Skeletal muscle is a highly adaptable organ, and its amount declines under catabolic conditions such as critical illness. Aging is accompanied by a gradual loss of muscle, especially when physical activity decreases. Intensive care unit-acquired weakness is a common and highly serious neuromuscular complication in critically ill patients. It is a consequence of critical illness and is characterized by a systemic inflammatory response, leading to metabolic stress, that causes the development of multiple organ dysfunction. Muscle dysfunction is an important component of this syndrome, and the degree of catabolism corresponds to the severity of the condition. The population of critically ill is aging; thus, we face another negative effect-sarcopenia-the age-related decline of skeletal muscle mass and function. Low-grade inflammation gradually accumulates over time, inhibits proteosynthesis, worsens anabolic resistance, and increases insulin resistance. The cumulative consequence is a gradual decline in muscle recovery and muscle mass. The clinical manifestation for both of the above conditions is skeletal muscle weakness, with macromolecular damage, and a common mechanism-mitochondrial dysfunction. In this review, we compare the molecular mechanisms underlying the two types of muscle atrophy, and address questions regarding possible shared molecular mechanisms, and whether critical illness accelerates the aging process.

• Klíčová slova
• intensive care unit-acquired weakness, muscle atrophy, proteostasis, rapamycin system, sarcopenia, ubiquitin–proteasome system,
• MeSH
• jednotky intenzivní péče MeSH
• kosterní svaly MeSH
• kritický stav MeSH
• lidé MeSH
• nemoci svalů * komplikace   MeSH
• sarkopenie * komplikace   MeSH
• svalová atrofie komplikace   MeSH
• svalová slabost etiologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: Functional mitochondria in skeletal muscle of patients with protracted critical illness and intensive care unit-acquired weakness are depleted, but remaining mitochondria have increased functional capacities of respiratory complexes II and III. This can be an adaptation to relative abundancy of fatty acid over glucose caused by insulin resistance. We hypothesized that the capacity of muscle mitochondria to oxidize fatty acid is increased in protracted critical illness. METHODS: We assessed fatty acid oxidation (FAO) and mitochondrial functional indices in vitro by using extracellular flux analysis in cultured myotubes obtained by isolating and culturing satellite cells from vastus lateralis muscle biopsy samples from patients with ICU-acquired weakness (n = 6) and age-matched healthy controls (n = 7). Bioenergetic measurements were performed at baseline and after 6 days of exposure to free fatty acids (FFAs). RESULTS: Mitochondrial density in myotubes from ICU patients was 69% of healthy controls ( P = .051). After adjustment to mitochondrial content, there were no differences in adenosine triphosphate (ATP) synthesis or the capacity and coupling of the respiratory chain. FAO capacity in ICU patients was 157% of FAO capacity in controls ( P = .015). In myotubes of ICU patients, unlike healthy controls, the exposure to FFA significantly ( P = .009) increased maximum respiratory chain capacity. CONCLUSION: In an in vitro model of skeletal muscle of patients with protracted critical illness, we have shown signs of adaptation to increased FAO. Even in the presence of glucose and insulin, elevation of FFAs in the extracellular environment increased maximal capacity of the respiratory chain.

• Klíčová slova
• ICU-acquired weakness, extracellular flux analysis, fatty acid oxidation, human skeletal muscle, mitochondrial function, protracted critical illness,
• MeSH
• čtyřhlavý sval stehenní MeSH
• energetický metabolismus * MeSH
• fyziologická adaptace MeSH
• inzulin krev   MeSH
• inzulinová rezistence MeSH
• jednotky intenzivní péče * MeSH
• kosterní svalová vlákna MeSH
• kosterní svaly cytologie   patofyziologie   MeSH
• krevní glukóza metabolismus   MeSH
• kritický stav * MeSH
• kyseliny mastné neesterifikované metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipolýza MeSH
• respirační komplex II metabolismus   MeSH
• senioři MeSH
• svalová slabost etiologie   metabolismus   patofyziologie   MeSH
• svalové mitochondrie fyziologie   MeSH
• transport elektronů MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• inzulin MeSH
• krevní glukóza MeSH
• kyseliny mastné neesterifikované MeSH
• respirační komplex II MeSH
• respiratory complex II MeSH Prohlížeč

BACKGROUND: Mitochondrial damage occurs in the acute phase of critical illness, followed by activation of mitochondrial biogenesis in survivors. It has been hypothesized that bioenergetics failure of skeletal muscle may contribute to the development of ICU-acquired weakness. The aim of the present study was to determine whether mitochondrial dysfunction persists until protracted phase of critical illness. METHODS: In this single-centre controlled-cohort ex vivo proof-of-concept pilot study, we obtained vastus lateralis biopsies from ventilated patients with ICU-acquired weakness (n = 8) and from age and sex-matched metabolically healthy controls (n = 8). Mitochondrial functional indices were measured in cytosolic context by high-resolution respirometry in tissue homogenates, activities of respiratory complexes by spectrophotometry and individual functional capacities were correlated with concentrations of electron transport chain key subunits from respiratory complexes II, III, IV and V measured by western blot. RESULTS: The ability of aerobic ATP synthesis (OXPHOS) was reduced to ~54% in ICU patients (p<0.01), in correlation with the depletion of complexes III (~38% of control, p = 0.02) and IV (~26% of controls, p<0.01) and without signs of mitochondrial uncoupling. When mitochondrial functional indices were adjusted to citrate synthase activity, OXPHOS and the activity of complexes I and IV were not different, whilst the activities of complexes II and III were increased in ICU patients 3-fold (p<0.01) respectively 2-fold (p<0.01). CONCLUSIONS: Compared to healthy controls, in ICU patients we have demonstrated a ~50% reduction of the ability of skeletal muscle to synthetize ATP in mitochondria. We found a depletion of complex III and IV concentrations and relative increases in functional capacities of complex II and glycerol-3-phosphate dehydrogenase/complex III.

• MeSH
• adenosintrifosfát metabolismus   fyziologie   MeSH
• biogeneze organel MeSH
• čtyřhlavý sval stehenní metabolismus   MeSH
• energetický metabolismus fyziologie   MeSH
• glycerolfosfátdehydrogenasa metabolismus   MeSH
• jednotky intenzivní péče MeSH
• kohortové studie MeSH
• kosterní svaly metabolismus   MeSH
• kritický stav MeSH
• lidé středního věku MeSH
• lidé MeSH
• mitochondrie metabolismus   patologie   MeSH
• oxidační stres fyziologie   MeSH
• pilotní projekty MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• svalová slabost etiologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adenosintrifosfát MeSH
• glycerolfosfátdehydrogenasa MeSH

BACKGROUND: Functional movement disorders, a common cause of neurological disabilities, can occur with heterogeneous motor manifestations including functional weakness. However, the underlying mechanisms related to brain function and connectivity are unknown. OBJECTIVE: To identify brain connectivity alterations related to functional weakness we assessed network centrality changes in a group of patients with heterogeneous motor manifestations using task-free functional MRI in combination with different network centrality approaches. METHODS: Task-free functional MRI was performed in 48 patients with heterogeneous motor manifestations including 28 patients showing functional weakness and 65 age- and sex-matched healthy controls. Functional connectivity differences were assessed using different network centrality approaches, i.e. global correlation, eigenvector centrality, and intrinsic connectivity. Motor symptom severity was assessed using The Simplified Functional Movement Disorders Rating Scale and correlated with network centrality. RESULTS: Comparing patients with and without functional weakness showed significant network centrality differences in the left temporoparietal junction and precuneus. Patients with functional weakness showed increased centrality in the same anatomical regions when comparing functional weakness with healthy controls. Moreover, in the same regions, patients with functional weakness showed a positive correlation between motor symptom severity and network centrality. This correlation was shown to be specific to functional weakness with an interaction analysis, confirming a significant difference between patients with and without functional weakness. CONCLUSIONS: We identified the temporoparietal junction and precuneus as key regions involved in brain connectivity alterations related to functional weakness. We propose that both regions may be promising targets for phenotype-specific non-invasive brain stimulation.

• Klíčová slova
• Brain connectivity, Functional connectivity, Functional magnetic resonance imaging, Functional movement disorders, Functional weakness, Motor conversion disorder, Precuneus, Temporoparietal junction,
• MeSH
• konverzní poruchy * MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mapování mozku MeSH
• mozek * diagnostické zobrazování   MeSH
• temenní lalok MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Obstructive sleep apnoea syndrome (OSAS) is a common disorder associated with upper airway muscle dysfunction. Agents that improve respiratory muscle performance may have considerable therapeutic value. We examined the effects of acute exposure to sustained and intermittent hypoxia on rat pharyngeal dilator muscle function. Additionally, we sought to test the efficacy of antioxidant treatment in ameliorating or preventing hypoxia-related muscle dysfunction. Isometric contractile and endurance properties of isolated rat sternohyoid muscle bundles were examined at 35 °C in vitro. Muscle bundles were exposed to one of four gas treatments: hyperoxia (control), sustained hypoxia (SH), intermittent hypoxia (IH) or hypoxia/re-oxygenation (HR), in the absence or presence of the superoxide scavenger--Tempol (10 mM). Stress-frequency relationship was determined in response to electrical stimulation (10-100 Hz in increments of 10-20 Hz, train duration: 300 ms). Muscle performance was also assessed during repetitive muscle stimulation (40 Hz, 300 ms every 2 s for 2.5 min). Compared to control, IH and HR treatments significantly decreased sternohyoid muscle force. The negative inotropic effect of the two gas protocols was similar, but both were of lesser magnitude than the effects of SH. SH, but not IH and HR, increased muscle fatigue. Tempol significantly increased sensitivity to stimulation in all muscle preparations and caused a leftward shift in the stress-frequency relationship of IH and SH treated muscles. Tempol did not ameliorate sternohyoid muscle fatigue during SH. We conclude that Tempol increases upper airway muscle sensitivity to stimulation but only modestly ameliorates respiratory muscle weakness during intermittent and sustained hypoxic conditions in vitro. Respiratory muscle fatigue during sustained hypoxia appears unrelated to oxidative stress.

• MeSH
• cyklické N-oxidy terapeutické užití   MeSH
• dýchací svaly patofyziologie   MeSH
• hypoxie patofyziologie   MeSH
• interpretace statistických dat MeSH
• isometrická kontrakce účinky léků   MeSH
• krysa rodu Rattus MeSH
• potkani Wistar MeSH
• scavengery volných radikálů terapeutické užití   MeSH
• spinové značení MeSH
• superoxidy metabolismus   MeSH
• svalová slabost patofyziologie   MeSH
• techniky in vitro MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cyklické N-oxidy MeSH
• scavengery volných radikálů MeSH
• spinové značení MeSH
• superoxidy MeSH
• tempol MeSH Prohlížeč

BACKGROUND: Intensive care unit (ICU)-acquired weakness is the most important cause of failed functional outcome in survivors of critical care. Most damage occurs during the first week when patients are not cooperative enough with conventional rehabilitation. Functional electrical stimulation-assisted cycle ergometry (FES-CE) applied within 48 h of ICU admission may improve muscle function and long-term outcome. METHODS: An assessor-blinded, pragmatic, single-centre randomized controlled trial will be performed. Adults (n = 150) mechanically ventilated for < 48 h from four ICUs who are estimated to need > 7 days of critical care will be randomized (1:1) to receive either standard of care or FES-CE-based intensified rehabilitation, which will continue until ICU discharge. PRIMARY OUTCOME: quality of life measured by 36-Item Short Form Health Survey score at 6 months. SECONDARY OUTCOMES: functional performance at ICU discharge, muscle mass (vastus ultrasound, N-balance) and function (Medical Research Council score, insulin sensitivity). In a subgroup (n = 30) we will assess insulin sensitivity and perform skeletal muscle biopsies to look at mitochondrial function, fibre typing and regulatory protein expression. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02864745. Registered on 12 August 2016.

• Klíčová slova
• Critically ill, Early rehabilitation, Functional electrical stimulation-assisted cycle ergometry, Intensive care unit, Mobility, Physical therapy,
• MeSH
• časové faktory MeSH
• cyklistika * MeSH
• elektrostimulační terapie * škodlivé účinky   MeSH
• ergometrie * MeSH
• jednotky intenzivní péče MeSH
• kosterní svaly inervace   MeSH
• kritický stav MeSH
• kvalita života MeSH
• lidé MeSH
• obnova funkce MeSH
• pragmatické klinické studie jako téma MeSH
• svalová kontrakce * MeSH
• svalová síla * MeSH
• svalová slabost diagnóza   patofyziologie   rehabilitace   MeSH
• výsledek terapie MeSH
• zátěžový test MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• protokol klinické studie MeSH
• Geografické názvy
• Česká republika MeSH

BACKGROUND: Patients with functional neurological disorders (FND) often present with multiple motor, sensory, psychological and cognitive symptoms. In order to explore the relationship between these common symptoms, we performed a detailed clinical assessment of motor, non-motor symptoms, health-related quality of life (HRQoL) and disability in a large cohort of patients with motor FND. To understand the clinical heterogeneity, cluster analysis was used to search for subgroups within the cohort. METHODS: One hundred fifty-two patients with a clinically established diagnosis of motor FND were assessed for motor symptom severity using the Simplified Functional Movement Disorder Rating Scale (S-FMDRS), the number of different motor phenotypes (i.e. tremor, dystonia, gait disorder, myoclonus, and weakness), gait severity and postural instability. All patients then evaluated each motor symptom type severity on a Likert scale and completed questionnaires for depression, anxiety, pain, fatigue, cognitive complaints and HRQoL. RESULTS: Significant correlations were found among the self-reported and all objective motor symptoms severity measures. All self-reported measures including HRQoL correlated strongly with each other. S-FMDRS weakly correlated with HRQoL. Hierarchical cluster analysis supplemented with gap statistics revealed a homogenous patient sample which could not be separated into subgroups. CONCLUSIONS: We interpret the lack of evidence of clusters along with a high degree of correlation between all self-reported and objective measures of motor or non-motor symptoms and HRQoL within current neurobiological models as evidence to support a unified pathophysiology of 'functional' symptoms. Our results support the unification of functional and somatic syndromes in classification schemes and for future mechanistic and therapeutic research.

• Klíčová slova
• Cluster analysis, conversion disorder, correlation, functional movement disorders, functional neurological disorder, gap statistics, medically unexplained symptoms, motor phenotypes,
• MeSH
• konverzní poruchy * MeSH
• kvalita života * psychologie   MeSH
• lidé MeSH
• syndrom MeSH
• úzkost diagnóza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Adsorption of cell-penetrating peptides (CPPs) at cellular membranes is the first and necessary step for their subsequent translocation across cellular membranes into the cytosol. It has been experimentally shown that CPPs rich in arginine (Arg) amino acid penetrate across phospholipid bilayers more effectively than their lysine (Lys) rich counterparts. In this work, we aim to understand the differences in the first translocation step, adsorption of Arg9 and Lys9 peptides at fully hydrated neutral phosphatidylcholine (PC) and phosphatidylethanolamine (PE) lipid bilayers and evaluate in detail the energetics of the process using molecular dynamics (MD) simulations and free energy calculations of adsorption of the single peptide. We show that the adsorption of Arg9 is energetically feasible, with the free energy of adsorption being ∼-5.0 kcal mol-1 at PC and ∼-5.5 kcal mol-1 at PE bilayers. In contrast, adsorption of Lys9 is not observed at PC bilayers, and their adsorption at PE bilayers is very weak, being ∼-0.5 kcal mol-1. We show by energy decomposition and analysis of peptide hydration along the membrane that significantly stronger electrostatic interactions of Arg9 with lipid phosphate groups, together with the greater loss of peptide hydration (and in turn stronger hydrophobic interactions) along the membrane translocation path, are the main driving factors governing the adsorption of Arg-rich peptides at neutral lipid bilayers in contrast to Lys-rich peptides. Finally, we also compare the energetics in lipid/bilayer systems with the density functional theory (DFT) calculations of the corresponding model systems in the continuum water model and reveal the energetic differences in different environments.

• MeSH
• fosfatidylcholiny chemie   MeSH
• fosfolipidy MeSH
• lipidové dvojvrstvy chemie   MeSH
• penetrační peptidy * chemie   MeSH
• polylysin * MeSH
• simulace molekulární dynamiky MeSH
• teorie funkcionálu hustoty MeSH
• termodynamika MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fosfatidylcholiny MeSH
• fosfolipidy MeSH
• lipidové dvojvrstvy MeSH
• penetrační peptidy * MeSH
• polyarginine MeSH Prohlížeč
• polylysin * MeSH

OBJECTIVES: The prevalence of restless legs syndrome (RLS) in functional movement disorders (FMD) is not known. Patients with FMD often present with multiple motor and sensory symptoms. Some of these symptoms might be due to comorbid RLS. Therefore, our objective was to evaluate possible association between FMD and RLS. DESIGN: Case-control study. SETTING: Movement Disorders Center, 1st Faculty of Medicine and General University Hospital in Prague, Czech Republic. PARTICIPANTS: 96 consecutive patients with clinically established FMD (80 females, mean age (SD) 45.0 (13) years), and 76 matched controls. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure was prevalence of RLS based on updated International RLS Study Group criteria. Secondary outcome measures included prevalence of periodic limb movements (PLM) using actigraphy; pain, motor and sensory symptoms in lower limbs; organic comorbidities and medication affecting RLS. RESULTS: RLS criteria were fulfilled in 43.8% of patients (95% CI 34 to 54) and in 7.9% of controls (95% CI 3 to 17, p<0.00001). Both RLS and PLM indices (PLMi) ≥22.5/hour were found in 21.2% of patients with FMD and 2.6% of controls. Patients with FMD with RLS had a higher mean PLMi (p<0.001) and a higher proportion of PLMi ≥22.5/hour (p<0.01) than RLS-negative patients. Patients with RLS had higher prevalence of pain and sensory symptoms in lower limbs, no difference was found in medication and prevalence of organic comorbidities in patients with FMD with and without RLS. CONCLUSIONS: We found an increased prevalence of RLS in patients with FMD. Clinical diagnosis of RLS was supported by actigraphic measurement of clinically relevant PLM in a significant proportion of patients with FMD. Although functional motor and sensory symptoms may mimic RLS, RLS may be unrecognised in patients with FMD. This finding may have clinical implications in management of FMD, and it raises the possibility of common pathophysiological mechanisms of FMD and RLS/PLM.

• Klíčová slova
• actigraphy, functional movement disorders, periodic limb movements, psychogenic movement disorders, restless legs syndrome, sensory symptoms,
• MeSH
• dospělí MeSH
• dystonie patofyziologie   MeSH
• konverzní poruchy epidemiologie   patofyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• myoklonus patofyziologie   MeSH
• neurologické poruchy chůze patofyziologie   MeSH
• pohybové poruchy epidemiologie   patofyziologie   MeSH
• poruchy hybnosti oka patofyziologie   MeSH
• poruchy řeči patofyziologie   MeSH
• prevalence MeSH
• studie případů a kontrol MeSH
• svalová slabost patofyziologie   MeSH
• syndrom neklidných nohou epidemiologie   MeSH
• tremor patofyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Intramural MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH

PURPOSE: Functional electrical stimulation-assisted cycle ergometry (FESCE) enables in-bed leg exercise independently of patients' volition. We hypothesised that early use of FESCE-based progressive mobility programme improves physical function in survivors of critical care after 6 months. METHODS: We enrolled mechanically ventilated adults estimated to need >7 days of intensive care unit (ICU) stay into an assessor-blinded single centre randomised controlled trial to receive either FESCE-based protocolised or standard rehabilitation that continued up to day 28 or ICU discharge. RESULTS: We randomised in 1:1 ratio 150 patients (age 61±15 years, Acute Physiology and Chronic Health Evaluation II 21±7) at a median of 21 (IQR 19-43) hours after admission to ICU. Mean rehabilitation duration of rehabilitation delivered to intervention versus control group was 82 (IQR 66-97) versus 53 (IQR 50-57) min per treatment day, p<0.001. At 6 months 42 (56%) and 46 (61%) patients in interventional and control groups, respectively, were alive and available to follow-up (81.5% of prespecified sample size). Their Physical Component Summary of SF-36 (primary outcome) was not different at 6 months (50 (IQR 21-69) vs 49 (IQR 26-77); p=0.26). At ICU discharge, there were no differences in the ICU length of stay, functional performance, rectus femoris cross-sectional diameter or muscle power despite the daily nitrogen balance was being 0.6 (95% CI 0.2 to 1.0; p=0.004) gN/m2 less negative in the intervention group. CONCLUSION: Early delivery of FESCE-based protocolised rehabilitation to ICU patients does not improve physical functioning at 6 months in survivors. TRIAL REGISTRATION NUMBER: NCT02864745.

• Klíčová slova
• complementary medicine, critical care,
• MeSH
• časové faktory MeSH
• elektrická stimulace MeSH
• ergometrie metody   MeSH
• jednotky intenzivní péče * MeSH
• kritický stav rehabilitace   MeSH
• kvalita života * MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• prospektivní studie MeSH
• svalová síla fyziologie   MeSH
• svalová slabost patofyziologie   rehabilitace   MeSH
• terapie cvičením metody   MeSH
• umělé dýchání metody   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH