Fong-Chin Su

Assessing Finger Joint Biomechanics by Applying Equal Force to Flexor Tendons In Vitro Using a Novel Simultaneous Approach

Background The flexor digitorum superficialis (FDS) and flexor digitorum profundus (FDP) are critical for finger flexion. Although research has recently focused on these tendons’ coactivity, their contributions in different tasks remain unclear. This study created a novel simultaneous approach to investigate the coactivity between the tendons and to clarify their contributions in different tasks. Methods Ten human cadaveric hands were mounted on our custom frame with the FDS and FDP of the third finger looped through a mechanical pulley connected to a force transducer. Joint range of motion, tendon excursion and loading force were recorded during individual joint motion and free joint movement from rest to maximal flexion. Each flexor tendon’s moment arm was then calculated. Results In individual motions, we found that the FDP contributed more than the FDS in proximal interphalangeal (PIP) joint motion, with an overall slope of 1.34 and all FDP-to-FDS excursion (P/S) ratios greater than 1.0 with force increase. However, the FDP contributed less than the FDS in metacarpophalangeal (MCP) joint motion, with an overall slope of 0.95 and P/S ratios smaller than 1.0 throughout the whole motion except between 1.9% and 13.1% force. In free joint movement, the FDP played a greater role than the FDS, with an overall ratio of 1.37 and all P/S ratios greater than 1.0. Conclusions The new findings include differences in finger performance and excursion amounts between the FDS and FDP throughout flexion. Such findings may provide the basis for new hand models and treatments.

Cyclic Stretch Facilitates Myogenesis in C2C12 Myoblasts and Rescues Thiazolidinedione-Inhibited Myotube Formation

Thiazolidinedione (TZD), a specific peroxisome proliferator-activated receptor γ (PPARγ) agonist, was developed to control blood glucose in diabetes patients. However, several side effects were reported that increased the risk of heart failure. We used C2C12 myoblasts to investigate the role of PPARs and their transcriptional activity during myotube formation. The role of mechanical stretch during myogenesis was also explored by applying cyclic stretch to the differentiating C2C12 myoblasts with 10% strain deformation at 1u2009Hz. The myogenesis medium (MM), composed of Dulbecco’s modified Eagle’s medium with 2% horse serum, facilitated myotube formation with increased myosin heavy chain and α-smooth muscle actin (α-SMA) protein expression. The PPARγ protein and PPAR response element (PPRE) promoter activity decreased during MM induction. Cyclic stretch further facilitated the myogenesis in MM with increased α-SMA and decreased PPARγ protein expression and inhibited PPRE promoter activity. Adding a PPARγ agonist (TZD) to the MM stopped the myogenesis and restored the PPRE promoter activity, whereas a PPARγ antagonist (GW9662) significantly increased the myotube number and length. During the myogenesis induction, application of cyclic stretch rescued the inhibitory effects of TZD. These results provide novel perspectives for mechanical stretch to interplay and rescue the dysfunction of myogenesis with the involvement of PPARγ and its target drugs.

Comparison of objective muscle strength in c5-c6 and c5-c7 brachial plexus injury patients after double nerve transfer

Purpose: The purpose of this study was to evaluate the quantitative muscle strength to distinguish the outcomes of different injury levels in upper arm type brachial plexus injury (BPI) patients with double nerve transfer. Methods: Nine patients with C5‐C6 lesions (ageu2009=u200932.2u2009±u200913.9 year old) and nine patients with C5‐C7 lesions (ageu2009=u200932.4u2009±u20097.9 year old) received neurotization of the spinal accessory nerve to the suprascapular nerve combined with the Oberlin procedure (fascicles of ulnar nerve transfer to the musculocutaneous nerve) were recruited. The average time interval between operation and evaluation were 27.3u2009±u200921.0 and 26.9u2009±u200920.6 months for C5‐C6 and C5‐C7, respectively. British Medical Research Council (BMRC) scores and the objective strength measured by a handheld dynamometer were evaluated in multiple muscles to compare outcomes between C5‐C6 and C5‐C7 injuries. Results: There were no significant differences in BMRC scores between the groups. C5‐C6 BPI patients had greater quantitative strength in shoulder flexor (Pu2009=u20090.02), shoulder extensor (Pu2009<u20090.01), elbow flexor (Pu2009=u20090.04), elbow extensor (Pu2009=u20090.04), wrist extensor (Pu2009=u20090.04), and hand grip (Pu2009=u20090.04) than C5‐C7 BPI patients. Conclusions: Upper arm type BPI patients have a good motor recovery after double nerve transfer. The different outcomes between C5‐C6 and C5‐C7 BPI patients appeared in muscles responding to hand grip, wrist extension, and sagittal movements in shoulder and elbow joints.

Assembling Composite Dermal Papilla Spheres with Adipose-derived Stem Cells to Enhance Hair Follicle Induction

Intradermal adipose tissue plays an essential role for hair follicles (HFs) regeneration by regulating hair cycles. However, the effect of reconstruction of HFs and the involvement of adipose-related cells are poorly understood. We investigated assembly strategies for the interactions of dermal papilla (DP) cells with adipose-derived stem cells (ASCs) in promoting hair formation. DP cells lose DP traits during adherent culture, but preserved DP markers with a unified sphere diameter by seeding on chitosan-coated microenvironments. Next, ASCs isolated from rats were co-cultured with DP spheres by different assembling approaches to determine their interactions; a mixed sphere of ASCs with DP cells (MA-DPS), or a core-shell structure, outer ASCs shell and an inner DP core (CSA-DPS). CSA-DPS exhibited superior DP characteristics compared to MA-DPS. Conditional medium from ASCs, but not differentiated adipocytes, promoted DP markers and functional alkaline phosphatase activity from the DP cells. In vivo patch assay showed the core-shell assembling of CSA-DPS can reconstruct cellular arrangements and microenvironmental niches as dominated by PPARα signal in ASCs to induce the greater hair induction than MA-DPS or DP spheres alone. Therefore, the assembling of a core-shell sphere for DP with ASCs could reconstruct the HF cellular arrangement for hair formation. This paper set the groundwork for further evaluation of the input of other cell types.

The effects of forearm fatigue on baseball fastball pitching, with implications about elbow injury

ABSTRACT This study investigated the contribution of flexor muscles to the forearm through fatigue; therefore, the differences in forearm mechanisms on the pitching motion in fastball were analysed. Fifteen baseball pitchers were included in this study. Ultrasonographical examination of participants’ ulnar nerve in the cubital tunnel with the elbow extended and at 45°, 90° and 120° of flexion was carried. A three-dimensional motion analysis system with 14 reflective markers attached on participants was used for motion data collection. The electromyography system was applied over the flexor carpi ulnaris, flexor carpi radialis and extensor carpi radialis muscles of the dominant arm. Flexor carpi ulnaris muscle activity showed a significant difference during the acceleration phase, with a peak value during fastball post-fatigue (P = 0.02). Significant differences in the distance between ulnar nerve and medial condyle on throwing arm and non-throwing arm were observed as the distance increased with the elbow movement from 0° to 120° of flexion (P = 0.01). The significant increase of the flexor carpi ulnaris muscle activity might be responsible for maintaining the stability of the wrist joint. The increased diameter might compress the ulnar nerve and cause several pathological changes. Therefore, fatigue in baseball pitchers still poses a threat to the ulnar nerve because the flexor carpi ulnaris and flexor carpi radialis all originate from the medial side of the elbow, and the swelling tendons after fatigue might be a key point.

High-molecular-weight hyaluronic acid attenuated matrix metalloproteinase-1 and -3 expression via CD44 in tendinopathy

Evidence indicates that hyaluronic acid (HA) mitigates tendinopathy, but the effect of molecular weight is unclear. We investigated the effects of different concentrations and different molecular weights of HA (350u2009kDa, 1500u2009kDa, and 3000u2009kDa) on matrix metalloproteinase (MMP)-1 and -3 expression in IL-1β-stimulated rat tenocytes, and on their dynamic expression in peritendinous effusion from patients with long head of biceps (LHB) tendinopathy after high-molecular-weight (HMW)-HA treatments. Reverse transcription PCR, real-time PCR, and ELISA were used to determine MMP-1 and -3expression. Because CD44 was clearly expressed in the plasma membranes of cultured tenocytes, OX-50, a CD44 antagonist, was used to inhibit CD44 to evaluate the HA mechanism. HA (3000u2009kDa) significantly (pu2009<u20090.001) downregulated the mRNA and protein expression of MMP-1 and -3 in IL-1β-stimulated tenocytes. Its attenuating effects were dose-dependent (pu2009<u20090.01). In OX-50-pretreated cells, the mRNA expression of CD44 was not significantly altered, but the mRNA expression of MMP-1 and -3 was significantly upregulated. Visual analogue scale scores were significantly lower, and MMP-1 and -3 expression was significantly (pu2009<u20090.05) lower one month posttreatment. HMW-HA attenuated tendinopathy by downregulating MMP-1 and -3 expression. Inhibiting CD44 blocked the effects of HMW-HA.

Impacts of elevated glycaemic haemoglobin and disease duration on the sensorimotor control of hands in diabetes patients

To understand the impacts of disease chronicity and hyperglycaemia on sensorimotor control of hands of diabetic patients, this study investigated the differences in hand sensation, strength and motor control by applying the pinch‐holding‐up activity test for patients with diabetes mellitus (DM) with different levels of glycaemic control and disease chronicity.

Is the Control of Applied Digital Forces During Natural Five-digit Grasping Affected by Carpal Tunnel Syndrome?

BackgroundThe impaired sensory function of the hand induced by carpal tunnel syndrome (CTS) is known to disturb dexterous manipulations. However, force control during daily grasping configuration among the five digits has not been a prominent focus of study. Because grasping is so important to normal function and use of a hand, it is important to understand how sensory changes in CTS affect the digit force of natural grasp.Questions/purposesWe therefore examined the altered patterns of digit forces applied during natural five-digit grasping in patients with CTS and compared them with those seen in control subjects without CTS. We hypothesized that the patients with CTS will grasp by applying larger forces with lowered pair correlations and more force variability of the involved digits than the control subjects. Specifically, we asked: (1) Is there a difference between patients with CTS and control subjects in applied force by digits during lift-hold-lower task? (2) Is there a difference in force correlation coefficient of the digit pairs? (3) Are there force variability differences during the holding phase?MethodsWe evaluated 15 female patients with CTS and 15 control subjects matched for age, gender, and hand dominance. The applied radial forces (Fr) of the five digits were recorded by respective force transducers on a cylinder simulator during the lift-hold-lower task with natural grasping. The movement phases of the task were determined by a video-based motion capture system.ResultsThe applied forces of the thumb in patients with CTS (7xa0±xa00.8xa0N; 95% CI, 7.2–7.4xa0N) versus control subjects (5xa0±xa00.8xa0N; 95% CI, 5.1–5.3xa0N) and the index finger in patients with CTS (3xa0±xa00.3xa0N; 95% CI, 3.2–3.3xa0N) versus control subjects (2xa0±xa00.3xa0N; 95% CI, 2.2–2.3xa0N) observed throughout most of the task were larger in the CTS group (p ranges 0.035–0.050 for thumb and 0.016–0.050 for index finger). In addition, the applied force of the middle finger in patients with CTS (1xa0±xa00.1xa0N; 95% CI, 1.3–1.4xa0N) versus the control subjects (2xa0±xa00.2xa0N; 95% CI, 1.9–2.0xa0N) during the lowering phase was larger in CTS group (p ranges 0.039–0.050). The force correlations of the thumb-middle finger observed during the lowering phase in the patients with CTS (0.8xa0±xa00.2; 95% CI, 0.6–0.9) versus the control subjects (0.9xa0±xa00.1; 95% CI, 0.8–1.0; pxa0=xa00.04) were weaker in the CTS group. The thumb-little finger during holding in the patients with CTS (0.5xa0±xa00.2; 95% CI, 0.3–0.7) versus the control subjects (0.8xa0±xa00.2; 95% CI, 0.6–0.9; pxa0=xa00.02), and the lowering phase in the patients with CTS (0.6xa0±xa00.2; 95% CI, 0.3–0.8) versus the control subjects (0.9xa0±xa00.1; 95% CI, 0.8–1.0; pxa0=xa00.01) also were weaker. The force variabilities of patients with CTS were greater in the CTS group than in the control subjects: in the thumb ([0.26xa0±xa00.11xa0N, 95% CI, 0.20–0.32xa0N] versus [0.19xa0±xa00.06xa0N; 95% CI, 0.16–0.22xa0N], pxa0=xa00.03); index finger ([0.09xa0±xa00.07xa0N; 95% CI, 0.05–0.13xa0N] versus [0.05xa0±xa00.03xa0N; 95% CI, 0.04–0.07xa0N], pxa0=xa00.03); middle finger ([0.06xa0±xa00.04xa0N; 95% CI, 0.04–0.08xa0N] versus [0.03xa0±xa00.01xa0N; 95% CI, 0.02–0.04xa0N], pxa0=xa00.02), and ring finger ([0.04xa0±xa00.03xa0N; 95% CI, 0.20–0.06xa0N] versus [0.02xa0±xa00.01xa0N; 95% CI, 0.02–0.02xa0N], pxa0=xa00.01).ConclusionsPatients with CTS grasped with greater digit force associated with weaker correlation and higher variability on specific digits in different task demands. These altered patterns in daily grasping may lead to secondary problems, which will need to be assessed in future studies with this model to see if they are reversible in patients undergoing carpal tunnel release.Clinical RelevanceThe current results helped to identify altered patterns of grasping force during simulated daily function in patients with CTS and to provide the clinician with potential information that might help guide the rehabilitation of grasp in these patients.

Reactive oxygen species are required for zoledronic acid-induced apoptosis in osteoclast precursors and mature osteoclast-like cells

Inhibiting osteoclasts and osteoclast precursors to reduce bone resorption is an important strategy to treat osteoclast-related diseases, such as osteoporosis, inflammatory bone loss, and malignant bone metastasis. However, the mechanism by which apoptosis is induced in the osteoclasts and their precursors are not completely understood. Here, we used nitrogen-containing bisphosphonate zoledronic acid (ZA) to induce cell apoptosis in human and murine osteoclast precursors and mature osteoclast-like cells. Caspase-3-mediated cell apoptosis occurred following the ZA (100u2009μM) treatment. Reactive oxygen species (ROS) were also generated in a time-dependent manner. Following knock-down of the p47phox expression, which is required for ROS activation, or co-treatment with the ROS inhibitor, N-acetyl-L-cysteine, ZA-induced apoptosis was significantly suppressed in both osteoclast precursors and mature osteoclast-like cells. The ROS-activated mitogen-activated protein kinases pathways did not trigger cell apoptosis. However, a ROS-regulated Mcl-1 decrease simultaneously with glycogen synthase kinase (GSK)-3β promoted cell apoptosis. These findings show that ZA induces apoptosis in osteoclast precursors and mature osteoclast-like cells by triggering ROS- and GSK-3β-mediated Mcl-1 down-regulation.

Role of Excessive Autophagy Induced by Mechanical Overload in Vein Graft Neointima Formation: Prediction and Prevention

Little is known regarding the interplays between the mechanical and molecular bases for vein graft restenosis. We elucidated the stenosis initiation using a high-frequency ultrasonic (HFU) echogenicity platform and estimated the endothelium yield stress from von-Mises stress computation to predict the damage locations in living rats over time. The venous-arterial transition induced the molecular cascades for autophagy and apoptosis in venous endothelial cells (ECs) to cause neointimal hyperplasia, which correlated with the high echogenicity in HFU images and the large mechanical stress that exceeded the yield strength. The ex vivo perfusion of arterial laminar shear stress to isolated veins further confirmed the correlation. EC damage can be rescued by inhibiting autophagy formation using 3-methyladenine (3-MA). Pretreatment of veins with 3-MA prior to grafting reduced the pathological increases of echogenicity and neointima formation in rats. Therefore, this platform provides non-invasive temporal spatial measurement and prediction of restenosis after venous-arterial transition as well as monitoring the progression of the treatments.