HFIP-Assisted C-H Functionalization by Cp*CoIII : Access to Key Reactive Cobaltacycles and Implication in Catalysis.

Described here is a synthetic approach to access two of the most widely invoked cationic cobaltacycles in Cp*CoIII -catalyzed C-H functionalization reactions by C-H activation. The unique stabilizing capability of MeCN was used to surmount the previously proposed reversible nature of the C-H metalation step. Moreover, it is revealed the boosting effect of 1,1,1,3,3,3-hexafluoroisopropanol in the metalation step and in the reaction between N-pyrimidinylindole and diphenylacetylene under catalytic conditions.

Nickel-Catalyzed Cyclopropanation with NMe4OTf and nBuLi.

Nickel was identified as a catalyst for the cyclopropanation of unactivated olefins by using in situ generated lithiomethyl trimethylammonium triflate as a methylene donor. A mechanistic hypothesis is proposed in which the generation of a reactive nickel carbene explains several interesting observations. Additionally, our findings shed light on a report by Franzen and Wittig published in 1960 that had been retracted later owing to irreproducibility, and provide a rational basis for the systematic development of the reaction for preparative purposes as an alternative to diazomethane or Simmons-Smith conditions.

Do rats (Rattus norvegicus) perceive octave equivalence, a critical human cross-cultural aspect of pitch perception?

Octave equivalence describes the perception that two notes separated by a doubling in frequency have a similar quality. In humans, octave equivalence is important to both music and language learning and is found cross-culturally. Cross-species studies comparing human and non-human animals can help illuminate the necessary pre-conditions to developing octave equivalence. Here, we tested whether rats (Rattus norvegicus) perceive octave equivalence using a standardized cross-species paradigm. This allowed us to disentangle concurring hypotheses regarding the evolutionary roots of this phenomenon. One hypothesis is that octave equivalence is directly connected to vocal learning, but this hypothesis is only partially supported by data. According to another hypothesis, the harmonic structure of mammalian vocalizations may be more important. If rats perceive octave equivalence, this would support the importance of vocal harmonic structure. If rats do not perceive octave equivalence, this would suggest that octave equivalence evolved independently in several mammalian clades due to a more complex interplay of different factors such as-but not exclusively-the ability to vocally learn. Evidence from our study suggests that rats do perceive octave equivalence, thereby suggesting that the harmonic vocal structure found in mammals may be a key pre-requisite for octave equivalence. Stage 1 approved protocol: the study reported here was originally accepted as a Registered Report and the study design was approved in Stage 1. We hereby confirm that the completed experiment(s) have been executed and analysed in the manner originally approved with any unforeseen changes in those approved methods and analyses clearly noted. The approved Stage 1 protocol can be found at: https://osf.io/gvf7c/?view_only=76dc1840f31c4f9ab59eb93cbadb98b7.

Abstract processing of syllabic structures in early infancy.

Syllables are one of the fundamental building blocks of early language acquisition. From birth onwards, infants preferentially segment, process and represent the speech into syllable-sized units, raising the question of what type of computations infants are able to perform on these perceptual units. Syllables are abstract units structured in a way that allows grouping phonemes into sequences. The goal of this research was to investigate 4-to-5-month-old infants' ability to encode the internal structure of syllables, at a target age when the language system is not yet specialized on the sounds and the phonotactics of native languages. We conducted two experiments in which infants were first familiarized to lists of syllables implementing either CVC (consonant-vowel-consonant) or CCV (consonant-consonant-vowel) structures, then presented with new syllables implementing both structures at test. Experiments differ in the degree of phonological similarity between the materials used at familiarization and test. Results show that infants were able to differentiate syllabic structures at test, even when test syllables were implemented by combinations of phonemes that infants did not hear before. Only infants familiarized with CVC syllables discriminated the structures at test, pointing to a processing advantage for CVC over CCV structures. This research shows that, in addition to preferentially processing the speech into syllable-sized units, during the first months of life, infants are also capable of performing fine-grained computations within such units.

Sensitivity to the sonority sequencing principle in rats (Rattus norvegicus).

Albeit diverse, human languages exhibit universal structures. A salient example is the syllable, an important structure of language acquisition. The structure of syllables is determined by the Sonority Sequencing Principle (SSP), a linguistic constraint according to which phoneme intensity must increase at onset, reaching a peak at nucleus (vowel), and decline at offset. Such structure generates an intensity pattern with an arch shape. In humans, sensitivity to restrictions imposed by the SSP on syllables appears at birth, raising questions about its emergence. We investigated the biological mechanisms at the foundations of the SSP, testing a nonhuman, non-vocal-learner species with the same language materials used with humans. Rats discriminated well-structured syllables (e.g., pras) from ill-structured ones (e.g., lbug) after being familiarized with syllabic structures conforming to the SSP. In contrast, we did not observe evidence that rats familiarized with syllables that violate such constraint discriminated at test. This research provides the first evidence of sensitivity to the SSP in a nonhuman species, which likely stems from evolutionary-ancient cross-species biological predispositions for natural acoustic patterns. Humans' early sensitivity to the SSP possibly emerges from general auditory processing that favors sounds depicting an arch-shaped envelope, common amongst animal vocalizations. Ancient sensory mechanisms, responsible for processing vocalizations in the wild, would constitute an entry-gate for human language acquisition.

Dyslipidaemias and their treatment in high complexity centres in Colombia. / Las dislipidemias y su tratamiento en centros de alta complejidad en Colombia.

BACKGROUND AND OBJECTIVE: Data is scarce on the distribution of different types of dyslipidaemia in Colombia. The primary objective was to describe the frequency of dyslipidaemias. The secondary objectives were: frequency of cardiovascular comorbidity, statins and other lipid-lowering drugs use, frequency of statins intolerance, percentage of patients achieving c-LDL goals, and distribution of cardiovascular risk (CVR). MATERIALS AND METHODS: Cross-sectional study with retrospective data collection from 461 patients diagnosed with dyslipidaemia and treated in 17 highly specialised centres distributed into six geographic and economic regions of Colombia. RESULTS: Mean (SD) age was 66.4 (±12.3) years and 53.4% (246) were women. Dyslipidaemias were distributed as follows in order of frequency: mixed dyslipidaemia (51.4%), hypercholesterolaemia (41.0%), hypertriglyceridaemia (5.4%), familial hypercholesterolaemia (3.3%), and low c-HDL (0.7%). The most prescribed drugs were atorvastatin (75.7%) followed by rosuvastatin (24.9%). As for lipid control, 55% of all patients, and 28.6% of those with coronary heart disease, did not achieve their personal c-LDL goal despite treatment. The frequency of statin intolerance was 2.6% in this study. CONCLUSIONS: Mixed dyslipidaemia and hypercholesterolaemia are the most frequent dyslipidaemias in Colombia. A notable percentage of patients under treatment with lipid-lowering drugs, including those with coronary heart disease, did not achieve specific c-LDL goals. This poor lipid control may worsen patient's CVR, so that therapeutic strategies need to be changed, either with statin intensification or addition of new drugs in patients with higher CVR.

Strict glycaemic control in patients hospitalised in a mixed medical and surgical intensive care unit: a randomised clinical trial.

INTRODUCTION: Critically ill patients can develop hyperglycaemia even if they do not have diabetes. Intensive insulin therapy decreases morbidity and mortality rates in patients in a surgical intensive care unit (ICU) and decreases morbidity in patients in a medical ICU. The effect of this therapy on patients in a mixed medical/surgical ICU is unknown. Our goal was to assess whether the effect of intensive insulin therapy, compared with standard therapy, decreases morbidity and mortality in patients hospitalised in a mixed ICU. METHODS: This is a prospective, randomised, non-blinded, single-centre clinical trial in a medical/surgical ICU. Patients were randomly assigned to receive either intensive insulin therapy to maintain glucose levels between 80 and 110 mg/dl (4.4 to 6.1 mmol/l) or standard insulin therapy to maintain glucose levels between 180 and 200 mg/dl (10 and 11.1 mmol/l). The primary end point was mortality at 28 days. RESULTS: Over a period of 30 months, 504 patients were enrolled. The 28-day mortality rate was 32.4% (81 of 250) in the standard insulin therapy group and 36.6% (93 of 254) in the intensive insulin therapy group (Relative Risk [RR]: 1.1; 95% confidence interval [CI]: 0.85 to 1.42). The ICU mortality in the standard insulin therapy group was 31.2% (78 of 250) and 33.1% (84 of 254) in the intensive insulin therapy group (RR: 1.06; 95%CI: 0.82 to 1.36). There was no statistically significant reduction in the rate of ICU-acquired infections: 33.2% in the standard insulin therapy group compared with 27.17% in the intensive insulin therapy group (RR: 0.82; 95%CI: 0.63 to 1.07). The rate of hypoglycaemia (< or = 40 mg/dl) was 1.7% in the standard insulin therapy group and 8.5% in the intensive insulin therapy group (RR: 5.04; 95% CI: 1.20 to 21.12). CONCLUSIONS: IIT used to maintain glucose levels within normal limits did not reduce morbidity or mortality of patients admitted to a mixed medical/surgical ICU. Furthermore, this therapy increased the risk of hypoglycaemia. TRIAL REGISTRATION: clinicaltrials.gov Identifiers: 4374-04-13031; 094-2 in 000966421.

Cost-effectiveness analysis of ticagrelor compared to clopidogrel for the treatment of patients with acute coronary syndrome in Colombia.

INTRODUCTION: Acute coronary syndrome is one of the most frequent medical emergencies in developing countries. OBJECTIVE: To determine, from the perspective of the Colombian health system, the cost-effectiveness of ticagrelor compared to clopidogrel for the treatment of patients with acute coronary syndrome. MATERIALS AND METHODS: We conducted a cost-effectiveness analysis from the perspective of the Colombian health system comparing ticagrelor and clopidogrel for the treatment of patients with acute coronary syndrome. To estimate the expected costs and outcomes, a Markov model was constructed in which patients could remain stable without experiencing new cardiovascular events, suffer from a new event, or die. For the baseline case, a 10-year time horizon and a discount ratio of 3% for costs and benefits were adopted. The transition probabilities were extracted from the PLATO (Platelet Inhibition and Patient Outcomes) clinical trial. Vital statistics were drawn from the Departmento Administrativo Nacional de Estadística (DANE) and additional information from Colombian patients included in the Access registry. To identify and measure resource use, a standard case was built by consulting guidelines and protocols. Unit costs were obtained from Colombian rate lists. A probabilistic sensitivity analysis was conducted in which costs were represented by a triangular distribution, and the effectiveness through a beta distribution. RESULTS: In the base case, the additional cost per quality-adjusted life-year gained with ticagrelor was COP$ 28,411,503. The results were sensitive to changes in the time horizon and the unit cost of clopidogrel. For a willingness-to-pay equivalent to three times the Colombian per capita gross domestic product, the probability of ticagrelor being cost-effective was 75%. CONCLUSIONS: Ticagrelor is a cost-effective strategy for the treatment of patients with acute coronary syndrome in Colombia.

A palladium-catalyzed methylenation of olefins using halomethylboronate reagents.

Methylenation of electron-rich olefins is a highly challenging reaction, for which we have developed a new methodology exploiting Pd-catalysis and halomethylboronate reagents, the latter replacing diazomethane and zinc carbenoids as methylene donors. Optimization of the reaction for norbornene and extension to several other olefins are reported, with reasonable-to-excellent yields of cyclopropanes in combination with ß-H elimination products. Several mechanisms are plausible for this methylenation reaction.

Ensayo clínico aleatorizado y controlado del efecto del consumo de cacao en pacientes con resistencia a la insulina / Randomized and controlled clinical trial of the effect of cocoa consumption in patients with insulin resistance

Resumen Objetivo: determinar el efecto del consumo de cacao en pacientes con sindrome metabólico. Diseño: se realizó un ensayo clínico aleatorizado, de grupos paralelos, controlado con placebo, prospectivo, doble enmascarado. Pacientes: personas entre 18 y 70 anos de edad, no diabéticos, con resistencia a la insulina. Intervención: durante ocho semanas se evaluó el efecto del consumo de 50 g de chocolate rico en polifenoles, el grupo control recibió placebo. Mediciones: al inicio y al final del estudio el índice HOMA-IR, circunferencia abdominal, índice de masa corporal (IMC), glucemia y perfil lipídico. Resultados: en el grupo experimental (n=37) hubo reducción del HOMA IR (3.24 inicial y 2.77 final, p= 0.02), reducción del peso corporal, en promedio 1.53 Kg (inicial 86.3 Kg y final de 84.8 Kg, p=0.002), disminución del IMC (34.3 Kg/m2 al inicio y 33.5 Kg/m2 al final, p= 0.0001) y disminución de la cintura abdominal (inicial 106.3 cm y final 102.5 cm, p= 0.0001). Al comparar los resultados del grupo tratado con chocolate negro con los del grupo control (n=38) hubo diferencia estadísticamente significativa en la media de cintura abdominal al final entre ambos grupos (102.5 cm para el experimental y 108.0 cm para el control, p=0.01). Conclusiones: este ensayo sugiere que el consumo de 50 gramos diarios de chocolate rico en sólidos de cacao durante ocho semanas se asocia con una disminución de la circunferencia abdominal y el índice HOMA-IR. Además, aporta una evidencia de mayor calidad que los estudios observacionales sobre el uso de cacao en la reducción de la obesidad, la adiposidad y en la prevención de la enfermedad cardiometabólica en pacientes colombianos. (Acta Med Colomb 2017: 42: 90-96). Registro en Clinical Trials: NCT03034291

Abstract Objective: to determine the effect of cocoa consumption in patients with metabolic syndrome. Design: a randomized, parallel-group, placebo-controlled, prospective, double-masked clinical trial was conducted. Patients: people between 18 and 70 years of age, non-diabetic, with insulin resistance. Intervention: the effect of consumption of 50 g of chocolate rich in polyphenols was evaluated for eight weeks. The control group received placebo. Measurements: at the beginning and at the end of the study, the HOMA-IR index, abdominal circumference, body mass index (BMI), blood glucose and lipid profile. Results: in the experimental group (n = 37) there was a reduction of HOMA IR (3.24 initial and 2.77 final, p = 0.02), reduction of body weight, on average 1.53 Kg (initial 86.3 Kg and final 84.8 Kg, p = 0.002), decreased BMI (34.3 at baseline and 33.5 at end, p = 0.0001) and decreased abdominal waist (initial 106.3 cm and final 102.5 cm, p = 0.0001). When comparing the results of the group treated with black chocolate with those of the control group (n = 38), there was a statistically significant difference in the mean abdominal waist at the end between both groups (102.5 cm for the experimental group and 108.0 cm for the control, p = 0.01). Conclusions: This study suggests that consumption of 50 grams of chocolate rich in cocoa solids daily for eight weeks is associated with a decrease in waist circumference and the HOMA-IR index. In addition, it provides evidence of higher quality than observational studies on the use of cocoa in the reduction of obesity, adiposity and in the prevention of cardiometabolic disease in Colombian patients. (Acta Med Colomb 2017: 42: 90-96). Register in Clinical Trials: NCT03034291

Cost-effectiveness analysis of ticagrelor compared to clopidogrel for the treatment of patients with acute coronary syndrome in Colombia / Análisis de costo-efectividad del ticagrelor en comparación con el clopidogrel para el tratamiento de pacientes con síndrome coronario agudo en Colombia

Introduction: Acute coronary syndrome is one of the most frequent medical emergencies in developing countries. Objective: To determine, from the perspective of the Colombian health system, the cost-effectiveness of ticagrelor compared to clopidogrel for the treatment of patients with acute coronary syndrome. Materials and methods: We conducted a cost-effectiveness analysis from the perspective of the Colombian health system comparing ticagrelor and clopidogrel for the treatment of patients with acute coronary syndrome. To estimate the expected costs and outcomes, a Markov model was constructed in which patients could remain stable without experiencing new cardiovascular events, suffer from a new event, or die. For the baseline case, a 10-year time horizon and a discount ratio of 3% for costs and benefits were adopted. The transition probabilities were extracted from the PLATO (Platelet Inhibition and Patient Outcomes) clinical trial. Vital statistics were drawn from the Departmento Administrativo Nacional de Estadística (DANE) and additional information from Colombian patients included in the Access registry. To identify and measure resource use, a standard case was built by consulting guidelines and protocols. Unit costs were obtained from Colombian rate lists. A probabilistic sensitivity analysis was conducted in which costs were represented by a triangular distribution, and the effectiveness through a beta distribution. Results: In the base case, the additional cost per quality-adjusted life-year gained with ticagrelor was COP$ 28,411,503. The results were sensitive to changes in the time horizon and the unit cost of clopidogrel. For a willingness-to-pay equivalent to three times the Colombian per capita gross domestic product, the probability of ticagrelor being cost-effective was 75%. Conclusions: Ticagrelor is a cost-effective strategy for the treatment of patients with acute coronary syndrome in Colombia.

Introducción. El síndrome coronario agudo es una de las emergencias médicas más frecuentes en los países en desarrollo. Objetivo. Determinar, desde la perspectiva del sistema de salud colombiano, la relación de costo-efectividad del ticagrelor comparado con el clopidogrel para el tratamiento de pacientes con síndrome coronario agudo. Materiales y métodos. Se hizo un análisis de costo-efectividad desde la perspectiva del sistema de salud colombiano, comparando el ticagrelor y el clopidogrel para el tratamiento de pacientes con síndrome coronario agudo. Para estimar los costos y resultados esperados de las dos alternativas, se construyó un modelo de Markov en el cual los pacientes podían permanecer estables sin experimentar nuevos eventos cardiovasculares, sufrir de un nuevo evento coronario o morir. Para el caso de base, se adoptó un horizonte temporal de 10 años y una tasa de descuento de 3 % para los costos y beneficios. Las probabilidades de transición se extrajeron del estudio Platelet Inhibition and Patient Outcomes , PLATO. Las estadísticas vitales se consultaron en informes del Departamento Administrativo Nacional de Estadística (DANE) y los parámetros adicionales del modelo se basaron en la información de los pacientes colombianos incluidos en el registro en Access. Para identificar y medir el uso de recursos, se construyó un caso estándar a partir de guías y protocolos. Los costos unitarios se obtuvieron de manuales tarifarios colombianos. Se hizo un análisis de sensibilidad probabilístico en el que los costos se representaron por una distribución triangular y, las probabilidades de transición, mediante una distribución beta. Resultados. En el caso de base, el costo adicional por años de vida ajustados por calidad ganados con el ticagrelor fue de COP$ 28´411.503. Los resultados fueron sensibles a los cambios en el horizonte temporal y al costo unitario del clopidogrel. Para un umbral de costo-efectividad equivalente a tres veces el producto interno bruto per cápita de Colombia, la probabilidad de que el ticagrelor fuera costo-efectivo fue de 75 %. Conclusiones. El ticagrelor es una estrategia costo-efectiva para el tratamiento de los pacientes con síndrome coronario agudo en Colombia.

Análisis de costo efectividad de prasugrel, comparado con clopidogrel para pacientes con síndrome coronario agudo sometidos a intervención coronaria percutánea en Colombia / Analysis of cost effectiveness of prasugrel compared with clopidogrel for patients with acute coronary syndrome undergoing percutaneous coronary intervention in Colombia

Objetivo: determinar, desde la perspectiva del sistema de salud colombiano, la relación de costo-efectividad del prasugrel comparado con clopidogrel, para el tratamiento de pacientes adultos con síndrome coronario agudo. Material y métodos: se construyó un modelo de Markov con ciclos anuales en el cual los pacientes pueden permanecer sin experimentar nuevos eventos cardiovasculares, sufrir un nuevo evento o morir. En el caso base se adoptó un horizonte temporal de 10 años y una tasa de descuento de 3%. Las probabilidades de transición se extrajeron del ensayo clínico TRITON-TIMI 38, de las estadísticas vitales del Departamento Nacional de Estadística y de la información de los pacientes colombianos del registro ACCESS. Para identificar y medir el uso de recursos se diseñó un caso típico a partir de la revisión de guías y protocolos; para la valoración se emplearon manuales tarifarios colombianos. Se realizaron análisis de sensibilidad determinísticos y probabilísticos. Resultados: en el caso base, el costo por año de vida ajustado por calidad ganado con prasugrel es $79 987 695 pesos colombianos. Los resultados son sensibles a cambios en el horizonte temporal y al costo del clopidogrel. Bajo un umbral de disposición a pagar de tres veces el PIB per cápita colombiano, la probabilidad de que el prasugrel sea costo efectivo es 7%. Conclusiones: la decisión respecto a la inclusión del prasugrel en el tratamiento de pacientes con síndrome coronario agudo, sometidos a intervención coronaria percutánea depende fundamentalmente del costo del clopidogrel que el decisor considere relevante para realizar la comparación. (Acta Med Colomb 2015; 40: 310-317).

Objective: to determine the cost-effectiveness relation of prasugrel compared with clopidogrel for the treatment of adult patients with acute coronary syndrome from the perspective of Colombian health system. Material and methods: a Markov model with annual cycles in which patients can remain without experiencing new cardiovascular events, have a new event or die, was built. In the base case a time horizon of 10 years and a discount rate of 3% was adopted. Transition probabilities were taken from the clinical trial TRITON-TIMI 38, of vital statistics from the National Department of Statistics and from the information of Colombian patients in ACCESS registry. To identify and measure the use of resources, a typical case was designed from the review of guidelines and protocols; Colombian tariff manuals were used for assessment. Deterministic and probabilistic sensitivity analyzes were performed. Results: in the base case, the cost per year of quality-adjusted life gained with prasugrel is $ 79,987,695 Colombian pesos. The results are sensitive to changes in the timeframe and cost of clopidogrel. Under a threshold willingness to pay three times the per capita GDP of Colombia, the probability that prasugrel may be cost-effective, is 7%. Conclusions: the decision on the inclusion of prasugrel in the treatment of patients with acute coronary syndrome undergoing percutaneous coronary intervention depends mainly on the cost of clopidogrel that the decision maker considers relevant to perform the comparison. (Acta Med Colomb 2015; 40: 310-317).

Eficacia y seguridad del acceso radial y femoral en pacientes con síndrome coronario agudo llevados a intervencionismo coronario Redial - Registro de intervención por vía radial / Efficacy and safety of radial and femoral access in patients with acute coronary syndrome undergoing coronary intervention Redial - Registration of intervention by radial access

Introducción: el acceso transradial ha surgido como una alternativa atractiva a la vía femoral para realizar coronariografías e intervenciones coronarias. Describimos nuestra experiencia, y comparamos el acceso radial con una cohorte de acceso femoral en un periodo de tiempo. Objetivo: identificar las complicaciones vasculares relacionadas con la coronariografía en pacientes de la unidad de dolor torácico de una institución de alta complejidad de la ciudad de Medellín. Materiales y métodos: estudio epidemiológico observacional, analítico, de una cohorte retrospectiva de pacientes mayores de 18 años que ingresaron a la unidad de dolor torácico del hospital Universitario San Vicente Fundación con diagnóstico de síndrome coronario agudo con y sin elevación del ST, y a los cuales se les realizó coronariografía por acceso radial y femoral. Resultados: se evaluaron 675 pacientes, de los cuales 59.6% (n=402) se les realizó acceso femoral y 40.4% (n=273) acceso radial con diferencias, en relación al sexo y aspectos personales como el tabaquismo y la enfermedad renal crónica. Respecto a las complicaciones según el tipo de acceso, se hallaron diferencias significativas en la presencia de hematoma femoral (OR= 5.6; IC 95%: 1.28; 24.63) y el espasmo radial (p<0.05). Conclusión: los accesos radial y femoral son seguros y efectivos, sin embargo la disminución significativa de las complicaciones vasculares puede ser una razón para preferir el acceso radial como técnica de elección en la mayoría de estos pacientes. (Acta Med Colomb 2015; 40: 209-217).

Introduction: the transradial access has emerged as an attractive alternative to the femoral access for coronary angiography and coronary interventions. We describe our experience, and compare the radial access with a cohort of femoral access in a time period. Objective: to identify vascular complications related to coronary angiography in patients of the chest pain unit of a high complexity institution of the city of Medellin. Materials and Methods: epidemiological, observational, analytical study of a retrospective cohort of patients over 18 years admitted to the chest pain unit of the University Hospital San Vicente Foundation with diagnosis of acute coronary syndrome with and without ST elevation in which coronary angiography by radial and femoral access was performed. Results: 675 patients were evaluated. 59.6% (n = 402) underwent femoral access, and 40.4% (n = 273) radial access with differences in relation to sex and personal aspects such as smoking and chronic kidney disease. Regarding complications according to the type of access, significant differences were found in regard to the presence of femoral hematoma (OR = 5.6; 95% CI: 1.28; 24.63) and radial artery spasm (p <0.05). Conclusion: the radial and femoral accesses are safe and effective; however, the significant decrease in vascular complications may be a reason to prefer the radial access as technique of choice in most of these patients. (Acta Med Colomb 2015; 40: 209-217).

Desempeño del APACHE II y el SAPS 3 Adaptación regional en una población de pacientes críticos de Colombia / Performance of APACHE II and SAPS 3 Regional adaptation in a population of critically Ill patients in Colombia

El puntaje fisiológico agudo simplificado, SAPS 3 (del inglés Simplified Acute Physiology Score 3) ha sido recientemente desarrollado con muestras de los cinco continentes, pero no ha sido validado en pacientes de las Unidades de Cuidados Intensivos (UCI) en Colombia. En este trabajo se comparó el desempeño del SAPS 3 con el APACHE II en pacientes colombianos de UCI. Métodos: en una población de una cohorte histórica de pacientes críticos admitidos a una UCI de un hospital universitario, entre enero 1º de 2006 a junio 30 de 2011, se midió el desempeño de los modelos de mortalidad. La probabilidad de muerte hospitalaria fue calculada con el APACHE II y el SAPS 3. Para mejorar la exactitud de los modelos fue realizada una adaptación de primer orden usandola regresión logística del puntaje original para el APACHE II, y para el SAPS 3 se hizo el cálculo de la probabilidad de muerte con las fórmulas para Europa oriental, Centro-Suramérica y Australasia. Resultados: el estudio incluye 2523 pacientes. La mortalidad hospitalaria fue 27%. La discriminación fue aceptable para todos los modelos, más baja para el APACHE II que mejora con la adaptación de 0.74 a 0.78. Para todas las formas de SAPS 3 el área bajo la curva ROC fue de 0.78. La calibración, medida con el estadístico de Hosmer-Lemeshow, fue pobre para el APACHE II, APACHE II adaptado,SAPS 3 adaptado para Centro-Suramérica, y Europa oriental, pero fue buena para el SAPS 3 global y el adaptado para Australasia. Conclusión: en una población de pacientes críticos colombianos, la adaptación logra mejorar la discriminación del APACHE II pero no su calibración. La calibración es adecuada sólo para el SAPS 3 global y el adaptado para Australasia. (Acta Med Colomb 2014; 39: 148-158).

The simplified acute physiological score (SAPS 3) has been recently developed with samples from the five continents, but has not been validated in patients in intensive care units (ICU) in Colombia. In this work the performance of SAPS 3 with APACHE II in Colombian ICU patients was compared. Methods: in a population of a historical cohort of critically ill patients admitted to an ICU of a university hospital between January 1°, 2006 to June 30, 2011, the performance of the mortality models was measured. The probability of hospital death was calculated with APACHE II and SAPS 3. To improve the accuracy of the models, a first order adaptation was realized, using the logistic regression of the original score for the APACHE II, and for SAPS 3 the calculation of the probability of death was done with the formulas for Eastern Europe, Central and South America and Australasia. Results: the study included 2523 patients. Hospital mortality was 27%. Discrimination was acceptable for all models, being lower for APACHE II, which improves with adaptation from 0.74 to 0.78. For all forms of SAPS 3, the area under the ROC curve was 0.78. Calibration, measured with the Hosmer-Lemeshow statistic was poor for the APACHE II, adjusted APACHE II, SAPS 3 adapted to Central South America and Eastern Europe, but it was good for the global SAPS 3 and for the one adapted to Australasia. Conclusion: in a population of Colombian critically ill patients, adaptation manages to improve discrimination of APACHE II but not its calibration. Calibration is appropriate only for the global SAPS 3 and the one adapted to Australasia. (Acta Med Colomb 2014; 39: 148-158).

Características epidemiológicas, clínicas, tratamiento y pronóstico de los pacientes con diagnóstico de síndrome coronario agudo en unidad especializada / Epidemiological and clinical characteristics, treatment and prognosis of patients with acute coronary syndrome in a specialized unit

Resumen Introduccion: el síndrome coronario agudo es una de las principales causas de consulta en los servicios de urgencias y cardiología, con una alta tasa de mortalidad y con altos costos para la sociedad.Existe muy poca información con respecto a población latinoamericana y de Colombia en los estudiosmulticéntricos internacionales. Se convierte en un reto conocer a profundidad las características epidemiológicas, clínicas, de laboratorio, escalas de riesgo usadas, hallazgos angiográficos, tratamientoinstaurado y mortalidad en pacientes que han sido atendidos en un hospital de cuarto nivel de la ciudadde Medellín. Material y métodos: estudio epidemiológico, observacional, descriptivo, longitudinal, retrospectivo tipo serie de casos. La población de estudio corresponde a los pacientes mayores de 18 años de edad, que consultaron a la unidad de dolor torácico del Hospital Universitario San Vicente Fundación con diagnóstico de síndrome coronario agudo en un periodo de tres meses. Los pacientes continuaron su tratamiento según las recomendaciones y guías tanto internacionales como locales para dolor torácico. Luego de seis meses del síndrome coronario agudo, se realizó un contacto con el paciente por varios medios, evaluaciones de consulta externa, historia clínica y llamada telefónica. Se obtuvo información de su evolución clínica, estado funcional y complicaciones incluyendo reintervención, hospitalización o muerte, de igual forma se evaluó la adherencia al manejo médico. Resultados: un total de 154 pacientes fueron analizados, 30% (n=47) por angina inestable, 37% (n=56) por IAMST y 33% (n=51) por IAMNST. El promedio de edad fue de 62 ± 13 años, hombres 54% (n=83). Los factores de riesgo asociados fueron: hipertensión arterial 66% (n=101), dislipidemia 23% (n=35), diabetes mellitus 18% (n=27), obesidad 5,1% (n=8) y tabaquismo 52% (n=80). El total de cateterismos realizados fue de 129; normales el 21.8% (n=28) y lesiones obstructivas significativas en 78.2% (n=101). De los pacientes con IAMST (n=56), sólo 28% recibieron reperfusión primaria. La mortalidad intrahospitalaria fue de 7% (n=11). Luego de seis meses de seguimiento se presentaron seis muertes más (12%). La adherencia a los tratamientos farmacológicos a los seis meses estuvo entre 54 y 86%. De los pacientes que egresaron con orden de rehabilitación cardiaca, sólo 3% la habían realizado luego de seis meses del egreso. Conclusiones: los pacientes que ingresan a la unidad de dolor torácico del Hospital San Vicente Fundación con síndrome coronario agudo presentan unas características epidemiológicas de base similares a las reportadas en la literatura médica. Sin embargo, la mortalidad es superior. Se documentó un bajo número de pacientes con IAMST que pudieron recibir tratamiento de reperfusión. También se encontró baja adherencia al manejo farmacológico y a la rehabilitación cardiaca, esto posiblemente en relación con acceso limitado a los servicios de salud de alta complejidad de forma oportuna. (Acta Med Colomb 2014; 39: 21-28).

Abstract Introduction: acute coronary syndrome is one of the major causes of consultation in the emergency and cardiology services, with a high mortality rate and high costs to society. There is very little information regarding Colombian and Latin American population in international multicenter studies. It becomes a challenge to know in depth the epidemiological, clinical and laboratory characteristics, the risk scales used, angiographic findings, established treatment and mortality in patients who have been treated at a fourth level hospital of Medellin. Material and methods: epidemiological , observational, descriptive , longitudinal , retrospective case series study. The study population corresponds to patients over 18 years of age, who consulted the chest pain unit of the Hospital Universitario San Vicente Foundation with diagnosis of acute coronary syndrome in a period of three months. Patients continued treatment according to the local and international chest pain recommendations and guidelines. After six months of the acute coronary syndrome, a patient contact was made by various means, including outpatient evaluations , medical records and telephone call. Details about clinical outcome, functional status and complications including reoperation,hospitalization or death was obtained, and the adherence to medical management was also assessed. Results: a total of 154 patients were analyzed , 30% (n = 47) for unstable angina, 37% (n = 56) for STEMI and 33% (n = 51) for NSTEMI . The mean age was 62 ± 13 years. 54% were men (n = 83). The associated risk factors were: hypertension 66 % (n = 101) , dyslipidemia 23% (n = 35), diabetes mellitus18% (n = 27), obesity 5.1% (n = 8) and 52% smoking (n = 80). The total catheterizations performed was 129; 21.8 % (n = 28) of these were normal and 78.2 % (n = 101) had significant obstructive lesions. Only 28 % of the patients with STEMI (n = 56) received primary reperfusion. In-hospital mortality was 7% (n = 11). After six months of follow-up 6 more deaths (12%) were presented. Adherence to drug treatment at six months was between 54 and 86%. Of the patients who were discharged with order of cardiac rehabilitation, only 3% had done it after 6 months of discharge. Conclusions: patients who are admitted to the chest pain unit at St. Vincent Hospital Foundation with acute coronary syndrome present epidemiological characteristics similar to those reported in the medical literature. However, mortality is higher. A low number of patients with STEMI who could receive reperfusion therapy was documented. Poor adherence to pharmacological management and cardiac rehabilitation was also found , possibly in relation with a limited access to health services of high complexity in a timely manner. (Acta Med Colomb 2014; 39: 21-28).

Different neurophysiological mechanisms underlying word and rule extraction from speech.

The initial process of identifying words from spoken language and the detection of more subtle regularities underlying their structure are mandatory processes for language acquisition. Little is known about the cognitive mechanisms that allow us to extract these two types of information and their specific time-course of acquisition following initial contact with a new language. We report time-related electrophysiological changes that occurred while participants learned an artificial language. These changes strongly correlated with the discovery of the structural rules embedded in the words. These changes were clearly different from those related to word learning and occurred during the first minutes of exposition. There is a functional distinction in the nature of the electrophysiological signals during acquisition: an increase in negativity (N400) in the central electrodes is related to word-learning and development of a frontal positivity (P2) is related to rule-learning. In addition, the results of an online implicit and a post-learning test indicate that, once the rules of the language have been acquired, new words following the rule are processed as words of the language. By contrast, new words violating the rule induce syntax-related electrophysiological responses when inserted online in the stream (an early frontal negativity followed by a late posterior positivity) and clear lexical effects when presented in isolation (N400 modulation). The present study provides direct evidence suggesting that the mechanisms to extract words and structural dependencies from continuous speech are functionally segregated. When these mechanisms are engaged, the electrophysiological marker associated with rule-learning appears very quickly, during the earliest phases of exposition to a new language.

Fundamentos biológicos en la extracción de regularidades del habla / Biological foundations in the extraction of regularities from speech

Uno de los mayores problemas en el estudio del lenguaje es la comprensión de sus fundamentos biológicos. Una forma de abordar este problema que ha resultado efectiva es la de estudiar hasta qué punto compartimos con otros animales algunos de los mecanismos responsables de su procesamiento. En este artículo se presentan una serie de experimentos que demuestran que las habilidades para extraer regularidades rítmicas y estadísticas del habla están ya presentes en algunos roedores. A su vez, otros estudios sugieren que los animales también pueden procesar ciertas estructuras abstractas tradicionalmente ligadas a la gramática. Estos estudios apuntan en la dirección de que muchos de los componentes básicos del procesamiento lingüístico son compartidos a través de diferentes especies animales. Sin embargo, existe todavía un amplio abanico de fenómenos lingüísticos que deben ser estudiados desde una perspectiva comparada para determinar hasta qué punto el lenguaje humano hace uso de habilidades ya existentes en otros animales.

One of the major problems in the study of language is to understand its biological roots. An effective way to tackle this issue is to explore to which extent we share with other animals some of the mechanisms responsible for its processing. In this paper we present a series of experiments that demonstrate that the abilities required to extract rhythmic and statistical regularities from speech are already present in rodents. Other studies also suggest that some animals might be able to process certain abstract structures that have been traditionally linked to grammar. Together, these studies point towards the idea that many of the basic components of language processing are shared across different species. Nevertheless, there is still a wide array of linguistic phenomena that should be studied from a comparative perspective to determine the extent to which human language uses abilities found in other animals.

Asociación entre títulos de anticuerpos anticardiolipinas y eventos trombóticos / Association between anticardiolipin titles and thrombotic events

Introducción: la trombosis es la manifestación principal del síndrome antifosfolípido (SAF); los marcadores serológicos de esta entidad son los anticuerpos anticardiolipinas (aCL), la anti-β2 glicoproteína 1 y el anticoagulante lúpico. Aún se discute si los títulos de aCL o la presencia de un "segundo hit" son factores de riesgo para trombosis. Objetivo: evaluar la asociación entre fenómenos trombóticos vasculares con la presencia y los títulos de aCL; además del papel de otros factores protrombóticos. Material y método: estudio descriptivo transversal. Se revisaron historias clínicas de pacientes con sospecha clínica de SAF y con al menos una medición de títulos de aCL, se evaluó la presencia o no de eventos trombóticos y de comorbilidades (segundo hit). Resultados: historias clínicas de 49 pacientes, 33 con un total de 36 eventos trombóticos de los cuales 23 ocurrieron en lechos venosos y 13 en lechos arteriales. Aunque la mayoría de los pacientes con títulos de aCL > 20 GLP o MLP se encontraban en el grupo de trombosis, no se encontró asociación significativa entre la presencia de trombosis y los títulos de aCL; como tampoco entre trombosis y la existencia de otras comorbilidades. Conclusiones: los hallazgos encontrados permiten sugerir la mayor frecuencia de eventos trombóticos en pacientes con títulos de aCL < 40 en dos mediciones y aportan información sobre las características clínicas de los pacientes con aCL y sospecha de SAF en nuestro medio; sin embargo, no son suficientes para categorizarlos como un factor de riesgo definitivo de trombosis.

Background: thrombosis is the main clinical manifestation of the antiphospholipid syndrome (APS); anticardiolipin antibodies (aCL), anti-β2 glycoprotein-1 antibodies and lupus anticoagulant are the serological markers of the disease. Whether the titles of aCL or the presence of a "second hit" are risk factors for thrombosis is an unresolved issue. Objective: to evaluate the association between vascular thrombotic events with the presence of aCL. The relationship between thrombosis and the titles of aCL, as well as other prothrombotic factors was also assessed. Methodology: descriptive cross-sectional study. The clinical charts of patients with possible APS and at least one laboratory measurement of aCL were reviewed. The presence of thrombotic events and the existence of comorbid states (second hit) were also evaluated. Results: the records of 49 patients were assessed, 33 with a total of 36 thrombotic events, 23 had occurred on veins, and 13 on arteries. Though the majority of the patients that had titles of aCL above of 20 GPL or MPL were located in the group of thrombosis, there was no significant association between the titles of aCL and the presence of thrombosis. Neither significant association was found between thrombosis and the presence of other comorbid states. Conclusions: these findings allow suggesting the increased frequency of thrombotic events in patients with titers of aCL lower than 40 twice and also add information about the clinical characteristics of patients with aCL and suspected APS in our region; however, they are not enough to categorize them as a definitive risk factor of thrombosis.