Characterization of Two Highly Specific Monoclonal Antibodies Targeting the Glycan Loop of the Zika Virus Envelope Protein.

Zika virus (ZIKV) is an emerging flavivirus associated with several neurological diseases such as Guillain-Barré syndrome in adults and microcephaly in newborn children. Its distribution and mode of transmission (via Aedes aegypti and Aedes albopictus mosquitoes) collectively cause ZIKV to be a serious concern for global health. High genetic homology of flaviviruses and shared ecology is a hurdle for accurate detection. Distinguishing infections caused by different viruses based on serological recognition can be misleading as many anti-flavivirus monoclonal antibodies (mAbs) discovered to date are highly cross-reactive, especially those against the envelope (E) protein. To provide more specific research tools, we produced ZIKV E directed hybridoma cell lines and characterized two highly ZIKV-specific mAb clones (mAbs A11 and A42) against several members of the Flavivirus genus. Epitope mapping of mAb A11 revealed glycan loop specificity in Domain I of the ZIKV E protein. The development of two highly specific mAbs targeting the surface fusion protein of ZIKV presents a significant advancement in research capabilities as these can be employed as essential tools to enhance our understanding of ZIKV identification on infected cells ex vivo or in culture.

Ventilator-associated pneumonia by Weeksella virosa: case report.

BACKGROUND: Weeksella virosa pneumonia is an infection that has been described as a healthcare-associated infection. This is a rare gram-negative anaerobic bacterium associated with the use of mechanical ventilation for a long period of time and is more frequent in immunosuppressed patients. This is the first case reported in the state of Veracruz and the second in Mexico. CASE PRESENTATION: We present the case of a 64-year-old female from Veracruz, Mexico who developed an infectious process in the right pelvic limb after a transcatheter aortic valve replacement procedure and subsequently developed sudden cardiorespiratory arrest requiring mechanical ventilation, with subsequent imaging studies demonstrating a pneumonic process associated with a nosocomial infection. DISCUSSION AND CONCLUSIONS: We should take into consideration that this pathogen affects not only adults with multiple comorbidities but also children with renal, hepatic, or oncological pathologies, as well as immunocompromised patients, who should be considered high-risk populations for W. virosa infection.

Oral cancer over six decades: a multivariable analysis of a clinicopathologic retrospective study.

Studies have reported changes in the epidemiological profile of patients with oral cancer in recent decades, especially regarding gender and age. This study aimed to evaluate a historical series of oral malignant lesions prevalence over six decades and define characteristics associated with the occurrence, mainly, of oral squamous cell carcinoma (OSCC). A retrospective review of histopathological records from 1953 to 2019 was conducted in three oral pathology laboratories in South Brazil about age, sex, anatomical site, clinical aspect, and histopathological diagnosis. Descriptive and analytical analyses were performed comparing the histopathological diagnoses with other variables. Multivariable logistic regression was applied to determine the associated predictors of OSCC. Of the 53,065 records available in the institutions, 986 were oral malignant tumors (including all malignant neoplasms), representing 1.86% of all diagnoses. The occurrence of OSCC in the 1960's was 80.0%, decreasing over time reaching the lowest percentage of cases in the 1990's (75.8%) and significantly increasing to 88.7% in the 2010s. Females had a lower chance than males of having OSCC independently of the decade (odds ratio=0.30, p<0.001). This was the same for older individuals compared to those younger than 40 years. No interactions between sex, age, and decade were observed. The number of diagnoses of oral malignant lesions increased over time, and the occurrence of OSCC varied. Older individuals and males had higher chances of having OSCC independently of the decade. Therefore, in this study sample, no changes were observed in the epidemiological profile over the years concerning these predictors.

Oral cancer over six decades: a multivariable analysis of a clinicopathologic retrospective study

Abstract Studies have reported changes in the epidemiological profile of patients with oral cancer in recent decades, especially regarding gender and age. This study aimed to evaluate a historical series of oral malignant lesions prevalence over six decades and define characteristics associated with the occurrence, mainly, of oral squamous cell carcinoma (OSCC). A retrospective review of histopathological records from 1953 to 2019 was conducted in three oral pathology laboratories in South Brazil about age, sex, anatomical site, clinical aspect, and histopathological diagnosis. Descriptive and analytical analyses were performed comparing the histopathological diagnoses with other variables. Multivariable logistic regression was applied to determine the associated predictors of OSCC. Of the 53,065 records available in the institutions, 986 were oral malignant tumors (including all malignant neoplasms), representing 1.86% of all diagnoses. The occurrence of OSCC in the 1960's was 80.0%, decreasing over time reaching the lowest percentage of cases in the 1990's (75.8%) and significantly increasing to 88.7% in the 2010s. Females had a lower chance than males of having OSCC independently of the decade (odds ratio=0.30, p<0.001). This was the same for older individuals compared to those younger than 40 years. No interactions between sex, age, and decade were observed. The number of diagnoses of oral malignant lesions increased over time, and the occurrence of OSCC varied. Older individuals and males had higher chances of having OSCC independently of the decade. Therefore, in this study sample, no changes were observed in the epidemiological profile over the years concerning these predictors.

Resumo Alguns estudos relataram mudanças no perfil epidemiológico dos pacientes com câncer bucal nas últimas décadas, principalmente quanto ao gênero e a idade. Este estudo teve como objetivo avaliar, em uma série histórica, a prevalência de todas as lesões malignas bucais ao longo de seis décadas e definir características associadas na ocorrência, principalmente, de carcinoma espinocelular (CEC). Um levantamento retrospectivo dos registros histopatológicos de 1953 a 2019 foi realizado em três laboratórios de Patologia Bucal no Sul do Brasil em relação à idade, gênero, sítio anatômico, aspecto clínico e diagnóstico histopatológico. Análises descritivas e analíticas foram realizadas comparando-se os diagnósticos histopatológicos com as outras variáveis. A regressão logística multivariada foi aplicada para determinar os possíveis preditores associados ao CEC. Dos 53.065 prontuários disponíveis nas instituições, 986 eram tumores malignos bucais (incluindo todas as neoplasias malignas), representando 1,86% de todos os diagnósticos. A ocorrência de CEC na década de 1960 foi de 80,0%, diminuindo ao longo do tempo, atingindo o menor percentual de casos na década de 1990 (75,8%) e aumentando significativamente para 88,7% na década de 2010. As mulheres tiveram menor risco de desenvolver CEC do que os homens, independentemente da década (OR=0,30, p<0,001). Este foi o mesmo para indivíduos com idade mais avançada em comparação com aqueles com menos de 40 anos de idade. Não foram observadas interações entre gênero, idade e década. O número de diagnósticos de lesões malignas bucais aumentou ao longo das décadas e a ocorrência de CEC variou. Indivíduos com mais de 40 anos e do sexo masculino tiveram maiores chances de ter CEC, independentemente da década analisada. Portanto, nessa amostra estudada, não foram observadas mudanças no perfil epidemiológico ao longo dos anos com relação a esses preditores.

Single-step rapid chromatographic purification and characterization of clinical stage oncolytic VSV-GP.

Purification of viruses, especially for therapeutic purposes, is a tedious and challenging task. The challenges arise due to the size and surface complexity of the virus particles. VSV-GP is a promising oncolytic virus, which has been approved for phase I clinical trials by the Food and Drug Administration (FDA) of United States and Paul Ehrlich Institute (PEI) of Germany. The virus particles of VSV-GP are larger in size than vectors commonly used for gene therapy (e.g., adenovirus, adeno-associated virus, etc.). The current established proprietary clinical-grade manufacturing process for the purification of VSV-GP encompasses several chromatographic and non-chromatographic steps. In this study, we describe a new single-step purification process for the purification of VSV-GP virus, using cation exchange convective flow column with relatively higher yields. The purified virus was characterized for its quality attributes using TCID50 assay (for viral infectivity), host cell protein contaminant ELISA, SDS-PAGE, size exclusion chromatography (SEC), and cryo-electron microscopy. Furthermore, the purified viral therapeutic material was tested in vivo for its efficacy and safety. All these characterization methods demonstrated a therapeutic virus preparation of high purity and yield, which can be readily used for various studies.

Manejo de la insuficiencia cardiaca con estimulación hisiana en bloqueo de rama derecha: reporte de caso / Management of heart failure with His bundle pacing in right bundle branch block: case report

Resumen La terapia de resincronización cardiaca mediante estimulación hisiana ha demostrado ser efectiva en pacientes con bloqueo de rama izquierda del haz de His e insuficiencia cardiaca. Paciente masculino, con 47 años de edad, con insuficiencia cardiaca, fracción de expulsión del 17% y miocardio dilatada idiopática, electrocardiograma en ritmo sinusal, bloqueo auriculoventricular de 1.er grado, intervalo PR 400 ms, bloqueo completo de rama derecha del haz de His, bloqueo del fascículo anterior de la rama izquierda del haz de His, duración del QRS 200 ms. Se decidió realizar estimulación selectiva del haz de His. La resincronización cardiaca biventricular convencional en pacientes con presencia de bloqueo completo de la rama derecha del haz de His no está indicada debido a la pobre respuesta al tratamiento. La estimulación hisiana permite reclutar la rama bloqueada y reestablecer la conducción a través de ella, de tal forma que, en ausencia de necrosis, se logre sincronía biventricular. En el caso presentado el reclutamiento de la rama derecha mediante estimulación hisiana se reflejó en el restablecimiento de la sincronía biventricular, medida por rastreo de marcas (speckle tracking) e incremento significativo de la fracción de expulsión del ventrículo izquierdo del 17 al 36.6%, con un incremento absoluto del 19.6%.

Abstract Cardiac resynchronization therapy has proven to be an effective therapy in patients with left bundle branch block and heart failure. Male, 47 years old, heart failure with a left ventricle ejection fraction of 17%, idiopathic heart failure. ECG with sinus rhythm, 1st degree AV block, PR 400 ms, complete right bundle branch block, anterior hemi-fascicle of the left bundle of His, and QRS duration 200 ms. We decided to perform a selective His bundle pacing. In patients with right bundle branch block the biventricular cardiac resynchronization is not indicated due to low treatment response. His bundle pacing allows recruiting the blocked branch and restoring conduction throughout it, therefore, in the absence of necrosis the biventricular synchrony is achieved. We presented a case of His bundle pacing with recruitment of the right bundle branch, which reestablish biventricular synchrony measured by speckle tracking, and with a significant increase of the left ventricle ejection fraction from 17 to 36.6%, with an absolute increase of 19.6%.

The inflammatory kinase IKKα phosphorylates and stabilizes c-Myc and enhances its activity.

BACKGROUND: The IκB kinase (IKK) complex, comprising the two enzymes IKKα and IKKß, is the main activator of the inflammatory transcription factor NF-κB, which is constitutively active in many cancers. While several connections between NF-κB signaling and the oncogene c-Myc have been shown, functional links between the signaling molecules are still poorly studied. METHODS: Molecular interactions were shown by co-immunoprecipitation and FRET microscopy. Phosphorylation of c-Myc was shown by kinases assays and its activity by improved reporter gene systems. CRISPR/Cas9-mediated gene knockout and chemical inhibition were used to block IKK activity. The turnover of c-Myc variants was determined by degradation in presence of cycloheximide and by optical pulse-chase experiments.. Immunofluorescence of mouse prostate tissue and bioinformatics of human datasets were applied to correlate IKKα- and c-Myc levels. Cell proliferation was assessed by EdU incorporation and apoptosis by flow cytometry. RESULTS: We show that IKKα and IKKß bind to c-Myc and phosphorylate it at serines 67/71 within a sequence that is highly conserved. Knockout of IKKα decreased c-Myc-activity and increased its T58-phosphorylation, the target site for GSK3ß, triggering polyubiquitination and degradation. c-Myc-mutants mimicking IKK-mediated S67/S71-phosphorylation exhibited slower turnover, higher cell proliferation and lower apoptosis, while the opposite was observed for non-phosphorylatable A67/A71-mutants. A significant positive correlation of c-Myc and IKKα levels was noticed in the prostate epithelium of mice and in a variety of human cancers. CONCLUSIONS: Our data imply that IKKα phosphorylates c-Myc on serines-67/71, thereby stabilizing it, leading to increased transcriptional activity, higher proliferation and decreased apoptosis.

Prevalence of inadequate intake of vitamins and minerals in the Mexican population correcting by nutrient retention factors, Ensanut 2016.

OBJECTIVE: To estimate the usual intake and the prevalence of inadequacy of selected nutrients in the Mexican population and the potential effect that the nutrient retention factors (NRF) could have on these estimates. Likewise, document the methodology used in the analysis of the 24 hours of the mid-way National Health and Nutrition Survey 2016 (Ensanut MC 2016). MATERIALS AND METHODS: Dietary information from the Ensanut MC 2016 was analyzed with and without the use of NRFs. RESULTS: Results. Most nutrients evaluated showed a relevant inadequacy prevalence above 10% in all age groups. Likewise, we documented that, when NRFs were not applied, estimated intakes and prevalence were significantly under-estimated in a range of 2% to 55.5%. CONCLUSIONS: We documented the relevance of the application of NRFs for adequate estimation of the prevalence of inadequate intake of selected nutrients in population studies.

OBJETIVO: Estimar la ingesta habitual y la prevalencia de inadecuación de nutrimentos selectos en la población mexicana y el efecto potencial de los factores de retención de nutrimentos (FRN). Asimismo, describir la metodología utilizada en el procesamiento del recordatorio de 24 horas de la Encuesta Nacional de Salud y Nutrición de Medio Camino 2016 (Ensanut MC 2016). MATERIAL Y MÉTODOS: Se analizó la información dietética de Ensanut MC 2016 con y sin utilización de FRN. RESULTADOS: En los nutrimentos evaluados, las prevalencias de inadecuación fueron superiores al 10% en todos los grupos de estudio. La no consideración de los FRN causó la subestimación en las prevalencias de inadecuación en un rango de 2% a 55.5%. CONCLUSIONES: . Se documenta la relevancia de la aplicación de FRN para la adecuada estimación de las prevalencias de inadecuación en estudios poblacionales.

Prevalence of inadequate intake of vitamins and minerals in the Mexican population correcting by nutrient retention factors, Ensanut 2016 / Prevalencia de consumo inadecuado de vitaminas y minerales en población mexicana, corrigiendo por factores de retención de nutrimentos, Ensanut 2016

Abstract Objective: To estimate the usual intake and the prevalence of inadequacy of selected nutrients in the Mexican population and the potential effect that the nutrient retention factors (NRF) could have on these estimates. Likewise, document the methodology used in the analysis of the 24 hours of the mid-way National Health and Nutrition Survey 2016 (Ensanut MC 2016). Materials and methods: Dietary information from the Ensanut MC 2016 was analyzed with and without the use of NRFs. Results: Most nutrients evaluated showed a relevant inadequacy prevalence above 10% in all age groups. Likewise, we documented that, when NRFs were not applied, estimated intakes and prevalence were significantly underestimated in a range of 2% to 55.5%. Conclusions: We documented the relevance of the application of NRFs for adequate estimation of the prevalence of inadequate intake of selected nutrients in population studies.

Resumen Objetivo: Estimar la ingesta habitual y la prevalencia de inadecuación de nutrimentos selectos en la población mexicana y el efecto potencial de los factores de retención de nutrimentos (FRN). Asimismo, describir la metodología utilizada en el procesamiento del recordatorio de 24 horas de la Encuesta Nacional de Salud y Nutrición de Medio Camino 2016 (Ensanut MC 2016). Material y métodos: Se analizó la información dietética de Ensanut MC 2016 con y sin utilización de FRN. Resultados: En los nutrimentos evaluados, las prevalencias de inadecuación fueron superiores al 10% en todos los grupos de estudio. La no consideración de los FRN causó la subestimación en las prevalencias de inadecuación en un rango de 2% a 55.5%. Conclusión: Se documenta la relevancia de la aplicación de FRN para la adecuada estimación de las prevalencias de inadecuación en estudios poblacionales.

Pediatric patients' head-up-tilt-test with pharmacological challenge, it is safe?

Syncope in pediatrics represents an important cause of visits to the emergency units. For this reason, excluding a cardiac or malignant origin is essential at the time of the initial approach to determine what is the next step in management, or if they need to be referred to a pediatric cardiologist and/or electrophysiologist. Vasovagal syncope is the most frequent cause of syncope in pediatrics, in which a detailed clinical history is enough to make the diagnosis. If no diagnosis is concluded by the history, or if it is necessary to define the hemodynamic response of the patients, the head-up-tilt-test is indicated; this will trigger syncope due to an orthostatic stress caused by the angulated table (passive phase). If a negative response remains, it can be followed by a pharmacologic challenge to trigger the hemodynamic response, which is still controversial in pediatrics. The pharmacologic challenge increases the sensitivity with a slight reduction in test specificity. Although there is not a specific drug for the challenge in pediatric patients yet, the most commonly drugs used are nitrates and isoproterenol, the latter related to a great number of adverse effects. Sublingual administration of nitrates in the challenge has been proven to be ideal, effective, and safe in this specific age group. The aim of this article is to make a literature search to demonstrate the effectiveness and safety of the pharmacologic challenge during the head-up-tilt-test in pediatrics, emphasizing a study conducted at the National Institute of Cardiology with isosorbide dinitrate.

El síncope en edades pediátricas representa una causa importante en las visitas a unidades de urgencias, por lo que excluir un origen cardíaco o maligno es fundamental al momento del abordaje inicial para determinar la conducta a seguir o la necesidad de derivar al cardiólogo pediatra o electrofisiólogo. El síncope vasovagal (SVV) es la causa más frecuente de síncope en pediatría, para cuyo diagnóstico basta una historia clínica detallada. Cuando ésta no es suficiente para determinar el diagnóstico de síncope reflejo o es necesario definir el tipo de respuesta que lo origina, está indicada una prueba de mesa inclinada que produce un estrés ortostático por la angulación y ello desencadena un síncope (fase pasiva). En pruebas no concluyentes está indicado un reto farmacológico para precipitar la respuesta hemodinámica, pero aún es un tema de controversia en edades pediátricas. El reto farmacológico incrementa la sensibilidad de la prueba, con una ligera reducción de la especificidad. Si bien no existe todavía un medicamento específico para la población pediátrica, los más empleados son los nitratos y el isoproterenol, este último relacionado con un mayor número de efectos adversos. La administración sublingual de los nitratos utilizados ha demostrado ser ideal, efectiva y segura en los pacientes pediátricos. El objetivo del artículo es realizar una revisión de las publicaciones médicas que demuestran la efectividad y seguridad del reto farmacológico durante la prueba de mesa inclinada en pacientes pediátricos, con énfasis en un estudio conducido en el Instituto Nacional de Cardiología con dinitrato de isosorbida (DNIS).

Pediatric patients head-up-tilt-test with pharmacological challenge, it is safe? / Mesa inclinada en pacientes pediátricos con reto farmacológico, ¿es seguro?

Abstract Syncope in pediatrics represents an important cause of visits to the emergency units. For this reason, excluding a cardiac or malignant origin is essential at the time of the initial approach to determine what is the next step in management, or if they need to be referred to a pediatric cardiologist and/or electrophysiologist. Vasovagal syncope is the most frequent cause of syncope in pediatrics, in which a detailed clinical history is enough to make the diagnosis. If no diagnosis is concluded by the history, or if it is necessary to define the hemodynamic response of the patients, the head-up-tilt-test is indicated; this will trigger syncope due to an orthostatic stress caused by the angulated table (passive phase). If a negative response remains, it can be followed by a pharmacologic challenge to trigger the hemodynamic response, which is still controversial in pediatrics. The pharmacologic challenge increases the sensitivity with a slight reduction in test specificity. Although there is not a specific drug for the challenge in pediatric patients yet, the most commonly drugs used are nitrates and isoproterenol, the latter related to a great number of adverse effects. Sublingual administration of nitrates in the challenge has been proven to be ideal, effective, and safe in this specific age group. The aim of this article is to make a literature search to demonstrate the effectiveness and safety of the pharmacologic challenge during the head-up-tilt-test in pediatrics, emphasizing a study conducted at the National Institute of Cardiology with isosorbide dinitrate.

Resumen El síncope en edades pediátricas representa una causa importante en las visitas a unidades de urgencias, por lo que excluir un origen cardíaco o maligno es fundamental al momento del abordaje inicial para determinar la conducta a seguir o la necesidad de derivar al cardiólogo pediatra o electrofisiólogo. El síncope vasovagal (SVV) es la causa más frecuente de síncope en pediatría, para cuyo diagnóstico basta una historia clínica detallada. Cuando ésta no es suficiente para determinar el diagnóstico de síncope reflejo o es necesario definir el tipo de respuesta que lo origina, está indicada una prueba de mesa inclinada que produce un estrés ortostático por la angulación y ello desencadena un síncope (fase pasiva). En pruebas no concluyentes está indicado un reto farmacológico para precipitar la respuesta hemodinámica, pero aún es un tema de controversia en edades pediátricas. El reto farmacológico incrementa la sensibilidad de la prueba, con una ligera reducción de la especificidad. Si bien no existe todavía un medicamento específico para la población pediátrica, los más empleados son los nitratos y el isoproterenol, este último relacionado con un mayor número de efectos adversos. La administración sublingual de los nitratos utilizados ha demostrado ser ideal, efectiva y segura en los pacientes pediátricos. El objetivo del artículo es realizar una revisión de las publicaciones médicas que demuestran la efectividad y seguridad del reto farmacológico durante la prueba de mesa inclinada en pacientes pediátricos, con énfasis en un estudio conducido en el Instituto Nacional de Cardiología con dinitrato de isosorbida (DNIS).

Cardioinhibitory syncope: from pathophysiology to treatment-should we think on cardioneuroablation?

Vasovagal syncope (VVS) is the most common type of syncope; the lone cardioinhibitory syncope represents only a small group of patients; however, the "cardioinhibitory component" is highly prevalent in reflex syncope and can be severe enough to produce asystole, lasting for a few seconds followed by a recovery to sinus beats. The environment in which syncope occurs can compromise life, and in-depth knowledge of the disease can prevent deaths and guide the appropriate management. The therapeutic cornerstone is general measures (increase water and salt) followed by pharmacologic therapy; for cardioinhibitory syncope, both treatments fail most of the time, and the next therapeutic option is pacemaker implantation. However, although the pacemaker causes a reduction in syncope, recurrence is high, and a one-time, effective, and safe intervention would be ideal. Cardioneuroablation (CNA) therapy has been proposed as a pacemaker alternative with these characteristics. CNA has shown a high reduction or even complete syncope elimination during 3 years of follow-up in some studies. Patients also reported prolonged prodromal periods, which allowed them enough time to abort the syncope. Invasive therapies like CNA require further extensive cohort studies, randomized clinical trials, and more substantial follow-up to evaluate adverse side effects. This review highlights syncope pathophysiology, dividing it into a central theory and a peripheral theory, the diagnosis explaining the head-up tilt test protocols, and treatments like CAN, representing it with figures for a simplified understanding.

Pediatrics patients head-up tilt test with pharmacological challenge, it is safe?

Syncope in pediatrics represents an important cause of visits to the emergency units. For this reason, excluding a cardiac or malignant origin is essential at the time of the initial approach in order to determine what is the next step in management, or if they need to be referred to a pediatric cardiologist and/or electrophysiologist. Vasovagal syncope is the most frequent cause of syncope in pediatrics, in which a detailed clinical history is enough to make the diagnosis. If no diagnosis is concluded by the history, or if it is necessary to define the hemodynamic response of the patients, the head-up tilt test is indicated; this will trigger syncope due to an orthostatic stress caused by the angulated table (passive phase). If a negative response remains, it can be followed by a pharmacologic challenge in order to trigger the hemodynamic response, which is still controversial in pediatrics. The pharmacologic challenge increases the sensitivity with a slight reduction in test specificity. Although there is not a specific drug for the challenge in pediatric patients yet, the most commonly drugs used are nitrates and isoproterenol, the latter related to a great number of adverse effects. Sublingual administration of nitrates in the challenge has been proven to be ideal, effective and safe in this specific age group. The aim of this article is to make a literature search in order to demonstrate the effectiveness and safety of the pharmacologic challenge during the head-up tilt test in pediatrics, emphasizing a study conducted at the National Institute of Cardiology with isosorbide dinitrate.

El síncope en edades pediátricas representa una causa importante en las visitas a unidades de urgencias, por lo que excluir un origen cardíaco o maligno es fundamental al momento del abordaje inicial para determinar la conducta a seguir o la necesidad de derivar al cardiólogo pediatra o electrofisiólogo. El síncope vasovagal (SVV) es la causa más frecuente de síncope en pediatría, para cuyo diagnóstico basta una historia clínica detallada. Cuando ésta no es suficiente para determinar el diagnóstico de síncope reflejo o es necesario definir el tipo de respuesta que lo origina, está indicada una prueba de mesa inclinada que produce un estrés ortostático por la angulación y ello desencadena un síncope (fase pasiva). En pruebas no concluyentes está indicado un reto farmacológico para precipitar la respuesta hemodinámica, pero aún es un tema de controversia en edades pediátricas. El reto farmacológico incrementa la sensibilidad de la prueba, con una ligera reducción de la especificidad. Si bien no existe todavía un medicamento específico para la población pediátrica, los más empleados son los nitratos y el isoproterenol, este último relacionado con un mayor número de efectos adversos. La administración sublingual de los nitratos utilizados ha demostrado ser ideal, efectiva y segura en los pacientes pediátricos. El objetivo del artículo es realizar una revisión de las publicaciones médicas que demuestran la efectividad y seguridad del reto farmacológico durante la prueba de mesa inclinada en pacientes pediátricos, con énfasis en un estudio conducido en el Instituto Nacional de Cardiología con dinitrato de isosorbida (DNIS).

Importancia del control glucémico durante el perioperatorio en pacientes con diabetes mellitus / Importance of glycemic control during the perioperative period in patients with diabetes mellitus

Resumen: La diabetes mellitus se ha convertido en un problema de salud pública en el mundo, ya que su incidencia y prevalencia se ha incrementado de manera exponencial en las últimas décadas, lo que ha traído consigo un aumento en las complicaciones agudas y crónicas asociadas a su diagnóstico tardío y poco apego a su tratamiento. Los pacientes con diabetes mellitus tienen una mayor probabilidad de requerir una cirugía en comparación con la población general, quienes podrían llegar a presentar complicaciones graves asociadas al evento quirúrgico como hipertensión, cardiopatía isquémica, nefropatía y neuropatía autonómica, las cuales se deben a un incremento de la resistencia a la insulina y a la hiperglucemia. Por lo anterior, el control metabólico es pieza clave en la conducta perioperatoria del paciente con diabetes mellitus donde la participación de un equipo multidisciplinario (médico internista, cirujano y anestesiólogo) definan de manera conjunta las mejores estrategias quirúrgicas y anestésicas para un mejor desenlace previo, durante y posterior a la cirugía.

Abstract. Diabetes mellitus has become a public health problem worldwide, its incidence and prevalence have exponentially increased in recent decades, bringing with it an increase in acute and chronic complications associated with late diagnosis and failure of adherence to treatment. Patients with diabetes mellitus are more likely to require surgery compared to the general population, they may have serious complications associated with the surgical event such as hypertension, ischemic heart disease, nephropathy and autonomic neuropathy, due to an increase in insulin resistance and hyperglycemia. Therefore, metabolic control is a key element in the perioperative behavior of patients with diabetes mellitus where the joint collaboration of a multidisciplinary team (internist, surgeon and anesthesiologist) to define the best surgical and anesthetic strategies for a better outcome before, during and after surgery.

Targeting the C-terminus of galectin-9 induces mesothelioma apoptosis and M2 macrophage depletion.

Galectin-9 has emerged as a promising biological target for cancer immunotherapy due to its role as a regulator of macrophage and T-cell differentiation. In addition, its expression in tumor cells modulates tumor cell adhesion, metastasis, and apoptosis. Malignant mesothelioma (MM) is an aggressive neoplasm of the mesothelial cells lining the pleural and peritoneal cavities, and in this study, we found that both human MM tissues and mouse MM cells express high levels of galectin-9. Using a novel monoclonal antibody (mAb) (Clone P4D2) that binds the C-terminal carbohydrate recognition domain (CRD) of galectin-9, we demonstrate unique agonistic properties resulting in MM cell apoptosis. Furthermore, the P4D2 mAb reduced tumor-associated macrophages differentiation toward a protumor phenotype. Importantly, these effects exerted by the P4D2 mAb were observed in both human and mouse in vitro experiments and not observed with another antigalectin-9 specific mAb (clone P1D9) that engages the N-terminus CRD of galectin-9. In syngeneic murine models of MM, P4D2 mAb treatment inhibited tumor growth and improved survival, with tumors from P4D2-treated mice exhibited reduced infiltration of tumor-associated M2 macrophages. This was consistent with an increased production of inducible nitric oxide synthase, which is a major enzyme-regulating macrophage inflammatory response to cancer. These data suggest that using an antigalectin 9 mAb with agonistic properties similar to those exerted by galectin-9 may provide a novel multitargeted strategy for the treatment of mesothelioma and possibly other galectin-9 expressing tumors.

Platelet activation patterns in platelet size sub-populations: differential responses to aspirin in vitro.

Circulating platelets are heterogeneous in size and structure. Whether this translates into differences in platelet function and efficacy of antiplatelet therapy is unclear. Hence, we decided to investigate the activation patterns among different platelet populations differentiated by size, and to compare the inhibitory effects of aspirin in these populations. Circulating platelets from 9 healthy volunteers were separated by size and stratified into the largest and smallest quintiles. Platelets were stimulated with 75 µM arachidonic acid (AA), 10 µM ADP or 25 µM TRAP. Alpha-granule protein secretion and expression (P-selectin, VWF, fibrinogen), surface-protein activation (activated integrin αIIbß3) were assessed. Platelet thromboxane B(2) (TxB(2)) synthesis following AA stimulation was measured in vitro before and after incubation with 265 µM aspirin. Reticulated (juvenile) platelets were assessed using thiazole orange staining. A greater number of large platelets in the largest quintile were reticulated compared with the smallest quintile (6.1 ± 2.8% vs. 1.2 ± 1.5% respectively, p < 0.001). Larger platelets also synthesized more TxB(2) than small platelets both before (1348 ± 276 pg/mL vs. 1023 ± 214 pg/mL, respectively, p = 0.01) and after aspirin (1029 ± 190 pg/mL vs. 851 ± 159 pg/mL, respectively, p = 0.03). After stimulation with each agonist, a greater proportion of large platelets bound fibrinogen, VWF, P-selectin and activated integrin αIIbß3 than small platelets both in the presence and in the absence of in vitro aspirin. In an in vitro setting, large platelets appear to be more active than small platelets and continue to be more active even after in vitro aspirin. Platelets exhibit heterogeneity in size and structure. Whether this translates into platelet function and efficacy of antiplatelet therapy is unclear. We evaluated platelet functional properties and the effects of aspirin on separated platelet subpopulations in an in vitro setting. Platelets were sorted into the largest and smallest size quintiles using flow cytometry forward scatter. Alpha-granule protein release, dense granule content, surface protein activation and thromboxane synthesis were significantly greater in large platelets compared with small platelets, before and after stimulation with arachidonic acid, ADP and TRAP. Even after incubation with aspirin, large platelets continued to be more active than small platelets. In conclusion, large platelets are more active than small platelets and aspirin fails to eliminate these differential activation properties.

Cuantificación de riboflavina (vitamina B2) en productos lácteos por HPLC / Quantification of riboflavin (vitamin B2) in dairy products by HPLC

La riboflavina (B2) es una vitamina hidrosoluble del complejo B, cuyo aporte nutritional es imprescindible para el buen funcionamiento del organismo. La leche es una de las principales fuentes de riboflavina en la dieta humana, sin embargo, en la mayoría de los alimentos se degrada durante los procesos térmicos convencionales y en el almacenamiento. En el presente trabajo se determinó el contenido de riboflavina en productos lácteos comerciales, leches para consumo directo y yogurt, por cromatografía líquida de alta resolución (HPLC) con detección por fluorescencia. La preparación de la muestra incluye una hidrólisis acida (HC10. IN), seguida por una digestión enzimática, y por último, la precipitación de proteínas (TCA100 por ciento). En el análisis cromatográfico se utilizó un sistema isocrático (acetato de amonio 5 mM-metanol, 72:28 v/v). El contenido de riboflavina de las muestras de yogurt estuvo en el rango de 0,289 - 3,078 u/g BS, mientras que en la leche ultrapasteurizada y pasteurizada de 0,61-13,64 ug/gBS y 11,73-15,41 ug/ g BS, respectivamente. Las leches para consumo directo y el yogurt comercial son fuentes de riboflavina, y su consumo regular puede ayudar a satisfacer los requerimientos diarios.

Riboflavin is a water-soluble vitamin of the B complex, and its contribution is essential for the good functioning of the body. Milk is one of the main sources of riboflavin in the human diet; however, in most foods is degraded during conventional thermal processes and storage. In this paper the content of riboflavin in commercial dairy products, milk for direct consumption and yogurt, was determined by high performance liquid chrornato graphic analysis (HPLC) with fluorescence detection. Sample preparation includedan acid hydrolysis (HCL 0.1 N) followed by an enzymatic digestion and a protein precipitation at the end (TCA100 percent). For the HPLC analysis an isocratic bomb program was used (0.005 M ammonium acetate-methanol, 72:28 vlv). Riboflavin concentrations in yogurt samples were 0.289-3.078 ugB2/gDW, while in the ultra-high-temperature pasteurized milk and pasteurized milk was 0.61 -13.64 ugB2/g DW and 11.73-15.41 ugB2/g DW, respectively. Milk for direct consumption and yogurt are good sources of riboflavin; its regular consumption helps to satisfy daily requirements.