Comorbidity in multiple sclerosis: Emphasis on patient-reported outcomes.

BACKGROUND: Aim of our study was to estimate the prevalence of comorbid conditions and adverse health behaviors in relapsing-remitting multiple sclerosis (RRMS) patients and evaluate association between comorbidity and MS outcomes (relapse rate, fatigue and quality of life) in Lithuanian setting. METHODS: A prospective cohort study was carried out in the MS center of Lithuanian University of Health Sciences Hospital Kaunas clinics from November 2016 to March 2021. People with MS filled a self-report comorbidity and adverse health behavior questionnaire, visual analogue fatigue scale (VAFS), a Short Form 36 (SF-36) v2 health related quality of life questionnaire (QoL). Information about disability and relapses was acquired from medical documentation and Lithuanian MS registry at baseline and after 24-month observational period. Chi square, t-test, ANOVA, Mann-Whitney U were used for basic statistical evaluation. Multivariable logistic regression models were used to prognose MS outcomes in association to comorbidity and adverse health behaviors, adjusting for age and baseline disability. RESULTS: Of 230 RRMS patients, 167 (72.6%) were women, average age was 42 years. 207 persons were followed through the observational period and included into relapse analysis. 112 (48.7%) of participants reported having at least one comorbidity, the most prevalent were arterial hypertension (19.1%) depression (16.5%) and anxiety (14.8%). People with comorbidities had higher fatigue (6.6 vs. 5.3, p < 0.001) and lower quality of life (overall SF-36 46.3 vs 59.1, p < 0.001). People consuming alcohol had fewer relapses per 24 months (0.56 vs. 0.82, p = 0.01), lower fatigue (5.7 vs. 6.4, p = 0.03), better quality of life (overall SF-36: 56.8 vs. 45.6, p < 0.001), compared to abstinents. In regression models, comorbidities were associated with severe (>7 VAFS) fatigue (Exp(B)=1.98, 95% CI [1.02, 3.86], p = 0.043), diminished (<50 SF-36) QoL (Exp(B)=3.50, 95% CI [1.72, 7.09], p = 0.001). Depression was independently associated with lower QoL (Exp(B)= 2.86, 95% CI [1.04, 7.88], p = 0.042) and severe fatigue (Exp(B)=4.65, 95% CI [2.39, 9.01], p < 0.001); anxiety with diminished QoL (Exp(B)= 4.99, 95%CI [1.67, 14.92], p = 0.002). Light alcohol consumption (compared to abstinents) was associated with decreased risk for: relapse during 24 months (Exp(B)=0.44, 95% CI[0.24, 0.77], p = 0.005), severe fatigue (Exp(B)=0.48, 95% CI [0.24, 0.98], p = 0.042) and lower QoL (Exp(B)= 0.32, 95% CI [0.16, 0.65], p = 0.002). CONCLUSION: Comorbidity is a relevant issue in multiple sclerosis as half of people with MS report concomitant conditions. Hypertension, depression, and anxiety are especially prevalent in MS. In our study, comorbidity is associated with quality of life and fatigue, but not relapse rate. Depression and anxiety are independently associated with lower quality of life and higher fatigue. Light alcohol consumption is associated with reduced relapse risk, less fatigue and better quality of life. Overweight and tobacco smoking do not seem to have negative impact on MS outcomes in our sample.

Rapid and sustained B-cell depletion with subcutaneous ofatumumab in relapsing multiple sclerosis: APLIOS, a randomized phase-2 study.

BACKGROUND: Ofatumumab, the first fully human anti-CD20 monoclonal antibody, is approved in several countries for relapsing multiple sclerosis (RMS). OBJECTIVE: To demonstrate the bioequivalence of ofatumumab administered by an autoinjector versus a pre-filled syringe (PFS) and to explore the effect of ofatumumab on B-cell depletion. METHODS: APLIOS (NCT03560739) is a 12-week, open-label, parallel-group, phase-2 study in patients with RMS receiving subcutaneous ofatumumab 20 mg every 4 weeks (q4w) (from Week 4, after initial doses on Days 1, 7, and 14). Patients were randomized 10:10:1:1 to autoinjector or PFS in the abdomen, or autoinjector or PFS in the thigh, respectively. Bioequivalence was determined by area under the curve (AUCτ) and maximum plasma concentration (Cmax) for Weeks 8-12. B-cell depletion and safety/tolerability were assessed. RESULTS: A total of 256 patients contributed to the bioequivalence analyses (autoinjector-abdomen, n = 128; PFS-abdomen, n = 128). Abdominal ofatumumab pharmacokinetic exposure was bioequivalent for autoinjector and PFS (geometric mean AUCτ, 487.7 vs 474.1 h × µg/mL (ratio 1.03); Cmax, 1.409 vs 1.409 µg/mL (ratio 1.00)). B-cell counts (median cells/µL) depleted rapidly in all groups from 214.0 (baseline) to 2.0 (Day 14). Ofatumumab was well tolerated. CONCLUSION: Ofatumumab 20 mg q4w self-administered subcutaneously via autoinjector is bioequivalent to PFS administration and provides rapid B-cell depletion.

Adding High-Intensity Interval Training to Classical Resistance Training Does Not Impede the Recovery from Inactivity-Induced Leg Muscle Weakness.

Inactivity is known to induce muscle weakness, and chronically increased levels of reactive oxygen species (ROS) are proposed to have a central causative role in this process. Intriguingly, high-intensity interval training (HIIT), which involves bursts of high ROS production, can have positive effects in pathological conditions with chronically increased ROS. Here, young male volunteers were exposed to 3 weeks of unloading of the dominant leg followed by 3 weeks of resistance training without (Ctrl group) or with the addition of all-out cycling HIIT. Changes in muscle thickness were assessed by ultrasonography, and contractile function was studied by measuring the torque during maximal voluntary contractions (MVC). The results show an ~6% decrease in vastus lateralis thickness after the unloading period, which was fully restored after the subsequent training period in both the Ctrl and HIIT groups. MVC torque was decreased by ~11% after the unloading period and recovered fully during the subsequent training period in both groups. All-out cycling performance was improved by the 3 weeks of HIIT. In conclusion, the decline in muscle size and function after 3 weeks of unloading was restored by 3 weeks of resistance training regardless of whether it was combined with HIIT.

Tai chi improves psychoemotional state, cognition, and motor learning in older adults during the COVID-19 pandemic.

The aim of this study was to determine the effect of a 10-week tai chi intervention on psychoemotional state, cognition, and motor learning in older adults during the COVID-19 pandemic. Participants aged 60-78 years were randomized to either a control group (n = 15) or a tai chi group (n = 15) for a 10-week period. The tai chi group received two, 8-form tai chi classes of 60 min duration per week. Changes in psychoemotional state, cognition, and the learning of fast and accurate reaching movements were assessed. In addition, the potential roles of the autonomic nervous system and brain-derived neurotrophic factor (BDNF) were investigated. Tai chi practice decreased (P < 0.05) perceived stress, whereas no change in autonomic nervous system activity was observed. Improvements in mental switching correlated with decreased depressive symptoms and increased BDNF levels (P < 0.05), whereas improvements in inhibitory control tended to correlate with BDNF levels (P = 0.08). Improvements in visuospatial processing tended to correlate with decreased depressive symptoms (P = 0.07) while improved visuospatial processing correlated with improved motor planning during learning tasks (P < 0.05). This study suggests that tai chi is an effective intervention that can be delivered under pandemic conditions to improve mental and physical function in older adults.

Effects of two nights of sleep deprivation on executive function and central and peripheral fatigue during maximal voluntary contraction lasting 60s.

PURPOSEː: The current study aimed at assessing the effect of a trial of two nights of sleep deprivation (SDT) on mood, sleepiness, motivation and cognitive and motor performance. METHODSː: Thirty-six healthy young and physically active adult men (17 in the control group and 19 in the SDT group) completed a 48-h control or 48-h SDT. For the SDT, participants did not sleep for 48 h. Executive function (attention and inhibitory control) in the Go/No-Go and Stroop tests, mood, sleepiness, motivation, heart rate variability (HRV), motor performance in a hand grip strength test, and 60-s maximal isometric contraction (MVC-60 s) of knee extension were evaluated at 9-11 am on consecutive days 1, 2, and 3. RESULTS: One night of sleep deprivation increased sleepiness, decreased mood, motivation and motor endurance but did not affect executive function (as measured in the Stroop and Go/No-Go tests), the MVC for hand and leg knee extensor muscles, and peripheral motor fatigue in the leg MVC-60 s task. However, the central activation ratio (CAR) decreased significantly during the MVC-60 s. The SDT significantly contributed to the decrease in these functions. That is, the SDT reduced executive function (increased reaction time during Go/No-Go test), MVC of knee extension, and the CAR before and after the MVC-60 s. By contrast, the SDT did not increase CAR immediately after the MVC-60 s and did not decrease the rate of torque development (RTD). CONCLUSIONSː: The SDT significantly impaired mood, motivation and increased sleepiness and HRV, reduced MVC of knee extensor muscles (but not RTD) and motor performance during the MVC-60 s and worsened executive function (attention and inhibitory control) only during the Go/No-Go task. However, the SDT did not reduce hand grip strength and CAR immediately after the MVC-60 s of knee extensor muscles.

A 10-week yoga practice has no effect on cognition, but improves balance and motor learning by attenuating brain-derived neurotrophic factor levels in older adults.

Despite studies investigating the effect of yoga on cognitive and motor functioning in older adults, the effect on dual-task performance and motor learning and the specific mechanisms underlying the positive effect of yoga remain unclear. Thus, the aim of this study was to investigate the effects of yoga on cognition, balance under single- and dual-task conditions, and motor learning. The potential role of brain-derived neurotrophic factor (BDNF) in induced improvement was also explored. Participants aged 60-79 years were randomized to either a control group (n = 15) or a yoga group (n = 18) for a 10-week period. The yoga group received 90-min duration yoga classes two times per week. Changes in cognition, balance under single- and dual-task conditions, and learning fast and accurate reaching movements were assessed. Yoga practice decreased (P < 0.05) the velocity vector of the center of pressure under single- and dual-task conditions, whereas no changes in cognitive performance were observed. Although reaction and movement times during learning were decreased in both groups (P < 0.05), a faster reaction time (P < 0.05) and shorter movement time (P < 0.05) were observed in the yoga group than in the control group. Significant moderate relationships (P < 0.05) between changes in BDNF levels and functional improvements were observed. Thus, 10 weeks of yoga practice resulted in improved balance and learning in the speed-accuracy motor task that were mediated by increased BDNF levels, but had no impact on cognition in older adults.

One night of sleep deprivation impairs executive function but does not affect psychomotor or motor performance.

The current study assessed the impact of one night of sleep deprivation on cognitive, motor and psychomotor performance. Thirty healthy young adult male subjects completed a 24 h control or 24 h sleep deprived trial. For the control trial, participants (N = 15) were allowed normal night sleep (~8 h). For the sleep deprived trial, participants (N = 15) did not sleep for 24 h. Cognitive performance during go/no-go, Stroop and simple reaction tasks, psychomotor performance during speed-accuracy tasks with fixed and unfixed targets, and motor performance during countermovement jump, hand grip strength, and 30-s maximal voluntary contraction tasks were evaluated on day 1 at 8 am and 7 pm and on day 2 at 8 am. One night of sleep deprivation impaired psychological well-being and executive function but did not affect simple reaction time, the capacity for arm and leg muscle contraction, motor control performance during a speed-accuracy task with both fixed and unfixed targets, and central and peripheral motor fatigue in the 30 s maximal voluntary contraction task. The present study showed that one night of sleep deprivation resulted in executive function deterioration but did not modify motor control or maximal effort requiring performance of motor tasks.

"Two sides of the same coin": constant motor learning speeds up, whereas variable motor learning stabilizes, speed-accuracy movements.

PURPOSE: The aim of this study was to determine the time course of the trade-off between speed and accuracy, intraindividual variability, and movement transfer and retention (4 weeks after learning) of speed-accuracy tasks. METHODS: The participants in this study were healthy adults randomly divided into three groups (control versus constant versus variable). They were aged 19-24 years, and 30 (15 men and 15 women) were in each group. Participants had to perform various tasks with the right dominant hand: (a) simple reaction test; (b) maximal velocity measurement; and (c) a speed-accuracy task. RESULTS: During constant and variable learning, the trade-off in a speed-accuracy task in specific situations shifted toward improved motor planning and motor execution speed, and to reduced intraindividual variability. However, during variable learning, the maximal velocity and variability of motor planning time did not change. Constant learning effectively transferred into variable tasks in terms of reaction time, average velocity and maximal velocity, and these effects were greater than those associated with variable learning. However, the effects of constant learning did not transfer fully into the performance variability of variable movements. Variable learning effectively transferred into constant tasks for the coefficient of variation of the path of movement, average velocity, maximal velocity and reaction time. The retention effect depended neither on learning nor task specificity (constant versus variable tasks). CONCLUSION: Constant learning speeds up but does not stabilize speed-accuracy movements in variable tasks; whereas, variable learning stabilizes but does not speed up speed-accuracy movements in constant tasks.

The Effect of Combined Aerobic Exercise and Calorie Restriction on Mood, Cognition, and Motor Behavior in Overweight and Obese Women.

BACKGROUND: The benefits of weight loss programs on mood, cognitive, and motor behavior are largely limited to those of calorie restriction or exercise alone. Our aim was to investigate the effect of combined calorie restriction and aerobic exercise intervention on mood, brain activity, and cognitive and motor behavior in overweight and obese women. METHODS: Participants aged 36-56 years were randomized to either a control or an experimental group (aerobic exercise + 12.5% energy intake reduction) for a 6-month period. Changes in brain-derived neurotrophic factor levels, mood, prefrontal cortex activity, cognitive and motor performance were assessed. RESULTS: Confusion and depression increased in the control group (P < .05), whereas tension decreased in the experimental group (P < .05). Brain-derived neurotrophic factor level and learning of a speed-accuracy task remained unchanged. Although prefrontal cortex activity and executive functions were not affected, the reaction time of visual scanning and associative learning were improved in the experimental group (P < .05). An improvement in reaction time during the speed-accuracy task was observed (P < .05). CONCLUSION: Combined calorie restriction and aerobic exercise intervention improved the psychosocial state, had little impact on cognition, and no effect on brain activity and learning of the speed-accuracy task.

The contribution of low-frequency fatigue to the loss of quadriceps contractile function following repeated drop jumps.

NEW FINDINGS: What is the central question of this study? Why do some subjects recover slowly following a bout of eccentric exercise and why is recovery faster following a repeated bout? What is the main finding and its importance? The results are consistent with two major causes of the reduction of quadriceps torque, the onset of low-frequency fatigue which recovered relatively fast and a second, delayed form of damage. Differences in the delayed damage process largely accounted for the differences in the rate of torque recovery between subjects after a first bout and it was suppression of the delayed damage which accounted for the faster recovery following a repeated bout of eccentric exercise. ABSTRACT: The purpose of this study was to determine the extent to which low-frequency fatigue (LFF) accounts for the loss of quadriceps strength and time course of recovery following a series of drop jumps (DJs). Seventeen female subjects (20.8 ± 1.4 years) undertook 100 DJs, which were repeated 4 weeks later. Maximum isometric torque (MIT) and the ratio of torque generated by 20 and 100 Hz electrical stimulation (20/100), as a measure of LFF, were measured over 7 days following each series of DJs. After the first series the 20/100 ratio fell to a greater extent than MIT (to 35 ± 8.7% and 69 ± 11%, respectively) but recovered over 2-3 days, while MIT showed little recovery over this time. Changes of the 20/100 ratio were similar between subjects with fast or slow MIT recovery. Following the second series of DJs, changes in the 20/100 ratio were similar to those of the first bout and there were no differences between fast and slow recovering subjects. MIT, however, recovered more rapidly than after the first bout; the faster recovery was confined to the subjects who recovered slowly following the first bout. The results are consistent with two major causes of the reduction of quadriceps torque, the onset of low-frequency fatigue which recovered relatively fast and a second, delayed, form of damage. The latter largely accounted for the differences in MIT recovery between subjects after the first bout, while suppression of the delayed damage accounted for the faster recovery following the repeated bout.

Absence of differences in the learning rate of a speed-accuracy movement task between women patients with mild and major depression and healthy adult women.

This study tested the hypothesis that women patients with depression should perform movements more slowly and with greater variability, and their learning rate should be lower compared with age-matched healthy adult women. Three groups of adult women subjects (aged 33-37 years, women patients with mild and major depression and healthy adult women, n = 20 in each group) performed five series (20 repetitions in each series) of a speed-accuracy hand-movement task (SAT). The mean movement speed (Va) of the SAT was lower and more stable (the coefficient of variation of Va was lower) in women patients with major depression compared with those with minor depression and healthy adult women during the first series of the SAT. Only the Va and movement accuracy (path of movement, S) of the SAT varied significantly in the five learning series regardless of the subject group (healthy women subjects and women patients with minor and major depression). The intraindividual variability of reaction time, Va, maximal movement velocity to the target (tVmax), time to tVmax, and S did not change significantly in any of the groups. Our research data showed that although women patients with depression performed speed-accuracy movements more slowly, the stability of the performance of their movements and their learning rate did not differ from those of age-matched healthy adult women.

What are the best isometric exercises of muscle potentiation?

PURPOSE: The aim of this study was to follow post-activation potentiation (PAP), low-frequency fatigue (LFF), metabolic-induced fatigue and post-contractile depression (PCD) in response to different isometric muscle contraction modalities. METHODS: Young healthy men (N = 120) were randomly assigned to one of ten exercise modality groups which differed in contraction duration (5-60 s), activation pattern (intermittent or continuous contractions), activation mode (voluntary or stimulated), and intensity [maximal or submaximal (50%)]. Isometric maximal voluntary contraction (MVC), and electrically induced knee extension torque were measured at baseline and at regular intervals for 60 min after exercise. RESULTS: Muscle contraction modalities involving 5 s MVC were the most effective for PAP, whereas the lowest PAP effectiveness was found after the 12 × 5-MVC modality. After all of the 5-15 s MVC and 6 × 5-MVC protocols, the potentiation of the twitch rate was significantly higher than that recorded after continuous 30-60 s protocols (P < 0.001). Tetanic maximal torque (100 Hz) potentiation occurred 5 min after 15-30 s repetitive MVC modalities and after modality involving 15 electrical stimuli (P < 0.05). CONCLUSIONS: The findings demonstrate that post-activation potentiation was most effective after brief duration continuous and repetitive MVC protocols. To understand the resultant warm-up of motor performance, it is necessary to recognize the coexistence of muscle PAP, tetanic maximal force potentiation, rapid recovery of metabolic muscle, and central muscle activation processes, as well as prolonged LFF and prolonged PCD.

Children, Young Adults, and Older Adults Choose Different Fast Learning Strategies.

The aim of the study was to establish whether there were differences in speed-accuracy movement learning strategies between children, young adults, and older adults. A total of 30 boys, 30 young adult men, and 30 older men were seated in a special chair at a table with a Dynamic Parameter Analyzer 1. Participants had to perform a speed-accuracy task with the right-dominant hand. It may be assumed that the motor variables of children are more prone to change during the fast learning process than those of young adults and older adults and that the development of internal models is more changeable in children than in young adults and the older adults during the fast adaptation-based learning process.

Detection of aquaporin-4 antibodies for patients with CNS inflammatory demyelinating diseases other than typical MS in Lithuania.

OBJECTIVES: Neuromyelitis optica (NMO) is frequently associated with aquaporin-4 autoantibodies (AQP4-Ab); however, studies of NMO in Lithuania are lacking. Therefore, the main objective of our study is to assess positivity for AQP4-Ab in patients presenting with inflammatory demyelinating central nervous system (CNS) diseases other than typical multiple sclerosis (MS) in Lithuania. MATERIALS AND METHODS: Data were collected from the two largest University hospitals in Lithuania. During the study period, there were 121 newly diagnosed typical MS cases, which were included in the MS registry database. After excluding these typical MS cases, we analyzed the remaining 29 cases of other CNS inflammatory demyelinating diseases, including atypical MS (n = 14), acute transverse myelitis, TM (n = 8), acute disseminated encephalomyelitis, ADEM (n = 3), clinically isolated syndrome, CIS (n = 2), atypical optic neuritis, ON (n = 1), and NMO (n = 1). We assessed positivity for AQP4-Ab for the 29 patients and evaluated clinical, laboratory, and instrumental differences between AQP4-Ab seropositive and AQP4-Ab seronegative patient groups. RESULTS: AQP4-Ab test was positive for three (10.3%) patients in our study, with initial diagnoses of atypical MS (n = 2) and ADEM (n = 1). One study patient was AQP4-Ab negative despite being previously clinically diagnosed with NMO. There were no significant clinical, laboratory, or instrumental differences between the groups of AQP4-Ab positive (3 [10.3%]) and negative (26 [89.7%]) patients. CONCLUSIONS: AQP4-Ab test was positive for one-tenth of patients with CNS inflammatory demyelinating diseases other than typical MS in our study. AQP4-Ab testing is highly recommended for patients presenting with not only TM and ON but also an atypical course of MS and ADEM.

Prefrontal Cortex Activity Predicts Mental Fatigue in Young and Elderly Men During a 2 h "Go/NoGo" Task.

Background: Although the effects of mental fatigue on cognitive-motor function and psychological state in young adults are well-documented, its effects in the elderly are not completely understood. The aim of this study was to estimate the effect of prolonged cognitive load on the indicators of psychological, cognitive, and motor functions. Methods: Fifteen young and 15 elderly men were asked to perform a 2 h "Go/NoGo" task. Psychological state (mood and motivation), cognitive (prefrontal cortex activity and cognitive performance), and motor (motor cortex excitability and grip strength) functions were measured before and after the task. During the 2 h task, both groups had a significantly similar increase in the number of "Incorrect NoGo" errors. Only in young men reaction time (RT) of "Incorrect NoGo" and intraindividual variability of RT of "Incorrect NoGo" significantly increased during task. After the task, handgrip strength decreased for the young men, whereas latency of motor evoked potentials prolonged both groups. Nevertheless, both groups indicated that they felt fatigue after the 2 h task; we observed that mental demand increased, whereas intrinsic motivation and mood decreased only in young men. Prolonged task decreased the switching/rest ratio of oxygenated hemoglobin for the young and the elderly men; however, greater for elderly than young men. Interestingly, the more the prefrontal cortex was activated before the 2 h task during the switching task, the fewer of "Incorrect NoGo" errors made by the young men and the greater the number of errors made by the elderly men. Conclusion: Because of the greater mental load and (possibly) greater activation of prefrontal cortex during the 2 h "Go/NoGo" task, there was greater mental and neuromuscular performance fatigue in young men than in elderly men.

Task-relevant cognitive and motor functions are prioritized during prolonged speed-accuracy motor task performance.

This study aimed to explore the effect of prolonged speed-accuracy motor task on the indicators of psychological, cognitive, psychomotor and motor function. Ten young men aged 21.1 ± 1.0 years performed a fast- and accurate-reaching movement task and a control task. Both tasks were performed for 2 h. Despite decreased motivation, and increased perception of effort as well as subjective feeling of fatigue, speed-accuracy motor task performance improved during the whole period of task execution. After the motor task, the increased working memory function and prefrontal cortex oxygenation at rest and during conflict detection, and the decreased efficiency of incorrect response inhibition and visuomotor tracking were observed. The speed-accuracy motor task increased the amplitude of motor-evoked potentials, while grip strength was not affected. These findings demonstrate that to sustain the performance of 2-h speed-accuracy task under conditions of self-reported fatigue, task-relevant functions are maintained or even improved, whereas less critical functions are impaired.

Prolonged force depression after mechanically demanding contractions is largely independent of Ca2+ and reactive oxygen species.

Increased production of reactive oxygen/nitrogen species (ROS) and impaired cellular Ca2+ handling are implicated in the prolonged low-frequency force depression (PLFFD) observed in skeletal muscle after both metabolically and mechanically demanding exercise. Metabolically demanding high-intensity exercise can induce PLFFD accompanied by ROS-dependent fragmentation of the sarcoplasmic reticulum Ca2+ release channels, the ryanodine receptor 1s (RyR1s). We tested whether similar changes occur after mechanically demanding eccentric contractions. Human subjects performed 100 repeated drop jumps, which require eccentric knee extensor contractions upon landing. This exercise caused a major PLFFD, such that maximum voluntary and electrically evoked forces did not recover within 24 h. Drop jumps induced only minor signs of increased ROS, and RyR1 fragmentation was observed in only 3 of 7 elderly subjects. Also, isolated mouse muscle preparations exposed to drop-jump-mimicking eccentric contractions showed neither signs of increased ROS nor RyR1 fragmentation. Still, the free cytosolic [Ca2+] during tetanic contractions was decreased by ∼15% 1 h after contractions, which can explain the exaggerated force decrease at low-stimulation frequencies but not the major frequency-independent force depression. In conclusion, PLFFD caused by mechanically demanding eccentric contractions does not involve any major increase in ROS or RyR1 fragmentation.-Kamandulis, S., de Souza Leite, F., Hernandez, A., Katz, A., Brazaitis, M., Bruton, J. D., Venckunas, T., Masiulis, N., Mickeviciene, D., Eimantas, N., Subocius, A., Rassier, D. E., Skurvydas, A., Ivarsson, N., Westerblad, H. Prolonged force depression after mechanically demanding contractions is largely independent of Ca2+ and reactive oxygen species.

The effects of 4 weeks stretching training to the point of pain on flexibility and muscle tendon unit properties.

PURPOSE: The purpose of this study was to compare the benefits and possible problems of 4 weeks stretching when taken to the point of pain (POP) and to the point of discomfort (POD). METHODS: Twenty-six physically active women (20 ± 1.1 years) took part in group-based stretching classes of the hamstring muscles, 4 times per week for 4 weeks, one group one stretching to POD, the other to POP. Passive stiffness, joint range of motion (ROM), maximal isometric torque and concentric knee flexion torque, were measured before training and 2 days after the last training session. RESULTS: Hip flexion ROM increased by 14.1° (10.1°-18.1°) and 19.8° (15.1°-24.5°) and sit-and-reach by 7.6 (5.2-10.0) cm and 7.5 (5.0-10.0) cm for POD and POP, respectively (Mean and 95% CI; p < 0.001 within group; NS between groups), with no evidence of damage in either group. Despite the large increases in flexibility there were no changes in either compliance or viscoelastic properties of the muscle tendon unit (MTU). CONCLUSION: Hamstrings stretching to POP increased flexibility and had no detrimental effects on muscle function but the benefits were no better than when stretching to POD so there is no justification for recommending painful stretching. The improvements in flexibility over 4 weeks of stretching training appear to be largely due to changes in the perception of pain rather than physical properties of the MTU although less flexible individuals benefited more from the training and increased hamstring muscle length.

Prevalence and burden of headache disorders in Lithuania and their public-health and policy implications: a population-based study within the Eurolight Project.

BACKGROUND: The Eurolight project assessed the impact of headache disorders in ten EU countries, using the same structured questionnaire but varying sampling methods. In Lithuania, sample selection employed methods in line with consensus recommendations for population-based burden-of-headache studies. METHODS: The survey was cross-sectional. We identified, from the Residents' Register Service, a sample of inhabitants of Kaunas city and surrounding Kaunas region reflecting age (in the range 18-65 years), gender and rural/urban distributions of Lithuania. Medical students called unannounced at their homes and conducted face-to-face interviews employing a structured questionnaire. RESULTS: Of 1137 people in the pre-identified sample, 573 (male 237 [41.4%], female 336 [58.6%]; mean age 40.9 ± 13.8 years) completed interviews (participation proportion: 50.4%). Gender-adjusted 1-year prevalences were: any headache 74.7%; migraine 18.8%; tension-type headache (TTH) 42.2%; all headache on ≥15 days/month 8.6%; probable medication-overuse headache (pMOH) 3.2%. Migraine (OR: 3.6) and pMOH (OR: 2.9) were associated with female gender. All headache types except TTH were associated with significantly diminished quality of life. Migraine caused a mean 4.5% loss in paid worktime per affected male and 3.5% per affected female. Lost per-person times due to TTH were much less, but to pMOH and other headache on ≥15 days/month much higher. Among the entire workforce, lost productivity to migraine was estimated at 0.7%, to TTH 0.3% and to pMOH or other headache on ≥15 days/month 0.5%. The total of 1.5% may translate directly into lost GDP. Alternative calculations based on headache yesterday (with little recall error) produced, for all headache, a corroborating 1.7%. Similar losses from household work would also drain the nation's economy. Our findings were comparable to those from earlier studies using similar methods in Russia and Georgia. CONCLUSIONS: The multiple burdens from headache in Lithuania indicate substantial ill-health and unmet need for health care. The heavy burdens on individuals are matched by heavy economic burden. Of particular concern is the high prevalence of headache on ≥15 days/month, seen also in Russia and Georgia. Health policy in Lithuania must heed WHO's advice that effective treatment of headache, clearly desirable for its health benefits, is also expected to be cost-saving.

Factors associated with adherence to disease modifying therapy in multiple sclerosis: An observational survey from a referral center in Lithuania.

AIM OF THE STUDY: To investigate adherence to disease modifying therapy (DMT) in Lithuanian population of multiple sclerosis patients and factors associated to it. METHODS: Patients receiving one of the following DMT's: Interferon ß 1a (Rebif) 44 micrograms three times a week subdermally (s/c) or Interferon ß 1a (Avonex) 30 micrograms weekly intramuscularly (i/m), or Interferon ß 1b (Betaferon, Extavia) 250 micrograms once in two days s/c, or Glatiramer acetate (Copaxone) 20mg daily s/c, were presented with a questionnaire inquiring their demographic and clinical characteristics and adherence to treatment profile, as well as HAD scale and SF-36 questionnaire. Those who missed at least one dose of DMT during last three months were considered non-adherent. RESULTS: In total, 207 patients were enrolled, 73 (35.3%) of them were non adherent during last three months. More patients with university education (p=0.004, χ2 =8.466 high school/vocational vs. university) as well as consuming >4 units/year of alcohol were non-adherent during last three months (p=0.005). Average score for anxiety (6.69±4.03 vs. 6.92±4.24) and depression (4.74±3.9 vs. 4.7±3.83) in HAD scale did not differ significantly between adherent and non-adherent groups. We did not find any significant difference in quality of life scores (SF-36 v.2) between the groups. No significant difference of adherence was found then comparing patients often suffering from drug side effects with those who experience rare or no side effects. In logistic regression model, patients consuming more than 4 alcohol units per year and patients with university education were more likely to miss at least one dose during last three months: 2.121 (95% CI: 1.143-3.937, p=0.017) and 2.409 (95% CI: 1.260-4.642, p=0.008) times accordingly. Patients with better quality of life scores were slightly less likely to be non adherent (OR 0.997 (95% CI: 0.994-0.999), p=0.0017). CONCLUSIONS: One third of patients were non-adherent during last three months. Worse adherence rates were associated with higher education and higher alcohol consumption. Education, alcohol consumption and quality of life scores were found to be significant factors for predicting non-adherence. We found no associations between adherence and anxiety, depression, or drugs side effects.