RESUMEN
BACKGROUND: Cardiopulmonary resuscitation (CPR) performance depends on individual ability and training. Well-trained or professional rescuers can maintain high-quality CPR for longer than laypeople. This study aimed to examine the effects of reducing resting intervals on CPR performance, physiological parameters, and hemodynamic parameters during prolonged CPR in well-trained providers. METHODS: The study enrolled 90 volunteers from the paramedic students of our institution. They were randomly divided into 3 groups: 2âminutes, 1âminute 45âseconds, and 1âminute 30âseconds rest groups. Each participant performed 5 cycles of chest compression only CPR (2âmin/cycle) with different resting intervals according to grouping. CPR quality, physiological variations, and hemodynamic variations were measured for each cycle and compared across the groups. RESULTS: Of the 90 volunteers, 79 well-trained providers were finally included. The variation of the average chest compression depth across the 5 cycles showed significant differences between the 3 groups: from cycle 1 to 2: 1.2 (3.1) mm, -0.8 (2.0) mm, and -2.0 (3.0) mm in the 2âminutes, 1âminute 45âseconds, and 1âminute 30âseconds groups, respectively (Pâ<â.001); from cycle 1 to 3: 0.0 (3.0) mm, -0.7 (3.2) mm, and -2.6 (3.9) mm, respectively (Pâ=â.030). However, all 3 groups maintained the recommended rate and chest compression depth for all 5 cycles. Physiological and hemodynamic parameters showed no significant differences between the groups. CONCLUSIONS: Well-trained providers were able to maintain high-quality CPR despite reducing rest intervals. Adjusting the rest interval may help maintain overall CPR quality in special situations or where layperson rescuers are involved.
Asunto(s)
Reanimación Cardiopulmonar/educación , Hemodinámica/fisiología , Calidad de la Atención de Salud/estadística & datos numéricos , Descanso/fisiología , Técnicos Medios en Salud/educación , Técnicos Medios en Salud/estadística & datos numéricos , Reanimación Cardiopulmonar/estadística & datos numéricos , Oscilación de la Pared Torácica/estadística & datos numéricos , Oscilación de la Pared Torácica/tendencias , Auxiliares de Urgencia/educación , Auxiliares de Urgencia/estadística & datos numéricos , Fatiga , Femenino , Humanos , Masculino , Fenómenos Fisiológicos/fisiología , Estudios Prospectivos , Entrenamiento Simulado/métodos , Estudiantes , Factores de Tiempo , Adulto JovenRESUMEN
The aim of this study was to evaluate and compare the hamstring (H) and quadriceps (Q) strength, bilateral difference and balance ratios in female soccer players. Ninety-three athletes from three age groups: under 13 (U13), 15 (U15) and 18 (U18) participated in the study performing isokinetic tests to measure peak torque, total work, average power and torque at 30º of thigh muscles. Conventional strength balance ratios, angle-specific balance ratio and bilateral strength difference were evaluated. There was bilateral strength difference for extensor muscles total work (p = 0.02) in U13 and flexor muscles peak torque (p = 0.02) in U15. All variables were superior in U15 than U13 (p <.05). There was no strength difference between U15 and U18. Balance ratios did not differ between sides or age groups. The study showed that although peak torque values were higher in U15 than in U13, balance ratios were similar.
Asunto(s)
Músculos Isquiosurales/fisiología , Fuerza Muscular/fisiología , Músculo Cuádriceps/fisiología , Fútbol/fisiología , Adolescente , Factores de Edad , Estatura , Peso Corporal , Niño , Estudios Transversales , Femenino , Humanos , Fenómenos Fisiológicos/fisiología , TorqueRESUMEN
BACKGROUND: Acute mountain sickness (AMS) is the mildest form of acute altitude illnesses, and consists of non-specific symptoms when unacclimatized persons ascend to elevation of ≥2500 m. Risk factors of AMS include: the altitude, individual susceptibility, ascending rate and degree of pre-acclimatization. In the current study, we examined whether physiological response at low altitude could predict the development of AMS. METHODS: A total of 111 healthy adult healthy volunteers participated in this trial; and 99 (67 men and 32 women) completed the entire study protocol. Subjects were asked to complete a 9-min exercise program using a mechanically braked bicycle ergometer at low altitude (500 m). Heart rate, blood pressure (BP) and pulse oxygen saturation (SpO2) were recorded prior to and during the last minute of exercise. The ascent from 500 m to 4100 m was completed in 2 days. AMS was defined as ≥3 points in a 4-item Lake Louise Score, with at least one point from headache wat 6-8 h after the ascent. RESULTS: Among the 99 assessable subjects, 47 (23 men and 24 women) developed AMS at 4100 m. In comparison to the subjects without AMS, those who developed AMS had lower proportion of men (48.9% vs. 84.6%, P < 0.001), height (168.4 ± 5.9 vs. 171.3 ± 6.1 cm, P = 0.019), weight (62.0 ± 10.0 vs. 66.7 ± 8.6 kg, P = 0.014) and proportion of smokers (23.4% vs. 51.9%, P = 0.004). Multivariate regression analysis revealed the following independent risks for AMS: female sex (odds ratio (OR) =6.32, P < 0.001), SpO2 change upon exercise at low altitude (OR = 0.63, P = 0.002) and systolic BP change after the ascent (OR = 0.96, P = 0.029). Women had larger reduction in SpO2 after the ascent, higher AMS percentage and absolute AMS score. Larger reduction of SpO2 after exercise was associated with both AMS incidence (P = 0.001) and AMS score (P < 0.001) in men but not in women. CONCLUSIONS: Larger SpO2 reduction after exercise at low altitude was an independent risk for AMS upon ascent. Such an association was more robust in men than in women. TRIAL REGISTRATION: Chinese Clinical Trial Registration, ChiCTR1900025728 . Registered 6 September 2019.
Asunto(s)
Mal de Altura/complicaciones , Altitud , Ejercicio Físico/fisiología , Fenómenos Fisiológicos/fisiología , Factores Sexuales , Adolescente , Adulto , Mal de Altura/epidemiología , China/epidemiología , Estudios de Cohortes , Correlación de Datos , Femenino , Humanos , Masculino , Estudios Prospectivos , Encuestas y Cuestionarios , Factores de TiempoRESUMEN
The conformation of the German shepherd dog (GSD) varies considerably within the breed. These differences may result in large variation in the movement and limb loading and undesirable consequences to their musculoskeletal health. This study aimed to investigate the relationship between conformation and biomechanical measures in 60 GSDs. Full body kinematic and kinetic measures were computed from 3D motion capture and pressure data. The dogs were divided into groups based on their back slope and curvature. Correlation analysis and statistical differences between groups showed that GSDs with a greater back slope have a greater contact area in their forelimbs and place them closer together when standing (n = 60). During trot, the dogs with sloped back showed a greater vertical force in the forelimbs and a greater mid-thoracic flexion (n = 60). Unilateral differences were found in the stifle flexion, hock flexion and hock adduction, suggesting greater movement asymmetry with an increase in the back slope (n = 30). In conclusion, several biomechanical parameters are affected by the GSD's slope of the back and not by its curvature. Further studies are required to determine whether the variation in movement, posture and conformation within the breed relates to an increased susceptibility to musculoskeletal disorders.
Asunto(s)
Movimiento/fisiología , Postura/fisiología , Somatotipos/fisiología , Animales , Fenómenos Biomecánicos/fisiología , Perros , Extremidades , Femenino , Miembro Anterior , Marcha , Cinética , Masculino , Apariencia Física/fisiología , Fenómenos Fisiológicos/fisiología , Posición de PieRESUMEN
Neuronal networks, especially those in the central nervous system (CNS), evolved to support extensive functional capabilities while ensuring stability. Several physiological "brakes" that maintain the stability of the neuronal networks in a healthy state quickly become a hinderance postinjury. These "brakes" include inhibition from the extracellular environment, intrinsic factors of neurons and the control of neuronal plasticity. There are distinct differences between the neuronal networks in the peripheral nervous system (PNS) and the CNS. Underpinning these differences is the trade-off between reduced functional capabilities with increased adaptability through the formation of new connections and new neurons. The PNS has "facilitators" that stimulate neuroregeneration and plasticity, while the CNS has "brakes" that limit them. By studying how these "facilitators" and "brakes" work and identifying the key processes and molecules involved, we can attempt to apply these theories to the neuronal networks of the CNS to increase its adaptability. The difference in adaptability between the CNS and PNS leads to a difference in neuroregenerative properties and plasticity. Plasticity ensures quick functional recovery of abilities in the short and medium term. Neuroregeneration involves synthesizing new neurons and connections, providing extra resources in the long term to replace those damaged by the injury, and achieving a lasting functional recovery. Therefore, by understanding the factors that affect neuroregeneration and plasticity, we can combine their advantages and develop rehabilitation techniques. Rehabilitation training methods, coordinated with pharmacological interventions and/or electrical stimulation, contributes to a precise, holistic treatment plan that achieves functional recovery from nervous system injuries. Furthermore, these techniques are not limited to limb movement, as other functions lost as a result of brain injury, such as speech, can also be recovered with an appropriate training program.
Asunto(s)
Regeneración Nerviosa/fisiología , Plasticidad Neuronal/fisiología , Recuperación de la Función/fisiología , Heridas y Lesiones/complicaciones , Sistema Nervioso Central/fisiopatología , Humanos , Fenómenos Fisiológicos/fisiología , Heridas y Lesiones/fisiopatologíaRESUMEN
The ability to maintain health, or recover to a healthy state after disease, is an active process involving distinct adaptation mechanisms coordinating interactions between all physiological systems of an organism. Studies over the past several decades have assumed the mechanisms of health and disease are essentially inter-changeable, focusing on the elucidation of the mechanisms of disease pathogenesis to enhance health, treat disease, and increase healthspan. Here, I propose that the evolved mechanisms of health are distinct from disease pathogenesis mechanisms and suggest that we develop an understanding of the biology of physiological health. In this Perspective, I provide a definition of, a conceptual framework for, and proposed mechanisms of physiological health to complement our understanding of disease and its treatment.
Asunto(s)
Adaptación Fisiológica/fisiología , Salud/tendencias , Fenómenos Fisiológicos/fisiología , Adaptación Fisiológica/genética , HumanosRESUMEN
Flamethrowers are widely considered one of warfare's most controversial weapons and are capable of inflicting gruesome physical injuries and intense psychological trauma. Despite being the last of the major combatants in World War II (WWII) to develop them, the United States military quickly became the most frequent and adept operator of portable flamethrowers. This gave the U.S. military ample opportunity to observe the effects of flamethrowers on enemy soldiers. However, while most people in modern times would consider immolation by flamethrower to be an unnecessarily painful and inhumane way to inflict casualties, immolation was, at one point during World War II (WWII), referred to as "mercy killing" by the U.S. Chemical Warfare Service (CWS). This mischaracterization arose from a series of first-hand accounts describing what were believed to be quick, painless, and unmarred deaths, as well as from a poor and incomplete understanding of flamethrower lethality. As a result, indirect mechanisms such as hypoxia and carbon monoxide poisoning were generally absent from accounts of the flamethrower's fatal effects. It was not until several years after flamethrowers were introduced to the frontlines that the CWS and National Defense Research Committee (NDRC) conducted a series of tests to better understand the physiological and toxicological effects of flamethrowers. This article examines how the initial absence of scientific data on the physiologic effects of flamethrowers led to an inaccurate understanding of their lethality, and bizarre claims that one of history's most horrific instruments of war was considered one of the more "humane" weapons on the battlefield.
Asunto(s)
Quemaduras Químicas/complicaciones , Fenómenos Fisiológicos/fisiología , Armas/estadística & datos numéricos , Segunda Guerra Mundial , Sesgo , Quemaduras Químicas/fisiopatología , Humanos , Estados Unidos , Armas/clasificaciónRESUMEN
INTRODUCTION: Military and civil aviation have documented physiological episodes among aircrews. Therefore, continued efforts are being made to improve the internal environment. Studies have shown that exposures to many organic compounds present in emissions are known to cause a variety of physiological symptoms. We hypothesize that these compounds may reversibly inhibit acetylcholinesterase, which may disrupt synaptic signaling. As a result, neural proteins leak through the damaged blood-brain barrier into the blood and in some, elicit an autoimmune response. MATERIALS AND METHODS: Neural-specific autoantibodies of immunoglobulin-G (IgG) class were estimated by the Western blotting technique in the sera of 26 aircrew members and compared with the sera of 19 normal healthy nonaircrew members, used as controls. RESULTS: We found significantly elevated levels of circulating IgG-class autoantibodies to neurofilament triplet proteins, tubulin, microtubule-associated tau proteins (Tau), microtubule-associated protein-2, myelin basic protein, and glial fibrillary acidic protein, but not S100 calcium-binding protein B compared to healthy controls. CONCLUSION: Repetitive physiological episodes may initiate cellular injury, leading to neuronal degeneration in selected individuals. Diagnosis and intervention should occur at early postinjury periods. Use of blood-based biomarkers to assess subclinical brain injury would help in both diagnosis and treatment.
Asunto(s)
Personal Militar/estadística & datos numéricos , Fenómenos Fisiológicos/fisiología , Medicina Aeroespacial/métodos , Medicina Aeroespacial/estadística & datos numéricos , Aeronaves , Autoanticuerpos/análisis , Autoanticuerpos/sangre , Biomarcadores/análisis , Biomarcadores/sangre , Western Blotting/métodos , Proteína Ácida Fibrilar de la Glía/análisis , Proteína Ácida Fibrilar de la Glía/sangre , Humanos , Inmunoglobulina G/análisis , Inmunoglobulina G/sangre , Proteínas Asociadas a Microtúbulos/análisis , Proteínas Asociadas a Microtúbulos/sangre , Proteína Básica de Mielina/análisis , Proteína Básica de Mielina/sangre , Proteínas de Neurofilamentos/análisis , Proteínas de Neurofilamentos/sangre , Proteínas S100/análisis , Proteínas S100/sangre , Tubulina (Proteína)/análisis , Tubulina (Proteína)/sangreRESUMEN
The microbialization of coral reefs predicts that microbial oxygen consumption will cause reef deoxygenation. Here we tested this hypothesis by analyzing reef microbial and primary producer oxygen metabolisms. Metagenomic data and in vitro incubations of bacteria with primary producer exudates showed that fleshy algae stimulate incomplete carbon oxidation metabolisms in heterotrophic bacteria. These metabolisms lead to increased cell sizes and abundances, resulting in bacteria consuming 10 times more oxygen than in coral incubations. Experiments probing the dissolved and gaseous oxygen with primary producers and bacteria together indicated the loss of oxygen through ebullition caused by heterogenous nucleation on algae surfaces. A model incorporating experimental production and loss rates predicted that microbes and ebullition can cause the loss of up to 67% of gross benthic oxygen production. This study indicates that microbial respiration and ebullition are increasingly relevant to reef deoxygenation as reefs become dominated by fleshy algae.
Asunto(s)
Antozoos/fisiología , Biofisica , Oxígeno/metabolismo , Fenómenos Fisiológicos/fisiología , Animales , Bacterias/metabolismo , Biomasa , Carbono/metabolismo , Arrecifes de Coral , Ecosistema , Procesos Heterotróficos , Metagenoma , Microalgas/metabolismo , Agua de Mar/microbiología , Microbiología del AguaRESUMEN
Despite a huge range in lung size between species, there is little measured difference in the ability of the lung to provide a well-matched air flow (ventilation) to blood flow (perfusion) at the gas exchange tissue. Here, we consider the remarkable similarities in ventilation/perfusion matching between species through a biophysical lens and consider evidence that matching in large animals is dominated by gravity but in small animals by structure.
Asunto(s)
Pulmón/fisiología , Animales , Gravitación , Humanos , Ratones , Fenómenos Fisiológicos/fisiología , Flujo Sanguíneo Regional/fisiología , RespiraciónRESUMEN
Purpose: Exploring real-life experiences of Chronic Obstructive Pulmonary Disease (COPD) patients during rehabilitation can contribute with new knowledge of what has significance for their participation and chance for improved health and well-being. Therefore, this study aims to gain in-depth knowledge of COPD patients' lived experiences while following standard pulmonary out-patient rehabilitation. Methods: Combined participant observations and interviews were conducted among 21 participants in pulmonary rehabilitation. A three-leveled phenomenological-hermeneutic interpretation was applied. Results: Living with COPD was challenging due to dyspnea and other physical troubles. This caused a lack of trust in the body and complicated rehabilitation participation. When improving management of breath during rehabilitation, the patients gained a new sense of trust in the body. This was accompanied by a nascent hope and increased well-being. However, not succeeding in this left patients with a persistent lack of hope. Conclusions: Comprehensive troubles in living with COPD paradoxically prevents patients' prospect of overcoming a perceived lack of trust in their body during standard pulmonary rehabilitation. Enhancing breath management has a significant impact on COPD patients' trust in own capabilities to improve well-being and health. Future rehabilitation must accommodate COPD patients' troubles by longer-lasting, well-coordinated, individually supportive and more easily accessible programmes.
Asunto(s)
Adaptación Psicológica , Pacientes/psicología , Fenómenos Fisiológicos/fisiología , Enfermedad Pulmonar Obstructiva Crónica/psicología , Enfermedad Pulmonar Obstructiva Crónica/rehabilitación , Calidad de Vida/psicología , Anciano , Anciano de 80 o más Años , Femenino , Hermenéutica , Humanos , Masculino , Persona de Mediana Edad , Investigación CualitativaRESUMEN
INTRODUCTION: Physiological events (PEs) are a growing problem for US military aviation with detrimental risks to safety and mission readiness. Seeking causative factors is, therefore, of high importance. There is no evidence to date associating carbon dioxide (CO2) pre-flight exposure and decompression sickness (DCS) in aviators. MATERIALS AND METHODS: This study is a case series of six aviators with PE after being exposed to a rapid decompression event (RDE) with symptoms consistent with type II DCS. The analysis includes retrospective review of flight and environmental data to further assess a possible link between CO2 levels and altitude physiologic events (PEs). IRB approval was obtained for this study. RESULTS: This case series presents six aviators with PE after being exposed to a rapid decompression event (RDE) with symptoms consistent with type II DCS. Another three aviators were also exposed to a RDE, but remained asymptomatic. All events involved tactical jet aircraft flying at an average of 35,600' Mean Sea Level (MSL) when a RDE occurred, Retrospective reviews led to the discovery that the affected individuals were exposed, pre-flight, to poor indoor air quality demonstrated by elevated levels of measured CO2. CONCLUSION: PEs are a growing safety concern for the aviation community in the military. As such, increasing measures are taken to ensure safety of flight and completion of the mission. To date, there is no correlation of CO2 exposure and altitude DCS. While elevated CO2 levels cannot be conclusively implicated as causative, this case series suggests a potential role of CO2 in altitude DCS through CO2 direct involvement with emboli gas composition, as well as pro-inflammatory cascade. Aviators exposed to elevated CO2 in poorly ventilated rooms developed PE symptoms consistent with DCS, while at the same command, aviators that were exposed to a well ventilated room did not. This report is far from an answer, but does demonstrate an interesting case series that draws some questions about CO2's role in these aviator's DCS experience. Other explanations are plausible, including the accurate diagnosis of DCS, health variables amongst the aviators, and differences in aircraft and On-Board Oxygen Generation Systems (OBOGS). For a better understanding, the role of environmental CO2 and pre-flight exposure as a risk of DCS should be reviewed.
Asunto(s)
Dióxido de Carbono/fisiología , Enfermedad de Descompresión/etiología , Exposición a Riesgos Ambientales/efectos adversos , Pilotos/estadística & datos numéricos , Adulto , Dióxido de Carbono/metabolismo , Enfermedad de Descompresión/sangre , Enfermedad de Descompresión/fisiopatología , Humanos , Masculino , Fenómenos Fisiológicos/fisiología , Estudios RetrospectivosRESUMEN
NEW FINDINGS: What is the topic for this review? We discuss the dichotomization of continuous-level physiological measurements into 'responders' and 'non-responders' when interventions/treatments are examined in robust parallel-group studies. What advances does it highlight? Sample responder counts are biased by pre-to-post within-subject variability. Sample differences in counts may be explained wholly by differences in mean response, even without individual response heterogeneity and even if test-retest measurement error informs the choice of response threshold. A less biased and more informative approach uses the SD of individual responses to estimate the chance a new person from the population of interest will be a responder. ABSTRACT: As a follow-up to our 2015 review, we cover more issues on the topic of 'response heterogeneity', which we define as clinically important individual differences in the physiological responses to the same treatment/intervention that cannot be attributed to random within-subject variability. We highlight various pitfalls with the common practice of counting the number of 'responders', 'non-responders' and 'adverse responders' in samples that have been given certain treatments or interventions for research purposes. We focus on the classical parallel-group randomized controlled trial and assume typical good practice in trial design. We show that sample responder counts are biased because individuals differ in terms of pre-to-post within-subject random variability in the study outcome(s) and not necessarily treatment response. Ironically, sample differences in responder counts may be explained wholly by sample differences in mean response, even if there is no response heterogeneity at all. Sample comparisons of responder counts also have relatively low statistical precision. These problems do not depend on how the response threshold has been selected, e.g. on the basis of a measurement error statistic, and are not rectified fully by the use of confidence intervals for individual responses in the sample. The dichotomization of individual responses in a research sample is fraught with pitfalls. Less biased approaches for estimating the proportion of responders in a population of interest are now available. Importantly, these approaches are based on the SD for true individual responses, directly incorporating information from the control group.
Asunto(s)
Fenómenos Fisiológicos/fisiología , Humanos , Fisiología/métodos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Biosensors are composed of (bio)receptors, transducers, and detection systems and are able to convert the biological stimulus into a measurable signal. This systematic review evaluates the current state of the art of innovation and research in this field, identifying the biosensors that in vitro monitor the musculoskeletal system cellular processes. Two databases found 20 in vitro studies, from January 1, 2008 to December 31, 2017, dealing with musculoskeletal system cells. The biosensors were divided into two groups based on the transduction mechanism: optical or electrochemical. The first group evaluated osteoblasts or mesenchymal stem cell (MSC) biocompatibility, viability, differentiation, alkaline phosphatase, enzyme, and protein detection. The second group detected cell impedance, ATP release, and superoxide concentration in tenocytes, osteoblasts, MSCs, and myoblasts. This review highlighted that the in vitro scenario is still at an early phase and limited for what concerns both the type of bioanalyte and for the type of system detector used.
Asunto(s)
Sistema Musculoesquelético/fisiopatología , Fenómenos Fisiológicos/fisiología , Animales , Técnicas Biosensibles/métodos , Humanos , Células Madre Mesenquimatosas/fisiología , Mioblastos/fisiología , Osteoblastos/fisiologíaRESUMEN
Six-month-old infants can store representations of multiple objects in working memory but do not always remember the objects' features (e.g., shape). Here, we asked whether infants' object representations (a) may contain conceptual content and (b) may contain this content even if perceptual features are forgotten. We hid two conceptually distinct objects (a humanlike doll and a nonhuman ball) one at a time in two separate locations and then tested infants' memory for the first-hidden object by revealing either the original hidden object or an unexpected other object. Using looking time, we found that infants remembered the categorical identity of the hidden object but failed to remember its perceptual identity. Our results suggest that young infants may encode conceptual category in a representation of an occluded object, even when perceptual features are lost.
Asunto(s)
Cognición/fisiología , Memoria a Corto Plazo/fisiología , Recuerdo Mental/fisiología , Fenómenos Fisiológicos/fisiología , Femenino , Humanos , Lactante , Masculino , Apego a Objetos , Psicología Social/métodos , TiempoRESUMEN
Recent studies have called into question the idea that facial masculinity is a condition-dependent male ornament that indicates immunocompetence in humans. We add to this growing body of research by calculating an objective measure of facial masculinity/femininity using 3D images in a large sample (n = 1,233) of people of European ancestry. We show that facial masculinity is positively correlated with adult height in both males and females. However, facial masculinity scales with growth similarly in males and females, suggesting that facial masculinity is not exclusively a male ornament, as male ornaments are typically more sensitive to growth in males compared with females. Additionally, we measured immunocompetence via heterozygosity at the major histocompatibility complex (MHC), a widely-used genetic marker of immunity. We show that, while height is positively correlated with MHC heterozygosity, facial masculinity is not. Thus, facial masculinity does not reflect immunocompetence measured by MHC heterozygosity in humans. Overall, we find no support for the idea that facial masculinity is a condition-dependent male ornament that has evolved to indicate immunocompetence.
Asunto(s)
Cara/fisiología , Complejo Mayor de Histocompatibilidad/fisiología , Adolescente , Adulto , Belleza , Conducta de Elección/fisiología , Femenino , Heterocigoto , Humanos , Inmunocompetencia/fisiología , Masculino , Masculinidad , Fenómenos Fisiológicos/fisiología , Caracteres Sexuales , Conducta Sexual/fisiología , Adulto JovenRESUMEN
Mechanism is a widely used concept in biology. In 2017, more than 10% of PubMed abstracts used the term. Therefore, searching for and reasoning about mechanisms is fundamental to much of biomedical research, but until now there has been almost no computational infrastructure for this purpose. Recent work in the philosophy of science has explored the central role that the search for mechanistic accounts of biological phenomena plays in biomedical research, providing a conceptual basis for representing and analyzing biological mechanism. The foundational categories for components of mechanisms-entities and activities-guide the development of general, abstract types of biological mechanism parts. Building on that analysis, we have developed a formal framework for describing and representing biological mechanism, MecCog, and applied it to describing mechanisms underlying human genetic disease. Mechanisms are depicted using a graphical notation. Key features are assignment of mechanism components to stages of biological organization and classes; visual representation of uncertainty, ignorance, and ambiguity; and tight integration with literature sources. The MecCog framework facilitates analysis of many aspects of disease mechanism, including the prioritization of future experiments, probing of gene-drug and gene-environment interactions, identification of possible new drug targets, personalized drug choice, analysis of nonlinear interactions between relevant genetic loci, and classification of diseases based on mechanism.
Asunto(s)
Clasificación/métodos , Biología Computacional/métodos , Enfermedad/clasificación , Fenómenos Biológicos , Investigación Biomédica , Biología Computacional/normas , Bases de Datos Factuales , Humanos , Fenómenos Fisiológicos/fisiologíaRESUMEN
Regular exercise has widespread health benefits. Fundamental to these beneficial effects is the ability of the heart to intermittently and substantially increase its performance without incurring damage, but the underlying homeostatic mechanisms are unclear. We identify the ROS-generating NADPH oxidase-4 (Nox4) as an essential regulator of exercise performance in mice. Myocardial Nox4 levels increase during acute exercise and trigger activation of the transcription factor Nrf2, with the induction of multiple endogenous antioxidants. Cardiomyocyte-specific Nox4-deficient (csNox4KO) mice display a loss of exercise-induced Nrf2 activation, cardiac oxidative stress and reduced exercise performance. Cardiomyocyte-specific Nrf2-deficient (csNrf2KO) mice exhibit similar compromised exercise capacity, with mitochondrial and cardiac dysfunction. Supplementation with an Nrf2 activator or a mitochondria-targeted antioxidant effectively restores cardiac performance and exercise capacity in csNox4KO and csNrf2KO mice respectively. The Nox4/Nrf2 axis therefore drives a hormetic response that is required for optimal cardiac mitochondrial and contractile function during physiological exercise.