Temporary meniscus extrusion is caused by cumulative stress from uphill and downhill tasks in healthy volunteers.

Purpose: Excessive mechanical stress accumulates and causes knee injury. Meniscal extrusion is a key factor in detecting the reaction to cumulative mechanical stress. The accumulation of stress strongly depends on environmental conditions such as flat ground or uphill/downhill, and accumulates in knee compartments; only a few studies have reported the effects of different environments on lateral and medial meniscus extrusion. This study aimed to investigate the effects of cumulative uphill/downhill stress on the meniscal extrusion in each compartment. Methods: A total of 30 healthy volunteers with 30 affected knees were involved in this cohort study (mean age, 22.0 ± 1.1 years; men, n = 14). The participants were divided into flat-walking, uphill/downhill-walking, and uphill/downhill-jogging groups and their numbers of steps taken were recorded during the effort. Moreover, medial and lateral meniscal extrusions during walking were evaluated using ultrasound three times, before and after efforts (T1) and (T2), and one day after efforts (T3), respectively. Results: In the flat-walking group, no significant differences were observed between the follow-up periods. Conversely, in the uphill/downhill-walking and jogging groups, the medial meniscus extrusion at T2 was significantly higher than that at T1. Conversely, the medial meniscus extrusion at T3 was significantly lower than that at T2. By contrast, the lateral meniscus did not show any difference between the follow-up periods in any group. Conclusion: Temporary extrusion of the meniscus occurred after uphill/downhill tasks in healthy volunteers, and its reaction was observed only in the medial meniscus.

Medial meniscus extrusion during gait is associated with decrease in knee rotation in early-stage knee osteoarthritis.

BACKGROUND: In patients with medial knee osteoarthritis (OA), medial meniscus extrusion during gait is aggravated by mechanical stress, such as knee adduction moment (KAM). Conversely, the decrease in the range of knee rotation during stance phase is also one of the important issues in early knee OA, whereas the correlation between medial meniscus extrusion and knee rotation during gait are unclear. RESEARCH QUESTION: To investigate the correlation between increase in medial meniscus extrusion and range of knee rotation during gait in patients with early- and late-stage of knee OA. METHODS: Forty patients with medial knee OA were enrolled and divided into early- and late-OA group by Kellgren-Lawrence grading scale. During gait tasks, the extent of medial meniscus extrusion was measured using ultrasonography and kinetic/kinematic data were measured using three-dimensional motion analysis system. The correlation between medial meniscus extrusion and the range of knee rotation or KAM were evaluated in the overall, early-, and late- OA groups. RESULTS: A significant negative correlation was observed between an increase in medial meniscus extrusion and range of knee rotation angle in early-OA group only. However, an increase in medial meniscus extrusion significantly correlated with the second KAM peak in the overall and early-OA groups. SIGNIFICANCE: The decrease in range of knee rotation during stance phase may be associated with the increase in medial meniscus extrusion during gait in patients with early knee OA.

Toe-out gait inhibits medial meniscus extrusion associated with the second peak of knee adduction moment during gait in patients with knee osteoarthritis.

Background: A medial meniscus extrusion (MME) gradually expands during activities of daily living according to the mechanical stress on the medial compartment of the knee. Increase in MME occurs during the stance phase of the gait cycle, which is key for its expand. The knee adduction moment (KAM) represents the mechanical stress on the medial compartment; however, the relationship between the increase in MME and KAM is still unknown. Therefore, the present study aimed to investigate the relationship between MME during gait and KAM. Methods: Twenty-one patients with medial knee osteoarthritis and 11 healthy middle-aged adults were recruited. Three-dimensional motion analysis system and ultrasonography were used to measure the KAM and MME in the stance phase. The increase in MME was identified as the difference in MME between the maximum and minimum (ΔMME). Patients with knee osteoarthritis performed two conditions as normal and toe-out gait. The difference in KAM and ΔMME between conditions were evaluated. Results: ΔMME was correlated with the KAM second peak in normal gait of knee osteoarthritis patients (r = 0.51, p < 0.05). Toe-out gait reduced the KAM second peak and the ΔMME, and these reductions were correlated (r = 0.50, p < 0.05). Conclusions: Toe-out gait immediately inhibited the expansion of MME associated with the KAM second peak.

Topological capture of mRNA for silencing gene expression.

We describe herein topological mRNA capture using branched oligodeoxynucleotides (ODNs) with multiple reactive functional groups. These fragmented ODNs efficiently formed topological complexes on template mRNA in vitro. In cell-based experiments targeting AcGFP mRNA, the bifurcated reactive ODNs showed a much larger gene silencing effect than the corresponding natural antisense ODN.

Effect of limb alignment correction on medial meniscus extrusion under loading condition in high tibial osteotomy.

Background: This study aimed to investigate the effect of high tibial osteotomy (HTO) on medial meniscus extrusion (MME) and the association between the changes in limb alignment and MME under weight-bearing (WB) conditions after HTO. Methods: We included 17 patients with knee osteoarthritis (OA) who underwent HTO. MME was evaluated using ultrasonography in supine and unipedal standing positions. Knee alignment was evaluated radiographically using WB, whole-leg radiographs with the hip-knee-ankle angle (HKAA), percentage of the mechanical axis (%MA), medial proximal tibial angle (MPTA), and joint line convergence angle (JLCA). All measurements were performed serially at four time points: preoperative and 3, 6, and 12 months postoperative. Clinical outcomes were assessed by knee injury and osteoarthrosis outcome score (KOOS) and visual analogue scale (VAS) value for pain. Results: Mean MME in the WB position was significantly greater than that in the supine position in the preoperative condition; however, MME in both supine and WB positions was significantly lowered postoperatively. The ΔMME, difference of MME between supine and WB positions, was significantly lowered postoperatively and maintained for up to 1 year. MME change in the WB position between preop and postoperative conditions was significantly correlated with change in HKAA and %MA at 1 year postoperative. KOOS and VAS score were significantly improved after HTO. Conclusions: HTO correcting varus alignment can decrease MME in WB position and minimise the change in MME between supine and WB positions. The changes in MME after HTO were correlated with changes in the mechanical alignments.

Evaluation of meniscus extrusion during stair ambulation in healthy volunteers using dynamic ultrasonography: a feasibility study.

PURPOSE: This study aimed to investigate the feasibility of evaluating medial meniscus extrusion (MME) during stair ambulation. METHODS: Twenty healthy young participants (mean age, 22.4 ± 0.9 years) were recruited for this cross-sectional study. Synchronization between the three-dimensional motion system and ultrasonography was used to quantify the extent of meniscal extrusion and knee angles during different tasks, including gait, stair ascent, and stair descent. In particular, ultrasonography was used to record the movements of both the middle and posterior segments of the meniscus to obtain detailed information about these movements in relation to the knee angle. The difference between the maximum MME and the MME at the initial contact (ΔMME) was evaluated during each task in the stance phase. RESULTS: Visualization of the meniscus in the middle segment was limited with increasing knee flexion angle, whereas the posterior segments were visible during all tasks. ΔMME of the posterior segment during stair ascent and descent was higher than that during gait (gait: 0.68 ± 0.20 mm, ascent: 1.00 ± 0.39 mm, descent: 0.90 ± 0.27 mm, gait-ascent: p = 0.009, gait-descent: p = 0.004). CONCLUSIONS: Evaluation that includes the posterior segment enables visualization of the medial meniscus and detection of its specific behavior during stair ambulation. These findings demonstrate the feasibility of evaluating meniscus dynamics during stair ambulation, and could contribute to a better understanding of these dynamics.

Measurement of the lumbrical muscle activity of the hand using electromyography supported by the ultrasound imaging technique with string navigation.

Although placing surface electrodes on small muscles by palpation is difficult, ultrasound guidance may enable electrode placement on the small muscles. This study aimed to examine whether ultrasound guidance is helpful for placement of electrodes on a small muscle, such as the hand lumbrical muscle. Twelve dominant hands of 12 healthy right-handed adults were included in this study. The first lumbrical muscle belly of the hands was identified using ultrasound guidance with a string navigation technique for placing surface electrodes. This technique was designed to identify the location of the center of the muscle belly under ultrasound imaging using a string. After the electrodes were placed on the muscle belly using this technique, the surface electromyographic signals of the first lumbrical, first dorsal interosseous, and adductor pollicis muscles were recorded. The activity of the lumbrical muscle could be separately measured of the first dorsal interosseous and adductor pollicis muscles. This technique has the potential to enable surface electromyography of small muscles for which placement of surface electrodes by palpation is challenging.

Unique patterns of medial meniscus extrusion during walking and its association with limb kinematics in patients with knee osteoarthritis.

Medial meniscus extrusion (MME) is exacerbated by repeated mechanical stress. Various factors would affect MME; however, there is limited information about the behaviour of the medial meniscus during walking in patients with knee osteoarthritis (KOA). This study aimed to investigate the pattern of MME during walking and its association with limb biomechanics in patients with KOA. Fifty-five patients with KOA and ten older adult volunteers as a control group were involved in this study. The MME and limb biomechanics during walking were evaluated simultaneously by ultrasound and a motion analysis system, respectively. The waveform was constructed from the values of MME, and the point showing the highest value of MME was identified during the gait cycle. According to the peak timing of MME in the waveform, the pattern of the waveform was evaluated and compared to the control group. Lateral thrust, knee adduction moment (KAM), and flexion moment were obtained from motion analysis, and their association with the MME was evaluated. The patients with KOA demonstrated unique peak timing during walking. Compared to the control group, there were three groups of MME waveforms, early (< 59%), normal (60-83%), and late (> 84%) from the peak timing in the gait cycle. The pattern of MME waveform in early, normal, and late groups was correlated with the first KAM and lateral thrust, second KAM, and knee flexion moment, respectively. A unique MME pattern during walking was demonstrated, and these patterns were associated with limb biomechanics in patients with KOA.

Age-specific incidence of joint disease in paediatric patients with haemophilia: A single-centre real-world outcome based on consecutive US examination.

INTRODUCTION: Joint health is one of the most important factors contributing to a healthy life in patients with haemophilia. Recent study revealed that starting early prophylaxis was not enough to prevent joint disease in most paediatric patients with haemophilia. AIM: In this study, we aimed to determine the age-specific incidence of acute joint disease during childhood at single haemophilia treatment centre (HTC). METHOD: The joint health in 48 patients was evaluated based on consecutive US testing for 5 years at annual multidisciplinary comprehensive care. RESULTS: During the study period, 23 patients (47.9%) had no joint disease since the initial examination, whereas 13 patients (27.0%) showed development from negative to positive findings. The incidence of joint disease increased with age: 0% in preschool, 5.3% in elementary school, 14.3% in junior high school and 35% beyond high school age. Among the 13 patients who developed joint disease, two experienced acquired synovitis that resolved during the follow-up period. Statistical analysis revealed that the patients who routinely underwent follow-up by the HTC exhibited a significantly lower incidence of joint disease than did those followed up at other institutions (p < .001). CONCLUSION: These results indicated that close check-up, including routine joint examination using US as well as frequent assessment of pharmacokinetic profile at the HTC, might play an important role in avoiding joint disease among paediatric patients with haemophilia.

Visualization of lateral meniscus extrusion during gait using dynamic ultrasonographic evaluation.

PURPOSE: Medial meniscus extrusion is one of the risk factors for knee osteoarthritis (OA). However, lateral meniscus extrusion has not been discussed, and detailed information remains unknown. In particular, the lateral meniscus has high mobility and is expected to be difficult to evaluate in terms of its behavior under static conditions. Dynamic ultrasonographic evaluation was introduced to detect the dynamic behavior of the meniscus during walking. In this study, we aimed to investigate the behavior of the lateral meniscus during walking using dynamic ultrasonographic evaluation. METHODS: Sixteen participants with knee OA were recruited in this study. The change of lateral meniscus extrusion during walking was recorded using ultrasonography. Medial and lateral meniscal extrusion during the stance phase was measured, and meniscal mobility was defined as the difference in meniscal extrusion between minimum and maximum values (mm), medial meniscal extrusion (∆MME), and lateral meniscal extrusion (∆LME), respectively. The walking cycle and gait forms of lateral thrust were also evaluated using three-dimensional motion analysis systems and analyzed in terms of the correlation with ∆MME and ∆LME. RESULTS: The lateral meniscus was depicted in the articular plane, and extrusion decreased during the stance phase of the gait cycle. The ∆LME was significantly higher than the ∆MME (p < 0.01). There was a significant positive correlation between ∆LME and lateral thrust (r = 0.62, p < 0.05). CONCLUSIONS: We found that dynamic ultrasonographic evaluation can be used to visualize lateral meniscus extrusion during walking, and that its behavior is correlated to the degree of lateral thrust.

Effects of metacarpophalangeal joint position and finger joint movement speed on lumbrical muscle activity.

OBJECTIVES: The effect of metacarpophalangeal joint position and finger joint movement speed on lumbrical muscle activity remains unproven and was examined in this study. MATERIAL AND METHODS: Twenty-four healthy adults performed flexion-extension movements of the index finger in different metacarpophalangeal joint positions (extension or flexion) and movement speeds (60, 120, 240, and 360 beats per minute). The activities of the first lumbrical, first dorsal interosseous, and extensor digitorum muscles were evaluated using surface electromyography, and compared with those during finger joint extension. RESULTS: The metacarpophalangeal joint positions affected only lumbrical muscle activity, which was greater during extension. Further, finger movement speed affected the lumbrical and extensor digitorum muscle activities, which increased with increasing movement speeds. CONCLUSION: The present study suggests that position and movement speed can influence the lumbrical muscle activity during metacarpophalangeal joint extension. These findings may help expound lumbrical function and develop suitable strategies for inducing lumbrical muscle activity.

Cap analogs with a hydrophobic photocleavable tag enable facile purification of fully capped mRNA with various cap structures.

Starting with the clinical application of two vaccines in 2020, mRNA therapeutics are currently being investigated for a variety of applications. Removing immunogenic uncapped mRNA from transcribed mRNA is critical in mRNA research and clinical applications. Commonly used capping methods provide maximum capping efficiency of around 80-90% for widely used Cap-0- and Cap-1-type mRNAs. However, uncapped and capped mRNA possesses almost identical physicochemical properties, posing challenges to their physical separation. In this work, we develop hydrophobic photocaged tag-modified cap analogs, which separate capped mRNA from uncapped mRNA by reversed-phase high-performance liquid chromatography. Subsequent photo-irradiation recovers footprint-free native capped mRNA. This approach provides 100% capping efficiency even in Cap-2-type mRNA with versatility applicable to 650 nt and 4,247 nt mRNA. We find that the Cap-2-type mRNA shows up to 3- to 4-fold higher translation activity in cultured cells and animals than the Cap-1-type mRNA prepared by the standard capping method.

The Effect of γ Phosphate Modified Deoxynucleotide Substrates on PCR Activity and Fidelity.

Controlling PCR fidelity is an important issue for molecular biology and high-fidelity PCR is essential for gene cloning. In general, fidelity control is achieved by protein engineering of polymerases. In contrast, only a few studies have reported controlling fidelity using chemically modified nucleotide substrates. In this report, we synthesized nucleotide substrates possessing a modification on Pγ and evaluated the effect of this modification on PCR fidelity. One of the substrates, nucleotide tetraphosphate, caused a modest decrease in Taq DNA polymerase activity and the effect on PCR fidelity was dependent on the type of mutation. The use of deoxyadenosine tetraphosphate enhanced the A : T→G : C mutation dramatically, which is common when using Taq polymerase. Conversely, deoxyguanosine tetraphosphate (dG4P) suppressed this mutation but increased the G : C→A : T mutation during PCR. Using an excess amount of dG4P suppressed both mutations successfully and total fidelity was improved.

The effect of gait modification on the response of medial meniscus extrusion during gait in patients with knee osteoarthritis.

BACKGROUND: An increase in medial meniscus extrusion during weight-bearing conditions is associated with the progression of medial knee osteoarthritis (OA). Toe-out gait modification has been known to reduce the knee adduction moment (KAM); however, its effect on reducing the increase in medial meniscus extrusion in patients with knee OA remains unclear. RESEARCH QUESTION: To (1) evaluate the effect of toe-out gait on the increase in medial meniscus extrusion and the KAM in patients with medial knee OA and (2) investigate the synergetic effect of lateral wedge insoles in combination with toe-out gait in determining the most effective intervention for reducing medial meniscus extrusion during gait. METHODS: Twenty-five patients with medial knee OA were enrolled in this study. Participants walked under four conditions: normal gait, toe-out gait, normal gait with lateral wedge insoles, and toe-out gait with lateral wedge insoles. Medial meniscus extrusion and KAM peaks during gait were measured using ultrasound and a three-dimensional motion analysis system in each condition. These parameters were compared among the four conditions using repeated measures analysis of variance. RESULTS: The increase in medial meniscus extrusion and the second KAM peak were significantly lower in all interventions compared with those observed during normal gait. However, there was no significant difference among the interventions. SIGNIFICANCE: This study suggested that toe-out gait reduces the increase in medial meniscus extrusion and is associated with the reduction of the second KAM peak. However, no synergistic effect of lateral wedge insoles and toe-out gait was observed.

Dynamic ultrasound reveals the specific behavior of the medial meniscus extrusion in patients with knee osteoarthritis.

BACKGROUND: In the dynamic condition, knee osteoarthritis (OA) usually presents with pain. In the weight-bearing condition, a medial meniscus extrusion (MME) may cause severe symptoms and pathological progression. However, the correlation between a dynamic MME and pain has not been elucidated. Now, an MME can be evaluated under dynamic conditions and reflect the characteristics of symptomatic knee OA. This study investigated MMEs during walking and their correlation with knee pain. METHODS: Thirty-two symptomatic patients with knee OA (mean age, 60.5 ± 9.9 years) were enrolled in this study. The medial meniscus was evaluated using ultrasonograms during walking, and in the static supine and unipedal standing positions, as dynamic and static conditions, respectively. The ΔMME (the difference between the maximum and minimum MMEs) was obtained in each condition. The intensity of the knee pain during walking was measured by the visual analog scale (VAS). RESULTS: The ΔMME in the dynamic condition was significantly higher than that in the static condition (P < 0.01). There was a significant correlation between VAS and ΔMME only in the dynamic condition. CONCLUSIONS: The dynamic evaluation is a valid tool for understanding the mechanisms of knee pain and the behavior of the medial meniscus in symptomatic knee OA.

Cumulative knee adduction moment during jogging causes temporary medial meniscus extrusion in healthy volunteers.

PURPOSE: The cumulative knee adduction moment (KAM) is a key parameter evaluated for the prevention of overload knee injuries on the medial compartment. Medial meniscus extrusion (MME), typical in hoop dysfunctions, is a measure for the cumulative mechanical stress in individual knees; however, its correlation with cumulative KAM is unknown. The aim of this study was to investigate the effect of temporary overload stress on MME and its correlation with cumulative KAM. METHODS: Thirteen healthy asymptomatic volunteers (13 knees) were recruited for a cohort study (mean age, 23.1 ± 3.3 years; males: n = 8). The cumulative KAM was calculated using a three-dimensional motion analysis system, in addition to the number of steps taken while jogging uphill or downhill. MME was evaluated using ultrasound performed in the standing position. The evaluations were performed four times: at baseline (T0), before and after (T1 and T2, respectively) jogging uphill or downhill, and 1 day after (T3) jogging. Additionally, the Δ-value was calculated using the change of meniscus after efforts as the difference in MME between T1 and T2. RESULTS: The MME in T2 was significantly greater than those in T0 and T1. Conversely, the MME in T3 was significantly lesser than that in T2. No significant difference was found between those in T0 and T1, and T3. ΔMME exhibited a significant positive correlation with the cumulative KAM (r = 0.68, p = 0.01), but not for peak KAM. CONCLUSION: The temporary reaction of MME observed in ultrasound correlates with the cumulative stress of KAM.

Point-of-care ultrasound in musculoskeletal field.

The musculoskeletal field is relatively new in point-of-care ultrasound (POCUS), a modality that has been gaining significance with the evolution of ultrasound (US) equipment and high-frequency probes. Images have become progressively clearer over the past decade, making it possible to diagnose many pathological conditions without exposure to radiation. Ultrasonography reveals many soft tissue pathologies that cannot be visualized using plain radiographs, which have historically been the first choice for the evaluation of musculoskeletal disorders. US saves money and time compared to magnetic resonance imaging (MRI). Although it is difficult to diagnose a disorder inside bone, its surface can be visualized very clearly, and it is also possible to visualize cartilage. Furthermore, with POCUS, it is possible to confirm a disorder and the continuity of the fibrous structures of muscles, tendons, and ligaments. In addition, the understanding of pathological conditions of motor disturbances, such as nerve or muscle/tendon injury, nerve paralysis, adhesions of the tendons, and joint instability, is deepened by observing the movement of these structures. Peripheral nerves, even small branches, can be visualized, and pathological conditions can be pinpointed by observing the nerve morphology, continuity, and relationship with the surrounding tissues. Children can be examined in a safe, relaxed environment, without leaving their parents. In addition, US is significantly different from other modalities in that it can be used for both diagnosis and treatment. Being able to visualize target sites improves safety and route accuracy of needle insertion for injection or puncture. Musculoskeletal POCUS is indispensable in routine medical care and is a technique that medical residents should acquire.

Knee adduction moment is correlated with the increase in medial meniscus extrusion by dynamic ultrasound in knee osteoarthritis.

BACKGROUND: An increase in medial meniscus extrusion (MME) due to abnormal biomechanical stress leads to knee osteoarthritis (OA) progression. MME evaluation during walking is a key method of detecting dynamic changes in the meniscus, and in combination with motion analysis, can provide a deeper understanding of the mechanisms involved in the increase of MME. OBJECTIVE: To validate the feasibility of MME dynamic evaluation in combination with a motion analysis system based on the correlation between the increase in MME and biomechanical factors. METHODS: Twenty-three knees from 23 patients with mild to moderate knee OA were analysed in this study. The medial meniscus during walking was evaluated by ultrasound. The increase in MME was calculated as the difference between the minimum and maximum MME during walking. A three-dimensional motion analysis system was synchronised with the ultrasound and then, biomechanical factors such as knee moment and ground reaction force were evaluated. RESULTS: The wave patterns of the mediolateral and vertical components of ground reaction forces and knee adduction moment were similar to those in the MME based on a high cross-correlation coefficient (>0.8). The increase in MME was significantly correlated with the peak value of the knee adduction moment (r = 0.54, P = 0.0073) but not with the mediolateral and vertical components of the ground reaction force. CONCLUSION: The findings show that knee adduction moment is correlated with an increase in MME during walking and indicates the validity and feasibility of the dynamic evaluation of MME in combination with a motion analysis system.

Dynamic response of medial meniscus extrusion to the lateral wedge insole is correlated with immediate pain reduction in knee osteoarthritis patients: real-time ultrasonographic study.

PURPOSE: To investigate the effect of lateral wedge insole (LWI) on medial meniscus extrusion (MME) observed during dynamic evaluation with ultrasound and its correlation with the alteration in knee pain in patients with knee osteoarthritis (OA). METHODS: This cohort study included 25 participants with knee OA. The medial meniscus was imaged during walking in video mode using ultrasonography. The degree of increase in MME (ΔMME) was calculated as the difference in the value of the maximum and minimum MME. The intensity of knee pain was evaluated immediately after the walking trial using the visual analogue scale (VAS). These measurements were performed with and without the LWI. The participants were categorised into the responder group, which was identified by the constant reduction in the VAS, and the non-responder group. RESULTS: MME, ΔMME, and knee pain during walking were significantly lower with the LWI than without the LWI (p < 0.01). The reduction in ΔMME with the LWI in the responder group was significantly higher than that in the non-responder group (p < 0.01). CONCLUSIONS: Our findings showed that MME and knee pain during walking decreased with LWI use, especially in patients whose reduction in knee pain was characterised by inhibition in the increase in MME observed during dynamic evaluation with ultrasound.