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      Resilience to orthostasis and haemorrhage: A pilot study of common genetic and conditioning mechanisms

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          Abstract

          A major challenge presently is not only to identify the genetic polymorphisms increasing risk to diseases, but to also find out factors and mechanisms, which can counteract a risk genotype by developing a resilient phenotype. The objective of this study was to examine acquired and innate vagal mechanisms that protect against physical challenges and haemorrhages in 19 athletes and 61 non-athletes. These include examining change in heart rate variability (HF-HRV; an indicator of vagus activity) in response to orthostatic challenge, platelet count (PLT), mean platelet volume (MPV), and single-nucleotide polymorphisms in genes that encode several coagulation factors, PAI-1, and MTHFR. Individual differences in PLT and MPV were significant predictors, with opposite effects, of the profiles of the HF-HRV changes in response to orthostasis. Regular physical training of athletes indirectly (through MPV) modifies the genetic predisposing effects of some haemostatic factors (PAI-1 and MTHFR) on vagal tone and reactivity. Individual differences in vagal tone were also associated with relationships between Factor 12 C46T and Factor 11 C22771T genes polymorphisms. This study showed that genetic predispositions for coagulation are modifiable. Its potential significance is promoting advanced protection against haemorrhages in a variety of traumas and injuries, especially in individuals with coagulation deficits.

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          Most cited references51

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          Resilience and mental health.

          The relationship between disease and good health has received relatively little attention in mental health. Resilience can be viewed as a defence mechanism, which enables people to thrive in the face of adversity and improving resilience may be an important target for treatment and prophylaxis. Though resilience is a widely-used concept, studies vary substantially in their definition, and measurement. Above all, there is no common underlying theoretical construct to this very heterogeneous research which makes the evaluation and comparison of findings extremely difficult. Furthermore, the varying multi-disciplinary approaches preclude meta-analysis, so that clarification of research in this area must proceed firstly by conceptual unification. We attempt to collate and classify the available research around a multi-level biopsychosocial model, theoretically and semiotically comparable to that used in describing the complex chain of events related to host resistance in infectious disease. Using this underlying construct we attempt to reorganize current knowledge around a unitary concept in order to clarify and indicate potential intervention points for increasing resilience and positive mental health. 2010 Elsevier Ltd. All rights reserved.
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            Sample size requirements for association studies of gene-gene interaction.

            In the study of complex diseases, it may be important to test hypotheses related to gene-gene (G x G) interaction. The success of such studies depends critically on obtaining adequate sample sizes. In this paper, the author investigates sample size requirements for studies of G x G interaction, focusing on four study designs: the matched-case-control design, the case-sibling design, the case-parent design, and the case-only design. All four designs provide an estimate of interaction on a multiplicative scale, which is used as a unifying theme in the comparison of sample size requirements. Across a variety of genetic models, the case-only and case-parent designs require fewer sampling units (cases and case-parent trios, respectively) than the case-control (pairs) or case-sibling (pairs) design. For example, the author describes an asthma study of two common recessive genes for which 270 matched case-control pairs would be required to detect a G x G interaction of moderate magnitude with 80% power. By comparison, the same study would require 319 case-sibling pairs but only 146 trios in the case-parent design or 116 cases in the case-only design. A software program that computes sample size for studies of G x G interaction and for studies of gene-environment (G x E) interaction is freely available (http://hydra.usc.edu/gxe).
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              Endurance training guided individually by daily heart rate variability measurements.

              Purpose of this study was to test utility of heart rate variability (HRV) in daily endurance exercise prescriptions. Twenty-six healthy, moderately fit males were randomized into predefined training group (TRA, n = 8), HRV-guided training group (HRV, n = 9), and control group (n = 9). Four-week training period consisted of running sessions lasting 40 min each at either low- or high-intensity level. TRA group trained on 6 days a week, with two sessions at low and four at high intensity. Individual training program for HRV group was based on individual changes in high-frequency R-R interval oscillations measured every morning. Increase or no change in HRV resulted in high-intensity training on that day. If there was significant decrease in HRV (below reference value [10-day mean-SD] or decreasing trend for 2 days), low-intensity training or rest was prescribed. Peak oxygen consumption (VO(2peak)) and maximal running velocity (Load(max)) were measured in maximal treadmill test before and after the training. In TRA group, Load(max) increased from 15.1 +/- 1.3 to 15.7 +/- 1.2 km h(-1) (P = 0.004), whereas VO(2peak) did not change significantly (54 +/- 4 pre and 55 +/- 3 ml kg(-1) min(-1) post, P = 0.224). In HRV group, significant increases were observed in both Load(max) (from 15.5 +/- 1.0 to 16.4 +/- 1.0 km h(-1), P < 0.001) and VO(2peak) (from 56 +/- 4 to 60 +/- 5 ml kg(-1) min(-1), P = 0.002). The change in Load(max) was significantly greater in HRV group compared to TRA group (0.5 +/- 0.4 vs. 0.9 +/- 0.2 km h(-1), P = 0.048, adjusted for baseline values). No significant differences were observed in the changes of VO(2peak) between the groups. We concluded that cardiorespiratory fitness can be improved effectively by using HRV for daily training prescription.
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                Author and article information

                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group
                2045-2322
                29 May 2015
                2015
                : 5
                : 10703
                Affiliations
                [1 ]Sholokhov Moscow State University for the Humanities, the Russian Institute for Advanced Study and Institute of Neurosciences and Cognitive Research, Verkhnyaya Radishevskaya 16-18, Moscow, 109240
                [2 ]Laboratory of Neuroimmunopathology, Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, 8 Baltiyskaia ul ., Moscow, 125315, Russia
                [3 ]Institute of Fundamental Medicine and Biology, Kazan (Volga region) Federal University, 18 Kremlin ul., Kazan , 420008, Russia
                [4 ]Pharmacogenomics laboratory, Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences , Novosibirsk, 630090, Russia
                Author notes
                Article
                srep10703
                10.1038/srep10703
                4650686
                26024428
                50aa239b-d719-443e-9b46-ce33ee2f2585
                Copyright © 2015, Macmillan Publishers Limited

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0.

                History
                : 05 September 2014
                : 27 April 2015
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