Changes in the Plantar Flexion Torque of the Ankle and in the Morphological Characteristics and Mechanical Properties of the Achilles Tendon after 12-Week Gait Retraining

Purpose: Although the Achilles tendon (AT) is the largest and strongest tendon, it remains one of the most vulnerable tendons among elite and recreational runners. The present study aims to explore the effects of 12-week gait retraining (GR) on the plantar flexion torque of the ankle and the morphological and mechanical properties of the AT. Methods: Thirty-four healthy male recreational runners (habitual rearfoot strikers) who never tried to run in minimal shoes were recruited, and the intervention was completed (20 in the GR group vs. 14 in the control (CON) group). The participants in the GR group were asked to run in minimal shoes (INOV-8 BARE-XF 210) provided by the investigators with forefoot strike patterns during the progressive 12-week GR. Meanwhile, the participants in the CON group were instructed to run in their own running shoes, which they were familiar with, with original foot strike patterns and intensities. The morphological properties of the AT, namely, length and cross-sectional area (CSA), were obtained by using an ultrasound device. A dynamometer was utilized simultaneously to measure and calculate the plantar flexion torque of the ankle, the rate of torque development, the peak force of the AT, and the stress and strain of the AT. Results: After 12-week GR, the following results were obtained: (1) A significant time effect in the peak ankle plantarflexion torque was observed (p = 0.005), showing a 27.5% increase in the GR group; (2) A significant group effect in the CSA was observed (p = 0.027), specifically, the increase in CSA was significantly larger in the GR group than the CON group; (3) A significant time effect in the peak AT force was observed (p = 0.005), showing a 27.5% increase in the GR group. Conclusion: The effect of 12 weeks of GR is an increase in AT CSA, plantar flexor muscle strength of the ankle, and peak AT force during a maximal voluntary isometric contraction test. These changes in AT morphology and function could be positive for tendon health and could prevent future AT injury.

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Dynamic changes in full blood count (FBC) occurring in patients treated with immune checkpoint inhibitors (ICIs) to predict responses in patients with metastatic renal cell carcinoma (mRCC).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e17110 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e17110-e17110

Author(s):

Yasmin Abu Ghanem ◽

Julia Choy ◽

Francesca Jackson-Spence ◽

Agne Jovaisaite ◽

Michael Grant ◽

...

Keyword(s):

Treatment Initiation ◽

Time Effect ◽

Full Blood Count ◽

Group Effect ◽

Significant Group Effect ◽

Significant Group ◽

Lymphocyte Ratio ◽

Significant Time ◽

Significant Time Effect ◽

Over Time

e17110 Background: ICI transformed the treatment of 1L mRCC, yet early clinical predictors of response are still unknown. Methods: Retrospective database analysis from Barts Cancer Institute, London was carried out. Patients with treatment naïve mRCC were identified and grouped according to their 1L treatment: 1: VEGF inhibitor 2: IO/IO 3: IO/VEGF Data on hemoglobin, neutrophil-to-lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR) at baseline, 6weeks and 12weeks after treatment initiation was correlated with outcome. Results: Between Jan 2014 - Dec 2019; 28, 29 and 21 patients received 1L VEGF, IO/IO or IO/VEGF respectively. Patient receiving 1L VEGF inhibitors showed a decrease in Hb levels both in responding and non-responding groups (significant group effect: F(1,6) = 6.6, p = 0.04); significant time effect:F(2,12) = 12.4, p = 0.001). Group x time interaction was not significant. NLR levels decreased both in responding and non-responding groups over time (significant time effect: F(2,12) = 16.7, p = 0.001. PLR levels in non-responders increased over time, whereas in responding group, PLR levels steadily decreased over 6 and 12 weeks (significant time effect: F(2,12) = 0.3, 0.044). Patients receiving IO/IO combination therapy; within the non-responder group, Hb levels didn’t change significantly whereas in the responding group Hb levels increased significantly and overtook Hb levels of non-responding group (P = 0.001). NLR levels significantly decreased in the responding group (0.041) and a similar trend was observed at 12 weeks with a decrease in PLR among non-responders, with a significant group affect (F(1,5) = 0.18, 0.035). In patient treated with 1L IO/VEGF, among non-responders Hb levels increased slightly, only to return to baseline levels again at 12 weeks after treatment initiation. Whereas, Hb levels in the responding group increased significantly in both 6weeks and 12weeks after starting therapy. Significant time effect:F(2,20) = 3.65, p = 0.044. NLR levels in the responding group presented a steady decrease over time with a significant group and time effect. Both responders and non-responders experienced an increase in PLR over time. However, while PLR decreased at 12 weeks among responders, it continued to increase among non responders (significant time effect: F(2,20) = 0.3, 0.03), (significant group effect: F(1,10) = 0.05, 0.005) and significant interaction: F(2,20) = 0.1, 0.01) Conclusions: Close monitoring of FBC changes may predict response to ICI.

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Mechanical properties of tendon and aponeurosis of human gastrocnemius muscle in vivo

Journal of Applied Physiology ◽

10.1152/jappl.2001.90.5.1671 ◽

2001 ◽

Vol 90 (5) ◽

pp. 1671-1678 ◽

Cited By ~ 150

Author(s):

Tadashi Muramatsu ◽

Tetsuro Muraoka ◽

Daisuke Takeshita ◽

Yasuo Kawakami ◽

Yuichi Hirano ◽

...

Keyword(s):

Mechanical Properties ◽

Achilles Tendon ◽

Gastrocnemius Muscle ◽

Plantar Flexion ◽

Medial Gastrocnemius ◽

Significant Difference ◽

Functional Implications ◽

Male Subjects ◽

Maximal Strain

Load-strain characteristics of tendinous tissues (Achilles tendon and aponeurosis) were determined in vivo for human medial gastrocnemius (MG) muscle. Seven male subjects exerted isometric plantar flexion torque while the elongation of tendinous tissues of MG was determined from the tendinous movements by using ultrasonography. The maximal strain of the Achilles tendon and aponeurosis, estimated separately from the elongation data, was 5.1 ± 1.1 and 5.9 ± 1.6%, respectively. There was no significant difference in strain between the Achilles tendon and aponeurosis. In addition, no significant difference in strain was observed between the proximal and distal regions of the aponeurosis. The results indicate that tendinous tissues of the MG are homogenously stretched along their lengths by muscle contraction, which has functional implications for the operation of the human MG muscle-tendon unit in vivo.

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The Effects of Exercise Induced Muscle Damage on Knee Joint Torque and Balance Performance

Sports ◽

10.3390/sports6030101 ◽

2018 ◽

Vol 6 (3) ◽

pp. 101

Author(s):

Nicole Dabbs ◽

Harish Chander

Keyword(s):

Knee Joint ◽

Muscle Damage ◽

Repeated Measures ◽

Time Effect ◽

Joint Torque ◽

Knee Extensors ◽

Balance Performance ◽

Significant Time ◽

Significant Time Effect ◽

Exercise Induced

The purpose of this investigation is to determine the effects of exercise induced muscle damage (EIMD) on balance and knee joint torque. Thirteen males and females volunteered to participate in the study. Following a familiarization session, baseline measures were obtained for isometric torque measured during a maximal voluntary isometric contraction (MVIC) for knee flexors and extensors, and ankle dorsi-flexors and plantar-flexors. Additionally, balance performance was tested in double leg (DL), and right single leg (RSL) static and dynamic unstable stability was measured. Participants then performed the muscle damage protocol of front loaded Bulgarian split squats. All measurements were re-assessed for torque and balance immediately and up to 72 h afterwards. A one-way repeated-measures analysis of variance (ANOVA) was used to analyze differences between baseline and all time-points for torque and balance measures. There was a significant time effect for knee extensors MVIC torque, where baseline measures are greater than post EIMD, 24 h and 48 h post EIMD. There was no significant time effect for all balance conditions. These results provide evidence of EIMD following high intensity eccentric exercises with significant reductions in knee extensor torque up to at least 48 h and show that balance was not compromised following EIMD.

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Effects of eccentric training on mechanical properties of the plantar flexor muscle-tendon complex

Journal of Applied Physiology ◽

10.1152/japplphysiol.01313.2011 ◽

2013 ◽

Vol 114 (5) ◽

pp. 523-537 ◽

Cited By ~ 42

Author(s):

Alexandre Fouré ◽

Antoine Nordez ◽

Christophe Cornu

Keyword(s):

Mechanical Properties ◽

Achilles Tendon ◽

Plantar Flexion ◽

Triceps Surae ◽

Elastic Component ◽

Plantar Flexor ◽

Eccentric Training ◽

Tendon Stiffness ◽

Series Elastic Component ◽

Series Elastic

Eccentric training is a mechanical loading classically used in clinical environment to rehabilitate patients with tendinopathies. In this context, eccentric training is supposed to alter tendon mechanical properties but interaction with the other components of the muscle-tendon complex remains unclear. The aim of this study was to determine the specific effects of 14 wk of eccentric training on muscle and tendon mechanical properties assessed in active and passive conditions in vivo. Twenty-four subjects were randomly divided into a trained group ( n = 11) and a control group ( n = 13). Stiffness of the active and passive parts of the series elastic component of plantar flexors were determined using a fast stretch during submaximal isometric contraction, Achilles tendon stiffness and dissipative properties were assessed during isometric plantar flexion, and passive stiffness of gastrocnemii muscles and Achilles tendon were determined using ultrasonography while ankle joint was passively moved. A significant decrease in the active part of the series elastic component stiffness was found ( P < 0.05). In contrast, a significant increase in Achilles tendon stiffness determined under passive conditions was observed ( P < 0.05). No significant change in triceps surae muscles and Achilles tendon geometrical parameters was shown ( P > 0.05). Specific changes in muscle and tendon involved in plantar flexion are mainly due to changes in intrinsic mechanical properties of muscle and tendon tissues. Specific assessment of both Achilles tendon and plantar flexor muscles allowed a better understanding of the functional behavior of the muscle-tendon complex and its adaptation to eccentric training.

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Physical and functional well-being in women with breast cancer taking gabapentin for hot flashes.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.9141 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 9141-9141

Author(s):

Kavita Dayal Chandwani ◽

Joseph Roscoe ◽

Charles E Heckler ◽

Supriya Gupta Mohile ◽

Karen Michelle Mustian ◽

...

Keyword(s):

Breast Cancer ◽

Mixed Model ◽

Linear Mixed Model ◽

Hot Flashes ◽

Well Being ◽

Time Effect ◽

Slight Reduction ◽

Modest Improvement ◽

Significant Time ◽

Significant Time Effect

9141 Background: Hot flashes reduce quality of life (QOL) in women with breast cancer. In a randomized, double-blind, placebo-controlled trial of gabapentin for hot flashes, 900 mg of the drug was found to reduce hot flashes in women with breast cancer; however, their QOL of has not been studied. We conducted secondary analyses to study two domains of QOL: physical (PWB) and functional well-being (FWB) in women in this trial. Methods: A nationwide sample of women with breast cancer and hot flashes ≥ 2/day was studied at baseline (T1), 4 weeks (T2), and 8 weeks (T3) of treatment with gabapentin 300mg/day (G300) and 900mg/day (G900) in divided doses, and a matching placebo (PL). PWB and FWB were assessed via subscales of the Functional Assessment of Cancer Therapy-Breast. Linear mixed model analyses of PWB and FWB were conducted, adjusted for demographic and treatment variables. Results: The mean age of women (N=384) was 54.9 years ± 8.07 (range: 31-81, 72% >50 years); 76% were married; 71% had more than high school education; 95% were Caucasian and 3% African-American; 10% were undergoing chemotherapy, and 9% radiotherapy (RT). PWB showed significant time effect (p<.0001) and interaction of time and treatment (p<.0001). There was an improvement in PWB in the G300 by T2 with no change at T3, while the improvement in PL and G900 was more modest at T2 and continued at T3 (PL - T1 20.7, T2 21.2, T3 21.6; G300 - T1 20.9, T2 22.2, T3 22.2; and G900 - T1 21.2, T2 21.5, T3 21.7). FWB also showed a significant time effect (p=.001) and interaction of time and treatment (p<.002). FWB in G300 improved by T2, with no additional improvement at T3; it was unchanged in G900 at T2 with a slight reduction at T3; PL showed a modest improvement at T2 followed by a modest worsening at T3 (PL - T1 17.8, T2 18.1, T3 17.9; G300 - T1 17.9, T2 18.6, T3 18.6; G900 - T1 18.6, T2 18.6, T3 18.5). Conclusions: As reported previously, G900 is effective in reducing hot flashes. In this analysis, however, PWB and FWB showed different patterns of change over time between the two gabapentin and placebo groups with G900 showing minimal effects on PWB and FWB. Future trials to further study the changes in physical and functional well-being of women with breast cancer taking gabapentin for hot flashes are needed.

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One-Week Self-Guided Internet Cognitive Behavioral Treatments for Insomnia in Adults With Situational Insomnia During the COVID-19 Outbreak

Frontiers in Neuroscience ◽

10.3389/fnins.2020.622749 ◽

2021 ◽

Vol 14 ◽

Author(s):

Chenxi Zhang ◽

Lulu Yang ◽

Shuai Liu ◽

Yan Xu ◽

Huirong Zheng ◽

...

Keyword(s):

Behavioral Treatment ◽

Depression Scale ◽

Severity Index ◽

Time Effect ◽

Cognitive Behavioral ◽

Cognitive Behavioral Treatment ◽

Significant Group ◽

Cognitive Score ◽

Significant Time ◽

Group Time

Objective: In the current global home confinement due to COVID-19, most individuals are facing unprecedented stress which can induce situational insomnia. We explored the efficacy of self-guided online cognitive behavioral treatment for insomnia (CBTI) on situational insomnia during the COVID-19 outbreak.Methods: Participants were recruited from March to April in 2020 in Guangzhou, China. A 1-week Internet CBTI intervention was performed for all individuals with situational insomnia. The Pre-sleep Arousal Scale (PSAS), Insomnia Severity Index (ISI), and Hospital Anxiety and Depression Scale (HADS) were measured before and after the intervention and compared between individuals who completed the intervention and those who did not.Results: One hundred and ninety-four individuals with situational insomnia were included. For PSAS score, significant group effects were found on total score (p = 0.003), somatic score (p = 0.014), and cognitive score (p = 0.009). Time effect was significant on total score (p = 0.004) and cognitive score (p < 0.001). There was a significant group × time effect of the somatic score (p = 0.025). For ISI total score, there were significant time effect (p < 0.001) and group × time effect (p = 0.024). For the HADS score, a significant group effect was found on the anxiety score (p = 0.045). The HADS had significant time effects for anxiety and depressive symptoms (all p < 0.001).Conclusion: Our study suggests good efficacy of CBTI on situational insomnia during COVID-19 for adults in the community, as well as on pre-sleep somatic hyperarousal symptom. The CBTI intervention is not applied to improve pre-sleep cognitive hyperarousal, depression, and anxiety symptoms.

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HOMA-IR increase after antidepressant treatment in depressed patients with the Met allele of the Val66Met BDNF genetic polymorphism

Psychological Medicine ◽

10.1017/s0033291718003240 ◽

2018 ◽

Vol 49 (14) ◽

pp. 2364-2369

Author(s):

Séverine Martin ◽

Romain Colle ◽

Khalil El Asmar ◽

Adrien Rigal ◽

Albane Vievard ◽

...

Keyword(s):

Insulin Resistance ◽

Antidepressant Treatment ◽

Time Effect ◽

Val66met Polymorphism ◽

Significant Time ◽

Depressed Patients ◽

Significant Time Effect ◽

Time Interaction ◽

Bdnf Val66met Polymorphism ◽

Fasting Glycaemia

AbstractBackgroundThe brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is associated with response to antidepressant drugs in depressed patients and with metabolic side effects after antipsychotic treatment. This study aims to assess the association between this polymorphism and insulin resistance after antidepressant treatment in depressed patients.MethodsOne hundred forty-eight Caucasian patients with a current unipolar major depressive episode (DSM IV-TR) were genotyped for the BDNF Val66Met polymorphism and assessed at baseline and after 3 and 6 months of antidepressant treatment for the ‘Homoeostasis model assessment of insulin resistance’ (HOMA-IR) index, a valid measure of insulin resistance based on fasting plasma insulinaemia and glycaemia. Because validity assumptions were fulfilled, data were analysed using analysis of variance for repeated measures.ResultsThe 52 (35%) Met carriers and 96 (65%) Val/Val patients were not different at baseline for clinical characteristics and HOMA-IR. A significant Val66Met × time interaction (p= 0.02), a significant time effect (p= 0.03) and a significant Val66Met effect (p= 0.0497) were shown for HOMA-IR. A significant Val66Met × time interaction (p= 0.01) and a significant time effect (p= 0.003) were shown for fasting glycaemia. HOMA-IR and fasting glycaemia changes after antidepressant treatment were significantly higher in Met carrier than in Val/Val patients (HOMA-IR changes: Met: 0.71 ± 3.29v.Val/Val: −0.16 ± 1.34,t= 2.3, df = 146,p= 0.02, glycaemia changes: Met: 0.09 ± 0.30v.Val/Val: 0.02 ± 0.16,t= −2.0, df = 146,p= 0.045).ConclusionsThe Met allele of the Val66Met BDNF polymorphism confers to depressed patients a higher risk of insulin-resistance after antidepressant treatment. These patients could benefit from specific monitoring of metabolism and preventive measures.

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Elastic properties of human Achilles tendon are correlated to muscle strength

Journal of Applied Physiology ◽

10.1152/japplphysiol.00624.2004 ◽

2005 ◽

Vol 99 (2) ◽

pp. 665-669 ◽

Cited By ~ 63

Author(s):

Tetsuro Muraoka ◽

Tadashi Muramatsu ◽

Tetsuo Fukunaga ◽

Hiroaki Kanehisa

Keyword(s):

Mechanical Properties ◽

Muscle Strength ◽

Achilles Tendon ◽

Elastic Energy ◽

Plantar Flexion ◽

Triceps Surae ◽

Medial Gastrocnemius ◽

Myotendinous Junction ◽

Men And Women ◽

The Difference

The purpose of this study was to investigate whether the mechanical properties of the Achilles tendon were correlated to muscle strength in the triceps surae in humans. Twenty-four men and twelve women exerted maximal voluntary isometric plantar flexion (MVIP) torque. The elongation (ΔX) and strain of the Achilles tendon (ε), the proximal part of which is the composite of the gastrocnemius tendon and the soleus aponeurosis, at MVIP were determined from the displacement of the distal myotendinous junction of the medial gastrocnemius using ultrasonography. The Achilles tendon force at MVIP (F) was calculated from the MVIP torque and the Achilles tendon moment arm. There were no significant differences in either the F-ΔX or F-ε relationships between men and women. ΔX and ε were 9.8 ± 2.6 mm and 5.3 ± 1.6%, respectively, and were positively correlated to F ( r = 0.39, P < 0.05; r = 0.39, P < 0.05), which meant that subjects with greater muscle strength could store more elastic energy in the tendon. The regression y-intercepts for the F-ΔX ( P < 0.01) and F-ε ( P < 0.05) relationship were significantly positive. These results might indicate that the Achilles tendon was stiffer in subjects with greater muscle strength, which may play a role in reducing the probability of tendon strain injuries. It was suggested that the Achilles tendon of subjects with greater muscle strength did not impair the potential for storing elastic energy in tendons and may be able to deliver the greater force supplied from a stronger muscle more efficiently. Furthermore, the difference in the Achilles tendon mechanical properties between men and women seemed to be correlated to the difference in muscle strength rather than gender.

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An Open Label, Non Randomized, Propspective Phase IV Clinical Trial Evaluating the Immunogenicity of Branded Enoxaparin Versus Biosimilars In Healthy Volunteers.

Blood ◽

10.1182/blood.v116.21.1086.1086 ◽

2010 ◽

Vol 116 (21) ◽

pp. 1086-1086

Author(s):

Marise Gomes ◽

Eduardo Ramacciotti ◽

Debra Hoppensteadt ◽

Jeanine M. Walenga ◽

Bruce E Lewis ◽

...

Keyword(s):

Healthy Volunteers ◽

Drug Effect ◽

Cross Reactivity ◽

Serotonin Release ◽

Time Effect ◽

Open Label ◽

Platelet Factor ◽

Significant Time ◽

Significant Time Effect ◽

Post Hoc

Abstract Abstract 1086 Biosimilar enoxaparin preparations are in use outside the U.S. Due to compositional variations, their interaction with platelet factor 4 (PF4) differs leading to differential immunogenic responses between branded and biosimilar agents. To compare their immunogenic response, branded enoxaparin (Clexane®, Sanofi-Aventis) and a biosimilar version (Cutenox®, Gland-Pharma) were administered to healthy volunteers (n=110/drug) at a dose of 40 mg SQ for10 days. Blood samples drawn on days 1 and 10 were analyzed for anti-heparin/PF4 antibody (A-HPF4-Ab) titers and subtypes by ELISA (GTI, Brookfield, WI). Treatment with each LMWH resulted in comparable A-HPF4-Ab generation as compared by using the total absorbance for each population (p<0.05). However in the thrombin generation assays clexane group showed a stronger inhibition (45+12% vs 32+9%). None of these antibodies activated platelets as determined by the serotonin release assay. The two groups alos showed comparable AXa and AIIa responses (p<0.05). Antibody subtyping demonstrated different profiles between LMWHs. For IgG (Clexane1=0.15±0.04, Clexane10=0.21±0.06, Cutenox1=0.17±0.04, Cutenox10=0.28±0.10) with a significant time effect (p<0.0001), a significant drug effect (p<0.0001), and a significant time by drug interaction (p=.0009). Post hoc comparisons showed a difference between the drugs at time 0 (p=0.03), a difference between the drugs at time 10 (p<0.0001) and a significant time effect for each drug (p<0.0001). For IgA (Clexane1=0.12±0.02, Clexane10=0.15±0.02, Cutenox1=0.12±0.03, Cutenox10=0.13±0.02) with significant effects for time (p<0.0001), drug (p=0.0078) and for the drug × time interaction (p<0.0001). The post hoc comparisons showed a significant drug effect at time 10 (p<0.0001). There was a significant time effect for Clexane (P<0.0001) but not for Cutenox. For IgM (Clexane1=0.11±0.01, Clexane10=0.13±0.02, Cutenox1=0.11±0.03, Cutenox10=0.13±0.02), there was only a time effect (p<0.0001). The post hoc comparisons showed no difference between drugs at either time, but significant time effects for each drug (p<0.0001). The immunogenic potential of LMWHs varies in terms of ability to generate A-HPF4-Ab, the antibody subtypes generated, and their cross-reactivity with pre-formed A-HPF4-Ab. Such parameters may be useful in defining the bioequivalence of generic LMWHs. Future studies evaluating the immunogenicity of different compounds in patients exposed to biosimilar drugs are warranted. Disclosures: Jeske: PolyMedix, Inc.: Research Funding.

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Sclerostin and bone remodeling biomarkers responses to whole-body cryotherapy (− 110 °C) in healthy young men with different physical fitness levels

Scientific Reports ◽

10.1038/s41598-021-95492-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Anna Straburzyńska-Lupa ◽

Tomasz Cisoń ◽

Marta Gomarasca ◽

Anna Babińska ◽

Giuseppe Banfi ◽

...

Keyword(s):

Physical Fitness ◽

Bone Remodeling ◽

Young Men ◽

Time Effect ◽

Whole Body ◽

Fitness Level ◽

Significant Time ◽

Significant Time Effect ◽

Cryogenic Chamber ◽

Whole Body Cryotherapy

AbstractWe investigated the effects of single and repeated exposures to whole-body cryotherapy on biomarkers of bone remodeling and osteo-immune crosstalk: sclerostin, osteocalcin (OC), C-terminal cross-linked telopeptide of type I collagen (CTx-I), osteoprotegerin (OPG) and free soluble receptor activator for nuclear factor κ B ligand (sRANKL). The study included 22 healthy males, grouped in high physical fitness level (HPhL) and low physical fitness level (LPhL), all undergone 10 consecutive sessions in a cryogenic chamber (− 110 °C). We observed a significant time-effect on sclerostin (p < 0.05), OC (p < 0.01), CTx-I (p < 0.001), OC/CTx-I (p < 0.05), and significant differences in sRANKL between the groups (p < 0.05) after the 1st cryostimulation; a significant time-effect on OC (p < 0.001) and OC/CTx-I (p < 0.001) after the 10th cryostimulation, and a significant time-effect on CTx-I (p < 0.001) and OC/CTx-I (p < 0.01) after 10 sessions of WBC. In conclusion, in young men, the first exposure to extreme cold induced significant changes in serum sclerostin. The changes in sRANKL, between groups, suggest that fitness level may modify the body's response to cold. The effects of the first stimulus and the whole session are not identical, probably due to the physiological development of habituation to cold.

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