Combination of whole body cryotherapy with static stretching exercises reduces fatigue and improves functioning of the autonomic nervous system in Chronic Fatigue Syndrome

Funding Information: This article has been supported by the Polish National Agency for Academic Exchange under Grant No. PPI/APM/2018/1/00036/U/001. Publisher Copyright: © 2022, The Author(s).Background: The aim of this study was to explore the tolerability and effect of static stretching (SS) and whole body cryotherapy (WBC) upon fatigue, daytime sleepiness, cognitive functioning and objective and subjective autonomic nervous system functioning in those with Chronic Fatigue Syndrome (CFS) compared to a control population. Methods: Thirty-two CFS and eighteen healthy controls (HC) participated in 2 weeks of a SS + WBC programme. This programme was composed of five sessions per week, 10 sessions in total. Results: A significant decrease in fatigue was noted in the CFS group in response to SS + WBC. Some domains of cognitive functioning (speed of processing visual information and set-shifting) also improved in response to SS + WBC in both CFS and HC groups. Our study has confirmed that WBC is well tolerated by those with CFS and leads to symptomatic improvements associated with changes in cardiovascular and autonomic function. Conclusions: Given the preliminary data showing the beneficial effect of cryotherapy, its relative ease of application, good tolerability, and proven safety, therapy with cold exposure appears to be an approach worth attention. Further studies of cryotherapy as a potential treatment in CFS is important in the light of the lack of effective therapeutic options for these common and often disabling symptoms.publishersversionPeer reviewe

Effects of whole-body cryotherapy and static stretching are maintained 4 weeks after treatment in most patients with chronic fatigue syndrome

Funding Information: This article/publication is based upon work from COST Action CA15111 ”European Network on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, EUROMENE,” supported by COST (European Cooperation in Science and Technology, weblink: www.cost.eu , access date: 09.06.2022). Publisher Copyright: © 2023 The AuthorsIn the previous study, whole-body cryotherapy (WBC)+static stretching (SS) has been shown 25 to reduce the severity of some symptoms in Chronic Fatigue Syndrome (CFS) noted just after 26 the therapy. Here we consider the effects of treatment and explore the sustainability of 27 symptom improvements at four weeks (one-month) follow-up. Twenty-two CFS patients were 28 assessed one month after WBC+SS programme. Parameters related to fatigue (Chalder 29 Fatigue Questionnaire (CFQ), Fatigue Impact Scale (FIS), Fatigue Severity Scale (FSS)), 30 cognitive function (Trial Making test part A and B (TMT A and TMT B and its difference 31 (TMT B-A)), Coding) hemodynamic, aortic stiffness (aortic systolic blood pressure (sBP 32 aortic)) and autonomic nervous system functioning were measured. TMT A, TMT B, TMT B33 A and Coding improved at one month after the WBC+SS programme. WBC+SS had a 34 significant effect on the increase in sympathetic nervous system activity in rest. WBC+SS had 35 a significant, positive chronotropic effect on the cardiac muscle. Peripheral and aortic systolic 36 blood pressure decreased one month after WBC+SS in comparison to before. Effects of 37 WBC+SS on reduction of fatigue, indicators of aortic stiffness and symptoms severity related 38 to autonomic nervous system disturbance and improvement in cognitive function were 39 maintained at one month. However, improvement in all three fatigue scales (CFQ, FIS and 40 FSS) was noted in 17 of 22 patients. In addition, ten patients were treated initially but they 41 were not assessed at 4 weeks, and are thus not included in the 22 patients who were examined 42 on follow-up. The overall effects of WBC+SS noted at one month post-treatment should be 43 interpreted with caution.publishersversionPeer reviewe

DMSO and TMAO—Differences in Interactions in Aqueous Solutions of the K-Peptide

Interactions between a solvent and their co-solute molecules in solutions of peptides are crucial for their stability and structure. The K-peptide is a synthetic fragment of a larger hen egg white lysozyme protein that is believed to be able to aggregate into amyloid structures. In this study, a complex experimental and theoretical approach is applied to study systems comprising the peptide, water, and two co-solutes: trimethylamide N-oxide (TMAO) or dimethyl sulfoxide (DMSO). Information about their interactions in solutions and on the stability of the K-peptide was obtained by FTIR spectroscopy and differential scanning microcalorimetry. The IR spectra of various osmolyte–water–model-peptide complexes were simulated with the DFT method (B3LYP/6-311++G(d,p)). The FTIR results indicate that both solutes are neutral for the K-peptide in solution. Both co-solutes affect the peptide to different degrees, as seen in the shape of its amide I band, and have different influences on its thermal stability. DFT calculations helped simplify the experimental data for easier interpretation

Modelling of Thyroid Peroxidase Reveals Insights into Its Enzyme Function and Autoantigenicity

Thyroid peroxidase (TPO) catalyses the biosynthesis of thyroid hormones and is a major autoantigen in Hashimoto’s disease—the most common organ-specific autoimmune disease. Epitope mapping studies have shown that the autoimmune response to TPO is directed mainly at two surface regions on the molecule: immunodominant regions A and B (IDR-A, and IDR-B). TPO has been a major target for structural studies for over 20 years; however, to date, the structure of TPO remains to be determined. We have used a molecular modelling approach to investigate plausible modes of TPO structure and dimer organisation. Sequence features of the C-terminus are consistent with a coiled-coil dimerization motif that most likely anchors the TPO dimer in the apical membrane of thyroid follicular cells. Two contrasting models of TPO were produced, differing in the orientation and exposure of their active sites relative to the membrane. Both models are equally plausible based upon the known enzymatic function of TPO. The “trans” model places IDR-B on the membrane-facing side of the myeloperoxidase (MPO)-like domain, potentially hindering access of autoantibodies, necessitating considerable conformational change, and perhaps even dissociation of the dimer into monomers. IDR-A spans MPO- and CCP-like domains and is relatively fragmented compared to IDR-B, therefore most likely requiring domain rearrangements in order to coalesce into one compact epitope. Less epitope fragmentation and higher solvent accessibility of the “cis” model favours it slightly over the “trans” model. Here, IDR-B clusters towards the surface of the MPO-like domain facing the thyroid follicular lumen preventing steric hindrance of autoantibodies. However, conformational rearrangements may still be necessary to allow full engagement with autoantibodies, with IDR-B on both models being close to the dimer interface. Taken together, the modelling highlights the need to consider the oligomeric state of TPO, its conformational properties, and its proximity to the membrane, when interpreting epitope-mapping data

Mapping epitopes onto the cis TPO dimer.

<p><b>(A)</b> Epitopes and residues identified in various studies as constituting immunodominant regions IDR-A (blue) and IDR-B (pink); <b>(B)</b> Lumen-facing side of MPO-like domain; <b>(C)</b> Close-up shows that much of the two immunodominant regions are on the lumen-facing surface of the MPO-like domain near the dimer interface, particularly IDR-B; <b>(D)</b> Membrane-facing side of TPO containing the heme (orange) cavity.</p

A comparison between membrane-embedded, dimeric models of TPO isoform1 in two different conformations.

<p><b>(A)</b> Schematic of trans model with active site facing away from follicular membrane. Coloring as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0142615#pone.0142615.g001" target="_blank">Fig 1</a>; <b>(B)</b> Cis model with active site facing towards follicular membrane; <b>(C)</b> perpendicular views of trans model; <b>(D)</b> perpendicular views of cis model. TPO represented as cartoon and space filling (subunits A and B, respectively) for clarity. Domains are coloured as follows: MPO-like domain (green), CCP-like domain (Shamrock green), EGF-like domain (cyan-blue), and TM domain (dark-blue). Catalytic heme represented as red spheres, and DMPC molecules represented as lines and coloured as CPK.</p