Publications by authors named "Christina Karatzaferi"

56 Publications

The vicious circle between physical, psychological, and physiological characteristics of shift work in nurses: a multidimensional approach.

Sleep Breath 2021 Apr 17. Epub 2021 Apr 17.

Department of Physical Education and Sport Science, University of Thessaly, Karies, 42100, Trikala, Thessaly, Greece.

Purpose: To compare physical, psychological, and physiological adaptations between rotating and morning shift health workers using objective and subjective approaches.

Methods: Forty nurses [n = 20 morning shift (MS) group; n = 20 rotating shift (RS) group] were evaluated for anthropometry, body composition, and handgrip strength. Quality of life, depression, fatigue, daytime sleepiness, and sleep quality were assessed with SF-36, Zung Self-Rating Depression Scale (SDS), Fatigue Severity Scale (FSS), Epworth Sleepiness Scale (ESS), and Pittsburgh Sleep Quality Index (PSQI), respectively. Physical activity was assessed by the International Physical Activity Questionnaire (IPAQ) and triaxial accelerometers. Sleep-related data were monitored with sleep actigraphy. Salivary melatonin levels were analyzed before/after sleep, and blood lipid profiles were measured the following morning.

Results: The RS group had higher mean BMI and total and abdominal fat and scored lower in the SF-36 (p < 0.01). All nurses showed reduced physical activity levels, which, in the RS group, were negatively correlated with FSS (p = 0.033) and SDS scores (p = 0.025). Poor sleep was revealed in 53% of nurses. The RS group had worse sleep quality by PSQI than the MS group (p = 0.045). PSQI scores were inversely related to SF-36 scores and positively correlated with FSS, BMI, waist circumference, and body fat (p < 0.05).

Conclusion: RS nurses showed increased body mass and total and abdominal fat along with decreased quality of life and sleep quality compared to MS counterparts. A strong relationship was found between physical, psychological, and physiological domains. Further studies should consider workplace interventions to prevent obesity, promote physical activity, and manage poor sleeping patterns in nurses.
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http://dx.doi.org/10.1007/s11325-021-02381-5DOI Listing
April 2021

The effects of training with high-speed interval running on muscle performance are modulated by slope.

Physiol Rep 2021 01;9(1):e14656

Experimental Physiology & Therapeutic Exercise Laboratory, Muscle Physiology and Mechanics Group, CREHP, School of Physical Education Sports Science and Nutrition, University of Thessaly, Trikala, Greece.

We examined changes in selected muscle performance parameters after 8 weeks of interval training using two opposite running inclinations. We hypothesized that the uphill training will affect endurance muscle performance outcomes, whereas the downhill training will affect power muscle performance outcomes. Fourteen physically active volunteers were randomly assigned into either the Uphill group (UG; n = 7; uphill interval running at +10% incline) or the Downhill group (DG; n = 7; downhill interval running at -10% incline) and completed 16 training sessions. Each session consisted of ten 30 s treadmill runs at 90% of maximum aerobic speed (MAS) with a work to rest ratio of 1:2. Vertical jump performance, isometric (MVC) and isokinetic torque of knee extensors and flexors, and fatigue of knee extensors were evaluated pre and post-training. Moreover, body composition (via bioimpedance) and vastus lateralis muscle architecture (via ultrasonography) were assessed pre and post-training. Relative lean tissue mass, relative fat mass, and squat jump (cm) significantly (p < .05) changed from baseline values by +4.5 ± 4.0%, -11.5 ± 9.6%, and +9.5 ± 11.7%, respectively, only in the DG. Similarly, DG improved absolute values of knee extension rate of torque development and impulse (p < .05), whereas knee flexion peak torque angle significantly decreased in both groups (p < .05). On the other hand, the UG increased the number of repetitions achieved during the fatigue protocol and total work by 21.2 ± 32.6% and 13.8 ± 21.2%, respectively (p < .05). No differences were found between groups in muscle architecture. Introducing variations in slope during HIIT could be used to induce specific improvements toward muscle endurance or power performance characteristics.
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http://dx.doi.org/10.14814/phy2.14656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785049PMC
January 2021

Long-term intradialytic hybrid exercise training on fatigue symptoms in patients receiving hemodialysis therapy.

Int Urol Nephrol 2021 Apr 2;53(4):771-784. Epub 2021 Jan 2.

Live Lab, Department of PE and Sport Science, University of Thessaly, 42100, Trikala, Greece.

Purpose: Hemodialysis (HD) patients suffer from generalized weakness, exercise intolerance and muscle atrophy, all leading to generalized fatigue and lack of energy. HD patients spend at least 50% of their time in a functionally "switch off" mode with their fatigue sensations reaching a peak in the immediate hours after the dialysis session. The purpose of the current study was to assess the effectiveness of a nine-month hybrid intradialytic exercise program on fatigue symptoms occurring during and after hemodialysis session.

Methods: Twenty stable hemodialysis patients were included in the study (59 ± 13.7 years; 16 males). All patients completed a 9-month supervised exercise training program composed of both aerobic cycling and resistance training during HD. Aspects related to physical and generalized fatigue were assessed via validated questionnaires, while physical performance was assessed by a battery of tests, before and after the intervention period.

Results: Exercise capacity and physical performance were increased by an average of 65 and 40%, respectively. Patients reported feeling better during post-dialysis hours in question 1 (p = 0.000), question 3 (p = 0.009) and question 4 (p = 0.003) after the 9-month intervention. In addition, exercise training improved scores in cognitive function (p = 0.037), vitality (p = 0.05), depression (p = 0.000) and fatigue (p = 0.039).

Conclusion: The present study showed that a 9-month hybrid (aerobic + resistance) exercise training program improved symptoms of post-dialysis fatigue and overall general perception of fatigue. Hybrid exercise training is a safe and effective non-pharmacological approach to ameliorate fatigue symptoms in HD patients.

Trial Registration Number: Trial registration number The study is registered at ClinicalTrials.gov (NCT01721551, 2012) as a clinical trial.
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http://dx.doi.org/10.1007/s11255-020-02711-8DOI Listing
April 2021

Separate and combined effects of cold dialysis and intradialytic exercise on the thermoregulatory responses of hemodialysis patients: a randomized-cross-over study.

BMC Nephrol 2020 12 2;21(1):524. Epub 2020 Dec 2.

School of Physical Education, Sport Science and Dietetics, University of Thessaly, Trikala, 42100, Greece.

Background: The separate and combined effects of intradialytic exercise training (IET) and cold dialysis (CD) on patient thermoregulation remain unknown. This study assessed the thermoregulatory responses of hemodialysis patients under four different hemodialysis protocols: a) one typical dialysis (TD) protocol (dialysate temperature at 37 °C), b) one cold dialysis (CD) protocol (dialysate temperature at 35 °C), c) one typical dialysis protocol which included a single exercise bout (TD + E), d) one cold dialysis protocol which included a single exercise bout (CD + E).

Methods: Ten hemodialysis patients (57.2 ± 14.9 years) participated in this randomized, cross-over study. Core and skin temperatures were measured using an ingestible telemetric pill and by four wireless iButtons attached on the skin, respectively. Body heat storage (S) calculated using the thermometric method proposed by Burton.

Results: The TD and TD + E protocols were associated with increased S leading to moderate effect size increases in core body temperature (as high as 0.4 °C). The low temperature of the dialysate during the CD and the CD + E protocols prevented the rise in S and core temperature (p > 0.05), even during the period that IET took place.

Conclusions: TD and IET are accompanied by a moderate level of hyperthermia, which can be offset by CD. We recommended that CD or with IET can prevent the excessive rise of S.

Trial Registration: Clinical Trial Registry number: NCT03905551 ( clinicaltrials.gov ), DOR: 05/04/2019.
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http://dx.doi.org/10.1186/s12882-020-02167-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709248PMC
December 2020

Effects of 12 months of detraining on health-related quality of life in patients receiving hemodialysis therapy.

Int Urol Nephrol 2020 Sep 14;52(9):1771-1778. Epub 2020 Aug 14.

Department of PE and Sport Science, University of Thessaly, Trikala, Greece.

Purpose: Limited data exist regarding the effects of detraining on functional capacity and quality of life (QoL) in the hemodialysis population. The aim of the current study was to assess whether the discontinuation from a systematic intradialytic exercise training program will affect aspects of health-related QoL and functional capacity in hemodialysis patients.

Methods: Seventeen hemodialysis patients (12 Males/5 Females, age 60.8 ± 13.6 year) participated in this study. Patients were assessed for functional capacity using various functional capacity tests while QoL, daily sleepiness, sleep quality, depression and fatigue were assessed using validated questionnaires at the end of a 12-month aerobic exercise program and after 12 months of detraining.

Results: The detraining significantly reduced patients' QoL score by 20% (P = 0.01). More affected were aspects related to the physical component summary of the QoL (P < 0.001) rather than those related to the mental one (P = 0.096). In addition, the performance in the functional capacity tests was reduced (P < 0.05), while sleep quality (P = 0.020) and daily sleepiness scores (P = 0.006) were significantly worse after the detraining period. Depressive symptoms (P = 0.214) and the level of fatigue (P = 0.163) did not change significantly.

Conclusions: Detraining has a detrimental effect in patients' QoL, functional capacity and sleep quality. The affected physical health contributed significantly to the lower QoL score. It is crucial for the chronic disease patients, even during emergencies such as lockdowns and restrictions in activities to maintain a minimum level of activity to preserve some of the acquired benefits and maintain their health status.
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http://dx.doi.org/10.1007/s11255-020-02560-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426199PMC
September 2020

Cardiac autonomic function during intradialytic exercise training.

Postgrad Med 2019 Sep 15;131(7):539-545. Epub 2019 Sep 15.

Department of Physical Education & Sport Science, University of Thessaly , Trikala , Greece.

: Cardiac autonomic nervous system (ANS) dysfunction is a common feature in patients receiving hemodialysis (HD) therapy, whilst is associated with an increased risk of ventricular arrhythmias and sudden cardiac death. The aim of this study is to investigate and compare the hemodynamic changes and responses of ANS function in HD patients using pupillometry and Heart Rate Variability (HRV) parameters. : Sixteen chronic kidney diseases (CKD) patients receiving HD (52.18 ± 17.7 years) underwent both pupillometric measurements using a portable handheld pupil-measuring device and standard HRV analysis pre HD, every hour and 30 min post-HD session under two different scenarios: at rest while the patient resting at HD bed and when the patient performed a single bout of intradialytic aerobic exercise lasting for 45 min during the second hour of the HD therapy. : No significant changes in ANS values were observed in neither of the pupillometric and the HRV values pre HD, for each hour and post-HD session. HRV parameters were significantly correlated with pupillometric parameters at pre HD and immediately after the single bout of intradialytic exercise. ANS activity did not differ during the conventional HD session and during the session included intradialytic exercise. Moreover, sympatho-vagal balance indices deriving from pupillometric assessment showed beneficial changes after the exercise event. : Pupillometry is a promising and robust technique with fewer artifacts compared to HRV especially in studies involving exercise sessions. Thus, pupillometry can be used as a complementary tool in the evaluation of cardiac autonomic dysfunction.
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http://dx.doi.org/10.1080/00325481.2019.1663707DOI Listing
September 2019

Evidence of Blood and Muscle Redox Status Imbalance in Experimentally Induced Renal Insufficiency in a Rabbit Model.

Oxid Med Cell Longev 2019 4;2019:8219283. Epub 2019 Apr 4.

Muscle Physiology & Mechanics Group, CREHP, DPESS, University of Thessaly, Trikala 42100, Greece.

Chronic kidney disease (CKD) is accompanied by a disturbed redox homeostasis, especially in end-stage patients, which is associated with pathological complications such as anemia, atherosclerosis, and muscle atrophy. However, limited evidence exists about redox disturbances before the end stage of CKD. Moreover, the available redox literature has not yet provided clear associations between circulating and tissue-specific (muscle) oxidative stress levels. The aim of the study was to evaluate commonly used redox status indices in the blood and in two different types of skeletal muscle (psoas, soleus) in the predialysis stages of CKD, using an animal model of renal insufficiency, and to investigate whether blood redox status indices could be reflecting the skeletal muscle redox status. Indices evaluated included reduced glutathione (GSH), oxidized glutathione (GSSG), glutathione reductase (GR), catalase (CAT), total antioxidant capacity (TAC), protein carbonyls (PC), and thiobarbituric acid reactive substances (TBARS). Results showed that blood GSH was higher in the uremic group compared to the control (17.50 ± 1.73 vs. 12.43 ± 1.01, = 0.033). In both muscle types, PC levels were higher in the uremic group compared to the control (psoas: 1.086 ± 0.294 vs. 0.596 ± 0.372, soleus: 2.52 ± 0.29 vs. 0.929 ± 0.41, < 0.05). The soleus had higher levels of TBARS, PC, GSH, CAT, and GR and lower TAC compared to the psoas in both groups. No significant correlations in redox status indices between the blood and skeletal muscles were found. However, in the uremic group, significant correlations between the psoas and soleus muscles in PC, GSSG, and CAT levels emerged, not present in the control. Even in the early stages of CKD, a disturbance in redox homeostasis was observed, which seemed to be muscle type-specific, while blood levels of redox indices did not seem to reflect the intramuscular condition. The above results highlight the need for further research in order to identify the key mechanisms driving the onset and progression of oxidative stress and its detrimental effects on CKD patients.
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http://dx.doi.org/10.1155/2019/8219283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6476063PMC
December 2019

Phosphorus nutritional knowledge among dialysis health care providers and patients: A multicenter observational study.

Clin Nutr ESPEN 2019 06 4;31:33-37. Epub 2019 Apr 4.

School of PE and Sport Sciences, University of Thessaly, Trikala, Greece; Faculty of Health, Plymouth Marjon University, Plymouth, UK.

Background-aims: Phosphorus nutritional knowledge level of hemodialysis patients and renal nurses has been found to be low, while respective knowledge of nephrologists has not been studied yet. There are equivocal results regarding the association of phosphorus nutritional knowledge level and serum phosphorus values. The aim of this study was to assess phosphorus nutritional knowledge of hemodialysis patients, nephrologists and renal nurses and seek potential interventions to improve patients' adherence to phosphorus and overall nutritional guidelines.

Methods: This cross-sectional observational study was conducted on sixty eight hemodialysis patients, 19 renal nurses and 11 nephrologists who were recruited from 3 hemodialysis units in Greece. Phosphorus nutritional knowledge of the participants was assessed by a 25-item item questionnaire (CKDKAT-N) which included 15 questions on phosphorus and 10 questions on protein, sodium, and potassium knowledge.

Results: Nephrologists had higher CKDKAT-N total (19.1 ± 3.6 vs 14.1 ± 2.8 and 13.2 ± 2.8, P < 0.01) and phosphorus knowledge scores (10.6 ± 2.7 vs 7.6 ± 2.2 and 7.3 ± 2.0, P < 0.01) compared to renal nurses and patients respectively. There were no differences in total and phosphorus knowledge scores between nurses and patients. Patients and nurses answered correctly significantly less questions regarding phosphorus compared with the rest of the questions (P < 0.01) while no such difference was found in nephrologists. Serum phosphorus was positively correlated with phosphorus knowledge score (r = 0.31, P = 0.02), and negatively correlated with patient age (r = -0.34, P < 0.05). None of the patients, 11% of the nurses and 27% of the nephrologists answered correctly all three questions regarding P, K and Na dietary recommendations (P < 0.01).

Conclusions: The study confirms that hemodialysis patients have low renal nutrition knowledge while higher nutritional phosphorus knowledge does not lead to lower serum phosphorus values. Alarmingly, renal nurses have been found to have a similar level of knowledge with hemodialysis patients, something that needs to be taken into account when training the new dialysis staff. Nephrologists have superior knowledge; however they are still lacking essential nutritional knowledge that could affect patients' and nurses' overall understanding. Continuing education on nutrition of nephrologists and renal nurses could improve nutrition care of hemodialysis patients.
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http://dx.doi.org/10.1016/j.clnesp.2019.03.005DOI Listing
June 2019

Nocturnal Activity Is Not Affected by a Long-Duration, Low-Intensity Single Exercise Bout.

Sports (Basel) 2019 Mar 1;7(3). Epub 2019 Mar 1.

School of PE and Sport Science, University of Thessaly, 42100 Trikala, Greece.

The aim of the current study was to examine whether prolonged low-intensity aerobic exercise could affect nocturnal activity in healthy individuals. Twenty-one healthy adults (24 ± 3.7 years; 9 females) were enrolled in this study. All participants participated in a 3-h low-intensity walking exercise protocol. Standard biochemical indices were assessed before the exercise protocol and at 72 h. Nocturnal activity and various indices of health were recorded for five consecutive days. The score of muscle pain peaked the night after the exercise protocol ( < 0.05) and returned to baseline two days after. No statistical differences were found in any of the parameters examined, including nocturnal activity. Prolonged low-intensity exercise does not affect nocturnal activity. The anecdotal reports suggesting that exercise or/and physical activity could worsen symptoms of motor restlessness during sleep in sleep disorders, such as restless legs syndrome and periodic limb movements, are not supported by this study. However, these findings need to be verified in clinical populations, as well as by using protocols with different forms of exercise.
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http://dx.doi.org/10.3390/sports7030056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6473573PMC
March 2019

Sleep Abnormalities in Multiple Sclerosis.

Curr Treat Options Neurol 2019 Jan 31;21(1). Epub 2019 Jan 31.

Sleep and Epilepsy Center, Neurocenter of Southern Switzerland, Civic Hospital (EOC) of Lugano, Lugano, Switzerland.

Purpose Of Review: This review summarizes the most well-documented sleep disorders seen in patients with multiple sclerosis (MS), with a special focus on the impact on quality of life.

Recent Findings: Sleep abnormalities in patients with MS are a multifactorial and relatively complex issue affecting approximately 60% of the patients while the pathophysiology of these symptoms is not fully understood. Circadian rhythm disorders and increased levels of pro-inflammatory cytokines have been recognized as potential players in affecting sleep homeostasis in MS patients. Medication-related side effects such as in immunotherapy and other factors such as lesion load can contribute to the disruption of normal sleep patterns. Most frequently encountered sleep disorders are insomnia, sleep-related movement disorders, sleep-related breathing disorders, and circadian rhythm disorders affecting both adults and paediatric MS populations. Aetiology still remains unknown with treatment options focusing on behavioural cognitive therapy and lifestyle modification including improvement in sleep hygiene as well as melatonin supplementation. Given MS prevalence is still rising affecting millions of people, more personalized medicine applications should possibly form the key approach for improving patients' quality of life and quality years.
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http://dx.doi.org/10.1007/s11940-019-0544-7DOI Listing
January 2019

Monitoring Exercise-Induced Muscle Fatigue and Adaptations: Making Sense of Popular or Emerging Indices and Biomarkers.

Sports (Basel) 2018 Nov 26;6(4). Epub 2018 Nov 26.

Muscle Physiology and Mechanics Group, School of Physical Education and Sports Science, University of Thessaly, Trikala 42100, Greece.

Regular exercise with the appropriate intensity and duration may improve an athlete's physical capacities by targeting different performance determinants across the endurance⁻strength spectrum aiming to delay fatigue. The mechanisms of muscle fatigue depend on exercise intensity and duration and may range from substrate depletion to acidosis and product inhibition of adenosinetriphosphatase (ATPase) and glycolysis. Fatigue mechanisms have been studied in isolated muscles; single muscle fibers (intact or skinned) or at the level of filamentous or isolated motor proteins; with each approach contributing to our understanding of the fatigue phenomenon. In vivo methods for monitoring fatigue include the assessment of various functional indices supported by the use of biochemical markers including blood lactate levels and more recently redox markers. Blood lactate measurements; as an accompaniment of functional assessment; are extensively used for estimating the contribution of the anaerobic metabolism to energy expenditure and to help interpret an athlete's resistance to fatigue during high intensity exercise. Monitoring of redox indices is gaining popularity in the applied sports performance setting; as oxidative stress is not only a fatigue agent which may play a role in the pathophysiology of overtraining syndrome; but also constitutes an important signaling pathway for training adaptations; thus reflecting training status. Careful planning of sampling and interpretation of blood biomarkers should be applied; especially given that their levels can fluctuate according to an athlete's lifestyle and training histories.
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http://dx.doi.org/10.3390/sports6040153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315493PMC
November 2018

Evidence of functional deficits at the single muscle fiber level in experimentally-induced renal insufficiency.

J Biomech 2019 01 3;82:259-265. Epub 2018 Nov 3.

Muscle Physiology & Mechanics Group, CREHP, DPESS, University of Thessaly, Trikala, Greece; Institute for Research and Technology Thessaly-CERTH, Trikala, Greece; Faculty of Sport and Health Sciences, University of St Mark and St John (Marjon), Plymouth, United Kingdom. Electronic address:

Chronic kidney disease patients present with metabolic and functional muscle abnormalities, called uremic myopathy, whose mechanisms have not yet been fully elucidated. We investigated whether chronic renal insufficiency (CRI) affects skeletal muscle contractile properties at the cellular level. CRI was induced surgically in New Zealand rabbits (UREM), with sham-operation for controls (CON), and samples were collected at 3 months post-surgery, following euthanasia. All protocols had University Ethics approval following national and European guidelines. Sample treatments and evaluations were blinded. Maximal isometric force was assessed in 382 permeabilized psoas fibers (CON, n = 142, UREM, n = 240) initially at pH7, 10 °C ('standard' conditions), in subsets of fibers in acidic conditions (pH6.2, 10 °C) but also at near physiological temperature (pH7, 30 °C and pH6.2, 30 °C). CRI resulted in significant smaller average cross sectional areas (CSAs) by ∼11% for UREM muscle fibers (vs CON, P < 0.01). At standard conditions, UREM fibers produced lower absolute and specific forces (i.e. normalized force per fiber CSA) (vs CON, P < 0.01); force increased in 30 °C for both groups (P < 0.01), but the disparity between UREM and CON remained significant. Acidosis significantly reduced force (vs pH7, 10 °C P < 0.01), similarly in both groups (in UREM by -48% and in CON by -43%, P > 0.05). For the first time, we give evidence that CRI can induce significant impairments in single psoas muscle fibers force generation, only partly explained by fiber atrophy, thus affecting muscle mechanics at the cellular level.
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http://dx.doi.org/10.1016/j.jbiomech.2018.10.035DOI Listing
January 2019

Meeting report: IUPS and ADInstruments 2017 Teaching Workshop.

Adv Physiol Educ 2018 Jun;42(2):334-339

Brody School of Medicine, East Carolina University , Greenville, North Carolina.

Every 4 yr, the International Union of Physiological Sciences (IUPS) Teaching Workshop is held as a traditional satellite event of the IUPS Congress. The 2017 satellite workshop was held August 5-8, 2017 in Búzios, Rio de Janeiro, Brazil. The workshop provided an opportunity for discussion and experiences in physiology teaching for educators at various levels, graduate students, and undergraduate students. This report describes the workshop activities and reports the participants' perceptions of this event. For evaluation of perception, an anonymous questionnaire was sent by e-mail to all participants, addressing nine items: appropriate topics, time of activities, poster session, congress venue, registration fee, attention of the organizing committee before and during the event, social event, and food. Responses were ranked according to a five-point Likert scale. Of the 145 participants, 77 answered the questionnaire. The participants' perception was positive, noting in particular opportunities to share knowledge, space for reflection of teaching practice, contact networks for future, exchanges of experience, and collaborations in research in physiological education.
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http://dx.doi.org/10.1152/advan.00015.2018DOI Listing
June 2018

Modulators of actin-myosin dissociation: basis for muscle type functional differences during fatigue.

Am J Physiol Cell Physiol 2017 12 20;313(6):C644-C654. Epub 2017 Sep 20.

School of Biosciences, University of Kent, Kent, United Kingdom.

The muscle types present with variable fatigue tolerance, in part due to the myosin isoform expressed. However, the critical steps that define "fatigability" in vivo of fast vs. slow myosin isoforms, at the molecular level, are not yet fully understood. We examined the modulation of the ATP-induced myosin subfragment 1 (S1) dissociation from pyrene-actin by inorganic phosphate (P), pH, and temperature using a specially modified stopped-flow system that allowed fast kinetics measurements at physiological temperature. We contrasted the properties of rabbit psoas (fast) and bovine masseter (slow) myosins (obtained from samples collected from New Zealand rabbits and from a licensed abattoir, respectively, according to institutional and national ethics permits). To identify ATP cycling biochemical intermediates, we assessed ATP binding to a preequilibrated mixture of actomyosin and variable [ADP], pH (pH 7 vs. pH 6.2), and P (zero, 15, or 30 added mM P) in a range of temperatures (5 to 45°C). Temperature and pH variations had little, if any, effect on the ADP dissociation constant ( K) for fast S1, but for slow S1, K was weakened with increasing temperature or low pH. In the absence of ADP, the dissociation constant for phosphate ( K) was weakened with increasing temperature for fast S1. In the presence of ADP, myosin type differences were revealed at the apparent phosphate affinity, depending on pH and temperature. Overall, the newly revealed kinetic differences between myosin types could help explain the in vivo observed muscle type functional differences at rest and during fatigue.
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http://dx.doi.org/10.1152/ajpcell.00023.2017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5814585PMC
December 2017

The Effect of Cold Dialysis in Motor and Sensory Symptoms of RLS/WED Occurring During Hemodialysis: A Double-Blind Study.

ASAIO J 2018 Jan/Feb;64(1):110-114

Restless legs syndrome/Willis-Ekbom disease (RLS/WED) is a common sensorimotory disorder affecting almost 30% of hemodialysis (HD) patients. RLS/WED induces discomfort during rest hours, and its symptoms have also been observed during HD sessions. Anecdotal reports suggest that cooling the dialysate solution during dialysis could help patients overcome those symptoms and improve restlessness. The aim of this double-blind study was to assess whether a reduction of the dialysate temperature by 1°C could reduce motor and sensory symptoms of RLS/WED occurring during HD. Thirty-two HD patients participated in the study. Patients were divided into two groups: the RLS (N=16) and the non-RLS groups (N=16). Patients were studied on two different scenarios for two consecutive HD sessions, 1 week apart: 1) standard temperature of the dialysate (37°C) and 2) low temperature of the dialysate (36°C cold dialysis scenario). In all sessions, motor (leg movement per hour of HD [LM/hHD]) and sensory symptoms were assessed. The reduction of dialysate temperature by 1°C was effective in reducing motor symptoms as they assessed the LM/hHD by 36% only in patients with RLS, while a significant interaction was found between "LM/hHD affected by temperature" and "RLS status" (p = 0.039). Sensory symptoms also reduced by 10% after the reduction of the dialysate temperature. The reduction of the dialysate temperature by 1°C reduced motor symptoms by 36-54% and sensory symptoms by 10% in HD patients with RLS/WED. Cold dialysis could be considered a safe nonpharmacological approach for the amelioration of RLS/WED symptoms occurring during HD.
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http://dx.doi.org/10.1097/MAT.0000000000000622DOI Listing
July 2018

Cold dialysis and its impact on renal patients' health: An evidence-based mini review.

World J Nephrol 2017 May;6(3):119-122

Giorgos K Sakkas, Christina Karatzaferi, Faculty of Sport and Health Sciences, University of St Mark and St John, Plymouth PL6 8BH, United Kingdom.

Chronic renal disease is associated with advanced age, diabetes, hypertension, obesity, musculoskeletal problems and cardiovascular disease, the latter being the main cause of mortality in patients receiving haemodialysis (HD). Cooled dialysate (35 °C-36 °C) is recently employed to reduce the incidence of intradialytic hypotension in patients on chronic HD. The studies to date that have evaluated cooled dialysate are limited, however, data suggest that cooled dialysate improves hemodynamic tolerability of dialysis, minimizes hypotension and exerts a protective effect over major organs including the heart and brain. The current evidence-based review is dealing with the protective effect of cold dialysis and the benefits of it in aspects affecting patients' quality of care and life. There is evidence to suggest that cold dialysis can reduce cardiovascular mortality. However, large multicentre randomized clinical trials are urgently needed to provide further supporting evidence in order to incorporate cold dialysis in routine clinical practice.
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http://dx.doi.org/10.5527/wjn.v6.i3.119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5424433PMC
May 2017

Restless legs syndrome/Willis-Ekbom disease prevalence in beta thalassemia patients.

Sleep Breath 2018 03 19;22(1):175-179. Epub 2017 Apr 19.

Department of PE and Sport Science, University of Thessaly, Trikala, Greece.

Purpose: Both beta thalassemia and restless legs syndrome (RLS) patients share some common pathophysiological characteristics related to iron handling. In the present study, the aim was to explore the prevalence of RLS as well as to explore potential association between the syndrome and various quality of life-related parameters in a sample of beta thalassemia patients.

Methods: One hundred fourteen (age 40 ± 11 yr, 59 M/55F) beta thalassemia patients participated in this cross-sectional descriptive study. Patients were screened for RLS based on the international RLS study group diagnostic criteria as well as a battery of validated questionnaires.

Results: The prevalence of RLS in this sample of beta thalassemia patients was zero. The quality of life score was low (78 ± 18). Iron levels were within normal range (191 ± 66 mcg/dL) while ferritin levels were high as expected (1836 ± 225 ng/dL).

Conclusions: Our sample of patients comes from central Greece where the prevalence of RLS in the general population is 4% while in renal failure patients is 27%. To our surprise, there was no presence of RLS among this sample of beta thalassemia patients. The adequate levels of iron and ferritin often seen in these patients could be the reason of the absence of RLS symptoms.
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http://dx.doi.org/10.1007/s11325-017-1497-2DOI Listing
March 2018

Developing and testing an instrument to assess aquaticity in humans.

J Bodyw Mov Ther 2016 Jul 9;20(3):497-503. Epub 2016 Jan 9.

School of Physical Education and Sport Science, University of Thessaly, Trikala, Greece. Electronic address:

We developed and validated an aquaticity assessment test (AAT) for the evaluation of human physical adequacy in the water. Forty-six volunteers (25M/21F; 20 ± 8 years) participated and performed 10 easy-to-administer and practical aquatic tasks. Group A was formed by 36 elite athletes (M/F 20/16, 24.7 ± 10yrs) from two sports categories depending on their affinity to the water environment: terrestrial (wrestling, cycling, dancing) and aquatic (swimming, synchronized swimming, free diving) sports. Group B was formed by 10 non-athlete participants (5M/5F, 14.4 ± 1.4yrs) and was assessed by two independent evaluators. Participants in Group A performed the aquatic tasks once to develop the final AAT items and cutoffs. Participants in Group B performed the aquatic tasks twice on different days to assess repeatability. Factor analysis recommended all 10 aquatic tasks to be included in the final AAT, resulting in scores ranging from 9.5 to 49.5. The AAT scores were statistically different between the terrestrial and the aquatic sports' participants (p < 0.001). The duration of the test was 25 min from the time of water entry. Receiver operating characteristics curve analyses demonstrated that the cutoffs for low and high aquaticity levels in this sample were ≤23.7 and ≥43.3, respectively. Reliability analyses demonstrated that the aquaticity scores obtained on different days and by different examiners highly correlated (p < 0.001) and were not significantly different (p > 0.05). The AAT appears to be a valid and reliable tool for the evaluation of human physical adequacy in the water. It is an easy and user-friendly test which can be performed in any swimming pool without a need for highly trained staff and specialized equipment, however more research needs to be done in order to be applied in other population group.
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http://dx.doi.org/10.1016/j.jbmt.2015.12.013DOI Listing
July 2016

Systemic Redox Imbalance in Chronic Kidney Disease: A Systematic Review.

Oxid Med Cell Longev 2016 3;2016:8598253. Epub 2016 Aug 3.

Department of Physical Education & Sport Science, University of Thessaly, Karyes, 421 00 Trikala, Greece; Department of Kinesiology, Institute for Research and Technology-CERTH, Thessaly, Karyes, 421 00 Trikala, Greece; Faculty of Sport and Health Sciences, University of St Mark and St John, Plymouth PL6 8BH, UK.

Patients with chronic kidney disease (CKD) experience imbalance between oxygen reactive species (ROS) production and antioxidant defenses leading to cell and tissue damage. However, it remains unclear at which stage of renal insufficiency the redox imbalance becomes more profound. The aim of this systematic review was to provide an update on recent advances in our understanding of how the redox status changes in the progression of renal disease from predialysis stages 1 to 4 to end stage 5 and whether the various treatments and dialysis modalities influence the redox balance. A systematic review was conducted searching PubMed and Scopus by using the Cochrane and PRISMA guidelines. In total, thirty-nine studies met the inclusion criteria and were reviewed. Even from an early stage, imbalance in redox status is evident and as the kidney function worsens it becomes more profound. Hemodialysis therapy per se seems to negatively influence the redox status by the elevation of lipid peroxidation markers, protein carbonylation, and impairing erythrocyte antioxidant defense. However, other dialysis modalities do not so far appear to confer advantages. Supplementation with antioxidants might assist and should be considered as an early intervention to halt premature atherogenesis development at an early stage of CKD.
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http://dx.doi.org/10.1155/2016/8598253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4987477PMC
March 2017

Antioxidant responses following active and passive smoking of tobacco and electronic cigarettes.

Toxicol Mech Methods 2016 Jul 27;26(6):455-61. Epub 2016 Jul 27.

a Department of Physical Education & Sport Science , University of Thessaly, TEFAA Karies , Trikala , Greece ;

Context: It has been indicated that acute active and passive tobacco cigarette smoking may cause changes on redox status balance that may result in significant pathologies. However, no study has evaluated the effects of active and passive e-cigarette smoking on redox status of consumers.

Objective: To examine the acute effects of active and passive e-cigarette and tobacco cigarette smoking on selected redox status markers.

Methods: Using a randomized single-blind crossover design, 30 participants (15 smokers and 15 nonsmokers) were exposed to three different experimental conditions. Smokers underwent a control session, an active tobacco cigarette smoking session (smoked 2 cigarettes within 30-min) and an active e-cigarette smoking session (smoked a pre-determined number of puffs within 30-min using a liquid with 11 ng/ml nicotine). Similarly, nonsmokers underwent a control session, a passive tobacco cigarette smoking session (exposure of 1 h to 23 ± 1 ppm of CO in a 60 m(3) environmental chamber) and a passive e-cigarette smoking session (exposure of 1 h to air enriched with pre- determined number of puffs in a 60 m(3) environmental chamber). Total antioxidant capacity (TAC), catalase activity (CAT) and reduced glutathione (GSH) were assessed in participants' blood prior to, immediately after, and 1-h post-exposure.

Results: TAC, CAT and GSH remained similar to baseline levels immediately after and 1-h-post exposure (p > 0.05) in all trials.

Conclusions: Tobacco and e-cigarette smoking exposure do not acutely alter the response of the antioxidant system, neither under active nor passive smoking conditions. Overall, there is not distinction between tobacco and e-cigarette active and passive smoking effects on specific redox status indices.
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http://dx.doi.org/10.1080/15376516.2016.1196281DOI Listing
July 2016

Higher insulin sensitivity in EDL muscle of rats fed a low-protein, high-carbohydrate diet inhibits the caspase-3 and ubiquitin-proteasome proteolytic systems but does not increase protein synthesis.

J Nutr Biochem 2016 08 6;34:89-98. Epub 2016 May 6.

Department of Chemistry, Federal University of Mato Grosso, Cuiabá, Mato Grosso, Brazil. Electronic address:

Compared with the extensor digitorum longus (EDL) muscle of control rats (C), the EDL muscle of rats fed a low-protein, high-carbohydrate diet (LPHC) showed a 36% reduction in mass. Muscle mass is determined by the balance between protein synthesis and proteolysis; thus, the aim of this work was to evaluate the components involved in these processes. Compared with the muscle from C rats, the EDL muscle from LPHC diet-fed rats showed a reduction (34%) in the in vitro basal protein synthesis and a 22% reduction in the in vitro basal proteolysis suggesting that the reduction in the mass can be associated with a change in the rate of the two processes. Soon after euthanasia, in the EDL muscles of the rats fed the LPHC diet for 15days, the activity of caspase-3 and that of components of the ubiquitin-proteasome system (atrogin-1 content and chymotrypsin-like activity) were decreased. The phosphorylation of p70(S6K) and 4E-BP1, proteins involved in protein synthesis, was also decreased. We observed an increase in the insulin-stimulated protein content of p-Akt. Thus, the higher insulin sensitivity in the EDL muscle of LPHC rats seemed to contribute to the lower proteolysis in LPHC rats. However, even with the higher insulin sensitivity, the reduction in p-E4-BP1 and p70(S6K) indicates a reduction in protein synthesis, showing that factors other than insulin can have a greater effect on the control of protein synthesis.
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http://dx.doi.org/10.1016/j.jnutbio.2016.04.008DOI Listing
August 2016

Aquaticity: A discussion of the term and of how it applies to humans.

J Bodyw Mov Ther 2016 Apr 7;20(2):219-23. Epub 2015 Nov 7.

School of Physical Education and Sport Sciences, Department of Sport Science, LIVE Laboratory, University of Thessaly, Karies, Trikala GR42100, Greece. Electronic address:

The relationship between humans and water and the effects on aspects related to human performance has never been studied scientifically. The aim of the current systematic review is to attempt to define the term "aquaticity", present the factors that describe it and reveal the form in which it presents itself in today's society, in order to become a distinct scientific field of study. A systematic review of the literature has been conducted using anecdotal reports from the internet and forums as well as scientific articles and books from databases on issues related to aquatic sports. To the best of our knowledge there are no scientific articles dealing with human's aquaticity. In the current systematic review, four factors have been recognized that are closely related to human aquaticity. Those are related to physical condition in the water, to apnea and ability to immerse, to mental health and to parameters related to body composition. According to our findings, "Aquaticity is the capacity of a terrestrial mammalian organism to function and habitualise in the aquatic environment. The level of aquaticity depends on mental and physical characteristics and can be improved by frequent exposure to the water element". The ideal state of aquaticity is achieved through the activation of the diving reflex, when the human body is totally immersed in water. The development of knowledge regarding the aquatic environment leads humans to an improved state of aquaticity.
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http://dx.doi.org/10.1016/j.jbmt.2015.11.001DOI Listing
April 2016

Intra-Renal Hemodynamic Changes After Habitual Physical Activity in Patients with Chronic Kidney Disease.

Curr Pharm Des 2016 ;22(24):3700-14

25, Karditsis, 42100, Trikala, Thessalia, Greece.

Background: Chronic Kidney Disease (CKD) is considered a silent epidemic with a continuously growing prevalence around the world. Due to uremia many functional and morphological abnormalities occur in almost all systems. Mostly affected, the cardiovascular system, leads to diminished cardiac function that affects patients' functional capacity and physical activity levels, reducing survival and increasing all-cause mortality. Systematic exercise training ameliorates uremia induced body deficits and significantly improves the survival of CKD patients. Intradialytic exercise training has been recommended as a complementary therapeutic modality equally important to hemodialysis.

Methods: The aim of this systematic review is to provide an update on recent advances in our understanding of how exercise training improves functionality of the cardiovascular system through the hemodynamic changes induced by habitual or intradialytic and/or home-based exercise training programs.

Results: Systematic exercise training induces beneficial adaptive responses and influences many sensitive physiological biomarkers, such as oxidative stress biomarkers that are implicated in the development of atherosclerosis. Additionally, exercise training decreases the cardiovascular risk by improving the autonomic nervous system activity and the left ventricular function and by reducing nontraditional risk factors such as epicardial adipose tissue. It seems that all these central and peripheral adaptations to exercise training significantly contribute to improvements in functional capacity and exercise tolerance among CKD patients and result in the risk reduction of CKD-associated disorders.

Conclusion: Exercise training could serve as a complimentary therapeutic strategy in CKD patients while health care providers should motivate patients to engage in any type of exercise training programs.
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http://dx.doi.org/10.2174/1381612822666160322144936DOI Listing
January 2018

Pharmacological and Non-pharmacological Treatment Options for Depression and Depressive Symptoms in Hemodialysis Patients.

Health Psychol Res 2015 Apr 13;3(1):1811. Epub 2015 Apr 13.

Department of Physical Education and Sport Science, University of Thessaly, Trikala; Institute of Research and Technology Thessaly, Centre for Research and Technology-Hellas , Trikala, Greece.

Depression is a mental disorder with a high prevalence among patients with end stage renal disease (ESRD). It is reported that depression afflicts approximately 20-30% of this patient population, being associated, amongst other, with high mortality rate, low adherence to medication and low perceived quality of life. There is a variety of medications known to be effective for the treatment of depression but due to poor adherence to treatment as well as due to the high need for medications addressing other ESRD comorbidities, depression often remains untreated. According to the literature, depression is under-diagnosed and undertreated in the majority of the patients with chronic kidney disease. In the current review the main pharmacological and non-pharmacological approaches and research outcomes for the management of depressive symptoms in hemodialysis patients are discussed.
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http://dx.doi.org/10.4081/hpr.2015.1811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4768541PMC
April 2015

Combination of Exercise Training and Dopamine Agonists in Patients with RLS on Dialysis: A Randomized, Double-Blind Placebo-Controlled Study.

ASAIO J 2015 Nov-Dec;61(6):738-41

From the *Department of Life and Health Sciences, University of Nicosia, Nicosia, Cyprus; †Department of Physical Education and Sport Science, ‡Department of Medicine, University of Thessaly, Trikala, Greece; and §Department of Physical Education and Sport Science, University of Athens, Athens, Greece.

Both exercise training and treatment with dopamine agonists (DA) have been used with success for the amelioration of uremic restless legs syndrome (RLS) symptoms. However, no data are available combining those two approaches. The aim of the current randomized, double-blind, placebo-controlled study was to investigate the effects of a 6 month intradialytic exercise training in combination with a low dose of DA in patients suffering from uremic RLS symptoms. Fourteen stable patients with RLS on hemodialysis were randomly assigned to the exercise training plus DA group and the exercise training plus placebo group. Both combinations were found to equally reduce uremic RLS symptoms by approximately 60%. The combination of low dose of DA with aerobic exercise training could be considered an alternative approach to high DA dosage regimes in reducing RLS symptoms' severity.
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http://dx.doi.org/10.1097/MAT.0000000000000271DOI Listing
July 2016

Ranolazine enhances nicardipine-induced relaxation of alpha1-adrenoceptor-mediated contraction on isolated rabbit aorta.

Acta Cardiol 2015 Apr;70(2):157-62

Ranolazine (RAN) and nicardipine (NIC) have been studied for their vasorelaxing effects but the combination of these agents against adrenergic vasoconstriction has not been tested. The present study aimed at investigating the vasorelaxing effect by the combination of the two agents on alpha1-adrenoceptor-mediated contraction on isolated rabbit aorta. Aortic rings were mounted for isometric tension recording in organ baths containing Krebs-Henseleit solution. Concentration-response curves of RAN (10(-9) to 10(-4) M), NIC (10(-1) to 10(-5) M), and RAN + NIC (3 x 10(-6) M) were obtained in a cumulative manner using phenylephrine (PE, 2 x 10(-6) M) as constrictor agent. The effective concentration (EC)50 values for RAN and NIC were 6.5 x 10(-6) M and 1.4 x 10(-5) M, respectively. The treatment of PE-precontracted aortic rings with either RAN or NIC up to 65 min revealed that both agents displayed a biphasic pattern of initial rising and late sustained phases of relaxation. At 35 min of incubation, RAN and NIC induced relaxation by 23 +/- 3% and 14 +/- 4%, respectively (N = 7, P=NS, RAN vs. NIC); their combination resulted in a 34 +/- 4% relaxation (N=7; P < 0.01, RAN + NIC vs. NIC). At 65 min the effect of NIC prevailed and tended to be closer to the values of the combination treatment (P < 0.01, RAN + NIC vs. RAN). The results indicate that RAN at therapeutic concentrations exerts a significant additive vasorelaxing effect when combined with NIC in rabbit aorta.
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http://dx.doi.org/10.1080/ac.70.2.3073506DOI Listing
April 2015

Cognitive function and exercise training for chronic renal disease patients: A literature review.

J Bodyw Mov Ther 2015 Jul 18;19(3):509-15. Epub 2015 Apr 18.

Department of PE and Sport Science, University of Thessaly, Trikala, Greece; Department of Medicine, Division of Nephrology, University of Thessaly, Greece.

Objective: Cognitive impairment is very often noted in patients with Chronic Kidney Disease (CKD). Even though, exercise is considered to be a quantifiable activity that improves cognition in animals and humans, it seems that few studies have examined the relationship between cognitive function and CKD from the perspective of physical activity and cognitive performance. Thus, this evidence based review summarizes the present level of knowledge regarding the effects of exercise training on cognitive function in CKD patients.

Data Sources: A comprehensive literature search was conducted in PubMed and Scopus from May 2014 through June 2014, by using the Cochrane and PRISMA guidelines.

Review Methods: Eligibility of the studies based on titles, abstracts and full-text articles was determined by two reviewers. Studies were selected using inclusion and exclusion criteria. We included only those studies that: assessed cognitive function in humans and animals using validated neuropsychological methods in chronic renal diseases patients; used exercise training protocols; addressed randomized control trials or controlled trials or clinical trials designed to evaluate cognitive impairment; and articles that were written in English. Studies were excluded when they concerned behavioral approaches and underpowered studies.

Results: According to the current review only a few studies have examined the issue of cognitive function in CKD patients. These studies indicate that these patients often exhibit cognitive impairment, which is highly associated with poor outcomes. It has been supported that exercise training can induce positive changes in brain metabolism favoring better scores in cognitive function in Chronic Kidney Disease patients although the physiological mechanisms, which explain the influence of physical activity on cognition, have focused on changes in neurotransmitters, neurotrophins and vasculature.

Conclusion: Systematic exercise training seems to improve cognitive function in Chronic Kidney Disease patients but further research is warranted to further clarify the mechanisms involved.
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http://dx.doi.org/10.1016/j.jbmt.2015.04.006DOI Listing
July 2015

Uremic myopathy: is oxidative stress implicated in muscle dysfunction in uremia?

Front Physiol 2015 30;6:102. Epub 2015 Mar 30.

Department of Physical Education and Sport Sciences (DPESS), School of Physical Education (PE), University of Thessaly Trikala, Greece.

Renal failure is accompanied by progressive muscle weakness and premature fatigue, in part linked to hypokinesis and in part to uremic toxicity. These changes are associated with various detrimental biochemical and morphological alterations. All of these pathological parameters are collectively termed uremic myopathy. Various interventions while helpful can't fully remedy the pathological phenotype. Complex mechanisms that stimulate muscle dysfunction in uremia have been proposed, and oxidative stress could be implicated. Skeletal muscles continuously produce reactive oxygen species (ROS) and reactive nitrogen species (RNS) at rest and more so during contraction. The aim of this mini review is to provide an update on recent advances in our understanding of how ROS and RNS generation might contribute to muscle dysfunction in uremia. Thus, a systematic review was conducted searching PubMed and Scopus by using the Cochrane and PRISMA guidelines. While few studies met our criteria their findings are discussed making reference to other available literature data. Oxidative stress can direct muscle cells into a catabolic state and chronic exposure to it leads to wasting. Moreover, redox disturbances can significantly affect force production per se. We conclude that oxidative stress can be in part responsible for some aspects of uremic myopathy. Further research is needed to discern clear mechanisms and to help efforts to counteract muscle weakness and exercise intolerance in uremic patients.
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http://dx.doi.org/10.3389/fphys.2015.00102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4378187PMC
April 2015

Current trends in the management of uremic restless legs syndrome: a systematic review on aspects related to quality of life, cardiovascular mortality and survival.

Sleep Med Rev 2015 Jun 15;21:39-49. Epub 2014 Aug 15.

Department of Nephrology, Faculty of Medicine, University of Thessaly, Larissa, Greece.

Restless legs syndrome (RLS) affects almost one out of three end-stage renal disease patients. This review assesses the current treatment options for uremic RLS and the potential benefits of those treatments on quality of life parameters, cardiovascular mortality and survival. A systematic review was conducted searching PubMed and Scopus by using the Cochrane and PRISMA guidelines. Fourteen studies met the inclusion criteria in which the international RLS study group criteria were used as the primary diagnostic tool. Both pharmacological and non-pharmacological approaches were found to reduce the severity of uremic RLS symptoms. Only four studies reported changes on aspects related to quality of life while those changes were also associated with health benefits that resulted in reduced cardiovascular risk. The severity of uremic RLS symptoms can be ameliorated by using dopamine agonists and gabapentin, intravenous iron, exercise or supplementation with vitamins C and E, although some of those treatment benefits may be transient. There is a lack of strong evidence regarding the effects of the pharmacological approaches on quality of life and cardiovascular survival and mortality. In contrast exercise has been proven beneficial in both reducing the RLS symptoms' severity score and improving the quality of life.
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http://dx.doi.org/10.1016/j.smrv.2014.07.006DOI Listing
June 2015