Abstract
The relationship between the age-associated decline in mitochondrial function and its effect on skeletal muscle physiology and function remain unclear. In the current study, we examined to ...what extent physical activity contributes to the decline in mitochondrial function and muscle health during aging and compared mitochondrial function in young and older adults, with similar habitual physical activity levels. We also studied exercise-trained older adults and physically impaired older adults. Aging was associated with a decline in mitochondrial capacity, exercise capacity and efficiency, gait stability, muscle function, and insulin sensitivity, even when maintaining an adequate daily physical activity level. Our data also suggest that a further increase in physical activity level, achieved through regular exercise training, can largely negate the effects of aging. Finally, mitochondrial capacity correlated with exercise efficiency and insulin sensitivity. Together, our data support a link between mitochondrial function and age-associated deterioration of skeletal muscle.
Background:
Clinical measures in multiple sclerosis (MS) face limitations that may be overcome by utilising smartphone keyboard interactions acquired continuously and remotely during regular typing.
...Objective:
The aim of this study was to determine the reliability and validity of keystroke dynamics to assess clinical aspects of MS.
Methods:
In total, 102 MS patients and 24 controls were included in this observational study. Keyboard interactions were obtained with the Neurokeys keyboard app. Eight timing-related keystroke features were assessed for reliability with intraclass correlation coefficients (ICCs); construct validity by analysing group differences (in fatigue, gadolinium-enhancing lesions on magnetic resonance imaging (MRI), and patients vs controls); and concurrent validity by correlating with disability measures.
Results:
Reliability was moderate in two (ICC = 0.601 and 0.742) and good to excellent in the remaining six features (ICC = 0.760–0.965). Patients had significantly higher keystroke latencies than controls. Latency between key presses correlated the highest with Expanded Disability Status Scale (r = 0.407) and latency between key releases with Nine-Hole Peg Test and Symbol Digit Modalities Test (ρ = 0.503 and r = −0.553, respectively), ps < 0.001.
Conclusion:
Keystroke dynamics were reliable, distinguished patients and controls, and were associated with clinical disability measures. Consequently, keystroke dynamics are a promising valid surrogate marker for clinical disability in MS.
Fatigue during walking is a common complaint in cerebral palsy (CP). The primary purpose of this study is to investigate muscle fatigue from surface electromyography (sEMG) measurements after a ...treadmill-based fatigue protocol with increasing incline and speed in children with CP with drop foot. The secondary purpose is to investigate whether changes in sagittal kinematics of hip, knee and ankle occur after fatigue. Eighteen subjects with unilateral spastic CP performed the protocol while wearing their ankle-foot orthosis and scored their fatigue on the OMNI scale of perceived exertion. The median frequency (MF) and root mean square (RMS) were used as sEMG measures for fatigue and linear mixed effects model were applied. The MF was significantly decreased in fatigued condition, especially in the affected leg and in the tibialis anterior and peroneus longus muscle. The RMS did not change significantly in fatigued condition, while the OMNI fatigue score indicated patients felt really fatigued. No changes in sagittal kinematics of hip, knee and ankle were found using statistical non-parametric mapping. In conclusion, the current fatigue protocol seems promising in inducing fatigue in a population with CP with drop foot and it could be used to expand knowledge on muscle fatigue during walking in CP.
Highlights ► Gait characteristics are different for elderly with different Tinetti scores. ► Speed has best discriminative power to classify elderly according to Tinetti score. ► Fall risk related ...subtleties in gait are not captured by subjective assessment. ► Objective gait assessment is of added value in fall risk screening.
Essentials
We performed a meta‐analysis on thrombosis risk in thrombophilic oral contraceptive (COC)‐users.
The results support discouraging COC‐use in women with a natural anticoagulant deficiency.
...Contrary, additive risk of factor V Leiden (FVL) or prothrombin‐G20210A (PT) mutation is modest.
Women with a FVL/PT‐mutation as single risk factor can use COCs if alternatives are not tolerated.
Summary
Background
Combined oral contraceptives (COCs) are associated with an increased risk of venous thromboembolism (VTE), which is shown to be more pronounced in women with hereditary thrombophilia. Currently, WHO recommendations state that COC‐use in women with hereditary thrombophilias (antithrombin deficiency, protein C deficiency, protein S deficiency, factor V Leiden and prothrombin‐G20210A mutation) is associated with an unacceptable health risk.
Objective
To perform a meta‐analysis evaluating the additional risk of VTE in COC‐users with thrombophilia.
Methods
The MEDLINE and EMBASE databases were searched on 10 February 2015 for potential eligible studies. A distinction was made between ‘mild’ (factor V Leiden and prothrombin‐G20210A mutation) and ‘severe’ thrombophilia (antithrombin deficiency, protein C deficiency, protein S deficiency, double heterozygosity or homozygosity of factor V Leiden and prothrombin‐G20210A mutation).
Results
We identified 12 case–control and three cohort studies. In COC‐users, mild and severe thrombophilia increased the risk of VTE almost 6‐fold (rate ratio RR, 5.89; 95% confidence interval CI, 4.21–8.23) and 7‐fold (RR, 7.15; 95% CI, 2.93–17.45), respectively. The cohort studies showed that absolute VTE risk was far higher in COC‐users with severe thrombophilia than in those with mild thrombophilia (4.3 to 4.6 vs. 0.49 to 2.0 per 100 pill‐years, respectively), and these differences in absolute risks were also noted in non‐affected women (0.48 to 0.7 vs. 0.19 to 0.0), but with the caveat that absolute risks were estimated in relatives of thrombophilic patients with VTE (i.e. with a positive family history).
Conclusion
These results support discouraging COC‐use in women with severe hereditary thrombophilia. By contrast, additive VTE risk of mild thrombophilia is modest. When no other risk factors are present, (e.g. family history) COCs can be offered to these women when reliable alternative contraceptives are not tolerated.
Ankle fractures involving the posterior malleolus generally lead to worse outcome. However, no studies on gait in trimalleolar ankle fractures have evaluated the influence of size and comminution of ...the posterior malleolar fragment.
We expected patients with more severely comminuted posterior malleolus, more severe fracture type and larger posterior fragment to have reduced gait kinematics and poorer patient-reported outcomes. 26 trimalleolar ankle fracture patients were compared with 14 healthy controls and kinematically analyzed using the Oxford Foot Model. Functional outcome was based on 4 patient reported outcome questionnaires. Effects of posterior fragment size, comminution and Haraguchi fracture classification were determined on conventional and 3D CT-scans.
Trimalleolar patients had lower walking speed and reduced range of motion between the hindfoot and tibia in both loading and push-off phases in the sagittal and transverse planes. The range between the hindfoot and tibia in the sagittal plane in the push-off phase correlated significantly with patient reported outcomes. The absolute and relative surface area of the posterior fragment on conventional CT-scans and 3D CT-scans, correlated significantly with range of motion. Patients with a posterior malleolus size >10% of the posterior malleolus had lower flexion-extension between forefoot and hindfoot during loading phase than patients with a size ≤10%.
Trimalleolar fractures reduce walking speed and range of motion in the talocrural joint. Reduced range in the talocrural joint is associated with poorer outcomes. Posterior fragment size correlated significantly with range of motion in talocrural and midfoot joints and with patient reported outcomes.
Level of evidence: Level 3, retrospective study.
•Malleolus tertius fracture size has impact on the range of motion of the ankle.•Patients with trimalleolar fractures have a lower walking speed.•Trimalleolar ankle fractures have decreased range of motion talocrural.•Decreased range of motion talocrural is related to worse functional outcome.
Highlights • An Inertial Measurement Unit (IMU) is proposed for ambulatory assessment of pelvic kinematics. • IMU is validated against an optoelectronic motion capture system by anatomical pelvic ...landmarks. • A single IMU allows assessment of gait, sit-to-stand transfers and block step-up transfers. • IMU measurements of pelvic range of motion compare well to an optoelectronic motion capture system. • IMU seems a valid tool to assess human body kinematics for rehabilitation applications.
Essentials
It is unclear whether there are differences between von Willebrand factor (VWF) activity assays.
We compared the four most used VWF activity assays in 661 von Willebrand disease (VWD) ...patients.
All assays correlated excellently, but a discrepant classification was seen in 20% of patients.
Differences between VWF activity assays have a large impact on the classification of VWD.
Summary
Background
Measuring the ability of von Willebrand factor (VWF) to bind to platelets is crucial for the diagnosis and classification of von Willebrand disease (VWD). Several assays that measure this VWF activity using different principles are available, but the clinical relevance of different assay principles is unclear.
Objective
To compare the four most widely used VWF activity assays in a large VWD patient population.
Methods
We measured VWF:RCo (ristocetin to activate VWF + whole platelets), VWF:GPIbR (ristocetin + platelet glycoprotein Ib receptor GPIb fragments), VWF:GPIbM (gain‐of‐function GPIb fragments that bind VWF spontaneously without ristocetin) and VWF:Ab (monoclonal antibody directed against the GPIb binding epitope of VWF to mimic platelets) in 661 VWD patients from the nationwide ‘Willebrand in the Netherlands’ (WiN) Study.
Results
All assays correlated excellently (Pearson r > 0.9), but discrepant results led to a different classification for up to one‐fifth of VWD patients. VWF:RCo was not sensitive enough to classify 18% of patients and misclassified half of genotypic 2B VWD patients, especially those with p.Arg1306Trp. VWF:GPIbR was more sensitive, accurately classified the vast majority of patients, and was unaffected by the p.Asp1472His variant that causes artificially low VWF:RCo. VWF:GPIbM was the most precise assay but misclassified over a quarter of genotypic 2A, 2B and 3 patients. VWF:Ab, often not considered an actual VWF activity assay, performed at least equally to the other assays with regard to accurate VWD classification.
Conclusion
Although the different VWF activity assays are often considered similar, differences between assays have a large impact on the classification of VWD.
The reproducibility of the 6-min walking test (6MWT) needs to be more solidly studied. This study aimed to investigate the reproducibility of two 6MWTs performed on subsequent days in a large and ...representative sample of patients with chronic obstructive pulmonary disease (COPD), and to quantify the learning effect between the two tests, as well as its determinants. In a retrospective observational study, 1,514 patients with COPD performed two 6MWTs on subsequent days. Other measurements included body composition (dual X-ray absorptiometry), dyspnoea (Medical Research Council scale) and comorbidity (Charlson index). Although the 6MWT was reproducible (intraclass correlation coefficient = 0.93), patients walked farther in the second test (391 m, 95% CI 155-585 m versus 418 m, 95% CI 185-605 m; p<0.0001). On average, the second 6MWT increased by 27 m (or 7%), and 82% of patients improved in the second test. Determinants of improvement ≥ 42 m in the second test (upper limit of the clinically important change) were as follows: first 6MWT <350 m, Charlson index <2 and body mass index <30 kg · m(-2) (OR 2.49, 0.76 and 0.60, respectively). The 6MWT was statistically reproducible in a representative sample of patients with COPD. However, the vast majority of patients improved significantly in the second test by an average learning effect of 27 m.
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