Biomechanics of the lower limb in patients with mild knee osteoarthritis during the sit-to-stand task.

BACKGROUND: Knee osteoarthritis (KOA) is a prevalent and debilitating condition that markedly affects the sit-to-stand (STS) activity of patients, a prerequisite for daily activities. Biomechanical recognition of movements in patients with mild KOA is currently attracting attention. However, limited studies have been conducted solely on the observed differences in sagittal plane movement and muscle activation. AIM: This study aimed to identify three-dimensional biomechanical and muscle activation characteristics of the STS activity in patients with mild KOA. METHODS: A cross-sectional study was conducted to observe the differences between patients with mild KOA and a control group (CG). It was conducted to observe the differences in muscle activation, including root mean square (RMS%) and integrated electromyography (items), kinematic parameters like range of motion (ROM) and maximum angular velocity, as well as dynamic parameters such as joint moment and vertical ground reaction force (vGRF). RESULTS: Patients with mild KOA had a higher body mass index and longer task duration. In the sagittal plane, patients with KOA showed an increased ROM of the pelvic region, reduced ROM of the hip-knee-ankle joint, and diminished maximum angular velocity of the knee-ankle joint. Furthermore, patients with KOA displayed increased knee-ankle joint ROM in the coronal plane and decreased ankle joint ROM in the horizontal plane. Integrated vGRF was higher in both lower limbs, whereas the vGRF of the affected side was lower. Furthermore, patients showed a decreased peak adduction moment (PADM) and increased peak external rotation moment in the knee joint and smaller PADM and peak internal rotation moment in the ankle joint. The affected side exhibited decreased RMS% and iEMG values of the gluteus medius, vastus medialis, and vastus lateralis muscles, as well as a decreased RMS% of the rectus femoris muscle. Conversely, RMS% and iEMG values of the biceps femoris, lateral gastrocnemius, and medial gastrocnemius muscles were higher. CONCLUSION: The unbalanced activation characteristics of the anterior and posterior muscle groups, combined with changes in joint moment in the three-dimensional plane of the affected joint, may pose a potential risk of injury to the irritated articular cartilage.

Effects of Exercise Training on the Phosphoproteomics of the Medial Prefrontal Cortex in Rats With Autism Spectrum Disorder Induced by Valproic Acid.

BACKGROUND: The key neural pathological characteristics of autism spectrum disorder (ASD) include abnormal synaptic plasticity of the medial prefrontal cortex (mPFC). Exercise therapy is widely used to rehabilitate children with ASD, but its neurobiological mechanism is unclear. METHODS: To clarify whether the structural and molecular plasticity of synapses in the mPFC are related to improvement in ASD behavioral deficits after continuous exercise rehabilitation training, we applied phosphoproteomic, behavioral, morphological, and molecular biological methods to investigate the impact of exercise on the phosphoprotein expression profile and synaptic structure of the mPFC in valproic acid (VPA)-induced ASD rats. RESULTS: Exercise training differentially regulated the density, morphology, and ultrastructure of synapses in mPFC subregions in the VPA-induced ASD rats. In total, 1031 phosphopeptides were upregulated and 782 phosphopeptides were downregulated in the mPFC in the ASD group. After exercise training, 323 phosphopeptides were upregulated, and 1098 phosphopeptides were downregulated in the ASDE group. Interestingly, 101 upregulated and 33 downregulated phosphoproteins in the ASD group were reversed after exercise training, and these phosphoproteins were mostly involved in synapses. Consistent with the phosphoproteomics data, the total and phosphorylated levels of the proteins MARK1 and MYH10 were upregulated in the ASD group and reversed after exercise training. CONCLUSIONS: The differential structural plasticity of synapses in mPFC subregions may be the basic neural architecture of ASD behavioral abnormalities. The phosphoproteins involved in mPFC synapses, such as MARK1 and MYH10, may play important roles in the exercise rehabilitation effect on ASD-induced behavioral deficits and synaptic structural plasticity, which requires further investigation.

Ratiometric NAD+ Sensors Reveal Subcellular NAD+ Modulators.

Mapping NAD+ dynamics in live cells and human is essential for translating NAD+ interventions into effective therapies. Yet, genetically encoded NAD+ sensors with better specificity and pH resistance are still needed for the cost-effective monitoring of NAD+ in both subcellular compartments and clinical samples. Here, we introduce multicolor, resonance energy transfer-based NAD+ sensors covering nano- to millimolar concentration ranges for clinical NAD+ measurement and subcellular NAD+ visualization. The sensors captured the blood NAD+ increase induced by NMN supplementation and revealed the distinct subcellular effects of NAD+ precursors and modulators. The sensors then enabled high-throughput screenings for mitochondrial and nuclear NAD+ modulators and identified α-GPC, a cognition-related metabolite that induces NAD+ redistribution from mitochondria to the nucleus relative to the total adenine nucleotides, which was further confirmed by NAD+ FRET microscopy.

Biomechanical analysis of lower limbs during stand-to-sit tasks in patients with early-stage knee osteoarthritis.

Background: Knee osteoarthritis (KOA) is a common degenerative disease among the older people that severely affects their daily life. Previous studies have confirmed that movement biomechanics are altered in patients with KOA during task performance. However, changes that occur in lower limb joints and muscles in the three planes during stand-to-sit (STS) tasks in patients with early-stage KOA are unclear. Method: Of the 36 participants recruited in this study, 24 (8 males and 16 females) and 12 (4 males and 8 females) were added to the KOA and control groups, respectively. The Nexus Vicon motion capture system along with Delsys wireless surface electromyography devices and plantar pressure measurement mat was used to record test data. A Visual 3D software was used to process the data and calculate the biomechanical and electromyographic parameters during STS tasks. Results: There was no significant difference in task duration between the two groups. Patients with KOA could perform a greater range of pelvic motion and smaller range of hip and knee joint motion with a lower maximum hip joint angular acceleration in the sagittal plane and greater knee and ankle joint motion in the coronal plane. There was no significant difference in the motion range in the horizontal plane. During the STS task, patients in the KOA group had a lower vertical ground reaction force (GRF) amplitude on the injured side but a higher integrated GRF on both sides than those in the control group. Moreover, patients with KOA demonstrated higher PERM and PABM of the lower limb joints and smaller knee PADM and ankle PEM. Additionally, maximum activation levels of GMed muscle, affected-side gluteus medius (GM), ST, rectus femoris (RF), and tibialis anterior (TA) muscles were lower in patients with KOA than in controls. Conversely, the activation level of biceps femoris (BF) was higher. Furthermore, the integral EMG values of GMed, GM, ST, VL, RF, vastus medialis VM, and TA muscles on the affected side were lower, except for the BF muscle, in patients with KOA. Conclusion: Compared with the participants in the control group, patients with early-stage KOA exhibited consistent changes in sEMG parameters and biomechanical alterations in the sagittal plane, as observed in previous studies. However, differences in parameters were observed in the coronal and transverse planes of these patients. The noninvasive analysis of the 3D parameters of the involved motion patterns may lead to the early detection of KOA.

Correlational analysis of three-dimensional spinopelvic parameters with standing balance and gait characteristics in adolescent idiopathic scoliosis: A preliminary research on Lenke V.

Background: Adolescent idiopathic scoliosis (AIS), the most common spinal deformity, possibly develops due to imbalanced spinal loading following asymmetric development. Since altered loading patterns may affect standing balance and gait, we investigated whether a correlation exists between balance ability, gait pattern, and the three-dimensional radiographic spinopelvic parameters in AIS patients. Methods: A cross-sectional observational study was conducted with 34 AIS patients (aged 10-18 years) and an equal number of healthy age and sex-matched teenagers (normal group). We obtained the spinopelvic three-dimensional parameters and balance parameters simultaneously through the EOS imaging system and gait and center of pressure (CoP) characteristics using a plantar pressure measurement mat. Besides determining the intergroup differences in balance and gait parameters, multiple linear regression analyses were performed to identify any correlation between the static plantar pressure and radiographic parameters. Results: Compared to the normal group, the CoPx is lower, the CoP path length and 90% confidence ellipse area were significantly higher in AIS patients (AIS: -13.7 ± 5.7 mm, 147.4 ± 58.1 mm, 150.5 ± 62.8 mm2; normal: -7.0 ± 5.4 mm, 78.8 ± 32.0 mm, 92.1 ± 41.7 mm2, respectively), correlated with apical vertebra translation, sagittal pelvic tilt, and pelvis axial rotation, respectively. Moreover, AIS patients had a shorter stance phase (61.35 ± 0.97 s vs. 62.39 ± 1.09 s), a longer swing phase (38.66 ± 0.97 s vs. 37.62 ± 1.08 s), and smaller maximum pressure peaks in the gait cycle, especially on the left foot, as compared to healthy subjects. Moreover, the CoP trajectory in AIS patients was different from the latter, and changes in the bipedal trend were not consistent. Conclusion: The standing balance and gait characteristics of AIS patients are different from those of healthy subjects, as reflected in their three-dimensional spinopelvic radiographic parameters. Trial registration: The study protocol was registered with the Chinese Clinical Trial Registry (Number ChCTR1800018310) and the Human Subject Committee of Guangzhou Sport University (Number: 2018LCLL003).

Do the three-dimensional parameters of brace-wearing patients with AIS change when transitioning from standing to sitting position? A preliminary study on Lenke I.

BACKGROUND: Bracing is the most common conservative treatment for preventing the progression of adolescent idiopathic scoliosis (AIS) in patients with a curve of 25°-40°. X-ray examinations are traditionally performed in the standing position. However, school-age teenagers may take more time to sit. Thus far, little is known about three-dimensional (3D) correction in the sitting position. Hence, this study aimed to determine the effects of standing and sitting positions on 3D parameters during brace correction. METHODS: We evaluated a single-center cohort of patients receiving conservative treatment for thoracic curvature (32 patients with AIS with a Lenke I curve). The 3D parameters of their standing and sitting positions were analyzed using the EOS imaging system during their first visit and after bracing. RESULTS: At the patients' first visit, sagittal plane parameters such as thoracic kyphosis (TK), lumbar lordosis (LL), and sacral slope decreased when transitioning from the standing position to the sitting position (standing 29° ± 6°, 42° ± 8°, and 42° ± 8° vs. sitting 22° ± 5°, 27° ± 6°, and 24° ± 4°; p < 0.001), whereas pelvic tilt (PT) increased and sagittal vertical axis shifted forward (standing 9° ± 6° and 1.6 ± 2.7 cm vs. sitting 24° ± 4° and 3.8 ± 2.3 cm; p < 0.001). After bracing, TK and LL decreased slightly (from 29° ± 6° and 42° ± 8° to 23° ± 3° and 38° ± 6°; p < 0.001), whereas the thoracolumbar junction (TLJ) value increased (from 3° ± 3° to 11° ± 3°; p < 0.001). When transitioning to the sitting position, similar characteristics were observed during the first visit, except for a subtle increase in the TLJ and PT values (standing 11° ± 3° and 9° ± 4° vs. sitting 14° ± 3° and 28° ± 4°; p < 0.001). Moreover, the coronal and axial parameters at different positions measured at the same time showed no significant change. CONCLUSIONS: In brace-wearing patients with thoracic scoliosis, compensatory sagittal plane straightening may be observed with a slight increase in thoracolumbar kyphosis, particularly when transitioning from the standing position to the sitting position, due to posterior rotation of the pelvis. Our results highlight that sagittal alignment in AIS with brace treatment is not completely analyzed with only standing X-Ray. TRIAL REGISTRATION: The study protocol was registered with the Chinese Clinical Trial Registry (ChiCTR1800018310).

Reliability and validity of Chinese version of brace questionnaire for adolescent idiopathic scoliosis: A cross-sectional study.

ABSTRACT: There is an increasing concern about the impact of bracing on the quality of life (QoL) of patients with adolescent idiopathic scoliosis (AIS). However, up to now, few multidimensional questionnaires on this impact are available in China. This study aimed to evaluate the reliability and validity of the Chinese version of Brace Questionnaire (C-BrQ).The BrQ was translated from Greek into Chinese with proper cross-cultural adaptation.An observational, cross-sectional study in Chinese patients with AIS was conducted to measure the temporal stability of C-BrQ using the intraclass correlation coefficient (ICC). The effects of ceiling and floor were evaluated and the reliability was verified by examining the internal consistency. The C-BrQ domains were compared with the domains in Chinese version of Scoliosis Research Society-22 Outcomes Questionnaire (C-SRS-22) using Pearson correlation coefficient to assess the concurrent validity.A total of 208 patients were included in the study. The results of test-retest reliability for each dimension of C-BrQ were desirable. The floor or ceiling effects were not demonstrated in the C-BrQ and C-SRS-22. Satisfactory internal consistency was found in all the C-BrQ domains. Most C-BrQ and C-SRS-22 domains showed satisfactory correlation coefficients, except when vitality and school activity in C-BrQ were compared with self-image, mental health, and management satisfaction in C-SRS -22, respectively.C-BrQ is reliable in evaluating the QoL of AIS patients receiving brace treatment.

Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind study.

BACKGROUND: Recent studies in rodents indicate that a combination of exercise training and supplementation with nicotinamide adenine dinucleotide (NAD+) precursors has synergistic effects. However, there are currently no human clinical trials analyzing this. OBJECTIVE: This study investigates the effects of a combination of exercise training and supplementation with nicotinamide mononucleotide (NMN), the immediate precursor of NAD+, on cardiovascular fitness in healthy amateur runners. METHODS: A six-week randomized, double-blind, placebo-controlled, four-arm clinical trial including 48 young and middle-aged recreationally trained runners of the Guangzhou Pearl River running team was conducted. The participants were randomized into four groups: the low dosage group (300 mg/day NMN), the medium dosage group (600 mg/day NMN), the high dosage group (1200 mg/day NMN), and the control group (placebo). Each group consisted of ten male participants and two female participants. Each training session was 40-60 min, and the runners trained 5-6 times each week. Cardiopulmonary exercise testing was performed at baseline and after the intervention, at 6 weeks, to assess the aerobic capacity of the runners. RESULTS: Analysis of covariance of the change from baseline over the 6 week treatment showed that the oxygen uptake (VO2), percentages of maximum oxygen uptake (VO2max), power at first ventilatory threshold, and power at second ventilatory threshold increased to a higher degree in the medium and high dosage groups compared with the control group. However, there was no difference in VO2max, O2-pulse, VO2 related to work rate, and peak power after the 6 week treatment from baseline in any of these groups. CONCLUSION: NMN increases the aerobic capacity of humans during exercise training, and the improvement is likely the result of enhanced O2 utilization of the skeletal muscle. TRIAL REGISTRATION NUMBER: ChiCTR2000035138 .

Biomechanical characteristics of tibio-femoral joint after partial medial meniscectomy in different flexion angles: a finite element analysis.

BACKGROUND: Recent studies have pointed out that arthroscopy, the commonly-used surgical procedure for meniscal tears, may lead to an elevated risk of knee osteoarthritis (KOA). The biomechanical factors of KOA can be clarified by the biomechanical analysis after arthroscopic partial meniscectomy (APM). This study aimed to elucidate the cartilage stress and meniscus displacement of the tibiofemoral joint under flexion and rotation loads after APM. METHODS: A detailed finite element model of the knee bone, cartilage, meniscus, and major ligaments was established by combining computed tomography and magnetic resonance images. Vertical load and front load were applied to simulate different knee buckling angles. At the same time, by simulating flexion of different degrees and internal and external rotations, the stresses on tibiofemoral articular cartilage and meniscus displacement were evaluated. RESULTS: Generally, the contact stress on both the femoral tibial articular cartilage and the meniscus increased with the increased flexion degree. Moreover, the maximum stress on the tibial plateau gradually moved backward. The maximum position shift value of the lateral meniscus was larger than that of the medial meniscus. CONCLUSION: Our finite element model provides a realistic three-dimensional model to evaluate the influence of different joint range of motion and rotating tibiofemoral joint stress distribution. The decreased displacement of the medial meniscus may explain the higher pressure on the knee components. These characteristics of the medial tibiofemoral joint indicate the potential biomechanical risk of knee degeneration.

Role of exercise and rapamycin on the expression of energy metabolism genes in liver tissues of rats fed a high­fat diet.

The mTOR pathway serves an important role in the development of insulin resistance induced by obesity. Exercise improves obesity­associated insulin resistance and hepatic energy metabolism; however, the precise mechanism of this process remains unknown. Therefore, the present study investigated the role of rapamycin, an inhibitor of mTOR, on exercise­induced expression of hepatic energy metabolism genes in rats fed a high­fat diet (HFD). A total of 30 male rats were divided into the following groups: Normal group (n=6) fed chow diets and HFD group (n=24) fed an HFD for 6 weeks. The HFD rats performed exercise adaptation for 1 week and were randomly divided into the four following groups (each containing six rats): i) Group of HFD rats with sedentary (H group); ii) group of HFD rats with exercise (HE group); iii) group of HFD rats with rapamycin (HR group); and iv) group of HFD rats with exercise and rapamycin (HER group). Both HE and HER rats were placed on incremental treadmill training for 4 weeks (from week 8­11). Both HR and HER rats were injected with rapamycin intraperitoneally at the dose of 2 mg/kg once a day for 2 weeks (from week 10­11). All rats were sacrificed following a 12­16 h fasting period at the end of week 11. The levels of mitochondrial and oxidative enzyme activities, as well as of the expression of genes involved in energy metabolism were assessed in liver tissues. Biochemical assays and oil red staining were used to assess the content of hepatic triglycerides (TGs). The results indicated that exercise, but not rapamycin, reduced TG content in the liver of HFD rats. Further analysis indicated that rapamycin reduced the activity of cytochrome c oxidase, but not the activities of succinate dehydrogenase and ß­hydroxyacyl­CoA dehydrogenase in the liver of HFD rats. Exercise significantly upregulated the mRNA expression of peroxisome proliferator­activated receptor γ coactivator 1 ß, while rapamycin exhibited no effect on the mRNA expression levels of hepatic transcription factors associated with energy metabolism enzymes in the liver of HFD rats. Collectively, the results indicated that exercise reduced TG content and upregulated mitochondrial metabolic gene expression in the liver of HFD rats. Moreover, this mechanism may not involve the mTOR pathway.

Effects of strength and neuromuscular training on functional performance in athletes after partial medial meniscectomy.

The aims of this study were to determine an effective knee function rehabilitation program for athletes undergoing partial medial meniscectomy. Participants were randomly assigned to neuromuscular training (NT) or strength training (ST) group and subjected to functional assessments before surgery and again at 4, and 8 weeks post hoc. Functional knee assessment, such as Lysholm knee scoring, star excursion balance, and BTE PrimusRS isokinetic performance tests were evaluated in each group. All postoperational symptoms were significantly improved after 4 and 8 weeks of NT and ST. Both NT and ST programs showed effective knee function recovery seen as an increase in muscular strength and endurance. However, the NT program showed the most significant functional improvement of dynamic balance and coordination.

Exercise improves skeletal muscle insulin resistance without reduced basal mTOR/S6K1 signaling in rats fed a high-fat diet.

Exercise improves high-fat diet (HFD)-induced skeletal muscle insulin resistance, but the mechanism is unresolved. This study aims to explore whether the improvement in response to exercise is associated with mTOR/S6K1 signaling and whether the signaling changes are muscle-specific. Male SD rats (150-180 g) were used for this study. After the experimental period, 6 weeks of exercise improved HFD-impaired intraperitoneal glucose tolerance and insulin-stimulated 2-deoxyglucose uptake in soleus (SOL) and extensor digitorum longus (EDL) muscles. Furthermore, 6 weeks of the HFD resulted in a reduced type I fiber ratio of SOL, an increased type I ratio of EDL, and a reduced fiber size of EDL, whereas exercise increased type I fiber ratio of SOL as well as type I fiber cross-sectional areas of EDL. However, the HFD had a main effect on basal cytosolic phosphorylation of S6K1 on Thr(389) content in SOL, which was also influenced by a significant interaction between the diet and exercise in EDL. Exercise had no direct effect on the basal phosphorylation of Akt on Ser(473), mTOR on Ser(2448), S6K1 on Thr(389) content in SOL. On the contrary, exercise prevented HFD-induced decrease in basal phosphorylation of S6K1 on Thr(389) content in EDL. These results indicate that 6 weeks of HFD and exercise lead to alterations in fiber type shift, fiber size, and basal phosphorylation of S6K1 on Thr(389) content in a muscle-specific pattern. Exercise prevents HFD-induced skeletal muscle insulin resistance, which is not associated with a reduced basal phosphorylation of mTOR/S6K1 alteration in the muscles.