Plan de negocio para el diseño de una empresa de búsqueda y seguimiento del talento humano en Colombia AIMS Colombia

53 Páginas.Se propone suscribir un contrato de franquicia con la red AIMS INTERNATIONAL para establecer formalmente en Colombia una sucursal, inicialmente en Bogotá, dedicada a brindar los servicios de búsqueda, selección, reclutamiento, aprovisionamiento y seguimiento de talento humano. De esta manera, la empresa a crear se apoyaría en la experiencia y en el reconocimiento internacional de AIMS INTERNATIONAL, con el objetivo de aprovechar estos factores y pretender obtener éxito en Colombia

Early polytherapy for benzodiazepine-refractory status epilepticus.

The transition from single seizures to status epilepticus (SE) is associated with malaptive trafficking of synaptic gamma-aminobutyric acid (GABAA) and glutamate receptors. The receptor trafficking hypothesis proposes that these changes are key events in the development of pharmacoresistance to antiepileptic drugs (AEDs) during SE, and that blocking their expression will help control drug-refractory SE (RSE). We tested this hypothesis in a model of SE induced by very high-dose lithium and pilocarpine (RSE), and in a model of SE induced by sc soman. Both models are refractory to benzodiazepines when treated 40 min after seizure onset. Our treatments aimed to correct the loss of inhibition because of SE-associated internalization of synaptic GABAA receptors (GABAAR), using an allosteric GABAAR modulator, sometimes supplemented by an AED acting at a nonbenzodiazepine site. At the same time, we reduced excitation because of increased synaptic localization of NMDA and AMPA (?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and N-methyl-D-aspartate) receptors (NMDAR, AMPAR (?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, N-methyl-D-aspartate receptors)) with an NMDAR channel blocker, since AMPAR changes are NMDAR-dependent. Treatment of RSE with combinations of the GABAAR allosteric modulators midazolam or diazepam and the NMDAR antagonists dizocilpine or ketamine terminated RSE unresponsive to high-dose monotherapy. It also reduced RSE-associated neuronal injury, spatial memory deficits, and the occurrence of spontaneous recurrent seizures (SRS), tested several weeks after SE. Treatment of soman-induced SE also reduced seizures, behavioral deficits, and epileptogenesis. Addition of an AED further improved seizure outcome in both models. Three-dimensional isobolograms demonstrated positive cooperativity between midazolam, ketamine, and valproate, without any interaction between the toxicity of these drugs, so that the therapeutic index was increased by combination therapy. The midazolam-ketamine-valproate combination based on the receptor trafficking hypothesis was far more effective in stopping RSE than the midazolam-fosphenytoin-valproate combination inspired from clinical guidelines for the treatment of SE. Furthermore, sequential administration of midazolam, ketamine, and valproate was far less effective than simultaneous treatment with the same drugs at the same dose. These data suggest that treatment of RSE should be based at least in part on its pathophysiology. The search for a better treatment should focus on the cause of pharmacoresistance, which is loss of synaptic GABAAR and gain of synaptic glutamate receptors. Both need to be treated. Monotherapy addresses only half the problem. Improved pharmacokinetics will not help pharmacoresistance because of loss of receptors. Waiting for one drug to fail before giving the second drugs gives pharmacoresistance time to develop. Future clinical trials should consider treating both the failure of inhibition and the runaway excitation which characterize RSE, and should include an early polytherapy arm. This article is part of the Special Issue "Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures"

El efecto antisenescente del resveratrol reduce la tasa de ablandamiento poscosecha de chirimoya

El fruto de chirimoya (Annona cherimolaMill.) es muy susceptible al deterioroposcosechadebido a sunaturaleza climatérica. Con el fin de observar el efecto antisenescente del resveratrol (RVS), éste bioreguladorvegetal se aplicó en frutos de Fino de Jete y Bronceada a 1,6; 0,16; 0,016 y 0 mM a los 0, 8 y 15 días antesde la cosecha (DAC). A los 1, 7 y 15 días después de la cosecha (DDC) se analizaron variables bioquímicas ybiofísicas. Al termino de 15 días de almacenamiento a temperatura ambiente, en relación al control, 1,6 mMRVS, aplicado 15 DAC, disminuyó el ablandamiento del fruto 78% para chirimoya Fino de Jete y 54% paraBronceada. A los 15 DDC se realizó la evaluación sensorial a frutos tratados 8 y15 DAC, los resultadosmostraron que los frutos de mayor aceptación fueron los tratados con 1,6 mM RVS ya sea a los 8 y 15 DAC,al ser calificados como de mejor aspecto, aroma y sabor

Rational polytherapy in the treatment of cholinergic seizures.

The initiation and maintenance phases of cholinergic status epilepticus (SE) are associated with maladaptive trafficking of synaptic GABAA and glutamate receptors. The resulting pharmacoresistance reflects a decrease in synaptic GABAA receptors and increase in NMDA and AMPA receptors, which tilt the balance between inhibition and excitation in favor of the latter. If these changes are important to the pathophysiology of SE, both should be treated, and blocking their consequences should have therapeutic potential. We used a model of benzodiazepine-refractory SE (RSE) (Tetz et al., 2006) and a model of soman-induced SE to test this hypothesis. Treatment of RSE with combinations of the GABAAR agonists midazolam or diazepam and the NMDAR antagonists MK-801 or ketamine terminated RSE unresponsive to high-dose monotherapy with benzodiazepines, ketamine or other antiepileptic drugs (AEDs). It also reduced RSE-associated neuronal injury, spatial memory deficits and the occurrence of spontaneous recurrent seizures (SRS), tested several weeks after SE. Treatment of sc soman-induced SE similarly showed much greater reduction of EEG power by a combination of midazolam with ketamine, compared to midazolam monotherapy. When treating late (40 min after seizure onset), there may not be enough synaptic GABAAR left to be able to restore inhibition with maximal GABAAR stimulation, and further benefit is derived from the addition of an AED which increases inhibition or reduces excitation by a non-GABAergic mechanism. The midazolam-ketamine-valproate combination is effective in terminating RSE. 3-D isobolograms demonstrate positive cooperativity between midazolam, ketamine and valproate, without any interaction between the toxicity of these drugs, so that the therapeutic index is increased by combination therapy between GABAAR agonist, NMDAR antagonist and selective AEDs. We compared this drug combination based on the receptor trafficking hypothesis to treatments based on clinical practice. The midazolam-ketamine-valproate combination is far more effective in stopping RSE than the midazolam-fosphenytoin-valproate combination inspired from clinical guidelines. Furthermore, sequential administration of midazolam, ketamine and valproate is far less effective than simultaneous treatment with the same drugs at the same dose. These data suggest that we should re-evaluate our traditional treatment of RSE, and that treatment should be based on pathophysiology. The search for a better drug has to deal with the fact that most monotherapy leaves half the problem untreated. The search for a better benzodiazepine should acknowledge the main cause of pharmacoresistance, which is loss of synaptic GABAAR. Future clinical trials should consider treating both the failure of inhibition and the runaway excitation which characterize RSE, and should include an early polytherapy arm

Labeling dating abuse: Undetected abuse among Spanish adolescents and young adults

El Instituto de la Mujer en España matiza la existencia de mujeres adultas auto-percibidas como maltratadas y técnicamente maltratadas (la víctima soporta algún tipo de violencia sin atribuirle la etiqueta de maltrato). El objetivo del presente estudio ex post facto es verificar ambos tipos de maltrato y desarrollar alternativas de evaluación en parejas jóvenes. Para ello, se utilizó una combinación de 13 ítems conductuales y de una pregunta sobre percepción de maltrato (evaluaciones atómica y molecular, respectivamente). A través de las preguntas contenidas en el Cuestionario de Violencia de Novios (CUVINO), se realizaron dos estudios diferenciados con muestra de mujeres adolescentes y jóvenes escolarizadas. El primero de ellos (N = 709; M = 18,5 años) replicó la evaluación de maltrato técnico llevada a cabo por el Instituto de la Mujer, encontrando un 6,2% de maltrato percibido y un 71% de maltrato técnico. En un segundo estudio (N = 1.327; M = 18,5), se evaluó la concordancia entre percepciones generales (sentirse maltratada, sentir miedo y sentirse atrapada en la relación), encontrando un 5,8% de mujeres maltratadas, un 11,9% de atemorizadas y un 26,8% atrapadas en sus relaciones. Se discuten las implicaciones que las inconsistencias encontradas en ambos estudios pueden tener sobre los esfuerzos preventivos.The Instituto de la Mujer in Spain highlights the existence of adult women being abused both with and without self-labeling as victims (situations of perceived abuse and technically abuse, respectively). The aims of this ex post facto study are assessing the existence of both types of abuse, and developing an alternative evaluation instrument for young couples, mixing behavioral items and a question on abuse perception (atomic and molecular evaluations). Using questions included in the Cuestionario de Violencia de Novios (CUVINO) we carried out two studies with different samples of adolescent and young women in school. The first one (N = 709; M = 18.5 years) replied the study conducted by the Instituto de la Mujer, finding 6.2% of women self-labeled as abused and 71% being technically abused. The second study (N = 1,327; M = 18.5) evaluated the relationship among different general perceptions (feeling abused, afraid and trapped in dating relationships), finding 5.8% of self-labeled abused women, 11.9% of afraid women, and 26.8% of women trapped in their relationships. Implications that these inconsistencies may have on prevention efforts are discussed.Universidad de Ovied

Drug abuse and criminal family records in the criminal history of prisoners

La relación entre el comportamiento criminal y los factores de riesgo, como el registro delictivo familiar y el consumo de drogas, ha sido establecida. Con el objetivo de definir el papel de estos factores de riesgo en el inicio y la evolución de la conducta criminal, se diseñó un estudio de campo con presos. Se aplicó a los datos de 157 reclusos en Villabona (Asturias, España) un análisis de supervivencia relacionado con la edad en que se cometió el primer delito no sancionado y la edad en la que entró por primera vez en la cárcel. Los resultados del análisis muestran que los reincidentes con abuso de drogas se iniciaron en actos delictivos a una edad más temprana (13 años) que los delincuentes primarios (16 años); los reincidentes con antecedentes penales en la familia comenzaron su actividad criminal a una edad anterior (13 años) a los primarios (16 años); Los reincidentes de familias sin antecedentes penales se iniciaban en actos delictivos a los 14 años, mientras que los primarios a los 16; los reincidentes con dependencia a las drogas entran por primera vez en la cárcel antes (19 años) que los primarios. Los delincuentes primarios que no consumen drogas ingresan en la cárcel por primera vez a la edad de 24 años, mientras que los reincidentes a la edad de 19; la primera entrada en prisión de los reincidentes con antecedentes penales de la familia se produce antes (19 años), que en los delincuentes primarios (23 años), y los presos reincidentes sin antecedentes penales de la familia cruzan el umbral de la cárcel por primera vez a una edad más joven (21 años) que los internos primarios (26 años). Las implicaciones de estos resultados pueden orientar una intervención más eficaz contra la delincuencia.The relationship between criminal behavior and the risk factors, family criminal records and drug use, has been firmly established. With the aim of defining the role of these risk factors in the initiation and evolution of criminal behavior, a field study with prison inmates was designed. A survival analysis with the age at which the first unsanctioned crime was committed and the age at which entered by first instance into prison was applied to the data of 157 prison inmates in Villabona (Asturias, Spain). The results of a survival analysis showed that drug abuse re-offenders initiated in criminal acts at an earlier age (13 years) than the primary offenders (16 years); re-offenders from family criminal records began his/her criminal activity earlier (13 years) than primary ones (16 years); re-offenders with non-criminal family records, initiate in criminal acts at 14 years, whereas primary at 16; the recidivist drug abusers enter by first instance into prison earlier (19 years) than the primary ones; non-drug consuming primary offenders enter prison for the first time at the age of 24 whereas recidivists do so at the age of 19; the first entrance into prison of the recidivist with family criminal records occurs early (19 years), than for the primary offenders (23 years); and the recidivist prisoners of non-family criminal records cross the threshold of the prison by first time youngsters (21 years) than the primary inmates (26 years). The implications of these results may lead towards a more effective intervention against crime

New cinnamic – N-benzylpiperidine and cinnamic – N,N-dibenzyl(N-methyl)amine hybrids as Alzheimer-directed multitarget drugs with antioxidant, cholinergic, neuroprotective and neurogenic properties

Here we describe new families of multi-target directed ligands obtained by linking antioxidant cinnamic-related structures with N-benzylpiperidine (NBP) or N,N-dibenzyl(N-methyl)amine (DBMA) fragments. Resulting hybrids, in addition to their antioxidant and neuroprotective properties against mitochondrial oxidative stress, are active at relevant molecular targets in Alzheimer’s disease, such as cholinesterases (hAChE and hBuChE) and monoamine oxidases (hMAO-A and hMAO-B). Hybrids derived from umbellic – NBP (8), caffeic – NBP (9), and ferulic – DBMA (12) displayed balanced biological profiles, with IC50s in the low-micromolar and submicromolar range for hChEs and hMAOs, and an antioxidant potency comparable to vitamin E. Moreover, the caffeic – NBP hybrid 9 is able to improve the differentiation of adult SGZ-derived neural stem cells into a neuronal phenotype in vitro.Financial support from the Spanish Ministry of Economy and Competitiveness (MINECO, grants SAF2012-31035 and SAF2015-64948-C2-1-R to MIRF; grant SAF2014-52940-R to APC) partially financed by FEDER funds, and Consejo Superior de Investigaciones Científicas (CSIC, grant PIE-201580E109) is gratefully acknowledged. ME thanks COLCIENCIAS (Colombia) for a Ph.D. fellowship.Peer reviewe

Antigenicity and diagnostic potential of vaccine candidates in human Chagas disease

Chagas disease is the most common cause of congestive heart failure related deaths among young adults in the endemic areas of South and Central America and Mexico. Diagnosis and treatment of T. cruzi infection has remained difficult and challenging after 100 years of its identification. In >95% of human cases, T. cruzi infection remains undiagnosed until several years later when chronic evolution of progressive disease results in clinical symptoms associated with cardiac damage. Diagnosis generally depends on the measurement of T. cruzi'specific antibodies that can result in false positives. A conclusive diagnosis of T. cruzi infection thus often requires multiple serological tests, in combination with epidemiological data and clinical symptoms. In this study, we investigated the antibody response to TcG1, TcG2, and TcG4 in clinically characterized chagasic patients. These antigens were identified as vaccine candidates and shown to elicit protective immunity to T. cruzi and Chagas disease in experimental animals. Our data show the serology test developed using the TcGmix (multiplex ELISA) is a significantly better alternative to epimastigote extracts currently used in T. cruzi serodiagnosis or the trypomastigote lysate used in this study for comparison purposes.Fil: Gupta, Shivali. University Of Texas Medical Branch. Department Of Pathology; Estados UnidosFil: Wan, Xianxu. University Of Texas Medical Branch. Department Of Pathology; Estados UnidosFil: Zago, María Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Salta. Instituto de Patología Experimental; ArgentinaFil: Martinez Sellers, Valena C.. University Of Texas Medical Branch. Department of Pathology; Estados UnidosFil: Silva, Trevor S.. University Of Texas Medical Branch. Department of Pathology; Estados UnidosFil: Assiah, Dadjah. University Of Texas Medical Branch. Department of Pathology; Estados UnidosFil: Dhiman, Monisha. University Of Texas Medical Branch. Department of Pathology; Estados UnidosFil: Nuñez, Sonia. Provincia de Salta. Hospital Público de Gestion Descentralizada San Bernardo; ArgentinaFil: Petersen, John R.. University Of Texas Medical Branch. Department of Pathology; Estados UnidosFil: Vazquez Chagoyán, Juan C.. Universidad Autónoma de Estado de México ; MéxicoFil: Estrada Franco, Jose G.. Universidad Autónoma de Estado de México; MéxicoFil: Garg, Nisha Jain. University Of Texas Medical Branch. Department of Pathology; Estados Unido