Exposición intermitente a altitud simulada y ejercicio para la recuperación del daño muscular: células madre circulantes y ajustes hemorreológicos en ratas entrenadas

[spa] La hipótesis general de este trabajo se basa en que un protocolo de hipoxia hipobárica intermitente (IHH) combinada con ejercicio aeróbico ligero en normoxia, puede tener un efecto beneficioso en la regeneración de musculatura esquelética dañada y contribuir a una recuperación más rápida en este tipo de lesiones. Sin embargo, el conocido efecto hematopoyético de la exposición a hipoxia y del ejercicio, y el consiguiente aumento de hematocrito, podrían afectar a la dinámica del aporte de oxígeno a los tejidos, por lo que se hace necesario conocer y estudiar los potenciales efectos de estos tratamientos sobre la hematología y la reología sanguínea. Además, se ha dedicado especial atención a la presencia de células madre circulantes (CD34+) y a la población de “side population” (SP) en médula ósea para obtener evidencias de su posible incidencia en la recuperación de la lesión muscular. El núcleo fundamental de esta tesis doctoral está compuesto por dos estudios que tienen como objetivos: 1. Determinar si la respuesta hematopoyética durante un programa IHH, podría provocar alteraciones en el comportamiento hemorreológico, generando efectos negativos en el suministro de oxígeno a los tejidos. 2. Cuantificar y contrastar los efectos de la IHH y el ejercicio en el aumento del número de células progenitoras en la circulación sanguínea periférica. 3. Determinar los efectos de la IHH combinada o no con el ejercicio aeróbico ligero en normoxia, genera cambios en la presencia de SP. 4. Establecer la dinámica temporal en las modificaciones de la concentración de células madre CD34+ y SP en los diferentes grupos de animales, según las diferentes condiciones experimentales. La muestra se obtuvo de ratas Sprague-Dawley que fueron estudiadas en dos estados basales (no entrenadas y entrenadas) y comparadas durante la fase de recuperación de una lesión por contracción excéntrica repetida (inducida a ratas entrenadas) los días 1, 3, 7 y 14 posteriores a la lesión muscular. Los tres grupos experimentales estudiados durante la recuperación de sus lesiones musculares fueron: ratas con recuperación pasiva (CTRL); ratas expuestas a IHH después del daño muscular (HYP); y ratas entrenadas que además de IHH, realizaron sesiones de ejercicio aeróbico ligero (EHYP). Los resultados obtenidos en los estudios, nos permiten extraer las siguientes conclusiones: 1. Después de dos semanas de tratamiento, la IHH en combinación con ejercicio aeróbico ligero en normoxia, muestra parámetros hemorreológicos alterados en comparación a las demás condiciones experimentales. 2. Aunque la respuesta eritropoyética provocada por la exposición IHH tiende a aumentar la viscosidad de la sangre en el grupo EHYP, otros parámetros microrreológicos tales como mayor elasticidad y menor tiempo de relajación pueden contribuir a compensar este aumento. 3. Los ajustes compensatorios reológicos pueden considerarse como positivos desde un punto de vista funcional, pues contribuyen a mantener la microcirculación normal y un suministro adecuado de oxígeno, nutrientes y agentes químicos a los tejidos durante su proceso de reparación después de daño sufrido en el músculo esquelético. 4. La tinción DyeCycle Violet se retiene selectivamente para las células CD34+, que permite la discriminación de los dos subconjuntos de células, denominadas internamente como CD34+/DCVhigh y CD34+/DCVlow, debido a una intensidad más brillante o atenuada de la tinción. 5. En el séptimo día de la recuperación después de una lesión muscular, el grupo EHYP aumentó claramente el número de progenitores CD34+/CD45neg y CD34+/CD45+. 6. El grupo HYP aunque no muestra un aumento en células progenitoras después de la lesión muscular, es altamente sensible a la expresión de células SP las primeras horas de exposición. 7. La exposición a IHH parece ser decisiva en la expresión de la población SP, aunque el estímulo inducido por el ejercicio mostró un efecto inverso sobre su cinética.[eng] The general hypothesis of this PhD dissertation document is based on the possible favorable effects of a protocol of intermittent hypobaric hypoxia (IHH) combined with light aerobic exercise in normoxia. We have tested if such IHH program can elicit a beneficial effect on the regeneration of skeletal muscle damage and contribute to a faster recovery in this type of injury. However, the well-known hematopoietic action of hypoxia exposure and exercise can alter the erythrocyte mass and even the circulatory dynamic at microcirculatory level. We have focused on the rheological properties of blood, presence of circulating stem cells and the dynamics of bone marrow side population (SP) cells. The core of this thesis is composed by two main studies whose general objective are: 1. To determine if the erythropoietic response elicited by intermittent hypobaric hypoxia exposure can alter blood rheology and thus affect in any way the oxygen delivery to tissues. 2. To outline if the IHH exposure can help to increase the number of peripheral blood circulating progenitor cells (CD34+) and bone marrow side population stem cells, in order to establish the usefulness of this intervention for skeletal muscle repair. Male Sprague-Dawley rats were studied in two basal states: untrained and trained and compared with trained rats that suffered skeletal muscle injury (down-hill running until exhaustion) at four stages (1, 3, 7 and 14 days) during damage recovery. Three experimental groups of wounded trained rats were studied: rats with passive recovery (CTRL); rats exposed to IHH after muscle damage (HYP); and, rats that, in addition to IHH, performed light aerobic exercise sessions (EHYP). The results obtained in this thesis allow us to conclude that the IHH in combination with light aerobic exercise in normoxia showed a higher erythropoietic effect, but without threatening the perfusion of damaged muscle because advantageous hemorheological adjustments. DyeCycle® Violet staining is selectively retained into CD34 + cells, thus allowing to the discrimination of two subsets of cells, internally referred as CD34+/DCVhigh and CD34+/DCVlow cells. Finally, IHH in combination with light aerobic exercise increased the number of CD34+/CD45neg and CD34+/CD45+ cells on the 7th day in EHYP group, although the exercise-induced stimulus showed a reverse effect on SP kinetics

Valoración del control neuromuscular de miembro inferior de futbolistas de alta competencia

The aim of this study was to assess neuromuscular control in high competition soccer players, since its early identification is of utmost importance to categorize their lower extremity injury risk profile. In this research, three gestures that subject the athlete to develop a correct neuromuscular control were proposed: change of direction (CD), deceleration (D) and vertical jump drop (CSV). Sixty soccer players between 15 and 41 years of age (20.7 ± 5.9) from the city of Punta Arenas were evaluated, giving as a result that a high percentage presented inadequate neuromuscular control, especially in the CD and D gesture, especially in the variables knee projection angle in the frontal plane (APRPF) and in the relation of the knee with the ground reaction force (GRF), which cause excessive dynamic valgus in the knee. El objetivo de este estudio fue valorar el control neuromuscular en futbolistas de alta competencia, ya que su identificación de manera temprana es de suma importancia para categorizar su perfil de riesgo de lesión de extremidad inferior. En esta investigación se proponen tres gestos que someten al deportista a desarrollar un correcto control neuromuscular: cambio de dirección (CD), desaceleración (D) y caída del salto vertical (CSV). Se evaluó a 60 futbolistas entre 15 y 41 años de edad (20,7 ± 5,9) de la ciudad de Punta Arenas, dando como resultado que un alto porcentaje presentaba un control neuromuscular inadecuado, especialmente en el gesto CD y D, sobre todo en las variables ángulo de proyección de la rodilla en el plano frontal (APRPF) y en la relación de la rodilla con la fuerza de reacción del suelo (GRF), las cuales provocan un valgo dinámico excesivo en el rodilla

A semiquantitative scoring tool to evaluate eccentric exercise-induced muscle damage in trained rats

Unaccustomed eccentric exercise is a welldocumented cause of exercise-induced muscle damage. However, in trained subjects muscle injury involves only light or moderate tissue damage. Since trained rats are widely used as a model for skeletal muscle injury, here we propose a semiquantitative scoring tool to evaluate muscle damage in trained rats. Twenty male Sprague-Dawley rats were trained for two weeks following a two-week preconditioning period, and randomly divided into two groups: control rats (CTL; n=5) and rats with eccentric exercise-induced muscle damage (INJ; n=15). Injured rats were sacrificed at three time points: 1, 3 and 7 days post injury (n=5 each). Transverse sections from the right soleus were cut (10 μm) and stained with haematoxylineosin. Samples were evaluated by two groups of observers (four researchers experienced in skeletal muscle histopathology and four inexperienced) using the proposed tool, which consisted of six items organised in three domains: abnormal fibre morphology, necrotic/(re) degenerating fibres (muscle fibre domain), endomysial and perimysial infiltration (inflammatory state domain) and endomysium and perimysium distension (interstitial compartment domain). We observed the expected time course in the six evaluated items. Furthermore, agreement among observers was evaluated by measuring the Intraclass Correlation Coefficient (ICC). Within the experienced group, items from the muscle fibre and interstitial compartment domains showed good agreement and the two items from the infiltration compartment domain showed excellent agreement. In conclusion, the proposed tool allowed quick and correct evaluation of light to moderate muscle damage in trained rats with good agreement between observers

Physical Activity, Seasonal Sensitivity and Psychological Well-Being of People of Different Age Groups Living in Extreme Environments

Physical activity can prevent many organic and mental pathologies. For people living in extreme southern high-latitude environments, weather conditions can affect these activities, altering their psychological well-being and favoring the prevalence of seasonal sensitivity (SS). This study aims to determine the relationships between the practice of physical activity, seasonal sensitivity and well-being in people living in high southern latitudes. A cross-sectional study was conducted, using the Seasonal Pattern Assessment Questionnaire (SPAQ), applying a psychological well-being scale, and determining sports practice according to the recommendations of the World Health Organization (WHO) for the 370 male (n = 209; 55%) and female (n = 173; 45%) participants. The main results indicated that 194 people (52 ± 7.7 years) reported physical activity. High-intensity physical activity practitioners recorded a significantly lower proportion of SS. In terms of psychological well-being, an adverse effect was found between the Seasonal Score Index (SSI) and five subcategories of the Ryff well-being scale. In conclusion, those who perform high-intensity physical activity have a lower SS, and those who have a higher SS have a lower psychological well-being

Diferencias morfológicas y de condición física en futbolistas adolescentes según posición de juego: una revisión sistemática

Introduction: The aim of this systematic review was to analyze the studies that evaluate morphological and physical fitness differences in young soccer players according to playing position.Material and Methods: For its elaboration, the PRISMA-P protocol was followed, the PubMed/MEDLINE database was used, and the Downs & Black methodological quality assessment was applied. Six studies met all the selection criteria, adding 784 soccer players (229 defenders [DF]; 271 midfielders [MF], 168 forwards [FW] and 69 goalkeepers [GK]) with a mean age of 16.2 years.Results: The analyzed studies indicate, that GK and DF have a height, body weight, endomorphic component and body fat higher than MF and FW, except for one study that reports higher values for body weight in FW and DF with respect to MF. In relation to physical fitness, the maximum squat exhibited higher values for FW compared to MF; cardiorespiratory fitness was higher in DF and MF when compared with GK and abdominal muscle resistance was greater in MF compared to DF. Conclusion: The GK and DF show greater height, body weight and body fat than the MF and FW. While physical fitness indicates that FW show greater lower body strength, MF and DF achieve greater cardiorespiratory fitness and MF present greater abdominal muscle resistance when young soccer players are analyzed according to playing position.Introducción: El objetivo de la presente revisión sistemática fue analizar los estudios que evalúan las diferencias morfológicas y de condición física en futbolistas adolescentes según posición de juego.Material y métodos: Para su elaboración se siguió el protocolo PRISMA-P, se utilizó la base de datos PubMed/MEDLINE y se aplicó la evaluación de calidad metodológica de Downs & Black. Seis estudios cumplieron con todos los criterios de selección, sumando 784 futbolistas (229 defensas [DF]; 271 mediocampistas [MC], 168 delanteros [DL] y 69 porteros [PT]) con una edad media de 16,2 años. Resultados: Los estudios analizados indican que los PT y DF poseen una altura, peso corporal, componente endomórfico y grasa corporal mayor que MC y DL, excepto un estudio que reporta valores más altos para peso corporal en DL y DF respecto a MC. En relación a la condición física, la sentadilla máxima exhibió valores más elevados para DL respecto a MC; la capacidad cardiorrespiratoria fue superior en DF y MC al compararlos con PT y la resistencia muscular abdominal fue mayor en MC respecto a DF. Conclusión: Los PT y DF ostentan mayor altura, peso corporal y grasa corporal que los MC y DL. Mientras que la condición física, indica que los DL demuestran mayor fuerza del tren inferior, los MC y DF consiguen mayor capacidad cardiorrespiratoria y los MC presentan mayor resistencia muscular abdominal cuando se analizan futbolistas adolescentes según posición de juego

A Molecular Characterization of the Allelic Expression of the BRCA1 Founder Δ9–12 Pathogenic Variant and Its Potential Clinical Relevance in Hereditary Cancer:International Journal of Molecular Sciences

Hereditary breast and ovarian cancer (HBOC) syndrome is a genetic condition that increases the risk of breast cancer by 80% and that of ovarian cancer by 40%. The most common pathogenic variants (PVs) causing HBOC occur in the BRCA1 gene, with more than 3850 reported mutations in the gene sequence. The prevalence of specific PVs in BRCA1 has increased across populations due to the effect of founder mutations. Therefore, when a founder mutation is identified, it becomes key to improving cancer risk characterization and effective screening protocols. The only founder mutation described in the Mexican population is the deletion of exons 9 to 12 of BRCA1 (BRCA1Δ9–12), and its description focuses on the gene sequence, but no transcription profiles have been generated for individuals who carry this gene. In this study, we describe the transcription profiles of cancer patients and healthy individuals who were heterozygous for PV BRCA1Δ9–12 by analyzing the differential expression of both alleles compared with the homozygous BRCA1 control group using RT–qPCR, and we describe the isoforms produced by the BRCA1 wild-type and BRCA1Δ9–12 alleles using nanopore long-sequencing. Using the Kruskal–Wallis test, our results showed a similar transcript expression of the wild-type allele between the healthy heterozygous group and the homozygous BRCA1 control group. An association between the recurrence and increased expression of both alleles in HBOC patients was also observed. An analysis of the sequences indicated four wild-type isoforms with diagnostic potential for discerning individuals who carry the PV BRCA1Δ9–12 and identifying which of them has developed cancer

Fatiga, el enemigo del movimiento en altura. VFC una opción viable de detección.

The move allows us to perform our daily life as normal under perfectly known parameters, however, there are circumstances where the locomotive is fully exposed to complex situations beyond the control of human beings, is the case of hypobaric hypoxia. Under hypoxic conditions the movement faces the constant threat of physical and mental fatigue, decreasing the chances of well executed movements, which often puts the risk to the individual and their environment. The control of motor actions based on heart rate variability, is shown to be an effective method for prevention and early indicators of fatigue, contributing to enhance the action of the individual psychomotor geographical height, proposing itself as a simple and low-cost motor control in hypobaric hypoxic.El movimiento nos permite diariamente realizar nuestra vida de manera normal bajo parámetros perfectamente conocidos. Sin embargo, existen circunstancias en donde el aparato locomotor se ve expuesto a situaciones completamente complejas y ajenas a la voluntad del ser humano, es el caso de la hipoxia hipobárica. Bajo condiciones hipóxicas el movimiento enfrenta la constante amenaza de fatiga física y mental, disminuyendo las posibilidades de movimientos bien ejecutados, que muchas veces ponen el riesgo al individuo y su entorno. El control de acciones motrices en base a la variabilidad de frecuencia cardiaca, muestra ser un método eficaz de prevención y anticipación de indicadores de fatiga, contribuyendo a mejorar la acción psicomotriz del individuo en altura geográfica, proponiéndose como un sistema simple y de bajo costo en el control motriz en hipóxica hipobárica

Redox modifications in synaptic components as biomarkers of cognitive status, in brain aging and disease

Aging is a natural process that includes several changes that gradually make organisms degenerate and die. Harman's theory proposes that aging is a consequence of the progressive accumulation of oxidative modifications mediated by reactive oxygen/nitrogen species, which plays an essential role in the development and progression of many neurodegenerative diseases. This review will focus on how abnormal redox modifications induced by age impair the functionality of neuronal redox-sensitive proteins involved in axonal elongation and guidance, synaptic plasticity, and intercellular communication. We will discuss post-transcriptional regulation of gene expression by microRNAs as a mechanism that controls the neuronal redox state. Finally, we will discuss how some brain-permeant antioxidants from the diet have a beneficial effect on cognition. Taken together, the evidence revised here indicates that oxidative-driven modifications of specific proteins and changes in microRNA expression may be useful biomarkers for aging and neurodegenerative diseases. Also, some specific antioxidant therapies have undoubtedly beneficial neuroprotective effects when administered in the correct doses, in the ideal formulation combination, and during the appropriate therapeutic window. The use of some antioxidants is, therefore, still poorly explored for the treatment of neurodegenerative diseases such as Alzheimer's disease.DIUV - CIDI 5/06 Comisión Nacional de Investigación Científica y Tecnológica (CONICYT) CONICYT FONDECYT 11150776 1170446 MAG1895 MAG1995 ANID/FONDAP 15150012 Chilean State Universities Network grant 1656-175

Effect of Confinement on Anxiety Symptoms and Sleep Quality during the COVID-19 Pandemic

Confinement during the COVID-19 pandemic has significantly impacted lifestyles worldwide. The aim of this study was to evaluate the effect of confinement on anxiety symptoms and sleep quality in people living in extreme southern latitudes. The Beck Anxiety Inventory (BAI) and the Pittsburgh Sleep Quality Index (PSQI) were administered to 617 people, 74.2% of whom were women. The sample was grouped according to confinement: the zone of confinement (CZ) (46.5%) and the zone of partial confinement (PZ) (53.5%). In addition, the sample was further categorized into four age subgroups (18–25 years; 26–40 years; 41–50 years; over 50 years). Higher levels of anxiety and worse sleep quality were found in the CZ group than in the PZ group. Women had higher levels of anxiety and worse sleep quality than men. A significant bidirectional relationship between anxiety and sleep quality was observed, even after controlling for sex. This study demonstrated that women and young adults were more vulnerable to the effects of confinement on anxiety symptoms and sleep quality in populations at southern latitudes

A three-criteria performance score for rats exercising on a running treadmill.

In this study, we propose a novel three-criteria performance score to semiquantitatively classify the running style, the degree of involvement and compliance and the validity of electric shock count for rats exercising on a treadmill. Each score criterion has several style-marks that are based on the observational registry of male Sprague-Dawley rats running for 4-7 weeks. Each mark was given a score value that was averaged throughout a session-registry and resulting in a session score for each criterion, ranging from "0" score for a hypothetical "worst runner", to score "1" for a hypothetical "perfect runner" rat. We found significant differences throughout a training program, thus providing evidence of sufficient sensitivity of this score to reflect the individual evolution of performance improvement in exercise capacity due to training. We hypothesize that this score could be correlated with other physiological or metabolic parameters, thus refining research results and further helping researchers to reduce the number of experimental subjects