avoid losing the resources invested in a flight that, regardless of their cause, they do not wish to make -- The figure will be addressed starting from the principles of protection of the air passenger, its differences with the consumer safeguard mandates established in the "Consumer Statute", the rules on passenger rights and the specific analysis of the right of withdrawal enshrined in our regulations, as well as the academic debates regarding its concept and similarity with other figures of private law -- Later we will evaluate the normative effectiveness of this faculty of the air consumer in our context

Este proyecto de grado tiene como objetivo general, compilar en un documento base, toda la normatividad colombiana existente en torno a la regulación de la pesca ilegal en el país, a fin de generar una fuente de información que destaque los pormenores legislativos que rigen actualmente el contexto pesquero en el país -- Para dar conformidad a este objetivo, se desarrolló un estudio con un enfoque de tipo cualitativo, ya que la investigación está dirigida a interpretar las normas de regulación de la pesca ilegal en Colombia; además el diseño de la investigación es de diagnóstico, pues se pretende presentar las conclusiones que describan la realidad actual de dichas normas y finalmente, el tipo de estudio desarrollado es exploratorio - descriptivo, ya que tiene como objetivo central, lograr la descripción o caracterización de las normas mencionadas -- Con esta base metodológica, el estudio se sustenta en la importancia de acceder a un documento que compile las normas más importantes en la protección del medio ambiente y en lo relacionado a la pesca ilegal, por ello la investigación dio respuesta a un problema inicial que consistió en determinar cuáles son las normas que regulan esta práctica en Colombia y así mismo, cuáles son sus características esenciales que las hacen efectivas, eficaces y eficientes en el contexto nacional actual, This project aims at general level, compiled into a document database, about Colombian law regarding the regulation of illegal fishing in the country, in order to generate a source of information that highlights the details of legislation currently governing fishing in the country context -- To accordance with this objective, we developed a study with a qualitative approach, since the investigation is directed to interpret the rules regulating illegal in Colombia, besides the design of diagnostic research is therefore intended present the findings to describe the current reality of such rules and finally, the type of study conducted is exploratory - descriptive, as its central objective, to achieve the description or characterization of these standards -- With this basic methodology, the study is based on the importance of access to a document compiled the most important standards in the protection of the environment and in relation to illegal fishing, so the research responded to an initial problem was to determine what are the rules governing the practice in Colombia and also, what are the essential characteristics that make them effective and effective in the current national context

Recent studies point to the cannabinoid CB2 receptors (CB2r) and the non-cannabinoid receptor GPR55 as potential key targets involved in the response to stress, anxiety, and depression. Considering the close relationship between neuropsychiatric disorders and suicide, the purpose of this study was to evaluate the potential alterations of CB2r and GPR55 in suicide victims. We analyzed gene and protein expression of both receptors by real-time PCR and western blot, respectively, in the dorsolateral prefrontal cortex (DLPFC) of 18 suicide victims with no clinical psychiatric history or treatment with anxiolytics or antidepressants, and 15 corresponding controls. We used in situ proximity ligation assay to evaluate whether the receptors formed heteromeric complexes and to determine the expression level of these heteromers, also assessing the co-expression of heteromers in neurons, astroglia, or microglia cells. CB2r and GPR55 gene expressions were significantly lower (by 33 and 41%, respectively) in the DLPFC of suicide cases. CB2r protein expression was higher, as were CB2-GPR55 heteroreceptor complexes. The results also revealed the presence of CB2-GPR55 receptor heteromers in both neurons and astrocytes, whereas microglial cells showed no expression. We did not observe any significant alterations of GPR55 protein expression. Additional studies will be necessary to evaluate if these alterations are reproducible in suicide victims diagnosed with different psychiatric disorders. Taken together, the results suggest that CB2r and GPR55 may play a relevant role in the neurobiology of suicide.

The search for synthetic selective compounds for G-protein-coupled receptors has provided a myriad of molecules with high selectivity and therapeutic potential. In some cases, however, selectivity is difficult to obtain. For instance, the selectivity ratio is relatively low for compounds acting on D and D dopamine receptors, which are targets of neurodegenerative diseases such as Parkinson's and Huntington's. From a therapeutic point of view, it is of interest the relative recent discovery of biased agonism, which is characterized by different signaling pathways engaged by different compounds acting on a given receptor. The aim of this paper was to investigate whether new piribedil-derived compounds could display higher selectivity for D or D receptor and/or provide biased signaling. The results show that selectivity was not different, but that one of the molecules described here, 5-((4-(pyrimidin-2-yl)piperazin-1-yl)methyl)quinolin-8-ol (10), does engage Gi-mediated signaling via D or D receptors, whereas it does not activate the mitogen-activated-protein kinase pathway, which is usually activated by dopamine receptor agonists.

OBJECTIVES: The aim of this study was to evaluate the efficacy of perioperative intra-aortic balloon pump use in high-risk cardiac surgery patients. DESIGN: A single-center randomized controlled trial and a meta-analysis of randomized controlled trials. SETTING: Heart Institute of São Paulo University. PATIENTS: High-risk patients undergoing elective coronary artery bypass surgery. INTERVENTION: Patients were randomized to receive preskin incision intra-aortic balloon pump insertion after anesthesia induction versus no intra-aortic balloon pump use. MEASUREMENTS AND MAIN RESULTS: The primary outcome was a composite endpoint of 30-day mortality and major morbidity (cardiogenic shock, stroke, acute renal failure, mediastinitis, prolonged mechanical ventilation, and a need for reoperation). A total of 181 patients (mean [SD] age 65.4 [9.4] yr; 32% female) were randomized. The primary outcome was observed in 43 patients (47.8%) in the intra-aortic balloon pump group and 42 patients (46.2%) in the control group (p = 0.46). The median duration of inotrope use (51 hr [interquartile range, 32-94 hr] vs 39 hr [interquartile range, 25-66 hr]; p = 0.007) and the ICU length of stay (5 d [interquartile range, 3-8 d] vs 4 d [interquartile range, 3-6 d]; p = 0.035) were longer in the intra-aortic balloon pump group than in the control group. A meta-analysis of 11 randomized controlled trials confirmed a lack of survival improvement in high-risk cardiac surgery patients with perioperative intra-aortic balloon pump use. CONCLUSIONS: In high-risk patients undergoing cardiac surgery, the perioperative use of an intra-aortic balloon pump did not reduce the occurrence of a composite outcome of 30-day mortality and major complications compared with usual care alone., SCOPUS: ar.j, info:eu-repo/semantics/published

En su ensayo “La herida de Babel”, Carlos Fuentes reconoce la enorme influencia que tuvo Jorge Luis Borges para la definición de su vocación literaria. Al referirse a la vertiente fantástica que ambos ejercitaron, él marca algunas diferencias: En Argentina, [país] circundado por la llanura chata e interminable, el escritor sólo puede evocar el solitario árbol del ombú. Borges inventa por ello un espacio, el Aleph, donde pueden verse, sin confundirse, “todos los lugares del orbe, vistos desde todos los ángulos”. Yo puedo hacer lo mismo en la capilla indobarroca de Tonantzintla, sin necesidad de escribir una línea. Borges debe inventar el jardín de senderos que se bifurcan, donde el tiempo es una serie infinita de tiempos. Yo puedo mirar eternamente el calendario azteca en el Museo de Antropología de la Ciudad de México hasta convertirme en tiempo–pero no en literatura. Según esta perspectiva, el “irreal” mundo de ficción construido por Borges en su literatura fantástica sería una necesidad inevitable ante la falta de acumulación histórico-cultural del Río de la Plata, que no puede ofrecer al creador los abigarrados referentes que, en cambio, sí están disponibles para Fuentes en México. El objetivo de este trabajo sería discutir, a partir de esta idea central de Carlos Fuentes, algunas probables diferencias entre las representaciones fantásticas de México y Argentina. De este modo, se revisará si en verdad hay contrastes notables en este sentido. Para ello, se efectuará una comparación general entre la literatura fantástica de Borges y la de Fuentes, sobre todo centrada en Ficciones y El Aleph, en el primer caso, y en Los días enmascarados y Aura,en el segundo

Background: Vasoplegic syndrome is a common complication after cardiac surgery and impacts negatively on patient outcomes. The objective of this study was to evaluate whether vasopressin is superior to norepinephrine in reducing postoperative complications in patients with vasoplegic syndrome. Methods: This prospective, randomized, double-blind trial was conducted at the Heart Institute, University of Sao Paulo, Sao Paulo, Brazil, between January 2012 and March 2014. Patients with vasoplegic shock (defined as mean arterial pressure less than 65 mmHg resistant to fluid challenge and cardiac index greater than 2.2 l · min -2 · m -2) after cardiac surgery were randomized to receive vasopressin (0.01 to 0.06 U/min) or norepinephrine (10 to 60 μg/min) to maintain arterial pressure. The primary endpoint was a composite of mortality or severe complications (stroke, requirement for mechanical ventilation for longer than 48 h, deep sternal wound infection, reoperation, or acute renal failure) within 30 days. Results: A total of 330 patients were randomized, and 300 were infused with one of the study drugs (vasopressin, 149; norepinephrine, 151). The primary outcome occurred in 32% of the vasopressin patients and in 49% of the norepinephrine patients (unadjusted hazard ratio, 0.55; 95% CI, 0.38 to 0.80; P = 0.0014). Regarding adverse events, the authors found a lower occurrence of atrial fibrillation in the vasopressin group (63.8% vs. 82.1%; P = 0.0004) and no difference between groups in the rates of digital ischemia, mesenteric ischemia, hyponatremia, and myocardial infarction. Conclusions: The authors' results suggest that vasopressin can be used as a first-line vasopressor agent in postcardiac surgery vasoplegic shock and improves clinical outcomes., SCOPUS: ar.j, info:eu-repo/semantics/published

En este nuevo número del EAFIT Journal of Interanational Law podrán encontrar análisis que dan cuenta de la constante construcción del sistema internacional y sus efectos en Colombia y otros países de la región.

The Reformation and Counter-Reformation transformed Christianity during modernity. In that transformation, the notion of purgatory remained a fundamental part of catholic eschatology. It was transmitted to the Spanish colonies through the process of evangelization and maintained with the establishment of the authority of the Catholic Church. In Colombia, the appropriation of purgatory followed the generalities of the Roman Catholic tradition. Like other eschatological notions of punishment; such appropriation was related with educational processes and political debates, until the trends of secularization limit its usefulness in the public sphere. Based on an analytic-descriptive methodology, and the use of primary and secondary sources, the present article aims to present the dogmatic generalities of purgatory, as well as the features of its appropriation and use in Colombia at the end of the nineteenth century and the first decades of the twentieth century., La Reforma y la Contrarreforma transformaron el cristianismo en la modernidad. En esa transformación, la noción del purgatorio permaneció como parte fundamental de la escatología católica; transmitida a las colonias españolas a través del proceso de evangelización y mantenida con el asentamiento de la autoridad de la Iglesia. En Colombia, la apropiación del purgatorio siguió las líneas generales de la tradición católica. Sin embargo, al igual que otras nociones escatológicas de castigo, fue útil en los procesos educativos y en debates políticos, hasta que las tendencias de secularización limitaron su utilización en la esfera pública. Con base en una metodología analítico-descriptiva y en la utilización de fuentes primarias y segundarias, el presente artículo tiene por objeto presentar las generalidades dogmáticas del purgatorio, así como las características de su apropiación y utilización en Colombia a finales del siglo XIX y en las primeras décadas del siglo XX.

En este último semestre la comunidad internacional ha afrontado, como siempre, nuevos retos. En temas de seguridad el denominado grupo “Estado Islámico” ha realizado ataques terroristas en Asia, África, Europa y Norte América, poniendo de manifiesto la dificultad de nuestros días en el control del sinnúmero de actividades derivadas de la interacción social. En Europa la decisión británica de retirarse de la Unión Europea se convierte en una nueva dificultad para las dinámicas de integración en el continente. Esta decisión ha afectado de diversas maneras el comercio, los mercados bursátiles y las relaciones internacionales del Reino Unido con países dentro y fuera de la Unión Europea. En materia nacional la firma del acuerdo de paz entre el gobierno colombiano y la guerrilla de las FARC, es sin duda uno de los asuntos trascendentales, tanto a nivel doméstico como internacional. Sin duda los retos continuarán.

In this paper, I focus on the journal that Uruguayan writer Horacio Quiroga (1878-1937) wrote to record his visit to Paris, from March to July, in the year 1900. It remained as a manuscript until Emir Rodríguez Monegal transcribed it and published it in 1950 as Diario de un viaje a París (Journal of a Visit to Paris). This is the title under which we know this work today. There are several reasons why this text constitutes an outstanding autobiographical record. First of all, it stands out as a striking vision of Paris by a Latin American author. Paris was considered then the world capital of culture and civilization; nevertheless, the image of Paris provided by Quiroga is very different from the ideal city depicted by such authors as Manuel Gutiérrez Nájera and Rubén Darío. In the second place, the journal is also the record of a formative period in Quiroga’s intellectual development. Some critics contend that the trip to Paris determined Quiroga’s decision to become a writer, but in the present paper, upon the careful analysis of the entries in the journal, I argue that this journey only marks the beginning of an incipient literary call. Finally, the journal is also an extraordinary record of the everyday experiences of a Latin American traveler in Paris, at the turn of the twentieth century.

The renin–angiotensin system (RAS) was initially considered as a circulating humoral system controlling blood pressure, being kidney the key control organ. In addition to the ‘classical’ humoral RAS, a second level in RAS, local or tissular RAS, has been identified in a variety of tissues, in which local RAS play a key role in degenerative and aging-related diseases. The local brain RAS plays a major role in brain function and neurodegeneration. It is normally assumed that the effects are mediated by the cell-surface-specific G-protein-coupled angiotensin type 1 and 2 receptors (AT1 and AT2). A combination of in vivo (rats, wild-type mice and knockout mice) and in vitro (primary mesencephalic cultures, dopaminergic neuron cell line cultures) experimental approaches (confocal microscopy, electron microscopy, laser capture microdissection, transfection of fluorescent-tagged receptors, treatments with fluorescent angiotensin, western blot, polymerase chain reaction, HPLC, mitochondrial respirometry and other functional assays) were used in the present study. We report the discovery of AT1 and AT2 receptors in brain mitochondria, particularly mitochondria of dopaminergic neurons. Activation of AT1 receptors in mitochondria regulates superoxide production, via Nox4, and increases respiration. Mitochondrial AT2 receptors are much more abundant and increase after treatment of cells with oxidative stress inducers, and produce, via nitric oxide, a decrease in mitochondrial respiration. Mitochondria from the nigral region of aged rats displayed altered expression of AT1 and AT2 receptors. AT2-mediated regulation of mitochondrial respiration represents an unrecognized primary line of defence against oxidative stress, which may be particularly important in neurons with increased levels of oxidative stress such as dopaminergic neurons. Altered expression of AT1 and AT2 receptors with aging may induce mitochondrial dysfunction, the main risk factor for neurodegeneration

A combination of molecular modeling and structure–activity relationship studies has been used to fine-tune CB2 selectivity in the chromenopyrazole ring, a versatile CB1/CB2 cannabinoid scaffold. Thus, a series of 36 new derivatives covering a wide range of structural diversity has been synthesized, and docking studies have been performed for some of them. Biological evaluation of the new compounds includes, among others, cannabinoid binding assays, functional studies, and surface plasmon resonance measurements. The most promising compound [43 (PM226)], a selective and potent CB2 agonist isoxazole derivative, was tested in the acute phase of Theiler’s murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD), a well-established animal model of primary progressive multiple sclerosis. Compound 43 dampened neuroinflammation by reducing microglial activation in the TMEV.

Endocannabinoids activate two types of specific G-protein-coupled receptors (GPCRs), namely cannabinoid CB1 and CB2. Contrary to the psychotropic actions of agonists of CB1 receptors, and serious side effects of the selective antagonists of this receptor, drugs acting on CB2 receptors appear as promising drugs to combat CNS diseases (Parkinson's disease, Huntington's chorea, cerebellar ataxia, amyotrohic lateral sclerosis). Differential localization of CB2 receptors in neural cell types and upregulation in neuroinflammation are keys to understand the therapeutic potential in inter alia diseases that imply progressive neurodegeneration. Medicinal chemistry approaches are now engaged to develop imaging tools to map receptors in the living human brain, to develop more efficacious agonists, and to investigate the possibility to develop allosteric modulators.

Video del congreso internacional figuraciones de lo insólito en las literaturas española e hispanoamericana

Video del congreso internacional figuraciones de lo insólito en las literaturas española e hispanoamericana

En su ensayo “La herida de Babel”, Carlos Fuentes reconoce la enorme influencia que tuvo Jorge Luis Borges para la definición de su vocación literaria. Al referirse a la vertiente fantástica que ambos ejercitaron, él marca algunas diferencias: En Argentina, [país] circundado por la llanura chata e interminable, el escritor sólo puede evocar el solitario árbol del ombú. Borges inventa por ello un espacio, el Aleph, donde pueden verse, sin confundirse, “todos los lugares del orbe, vistos desde todos los ángulos”. Yo puedo hacer lo mismo en la capilla indobarroca de Tonantzintla, sin necesidad de escribir una línea. Borges debe inventar el jardín de senderos que se bifurcan, donde el tiempo es una serie infinita de tiempos. Yo puedo mirar eternamente el calendario azteca en el Museo de Antropología de la Ciudad de México hasta convertirme en tiempo–pero no en literatura. Según esta perspectiva, el “irreal” mundo de ficción construido por Borges en su literatura fantástica sería una necesidad inevitable ante la falta de acumulación histórico-cultural del Río de la Plata, que no puede ofrecer al creador los abigarrados referentes que, en cambio, sí están disponibles para Fuentes en México. El objetivo de este trabajo sería discutir, a partir de esta idea central de Carlos Fuentes, algunas probables diferencias entre las representaciones fantásticas de México y Argentina. De este modo, se revisará si en verdad hay contrastes notables en este sentido. Para ello, se efectuará una comparación general entre la literatura fantástica de Borges y la de Fuentes, sobre todo centrada en Ficciones y El Aleph, en el primer caso, y en Los días enmascarados y Aura,en el segundo

Objective The aim of this study was to compare outcomes in patients undergoing cardiac surgery who are aged 60 years or more or less than 60 years after implementation of a restrictive or a liberal transfusion strategy. Methods This is a substudy of the Transfusion Requirements After Cardiac Surgery (TRACS) randomized controlled trial. In this subgroup analysis, we separated patients into those aged 60 years or more (elderly) and those aged less than 60 years randomized to a restrictive or a liberal strategy of red blood cell transfusion. The primary outcome was a composite defined as a combination of 30-day all-cause mortality and severe morbidity. Results Of the 502 patients included in the Transfusion Requirements After Cardiac Surgery study, 260 (51.8%) were aged 60 years or more and 242 (48.2%) were aged less than 60 years and were included in this study. The primary end point occurred in 11.9% of patients in the liberal strategy group and 16.8% of patients in the restrictive strategy group (P =.254) for those aged 60 years or more and in 6.8% of patients in the liberal strategy group and 5.6% of patients in the restrictive strategy group for those aged less than 60 years (P =.714). However, in the older patients, cardiogenic shock was more frequent in patients in the restrictive transfusion group (12.8% vs 5.2%, P =.031). Thirty-day mortality, acute respiratory distress syndrome, and acute renal injury were similar in the restrictive and liberal transfusion groups in both age groups. Conclusions Although there was no difference between groups regarding the primary outcome, a restrictive transfusion strategy may result in an increased rate of cardiogenic shock in elderly patients undergoing cardiac surgery compared with a more liberal strategy. Cardiovascular risk of anemia may be more harmful than the risk of blood transfusion in older patients., SCOPUS: ar.j, info:eu-repo/semantics/published

Background: 5'-deoxy-5'-methylthioadenosine (MTA) is an endogenous compound produced through the metabolism of polyamines. The therapeutic potential of MTA has been assayed mainly in liver diseases and, more recently, in animal models of multiple sclerosis. The aim of this study was to determine the neuroprotective effect of this molecule in vitro and to assess whether MTA can cross the blood brain barrier (BBB) in order to also analyze its potential neuroprotective efficacy in vivo. Methods: Neuroprotection was assessed in vitro using models of excitotoxicity in primary neurons, mixed astrocyte-neuron and primary oligodendrocyte cultures. The capacity of MTA to cross the BBB was measured in an artificial membrane assay and using an in vitro cell model. Finally, in vivo tests were performed in models of hypoxic brain damage, Parkinson's disease and epilepsy. Results: MTA displays a wide array of neuroprotective activities against different insults in vitro. While the data from the two complementary approaches adopted indicate that MTA is likely to cross the BBB, the in vivo data showed that MTA may provide therapeutic benefits in specific circumstances. Whereas MTA reduced the neuronal cell death in pilocarpine-induced status epilepticus and the size of the lesion in global but not focal ischemic brain damage, it was ineffective in preserving dopaminergic neurons of the substantia nigra in the 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP)-mice model. However, in this model of Parkinson's disease the combined administration of MTA and an A(2A) adenosine receptor antagonist did produce significant neuroprotection in this brain region. Conclusion: MTA may potentially offer therapeutic neuroprotection.

The objective of this study was to determine the monetary income per animal and the effects of herd composition, physical yields per animal and prices in the Gross Value of Production (GVP) of dairy subsector in the Laguna Region in 2012. We used descriptive methodology of economics, macroeconomic approaches and static-comparative, when contrasting 2012 against 2002. We analyzed the statistical data of milk production from cattle and goats for 2012 versus 2002. Los results indicate that monetary income per animal increased only in two species: dairy cattle (from $ 28, 499 to $ 46, 935 animal-1) and dairy goats (from $ 1, 272 to $ 1, 866 animal-1), which increased the VBP from dairy sector 24.1% going from $ 9, 653 to $ 11, 977 millions of pesos (constant of 2012). This increase particularly because the herd composition and physical performance were favorable to economic growth, because its value multiplied by 1.15 and 1.10 percentage points for the GVP really would have been obtained, while the real price of a liter of milk did decrease the VBP 2.0%, El objetivo del trabajo fue determinar cómo el ingreso monetario - animal y los efectos composición del hato, los rendimientos físicos - animal y los precios influyeron sobre el Valor Bruto de la Producción (VBP) del subsector lácteo en la Comarca Lagunera en 2012. Se utilizó Economía Descriptiva, con enfoques macroeconómico y estáticocomparativo, al contrastar 2012 contra 2002. Se analizaron los datos estadísticos de la producción de leche bovina y caprina, para los años 2012 versus 2002. Los resultados muestran que las Unidades Animal en la región aumentaron 10.6% en el periodo analizado, debido al incremento en el ingreso monetario por animal en ambas especies: bovino lechero (de $28, 499 a $46, 935 animal-1) y caprino lechero (de $1, 272 a $1, 866 animal-1), lo que elevó el VBP del subsector lácteo 24.1% al pasar de $9, 653 a $11, 977 millones de pesos (constantes de 2012). Este incremento se debe particularmente a que la composición del hato y los rendimientos físicos fueron favorables al crecimiento económico, pues multiplicaron su valor por 1.15 y por 1.10 puntos porcentuales el VBP que realmente se habría obtenido, mientras que los precios reales del litro de leche hicieron decrecer el VBP en 2.0%

The objective of this study was to determine the monetary income per animal and the effects of herd composition, physical yields per animal and prices in the Gross Value of Production (GVP) of cattle in the Laguna Region in 2011. Economics descriptive methodology, macroeconomic and static-comparative approaches were used contrasting 2011 against 1990. Statistical data of livestock production sub-sectors: meat, milk and eggs were analyzed for 2011 versus 1990. Results indicated that monetary income per animal increased only in three species: goat milk (from $ 768 to $ 2.070) and goat meat (from $ 319 to $ 750), and cow milk ($ 39.129 to $ 45.379), and it decreased in the remaining animal species (beef cattle, pork, sheep meat and broiler chicken), also that the VBP livestock grew 129.6%, from $ 10759.86 to $ 24705.5 million (constant June 2012), and herd composition and physical yields were positive for economic growth, because these increased by 3.69 and 1.01 times the GVP that it would have had with their effects, but real prices when falling precipitously decreased the GVP 38%, El objetivo del trabajo fue determinar como el ingreso monetario/ animal y los efectos composición del hato, los rendimientos físicos/animal y los precios influyeron sobre el Valor Bruto de la Producción (VBP) del sector pecuario en la Comarca Lagunera en 2011. Se utilizó la metodología de la Economía Descriptiva, con enfoques macroeconómico y estático-comparativo, al contrastar 2011 en contra de 1990. Se analizaron los datos estadísticos de la producción pecuaria de los subsectores: carne, leche y huevo para los años 2011 versus 1990. Los resultados obtenidos indican que el ingreso monetario por animal aumentó solo en tres especies: caprinos leche (de $768 a $2,070 animal-1) y caprinos carne (de $319 a $750 animal-1), y en bovinos leche (de $39,129 a $45,379 animal-1), disminuyendo en los bovinos carne, cerdos, ovinos carne y aves carne, asimismo, que el VBP ganadero creció 129.6%, al pasar de $10,759.86 a $24,705.5 millones de pesos (constantes de 2012), y que la composición del hato y los rendimientos físicos fueron favorables al crecimiento económico, pues multiplicaron por 3.69 y por 1.01 veces el VBP que se habría tenido con sus efectos, pero que los precios reales, al caer estrepitosamente, hicieron disminuir el VBP en un 38%

El Premi Nobel de Química 2012 va reconèixer el treball dels professors Robert J. Lefkowitz i Brian K. Kobilka sobre els receptors β-adrenèrgics, que han estat el paradigma per a la comprensió del mecanisme d’acció dels receptors acoblats a proteïnes G heterotrimèriques (GPCRs). De fet, el descobriment de centenars de membres d’aquesta família de receptors de la superfície cel·lular ha permès entendre detalladament com detecten les cèl·lules el seu entorn. Aquest breu article està basat en el resum utilitzat per la Reial Acadèmia Sueca de Ciències per donar suport a la concessió del premi de 2012, i considera també les diverses aplicacions dels GPCRs.Paraules clau: receptor acoblat a proteïnes G · receptors d’adenosina · receptors adrenèrgics · heteròmers de receptors, The 2012 Nobel Prize in Chemistry recognized Professors Robert J. Lefkowtiz and Brian K. Kobilka for their work on β-adrenergic receptors, which have been the paradigm for understanding the mechanism of action of receptors coupled to heterotrimeric G proteins (GPCRs). In fact, the discovery of hundreds of members of this family of cell-surface receptors has provided a detailed understanding of how cells sense their environment. This brief article draws from the summary used by the Royal Swedish Academy of Sciences to support its choice of Lefkowitz and Kobilka for the 2012 award. It also considers some of the diverse applications of GPCRs.Keywords: G-protein-coupled receptors · adenosine receptors · adrenergic receptors · receptor heteromers

La Universidad EAFIT (Medellín, Colombia) es una universidad abierta al mundo. El EAFIT Journal of International Law, celebra en este número su cercanía con la Universidad Autónoma de México y la Universidad de Querétaro (México). Entre el 18 y 19 de septiembre de 2013 se celebró en estas universidades el Seminario Permanente del Anuario Mexicano de Derecho Internacional, la presente edición ha decidido publicar una selección de los artículos más rigurosos de las ponencias realizadas en este evento. En ellos se presentan y analizan temas de derecho internacional de particular relevancia para América Latina.

De manera rápida y casi imperceptible, el Internet se ha convertido en una herramienta indispensable para la cotidianidad de un gran número ciudadanos en todos los rincones del planeta y continua creciendo. Para el primer trimestre de año 2012 la red contaba con 2.3 billones de usuarios a nivel mundial.1 Esto comienza a construir un complicado entorno, que según el reconocido periodista Misha Glenny “provee un nuevo contexto para el viejo dilema que enfrenta a las exigencias de seguridad contra el deseo de libertad., 172 p., Contenido parcial: Los derechos en el internet -- Análisis del derecho a la libertad de expresión y el derecho a la privacidad en el contexto del internet -- Fenómenos sociales y políticos recientes relevantes al disfrute de los derechos humanos en internet.