Dysregulation in CD39/CD73 Axis May Trigger the Upsurge of the Immune Suppressive Agent Adenosine in OSA Patients

Introduction Although higher incidence of cancer represents a major burden for obstructive sleep apnea (OSA) patients, the molecular pathways driving this association are not completely understood. Interestingly, adenosinergic signaling has emerged as a powerful immune checkpoint driving tumor development and progression. Methods Here, we explored the expression of the adenosinergic ecto-enzymes CD39 and CD73 in T-lymphocytes of OSA patients without any evidence of cancer, as well as their soluble forms in plasma (sCD39 and sCD73), along with adenosine. In addition, we explored the role of intermittent hypoxia (IH) in this context by in vitro models. Results Our results showed that CD39 is upregulated while CD73 is downregulated in OSA T-cells’ membrane. Moreover, our findings suggest that IH, through HIF-1, mediates the upregulation of both CD39 and CD73; and that CD73 downregulation could be mediated by a higher release of sCD73 by OSA T-lymphocytes. Importantly, we found that both sCD39 and sCD73 are upregulated in OSA plasma, suggesting T-lymphocytes as a potential source for plasmatic sCD73. Finally, our data propose the alterations in CD39/CD73 axis could underlie the upsurge of adenosine levels in the plasma of OSA patients. Conclusion Our study reveals a hypoxia-mediated alteration of the CD39/CD73 axis in OSA patients, which could trigger ADO upregulation, thus potentially contributing to the immune suppressive environment and ultimately facilitating tumor development and progression. Therefore, our data highlights the need for new longitudinal studies evaluating CD39 and/or CD73 as potential cancer-risk prognostic biomarkers in OSA patients. (AU)

Silencing suppressor of cytokine signaling 3 induces apoptosis and activates the p-STAT3/NF-κ B pathway in hypoxic cultivated H9c2 cells

Suppressor of cytokine signaling 3 (SOCS3) plays a significant role in the process of myocardial adaptation to chronic hypoxia. SOCS3 finely regulates cell signaling cross-talk that occurs between NF-κB and STAT3 during the compensatory protective response. However, the role and mechanism of SOCS3 in hypoxic cardiomyocytes are not fully understood. In the study, we investigated the effect of SOCS3 on the p65 and STAT3 signaling pathways and further examined the potential molecular mechanism involved in regulating apoptosis. Our data showed that SOCS3 silencing could upregulate Ac-p65, p-p65, and p-STAT3 expression in nuclear extracts of H9c2 cells that received hypoxic treatment for 24, 48, and 72 h. SOCS3 silencing also remarkably increased the DNA-binding activity of the p65 motif in hypoxic cultivated H9c2 cells. We also found that SOCS3 knockdown increased cleaved-caspase-3, Bax, and PUMA expression and decreased cleaved PARP and Bcl-2 in expression in hypoxic H9c2 cells. Silencing of SOCS3 caused an increase in LDH leakage from injured cardiomyocytes and reduced cell viability under conditions of hypoxic stress. Furthermore, SOCS3 silencing enhanced the apoptosis of H9c2 cells at 72 h of hypoxia. These findings suggest that knockdown of SOCS3 leads to excessive activation of the NF-κB pathway, which, in turn, might promote apoptosis under conditions of chronic hypoxia. (AU)

Influencia del pH de cordón umbilical en el resultado del cribado auditivo con otoemisiones en recién nacidos sanos / Influence of umbilical cord pH on the outcome of hearing screening with otoacoustic emissions in healthy newborns

Objetivo Es conocido el efecto de la hipoxia sobre el funcionamiento de las células ciliadas externas de la cóclea, que son las responsables de la respuesta a las otoemisiones utilizadas en el cribado auditivo neonatal. El objetivo de este estudio es conocer la influencia de variaciones leves o moderadas del pH de cordón umbilical al nacer en el resultado del cribado auditivo con otoemisiones en recién nacidos sanos sin factores de riesgo auditivo. Resultados La muestra está compuesta de 4.536 niños sanos. Los resultados no muestran diferencias significativas en el resultado del cribado auditivo entre el grupo de pH asfíctico (<7,20) y normal. Tampoco se detecta una cifra de pH inferior a 7,20 en la muestra que se relacione con alteración en el cribado. Desglosando en subgrupos con factores conocidos de variación en el resultado del cribado, como es el género o la lactancia, tampoco se detectan diferencias significativas de respuesta. El Apgar ≤ 7 sí se relaciona significativamente con un pH<7,20. Conclusiones En conclusión, las situaciones de asfixia leve-moderada asociadas al parto de recién nacidos sanos sin factores de riesgo auditivo no alteran el resultado del cribado con otoemisiones. (AU)

Objective The effect of hypoxia on the functioning of the outer hair cells of the cochlea, which are responsible for the response to otoemissions used in neonatal hearing screening, is well known. The aim of this study is to determine the influence of mild to moderate variations in umbilical cord pH at birth on the outcome of hearing screening with otoemissions in healthy newborns without hearing risk factors. Results The sample is composed of 4536 healthy infants. The results show no significant differences in the hearing screening outcome between the asphyctic (<7.20) and normal pH group. Nor is a figure below 7.20 detected in the sample that is related to an alteration in the screening. When broken down into subgroups with known factors of variation in the screening result, such as gender or lactation, no significant differences in response were detected. Apgar ≤ 7 is significantly related to pH<7.20. Conclusions In conclusion, mild-moderate asphyxia associated with delivery of healthy newborns, without auditory risk factors, does not alter the outcome of otoemission screening. (AU)

Silencing suppressor of cytokine signaling 3 induces apoptosis and activates the p-STAT3/NF-κ B pathway in hypoxic cultivated H9c2 cells

Suppressor of cytokine signaling 3 (SOCS3) plays a significant role in the process of myocardial adaptation to chronic hypoxia. SOCS3 finely regulates cell signaling cross-talk that occurs between NF-κB and STAT3 during the compensatory protective response. However, the role and mechanism of SOCS3 in hypoxic cardiomyocytes are not fully understood. In the study, we investigated the effect of SOCS3 on the p65 and STAT3 signaling pathways and further examined the potential molecular mechanism involved in regulating apoptosis. Our data showed that SOCS3 silencing could upregulate Ac-p65, p-p65, and p-STAT3 expression in nuclear extracts of H9c2 cells that received hypoxic treatment for 24, 48, and 72 h. SOCS3 silencing also remarkably increased the DNA-binding activity of the p65 motif in hypoxic cultivated H9c2 cells. We also found that SOCS3 knockdown increased cleaved-caspase-3, Bax, and PUMA expression and decreased cleaved PARP and Bcl-2 in expression in hypoxic H9c2 cells. Silencing of SOCS3 caused an increase in LDH leakage from injured cardiomyocytes and reduced cell viability under conditions of hypoxic stress. Furthermore, SOCS3 silencing enhanced the apoptosis of H9c2 cells at 72 h of hypoxia. These findings suggest that knockdown of SOCS3 leads to excessive activation of the NF-κB pathway, which, in turn, might promote apoptosis under conditions of chronic hypoxia. (AU)

Funciones ejecutivas en pacientes con apnea obstructiva del sueño: explorando el modelo prefrontal / Executive functions in patients with obstructive sleep apnea: exploring the prefrontal model

Introducción El modelo prefrontal propone que los individuos con apnea obstructiva del sueño (AOS) manifiestan conductas similares a un síndrome disejecutivo como resultado de las alteraciones de gases en la sangre y la fragmentación del sueño. Objetivo Comparar las funciones ejecutivas en pacientes con AOS con valores normativos y explorar su relación con las alteraciones de gases en la sangre y la fragmentación del sueño. Pacientes y métodos Se reclutó a pacientes de la comunidad general y de un hospital de tercer nivel. La puntuación obtenida en la evaluación neuropsicológica se contrastó con la t de Student para una muestra. Posteriormente, se estimó un análisis de regresión lineal múltiple mediante parámetros polisomnográficos de hipercapnia, hipoxemia y fragmentación del sueño como variables predictoras, y la puntuación de funciones ejecutivas como variable que se debe predecir. Resultados Pese a que el desempeño en la evaluación neuropsicológica del 26% de esta muestra se clasificó como alteración ejecutiva, los indicadores de fragmentación del sueño y alteraciones de gases no predijeron el desempeño ejecutivo. Conclusión Una fracción de los pacientes con AOS mostró un desempeño similar a un síndrome disejecutivo; no obstante, permanecen indefinidos los factores que subyacen y favorecen este tipo de manifestaciones cognitivas. La atención temprana de este problema de salud pública podría ser la mejor herramienta disponible en aras de mejorar la calidad de vida y prevenir riesgos a la salud. (AU)

INTRODUCTION According to the prefrontal model, individuals with obstructive sleep apnea (OSA) manifest behaviours mimicking dysexecutive syndrome as a result of blood gas abnormalities and sleep fragmentation. OBJECTIVE. To compare executive functions in OSA patients with normative values and explore their relationship with blood gas abnormalities and sleep fragmentation. PATIENTS AND METHODS Patients were recruited from the wider community and from a tertiary care hospital. The score obtained in the neuropsychological assessment was compared with Student’s t-test for a sample. A multiple linear regression analysis was subsequently estimated, using polysomnographic parameters of hypercapnia, hypoxemia and sleep fragmentation as the predictor variables, and the executive function score as the variable to be predicted. RESULTS Although the neuropsychological assessment performance of 26% of this sample was classified as executive impairment, indicators of sleep fragmentation and gas abnormalities failed to predict the performance of executive functions. CONCLUSION. A proportion of the patients with OSA presented performance similar to a dysexecutive syndrome; however, the factors underlying and fostering this type of cognitive manifestation remain unclear. Early treatment for this public health problem could be the best tool available for improving quality of life and preventing health risks. (AU)

Intermittent hypoxia in sport nutrition, performance, health status and body composition / Hipoxia intermitente en nutrición deportiva, rendimiento, estado de salud y composición corporal

Intermittent hypoxia refers to the discontinuous use of low oxygen levels in normobaric environment. These conditions can be reproduced in hypoxic tents or chambers while the individual is training in different physical activity protocols. Intermittent hypoxia can affect several body systems, impacting nutrition, physical performance, health status and body composition. Therefore, it is necessary to assess protocols, regarding time and frequency of exposure, passive exposure or training in hypoxia, and the simulated altitude. At the molecular level, the hypoxia-inducible factor-1α is the primary factor mediating induction of target genes, including vascular endothelial growth factor and erythropoietin. The goal of these molecular changes is to preserve oxygen supply for cardiac and neuronal function. In addition, hypoxia produces a sympathetic adrenal activation that can increase the resting metabolic rate. Altogether, these changes are instrumental in protocols designed to improve physical performance as well as functional parameters for certain pathological disorders. In addition, nutrition must adapt to the increased energy expenditure. In this last context, performing physical activity in intermittent hypoxia improves insulin sensitivity by increasing the presence of the glucose transporter GLUT-4 in muscle membranes. These changes could also be relevant for obesity and type 2 diabetes treatment. Also, the anorectic effect of intermittent hypoxia modulates serotonin and circulating leptin levels, which may contribute to regulate food intake and favor body weight adaptation for optimal sport performance and health. All these actions suggest that intermittent hypoxia can be a very effective tool in sports training as well as in certain clinical protocols.(AU)

La hipoxia intermitente se refiere al uso discontinuo de bajas concentraciones de oxígeno en un entorno normobárico. Estas condiciones puedenser reproducidas en tiendas de hipoxia o en cámaras mientras el sujeto está entrenando diferentes protocolos de actividad física. La hipoxiaintermitente puede afectar a varios sistemas corporales, impactando sobre la nutrición, el estado de salud y la composición corporal. Por lotanto, es necesario establecer protocolos que consideren el tiempo y la frecuencia de exposición, exposición pasiva o entrenamiento en hipoxia,así como la altitud simulada. A nivel molecular, el factor inducible por hypoxia-1α es el primer factor que media la activación de genes diana,incluidos el factor de crecimiento del endotelio vascular y la eritropoyetina. La finalidad de estos cambios es preservar el aporte de oxígeno parala función cardiaca y neuronal. Además, la hipoxia produce activación simpático-adrenal, que puede incrementar el metabolismo basal. Todosestos cambios son necesarios en protocolos diseñados para mejorar el rendimiento físico al igual que parámetros funcionales para el tratamientode ciertas patologías. Además, la nutrición debe adaptarse al gasto energético incrementado. En este contexto, la ejecución de actividad físicaen hipoxia intermitente mejora la sensibilidad a la insulina incrementando la presencia del transportador de glucosa GLUT-4 en las membranasmusculares. Estos cambios podrían ser también relevantes para el tratamiento de la obesidad y la diabetes tipo 2. Además, el efecto anoréxicode la hipoxia intermitente modula los niveles de serotonina y leptina, contribuyendo a regular la ingesta de comida y favoreciendo una adaptaciónóptima del peso corporal para el desempeño deportivo y la salud. Todas estas acciones sugieren que la hipoxia intermitente puede ser una herramienta muy efectiva en entrenamiento deportivo, al igual que en ciertos protocolos clínicos.(AU)

Complicaciones y grado de dificultad de la intubación orotraqueal en la unidad de cuidados intensivos pre-post instauración de un protocolo de intubación para el paciente crítico. Estudio prospectivo y observacional / Complications and degree of difficulty of orotracheal intubation in the intensive care unit before and after the establishment of an intubation protocol for critically ill patients: A prospective, observational study

Objetivo: El objetivo de nuestro estudio fue comparar el grado de dificultad y las complicaciones relacionadas con la intubación orotraqueal en una unidad de cuidados intensivos (UCI), pre y post instauración de un protocolo de intubación basado en la guía de práctica clínica para el manejo de la vía aérea difícil específica para el paciente crítico, publicada en 2018 por la Difficult Airway Society (Reino Unido). Métodos: Estudio prospectivo, observacional, comparando todas las intubaciones realizadas en nuestra UCI en un periodo pre-protocolo (enero 2015-enero 2019) con un periodo post-protocolo (febrero 2019-julio 2022). Durante el procedimiento se registró el material utilizado para la intubación, el grado de dificultad de la intubación y las complicaciones asociadas. Resultados: Durante el periodo de estudio fueron intubados 661 pacientes: 437 en el periodo pre-protocolo (laringoscopia directa 96%) y 224 en el post-protocolo (laringoscopia directa 53%, videolaringoscopio 46%). En el periodo post-protocolo observamos una mejoría de la visión laringoscópica en comparación con el pre-protocolo (Cormack-Lehane ≥2b en el 7,6% vs 29,8%, p<0,001), y una disminución de las intubaciones calificadas de dificultad moderada-severa (6,7% vs 17,4%, p<0,001). La intubación al primer intento fue del 92,8% en el periodo post-protocolo frente al 90,2% pre-protocolo (p=0,508). No encontramos diferencias significativas en las complicaciones en los dos periodos estudiados. Conclusiones: Las intubaciones realizadas en el periodo post-protocolo se han asociado a una mejoría de la visión laringoscópica y a una menor dificultad de intubación en comparación con el periodo pre-protocolo.(AU)

Objective: The objective of our study was to compare the degree of difficulty and complications related to tracheal intubation in an intensive care unit (ICU) before and after the introduction of an intubation protocol based on the Difficult Airway Society guidelines for the management of tracheal intubation in critically ill adults, published in 2018. Methods: Prospective, observational study comparing all intubations performed in our ICU over two periods: pre-protocol (January 2015-January 2019) and post-protocol (February 2019-July 2022). The material used for intubation, the degree of difficulty, and intubation-related complications were recorded. Results: During the study period, 661 patients were intubated —437 in the pre-protocol period (96% by direct laryngoscopy) and 224 in the post-protocol period (53% with direct laryngoscopy, 46% with video laryngoscopy). We observed an improvement in laryngeal view in the post-protocol period compared to the pre-protocol period (Cormack-Lehane ≥2b in 7.6% vs 29.8%, P<.001), and a decrease in the number of moderate-to-severely difficult intubations (6.7% vs 17.4%, P<.001). The first-pass success rate was 92.8% in the post-protocol period compared to 90.2% pre-protocol (P=.508). We did not find significant differences in complications between the periods studied. Conclusions: Intubations performed in the post-protocol period were associated with improved laryngeal view and fewer cases of difficult intubation compared with the pre-protocol period.(AU)

Bioinformatic Identification of Signaling Pathways and Hub Genes in Vascular Dementia

Background: Vascular dementia (VaD) is a prevalent neurodegenerative disease characterized by cognitive impairment due to cerebrovascular factors, affecting a significant portion of the aging population and highlighting the critical need to understand specific targets and mechanisms for effective prevention and treatment strategies. We aimed to identify pathways and crucial genes involved in the progression of VaD through bioinformatics analysis and subsequently validate these findings. Methods: We conducted differential expression analysis, Weighted Gene Co-expression Network Analysis (WGCNA), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and Protein-Protein Interaction (PPI) analysis. We utilized pheochromocytoma 12 (PC12) cells to create an in vitro oxygen-glucose deprivation (OGD) model. We investigated the impact of overexpression and interference of adrenoceptor alpha 1D (ADRA1D) on OGD PC12 cells using TdT-mediated dUTP nick-end labeling (TUNEL), reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blot (WB), and Fluo-3-pentaacetoxymethyl ester (Fluo-3 AM) analysis. Results: We found 187 differentially expressed genes (DEGs) in the red module that were strongly associated with VaD and were primarily enriched in vasoconstriction, G protein-coupled amine receptor activity, and neuroactive ligand-receptor interaction, mitogen-activated protein kinase (MAPK) signaling pathway, and cell adhesion. Among these pathways, we identified ADRA1D as a gene shared by vasoconstriction, G protein-coupled amine receptor activity, and neuroactive ligand-receptor interaction. The TUNEL assay revealed a significant decrease in PC12 cell apoptosis with ADRA1D overexpression (p < 0.01) and a significant increase in apoptosis upon silencing ADRA1D (p < 0.01). RT-qPCR and WB analysis revealed elevated ADRA1D expression (p < 0.001) ... (AU)

Recovery Mimicking “Ideal” CPAP Adherence Does Not Improve Wakefulness or Cognition in Chronic Murine Models of OSA: Effect of Wake-Promoting Agents

Introduction: Obstructive sleep apnea (OSA) is a chronic condition characterized by intermittent hypoxia (IH) and sleep fragmentation (SF). OSA can induce excessive daytime sleepiness (EDS) and is associated with impaired cognition and anxiety. Solriamfetol (SOL) and modafinil (MOD) are widely used wake-promoting agents in OSA patients with EDS. Methods: Male C57Bl/6J mice were exposed to SF along with sleep controls (SC) or to IH and room air (RA) controls during the light (inactive) phase for 4 and 16 weeks, respectively. Both IH and SF exposures were then discontinued to mimic “ideal” continuous positive airway pressure (CPAP) adherence. All groups were then randomly assigned to receive once daily intraperitoneal injections of SOL, MOD, or vehicle (VEH) for 6 days. Sleep/wake activity was assessed along with tests of explicit memory, anxiety and depression were performed before and after treatments. Results: IH and SF exposures increased sleep percentage in the dark phase and reduced wake bouts lengths (i.e., EDS), and induced cognitive deficits and impulsivity in mice. Both SOL and MOD treatments effectively mitigated EDS when combined with recovery, while recovery alone did not improve EDS over the 6-day period. Furthermore, improvements explicit memory emerged only after SOL. Conclusion: Chronic IH and SF induce EDS in young adult mice that is not ameliorated by recovery except when combined with either SOL or MOD. SOL, but not MOD, significantly improves IH-induced cognitive deficits. Thus, SOL emerges as a viable adjuvant medication for residual EDS in OSA along with its positive impact on cognition. (AU)

Mechanisms of myocardial hypoxia-induced endoplasmic reticulum stress and mitochondrial autophagy on cardiac arrhythmias in fitness enthusiasts and athletes

Arrhythmias are a prevalent cardiovascular condition, frequently seen in athletes and fitness enthusiasts due to their high-intensity physical activities, which can complicate or be secondary to heart failure, myocardial hypoxia, ischemia, and in severe cases, lead to sudden death. In the context of athletic and fitness-oriented lifestyles, myocardial hypoxia—often a result of intense physical exertion—can significantly impact endoplasmic reticulum stress and mitochondrial autophagy. The endoplasmic reticulum (ER) plays a crucial role in cellular protein synthesis. Disruptions in ER homeostasis, due to various factors including strenuous physical activity, can lead to an accumulation of misfolded proteins in the ER, triggering ER stress. This stress has been identified in various diseases and is of particular interest in the athletic population, where the body's systems, including the heart, are often pushed to their limits. Furthermore, mitochondrial autophagy, a process vital for maintaining cellular health by degrading and recycling mitochondrial components, has been linked to arrhythmia. This connection is especially pertinent in athletes, as their hearts undergo considerable physiological stress and adaptation in response to ongoing physical demands. This study aims to explore the mechanisms by which myocardial hypoxia induces ER stress and mitochondrial autophagy, and how these processes contribute to the development of cardiac arrhythmias in athletes and fitness enthusiasts. By focusing on this specific group, the research seeks to provide a deeper understanding of the cardiac risks associated with high levels of physical activity and to inform preventative and therapeutic strategies tailored to this population (AU)

Decúbito prono en el tercer trimestre del embarazo durante la era COVID-19: un abordaje transdisciplinar / Prone position in the third trimester of pregnancy during the COVID-19 era: A transdisciplinary approach

Existe evidencia muy limitada respecto del uso de la ventilación en decúbito prono como parte del tratamiento de un síndrome de distrés respiratorio agudo severo para pacientes en periodo de gestación. Actualmente las recomendaciones para el manejo ventilatorio invasivo en esta población son muy escasas y se basan en la extrapolación de las conclusiones obtenidas en estudios de pacientes no gestantes. La literatura disponible asevera que la anatomía y la fisiología de la gestante experimentan complejos cambios adaptativos que deben ser considerados durante el soporte ventilatorio invasivo y el prono. Con la ventilación en decúbito prono, los beneficios obtenidos para el binomio superan ampliamente a los eventuales riesgos. La programación adecuada del ventilador mecánico se correlaciona con un concepto claro y simple: la individualización del soporte. De todas maneras, la decisión del momento oportuno para la interrupción del embarazo debe fundamentarse con un adecuado juicio clínico multidisciplinario y además debe ser respaldado con una estricta monitorización fetal.(AU)

There is very limited evidence regarding the use of prone position as part of the treatment of severe acute respiratory distress syndrome in pregnant patients. Currently, recommendations for invasive ventilatory management in this population are very scarce and are based on the extrapolation of conclusions obtained in studies of non-pregnant patients. The available literature asserts that the anatomy and physiology of the pregnant woman undergoes complex adaptive changes that must be considered during invasive ventilatory support and prone position. With prone ventilation, the benefits obtained for the couple far outweigh the eventual risks. Adequate programming of the mechanical ventilator correlates with a clear and simple concept: individualization of support. In any case, the decision on the timing of termination of pregnancy should be based on adequate multidisciplinary clinical judgment and should be supported by strict monitoring of the product.(AU)

Intervención mediante imaginería motora tras una encefalopatía post-hipóxica. A propósito de un caso / Motor imagery intervention after hipoxic brain injury. A case study

Objetivos: valorar las diferencias pre y post intervención en la motricidad fina, funcionalidad de miembros superiores y control de espasmos a través de la imaginería motora en una persona que ha sufrido una encefalopatía post-hipoxia. Métodos: el paciente es un varón de 52 años que sufrió una encefalopatía post-hipoxia que cursó con una alteración de la respuesta motora en forma de espasmos incontrolados ante estímulos inesperados que provocaba una imposibilidad de manipulación o uso funcional de objetos. Se realizó una intervención a través de imaginería motora con el fin de reducir el número de espasmos y aumentar la funcionalidad de miembros superiores. Se estructuró en sesiones de 45 minutos, dos sesiones semanales durante tres meses. Se realizó una valoración a través de las escalas Motor Assessment Scale, Purdue Pegboard Test y Nine Hole Peg Test, además de una serie de tareas funcionales para medir el número de espasmos durante la ejecución de cada actividad. Conclusión: al finalizar la intervención se evidenció una mejoría tanto en motricidad fina como en funcionalidad de miembros superiores. Por lo tanto, la imaginería motora podría suponer una herramienta eficaz a la hora de abordar este tipo de clínica tan específica.(AU)

Objective: An intervention was designed and carried out to increase To assess pre- and post-intervention differences in fine motor skills, upper limb functionality and spasm control through motor imagery in a person who has suffered post-hypoxic encephalopathy. Methods: The patient is a 52-year-old male who has suffered post-hypoxic encephalopathy with an altered motor response in the form of uncontrolled spasms to unexpected stimuli that made it impossible to manipulate or functionally use objects. An intervention was carried out through motor imagery to reduce the number of spasms and increase the functionality of the upper limbs. It was structured in 45-minute sessions, twice a week for three months. An assessment was performed using the Motor Assessment Scale, Purdue Pegboard Test and Nine Hole Peg Test, as well as a series of functional tasks to measure the number of spasms during the execution of each activity. Conclusion: At the end of the intervention there was an improvement in both fine motor skills and upper limb function. Therefore, motor imagery could be an effective tool when dealing with this type of very specific clinical condition.(AU)

Intermittent Hypoxia Mediates Cancer Development and Progression Through HIF-1 and miRNA Regulation

Introduction: There is still a debate for the link between obstructive sleep apnoea (OSA) and cancer. The mechanisms underlying this causality are poorly understood. Several miRNAs are involved in cancer development and progression with expression being influenced by hypoxia. The aims of this work were (i) to compare miRNAs expression in controls versus patients affected by OSA without or with cancer (ONCO-OSA) and (ii) in colorectal cancer cells exposed to intermittent hypoxia (IH), to evaluate miRNAs impact on tumor progression in vitro. Methods: We detected miRNAs by qRT-PCR in patients’ sera and in CaCo2 cells exposed to 2–32h of IH with or without acriflavine (ACF), a HIF-1 inhibitor. Viability and transwell invasion test were applied to investigate the proliferation and migration of CaCo2 exposed to IH and treated with miRNA inhibitors or acriflavine. HIF-1α activity was evaluated in CaCo2 cells after IH. Results: The levels of miR-21, miR-26a and miR-210 increased in OSA and ONCO-OSA patients compared to controls. MiR-23b increased in ONCO-OSA patients, and miR-27b and miR-145 increased in OSA but not ONCO-OSA patients. MiR-21, miR-26a, miR-23b and miR-210 increased in cells after IH. IH stimulated cell proliferation and migration. This effect was reduced after either miRNA inhibition or acriflavine treatment. MiRNA inhibition reduces HIF-1α gene expression. Conversely, acriflavine reduced the expression of these miRNAs. Conclusions: We identified a signature of miRNAs, induced by the IH environment. They could be implicated in cancer development and progression through a regulatory loop involving HIF-1. (AU)

Lung diffusing capacity after different modalities of exercise at sea level and hypobaric simulated altitude of 4.000 m / Capacidad de difusión pulmonar bajo diferentes modalidades de ejercicio a nivel del mar y en hipoxia hipobárica simulada de 4.000 m

Introduction: Lung diffusion capacity of carbon monoxide (DLCO) provides a measure of gas transfer in the lungs, which increase in relation to exercise and decrease in the presence of lung interstitial disease. The aim of this study is to evaluate the changes in lung diffusion after anaerobic and aerobic exercise in a cycle ergometer. Material and method: The participants were 9 healthy active subjects, including six females and three males (age: 24.3 ± 3.1 years). Lung diffusion capacity for carbon monoxide (DLCO) was studied under two different protocols: In the first day, DLCO was measured at SL at rest (SL-R), after 30-s maximal exercise (SL-ANA), and after 15-min moderate continuous exercise (SL-AER). In the second day, DLCO was evaluated at rest at SL, and then at HA (4,000 m) at rest (HA-R) and after 30-min of moderate interval exercise (HA-AER). Results: There was an increase in DLCO from rest to after SL-ANA (32.5 ± 6.4 to 40.3 ± 11.6 mL·min-1·mmHg-1, P = 0.027). In the second day, DLCO was evaluated at rest at SL, and then at HA (4,000 m) at rest (HA-R) and after 30-min of moderate interval exercise (HA-AER). During HA exposure, there was no changes in DLCO, either at HA-R, or after HA-AER. Conclusions: Lung diffusion capacity largely increased after 30-s maximal exercise in a cycle ergometer, although the O2-dependence is small during this type of anaerobic exercise. Thus, exercise intensity may be a key modulator of the changes in lung diffusing capacity in relation to exercise.(AU)

Introducción: La difusión pulmonar para el monóxido de carbono (DLCO) proporciona una medida de la transferencia de gas en los pulmones, que aumenta con relación al ejercicio y disminuye en presencia de una lesión intersticial pulmonar. El objetivo de este estudio es fue evaluar los cambios en la difusión pulmonar después de un ejercicio aeróbico y anaeróbico en cicloergómetro. Material y método: Los participantes fueron 9 sujetos físicamente activos, incluyendo seis mujeres (edad: 24,6 ± 3,6 años) y tres hombres (edad: 23,7 ± 1,5 años). La DLCO se estudió bajo dos protocolos diferentes: El primer día, la DLCO fue medida a nivel del mar en reposo (SL-R), después de un esfuerzo máximo de 30 segundos (SL-ANA), y después de un ejercicio moderado continuo de 15-min (SL-AER). El segundo día, la DLCO fue evaluada a nivel del mar en reposo (SL-R, y luego en altitud (4.000 m) en reposo (HA-R) y después de un ejercicio interválico de 30 minutos (HA-AER). Resultados: Se produjo un aumento de la DLCO de la SL-R a la SL-ANA (32,5 ± 6,4 a 40,3 ± 11,6 mL·min-1·mmHg-1, p = 0,027). En el segundo día, la DLCO no se modificó después de la exposición en altitud, ya sea en reposo a 4.000 m (HA-R) o después del ejercicio interválico moderado a dicha intensidad (HA-AER). Conclusiones: La difusión pulmonar aumentó ampliamente después de un esfuerzo máximo de 30 segundos en cicloergómetro, aunque la dependencia del oxígeno en este tipo de esfuerzos es pequeña. La intensidad del esfuerzo es un modulador determinante en las modificaciones de la difusión pulmonar con relación al ejercicio.(AU)

Biochemical and haematological abnormalities in severe acute organophosphorus poisoning / Anomalías bioquímicas y hematológicas en la intoxicación grave por organofosforados. Estudio prospectivo en un solo centro

Background: Organophosphorus insecticides are considered one of the commonest causes of morbidity and mortality due to poisoning worldwide. Severe organophosphorus poisoning can lead to multiple sometimes lethal metabolic and haematological abnormalities. Methods: A total of 141 OP poisoning patients were admitted during the study period and their blood samples were collected on admission and analysed for the biochemical abnormalities. Results: Out of 141 patients 76 were males (53.9%) and 65 were females (46.1%). Bradycardia with Pulse rate of less than 60 was seen in in 21 patients (14.7). Hypoxemia with oxygen saturation of less than 94% was seen in 32 (22.7%). leucocytosis with TLC o 11000 or more was seen in 19 patients (13.5%).101 patients (83.5%) had low serum choline esterase levels less than 1.5kU/L. Hypokalaemia with K+ of less than 3.5 was seen in 16 patients (9.9%). Five patients died out of 141 (3.5%). Hypoxemia Spo2 of less than 90% was seen in 3 (60%) patients who died and hypoglycaemia with blood glucose of less than 70mg/dl was seen in 2 out of 5 Patients (40%). Conclusions: low choline esterase levels less than 1.5kU/L was the most common abnormality indicating severe poisoning followed by hypoxemia. Both Hypoxemia and low acetylcholine esterase levels are bad prognostic signs and result in high mortality in organophosphorus poisoning. (AU)

Introducción: De entre todos los procesos de intoxicación, el envenenamiento por organofósforados se considera una de las causas más comunes de morbilidad y mortalidad en todo el mundo. La intoxicación grave por organofósforo puede provocar múltiples anomalías metabólicas y hematológicas, a veces letales. Métodos: Un total de 141 pacientes intoxicados por organofósforados fueron ingresados durante el periodo de estudio y sus muestras e sangre fueron recogidas al ingreso y analizadas para detectar las anomalías bioquímicas. Resultados: De los 141 pacientes, 76 eran varones (53,9%) y 65 mujeres (46,1%). Se observó bradicardia con una frecuencia de pulso inferior a 60 en 21 pacientes (14,7). Se observó hipoxemia con una saturación de oxígeno inferior al 94% en 32 (22,7%). Leucocitosis con un recuento total de leucocitos de 11.000 o más en 19 pacientes (13,5%). 101 pacientes (83,5%) tenían niveles bajos de colina esterasa sérica inferiores a 1,5 kU/L. Se observó hipopotasemia con K+ inferior a 3,5 en 16 pacientes (9,9%). Cinco pacientes fallecieron de un total de 141 (3,5%). Se observó hipoxemia Spo2 inferior al 90% en 3 (60%) pacientes que fallecieron e hipoglucemia con glucemia inferior a 70 mg/dl en 2 de 5 pacientes (40%). Conclusiones: Los niveles bajos de colinesterasa inferiores a 1,5 kU/L fueron la anomalía más frecuente que indicaba intoxicación grave, seguida de hipoxemia. La hipoxemia, la hipoglucemia y los niveles bajos de acetilcolinesterasa son signos de mal pronóstico y dan lugar a una elevada mortalidad en la intoxicación por organofosforados. (AU)

HIF-1 signaling: an emerging mechanism for mitochondrial dynamics

A growing emphasis has been paid to the function of mitochondria in tumors, neurodegenerative disorders (NDs), and cardiovascular diseases. Mitochondria are oxygen-sensitive organelles whose function depends on their structural basis. Mitochondrial dynamics are critical in regulating the structure. Mitochondrial dynamics include fission, fusion, motility, cristae remodeling, and mitophagy. These processes could alter mitochondrial morphology, number, as well as distribution, to regulate complicated cellular signaling processes like metabolism. Meanwhile, they also could modulate cell proliferation and apoptosis. The initiation and progression of several diseases, such as tumors, NDs, cardiovascular disease, were all interrelated with mitochondrial dynamics. HIF-1 is a nuclear protein presented as heterodimers, and its transcriptional activity is triggered by hypoxia. It plays an important role in numerous physiological processes including the development of cardiovascular system, immune system, and cartilage. Additionally, it could evoke compensatory responses in cells during hypoxia through upstream and downstream signaling networks. Moreover, the alteration of oxygen level is a pivotal factor to promote mitochondrial dynamics and HIF-1 activation. HIF-1α might be a promising target for modulating mitochondrial dynamics to develop therapeutic approaches for NDs, immunological diseases, and other related diseases. Here, we reviewed the research progress of mitochondrial dynamics and the potential regulatory mechanism of HIF-1 in mitochondrial dynamics. (AU)

Effect of hypobaric hypoxia on the fiber type transition of skeletal muscle: a synergistic therapy of exercise preconditioning with a nanocurcumin formulation

Hypobaric hypoxia (HH) leads to various adverse effects on skeletal muscles, including atrophy and reduced oxidative work capacity. However, the effects of HH on muscle fatigue resistance and myofiber remodeling are largely unexplored. Therefore, the present study aimed to explore the impact of HH on slow-oxidative fibers and to evaluate the ameliorative potential of exercise preconditioning and nanocurcumin formulation on muscle anti-fatigue ability. C2C12 cells (murine myoblasts) were used to assess the effect of hypoxia (0.5%, 24 h) with and without the nanocurcumin formulation (NCF) on myofiber phenotypic conversion. To further validate this hypothesis, male Sprague Dawley rats were exposed to a simulated HH (7620 m) for 7 days, along with NCF administration and/or exercise training. Both in vitro and in vivo studies revealed a significant reduction in slow-oxidative fibers (p < 0.01, 61% vs. normoxia control) under hypoxia. There was also a marked decrease in exhaustion time (p < 0.01, 65% vs. normoxia) in hypoxia control rats, indicating a reduced work capacity. Exercise preconditioning along with NCF supplementation significantly increased the slow-oxidative fiber proportion and exhaustion time while maintaining mitochondrial homeostasis. These findings suggest that HH leads to an increased transition of slow-oxidative fibers to fast glycolytic fibers and increased muscular fatigue. Administration of NCF in combination with exercise preconditioning restored this myofiber remodeling and improved muscle anti-fatigue ability. (AU)

Efecto de vesículas extracelulares derivadas de células madre mesenquimales humanas precondicionadas en hipoxia sobre la osteoblastogénesis y la adipogénesis in vitro / Effect of stem cell-derived extracellular vesicles human mesenchymal cells preconditioned in hypoxia on osteoblastogenesis and adipogenesis in vitro

Objetivos: las células madre mesenquimales (MSC) se caracterizan por su actividad antiinflamatoria, inmunosupresora y sucapacidad de diferenciación. Esto las convierten en una interesante herramienta terapéutica en terapia celular y medicinaregenerativa. En parte, el efecto terapéutico de las MSC, está mediado por la secreción de vesículas extracelulares (EV). Elprecondicionamiento en hipoxia de las MSC puede mejorar la capacidad regenerativa de las EV secretadas. En este con-texto, el objetivo del estudio ha sido evaluar si EV derivadas de MSC humanas cultivadas en hipoxia y normoxia afectan ala osteoblastogénesis y adipogénesis de las MSC.Material y métodos: se aislaron EV de MSC mantenidas 48 h en normoxia o hipoxia (3 % O2) mediante ultrafiltración ycromatografía de exclusión por tamaño. Las EV fueron caracterizadas por “Western blot”, microscopía electrónica y análisisde seguimiento de nanopartículas. En cultivos de MSC se evaluó el efecto de las EV sobre la viabilidad por ensayo con MTT,la migración por “Oris assay” y la diferenciación a osteoblastos y adipocitos.Resultados: las EV aumentaron la viabilidad y migración, pero no hubo diferencias entre las derivadas de normoxia ehipoxia. Las EV, principalmente las derivadas de hipoxia, aumentaron la mineralización y la expresión de genes osteoblás-ticos. Sin embargo, no afectaron significativamente a la adipogénesis.Conclusiones: las EV derivadas de MSC en hipoxia no afectan a la adipogénesis, pero tienen una mayor capacidad de inducirla osteoblastogénesis. Por lo tanto, podrían potencialmente ser utilizadas en terapias de regeneración ósea y tratamientosde patologías óseas como la osteoporosis.(AU)