Estimating myofiber cross-sectional area and connective tissue deposition with electrical impedance myography: A study in D2-mdx mice.

INTRODUCTION: Surface electrical impedance myography (sEIM) has the potential for providing information on muscle composition and structure noninvasively. We sought to evaluate its use to predict myofiber size and connective tissue deposition in the D2-mdx model of Duchenne muscular dystrophy (DMD). METHODS: We applied a prediction algorithm, the least absolute shrinkage and selection operator, to select specific EIM measurements obtained with surface and ex vivo EIM data from D2-mdx and wild-type (WT) mice (analyzed together or separately). We assessed myofiber cross-sectional area histologically and hydroxyproline (HP), a surrogate measure for connective tissue content, biochemically. RESULTS: Using WT and D2-mdx impedance values together in the algorithm, sEIM gave average root-mean-square errors (RMSEs) of 26.6% for CSA and 45.8% for HP, which translate into mean errors of ±363 µm2 for a mean CSA of 1365 µm2 and of ±1.44 µg HP/mg muscle for a mean HP content of 3.15 µg HP/mg muscle. Stronger predictions were obtained by analyzing sEIM data from D2-mdx animals alone (RMSEs of 15.3% for CSA and 34.1% for HP content). Predictions made using ex vivo EIM data from D2-mdx animals alone were nearly equivalent to those obtained with sEIM data (RMSE of 16.59% for CSA), and slightly more accurate for HP (RMSE of 26.7%). DISCUSSION: Surface EIM combined with a predictive algorithm can provide estimates of muscle pathology comparable to values obtained using ex vivo EIM, and can be used as a surrogate measure of disease severity and progression and response to therapy.

Effect of storage and preconditioning of healing rat Achilles tendon on structural and mechanical properties.

Tendon tissue storage and preconditioning are often used in biomechanical experiments and whether this generates alterations in tissue properties is essential to know. The effect of storage and preconditioning on dense connective tissues, like tendons, is fairly understood. However, healing tendons are unlike and contain a loose connective tissue. Therefore, we investigated if storage of healing tendons in the fridge or freezer changed the mechanical properties compared to fresh tendons, using a pull-to-failure or a creep test. Tissue morphology and cell viability were also evaluated. Additionally, two preconditioning levels were tested. Rats underwent Achilles tendon transection and were euthanized 12 days postoperatively. Statistical analyzes were done with one-way ANOVA or Student's t-test. Tissue force and stress were unaltered by storage and preconditioning compared to fresh samples, while high preconditioning increased the stiffness and modulus (p ≤ 0.007). Furthermore, both storage conditions did not modify the viscoelastic properties of the healing tendon, but altered transverse area, gap length, and water content. Cell viability was reduced after freezing. In conclusion, preconditioning on healing tissues can introduce mechanical data bias when having extensive tissue strength diversity. Storage can be used before biomechanical testing if structural properties are measured on the day of testing.

Subsynovial connective tissue development in the rabbit carpal tunnel.

The carpal tunnel contains the digital flexor tendons and the median nerve, which are embedded in a unique network of fibrovascular interconnected subsynovial connective tissue (SSCT). Fibrous hypertrophy of the SSCT and subsequent adaptations in mechanical response are found in patients with carpal tunnel syndrome (CTS), but not much is known about the development of the SSCT. This observational study describes the morphological development of SSCT using histology and ultramicroscopy in an animal model at four time points between late-term fetuses through adulthood. A transition is seen between 3 days and 6 weeks post-partum from a dense solid SSCT matrix to a complex multilayered structure connected with collagenous fibrils. These preliminary data show a developmental pattern that matches an adaptive response of the SSCT to loading and motion. Understanding the anatomical development aids in recognizing the pathophysiology of CTS and supports research on new therapeutic approaches.

Does a staged treatment of high energy tibial plateau fractures affect functional results and bony union? A case series.

PURPOSE: Tibial plateau fracture (TPF) is a devastating injury as it shatters lower articular surface of the largest joint. Apart from bony injury, TPF can lead to great soft tissue envelope compromise which affects the treatment plan and outcome. In the present study, clinical results were assessed in cases of high energy TPFs treated in staged manner. METHODS: Twenty-three (20 males and 3 females) patients of high energy communited TPFs (Schatzker type V and VI) were consecutively treated.1 All the patient had compromise of overlying skin conditions. They were all successively scheduled for staged treatment plan which comprised of application of bridging knee external fixator on the first day of admission and definitive internal fixation after skin and soft tissue overlying the fracture were healed. Schatzker type I, II, III and IV were excluded from the study. Primary survey was done and patient who had head injury, chest and abdominal injury, pelvic injury and contralateral limb injury and open fractures were excluded from the study. The patients were also evaluated in terms of wound complications, axial and rotary alignment of limb, fixation failure, articular congruity and range of motion of the knees and post injury employment. Statistical analysis was done using SPSS software. RESULTS: Maximum follow-up period was 13 months. All the fractures were united at final follow-up. Clinical evaluation was done with the Tegner Lysholm knee scoring scale.2 Excellent results were found in 78% cases and good and fair results in 22% cases. There was significant correlation between range of motion and the Tegner Lysholm knee score (p < 0.001, Pearson correlation coefficient = 0.741). The correlation between the score and the radiographical union duration was significant (p = 0.006, Pearson correlation coefficient = -0.554). CONCLUSION: A staged treatment plan allows healing of soft tissue envelope, with avoidance of dreadful complications such as compartment syndrome and chronic infection. In addition, a staged treatment strategy does not hamper the fracture reduction, bony union and the functional results.

Diagnostics of Hereditary Connective Tissue Disorders by Genetic Next-Generation Sequencing.

Aims: This quality analysis study was designed to review the indications, reports, and clinical consequences of 438 diagnostic next-generation sequencing (NGS) gene panel analyses for hereditary connective tissue disorders (HCTD). Methods: Molecular analyses were retrieved from laboratory databases and patient records, and compared to the clinical information in the requisition and classified according to the Human Phenotype Ontology. Results: In 123 of 438 NGS analyses, 156 sequence variants were reported in 33 of 54 genes analyzed. NGS analyses and, in some cases, postanalytic assessment resulted in identification of pathogenic variants in 40 (9%) of patients, and variants of uncertain significance were identified in 83 (19%) of cases analyzed. While cardiovascular abnormalities were the most common phenotype noted in the requisitions, no specific organ system could be identified in which the reported symptoms provided an actionable indication for the analysis. Certain health issues recorded in the patients' records were found to be frequently left out of requisitions. Conclusions: The interpretation of genetic sequence variants continues to be a significant challenge in HCTD. Although not associated with the highest diagnostic yield, cardiovascular disease and family history may be suitable indications for NGS due to the clinical consequences of the identification of a known or likely causative sequence variant for a vascular HCTD in patients and relatives.

Diagnóstico de esclerose sistêmica em pacientes com hipertensão pulmonar inicialmente considerada idiopática / Diagnosis of systemic sclerosis in patients with pulmonary hypertension initially considered idiopathic

Introdução: A Hipertensão Arterial Pulmonar está associada a uma ampla gama de doenças, sendo comum nas doenças do tecido conjuntivo. Porém, um dos maiores desafios diagnósticos em relação à Hipertensão Arterial Pulmonar inclui doenças do tecido conjuntivo clinicamente não identificadas ou tardiamente evidenciadas, principalmente Esclerose Sistêmica. Objetivos: Relatar casos de Hipertensão Arterial Pulmonar secundária à Esclerose Sistêmica que inicialmente foi classificada como Idiopática. Materiais e métodos: Estudo observacional analítico transversal no qual sete pacientes com diagnóstico de Hipertensão Arterial Pulmonar Idiopática foram avaliados quanto ao quadro clínico, exame físico, pesquisa de autoanticorpos e capilaroscopia periungueal na busca de critérios que os classificassem como Esclerose Sistêmica. Resultados: Todos os pacientes preencheram os Critérios Classificatórios para Esclerose Sistêmica ACR/EULAR 2013, sendo que Fenômeno de Raynaud, telangiectasias e positividade de autoanticorpos estiveram presentes em 100% dos casos. A maioria dos pacientes apresentava Esclerose Sistêmica forma cutânea limitada. Conclusões: A determinação do diagnóstico de Hipertensão Arterial Pulmonar secundária à Esclerose Sistêmica é fundamental, pois tais pacientes têm menor sobrevida quando comparados aos casos Idiopáticos. A presença de Fenômeno de Raynaud tem grande relevância no diagnóstico dos pacientes com Hipertensão Arterial Pulmonar associada à Esclerose Sistêmica.

Introduction: Pulmonary Arterial Hypertension is associated with a wide range of diseases. It is common in connective tissue diseases. However, one of the major diagnostic challenges in relation to Pulmonary Arterial Hypertension includes clinically unidentified or late-onset diseases of the connective tissue, mainly Systemic Sclerosis. Objectives: To report cases of Pulmonary Arterial Hypertension secondary to Systemic Sclerosis, which was initially classified as Idiopathic. Patients and methods: We carried out a cross-sectional observational study in which seven patients with a diagnosis of Idiopathic Pulmonary Arterial Hypertension was evaluated for clinical examination, physical examination, autoantibody and nailfold capillaroscopy examination in search of criteria that reclassified them as Systemic Sclerosis. Results: All patients met the Classification Criteria for Systemic Sclerosis ACR/EULAR 2013, with Raynaud's Phenomenon, telangiectasia and autoantibody positivity being present in 100% of the cases. The majority of patients presented limited cutaneous Systemic Sclerosis. Conclusions: The diagnosis of Pulmonary Arterial Hypertension secondary to Systemic Sclerosis is essential, considering the association with lower survival when compared to the idiopathic cases. The presence of Raynaud's Phenomenon has an important relevance in the diagnosis of patients with Pulmonary Arterial Hypertension associated with Systemic Sclerosis.

Ehlers-Danlos syndrome and other heritable connective tissue disorders that impact pregnancies can be detected using next-generation DNA sequencing.

Ehlers-Danlos syndromes (EDS) are a genetically heterogeneous group of inherited connective tissue disorders classified into six major types with a variable collection of findings and different inheritance patterns. Although complications occur in about one-half of pregnancies in women with EDS, the majority can have a good outcome if managed appropriately. Classic EDS is characterized by joint hypermobility, loose skin with poor healing and easy bruising, musculoskeletal problems with chronic pain and at risk for pre-term delivery. In addition, the vascular form of EDS can have cardiac anomalies, aneurysms, gastrointestinal perforation and uterine rupture during pregnancy. Due to overlapping features among the connective tissue disorders, it is difficult to categorize the disorder into specific types without detailed genetic testing which is now available through advanced genomic technology using next-generation DNA sequencing, searching genomic databases and bioinformatics approach. Therefore, obstetrical complications are variable but relate to specific connective tissue disorders requiring an exact diagnosis. There are several dozen genes causing connective tissue disorders that are currently available for testing using next-generation sequencing and bioinformatics to provide pertinent care, treatment and surveillance of the affected pregnant woman but also for her at-risk fetus related to the specific heritable condition.

Structural features of eyelid connective tissue in patients with primary open-angle glaucoma.

PURPOSE: To study the connective tissue (CT) structure of upper eyelid skin of primary open-angle glaucoma (POAG) patients. PATIENTS AND METHODS: Forty-seven patients aged 47-91 expecting blepharoplasty formed 3 groups: group 1 [16 subjects without POAG, median age 55 years (interquartile range 54-55.5)], group 2 [12 subjects without POAG, median age 73 (72-76.5)], and group 3 [(19 subjects with POAG, median age 74 (70-80.5)]. Age differences between groups 1 and 2 and groups 1 and 3 are significant (p < 0.05). Thermodynamic parameters of skin samples taken during blepharoplasty: Endothermic peak ([Formula: see text], °C) and denaturation enthalpy ([Formula: see text], J/g of dry weight) were determined using differential scanning calorimetry. RESULTS: [Formula: see text] and [Formula: see text] in groups 1-3 were, respectively, 8.41 (7.42-10.25) and 66.55 (59.9-66.7); 7.10 (5.76-10.17) and 67.35 (67.0-68.03); 11.40 (9.0-14.9) and 67.70 (67.05-68.45). [Formula: see text] differences between groups 1 and 2 are significant (p < 0.05), and Spearman's correlation between the age and [Formula: see text] is direct, medium (R = 0.638) and significant. [Formula: see text] in group 3 is significantly higher than in group 2. [Formula: see text] and [Formula: see text] in patients without POAG (groups 1 and 2) and those with POAG (group 3) are, respectively, 7.79 (6.9-10.17) and 66.6 (61.2-67,3); 11.40 (9.0-14.9); 67.7 (67.05-68.45); the respective differences are significant. CONCLUSION: Patients without POAG show a significant increase in [Formula: see text] with age, while [Formula: see text] slightly decreases. In POAG, [Formula: see text] is significantly higher and [Formula: see text] tends to grow, which may indicate structural changes in eyelid CT (collagen accumulation and cross-linking level rise). Since the upper lid is unaffected by increasing IOP directly, the changes may be viewed as manifestations of systemic CT pathology.

Fragile X syndrome and connective tissue dysregulation.

Fragile X syndrome (FXS) is the most common cause of inherited intellectual disabilities and autism spectrum disorders, and it is an X-linked disorder in which there is a deficiency of the fragile X mental retardation 1 protein. This protein is crucial in regulating translation of mRNAs related to dendritic maturation and cognitive development. The phenotype of FXS is characterized by neurobehavioral alterations, social deficits, communication difficulties, and findings which suggest an alteration of connective tissue, especially in the ligaments and muscles, cardiovascular system and genitourinary system. Connective tissue connects and supports all other tissues of the body and is composed of cells and extracellular matrix (ECM). Several proteins have been involved in the connective tissue abnormalities associated with the FXS, such as matrix metalloproteinase 9, which plays an important role in the homeostasis of the ECM, being a potential therapeutic target for certain tetracycline antibiotics that have shown beneficial effects in FXS. Here, we review connective tissue problems described in FXS.

The Intervertebral Disc: Physiology and Pathology of a Brittle Joint.

BACKGROUND: Intervertebral disc (ID) degeneration represents the number one cause for outpatient clinic visits worldwide. Mechanisms are discussed but not yet clearly established. Consequently, back pain management is commonly limited to symptomatic treatment therapies. OBJECTIVES: The aim of this review is to evaluate major progress and to unravel the biology and pathology of ID discogenic pain. METHODS: The design of this study is a systematic review. A literature search was conducted using Medline, EMBASE, and Google Scholar databases, with no time constraints to locate relevant literature. Significant articles (literature reviews, therapeutic essays, clinical-human-research studies, animal research, and laboratory research) on the intervertebral disc were identified and reviewed. The exclusion criteria were the following: case reports and clinical studies with <10 patients. RESULTS: Through a dense review of the literature, the ID is deciphered and described as a fragile anatomic entity. For this systematic review, 132 studies were identified and 79 were retained. The main deterioration and alteration mechanisms that lead to the programmed death of the ID are summarized. In addition, the large variety of biological therapies that override surgical treatment are determined. CONCLUSIONS: The degeneration mechanisms of the ID are well defined and decrypted. Although therapies have progressed, none has been effective. The regeneration of the ID remains highly challenging because of the complexity of its natural composition, microstructure, and mechanical properties.

Effects of Connective Tissue Massage on Pain in Primiparous Women After Cesarean Birth.

OBJECTIVE: To evaluate the efficacy of connective tissue massage to reduce postoperative pain in primiparous women on Postoperative Day 1 after unplanned cesarean birth. DESIGN: A randomized controlled trial with three groups: intervention (Group 1), control or standard care (Group 2), and individualized attention (Group 3). SETTING: Family/newborn units of a large teaching hospital in the Northeastern United States. PARTICIPANTS: A total of 165 women who experienced unplanned cesarean births of singleton newborns at term gestation. METHODS: Participants were randomized to three groups: those in Group 1 received a 20-minute massage, those in Group 2 received the usual standard of care, and those in Group 3 received 20 minutes of individualized attention. On Postoperative Day 1, participants completed questionnaires to measure overall pain, stress, and relaxation at Time 1 and again 60 minutes later. Daily numeric pain ratings and medication consumption data were retrieved from the electronic health care records. Latent growth modeling and analysis of variance were used to analyze data, as appropriate. RESULTS: Participants in Group 1 had increased relaxation (p < .001), decreased pain (p < .001), decreased stress (p < .001), and decreased opioid use on Day 1 (p = .031) and Day 2 (p = .006) of the hospital stay after the intervention compared with the other groups. Additionally, opioid use in Group 1 decreased linearly, whereas the control groups had a nonlinear pattern of change. CONCLUSION: Using massage therapy during postoperative hospitalization improved relaxation and decreased pain, stress, and opioid use in this sample of women after unplanned cesarean births.

The biomechanics of subsynovial connective tissue in health and its role in carpal tunnel syndrome.

Carpal Tunnel Syndrome (CTS) is the most common surgically treated problem in the hand. Aside from the neuropathy itself, the most common findings are fibrosis of the subsynovial connective tissue (SSCT) and increased intra carpal tunnel pressure. Normally, the SSCT is a multilayer tissue interspersed among the carpal tendons and nerve. As the tendons move, successive SSCT layers are recruited, forming a gliding unit and providing a limit to differential movement. Exceeding this limit, damages the SSCT as has been shown in both cadavers and animal models. This damage leads to a non-inflammatory response with progressive fibrosis and nerve ischemia leaving the SSCT more susceptible to injury. Although the direct consequences for patients are not fully understood, ultrasound research shows that this fibrosis restricts median nerve displacement during tendon loading. This article aims to provide insights into the mechanical properties of SSCT described so far and place it in the context of CTS pathophysiology. A theoretical damage model concerning the SSCT is proposed showing a chain of events and vicious cycles that could lead to the nerve compression as it is found in CTS. Although not complete, this model could explain the pathophysiological pathway of idiopathic CTS.

The effects of connective tissue manipulation and Kinesio Taping on chronic constipation in children with cerebral palsy: a randomized controlled trial.

PURPOSE: The aim of this study was to investigate the effects of connective tissue manipulation (CTM) and Kinesio Taping® (KT) on constipation and quality of life in children with cerebral palsy (CP). METHOD: This study was designed as a randomized controlled trial. Forty children diagnosed with chronic constipation based on Rome III criteria were randomly assigned to CTM group [6 females, 7 males; 8 y 6 mo (SD = 3y 4 mo)], KT group [7 female, 7 male; 8y 7 mo (SD =3y 5 mo)] or control group [6 female, 7 male; 8y 3 mo (SD = 3y 6 mo)]. All patients were assessed with 7-day bowel diaries, Bristol Stool Form Scale (BSFS), Visual Analog Scale (VAS), and Pediatric Quality of Life Inventory (PEDsQL). Kruskal-Wallis, Wilcoxon's signed-rank, and Mann-Whitney U tests were used to determine intra-group and inter-group differences. The level of significance was p < 0.05. RESULTS: Among the CTM, KT, and control groups, there were statistically significant differences regarding the changes in defecation frequency (2.46, 3.00, 0.30, ES 1.16, p < 0.001), duration of defecation (5.07, 5.35, 0.15, ES 2.37, p = 0.003), BSFS (1.84, 2.14, 0.07, ES 0.91, p < 0.001), VAS (4.83, 3.87, 0.23, ES 1.98, p < 0.001), and PEDsQL total scores (7, 14, 8.36, -0.85, ES 4.08, p < 0.001). CONCLUSIONS: This study revealed that CTM and KT seem equally effective physiotherapy approaches for the treatment of pediatric constipation and these approaches may be added to bowel rehabilitation program. Implications for rehabilitation CTM and KT have similar effectiveness in alleviating the constipation-related symptoms and improving quality of life in children with CP. CTM and KT can be integrated into bowel rehabilitation programs. Considering the characteristics of patients, these treatment options can be used as an alternative of each other by physiotherapists.

Histomorphological and biochemical properties of plantar soft tissue in diabetes.

BACKGROUND: Diabetes results in pathophysiological changes, leading to tissue that is unable to withstand and adapt to the same loads, resulting in breakdown. Certain locations are more susceptible to breakdown, yet differences between locations are largely not well understood. The authors performed a histological and biochemical analysis of isolated plantar adipose tissue at six relevant locations. METHODS: Tissue from six plantar locations (hallux, first, third and fifth metatarsal heads, lateral midfoot and calcaneus) was taken from fresh cadaveric feet of older diabetic and older non-diabetic intact donors. Histomorphological and biochemical analysis of isolated plantar tissue from both diabetic and non-diabetic feet at six relevant locations was performed. RESULTS: The main differences found between diabetic and non-diabetic tissue were in the thickness of the septal walls and the elastin content. Diabetic tissue had significantly thicker septal walls and an increased elastin concentration. When comparing the calcaneus to other locations, although there were no differences found in the thickness of the septal walls of diabetic tissue, elastin content was lower in the calcaneous tissue compared to the non-calcaneus sites. CONCLUSIONS: Modifications in the structural and biochemical properties could translate to changes in the mechanical properties. This information could lead to an understanding of how the structural and biochemical changes result in an increase in susceptibility of tissue to breakdown with load at the different locations of the foot.

The contribution of a directional preference of stiffness to the efficacy of prophylactic sacral dressings in protecting healthy and diabetic tissues from pressure injury: computational modelling studies.

The sacral region is the most common site for pressure injuries (PIs) associated with lying in bed, and such sacral PIs often commence as deep tissue injuries (DTIs) that later present as open wounds. In complex patients, diabetes is common. Because, among other factors, diabetes affects connective tissue stiffness properties, making these tissues less able to dissipate mechanical loads through physiological deformations, diabetes is an additional biomechanical risk factor for PIs and DTIs. A preventive measure with established successful clinical outcomes is the use of sacral prophylactic dressings. The objective of this study has been to expand our previous work regarding the modes of action and biomechanical efficacy of prophylactic dressings in protecting the soft tissues adjacent to the sacrum by specifically examining the role of a directional stiffness preference (anisotropy) of the dressing while further accounting for diabetic tissue conditions. Multiple three-dimensional anatomically detailed finite element (FE) model variants representing diabetic tissue conditions were used, and tissue loading state data were compared with healthy tissue simulations. We specifically compared soft tissue exposures to elevated internal shear stresses and strain energy densities (SED) near the sacrum during supine weight bearing on a standard (foam) hospital mattress without a dressing, with a prophylactic dressing lacking directional stiffness preferences and with an anisotropic dressing. Our results have clearly shown that an anisotropic dressing design reduces the peak tissue stresses and exposure to sustained tissue deformations in both healthy and diabetic cases. The present study provides additional important insights regarding the optimal structural and material design of prophylactic dressings, which in turn, informs clinicians and decision makers regarding beneficial features.

Biallelic COL3A1 mutations result in a clinical spectrum of specific structural brain anomalies and connective tissue abnormalities.

Vascular Ehlers-Danlos syndrome (type IV) is an autosomal dominant disorder caused by heterozygous variants of COL3A1. We identified biallelic COL3A1 variants in two unrelated families. In a 3-year-old female with developmental delay the nonsense variant c.1282C>T, p.(Arg428*) was detected in combination the c.2057delC, p.(Pro686Leufs*105) frame shift variant. Both compound heterozygous variants were novel. This patient was born with bilateral clubfoot, joint laxity, and dysmorphic facial features. At the age of 2 years she developed an aneurysmal brain hemorrhage. Cerebral MRI showed a peculiar pattern of profound cerebral abnormalities including bilateral frontoparietal polymicrogyria of the cobblestone variant. In the second family, the two affected siblings were homozygous for the missense variant c.145C

Effect of MELT method on thoracolumbar connective tissue: The full study.

Altered connective tissue structure has been identified in adults with chronic low back pain (LBP). A self-care treatment for managing LBP is the MELT method. The MELT method is a hands-off, self-treatment that is said to alleviate chronic pain, release tension and restore mobility, utilizing specialized soft treatments balls, soft body roller and techniques mimicking manual therapy. The objective of this study was to determine whether thickness of thoracolumbar connective tissue and biomechanical and viscoelastic properties of myofascial tissue in the low back region change in subjects with chronic LBP as a result of MELT. This study was designed using a quasi experimental pre-post- design that analyzed data from subjects who performed MELT. Using ultrasound imaging and an algorithm developed in MATLAB, thickness of thoracolumbar connective tissue was analyzed in 22 subjects. A hand-held digital palpation device, called the MyotonPRO, was used to assess biomechanical properties such as stiffness, elasticity, tone and mechanical stress relaxation time of the thoracolumbar myofascial tissue. A forward bending test assessing flexibility and pain scale was added to see if MELT affected subjects with chronic LBP. A significant decrease in connective tissue thickness and pain was observed in participants. Significant increase in flexibility was also recorded.

Altered mechanical interaction between rat plantar flexors due to changes in intermuscular connectivity.

Connective tissue formation following muscle injury and remedial surgery may involve changes in the stiffness and configuration of the connective tissues linking adjacent muscles. We investigated changes in mechanical interaction of muscles by implanting either a tissue-integrating mesh (n = 8) or an adhesion barrier (n = 8) to respectively increase or decrease the intermuscular connectivity between soleus muscle (SO) and the lateral gastrocnemius and plantaris complex (LG+PL) of the rat. As a measure of mechanical interaction, changes in SO tendon forces and proximal-distal LG+PL force differences in response to lengthening LG+PL proximally were assessed 1 and 2 weeks post-surgery. The extent of mechanical interaction was doubled 1 week post-implantation of the tissue-integrating mesh compared to an unaffected compartment (n = 8), and was more than four times higher 2 weeks post-surgery. This was found only for maximally activated muscles, but not when passive. Implanting the adhesion barrier did not result in a reduction of the mechanical interaction between these muscles. Our findings indicate that the ratio of force transmitted via myofascial, rather than myotendinous pathways, can increase substantially when the connectivity between muscles is enhanced. This improves our understanding of the consequences of connective tissue formation at the muscle boundary on skeletal muscle function.

Connective tissue regeneration in skeletal muscle after eccentric contraction-induced injury.

Human skeletal muscle has the potential to regenerate completely after injury induced under controlled experimental conditions. The events inside the myofibers as they undergo necrosis, followed closely by satellite cell-mediated myogenesis, have been mapped in detail. Much less is known about the adaptation throughout this process of both the connective tissue structures surrounding the myofibers and the fibroblasts, the cells responsible for synthesizing this connective tissue. However, the few studies investigating muscle connective tissue remodeling demonstrate a strong response that appears to be sustained for a long time after the major myofiber responses have subsided. While the use of electrical stimulation to induce eccentric contractions vs. voluntary eccentric contractions appears to lead to a greater extent of myofiber necrosis and regenerative response, this difference is not apparent when the muscle connective tissue responses are compared, although further work is required to confirm this. Pharmacological agents (growth hormone and angiotensin II type I receptor blockers) are considered in the context of accelerating the muscle connective tissue adaptation to loading. Cautioning against this, however, is the association between muscle matrix protein remodeling and protection against reinjury, which suggests that a (so far undefined) period of vulnerability to reinjury may exist during the remodeling phases. The role of individual muscle matrix components and their spatial interaction during adaptation to eccentric contractions is an unexplored field in human skeletal muscle and may provide insight into the optimal timing of rest vs. return to activity after muscle injury.

Relative displacement of the tendon and subsynovial connective tissue using ultrasound captures different phenomena than mechanical tendon shear.

The most common finding in carpal tunnel syndrome is fibrosis and thickening of the subsynovial connective tissue (SSCT). While the SSCT mediates tendon gliding in the carpal tunnel, this histopathology suggests excessive shear forces are involved in injury development. Ultrasound is often used to quantify relative motion between the finger flexor tendons and SSCT as an indirect measure of "shear-strain"; however, the underlying mechanical implications of using ultrasound are not well understood. The middle flexor digitorum superficialis (FDS) tendon of 8 cadavers was moved in a combination of 2 wrist postures (neutral, flexed), 3 velocities (5, 10, 15cm/s), and 3 forces (10, 20, 30N) to assess ultrasound-based FDS-SSCT relative displacement while simultaneously quantifying tendon frictional work in the carpal tunnel. We found independent velocity effects for both constructs (relative displacement, ηp2=0.862, p<0.05; frictional work, ηp2=0.937, p<0.05), indicating ultrasound captured viscous gliding resistance owing to the gel-like inter-fibrillar matrix of the SSCT. FDS-SSCT relative displacement also increased independently in a flexed wrist posture (p=0.010) and with greater tendon force (p=0.036), likely representing strain dependant changes with tendon position. Alternatively, we found a significant posture×force interaction on tendon frictional work (p<0.01), due to, in part, greater surface friction against the transverse carpal ligament with a flexed wrist and high force. While ultrasound provided a different interpretation compared to direct measurement of mechanical shear, FDS-SSCT relative displacement successfully localized viscoelastic shear-strain, which may help elucidate the role of hand motion in SSCT pathology and CTS.