Stretch-Induced Healing of Injured Muscles Is Associated With Myogenesis and Decreased Fibrosis.

BACKGROUND: Alghouth therapeutic stretching exercise has been applied to accelerate the healing of injured skeletal muscles, mechanisms behind the mechanical stretch-induced muscle recovery remain unclear. PURPOSE: To examine stretch-associated antifibrotic and myogenic responses in injured muscles and to evaluate the feasibility of the ultrasonic Nakagami parametric index (NPI) in assessing muscle morphology during recovery. STUDY DESIGN: Controlled laboratory study. METHODS: Skeletal muscle fibrosis was induced in the right hind legs of 48 rats by making a posterior transverse incision in the gastrocnemius muscle; the left hind legs remained intact as a comparative normal reference. After surgery, the 48 rats were randomly divided into the stretch (S) and control (C) groups. The S group received stretching interventions on the injured hind leg from week 3 to week 7 after surgery, while the C group did not receive stretching throughout the study period. The muscle fibrosis percentage and the ultrasonic NPI were examined sequentially after surgery. Relative expressions of myogenesis-related proteins, including myoblast determination protein 1 (MyoD), myogenin, and embryonic myosin heavy chain (MHCemb), were also evaluated during the follow-up. RESULTS: Mean fibrosis percentages in the injured hind leg were approximately 25% at week 3 in both groups, but they were significantly decreased by approximately 20% from week 4 to the end of the follow-up in the S group only (all, P < .05). Upon injury, the NPI values of injured hind legs in both groups dramatically dropped. Within the S group, stretching increased the NPI values of injured hind legs, which approached those of control hind legs at weeks 6 and 7. The highest MyoD, myogenin, and MHCemb levels were observed at week 6 in both groups. The NPI values corresponded to the MyoD expression in the S group during the follow-up. CONCLUSION: Stretching induced a decrease in muscle fibrosis and an increase in myogenesis in injured muscles. The NPI values correspond to the myogenesis process. CLINICAL RELEVANCE: The NPI may be capable of continuously monitoring the injured skeletal muscle morphology during the healing process in clinical settings.

Simple score to predict risk of hepatocellular carcinoma in chronic hepatitis C patients with advanced fibrosis after pegylated interferon and ribavirin therapy.

PURPOSE: Eradication of chronic hepatitis C virus (HCV) after interferon-based therapy and its association with the reduction of risk of hepatocellular carcinoma (HCC) in HCV-infected patients with advanced fibrosis is controversial. The study is aimed to develop a simple scoring model for HCC prediction among advanced fibrotic chronic hepatitis C (CHC) patients after pegylated interferon (pegIFN) and ribavirin (RBV) therapy. PATIENTS AND METHODS: We enrolled 271 biopsy-proven CHC patients with advanced fibrosis between 2003 and 2016, and divided them into non-HCC (n=211) and HCC (n=60) groups. The median observation duration was 6.0 years (range: 0.9-12.6 years). RESULTS: The HCC prevalence after pegIFN and RBV therapy in CHC patients with sustained virologic response (SVR) and without SVR was 14.7% and 32.2%, respectively. Multivariate Cox regression showed age ≥59.5 years old at initiation of therapy (HR: 2.542, 95% CI: 1.390-4.650, P=0.002), pretreatment total bilirubin ≥1.1 mg/dL (HR: 2.630, 95% CI: 1.420-4.871, P=0.002), pretreatment platelet counts <146.5 × 103/µL (HR: 2.751, 95% CI: 1.373-5.511, P=0.004), no achievement of SVR (HR: 2.331, 95% CI: 1.277-4.253, P=0.006), and no diabetes at treatment initiation (HR: 3.085, 95% CI: 1.283-7.418, P=0.012) were significant predictors of HCC development. The scoring model consisted of the five categorical predictors and had an optimal cutoff point of 2.5. The area under receiver operating characteristic (AUROC) of the scoring model was 0.774±0.035 (P<0.001). The sensitivity and specificity of the cutoff value to detect HCC were 81.3% and 57.5%. The 5-year and 10-year cumulative incidence of HCC was 4.9% and 10.0% in patients with simple score ≤2; and 25.9% and 44.6% in patients with simple score ≥3 (P<0.001). CONCLUSION: The simple clinical-guided score has high discriminatory power for HCC prediction in advanced fibrotic CHC patients after pegIFN and RBV therapy.

Longitudinal follow-up of muscle echotexture in infants with congenital muscular torticollis.

Unilateral fibrous contracture of the sternocleidomastoid (SCM) muscle is the major pathophysiology in infants with congenital muscular torticollis (CMT). Physical examination is not always sufficient to detect minimal muscle fibrosis in involved SCM muscles.A prospective study for SCM muscle fibrosis in CMT infants by quantifying echotexture and muscle thickness during the course of treatment is highlighted in the study.Convenience samples of 21 female and 29 male infants with CMT, who were 1 to 12 months old, underwent physiotherapy for at least 3 months and were followed for 4.7 ±â€Š0.4 months. All infants had at least 2 clinical assessments and ultrasonographic examinations for bilateral SCM muscles during follow-up. The K value, derived from the difference in echo intensities between the involved and uninvolved SCM muscles on longitudinal sonograms, was used to represent the severity of muscle fibrosis. Bilateral SCM muscle thickness and ratio of involved to uninvolved muscle thickness (Ratio I/U) were obtained simultaneously. Clinical outcome was also recorded.No subjects underwent surgical intervention during follow-up. The K value decreased from 6.85 ±â€Š0.58 to 1.30 ±â€Š0.36 at the end of follow-up (P < 0.001), which reflected the decrease of muscle fibrosis. The Ratio I/U decreased from 1.11 ±â€Š0.04 to 0.97 ±â€Š0.02 during treatment, which was possibly related to the increased uninvolved SCM muscle thickness.In conclusion, echotexture is an efficient indicator for reflecting a wide degree of muscle fibrosis in infants with CMT and is informative during the treatment course.

Quantification of skeletal muscle fibrosis at different healing stages using sonography: a morphologic and histologic study in an animal model.

OBJECTIVES: This study attempted to quantify the degree of muscle fibrosis on sonograms of injured gastrocnemius muscles at different healing stages in a rat model. Correlations between the quantifications and histologic assessments of the injured muscles were also determined. METHODS: Sonograms and histologic findings of gastrocnemius muscle fibrosis were obtained during the second, third, and fourth weeks after surgically induced lesions in the right gastrocnemius muscles of 15 Wistar rats. The echo intensity, reflecting the degree of brightness on a sonogram, was divided into 256 gray levels instead of decibels. The mean echo intensity of each pixel in the region of interest was calculated as a summation of the echo intensities in all pixels divided by the pixel numbers in the region. To control individual variations among the rats, we calculated a K value, defined as the difference in the mean echo intensity between normal and affected muscles. RESULTS: Significant correlations (r > 0.7; P < .05) between mean echo intensity and K values and the fibrous tissue percentage were identified. The mean echo intensity in the injured gastrocnemius muscles was significantly (P = .029) greater than that in the normal muscles 3 weeks after injury. In histologic assessments, muscle fibrosis was most prominent 3 weeks after injury. However, the differences in fibrosis at different healing stages were not significant. CONCLUSIONS: Mean echo intensity and K values can reflect the extent of fibrosis in affected muscles and may be valuable for quantifying muscle fibrosis in clinical practice.

Influence of magnetic knee wraps on joint proprioception in individuals with osteoarthritis: a randomized controlled pilot trial.

OBJECTIVE: To determine the effects of magnetic knee wraps (MKWs) on joint position sense (JPS) in individuals with mild-to-moderate knee osteoarthritis. DESIGN: Randomized, double-blind, placebo-controlled pilot trial. SETTING: Rehabilitation clinic of a tertiary hospital. SUBJECTS: Fifty volunteers with mild-to-moderate knee osteoarthritis participated and 33 (66%) completed the trial; only one (2%) withdrew due to study-related adverse effects. INTERVENTIONS: Knee wraps with a static magnetic field (35 mT) were compared with control knee wraps for 12 weeks. MAIN MEASURES: The main outcome measure was JPS at first, fourth, and twelfth week while applying of the knee wrap, quantified as the ability to replicate target knee joint angles. The secondary outcome was the Comprehensive Osteoarthritis Test (COAT) total score. RESULTS: In the intention-to-treat analysis with an alpha-level of 0.05, 12-week application of the MKWs did not significantly reduce the mean absolute error (MAE) of JPS (n = 18; P = 0.627); contrarily, the MAE was found to decrease significantly after wearing the sham MKWs (n = 20; P = 0.01). The COAT total score gradually improved in both groups (P < 0.05). When comparing the improvement of MAE and COAT total score at each follow-up between two groups, no significant differences were found; the maximal difference in the improvement of MAE between two groups was noted at week 12 (mean difference: 1.2°; 95% confidence interval -0.4 to 2.9; P = 0.144). In the per-protocol analysis, the study group showed better improvement in the COAT total score at week 12 (P = 0.033). CONCLUSION: The 35-mT MKWs could not significantly influence knee JPS in individuals with mild-to-moderate knee osteoarthritis.

Relationship between unstimulated salivary flow rate and saliva composition of healthy children in Taiwan.

BACKGROUND: Saliva is one of the most important factors in regulating oral health, with flow rate and composition changing throughout development and during disease. In view of the shortage of data, the present study aimed to shed light on the relationship between unstimulated salivary flow rate and saliva composition of healthy children in Taiwan. METHODS: Forty-four normal, healthy children from 3-14 years of age were divided into three age groups: pre-school, elementary school and junior-high school. All participants received salivary flow rate, pH and saliva composition analysis under unstimulated conditions. One-way ANOVA and Pearson's correlation were used. Statistical significance was set at p < 0.05. RESULTS: Our results suggest that, under unstimulated conditions, the salivary flow rate of the elementary school group was greater than that of the pre-school group (p < 0.05). No difference in pH was found among the three groups. Intergroup salivary calcium, phosphorus and amylase did not reach statistical difference. As the flow rate increased, the pH increased (r = 0.364, p < 0.05) but the protein level decreased (r = -0.473, p < 0.05). In addition, salivary protein was positively correlated to age (r = 0.479, p < 0.05) and negatively correlated to pH (r = -0.361, p < 0.01). CONCLUSION: Age-related increase in the unstimulated salivary flow rate of pre-school and elementary school groups was noted. As the flow rate increased, the pH increased but the protein level decreased. The information obtained may serve as reference values for the growing interest in saliva as a diagnostic tool, especially monitoring those with neurological or oral motor dysfunction.

Altered energy dissipation ratio of the plantar soft tissues under the metatarsal heads in patients with type 2 diabetes mellitus: a pilot study.

BACKGROUND: Foot ulceration occurs frequently on the plantar aspect of the metatarsal head region, in which the altered foot biomechanics has been mentioned as a contributor. This study attempted to compare the energy dissipation in the plantar soft tissue under the metatarsal head between type 2 diabetic patients and age-matched healthy subjects in vivo. METHODS: The plantar soft tissues under the metatarsal heads in each left foot of 13 patients with type 2 diabetes mellitus and eight age-matched healthy subjects were measured with a loading-unloading device. The system comprised a 5-12 MHz linear-array ultrasound transducer and a load cell that operated at an impact velocity of about 5 cm/s. The stress-strain plot was derived by simultaneously recording the stress response and tissue deformation during a loading-unloading cycle. The energy dissipation ratio in all subjects could then be analyzed. FINDINGS: Although only the plantar soft tissue under the fourth metatarsal head in the diabetic patients endured significantly greater energy (P=0.035) than the healthy subjects, a trend of an increased energy dissipation ratio for the metatarsals in the diabetic patients was observed. INTERPRETATION: The plantar soft tissue under the metatarsal head in the diabetic patients endures high dissipated energy during a simulating walking status in the study. The increased dissipated energy in the tissue may be responsible for the tissue breakdown in the diabetic patients.

Ultrasound stimulation of types I and III collagen expression of tendon cell and upregulation of transforming growth factor beta.

Traumatic tendon injuries are commonly treated with ultrasound. However, previous research has not examined the molecular mechanism of this therapeutic effect on collagen synthesis of tendon cells. This study was designed to determine the effect of ultrasound on the expression of type I and type III collagen of tendon cells intrinsic to rat Achilles tendon. Whether a correlation exits between this effect and the expression of transforming growth factor beta (TGF-beta), which enhances collagen synthesis, was also investigated. Tendon cells after ultrasound treatment and protein expression of types I and III collagen were determined by immunocytochemistry. The mRNA expressions of alpha1(I) procollagen, alpha1(III) procollagen, and TGF-beta were determined by reverse transcription-polymerase chain reaction (RT-PCR). Furthermore, the concentration of TGF-beta in conditioned medium was evaluated by enzyme-linked immunosorbent assay (ELISA). Immunocytochemical staining revealed that ultrasound-treated tendon cells were stained more strongly for types I and III collagen than were control cells. Upregulation of procollagen alpha1(I) gene, procollagen alpha1(III) gene, and TGF-beta at the mRNA level was confirmed by RT-PCR. A dose-dependent increase in the concentration of TGF-beta in conditioned medium obtained from cells treated with ultrasound was demonstrated by ELISA assay (p = 0.043). In conclusion, ultrasound stimulates the expression of type I and type III collagen in a process that is likely mediated by the upregulation of TGF-beta.