The role of cognitive reserve in traumatic brain injury: a systematic review of observational studies.

OBJECTIVE: Evaluate the role of cognitive reserve (CR) on cognitive and physical sequelae in traumatic brain injury (TBI). METHODS: A comprehensive search strategy was conducted in four databases in English and Spanish in the last 12 years (2011-2023). Inclusion criteria: original cross-sectional and longitudinal studies whose main or secondary objective was to evaluate the effect of CR in adult patients with TBI. PRISMA guidelines were used to report the search and selection method and STROBE checklist was used to evaluate the quality of studies. RESULTS: Eighteen observational studies were included in this review. Multiple sources of variability were observed: number of patients, time of evolution, severity of the TBI, type of CR proxy, cognitive assessment instrument, etc. However, the most commonly used indicators of CR were premorbid IQ and educational attainment. A positive and consistent association between CR and performance on cognitive tests after injury was found. CONCLUSIONS: CR has a consistent positive effect on cognition and on some other aspects of recovery in traumatic brain injury. In future studies, it will be necessary to promote the use of CR indices based on various indicators and explore the effects of CR on other aspects related to the recovery of brain trauma.

The association of the RSC remodeler complex with chromatin is influenced by the prefoldin-like Bud27 and determines nucleosome positioning and polyadenylation sites usage in Saccharomyces cerevisiae.

The tripartite interaction between the chromatin remodeler complex RSC, RNA polymerase subunit Rpb5 and prefoldin-like Bud27 is necessary for proper RNA pol II elongation. Indeed lack of Bud27 alters this association and affects transcription elongation. This work investigates the consequences of lack of Bud27 on the chromatin association of RSC and RNA pol II, and on nucleosome positioning. Our results demonstrate that RSC binds chromatin in gene bodies and lack of Bud27 alters this association, mainly around polyA sites. This alteration impacts chromatin organization and leads to the accumulation of RNA pol II molecules around polyA sites, likely due to pausing or arrest. Our data suggest that RSC is necessary to maintain chromatin organization around those sites, and any alteration of this organization results in the widespread use of alternative polyA sites. Finally, we also find a similar molecular phenotype that occurs upon TOR inhibition with rapamycin, which suggests that alternative polyadenylation observed upon TOR inhibition is likely Bud27-dependent.

Integrated, Selective, Simultaneous Multigas Sensing Based on Nondispersive Infrared Spectroscopy-Type Photoacoustic Spectroscopy.

Most chemical sensing scenarios require the selective and simultaneous determination of the concentrations of multiple gas species. In order to enable large-scale monitoring, reliability, robustness, and the potential for integration and miniaturization are key parameters that next-generation sensing technologies must comply with. Due to their superior sensitivity and selectivity as compared to standard NDIR-type systems, photoacoustic NDIR-approaches offer a means for selective detection at much reduced system dimensions such that microintegration becomes feasible. This contribution presents an acoustic frequency multiplexing method to integrate sensing capabilities for the parallel analysis of multiple gases in a single device without loss in selectivity via sound frequency separation. The approach is demonstrated using mid-infrared light emitting diodes and a multigas photoacoustic detector to monitor some of the most important greenhouse gases: carbon dioxide and methane. The number of gas species the sensor concept is able to detect simultaneously can be expanded without increasing the size of the system or its complexity. Additionally, the results demonstrate that the integrated device features the same selectivity and sensitivity as the currently used single gas photoacoustic NDIR systems. Furthermore, the possibility of an extension to any number of gas species is argued.

Confirmation of the presence of serotonergic cells in the fetal cerebral cortex in cultures and in situ.

BACKGROUND: Early appearance of serotonin in the fetal brain and its effects on brain morphogenesis support its neurotrophic role. OBJECTIVE: To determine the presence of serotonergic cells and the expression of tryptophan-5-hydroxylase (TPH), 5-hydroxytryptamine (5-HT), serotonin transporter (SERT), 5-HT1A receptor and Pet-1 during the development of the cerebral cortex, both in situ and in tissue cultures. MATERIAL AND METHODS: A descriptive, observational study was carried out in pregnant Wistar rats. The presence of the plug was regarded as the beginning of gestation. On days 13, 16 and 17, cesarean sections were performed to obtain the fetuses, and the brains were then immediately dissected to identify the presence of serotonergic cells, TPH, 5-HT, SERT, 5-HT1A and Pet-1 in tissue cultures and in situ by immunostaining detected on a confocal microscope. RESULTS: Serotonergic cells and terminals were observed in the midbrain on day 17 of gestation, and in neopallium cocultures on days 13 and 16. TPH, 5-HT, SERT and Pet-1 immunopositive cells were also observed in the neopallium on day 12 of culture. CONCLUSIONS: The presence of serotonergic cells and other elements of the serotonergic system in the early cerebral cortex was confirmed, which may be transient and participate in cortical maturation processes during brain development.

ANTECEDENTES: La aparición temprana de serotonina en el cerebro fetal y sus efectos en la morfogénesis cerebral apoyan su papel neurotrófico. OBJETIVO: Determinar la presencia de células serotoninérgicas y la expresión de triptófano-5-hidroxilasa (TPH), 5-hidroxitriptamina (5-HT), transportador de serotonina (SERT), receptor 5-HT1A y Pet-1 durante el desarrollo de la corteza cerebral, tanto in situ como en cultivo de tejidos. MATERIAL Y MÉTODOS: Se realizó estudio observacional descriptivo en ratas Wistar preñadas. La presencia del tapón se consideró el inicio de la gestación; en los días 13, 16 y 17 se practicaron cesáreas para obtener los fetos e inmediatamente se disecaron los cerebros para identificar células serotoninérgicas, TPH, 5-HT, SERT, 5-HT1A y Pet-1 en cultivo de tejido e in situ mediante inmunomarcaje detectado en un microscopio confocal. RESULTADOS: Células y terminales serotoninérgicas fueron observadas en el mesencéfalo el día 17 de gestación y en cocultivos de neopalio los días 13 y 16. También se observaron células inmunopositivas a TPH, 5-HT, SERT y Pet-1 en el neopalio en el día 12 del cultivo. CONCLUSIONES: Se confirmó la presencia de células serotoninérgicas y otros elementos del sistema serotoninérgico en la corteza cerebral temprana, la cual puede ser transitoria y participar en los procesos de maduración cortical durante el desarrollo cerebral.

Impact of the Five-Year Intervention of an Antimicrobial Stewardship Program on the Optimal Selection of Surgical Prophylaxis in a Hospital without Antibiotic Prescription Restrictions in Costa Rica: A Retrospective Study.

This study aims to characterize the impact of the implementation of an antimicrobial stewardship program (AMS) on the optimal selection of surgical antibiotic prophylaxis in adult patients. This is a retrospective quasi-experimental study that compared the selection and duration of antibiotics for all surgical prophylaxis prescriptions over six months, both before (pre-AMS) and after a five-year intervention of AMS (post-AMS). In addition, data related to the consumption of antibiotics, adverse drug reactions, and surgical site infections throughout the years of the intervention were analyzed. The rate of appropriate selection of antibiotic prophylaxis in surgical procedures improved to 80% during the post-AMS period. The percentage of optimal duration increased from 69.1% (N = 1598) in the pre-AMS period to 78.0% (N = 841) in the post-AMS period (p < 0.001). The consumption of ceftriaxone significantly decreased, while the use of cefazolin increased more than nine times. No severe adverse reactions or increases in surgical site infections were detected after the intervention. The implementation of an AMS in the surgical ward demonstrated a trend towards a positive overall impact on the selection and duration of prophylactic antibiotics for surgery, with positive results also observed in other variables associated with the prescription of these antibiotics.

Confirmación de la presencia de células serotoninérgicas en la corteza cerebral fetal en cultivos e in situ / Confirmation of the presence of serotonergic cells in the fetal cerebral cortex in cultures and in situ

Resumen Antecedentes: La aparición temprana de serotonina en el cerebro fetal y sus efectos en la morfogénesis cerebral apoyan su papel neurotrófico. Objetivo: Determinar la presencia de células serotoninérgicas y la expresión de triptófano-5-hidroxilasa (TPH), 5-hidroxitriptamina (5-HT), transportador de serotonina (SERT), receptor 5-HT1A y Pet-1 durante el desarrollo de la corteza cerebral, tanto in situ como en cultivo de tejidos. Material y métodos: Se realizó estudio observacional descriptivo en ratas Wistar preñadas. La presencia del tapón se consideró el inicio de la gestación; en los días 13, 16 y 17 se practicaron cesáreas para obtener los fetos e inmediatamente se disecaron los cerebros para identificar células serotoninérgicas, TPH, 5-HT, SERT, 5-HT1A y Pet-1 en cultivo de tejido e in situ mediante inmunomarcaje detectado en un microscopio confocal. Resultados: Células y terminales serotoninérgicas fueron observadas en el mesencéfalo el día 17 de gestación y en cocultivos de neopalio los días 13 y 16. También se observaron células inmunopositivas a TPH, 5-HT, SERT y Pet-1 en el neopalio en el día 12 del cultivo. Conclusiones: Se confirmó la presencia de células serotoninérgicas y otros elementos del sistema serotoninérgico en la corteza cerebral temprana, la cual puede ser transitoria y participar en los procesos de maduración cortical durante el desarrollo cerebral.

Abstract Background: Early appearance of serotonin in the fetal brain and its effects on brain morphogenesis support its neurotrophic role. Objective: To determine the presence of serotonergic cells and the expression of tryptophan-5-hydroxylase (TPH), 5-hydroxytryptamine (5-HT), serotonin transporter (SERT), 5-HT1A receptor and Pet-1 during the development of the cerebral cortex, both in situ and in tissue cultures. Material and methods: A descriptive, observational study was carried out in pregnant Wistar rats. The presence of the plug was regarded as the beginning of gestation. On days 13, 16 and 17, cesarean sections were performed to obtain the fetuses, and the brains were then immediately dissected to identify the presence of serotonergic cells, TPH, 5-HT, SERT, 5-HT1A and Pet-1 in tissue cultures and in situ by immunostaining detected on a confocal microscope. Results: Serotonergic cells and terminals were observed in the midbrain on day 17 of gestation, and in neopallium cocultures on days 13 and 16. TPH, 5-HT, SERT and Pet-1 immunopositive cells were also observed in the neopallium on day 12 of culture. Conclusions: The presence of serotonergic cells and other elements of the serotonergic system in the early cerebral cortex was confirmed, which may be transient and participate in cortical maturation processes during brain development.

Performance of 3 frailty scales for predicting adverse outcomes at 30 days in older patients discharged from emergency departments. / Rendimiento de tres escalas de fragilidad para predecir resultados adversos a 30 días en los pacientes mayores dados de alta en los servicios de urgencias.

OBJECTIVES: To compare the ability of 3 frailty scales (the Clinical Frailty Scale [CFS], the Functional Index - eMergency [FIM], and the Identification of Seniors at Risk [ISAR] scale) to predict adverse outcomes at 30 days in older patients discharged from hospital emergency departments (EDs). MATERIAL AND METHODS: Secondary analysis of data from the FRAIL-Madrid registry of patients aged 75 years or older who were discharged from Madrid EDs over a period of 3 months in 2018 and 2019. Frailty was defined by a CFS score over 4, a FIM score over 2, or an ISAR score over 3. The outcome variables were revisits to an ED, hospitalization, functional decline, death, and a composite variable of finding any of the previously named variables within 30 days of discharge. RESULTS: A total of 619 patients were studied. The mean (SD) age was 84 (7) years, and 59.1% were women. The CFS identified as frail a total of 339 patients (54.8%), the FIM 386 (62.4%), and the ISAR 301 (48.6%). An adverse outcome occurred within 30 days in 226 patients (36.5%): 21.5% revisited, 12.6% were hospitalized, 18.4% experienced functional decline, and 3.6% died. The areas under the receiver operating characteristic curves were as follows: CFS, 0.66 (95% CI, 0.62-0.70; P = .022); FIM, 0.67 (95% CI, 0.62-0.71; P = .021), and ISAR, 0.64 (95% CI, 0.60-0.69; P = .023). Adjusted odds ratios (aOR) showed that frailty was an independent risk factor for presenting any of the named adverse outcomes: aOR for CFS >4, 3.18 (95% CI, 2.02-5.01), P .001; aOR for FIM > 2, 3.49 (95% CI, 2.15-5.66), P .001; and aOR for ISAR >3, 2.46 (95% CI, 1.60-3.79), P .001. CONCLUSION: All 3 scales studied - the CFS, the FIM and the ISAR - are useful for identifying frail older patients at high risk of developing an adverse outcome (death, functional decline, hospitalization, or revisiting the ED) within 30 days after discharge.

OBJETIVO: Comparar la capacidad de tres escalas de fragilidad, Clinical Frailty Scale (CFS), Functional Index ­ eMergency (FIM) e Identification Senior at Risk (ISAR), para predecir resultados adversos (RA) a 30 días en los pacientes mayores dados de alta desde el servicio de urgencias hospitalario (SUH). METODO: Análisis secundario del registro FRAIL-Madrid que incluyó pacientes 75 años dados de alta de 10 SUH de Madrid durante un periodo de 3 meses entre 2018 y 2019. Se definió fragilidad como CFS 4, FIM 2 e ISAR 3. Las variables de resultado fueron revisita en urgencias, hospitalización, deterioro funcional, muerte y la variable compuesta por algún RA de los anteriores en los 30 días posteriores al alta del SUH. RESULTADOS: Se incluyeron 619 pacientes, la edad media fue de 84 años (DE 7), 59,1% eran mujeres. Hubo 339 pacientes (54,8%) identificados como frágiles en el SUH según CFS 4, 386 (62,4%) según FIM 2 y 301 (48,6%) según ISAR 3. Hubo 226 pacientes (36,5%) que presentaron algún RA a los 30 días tras el alta (21,5% revisita, 12,6% hospitalización,18,4% deterioro funcional y 3,6% muerte). El área bajo la curva (ABC) de la escala CFS fue de 0,66 (0,62-0,70; p = 0,022), de FIM 0,67 (0,62-0,71; p = 0,021) y de ISAR 0,64 (0,60-0,69; p = 0,023). La presencia de fragilidad fue un factor independiente de presentar algún RA a los 30 días tras el alta (CFS 4 ORa 3,18 [IC 95% 2,02-5,01, p 0,001], FIM 2 ORa 3,49 [IC 95% 2,15-5,66, p 0,001] e ISAR 3 ORa 2,46 [IC 95% 1,60-3,79, p 0,001]). CONCLUSIONES: Las tres escalas estudiadas ­CFS, FIM, ISAR­ son útiles y tienen una capacidad similar para identificar al paciente mayor frágil dado de alta del SUH con alto riesgo de presentar RA (muerte, deterioro funcional, hospitalización o revisita al SUH) a los 30 días.

Rendimiento de tres escalas de fragilidad para predecir resultados adversos a 30 días en los pacientes mayores dados de alta en los servicios de urgencias / Performance of 3 frailty scales for predicting adverse outcomes at 30 days in older patients discharged from emergency departments

Objetivo: Comparar la capacidad de tres escalas de fragilidad, Clinical Frailty Scale (CFS), Functional Index eMergency (FIM) e Identification Senior at Risk (ISAR), para predecir resultados adversos (RA) a 30 días en los pacientes mayores dados de alta desde el servicio de urgencias hospitalario (SUH). Método: Análisis secundario del registro FRAIL-Madrid que incluyó pacientes $ 75 años dados de alta de 10 SUH de Madrid durante un periodo de 3 meses entre 2018 y 2019. Se definió fragilidad como CFS $ 4, FIM $ 2 e ISAR $ 3. Las variables de resultado fueron revisita en urgencias, hospitalización, deterioro funcional, muerte y la variable compuesta por algún RA de los anteriores en los 30 días posteriores al alta del SUH. Resultados: Se incluyeron 619 pacientes, la edad media fue de 84 años (DE 7), 59,1% eran mujeres. Hubo 339 pacientes (54,8%) identificados como frágiles en el SUH según CFS $ 4, 386 (62,4%) según FIM $ 2 y 301 (48,6%) según ISAR $ 3. Hubo 226 pacientes (36,5%) que presentaron algún RA a los 30 días tras el alta (21,5% revisita, 12,6% hospitalización, 18,4% deterioro funcional y 3,6% muerte). El área bajo la curva (ABC) de la escala CFS fue de 0,66 (0,62-0,70; p = 0,022), de FIM 0,67 (0,62-0,71; p = 0,021) y de ISAR 0,64 (0,60-0,69; p = 0,023). La presencia de fragilidad fue un factor independiente de presentar algún RA a los 30 días tras el alta (CFS $ 4 ORa 3,18 [IC 95% 2,02-5,01, p < 0,001], FIM $ 2 ORa 3,49 [IC 95% 2,15-5,66, p < 0,001] e ISAR $ 3 ORa 2,46 [IC 95% 1,60-3,79, p < 0,001]). Conclusiones: Las tres escalas estudiadas –CFS, FIM, ISAR– son útiles y tienen una capacidad similar para identificar al paciente mayor frágil dado de alta del SUH con alto riesgo de presentar RA (muerte, deterioro funcional, hospitalización o revisita al SUH) a los 30 días. (AU)

Objective: To compare the ability of 3 frailty scales (the Clinical Frailty Scale [CFS], the Functional Index – eMergency [FIM], and the Identification of Seniors at Risk [ISAR] scale) to predict adverse outcomes at 30 days in older patients discharged from hospital emergency departments (EDs). Methods: Secondary analysis of data from the FRAIL-Madrid registry of patients aged 75 years or older who were discharged from Madrid EDs over a period of 3 months in 2018 and 2019. Frailty was defined by a CFS score over 4, a FIM score over 2, or an ISAR score over 3. The outcome variables were revisits to an ED, hospitalization, functionaldecline, death, and a composite variable of finding any of the previously named variables within 30 days of discharge. Results: A total of 619 patients were studied. The mean (SD) age was 84 (7) years, and 59.1% were women. The CFS identified as frail a total of 339 patients (54.8%), the FIM 386 (62.4%), and the ISAR 301 (48.6%). An adverse outcome occurred within 30 days in 226 patients (36.5%): 21.5% revisited, 12.6% were hospitalized, 18.4% experienced functional decline, and 3.6% died. The areas under the receiver operating characteristic curves were as follows: CFS, 0.66 (95% CI, 0.62-0.70; P = .022); FIM, 0.67 (95% CI, 0.62-0.71; P = .021), and ISAR, 0.64 (95% CI, 0.60-0.69; P = .023). Adjusted odds ratios (aOR) showed that frailty was an independent risk factor for presenting anyof the named adverse outcomes: aOR for CFS >4, 3.18 (95% CI, 2.02-5.01), P < .001; aOR for FIM > 2, 3.49 (95% CI, 2.15-5.66), P < .001; and aOR for ISAR >3, 2.46 (95% CI, 1.60-3.79), P < .001. Conclusions: All 3 scales studied — the CFS, the FIM and the ISAR — are useful for identifying frail older patients at high risk of developing an adverse outcome (death, functional decline, hospitalization, or revisiting the ED) within 30 days after discharge. (AU)

Conocimientos de lactancia materna en embarazadas antes y después de una intervención educativa / Knowledge of breastfeeding in pregnant women before and after an educational intervention

Introducción: la lactancia materna es el mejor alimento para el recién nacido y hasta los 6 meses de edad, proporciona nutrientes y anticuerpos para el correcto desarrollo, por lo que se debe dar educación sobre lactancia materna a la mujer desde el embarazo para que pueda llevar a cabo adecuadamente este proceso. Objetivo: evaluar el nivel de conocimiento de lactancia materna en embarazadas antes y después de una intervención educativa. Material y métodos: estudio cuasiexperimental, longitudinal, en 150 embarazadas primigestas y multigestas mayores de 18 años. Se aplicó el instrumento validado en 2019 por Palomino et al. denominado Conocimientos sobre lactancia materna, con un coeficiente alfa de Cronbach de 0.7058. Posteriormente se realizó una intervención educativa y se les pidió que contestaran nuevamente el cuestionario. Se analizaron los datos con estadística descriptiva y medidas de tendencia central, así como proporciones, para evaluar las medianas de nivel de conocimiento antes y después de la intervención educativa se utilizó la prueba estadística Wilcoxon. Resultados: el promedio de edad fue 27.06 + 5.956 años. La escolaridad fue preparatoria 42.7%, en unión libre 48.7%, amas de casa 45.3%, el nivel de conocimiento alto postintervención en concepto general fue de 98.7%, respecto a posición y técnica 96.7% y para beneficios 96%. Con la prueba de Wilcoxon para conocimiento general se reportó z = -10.598, p = 0.000. Conclusiones: existe diferencia estadísticamente significativa entre la mediana de conocimiento al inicio y al final del estudio, con un 95% de confianza.

Introduction: Breastfeeding is the best food for the neonate and up to 6 months of age, it provides nutrients and antibodies for proper development, so the woman must be educated about breastfeeding from pregnancy so that she can properly carry out this process. Objective: To evaluate the level of breastfeeding knowledge in pregnant women before and after an educational intervention. Material and methods: Quasi experimental, longitudinal study in 150 primigravida and multigravida women between 20 and 35 years old. The validated instrument in 2019 by Palomino et al. called Breastfeeding Knowledge with a Cronbach's Alpha coefficient of 0.7058 was used. Educational intervention was given, and the questionnaire was reapplied. The data was analyzed with descriptive statistics and measures of central tendency and proportions. The Wilcoxon statistical test was used to evaluate the median levels of knowledge before and after the educational intervention. Results: The average age was 27.06 + 5.956 years. In total, 42.7% in High school, 48.7% in common law, 45.3% were housewives. The post-intervention high level of knowledge in general concept was 98.7%, respect position and technique 96.7% and for benefits 96%. Wilcoxon test for general knowledge reported z = -10.598 p = 0.000. Conclusions: There is a statistically significant difference between the median knowledge at baseline and at the end of the study with 95% confidence.

Reforma al Sistema de Salud Colombiano. Introducción / Reform of the Colombian Health System. Introduction

E n el año 2013, la Academia Nacional de Medicina convocó la Gran Junta Médica conformada, además de la Academia, por la Federación Médica Colombiana, el Colegio Médico Colombiano, la Asociación Colombiana de Sociedades Científicas (ACSC), ASMEDAS y la Asociación Nacional de Internos y Residentes (ANIR) y se hizo un análisis del Sistema General de Seguridad Social en Salud ­SGSSS- encontrando dificultades, inequidades y deficiencias que llevaron a la propuesta de una reforma al sistema de salud que se presentó al Congreso de la República por el entonces presidente Juan Manuel Santos y la Gran Junta Médica, y se promulgó como LEY ESTATUTARIA DE SALUD (LES) 1751 2015. La Academia, observando que a pesar de haber sido promulgada la LES ni se reglamentaba cabalmente ni se implementaba como era de esperarse, propuso al Ministerio de Salud y Protección Social la conformación de un comité conjunto, con participación de otras organizaciones del sector. Este comité propuso 89 recomendaciones para desarrollar la Ley Estatutaria aprobada en 2015. No obstante, la LES continuaba sin implementarse, y no se generaron cambios estructurales al sistema que se requerían para una reforma al sistema de salud en Colombia.

Audiencia Pública ­ Senado de la República Intervención del Dr. Gabriel Carrasquilla¹, Presidente de la Academia Nacional de Medicina, entidad vocera del grupo de Acuerdos Fundamentales / Public Hearing - Senate of the Republic Intervention by Dr. Gabriel Carrasquilla¹, President of the National Academy of Medicine, spokesperson of the Fundamental Agreements group

En el año 2013 la Academia Nacional de Medicina invitó a las más representativas organizaciones médicas del país a conformar lo que se denominó La Gran Junta Médica. Coordinada por la Academia Nacional (600 miembros en 9 capítulos y residentes fuera de Colombia) hicieron parte de ella la Asociación Colombiana de Sociedades Científicas (64 sociedades y 45.000 afiliados), el Colegio Médico Colombiano, ASMEDAS, Federación Médica Colombiana y la Asociación Nacional de Internos y Residentes (ANIR). El resultado de esta alianza fue la propuesta al gobierno nacional y al Congreso de una necesaria reforma al SGSSS que terminó siendo aprobada como Ley Estatutaria de Salud (LES) 1751 en el año 2015

Introducción / Introduction

Esta sección es de especial relevancia por ser la revista uno de los medios de comunicación institucional y porque a través de ella se presentan los conceptos y lineamientos éticos y de desarrollo de política pública que la Academia realiza. En este número se publican tres comunicados y un concepto ético realizados durante el segundo trimestre de 2023.

Viral delivery of a peptide-based immunomodulator enhances T cell priming during vaccination.

Modern, subunit-based vaccines have so far failed to induce significant T cell responses, contributing to ineffective vaccination against many pathogens. Importantly, while today's adjuvants are designed to trigger innate and non-specific immune responses, they fail to directly stimulate the adaptive immune compartment. Programmed cell death 1 (PD-1) partly regulates naïve-to-antigen-specific effector T cell transition and differentiation by suppressing the magnitude of activation. Indeed, we previously reported on a microbial-derived, peptide-based PD-1 checkpoint inhibitor, LD01, which showed potent T cell-stimulating activity when combined with a vaccine. Here we sought to improve the potency of LD01 by designing and testing new LD01 derivatives. Accordingly, we found that a modified version of an 18-amino acid metabolite of LD01, LD10da, improved T cell activation capability in a malaria vaccine model. Specifically, LD10da demonstrates improved antigen-specific CD8+ T cell expansion when combined prophylactically with an adenovirus-based malaria vaccine. A single dose of LD10da at the time of vaccination is sufficient to increase antigen-specific CD8+ T cell expansion in wild-type mice. Further, we show that LD10 can be encoded and delivered by a Modified Vaccinia Ankara viral vector and can enhance antigen-specific CD8+ T cell expansion comparable to that of synthetic peptide administration. Therefore, LD10da represents a promising biologic-based immunomodulator that can be genetically encoded and delivered, along with the antigen, by viral or other nucleic acid vectors to improve the efficacy and delivery of vaccines for ineradicable and emerging infectious diseases.

Triptófano-5-hidroxilasa, transportador de serotonina y receptores serotoninérgicos en miocardiopatía dilatada.

BACKGROUND: Cardiomyocytes synthesize, utilize and reuptake serotonin, which is involved in the paracrine and autocrine modulation of heart activity and in the pathophysiology of some cardiovascular diseases. OBJECTIVE: To determine the expression of tryptophan-5-hydroxylase (TPH) 1 and 2, serotonin transporter protein (SERT) and serotonergic receptors in hearts with dilated cardiomyopathy (DCM) compared to controls. METHOD: A comparative study was performed in six tissue blocks of the left ventricular free wall (LVWL) and inter-ventricular septum from patients who died of DCM and six who died of no cardiovascular diseases (controls). Five slices from each block were obtained to determine the expression of TPH1 and TPH2, SERT and serotonergic receptors with antibodies specific for immunofluorescence. Immunofluorescence was analyzed by Student's t-test, accepting a significance level of p < 0.05. RESULTS: An increase in TPH1, TPH2, 5-HT2A and 5-HT2B receptors expression were observed in dilated structures compared to controls (p < 0.05). For dilated inter-ventricular septum, the 5-HT4 receptor increased its expression (p < 0.05), and SERT in PLVI compared to controls (p < 0.05). CONCLUSIONS: These results suggest that the increases observed in the expression of TPH, SERT, and serotonergic receptors in hearts with DCM compared to controls could play an important role in the pathophysiology of MCD in humans.

ANTECEDENTES: Los cardiomiocitos sintetizan, utilizan y recapturan serotonina, la cual participa en la modulación parácrina y autócrina de la actividad del corazón y en la fisiopatología de algunas enfermedades cardiovasculares. OBJETIVO: Determinar la expresión de triptófano-5-hidroxilasa (TPH) 1 y 2, transportador de serotonina (SERT) y receptores serotoninérgicos en corazones con miocardiopatía dilatada (MCD) en comparación con controles. MÉTODO: Estudio comparativo en seis bloques de la pared libre del ventrículo izquierdo (PLVI) y del septum interventricular de pacientes fallecidos por MCD y seis que murieron por enfermedades no cardiovasculares. Se obtuvieron cinco cortes de cada bloque para determinar la expresión de TPH1 y TPH2, SERT y receptores serotoninérgicos con anticuerpos específicos por inmunofluorescencia. La inmunofluorescencia fue analizada por la t de Student, aceptando un nivel de significancia de p < 0.05. RESULTADOS: Se observó un aumento en la expresión de TPH1 y TPH2 y en los receptores 5-HT2A y 5-HT2B en las estructuras dilatadas en comparación con las controles (p < 0.05). El receptor 5-HT4 aumentó su expresión en el septum interventricular dilatado (p < 0.05) y el SERT en la PLVI en comparación con los controles (p < 0.05). CONCLUSIONES: Estos resultados sugieren que los aumentos observados en las expresiones de TPH, SERT y receptores serotoninérgicos en corazones con MCD en comparación con controles podrían desempeñar un papel importante en la fisiopatología de la MCD en los humanos.

La miocardiopatía hipertrófica induce cambios en la expresión de la triptófano-5-hidroxilasa, el transportador de serotonina y receptores serotoninérgicos / Hypertrophic cardiomyopathy induces changes in the tryptophan-5-hydroxylase, serotonin transporter and serotonergic receptors expressions

Resumen Introducción: Los cardiomiocitos poseen la maquinaria bioquímica capaz de sintetizar, utilizar y recapturar serotonina. Objetivo: Determinar si la miocardiopatía hipertrófica (MCH) induce cambios en la expresión de la triptófano-5-hidroxilasa (TPH) 1 y 2, el transportador de serotonina (SERT) y los receptores serotoninérgicos (RS). Métodos: Estudio transversal de cinco bloques de tejido de corazones con MCH y cinco bloques de corazones de control. Se obtuvieron cinco cortes de la pared libre del ventrículo izquierdo (PLVI) y del septum interventricular (SIV) de cada bloque, para determinar la expresión de TPH1 y TPH2, SERT y RS con anticuerpos por inmunofluorescencia. La inmunofluorescencia fue evaluada mediante t de WELCH, con nivel de significación de p < 0.05. Resultados: La PLVI y el SIV de los corazones con MCH mostraron aumento de la expresión de TPH1 y TPH2, así como de los receptores 5-HT2A y 5-HT2B en comparación con los controles (p < 0.01). El receptor 5-HT4 y SERT aumentaron en el SIV de los corazones con MCH (p < 0.01). Conclusiones: Se demostró aumento de las expresiones de TPH, SERT y RS en los cardiomiocitos de los corazones con MCH en comparación con los controles, lo cual podría participar en la fisiopatología de la MCH en los humanos.

Abstract Introduction: Cardiomyocytes have a biochemical machinery with the capacity to synthesize, utilize and reuptake serotonin. Objective: To determine whether hypertrophic cardiomyopathy (HCM) induces changes in the expression of tryptophan-5-hydroxylase (TPH) 1 and 2, serotonin transporter (SERT) and serotonergic receptors (SR). Methods: Cross-sectional study of five tissue blocks from hearts with HCM and five controls. Five sections of the left ventricular free wall (LVFW) and interventricular septum (IVS) were obtained from each block to determine the expression of TPH1 and TPH2, SERT and SRs by immunofluorescence with specific antibodies. Immunofluorescence was evaluated by WELCH t-test, with a level of significance of p < 0.05. Results: LVFW and IVS of hearts with HCM showed an increase in the expression of TPH1 and TPH 2 and 5-HT2A and 5-HT2B receptors in comparison with controls (p < 0.01). The 5-HT4 receptor and SERT showed an increase in the IVS of hearts with HCM (p < 0.01). Conclusions: This study demonstrated an increased expression of TPH, SERT and SRs in cardiomyocytes from hearts with HCM in comparison with controls, which could be involved in the pathophysiology of HCM in humans.

Calmodulin in Paramecium: Focus on Genomic Data.

Calcium (Ca2+) is a universal second messenger that plays a key role in cellular signaling. However, Ca2+ signals are transduced with the help of Ca2+-binding proteins, which serve as sensors, transducers, and elicitors. Among the collection of these Ca2+-binding proteins, calmodulin (CaM) emerged as the prototypical model in eukaryotic cells. This is a small protein that binds four Ca2+ ions and whose functions are multiple, controlling many essential aspects of cell physiology. CaM is universally distributed in eukaryotes, from multicellular organisms, such as human and land plants, to unicellular microorganisms, such as yeasts and ciliates. Here, we review most of the information gathered on CaM in Paramecium, a group of ciliates. We condense the information here by mentioning that mature Paramecium CaM is a 148 amino acid-long protein codified by a single gene, as in other eukaryotic microorganisms. In these ciliates, the protein is notoriously localized and regulates cilia function and can stimulate the activity of some enzymes. When Paramecium CaM is mutated, cells show flawed locomotion and/or exocytosis. We further widen this and additional information in the text, focusing on genomic data.

Diabetes mellitus causes changes in the activity and expression of brain tryptophan-5-hydroxylases and in the number of serotonergic neurons, which do not return to normal with insulin treatment.

INTRODUCTION: Diabetes mellitus (DM) inhibits brain serotonin biosynthesis through changes in tryptophan-5-hydroxylase (TPH) activity and expression. OBJECTIVES: To determine whether DM-induced changes in brain TPH1 or TPH2 expression and in the number of serotonergic neurons return to normal in diabetic rats treated with insulin. METHODS: Rats with streptozotocin-induced diabetes were divided in two groups: one treated with insulin and the other without treatment. On day 14, brain stems were obtained in order to quantify L-tryptophan and 5-hydroxytryptamine levels, as well as to determine TPH activity. The expression of TPH1 and TPH2 by West-ern blot, and the number of serotonergic neurons by immunohistochemistry. RESULTS: In diabetic rats, a decrease in the levels of L-tryptophan, 5-hydroxytryptamine, and TPH activity was confirmed, as well as lower TPH1 and TPH2 expression and lower numbers of serotonergic neurons. When diabetic rats were treated with insulin, L-tryptophan returned to normal, but not 5-hy-droxytryptamine, TPH expression, or the number of serotonergic neurons. CONCLUSIONS: DM chronically inhibits the synthesis of brain 5-hydroxytryptamine through changes in TPH1 and TPH2 expression and a decrease in the number of serotonergic neurons, which persist despite insulin treatment.

INTRODUCCIÓN: La diabetes mellitus (DM) inhibe la biosíntesis de serotonina cerebral mediante cambios en la actividad y expresión de la triptófano-5-hidroxilasa (TPH). OBJETIVOS: Determinar si los cambios en la expresión de TPH1 o TPH2 cerebral y en el número de neuronas serotoninérgicas causados por la DM retornan a la normalidad en las ratas con diabetes tratadas con insulina. MÉTODOS: Ratas con diabetes inducida con estreptozotocina se dividieron en dos grupos: uno tratado con insulina y otro sin tratamiento. En el día 14, se obtuvieron tallos cerebrales para cuantificar niveles de L-triptófano, 5-hidroxitriptamina y la actividad de la TPH. La expresión de TPH1 y TPH2 fue mediante Western blot y el número de neuronas serotoninérgicas por inmu­nohistoquímica. RESULTADOS: En las ratas con diabetes se confirmó disminución de los niveles de L-triptófano, 5-hidroxitriptamina y la actividad de la TPH, así como una menor expresión de TPH1 y 2 y un menor número de neuronas serotoninérgicas. Cuando las ratas diabéticas fueron tratadas con insulina, el L-triptófano regreso a la normalidad, no así la 5-hidroxitriptamina, la expresión de TPH y el número de neuronas serotoninérgicas. CONCLUSIONES: La DM inhibe crónicamente la síntesis de 5-hidroxitriptamina cerebral mediante modificaciones en la expresión de TPH1 y TPH2 y disminución de las neuronas seroto­ninérgicas, que persisten a pesar del tratamiento con insulina.

Clinical presentation and outcomes of hospitalized children with COVID-19 in Mexico City.

We describe the demographic, clinical, radiological, and laboratory findings relating them also to the severity and clinical outcome of 129 children (0-18 years) who were admitted to a tertiary care pediatric hospital in Mexico City due to severe acute respiratory syndrome coronavirus 2 infection between April 1, 2020 and March 31, 2021. The infection was confirmed using reverse transcription-polymerase chain reaction Fever (82.2%), tachypnea (72.1%), and cough (71.3%) were the most reported signs at the moment of hospitalization. The most frequent radiological pattern that stood out was the interstitial pattern (66.7%). History of oncologic pathology (25.6%) was the most frequent past medical history. Non-steroidal anti-inflammatory drugs (93%), antibiotics (57.4%), and steroids (40.3%) were the most common medication given. The average hospitalization stay was 14.2 days, and 21.7% of the total patients required transfer to the intensive care unit. At discharge, 20.2% required oxygen on an outpatient basis, and unfortunately, 7.0% of the patients who were admitted to the institute for COVID-19 died. Our findings confirm that COVID-19 in children has a mild presentation except for patients with hematologic/oncologic comorbidities who had severe presentations.

Transcriptional Regulation by the Velvet Protein VE-1 during Asexual Development in the Fungus Neurospora crassa.

Asexual reproduction in fungi facilitates the dispersal and colonization of new substrates and, in pathogenic fungi, allows infection of plants and animals. The velvet complex is a fungus-specific protein complex that participates in the regulation of gene expression in response to environmental signals like light, as well as developmental processes, pathogenesis, and secondary metabolism. The velvet complex in the fungus Neurospora crassa is composed of three proteins, VE-1, VE-2, and LAE-1. Mutations in ve-1 or ve-2, but not in lae-1, led to shorter heights of aerial tissue, a mixture of aerial hyphae and developing macroconidia, and increased microconidiation when they were combined with mutations in the transcription factor gene fl. VE-2 and LAE-1 were detected during vegetative growth and conidiation, unlike VE-1, which was mostly observed in samples obtained from submerged vegetative hyphae. We propose that VE-1 is the limiting component of the velvet complex during conidiation and has a major role in the transcriptional regulation of conidiation. Characterization of the role of VE-1 during mycelial growth and asexual development (conidiation) by transcriptome sequencing (RNA-seq) experiments allowed the identification of a set of genes regulated by VE-1 that participate in the regulation of conidiation, most notably the transcription factor genes vib-1 and fl. We propose that VE-1 and VE-2 regulate the development of aerial tissue and the balance between macro- and microconidiation in coordination with FL and VIB-1. IMPORTANCE Most fungi disperse in nature and infect new hosts by producing vegetative spores or conidia during asexual development. This is a process that is regulated by environmental signals like light and the availability of nutrients. A protein complex, the velvet complex, participates in the integration of environmental signals to regulate conidiation. We have found that a key component of this complex in the fungus Neurospora crassa, VE-1, has a major role in the regulation of transcription during conidiation. VE-1 regulates a large number of genes, including the genes for the transcription factors FL and VIB-1. Our results will help to understand how environmental signals are integrated in the fungal cell to regulate development.

Cambios en la actividad y expresión de las triptófano-5-hidroxilasas cerebrales y en el número de neuronas serotoninérgicas por la diabetes mellitus, que no retornan a la normalidad con la insulina / Diabetes mellitus causes changes in brain tryptophan-5-hydroxylases activity and expression and in the number of serotonergic neurons, which do not return to normal with insulin treatment

Resumen Introducción: La diabetes mellitus (DM) inhibe la biosíntesis de serotonina cerebral mediante cambios en la actividad y expresión de triptófano-5-hidroxilasa (TPH). Objetivos: Determinar si los cambios en la expresión de TPH1 y TPH2 cerebral y en el número de neuronas serotoninérgicas causados por la DM retornan a la normalidad en ratas con diabetes tratadas con insulina. Métodos: Ratas con diabetes inducida con estreptozotocina se dividieron en dos grupos uno tratado con insulina y otro sin tratamiento. En el día 14, se obtuvieron tallos cerebrales para cuantificar niveles de L-triptófano, 5-hidroxitriptamina y la actividad de la TPH. La expresión de TPH1 y TPH2 fue mediante Western blot y el número de neuronas serotoninérgicas por inmunohistoquímica. Resultados: En las ratas con diabetes se confirmó disminución de los niveles de L-triptófano, 5-hidroxitriptamina y la actividad de la TPH, así como menor expresión de TPH1 y TPH2 y menor número de neuronas serotoninérgicas. Cuando las ratas diabéticas fueron tratadas con insulina, el L-triptófano regresó a la normalidad, no así la 5-hidroxitriptamina, la expresión de TPH ni el número de neuronas serotoninérgicas. Conclusiones: La DM inhibe crónicamente la síntesis de 5-hidroxitriptamina cerebral mediante modificaciones en la expresión de TPH1 y TPH2 y disminución de las neuronas serotoninérgicas, que persisten a pesar del tratamiento con insulina.

Abstract Introduction: Diabetes mellitus (DM) inhibits brain serotonin biosynthesis through changes in tryptophan-5-hydroxylase (TPH) activity and expression. Objectives: To determine whether DM-induced changes in brain TPH1 and TPH2 expression and in the number of serotonergic neurons return to normal in diabetic rats treated with insulin. Methods: Rats with streptozotocin-induced diabetes were divided in two groups: one treated with insulin and the other without treatment. On day 14, brain stems were obtained in order to quantify L-tryptophan and 5-hydroxytryptamine levels, as well as to determine TPH activity. The expressión of TPH1 and THP2 by Western blot, and the number of serotonergic neurons by immunohistochemistry. Results: In diabetic rats, a decrease in the levels of L-tryptophan, 5-hydroxytryptamine and TPH activity was confirmed, as well as lower TPH1 and TPH2 expression and lower numbers of serotonergic neurons. When diabetic rats were treated with insulin, L-tryptophan returned to normal, but not 5-hydroxytryptamine, TPH expression, or the number of serotonergic neurons. Conclusions: DM chronically inhibits the synthesis of brain 5-hydroxytryptamine through changes in TPH1 and TPH2 expression and a decrease in the number of serotonergic neurons, which persist despite insulin treatment.