Effects of a motor and cognitive training program on executive function and different biomarkers related to muscle-brain crosstalk in breast cancer survivors: 3-arm randomised controlled BRAINonFIT study protocol.

INTRODUCTION: Cancer-related cognitive impairment (CRCI) is a significant but often neglected issue for breast cancer survivors that reduces their quality of life. Physical exercise and cognitive training have emerged as promising strategies for CRCI; however, evidence regarding its effectiveness is still unknown. A recently developed motor-cognitive training (dual-tasks) is proposed to examine its efficacy on executive function, physical fitness, emotional symptomatology, and important muscle-brain crosstalk biomarkers. METHODS: The BRAINonFIT study is a randomised, controlled, longitudinal (20 weeks), three-arm, parallel study with a follow-up phase (12 weeks). Breast cancer survivors (stage I-IIIA) with completed chemotherapy are recruited from QuirónSalud Hospital in Seville. Principal outcomes are executive functions, measured by the Trail Making Test, Stroop and Digit Span Backwards; physical fitness, assessed by muscle strength, cardiorespiratory fitness, and body composition; and several muscle-brain biomarkers analysed by immunoenzymatic assay (ELISA). Secondary endpoints are memory function, intelligence, learning ability, self-reported cognitive function, and emotional symptomatology. Assessments take place after the enrolment (baseline; T1), after completing the interventions (5 months after baseline; T2), and after completing the follow-up period (8 months after baseline; T3). DISCUSSION: Given the importance of improving care for breast cancer survivors, this study will provide preliminary evidence for the effectiveness of cognitive-motor training (dual task) as a therapeutic strategy to improve CRCI. Moreover, addressing muscle-brain crosstalk by representative biomarkers will help to elucidate the underlying mechanisms by which this intervention may beneficially impact CRCI. CLINICALTRIALS: gov: NCT06073717.

Alternative splicing: the pledge, the turn, and the prestige : The key role of alternative splicing in human biological systems.

Alternative pre-mRNA splicing is a tightly controlled process conducted by the spliceosome, with the assistance of several regulators, resulting in the expression of different transcript isoforms from the same gene and increasing both transcriptome and proteome complexity. The differences between alternative isoforms may be subtle but enough to change the function or localization of the translated proteins. A fine control of the isoform balance is, therefore, needed throughout developmental stages and adult tissues or physiological conditions and it does not come as a surprise that several diseases are caused by its deregulation. In this review, we aim to bring the splicing machinery on stage and raise the curtain on its mechanisms and regulation throughout several systems and tissues of the human body, from neurodevelopment to the interactions with the human microbiome. We discuss, on one hand, the essential role of alternative splicing in assuring tissue function, diversity, and swiftness of response in these systems or tissues, and on the other hand, what goes wrong when its regulatory mechanisms fail. We also focus on the possibilities that splicing modulation therapies open for the future of personalized medicine, along with the leading techniques in this field. The final act of the spliceosome, however, is yet to be fully revealed, as more knowledge is needed regarding the complex regulatory network that coordinates alternative splicing and how its dysfunction leads to disease.

Optical trapping for biosensing: materials and applications.

Since the 70's, when Arthur Ashkin and coworkers demonstrated that optical forces could displace and levitate microsized particles, optical trapping has seen a steady stream of developments and applications, particularly in the biological field. Since that demonstration, optical trapping has been especially exploited as a powerful tool for non-invasive sensitive measurements. The recent development of synthesis routes has further expanded the possibilities of optical trapping in the area of biosensing where new multifunctional particles are used as a single probe. The synergy between the development of new materials and experimental techniques has led to the appearance of numerous studies in which novel biosensing applications are demonstrated. The design of new materials and optical systems to face new challenges makes it necessary to have a clear idea about the latest developments achieved in the field. In this work, we summarize recent experimental advances in biosensing achieved by optical manipulation of micro- and nanoparticles providing a critical review on the state of the art and future prospects.

Uso de máscara laríngea en un lactante con estenosis subglótica. Reporte de caso y revisión de la literatura / The use of laryngeal mask in an infant with subglottic stenosis - Case report and literature review

La máscara laríngea se ha convertido en una alternativa para el manejo de la vía aérea en el paciente pediátrico. Se presenta un caso clínico de un lactante con asociación VACTER que requiere anestesia para cierre de fistula traqueoesofágica y anastomosis esofágica, el cual no se logra intubar y es manejado exitosamente con una máscara laríngea. El uso de la máscara laríngea es una opción en el manejo de la vía aérea de neonatos y lactantes con malformaciones craneofaciales como manejo único, o como adyuvante para la intubación traqueal, y también en neonatos con vía aérea normal para cirugías complejas, incluso cirugía cardiaca. La evidencia apunta hacia el uso de dispositivos de segunda generación que permiten un mejor sello de la vía aérea y la succión de la vía digestiva (Proseal® o Supreme®). Es también un dispositivo alterno durante la reanimación neonatal en pacientes más de 2.000 g que no se pueden manejar adecuadamente con máscara facial y no pueden ser intubados.

The laryngeal mask has become an alternative to manage the pediatric airway. This is a clinical case of an infant with VACTERL association requiring anesthesia for tracheoesophageal fistula closure and esophageal anastomosis; the infant was successfully managed with laryngeal mask upon failed intubation. The use of the laryngeal mask is an option for the management of the airway in neonates and infants with craniofacial malformations, either alone or as an adjuvant for tracheal intubation and also in neonates with normal airway for complex surgeries, including heart surgery. The evidence points to the use of second-generation devices that allow for an improved airway seal and suction of the GI tract (Proseal® or Supreme®). It is also an alternate device during neonatal resuscitation in patients over 2000 g that cannot be properly managed with a face mask or intubated.

Anestesia regional versus general para parto por cesárea / Regional versus general anesthesia for cesarean section delivery

Introducción: No existe una técnica estándar de anestesia para el parto por cesárea. La anestesia general ha sido asociada con mayor morbimortalidad; sin embargo, estudios recientes parecen no estar de acuerdo con esta afirmación. Objetivo:Hacer una reflexión a través de los resultados de estudios que comparan anestesia regional y general para cesárea desde 3 aspectos: mortalidad, morbilidad y desenlaces neonatales, a partir de una búsqueda de la literatura Métodos:Artículo de reflexión. Se realizó una búsqueda no sistemática de la literatura referente a este tema en las bases de datos Medline/Pubmed, Embase, Cochrane y Lilacs usando términos Mesh incluidos en las palabras clave. Resultados: Aunque la tasa de cesáreas se ha mantenido constante, el uso de anestesia general ha disminuido progresivamente. La mortalidad materna asociada a anestesia general durante cesárea ha descendido hasta prácticamente ser igual a la de anestesia regional 1,7 (IC 95%, 0,6-4,6). La morbilidad es menor con anestesia regional: menor sangrado, menor riesgo de infección del sitio operatorio y menor dolor posoperatorio. Los desenlaces neonatales son prácticamente iguales. Conclusión: Las técnicas de anestesia neuroaxial son la elección para parto por cesárea siempre que no esté contraindicada, porque se asocia con menor morbilidad, aunque la mortalidad y los desenlaces neonatales son similares cuando se compara con anestesia general.

Introduction:There is no standard anesthesia technique for cesarean section. General anesthesia has been associated with higher morbidity-mortality; however, recent studies seem to disagree with such statement. Objectiue:Based on a search in the literature, to reflect on the comparative results of regional vs. general anesthesia for C-section considering three aspects: mortality, morbidity and neonatal outcomes. Methods: Article for reflection. A non-systematic search of the literature on the topic was performed in the Medline/Pubmed, Embase, Cochrane and Lilacs databases, using Mesh terms included in the key words. Results:Although the rates for cesarean sections have been constant, the use of general anesthesia has decreased progressively. Maternal mortality associated to general anesthesia during cesarean section has dropped to practically the same level as regional anesthesia: 1.7 (95% CI, 0.6-4.6). Mortality is lower with regional anesthesia: less bleeding, lower risk of surgical site infection, less post-operative pain. The neonatal outcomes are practically the same. Conclusion: As long as they are not contraindicated, neuraxial anesthetic techniques are the method of choice for C-section delivery, because they are associated with lower morbidity, though mortality and neonatal outcomes are similar as compared to general anesthesia.

Identificación de la adherencia al tratamiento nutricional aplicando el modelo de conocimientos, actitudes y prácticas en un grupo de personas con diabetes mellitus tipo 2 atendidas en la asociación colombiana de diabetes / Identification of adherence to nutritional therapy using the model of knowledge, attitudes and practices in a group of people with diabetes mellitus type 2 treated by Colombian diabetes association

Introducción: el tratamiento nutricional es uno de los pilares en el manejo de la diabetes; sin embargo se reportan bajos niveles de adherencia, constituyendo una dificultad importante para el alcance de las metas metabólicas. Objetivo: identificar la adherencia al tratamiento nutricional en un grupo de personas con Diabetes Mellitus tipo 2, aplicando el modelo de Conocimientos, Actitudes y Prácticas. Material y métodos: estudio descriptivo transversal realizado con un grupo de personas con Diabetes Mellitus tipo 2 afiliados a la Asociación Colombiana de Diabetes, en quienes se evaluaron conocimientos, actitudes y prácticas acerca del tratamiento y se relacionaron con el consumo de calorías y macronutrientes. Los datos se analizaron aplicando estadística descriptiva, prueba de correlación interna, chi cuadrado y prueba exacta de Fisher. Resultados: no hubo adherencia completa a las recomendaciones nutricionales, el 30% de los participantes se adhirió a la prescripción de calorías, 13% a la de carbohidratos, 23% a la de grasa y3% a la de proteína. Los conocimientos sobre la enfermedad fueron suficientes, pero los relacionados con el intercambio de alimentos no lo fueron; se encontraron actitudes positivas en la mayoría de los participantes y menos de la mitad refirió prácticas adecuadas.Discusión y conclusiones: la relación entre conocimientos, actitudes y prácticas con la adherencia no fue estadísticamente significativa, sin embargo, la correlación entre conocimientos (p = 0,057) y prácticas (p=0,053) fueron las de mayor valor. Debido a que la adherencia es un fenómeno múltiple y complejo que implica diversidad de conductas, es importante seguir explorando metodologías para identificar las variables que la condicionan.

Controversias sobre la presión cricoidea o maniobra de Sellick / Controversial issue of cricoid pressure or Sellick maneuver

Introducción. La maniobra de Sellick o presión cricoidea es un procedimiento que se realiza de rutina en la profilaxis de la aspiración pulmonar como parte de la inducción/intubación de secuencia rápida. Ha sido objeto de múltiples controversias especialmente sobre su utilidad como práctica estándar de seguridad en el manejo de la vía aérea en urgencias. Se ha considerado la maniobra como una presión, sin embargo se designa la medida en Newton (N), sin tener en cuentael área del cartílago cricoides, de este modo es preciso referirse a la maniobra no en términos de presión cricoidea sino de fuerza cricoidea. Objetivo. Destacar la importancia de revisar las controversias que ha tenido una maniobra que se acerca a los 50 años de vigencia en el manejo de la vía aérea y la prevención de la broncoaspiración; incluso resaltar que ha habido errores en su descripción utilizando medidas de fuerza y no de presión Método. Mediante la revisión de la literatura se realiza este artículo de reflexión sobre las controversias de una maniobra usual en la práctica de urgencias del anestesiólogo, la Maniobra de Sellick. Conclusión. Desde 1961 cuando el doctor Brian Arthur Sellick describió la presión cricoidea como una maniobra útil para prevenir la regurgitación del contenido gástrico hacia la faringe, hasta la actualidad cuando se utiliza como medida importante en la técnica de inducción/intubación de secuencia rápida, se han venido encontrando una serie de controversias en cuanto a la seguridad que puede brindar en el manejo de la vía aérea, dignas de revisar y de discutir, y además, de recomendar una aclaración en cuanto a la designación de los términos presión y fuerza, que se han venido utilizando de manera indistinta para referirse a esta maniobra sin tener en cuenta el área del cartílago cricoides, que de hecho es diferente entre los individuos.

Introduction. The Sellick maneuver or cricoid pressure is a procedure that is routinely performed in the prophylaxis for pulmonary aspiration as part of a rapid sequence intubation. It has been considered very controversial specifically on its usefulness as a standard safety practice in the emergent airway management. Itusually has been considered a pressure maneuver, however it usually has seen assessed measuring Newtons (N) without considering the area of the cricoid cartilage. For this reason, it mustbe understood in terms of cricoid force instead of cricoid pressure. Objetive. To highlight the controversial issues this maneuver has had over the 50 years of its use in airway management and pulmonary aspiration prevention. To explain the common error of describing it in terms of force and not pressure. Methods. Literature review about the controversial aspects of the Sellick maneuver in emergent scenarios in anesthesia. Conclusion. Since the initial description by Dr. Brian Arthur Sellick in 1961 of the maneuver, using cricoid pressure to prevent them regurgitationof gastric contents to the pharynx used as part of the rapid sequence induction/ intubation, there have been multiple criticisms worthwhile to review, regarding the safety it provides in protecting the airway. We recommend that the terms pressure and force be differentiated and be used more appropriately when describing the maneuver, as the area of the cartilage should be considered in these measurements.

Selective decrease of Na+/k+ -ATPase activity in the brain of hypothyroid rats.

The present work was performed in order to know if mild hypothyroidism in rats modifies the activity of the Na+/K+ -ATPase in different regions of the brain. Male Wistar rats (300-350 g) were randomly divided into three groups: (1) control group (n=8) drank tap water. (2) hypothyroid group (n=8) treated with 60 mg/kg of methimazole in drinking water; and (3) replaced group (n=8) treated with 60 mg/kg of methimazole plus 35 microg/kg of thyroid hormone (T3) in drinking water. After four weeks of treatment, the rats of all groups were sacrificed by decapitation. The cortex, amygdala, hippocampus and cerebellum were dissected and frozen at -70 degrees C until assay. For enzymatic assay, the tissues were homogenized. The Na+/K+ -ATPase activity was determined by quantifying inorganic phosphate after the samples were incubated with ATP in the presence and absence of 1 mM ouabain. The Na+/K+ -ATPase activity is expressed as pmoles Pi/hr/mg protein. The results showed that the Na+/K+ -ATPase activity in the cortex, amygdala and hippocampus, but not in cerebellum, was lower in hypothyroid group than in control group (p<0.05). The co-administration of methimazole and T3 avoided the decrease of Na+/K+ -ATPase activity, except in amygdala. According to the results obtained we concluded that methimazole treatment decreased the Na+/K+- ATPase activity in the brain's regions which are related to seizures onset. That decrement in enzyme activity was avoided with the coadministration of thyroid hormone.

Alpha-asarone inhibits HMG-CoA reductase, lowers serum LDL-cholesterol levels and reduces biliary CSI in hypercholesterolemic rats.

Our results showed that alpha-asarone was an inhibitor of hepatic HMG-CoA reductase and that the administration of alpha-asarone at 80 mg/kg body wt. for 8 days decreased serum cholesterol by 38% (p < 0.001) in hypercholesterolemic rats. This alpha-asarone treatment affected mainly the serum LDL-cholesterol levels, leaving serum HDL-cholesterol lipoproteins unaffected, with a consequent decrease of 74% in the LDL/HDL ratio. In addition, alpha-asarone especially stimulated bile flow in hypercholesterolemic rats (60%), increasing the secretion of bile salts, phospholipids and bile cholesterol. The drug also reduced the cholesterol levels of gallbladder bile, whereas the concentration of phospholipids and bile salts increased only slightly, leading to a decrease in the cholesterol saturation index (CSI) of bile in the hypercholesterolemic rats. This CSI decrease and the increase in bile flow induced by alpha-asarone may account for the cholelitholytic effect of alpha-asarone. It seems that alpha-asarone induced clearance of cholesterol from the bloodstream and that the excess of hepatic cholesterol provided by LDL-cholesterol is diverted to bile sterol secretion via a bile choleresis process. The inhibition of HMG-CoA reductase and the increase in bile flow induced by alpha-asarone, as well as the decrease in the CSI, could then explain the hypocholesterolemic and cholelitholytic effects of alpha-asarone.

Tratamiento de dislipidemias con ácido nicotínico / Treatment of dyslipidemia with Nicotinic acid

El ácido nicotínico fue el primer agente para el tratamiento de dislipidemias. Con la aparición de las estatinas su uso disminuyó ya que éstas no presentaban los efectos molestos de ruborizacioón causados por el ácido nicotínico. Las estatinas no han demostrado ser tan efectivas para la reducción de los triglicéridos y en el aumento de las lipoproteínas de alta densidad como el ácido nicotínico. Se han desarrollado dos variaciones adicionales de ácido nicotínco con el objetivo de disminuir su poder de causar ruborización y de suministrar un mejor efecto de regulación sobre esos lípidos. En el presente artículo se realiza una revisión de la literatura médica sobre el uso del ácido nicotínico como agente para el control de las dislipidemias. Las dislipidemias son un grupo de trastornos caracterizados por anomalías tanto cuantitativas como cualitativas de las lipoproteínas plasmáticas. La excesiva aucumulación de una se acompaña generalmente de una disminución en la concentración de la otra. Se pueden considerar como el resultado de defectos en el sistema catabólico por anomalías en las enzimas, receptores celulares de superficie, o bien de una estructura anormal de la partícula lipoprotéica que disminuye su capacidad para interactuar con los mecanismo catabólicos. La mayoría de las dislipidemias son poligénicas o el producto de la interacción entre factores ambientales y cierta predisposición genética.

Trypanocidal activity of 4 isopropyl salicylaldehyde and 4-isopropyl salicylic acid on Trypanosoma cruzi.

We synthesized and study the possible trypanocidal activity of 4-isopropyl salicylaldehyde and 4-isopropyl salicylic acid, these compounds were chemical derivatives of gossypol, a drug that inhibits the growth of T. cruzi in culture. These derivatives were tested in two T. cruzi strains with different in vitro susceptibility to benznidazole and nifurtimox, used as a reference drugs. It was found that they were better inhibitors of T. cruzi alpha-hydroxyacid dehydrogenase than gossypol, in both strains. The in vitro and in vivo pharmacological tests were performed and in both test, the gossypol derivatives showed a higher and better trypanocidal effect than gossypol, and a higher and much better trypanocidal effect than nifurtimox and benznidazole in the two studied T. cruzi strains. The trypanocidal effect was higher in the NINOA strain than in the MIGUZ strain.

Experiencia de la prostatectomia radical en pacientes con cancer localizado de prostata en el Hospital de San Jose de Bogotá / Experience in radical prostatectomy with cancer of prostate patients in San Jose Hospital, Bogotá

Objetivos: Presentar los resultados de la prostatectomía radical como tratamiento del cáncer localizado de próstata en la serie estudiada. Compararlos con las series publicadas. Determinar los valores predictivos del PSA y Gleason preoperatorios relacionados con la patología definitiva. Establecer complicaciones perioperatorias, morbi-mortalidad, recidiva tumoral, incontinencia e impotencia asociados a la cirugía. Diseño: Estudio descriptivo de casos con información de historias clínicas, seguimiento y entrevistas con pacientes. Población y lugar: 88 pacientes con diagnóstico de cáncer de próstata localizado, intervenidos entre septiembre/1992 y abril/1997. Intervención: prostatectomía radical con técnica modificada de Waish, previa linfadenectomía ilio-obturadora bilateral examinada por congelación. Medición y resultados: Se utilizaron medidas de tendencia central y de dispersión, mediante EpiInfo 6.04b. La patología definitiva fue organoconfinado 58,8 por ciento, extracapsular 13,8 por ciento, márgenes positivas 15 por ciento y otros 12,5 por ciento. Grado de diferenciación: bien 20.5 por ciento, moderado 39,7 por ciento y mal 39,77o. Tiempo quirúrgico promedio: 3,7 horas, complicaciones perioperatorias: 5,8 por ciento, sin mortalidad. La continencia: 95 por ciento, potencia: 23,4 por ciento POP. El 34,5 por ciento de los pacientes requirieron dilataciones uretrales, con promedio de 2,5/paciente. Recurrencia serológica: 31,87o, recidiva local comprobada: 4,17o y 2 pacientes tienen gamagrafías óseas positivas. Promedio de seguimiento: 17,3 meses. Conclusiones: Se observó subestadificación del 357o. Es una cirugía segura, con baja morbilidad, sin mortalidad perioperatoria. Los índices de continencia y potencia son similares a los reportados en la literatura. No hay un parámetro objetivo que permita predecir la recurrencia real

Selective inhibition of the sperm-specific lactate dehydrogenase isozyme-C4 by N-isopropyl oxamate.

In the present study, we demonstrated that the attachment of the nonpolar isopropylic carbon chain in the nitrogen of oxamate, converted this competitive inhibitor of LDH isozymes into a powerful selective inhibitor of mouse LDH-C4. The comparative study of the inhibitory effect of oxamate and N-isopropyl oxamate on mouse LDH isozymes pointed out that the isopropylic carbon chain conferred upon N-isopropyl oxamate a high affinity for LDH-C4 and a marked decrease in the affinity for the other isozymes since oxamate showed more inhibitory effect on LDH-1 (Ki = 0.06 mM) and LDH-5 (Ki = 0.08 mM), and less inhibitory effect on LDH-C4 (Ki = 0.25 mM). On the other hand, N-isopropyl oxamate showed the highest inhibitory effect on LDH-C4 (Ki = 0.014 mM) and poor inhibitory effect on LDH-1 (Ki = 0.4 mM) and LDH-5 (Ki = 0.8 mM). Apparently, the enzymatic inactivation proceeded through a reversible binding of N-isopropyl oxamate, facilitated by nonpolar interactions with a hydrophobic region present only in the active site of mouse LDH-C4, resulting in a selective inhibition of this isozyme in comparison with the other LDH isozymes. N-isopropyl oxamate was also a powerful competitive inhibitor of LDH-C4 (Ki = 0.015 mM) compared with oxamate (Ki = 0.35 mM), using alpha-ketoisocaproate as a substrate.

Synthesis of putrescine under possible primitive Earth conditions.

The synthesis of putrescine was accomplished by decarboxylation of L-ornithine when this amino acid was heated in aqueous solution and in the absence of oxygen. Chromatographic, radioisotopic, and enzymatic techniques were used to demonstrate that one mole of non-radioactive putrescine and one mole of 14CO2 was formed during the heating of L-(l-14C)-ornithine. This work indicates that the synthesis of putrescine can occur starting with ornithine and in conditions that are presumed could have existed on the primitive Earth. The possible significance of these results in the prebiotic molecular evolution is briefly discussed.