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.

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.

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.

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.

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

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.

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.

Aberrant immune response with consequent vascular and connective tissue remodeling - causal to scleroderma and associated syndromes such as Raynaud phenomenon and other fibrosing syndromes?

PURPOSE OF REVIEW: Scleroderma and other autoimmune-induced connective tissue diseases are characterized by dysfunctions in the immune system, connective tissue and the vasculature. We are focusing on systemic sclerosis (SSc)-associated pulmonary hypertension, which remains a leading cause of death with only a 50-60% of 2-year survival rate. RECENT FINDINGS: Much research and translational efforts have been directed at understanding the immune response that causes SSc and the networked interactions with the connective tissue and the vasculature. One of the unexpected findings was that in some cases the pathogenic immune response in SSc resembles the immune response to helminth parasites. During coevolution, means of communication were developed which protect the host from over-colonization with parasites and which protect the parasite from excessive host responses. One explanation for the geographically clustered occurrence of SSc is that environmental exposures combined with genetic predisposition turn on triggers of molecular and cellular modules that were once initiated by parasites. SUMMARY: Future research is needed to further understand the parasite-derived signals that dampen the host response. Therapeutic helminth infection or treatment with parasite-derived response modifiers could be promising new management tools for autoimmune connective tissue diseases.

Psychopathological manifestations of joint hypermobility and joint hypermobility syndrome/ Ehlers-Danlos syndrome, hypermobility type: The link between connective tissue and psychological distress revised.

Psychological distress is a known feature of generalized joint hypermobility (gJHM), as well as of its most common syndromic presentation, namely Ehlers-Danlos syndrome, hypermobility type (a.k.a. joint hypermobility syndrome - JHS/EDS-HT), and significantly contributes to the quality of life of affected individuals. Most published articles dealt with the link between gJHM (or JHS/EDS-HT) and anxiety-related conditions, and a novel generation of studies is emerging aimed at investigating the psychopathologic background of such an association. In this paper, literature review was carried out with a semi-systematic approach spanning the entire spectrum of psychopathological findings in gJHM and JHS/EDS-HT. Interestingly, in addition to the confirmation of a tight link between anxiety and gJHM, preliminary connections with depression, attention deficit (and hyperactivity) disorder, autism spectrum disorders, and obsessive-compulsive personality disorder were also found. Few papers investigated the relationship with schizophrenia with contrasting results. The mind-body connections hypothesized on the basis of available data were discussed with focus on somatotype, presumed psychopathology, and involvement of the extracellular matrix in the central nervous system. The hypothesis of positive Beighton score and alteration of interoceptive/proprioceptive/body awareness as possible endophenotypes in families with symptomatic gJHM or JHS/EDS-HT is also suggested. Concluding remarks addressed the implications of the psychopathological features of gJHM and JHS/EDS-HT in clinical practice.

Effect of a tunnel-structured ß-tricalcium phosphate graft material on periodontal regeneration: a pilot study in a canine one-wall intrabony defect model.

BACKGROUND AND OBJECTIVE: Tissue regeneration is affected by the porosity, chemical properties and geometric structure of graft materials. Regeneration of severe periodontal defects, such as one-wall intrabony defects, is difficult because of reduced tissue support, and bone grafts are commonly used in such cases. In the present study, a tunnel-structured ß-tricalcium phosphate (tunnel ß-TCP) graft material designed to stimulate bone formation was fabricated. The objective of this pilot study was to evaluate the effect of this graft material on periodontal regeneration in one-wall intrabony defects in dogs. MATERIAL AND METHODS: Six male beagle dogs were used in this study. First, the mandibular second and third incisors were extracted. Experimental surgery was performed 12 wk after tooth extraction. Bilateral 4 × 8 mm (width × depth) one-wall intrabony defects were created in the mesial side of the mandibular canines. At the experimental sites, the defects were filled with tunnel ß-TCP, whereas the control defects were left empty. Twelve weeks after surgery, qualitative and quantitative histological analyses were performed. RESULTS: There were no signs of clinical inflammation 12 wk after surgery. Coronal extension indicative of new bone formation was higher at the experimental sites than at the control sites, although the differences between both the sites in the newly formed cementum and connective tissue attachment were not significant. Newly formed periodontal ligament and cementum-like tissue were evident along the root surface at the experimental sites. The inner surface of the tunnels was partially resorbed and replaced with new bone. New blood vessels were observed inside the lumens of tunnel ß-TCP. CONCLUSION: Tunnel ß-TCP serves as a scaffold for new bone formation in one-wall intrabony defects.

Role of Age-Associated Alterations of the Dermal Extracellular Matrix Microenvironment in Human Skin Aging: A Mini-Review.

Human skin is largely composed of a collagen-rich connective tissue, which provides structural and functional support. The collagen-rich connective tissue is produced, organized, and maintained by dermal fibroblasts. During aging, dermal collagen fibrils undergo progressive loss and fragmentation, leading to thin and structurally weakened skin. Age-related alterations of collagen fibrils impairs skin structure and function and creates a tissue microenvironment that promotes age-related skin diseases, such as delayed wound healing and skin cancer development. This mini-review describes cellular mechanisms that give rise to self-perpetuating, collagen fibril fragmentation that creates an age-associated dermal microenvironment, which contributes to decline of human skin function.

The future of bioactive ceramics.

Two important worldwide needs must be satisfied in the future; (1) treatment of the deteriorating health of an aging population and, (2) decreasing healthcare costs to meet the needs of an increased population. The ethical and economic dilemma is how to achieve equality in quality of care while at the same time decreasing cost of care for an ever-expanding number of people. The limited lifetime of prosthetic devices made from first-generation nearly inert biomaterials requires new approaches to meet these two large needs. This paper advises an expanded emphasis on: (1) regeneration of tissues and (2) prevention of tissue deterioration to meet this growing need. Innovative use of bioactive ceramics with genetic control of in situ tissue responses offers the potential to achieve both tissue regeneration and prevention. Clinical success of use of bioactive glass for bone regeneration is evidence that this concept works. Likewise the use of micron sized bioactive glass powders in a dentifrice for re-mineralization of teeth provides evidence that prevention of tissue deterioration is also possible. This opinion paper outlines clinical needs that could be met by innovative use of bioactive glasses and ceramics in the near future; including: regeneration of skeletal tissues that is patient specific and genetic based, load-bearing bioactive glass-ceramics for skeletal and ligament and tendon repair, repair and regeneration of soft tissues, and rapid low-cost analysis of human cell-biomaterial interactions leading to patient specific diagnoses and treatments using molecularly tailored bioceramics.

Effect of Connective Tissue Manipulation on Symptoms and Quality of Life in Patients With Chronic Constipation: A Randomized Controlled Trial.

OBJECTIVE: The purpose of this study was to examine the effects of connective tissue manipulation (CTM) on the severity of constipation and health-related quality of life in individuals diagnosed with chronic constipation. METHODS: Fifty patients with a diagnosis of chronic constipation according to Rome III criteria were recruited and randomized to an intervention (n = 25) or control group (n = 25). The intervention group received CTM in addition to the lifestyle advice, whereas the control group was given only lifestyle advice for constipation. All assessments were performed at baseline and at the end of 4 weeks. The primary outcome measure was the Constipation Severity Instrument. Secondary outcomes included Patient Assessment of Constipation Quality of Life Questionnaire, Bristol Stool Scale, and 7-day bowel diary. Differences between groups were analyzed with t tests, Mann-Whitney U test and χ(2) test. RESULTS: Compared with the control group, subjects in the intervention group reported significantly greater improvement in total and subscale scores of the Constipation Severity Instrument and Patient Assessment of Constipation Quality of Life Questionnaire (P < .05). Based on the results from bowel diaries, the improvements in the number of bowel movements, duration of defecation, stool consistency, and the feeling of incomplete evacuation in the intervention group were also significantly more than the control group (P < .05). CONCLUSION: This study showed that CTM and lifestyle advice were superior to reducing symptoms of constipation and quality of life compared with lifestyle advice alone for patients with chronic constipation.

[Connective tissue dysplasia in patients with celiac desease as a problem of violation of adaptation reserve islands of the body].

Clinically significant dysplasia of connective tissue in patients with celiac disease is often responsible for various visceral disorders. Different disturbances of motor and evacuation functions are often determined in this patients (gastroesophageal reflux, duodenogastral reflux, spastic and hyperkinetic dyskinesia). The clinical course of the celiac disease, associated with connective tissue dysplasia, is characterized by asthenovegetative syndrome, reduced tolerance to physical activity, general weakness, fatigue and emotional instability. These data should be considered in choosing a treatment.

Heat-shock proteins in stromal joint tissues: innocent bystanders or disease-initiating proteins?

Heat-shock proteins (HSPs) are molecular chaperones that are highly conserved between species. In recent decades it has become clear that these proteins play an important role in the pathogenesis of inflammatory and degenerative joint diseases by (dys)regulating the immune system and by direct effects on the stromal tissues of the joint. In this review we discuss current insights into the expression pattern of HSPs in connective tissues, the direct biological role of HSPs in stromal tissues and the potential clinical applications.

CT Hounsfield numbers of soft tissues on unenhanced abdominal CT scans: variability between two different manufacturers' MDCT scanners.

OBJECTIVE: The purpose of this study is to determine whether Hounsfield numbers of soft tissues on unenhanced abdominal CT of the same patient vary on repeat scans done on two different manufacturers' MDCT scanners. MATERIALS AND METHODS: A database search was performed to identify patients older than 18 years who underwent unenhanced CT of the abdomen and pelvis performed both on a Volume CT (GE Healthcare) and a Definition AS Plus (Siemens Healthcare) 64-MDCT scanner within 12 months of each other. After excluding those patients for whom Hounsfield unit measurements would be affected by mitigating factors, 48 patients (mean age, 58.8 years) were identified. Hounsfield unit measurements were obtained in nine different soft-tissue anatomic locations on each scan, and the location of these sites was kept identical on each scan pair. Data were analyzed to evaluate Hounsfield unit differences between these scanners. RESULTS: In general, there was a low consistency in the Hounsfield unit measurements for each of these sites on scans obtained by the two scanners, with the subcutaneous fat in the left posterolateral flank showing the lowest correlation (intraclass correlation coefficient, 0.198). There were differences in the Hounsfield unit measurements obtained in all anatomic sites on scans obtained by both scanners. Mean Hounsfield unit measurements obtained on the Definition AS Plus scanner were lower than those obtained on the Volume CT scanner, with the intriguing exception of the anterior midline subcutaneous fat Hounsfield unit measurements, which were higher on the Definition AS Plus scanner. All differences were statistically significant (p < 0.05). CONCLUSION: Hounsfield unit measurements for unenhanced abdominal soft tissues of the same patient vary between scanners of two common MDCT manufacturers.

Painful connections: densification versus fibrosis of fascia.

Deep fascia has long been considered a source of pain, secondary to nerve pain receptors becoming enmeshed within the pathological changes to which fascia are subject. Densification and fibrosis are among such changes. They can modify the mechanical properties of deep fasciae and damage the function of underlying muscles or organs. Distinguishing between these two different changes in fascia, and understanding the connective tissue matrix within fascia, together with the mechanical forces involved, will make it possible to assign more specific treatment modalities to relieve chronic pain syndromes. This review provides an overall description of deep fasciae and the mechanical properties in order to identify the various alterations that can lead to pain. Diet, exercise, and overuse syndromes are able to modify the viscosity of loose connective tissue within fascia, causing densification, an alteration that is easily reversible. Trauma, surgery, diabetes, and aging alter the fibrous layers of fasciae, leading to fascial fibrosis.

Basic components of connective tissues and extracellular matrix: elastin, fibrillin, fibulins, fibrinogen, fibronectin, laminin, tenascins and thrombospondins.

Collagens are the most abundant components of the extracellular matrix and many types of soft tissues. Elastin is another major component of certain soft tissues, such as arterial walls and ligaments. Many other molecules, though lower in quantity, function as essential components of the extracellular matrix in soft tissues. Some of these are reviewed in this chapter. Besides their basic structure, biochemistry and physiology, their roles in disorders of soft tissues are discussed only briefly as most chapters in this volume deal with relevant individual compounds. Fibronectin with its muldomain structure plays a role of "master organizer" in matrix assembly as it forms a bridge between cell surface receptors, e.g., integrins, and compounds such collagen, proteoglycans and other focal adhesion molecules. It also plays an essential role in the assembly of fibrillin-1 into a structured network. Laminins contribute to the structure of the extracellular matrix (ECM) and modulate cellular functions such as adhesion, differentiation, migration, stability of phenotype, and resistance towards apoptosis. Though the primary role of fibrinogen is in clot formation, after conversion to fibrin by thrombin, it also binds to a variety of compounds, particularly to various growth factors, and as such fibrinogen is a player in cardiovascular and extracellular matrix physiology. Elastin, an insoluble polymer of the monomeric soluble precursor tropoelastin, is the main component of elastic fibers in matrix tissue where it provides elastic recoil and resilience to a variety of connective tissues, e.g., aorta and ligaments. Elastic fibers regulate activity of TGFßs through their association with fibrillin microfibrils. Elastin also plays a role in cell adhesion, cell migration, and has the ability to participate in cell signaling. Mutations in the elastin gene lead to cutis laxa. Fibrillins represent the predominant core of the microfibrils in elastic as well as non-elastic extracellular matrixes, and interact closely with tropoelastin and integrins. Not only do microfibrils provide structural integrity of specific organ systems, but they also provide a scaffold for elastogenesis in elastic tissues. Fibrillin is important for the assembly of elastin into elastic fibers. Mutations in the fibrillin-1 gene are closely associated with Marfan syndrome. Fibulins are tightly connected with basement membranes, elastic fibers and other components of extracellular matrix and participate in formation of elastic fibers. Tenascins are ECM polymorphic glycoproteins found in many connective tissues in the body. Their expression is regulated by mechanical stress both during development and in adulthood. Tenascins mediate both inflammatory and fibrotic processes to enable effective tissue repair and play roles in pathogenesis of Ehlers-Danlos, heart disease, and regeneration and recovery of musculo-tendinous tissue. One of the roles of thrombospondin 1 is activation of TGFß. Increased expression of thrombospondin and TGFß activity was observed in fibrotic skin disorders such as keloids and scleroderma. Cartilage oligomeric matrix protein (COMP) or thrombospondin-5 is primarily present in the cartilage. High levels of COMP are present in fibrotic scars and systemic sclerosis of the skin, and in tendon, especially with physical activity, loading and post-injury. It plays a role in vascular wall remodeling and has been found in atherosclerotic plaques as well.

Development of a computational biomechanical model of the human upper-airway soft-tissues toward simulating obstructive sleep apnea.

Numerous challenges are faced in investigations aimed at developing a better understanding of the pathophysiology of obstructive sleep apnea (OSA). The anatomy of the tongue and other upper-airway tissues, and the ability to model their behavior, are central to such investigations. We present details of the construction and development of a soft-tissue model of the human upper airway, with the ultimate goal of simulating obstructive sleep apnea. The steps taken to produce a representative anatomical geometry, of which the associated muscle histology is also captured, are documented. An overview of the mathematical models used to describe tissue behavior, both at a macro- and microscopic level, is given. A neurological model, which mimics the proprioceptive capabilities of the body, is described as it is applies to control of the active dynamics of the tongue. A simplified scenario, which allows for the manipulation of several environmental influences, is presented. It is demonstrated that the response of the genioglossus is qualitatively similar to that determined through experimental techniques. Furthermore, insights into the stress distribution developed within the tongue are discussed. It is shown that changes in almost any aspect of the breathing or physiological conditions invoke a significant change in the response of the airway dilators. The results of this study provide further evidence of the importance of modeling and simulation techniques as an aid in understanding the complex behavior of the human body.