• Nikos C. Apostolopoulos


The physicist Richard Feynman, during his commencement address at Cal Tech (1974), once uttered that it was necessary to be honest. This he believed was a cornerstone of scientific integrity. As scientists, we often strive to create open forums of dialogue through experiments and publications. However, an important and a necessary step, which is often neglected, is the reporting of the limitations. The fear is that this will jeopardize the acceptance of our material. Nothing could be furthest from the truth. The reporting of potential limitations offers incentives to authors, scientists, and researchers, for their discussion helps to foster as well as shape future research, benefiting scientific inquiry. In this chapter, several limitations are discussed in order to provide a frank and unbiased discourse of the importance of stretch intensity and the inflammatory response. What is presented is the reasoning behind the judgement of the limitation(s).


Blood collection Methodology Compliance Stretching intensity Duration Frequency Nutrition Mental stress Age 


  1. Akira, S., Hirano, T., Taga, T., & Kishimoto, T. (1990). Biology of multifunctional cytokines: il-6 and related molecules (Il-1 and Tnf). FASEB, 4, 2860–2867.CrossRefGoogle Scholar
  2. Bauer, J., Lengyel, G., Bauer, T. M., Acs, G., & Gerok, W. (1989). Regulation of interleukin-6 receptor expression in human monocytes and hepatocytes. FEBS Letters, 249, 27–30.CrossRefGoogle Scholar
  3. Brookes, S. T., Whitley, E., Peters, T. J., Mulheran, P. A., Egger, M., & Davey Smith, G. (2001). Subgroup analyses in randomised controlled trials: quantifying the risks of false-positives and false-negatives. Health Technology Assessment, 5, 1–56.CrossRefGoogle Scholar
  4. Campbell, M., Fitzpatrick, R., Haines, A., Kinmouth, A. L., Sandercock, P., & Spiegelhalter, D. (2000). Framework for design and evaluation of complex interventions to improve health. BMJ, 32, 694–696.CrossRefGoogle Scholar
  5. Dandona, P., Aljada, A., Chaudhuri, A., Mohanty, P., & Garg, R. (2005). A comprehensive perspective based on interactions between obesity, diabetes, and inflammation. Circulation, 111, 1448–1454.CrossRefGoogle Scholar
  6. Esposito, K., & Giugliano, D. (2006). Diet and inflammation: a link to metabolic and cardiovascular disease. European Heart Journal, 27, 15–20.CrossRefGoogle Scholar
  7. Feland, J. B., Myrer, J. W., & Merrill, R. M. (2001). Acute changes in hamstring flexibility: pnf versus static stretch in senior athletes. Physical Therapy in Sport, 2, 186–193.CrossRefGoogle Scholar
  8. Fielding, R. A. (1995). Symposium on ‘nutrition for the elderly’. The Proceedings of the Nutrition Society, 54, 665–675.CrossRefGoogle Scholar
  9. Fuller, G. M., & Grenett, H. E. (1989). The structure and function of the mouse hepatocyte stimulating factor. Annals of the New York Academy of Sciences, 557, 31–44.CrossRefGoogle Scholar
  10. Gabay, C., & Kushner, I. (1999). Acute-phase proteins and other systemic responses to inflammation. The New England Journal of Medicine, 340, 448–454.CrossRefGoogle Scholar
  11. Gruys, E., Toussaint, M. J. M., Niewold, T. A., & Koopmans, S. J. (2005). Acute phase reaction and acute phase proteins. Journal of Zhejiang University. Science. B, 6, 1045–1056.CrossRefGoogle Scholar
  12. Hazuda, D. J., Lee, J. C., & Young, P. R. (1988). The kinetics of interleukin 1 secretion from activated monocytes. The Journal of Biological Chemistry, 263, 8473–8479.PubMedGoogle Scholar
  13. Kehoe, S. H., Chheda, P. S., Sahariah, S. A., Baird, J., & Fall, C. H. D. (2009). Reporting of participant compliance in randomized controlled trials of nutrition supplements during pregnancy. Maternal & Child Nutrition, 5, 97–103.CrossRefGoogle Scholar
  14. Kopf, M., Baumann, H., Freer, G., Freudenberg, M., Lamers, M., Kishimoto, T., et al. (1994). Impaired immune and acute-phase responses in interleukin-6-deficient mice. Nature, 368, 339–342.CrossRefGoogle Scholar
  15. Kunz-Ebrecht, S. R., Mohamed-Ali, V., Feldman, P. J., Kirschbaum, C., & Steptoe, A. (2003). Cortisol responses to mild psychological stress are inversely associated with proinflammatory cytokines. Brain, Behavior, and Immunity, 17, 373–383.CrossRefGoogle Scholar
  16. Lacy, P., & Stow, J. L. (2011). Cytokine release from innate immune cells: association with diverse membrane trafficking pathways. Blood, 118, 9–18.CrossRefGoogle Scholar
  17. Maes, M., Song, C., Lin, A., De Jongh, R., Van Gastel, A., Kenis, G., et al. (1998). The effects of psychological stress on humans: increased production of pro-inflammatory cytokines and a th1-like response in stress induced anxiety. Cytokine, 10, 313–318.CrossRefGoogle Scholar
  18. Marino, A., & Giotta, N. (2008). Cinacalcet, fetuin-A and interleukin-6. Nephrology, Dialysis, Transplantation, 23, 1461.Google Scholar
  19. Mcfarland-Mancini, M. M., Funk, H. M., Paluch, A. M., Zhou, M., Giridhar, P. V., Mercer, C. A., et al. (2010). Differences in wound healing in mice with deficiency of Il-6 versus Il-6 receptor. Journal of Immunology, 184, 7219–7228.CrossRefGoogle Scholar
  20. Moher, D., Jones, A., & Lepage, L. (2001a). Use of the consort statement and quality of reports of randomized trials: a comparative before-and-after evaluation. JAMA, 285, 1992–1995.CrossRefGoogle Scholar
  21. Moher, D., Schulz, K. F., & Altman, D. (2001b). The consort statement: revised recommendations for improving quality of reports of parallel-group randomized trials. JAMA, 285, 1987–1991.CrossRefGoogle Scholar
  22. Nz, R. (2011). Macronutrients. New York: Plenum Press.Google Scholar
  23. Oba, K., Morita, S., Rahman, M., & Sakamoto, J. (2006). Factors associated with compliance and non-compliance by physicians in a large-scale randomized clinical trial. Trials, 7, 1–7.CrossRefGoogle Scholar
  24. Oliver, J. C., Bland, L. A., Oettinger, C. W., Arduino, M. J., Mcallister, S. K., Aquero, S. M., et al. (1993). Cytokine kinetics in an in vitro whole blood model following an endotoxin challenge. Lymphokine and Cytokine Research, 12, 115–120.PubMedPubMedCentralGoogle Scholar
  25. Paschalis, V., Giakas, G., Baltzopoulos, V., Jamurtas, A. Z., Theoharis, V., Kotzamanidis, C., et al. (2007). The effects of muscle damage following eccentric exercise on gait biomechanics. Gait & Posture, 25, 236–242.CrossRefGoogle Scholar
  26. Pedersen, B. K. (2000). Exercise and cytokines. Immunology and Cell Biology, 78, 532–535.CrossRefGoogle Scholar
  27. Rohde, T., Maclean, D. A., Richter, E. A., Kiens, B., & Pedersen, B. K. (1997). Prolonged submaximal eccentric exercise is associated with increased levels of plasma Il-6. The American Journal of Physiology, 273, E85–E91.CrossRefGoogle Scholar
  28. Samols, D., Agrawal, A., & Kushner, I. (2002). Acute phase proteins. Cytokine Reference On-line, (Feldman, J.J. and Oppenheim, J.J., ed). Academic Press, Harcourt, London, 1–16.Google Scholar
  29. Shephard, R. J. (2002). Cytokine responses to physical activity, with particular reference to Il-6: sources, actions, and clinical implications. Critical Reviews in Immunology, 22, 165–182.PubMedGoogle Scholar
  30. Steptoe, A., Willemson, G., Owen, N., Flower, L., & Mohamed-Ali, V. (2001). Acute mental stress elicits delayed increases in circulating inflammatory cytokine levels. Clinical Science, 101, 185–192.CrossRefGoogle Scholar
  31. Stevens, S. S. (1971). Issues in psychophysical measurement. Psychological Review, 78, 426–450.CrossRefGoogle Scholar
  32. Streetz, K. L., Wustefeld, T., Klein, C., Manns, M. P., & Trautwein, C. (2001). Mediators of inflammation and acute phase response in the liver. Cellular and Molecular Biology (Noisy-le-Grand, France), 47, 661–673.Google Scholar
  33. Taylor, D. C., Dalton, J. D., Seaber, A. V., & Garrett, W. E. (1990). Viscoelastic properties of muscle-tendon units. The biomechanical effects of stretching. The American Journal of Sports Medicine, 18, 300–309.CrossRefGoogle Scholar
  34. Whitney, C. W., & Dworkin, S. F. (1997). Practical implications of noncompliance in randomized clinical trials for temporomandibular disorders. Journal of Orofacial Pain, 11, 130–138.PubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Nikos C. Apostolopoulos
    • 1
  1. 1.University of TorontoTorontoCanada

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