Variants in the Kallikrein Gene Family and Hypermobile Ehlers-Danlos Syndrome.

Hypermobile Ehlers-Danlos syndrome (hEDS) is a common heritable connective tissue disorder that lacks a known genetic etiology. To identify genetic contributions to hEDS, whole exome sequencing was performed on families and a cohort of sporadic hEDS patients. A missense variant in Kallikrein-15 (KLK15 p. Gly226Asp), segregated with disease in two families and genetic burden analyses of 197 sporadic hEDS patients revealed enrichment of variants within the Kallikrein gene family. To validate pathogenicity, the variant identified in familial studies was used to generate knock-in mice. Consistent with our clinical cohort, Klk15 G224D/+ mice displayed structural and functional connective tissue defects within multiple organ systems. These findings support Kallikrein gene variants in the pathogenesis of hEDS and represent an important step towards earlier diagnosis and better clinical outcomes.

Engineering Stem Cell Fate Controlling Biomaterials to Develop Muscle Connective Tissue Layered Myofibers.

Skeletal muscle connective tissue (MCT) surrounds myofiber bundles to provide structural support, produce force transduction from tendons, and regulate satellite cell differentiation during muscle regeneration. Engineered muscle tissue composed of myofibers layered within MCT has not yet been developed. Herein, a bioengineering strategy to create MCT-layered myofibers through the development of stem cell fate-controlling biomaterials that achieve both myogenesis and fibroblast differentiation in a locally controlled manner at the single construct is introduced. The reciprocal role of transforming growth factor-beta 1 (TGF-ß1) and its inhibitor as well as 3D matrix stiffness to achieve co-differentiation of MCT fibroblasts and myofibers from a human-induced pluripotent stem cell (hiPSC)-derived paraxial mesoderm is studied. To avoid myogenic inhibition, TGF-ß1 is conjugated on the gelatin-based hydrogel to control the fibroblasts' populations locally; the TGF-ß1 degrades after 2 weeks, resulting in increased MCT-specific extracellular matrix (ECM) production. The locations of myofibers and fibroblasts are precisely controlled by using photolithography and co-axial wet spinning techniques, which results in the formation of MCT-layered functional myofibers in 3D constructs. This advanced engineering strategy is envisioned as a possible method for obtaining biomimetic human muscle grafts for various biomedical applications.

The preliminary analysis of lymphatic flow around the connective tissues surrounding SMA and SpA elucidates patients' oncological condition in borderline-resectable pancreatic cancer.

BACKGROUND: In pancreatic ductal adenocarcinoma (PDAC), invasion of connective tissues surrounding major arteries is a crucial prognostic factor after radical resection. However, why the connective tissues invasion is associated with poor prognosis is not well understood. MATERIALS AND METHODS: From 2018 to 2020, 25 patients receiving radical surgery for PDAC in our institute were enrolled. HyperEye Medical System (HEMS) was used to examine lymphatic flow from the connective tissues surrounding SMA and SpA and which lymph nodes ICG accumulated in was examined. RESULTS: HEMS imaging revealed ICG was transported down to the paraaortic area of the abdominal aorta along SMA. In pancreatic head cancer, 9 paraaortic lymph nodes among 14 (64.3%) were ICG positive, higher positivity than LN#15 (25.0%) or LN#18 (50.0%), indicating lymphatic flow around the SMA was leading directly to the paraaortic lymph nodes. Similarly, in pancreatic body and tail cancer, the percentage of ICG-positive LN #16a2 was very high, as was that of #8a, although that of #7 was only 42.9%. CONCLUSIONS: Our preliminary result indicated that the lymphatic flow along the connective tissues surrounding major arteries could be helpful in understanding metastasis and improving prognosis in BR-A pancreatic cancer.

Recent Advances in the Nutrition and Metabolism of Dogs and Cats.

Domestic dogs (facultative carnivores) and cats (obligate carnivores) have been human companions for at least 12,000 and 9000 years, respectively. These animal species have a relatively short digestive tract but a large stomach volume and share many common features of physiological processes, intestinal microbes, and nutrient metabolism. The taste buds of the canine and feline tongues can distinguish sour, umami, bitter, and salty substances. Dogs, but not cats, possess sweet receptors. α-Amylase activity is either absent or very low in canine and feline saliva, and is present at low or substantial levels in the pancreatic secretions of cats or dogs, respectively. Thus, unlike cats, dogs have adapted to high-starch rations while also consuming animal-sourced foods. At metabolic levels, both dogs and cats synthesize de novo vitamin C and many amino acids (AAs, such as Ala, Asn, Asp, Glu, Gln, Gly, Pro, and Ser) but have a very limited ability to form vitamin D3. Compared with dogs, cats have higher requirements for AAs, some B-complex vitamins, and choline; greater rates of gluconeogenesis; a higher capacity to tolerate AA imbalances and antagonism; a more limited ability to synthesize arginine and taurine from glutamine/proline and cysteine, respectively; and a very limited ability to generate polyunsaturated fatty acids (PUFAs) from respective substrates. Unlike dogs, cats cannot convert either ß-carotene into vitamin A or tryptophan into niacin. Dogs can thrive on one large meal daily and select high-fat over low-fat diets, whereas cats eat more frequently during light and dark periods and select high-protein over low-protein diets. There are increasing concerns over the health of skin, hair, bone, and joints (specialized connective tissues containing large amounts of collagen and/or keratin); sarcopenia (age-related losses of skeletal-muscle mass and function); and cognitive function in dogs and cats. Sufficient intakes of proteinogenic AAs and taurine along with vitamins, minerals, and PUFAs are crucial for the normal structures of the skin, hair, bone, and joints, while mitigating sarcopenia and cognitive dysfunction. Although pet owners may have different perceptions about the feeding and management practice of their dogs and cats, the health and well-being of the companion animals critically depend on safe, balanced, and nutritive foods. The new knowledge covered in this volume of Adv Exp Med Biol is essential to guide the formulation of pet foods to improve the growth, development, brain function, reproduction, lactation, and health of the companion animals.

Simultaneous fingerprinting of multiplex collagen biomarkers in connective tissues by multicolor quantum dots-based peptide probes.

The accurate detection of multiplex collagen biomarkers is vital for diagnosing and treating various critical diseases such as tumors and fibrosis. Despite the attractive optical properties of quantum dots (QDs), it remains technically challenging to create stable and specific QDs-based probes for multiplex biological imaging. We report for the first time the construction of multi-color QDs-based peptide probes for the simultaneous fingerprinting of multiplex collagen biomarkers in connective tissues. A bipeptide system composed of a glutathione (GSH) host peptide and a collagen-targeting guest peptide (CTP) has been developed, yielding CTP-QDs probes that exhibit exceptional luminescence stability when exposed to ultraviolet irradiation and mildly acidic conditions. The versatile bipeptide system allows for facile one-pot synthesis of high-quality multicolor CTP-QDs probes, exhibiting superior selectivity in targeting critical collagen biomarkers including denatured collagen, type I collagen, type II collagen, and type IV collagen. The multicolor CTP-QDs probes have demonstrated remarkable efficacy in simultaneously fingerprinting multiple collagen types in diverse connective tissues, irrespective of their status, whether affected by injury, diseases, or undergoing remodeling processes. The innovative multicolor CTP-QDs probes offer a robust toolkit for the multiplex fingerprinting of the collagen suprafamily, demonstrating significant potential in the diagnosis and treatment of collagen-related diseases.

Extracellular matrix biomechanical roles and adaptation in health and disease.

Extracellular matrices (ECMs) are dynamic 3D macromolecular networks that exhibit structural characteristics and composition specific to different tissues, serving various biomechanical and regulatory functions. The interactions between ECM macromolecules such as collagen, elastin, glycosaminoglycans (GAGs), proteoglycans (PGs), fibronectin, and laminin, along with matrix effectors and water, contribute to the unique cellular and tissue functional properties during organ development, tissue homoeostasis, remodeling, disease development, and progression. Cells adapt to environmental changes by adjusting the composition and array of ECM components. ECMs, forming the 3D bioscaffolds of our body, provide mechanical support for tissues and organs and respond to the environmental variables influencing growth and final adult body shape in mammals. Different cell types display distinct adaptations to the respective ECM environments. ECMs regulate biological processes by controlling the diffusion of infections and inflammations, sensing and adapting to external stimuli and gravity from the surrounding habitat, and, in the context of cancer, interplaying with and regulating cancer cell invasion and drug resistance. Alterations in the ECM composition in pathological conditions drive adaptive responses of cells and could therefore result in abnormal cell behavior and tissue dysfunction. Understanding the biomechanical functionality, adaptation, and roles of distinct ECMs is essential for research on various pathologies, including cancer progression and multidrug resistance, which is of crucial importance for developing targeted therapies. In this Viewpoint article, we critically present and discuss specific biomechanical functions of ECMs and regulatory adaptation mechanisms in both health and disease, with a particular focus on cancer progression.

Nail Whispers Revealing Dermatological and Systemic Secrets: An Analysis of Nail Disorders Associated With Diverse Dermatological and Systemic Conditions.

Background and objective Nail disorders encompass a wide spectrum of conditions, spanning congenital, developmental, infectious, neoplastic, degenerative, dermatological, and systemic diseases. A comprehensive exploration of their clinical manifestations, incidence, and associations is crucial for precise diagnosis and effective management. Methods This observational cross-sectional study conducted at B.J. Medical College and Civil Hospital, Ahmedabad involved 300 consecutive patients with nail changes from July 2017 to June 2019 reporting diverse dermatological and systemic conditions. The inclusion criteria involved patients of both genders and all age groups displaying nail changes associated with dermatological and systemic diseases. Data collection entailed a comprehensive clinical history, systemic and dermatological examinations, nail assessment using Dermoscope (DermLite 3, 10x), and supplementary tests. Analyses were performed on Microsoft Excel 2007 software. The study was approved by the Institute Ethics Committee. Results Among the 300 cases, females had a higher prevalence of nail involvement (57%), with a female-to-male ratio of 1.3:1. The most affected age group was 21-40 years, with 6-10 nails typically affected. Notably, housewives showed a higher prevalence. The most frequent nail condition was onychomycosis (24.33%) followed by psoriatic nail changes (20%). Less frequent nail changes involved eczema (5.7%), paronychia (5%), drug-induced (4.3%), lichen planus (3.7%), trauma-induced (3%), twenty nail dystrophy (2.33%), Darier's disease (2%), pemphigus vulgaris (2%), alopecia areata (1.67%), median Heller dystrophy (1.33%), atopic dermatitis (1%), epidermolysis bullosa (1%), racquet nail (1%), leprosy (1%), pityriasis rubra pilaris (0.67%), vitiligo (0.67%), secondary syphilis (0.67%), pachyonychia congenita (0.67%), as well as a case each of total leukonychia, subungual warts, Koenen tumor, and periungual fibroma(0.33%). Systemic autoimmune connective tissue disorders (CTD) accounted for 9%; the most common nail finding observed was nail fold erythema (48.1%) followed by nail fold telangiectasis (44.4%). In systemic sclerosis (SS), the most common finding was nail fold telangiectasia, and in systemic lupus erythematosus (SLE), the most common was nail fold erythema. Scleroderma capillary pattern on nail fold capillaroscopy was found in seven patients with SS, two patients with dermatomyositis, and only one patient with SLE. Nail changes observed in systemic diseases include onychomycosis in diabetes mellitus and chronic renal failure patients, splinter hemorrhages in ischemic heart disease and hypertension, longitudinal melanonychia in HIV, and koilonychia and platynychia in iron deficiency anemia. Other systemic diseases, such as Addison's disease and renal failure, also exhibited various nail changes. Conclusions Beyond their cosmetic importance, nails hold a vital pathologic role. Proficiency in nail terminology and classification is key for skillful evaluation. Understanding normal and abnormal nail variants, along with their disease associations, benefits diagnosis and tailored management. Nails, often overlooked but accessible, serve as a window into patients' general health and should be an integral part of thorough examinations. This study highlights an intricate clinical panorama of nail disorders, highlighting their significant role in both dermatological and systemic contexts.

"Knowing It Before Blocking It," the ABCD of the Peripheral Nerves: Part A (Nerve Anatomy and Physiology).

Regional anesthesia (RA) is an interplay between the local anesthetic (LA) solution and the neural structures, resulting in nerve conduction blockade. For that, it is necessary to understand which hurdles the LA has to overcome and which components of the nerves are involved. Background knowledge of the neural and non-neural components of the nerve helps locate the safest area for LA deposition. In addition, knowledge of nerve physiology and the conduction process helps to understand the patterns of block onset, involved fibers, and block regression. Neural connective tissue protects the nerve on the one hand and influences the overall effect of the blockade and the occurrence of nerve injuries on the other. The arrangement of the nerve fibers explains the science behind the differential blockage after LA deposition. This article describes the important aspects of nerve anatomy (nerve formation and composition) and nerve physiology (impulse generation and propagation). It also provides insight into the physiological processes involved when a damaged neural structure leads to potential clinical symptoms. It will help readers sharpen their skills and knowledge to execute safe RA without damaging any vital structures in the nerve.

Biocompatibility of Ajwain Oil Combined with Eugenol and Zinc Oxide as a Deciduous Root Canal Obturating Material: An In Vivo Study.

Aim and objectives: The present study was intended to assess the biocompatibility of newly formulated materials such as zinc oxide (ZO) admixed with ajwain oil (A) as well as ajwain eugenol (E) (1:1 ratio) against ZOE through an animal model as root canal obturating materials in deciduous teeth. Materials and methods: The study involved randomly selected 24 albino rats, which were divided into three groups based on test materials. Two polyethylene tubes (PETT) (8 mm long × 1 mm internal diameter) were inserted into connective tissues of the dorsal side on either side of each rat viz empty tube (negative control) and another containing test material (test group). Animals were sacrificed at the end of the 7th and 21st days. PETT with surrounding connective tissues were excised. Histopathological evaluations of the material's biocompatibility were done by determining inflammatory tissue responses. Non-parametric tests such as Kruskal-Wallis and Mann-Whitney U were used for statistical analysis (p < 0.05). Results: Histopathological examination on the 7th day showed increased polymorphonuclear cells for all test materials compared to the negative control (p = 0.92), suggesting acute inflammation. The inflammation subsided gradually after 21 days (p = 0.48). The lymphocytes increased after 21 days for all the materials indicating chronic inflammation (p = 0.79), as well as fibroblasts (p = 0.34) and capillaries (p = 0.35), indicating healing and repair. Conclusion: The newly formulated obturating materials were found to be biocompatible compared to ZOE. How to cite this article: Dahake PT, Joshi SS, Kale YJ, et al. Biocompatibility of Ajwain Oil Combined with Eugenol and Zinc Oxide as a Deciduous Root Canal Obturating Material: An In Vivo Study. Int J Clin Pediatr Dent 2023;16(3):431-436.

Autoantibodies testing in autoimmunity: Diagnostic, prognostic and classification value.

Diagnosis of autoimmune diseases is in most cases challenging for clinicians as there is not a single specific laboratory or histological marker to diagnose or exclude the presence of the conditions. This review focused on the current knowledge of the role of autoantibodies' testing in various diseases, such as systemic lupus erythematosus, rheumatoid arthritis, antiphospholipid syndrome, undifferentiated connective tissues disease, primary biliary cholangitis and primary sclerosing cholangitis. Similarly, the prognostic and diagnostic values of autoantibodies testing in patients with interstitial lung disease have been reviewed. In-depth research on the molecular action of these autoantibodies on immune regulation and diseases pathogenesis has been explored beyond their correlation with disease phenotypes, highlighting the impact of autoantibodies targeting on disease outcomes and etiopathogenesis.

Splenic artery pathology presentation, operative interventions, and outcomes in 88 patients with vascular Ehlers-Danlos syndrome.

OBJECTIVE: Vascular Ehlers-Danlos syndrome (VEDS) is rare and associated with arteriopathies. The aim of this study is to investigate the presentation, operative interventions, and outcomes of splenic arterial pathology in a population of more than 1500 individuals with genetically confirmed VEDS due to pathogenic COL3A1 variants. METHODS: Cross-sectional analysis of 1547 individuals was performed. The data were assembled by harmonizing data from three overlapping cohorts with genetically confirmed VEDS: the VEDS Collaborative Natural History Study (N = 242), a single-center cohort (N = 75), and the University of Washington Collagen Diagnostic Lab cohort (N = 1231). Duplicates were identified and removed. Patients were selected for analysis if they had splenic artery aneurysm (SAA), pseudoaneurysm, dissection, thrombosis, or rupture. Demographics, COL3A1 variants, interventions, and outcomes were analyzed. Comparisons by splenic artery rupture were made. RESULTS: A total of 88 patients presented between 1992 and 2021 with splenic artery pathology (5.7% of the cohort; mean age at diagnosis, 37 ± 11.1 years; 50% male). One-third were diagnosed with VEDS prior to the splenic artery pathology diagnosis, and 17% were diagnosed post-mortem. Most had a positive family history (61%). Most had COL3A1 variants associated with minimal normal collagen production (71.6%). Median follow up was 8.5 years (interquartile range, 0.9-14.7 years). Initial presentation was rupture in 47% of the cases. Splenic artery rupture overall was 51% (n = 45), including four cases of splenic rupture. There were no major differences in VEDS-related manifestations or COL3A1 variant type by rupture status. SAA was noted in 39% of the cases. Only 12 patients had splenic artery diameter documented in 12 cases with a median diameter of 12 mm (interquartile range, 10.3-19.3 mm). A total of 34 patients (38.6%) underwent 40 splenic arterial interventions: 21 open surgical, 18 embolization, and one unknown procedure. More than one splenic artery intervention was performed in five cases (14.7%). Open repair complications included arteriovenous fistula (n = 1), intestinal or pancreatic injury (n = 1 each), and four intraoperative deaths. There were no deaths or access site complications related to splenic artery embolization. Four patients (23.5%) developed a new SAA in the remaining splenic artery post embolization. All-cause mortality was 35% (n = 31), including 22 related to a ruptured splenic artery. CONCLUSIONS: Splenic arteriopathy in VEDS is associated with variants that affect the structure and secretion of type III collagen and frequently present with rupture. Rupture and open repair are associated with high morbidity and mortality, whereas embolization is associated with favorable outcomes. Suggest repair considerations at SAA diameter of 15 mm. Long-term follow-up is indicated as secondary splenic arteriopathy can occur.

Clinical Evaluation of Bilateral Multiple Gingival Recession Treatment with Autogenous Connective Tissue Graft Associated with Low-Level Laser Therapy.

BACKGROUND: Gingival recession (GR) is described as an apical displacement of the gingival margin in relation to the cementoenamel junction, exposing the root surface to the oral cavity environment. This study aimed to evaluate the clinical results of a bilateral root coverage (RC) of GR associated with an autogenous connective tissue graft (aCTG) alone or combined with low-level laser therapy (aCTG + LLLT). METHODS: This cross-sectional, split-mouth, double-blind, clinical pilot study featured three individuals who attended a periodontics post-graduate program with the main complaint of GR and dental hypersensitivity (DHS). Of these, only one patient met the inclusion criteria and the parameters evaluated were: DHS, the keratinized tissue's thickness and width clinical attachment level (CAL), probing on depth (PD), and bilateral GR based on Cairo RT I. The patient was evaluated by a first clinical evaluator and the treatment was randomly divided into two groups, G1: aCTG only (control group, n = 3 teeth per side) and G2: aCTG + LLLT (test group, n = 3 teeth per side). LLLT used a diode laser (660 nm) with a dose of 3 J/cm2 per point and 4 s per point was applied in four different periods, preoperatively; transoperatively and immediately postoperatively, the application was performed in three points (eight applications) on alternate days for 7 days and a 90-day follow-up was performed for clinical evaluations of the periodontal parameters and the collected data were analyzed by Kruskal-Wallis and Dunn tests. RESULTS: the RC mean percentage was <95% in both groups after 90 days. Comparing treatment sides, G1 (n = 3/3, 100%) had a higher prevalence of RC than G2 had (n = 3/3, 95%). DHS significantly decreased after 90 days in both groups. Both groups showed an improvement in the other periodontal parameters evaluated during the short-term follow-up; mainly, PD had a statistically significant (p ˂ 0.05) increase after 90 days and a CAL decrease during this period; KTW and KTT also had a significant increase in both groups (p ˂ 0.05). CONCLUSIONS: the results indicated that aCTG + LLLT might have an additional benefit to GR root coverage within the evaluated time and this section also includes the within-study limitations.

Pirfenidone affects human cardiac fibroblast proliferation and cell cycle activity in 2D cultures and engineered connective tissues.

The anti-fibrotic drug pirfenidone (PFD) is currently in clinical testing for the treatment of heart failure with preserved ejection fraction; however, its effects on human cardiac cells have not been fully investigated. Therefore, we aimed to characterize the impact of PFD on human cardiac fibroblasts (CF) in 2D culture as well as in 3D-engineered connective tissues (ECT). We analyzed proliferation by automated cell counting and changes in signaling by immunoblotting. We generated ECT with different geometries to modify the cellular phenotype and investigated the effects of PFD on cell number and viability as well as on cell cycle activity. We further studied its effect on ECT compaction, contraction, stiffening, and strain resistance by ECT imaging, pole deflection analysis, and ultimate tensile testing. Our data demonstrate that PFD inhibits human CF proliferation in a concentration-dependent manner with an IC50 of 0.43 mg/ml and its anti-mitogenic effect was further corroborated by an inhibition of MEK1/2, ERK1/2, and riboprotein S6 (rpS6) phosphorylation. In ECT, a lower cell cycle activity was found in PFD-treated ECT and fewer cells resided in these ECT after 5 days of culture compared to the control. Moreover, ECT compaction as well as ECT contraction was impaired. Consequently, biomechanical analyses demonstrated that PFD reduced the stiffness of ECT. Taken together, our data demonstrate that the anti-fibrotic action of PFD on human CF is based on its anti-mitogenic effect in 2D cultures and ECT.

First-in-Human Study to Investigate the Safety Assessment of Peri-Implant Soft Tissue Regeneration with Micronized-Gingival Connective Tissue: A Pilot Case Series Study.

Background: We have recently proposed an alternative strategy of free gingival graft (FGG) and connective tissue graft (CTG) using micronized-gingival connective tissues (MGCTs). The advantage of this strategy is that MGCTs from a small piece of maxillary tuberosity can regenerate the keratinized tissue band. However, safety and efficacy have not yet been established in patients. This clinical study was a pilot case series, and the objective was to assess the safety and the preliminary efficacy of MGCTs on peri-implant mucosa regeneration. Methods: This was a pilot interventional, single-center, first-in-human (FIH), open (no masking), uncontrolled, and single-assignment study. A total of 4 patients who needed peri-implant soft tissues reconstruction around dental implants received transplantation of atelocollagen-matrix with MGCTs micronized by the tissue disruptor technique. The duration of intervention was 4 weeks after surgery. Results: This first clinical study demonstrated that using MGCTs did not cause any irreversible adverse events, and it showed the preliminary efficacy for peri-implant soft tissues reconstruction in dental implant therapy. Conclusions: Though further studies are needed on an appropriate scale, as an alternative strategy of FGG or CTG, MGCTs might be promising for peri-implant mucosa reconstruction without requiring a high level of skills and morbidity to harvest graft tissues.

The Stiffness-Sensitive Transcriptome of Human Tendon Stromal Cells.

Extracellular matrix stiffness is a major regulator of cellular states. Stiffness-sensing investigations are typically performed using cells that have acquired "mechanical memory" through prolonged conditioning in rigid environments, e.g., tissue culture plastic (TCP). This potentially masks the full extent of the matrix stiffness-driven mechanosensing programs. Here, a biomaterial composed of 2D mechanovariant silicone substrates with simplified and scalable surface biofunctionalization chemistry is developed to facilitate large-scale cell culture expansion processes. Using RNA sequencing, stiffness-mediated mechano-responses of human tendon-derived stromal cells are broadly mapped. Matrix elasticity (E.) approximating tendon microscale stiffness range (E. ≈ 35 kPa) distinctly favors transcriptional programs related to chromatin remodeling and Hippo signaling; whereas compliant stiffnesses (E. ≈ 2 kPa) are enriched in processes related to cell stemness, synapse assembly, and angiogenesis. While tendon stromal cells undergo dramatic phenotypic drift on conventional TCP, mechanovariant substrates abrogate this activation with tenogenic stiffnesses inducing a transcriptional program that strongly correlates with established tendon tissue-specific expression signature. Computational inference predicts that AKT1 and ERK1/2 are major stiffness-sensing signaling hubs. Together, these findings highlight how matrix biophysical cues may dictate the transcriptional identity of tendon cells, and how matrix mechano-reciprocity regulates diverse sets of previously underappreciated mechanosensitive processes in tendon fibroblasts.

The relationship between clinical examination measures and ultrasound measures of fascia thickness surrounding trunk muscles or lumbar multifidus fatty infiltrations: An exploratory study.

Patients with chronic low back pain (CLBP) exhibit remodelling of the lumbar soft tissues such as muscle fatty infiltrations (MFI) and fibrosis of the lumbar multifidus (LuM) muscles, thickness changes of the thoracolumbar fascia (TLF) and perimuscular connective tissues (PMCT) surrounding the abdominal lateral wall muscles. Rehabilitative ultrasound imaging (RUSI) parameters such as thickness and echogenicity are sensitive to this remodelling. This experimental laboratory study aimed to explore whether these RUSI parameters (LuM echogenicity and fascia thicknesses), hereafter called dependent variables (DV) were linked to independent variables (IV) such as (1) other RUSI parameters (trunk muscle thickness and activation) and (2) physical and psychological measures. RUSI measures, as well as a clinical examination comprising physical tests and psychological questionnaires, were collected from 70 participants with LBP. The following RUSI dependent variables (RUSI-DV), measures of passive tissues were performed bilaterally: (1) LuM echogenicity (MFI/fibrosis) at three vertebral levels (L3/L4, L4/L5 and L5/S1); (2) TLF posterior layer thickness, and (3) PMCT thickness of the fasciae between subcutaneous tissue thickness (STT) and external oblique (PMCTSTT/EO ), between external and internal oblique (PMCTEO/IO ), between IO and transversus abdominis (PMCTIO/TrA ) and between TrA and intra-abdominal content (PMCTTrA/IA ). RUSI measures of trunk muscle's function (thickness and activation), also called measures of active muscle tissues, were considered as independent variables (RUSI-IV), along with physical tests related to lumbar stability (n = 6), motor control deficits (n = 7), trunk muscle endurance (n = 4), physical performance (n = 4), lumbar posture (n = 2), and range of motion (ROM) tests (n = 6). Psychosocial measures included pain catastrophizing, fear-avoidance beliefs, psychological distress, illness perceptions and concepts related to adherence to a home-based exercise programme (physical activity level, self-efficacy, social support, outcome expectations). Six multivariate regression models (forward stepwise selection) were generated, using RUSI-DV measures as dependent variables and RUSI-IV/physical/psychosocial measures as independent variables (predictors). The six multivariate models included three to five predictors, explaining 63% of total LuM echogenicity variance, between 41% and 46% of trunk superficial fasciae variance (TLF, PMCTSTT/EO ) and between 28% and 37% of deeper abdominal wall fasciae variance (PMCTEO/IO , PMCTIO/TrA and PMCTTrA/IA ). These variables were from RUSI-IV (LuM thickness at rest, activation of IO and TrA), body composition (percent fat) and clinical physical examination (lumbar and pelvis flexion ROM, aberrant movements, passive and active straight-leg raise, loaded-reach test) from the biological domain, as well as from the lifestyle (physical activity level during sports), psychological (psychological distress-cognitive subscale, fear-avoidance beliefs during physical activities, self-efficacy to exercise) and social (family support to exercise) domains. Biological, psychological, social and lifestyle factors each accounted for substantial variance in RUSI-passive parameters. These findings are in keeping with a conceptual link between tissue remodelling and factors such as local and systemic inflammation. Possible explanations are discussed, in keeping with the hypothesis-generating nature of this study (exploratory). However, to impact clinical practice, further research is needed to determine if the most plausible predictors of trunk fasciae thickness and LuM fatty infiltrations have an effect on these parameters.

An open-source OpenSim® ankle-foot musculoskeletal model for assessment of strains and forces in dense connective tissues.

BACKGROUND: The ankle and foot are among the most critical load-bearing joints in the human anatomy. Anatomically accurate human body models are imperative to understanding the mechanics of injury and musculoskeletal disorders. A typical human ankle-foot anatomy consists of 25 DOFs, 112 dense connective tissues (DCTs) (92 ligaments, one capsule and 19 fasciae), 30 tendons, and 65 muscles. Existing models possess less than half of the DOFs and physiological elements. In this work, we have developed an ankle-foot joint complex musculoskeletal model for the OpenSim® platform by incorporating 24 degrees of freedom (DOF) comprising of 66 DCTs (46 ligaments, one 1 capsule and 19 fasciae), 30 tendons, and 65 muscles. METHODS: Computed tomography (CT) data of human ankle joint-foot complex was segmented using Mimics ® (Version 17.0, Materialise, Belgium) to obtain models of the cartilages and bones of the ankle joint-foot complex. The position and resting lengths of the DCTs were attained from the MRI data and literature. Five joints, namely, tibiotalar, subtalar, chopart, tarsometatarsal (TMT), and metatarsophalangeal (MTP) joints and their joint axes were formulated to yield 24 DOFs. A forward simulation was carried out at each joint of the ankle-foot complex within their respective range of motions. The strains, instantaneous strain rates, and forces developed in the ligaments during the simulation were studied. RESULTS: During plantar-dorsiflexion of the tibiotalar joint, the anterior tibio-talar ligament (aTTL) yielded the maximum strain compared to all other ligaments. Anterior tibio-fibular ligament (aTFL) experienced extreme strain during subtalar inversion. Hence, the coupled kinematics of subtalar inversion and plantar flexion are failure-prone activities for aTFL. The chopart, TMT, and MTP joints yielded maximum strains or forces for several bundles at the extremes of the range of motion. This signifies that rotations of these joints to their extreme range of motion are prone to failure for the bundles attached to the joint complex. CONCLUSION: The results illustrate the potential application of the proposed OpenSim® ankle-foot model in understanding the ligament injury mechanism during sports activity and its prevention. Researchers can use the proposed model or customise it to study complex kinematics, understanding injury mechanisms, testing fixtures, orthosis or prosthesis, and many more in the domain of musculoskeletal research.

The anatomical myofascial continuum between the neck and eyes.

The posterior myofascial chain (PMC) or superficial back line encompasses a series of muscles interlinked by the deep fascia, extending from the foot to the fascial sheath of the eyeball. The deep cervical fascia of the neck, the epicranial aponeurosis of the head, and the fascial sheath of eyeball, form the proximal PMC. Although the literature has reported an anatomical myofascial continuum between the neck, head, and eyes, the anatomical descriptions vary substantially. Moreover, there is still no plausible functional interrelationship between the proximal structural myofascial links. Chronic neck pain is usually associated with a plethora of symptoms including craniofacial pain and oculomotor disorders. Understanding the anatomy of the proximal myofascial chain could help clinicians improvise treatment strategies for managing such painful head and neck disorders.

Donor age and sex have limited effects on the mechanical and microstructural properties of human connective tissues.

Connective tissues, such as tendons, ligaments, and capsules, play a large role in locomotion and joint stability and are often subjected to traumatic injuries and degeneration. The purpose of this study was to evaluate if the mechanical and microstructural properties of connective tissues correlate with the age and sex of the human donor. Dissected samples were prepared for mechanical testing, consisting of 10 cycles of preconditioning, a stress-relaxation ramp and hold, and a quasi-static ramp to failure. During the testing protocol, the microstructural organization of tissues was analyzed using quantitative polarized light imaging. A linear mixed model was used to assess whether tissue type, donor age, or donor sex were significantly associated with mechanical and microstructural tissue properties. Tissue type had a significant effect on all parameters, while donor age and sex did not. Groupings by tissue type (i.e., tendon vs. ligament vs. capsule) were evident for microstructural data, with tendons having a tighter grouping and ligaments having a larger spread of values. The interaction of tissue type and age yielded a significant effect for linear modulus only (p = 0.007), with the palmaris tendon appearing to have the largest contribution to this effect. There were no significant interaction effects between sex and tissue type or donor age. Donor age appears to affect linear modulus in some, but not all, tissue types. Otherwise, age and sex do not have significant effects on the mechanical and microstructural properties of the range of connective tissues that were analyzed in this study.

Urogynaecology and Ehlers-Danlos syndrome.

Ehlers-Danlos syndrome (EDS) can lead to a presentation to urogynaecology services with multiple symptoms including vaginal prolapse, overactive bladder symptoms, voiding dysfunction, bladder pain syndrome, recurrent urinary tracts infections, stress urinary incontinence, recurring bladder diverticula, vesicoureteral reflux, pelvic floor pain or spasms, and complicated postnatal perineal wounds. This article explores the pathophysiology of these conditions in causing urinary urgency, incontinence, and infections; highlighting the key investigations and management considerations for women with EDS including conservative, pharmacological, and surgical.