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Collagen XI is ubiquitous in tissues such as joint cartilage, cancellous bone, muscles, and tendons and is an important contributor during a crucial part in fibrillogenesis. The COL11A1 gene encodes one of three alpha chains of collagen XI. The present study elucidates the role of collagen XI in the establishment of mechanical properties of tendons and ligaments. We investigated the mechanical response of three tendons and one ligament tissues from wild type and a targeted mouse model null for collagen XI: Achilles tendon (ACH), the flexor digitorum longus tendon (FDL), the supraspinatus tendon (SST), and the anterior cruciate ligament (ACL). Area was substantially lower in Col11a1ΔTen/ΔTen ACH, FDL, and SST. Maximum load and maximum stress were significantly lower in Col11a1ΔTen/ΔTen ACH and FDL. Stiffness was lower in Col11a1ΔTen/ΔTen ACH, FDL, and SST. Modulus was reduced in Col11a1ΔTen/ΔTen FDL and SST (both insertion site and midsubstance). Collagen fiber distributions were more aligned under load in both wild type group and Col11a1ΔTen/ΔTen groups. Results also revealed that the effect of collagen XI knockout on collagen fiber realignment is tendon-dependent and location-dependent (insertion versus midsubstance). In summary, this study clearly shows that the regulatory role of collagen XI on tendon and ligament is tissue specific and that joint hypermobility in type II Stickler's Syndrome may in part be due to suboptimal mechanical response of the soft tissues surrounding joints., (Copyright © 2025 by ASME.)

During pregnancy and breastfeeding, women undergo hormonal fluctuations required for fetal development, parturition, and infant growth. These changes have secondary consequences on the maternal musculoskeletal system, increasing the risk for joint pain and osteoporosis. Though hormone levels return to prepregnancy levels postpartum, women may experience lasting musculoskeletal pain. Sex disparities exist in the prevalence of musculoskeletal disorders, but it remains unclear how reproductive history may impact sex differences. Specifically, the effects of both reproductive history and sex on the rotator cuff have not been studied. Pregnancy and lactation affect bone microstructure, suggesting possible impairments at the enthesis of rotator cuff tendons, where tears commonly occur. Therefore, our objective was to evaluate how reproductive history affects sex differences of the supraspinatus tendon and proximal humerus using male, virgin female, and female rats with a history of reproduction (referred to as reproductive females). We hypothesized tendon mechanical properties and humeral bone microstructure would be inferior in reproductive females compared to virgin females. Results showed sex differences independent of reproductive history, including greater tendon midsubstance modulus but lower subchondral bone mineral density (BMD) in females. When considering reproductive history, reproductive rats exhibited reduced tendon insertion site modulus and trabecular bone micro-architecture compared to virgin females with no differences from males. Overall, our study identified long-term changes in supraspinatus tendon mechanical and humeral trabecular bone properties that result following pregnancy and lactation, highlighting the importance of considering reproductive history in investigations of sex differences in the physiology and pathology of rotator cuff injuries., (Copyright © 2024 by ASME.)

Collagen V (Col5) is a quantitatively minor component of collagen fibrils comprising tendon, however, plays a crucial role in regulation of development and dynamic healing processes. Clinically, patients with COL5a1 haploinsufficiency, known as classic Ehlers-Danlos Syndrome (cEDS), present with hyperextensible skin, joint instability and laxity, with females more likely to be affected. Previous studies in Col5-deficient mice indicated that reduced Col5a1 expression leads to a reduction in stiffness, fibril deposition, and altered fibril structure. Additionally, Col5-deficient male tendons demonstrated altered healing compared to wild-type tendons, however female mice have not yet been studied utilizing this model. Along with clinical differences between sexes in cEDS patient populations, differences in hormone physiology may be a factor influencing tendon health. Therefore, the objective of this study was to utilize a Col5a1 +/ - female mouse model, to determine the effect of Col5 on tendon cell morphology, cell density, tissue composition, and mechanical properties throughout healing. We hypothesized that reduction in Col5 expression would result in an abnormal wound matrix post-injury, resulting in reduced mechanical properties compared to normal tendons. Following patellar tendon surgery, mice were euthanized at 1, 3, and 6-week post-injury. Col5-deficient tendons demonstrated altered and decreased healing compared to WT tendons. The lack of resolution in cellularity by 6-week post-injury in Col5-deficient tendons influenced the decreased mechanical properties. Stiffness did not increase post-injury in Col5-deficient mice, and collagen fiber realignment was delayed during mechanical loading. Therefore, increased Col5a1 expression post-injury is necessary to re-establish matrix engagement and cellularity throughout tendon healing., (© 2023 Orthopaedic Research Society.)

Several tendon and ligament animal models were presented at the 2022 Orthopaedic Research Society Tendon Section Conference held at the University of Pennsylvania, May 5 to 7, 2022. A key objective of the breakout sessions at this meeting was to develop guidelines for the field, including for preclinical tendon and ligament animal models. This review summarizes the perspectives of experts for eight surgical small and large animal models of rotator cuff tear, flexor tendon transection, anterior cruciate ligament tear, and Achilles tendon injury using the framework: "Why, Who, What, Where, When, and How" (5W1H). A notable conclusion is that the perfect tendon model does not exist; there is no single gold standard animal model that represents the totality of tendon and ligament disease. Each model has advantages and disadvantages and should be carefully considered in light of the specific research question. There are also circumstances when an animal model is not the best approach. The wide variety of tendon and ligament pathologies necessitates choices between small and large animal models, different anatomic sites, and a range of factors associated with each model during the planning phase. Attendees agreed on some guiding principles including: providing clear justification for the model selected, providing animal model details at publication, encouraging sharing of protocols and expertise, improving training of research personnel, and considering greater collaboration with veterinarians. A clear path for translating from animal models to clinical practice was also considered as a critical next step for accelerating progress in the tendon and ligament field., (© 2023 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

A 53-year-old female, with a known case of adrenocortical carcinoma (ACC), underwent F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for initial staging, which revealed FDG avid large left suprarenal mass contiguous with hypermetabolic tumor thrombus in the inferior vena cava (IVC) through the left renal vein. Thereafter, she underwent angiogenesis imaging using Ga-68-NODAGA-RGD PET/CT, which showed similar avid tracer uptake in both primary and IVC thrombus. Demonstration of RGD avidity in ACC in this case opens a new horizon for targeted radionuclide therapy (e.g., Lu-177 RGD) in selected patients, who may have limited therapeutic options., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Indian Journal of Nuclear Medicine.)

Mucopolysaccharidosis (MPS) VII is an inherited lysosomal storage disorder characterized by deficient activity of the enzyme β-glucuronidase. Skeletal abnormalities are common in patients and result in diminished quality of life. Enzyme replacement therapy (ERT) for MPS VII using recombinant human β-glucuronidase (vestronidase alfa) was recently approved for use in patients; however, to date there have been no studies evaluating therapeutic efficacy in a large animal model of MPS VII. The objective of this study was to establish the effects of intravenous ERT, administered at either the standard clinical dose (4 mg/kg) or a high dose (20 mg/kg), on skeletal disease progression in MPS VII using the naturally occurring canine model. Untreated MPS VII animals exhibited progressive synovial joint and vertebral bone disease and were no longer ambulatory by age 6 months. Standard-dose ERT-treated animals exhibited modest attenuation of joint disease, but by age 6 months were no longer ambulatory. High-dose ERT-treated animals exhibited marked attenuation of joint disease, and all were still ambulatory by age 6 months. Vertebral bone disease was recalcitrant to ERT irrespective of dose. Overall, our findings indicate that ERT administered at higher doses results in significantly improved skeletal disease outcomes in MPS VII dogs., Competing Interests: This study was funded in part by Ultragenyx Pharmaceutical, the company that produces vestronidase alfa (the drug that was evaluated). In addition, the drug used in the study was provided by the company at no cost to the investigators. Specific author conflicts: L.J.S., Research grant from Ultragenyx Pharmaceutical; Scientific Advisory Board, National MPS Society; Scientific Advisory Board, JOR Spine. G.R.D., co-founder and CEO, Mechano-Therapeutics LLC. W.M., book royalties, “Diagnostic MRI in Dogs and Cats,” Taylor & Francis. R.G., consultant, Acorn Biolabs; Scientific Advisory Board, JOR Spine. C.R.S., G.L., C.Z., Z.J., Y.K.L., S.S.S., S.Y.J., and K.A., no relevant disclosures., (© 2022 The Authors.)

Decorin and biglycan are two small leucine-rich proteoglycans (SLRPs) that regulate collagen fibrillogenesis and extracellular matrix assembly in tendon. The objective of this study was to determine the individual roles of these molecules in maintaining the structural and mechanical properties of tendon during homeostasis in mature mice. We hypothesized that knockdown of decorin in mature tendons would result in detrimental changes to tendon structure and mechanics while knockdown of biglycan would have a minor effect on these parameters. To achieve this objective, we created tamoxifen-inducible mouse knockdown models targeting decorin or biglycan inactivation. This enables the evaluation of the roles of these SLRPs in mature tendon without the abnormal tendon development caused by conventional knockout models. Contrary to our hypothesis, knockdown of decorin resulted in minor alterations to tendon structure and no changes to mechanics while knockdown of biglycan resulted in broad changes to tendon structure and mechanics. Specifically, knockdown of biglycan resulted in reduced insertion modulus, maximum stress, dynamic modulus, stress relaxation, and increased collagen fiber realignment during loading. Knockdown of decorin and biglycan produced similar changes to tendon microstructure by increasing the collagen fibril diameter relative to wild-type controls. Biglycan knockdown also decreased the cell nuclear aspect ratio, indicating a more spindle-like nuclear shape. Overall, the extensive changes to tendon structure and mechanics after knockdown of biglycan, but not decorin, provides evidence that biglycan plays a major role in the maintenance of tendon structure and mechanics in mature mice during homeostasis., (© 2022 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

The seasonal and spatial distribution of total organic carbon (TOC) is presented for the coastal waters of the eastern Arabian Sea, which experiences seasonal suboxia during the late southwest monsoon (SWM). This study reveals that high TOC was observed off Kochi as compared to Goa and Mangalore transects, and may be attributed to stronger upwelling along the Kerala coast. This is also supported by the excess carbon due to upwelling during the late SWM that varied from 37 μM (Goa), 39 μM (Mangalore), to 51 μM (Kochi). Our seasonal data from 2014 to 2020 at the Goa transect indicates that high TOC is seen during late SWM to fall inter monsoon (FIM) and between the late northeast monsoon (NEM) to the early spring inter monsoon (SIM). The high TOC concentrations and C/N ratios observed during the FIM are a combination of high primary production, the buildup of remnant organic matter from the previous season (due to prevailing low oxygen conditions), accumulation of refractory organic carbon, and release from diatoms (especially Chaetoceros sp.). Inter-annual variations indicate that phytoplankton blooms resulted in higher TOC concentrations, especially during the year 2020. Based on a comparison with an Elnino-Southern Oscillation (ENSO) year (2015), we can infer that the partitioning of carbon may increase from particulate to dissolved phase in future warming scenarios., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Injured tendons do not regain their native structure except at fetal or very young ages. Healing tendons often show mucoid degeneration involving accumulation of sulfated glycosaminoglycans (GAGs), but its etiology and molecular base have not been studied substantially. We hypothesized that quality and quantity of gene expression involving the synthesis of proteoglycans having sulfated GAGs are altered in injured tendons and that a reduction in synthesis of sulfated GAGs improves structural and functional recovery of injured tendons. C57BL6/j mice were subjected to Achilles tendon tenotomy surgery. The injured tendons accumulated sulfate proteoglycans as early as 1-week postsurgery and continued so by 4-week postsurgery. Transcriptome analysis revealed upregulation of a wide range of proteoglycan genes that have sulfated GAGs in the injured tendons 1 and 3 weeks postsurgery. Genes critical for enzymatic reaction of initiation and elongation of chondroitin sulfate GAG chains were also upregulated. After the surgery, mice were treated with the 2-deoxy-d-glucose (2DG) that inhibits conversion of glucose to glucose-6-phosphate, an initial step of glucose metabolism as an energy source and precursors of monosaccharides of GAGs. The 2DG treatment reduced accumulation of sulfated proteoglycans, improved collagen fiber alignment, and reduced the cross-sectional area of the injured tendons. The modulus of the 2DG-treated groups was higher than that in the vehicle group, but not of statistical significance. Our findings suggest that mucoid degeneration in injured tendons may result from the upregulated expression of genes involved the synthesis of sulfate proteoglycans and can be inhibited by reduction of glucose utilization., (© 2021 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Appropriate timing of cervical remodeling (CR) is key to normal term parturition. To date, mechanisms behind normal and abnormal (premature or delayed) CR remain unclear. Recent studies show regional differences exist in human cervical tissue structure. While the entire cervix contains extracellular matrix (ECM), the internal os is highly cellular containing 50-60% cervical smooth muscle (CSM). The external os contains 10-20% CSM. Previously, we reported ECM rigidity and different ECM proteins influence CSM cell function, highlighting the importance of understanding not only how cervical cells orchestrate cervical ECM remodeling in pregnancy, but also how changes in specific ECM proteins can influence resident cellular function. To understand this dynamic process, we utilized a systematic proteomic approach to understand which soluble ECM and cellular proteins exist in the different regions of the human cervix and how the proteomic profiles change from the non-pregnant (NP) to the pregnant (PG) state. We found the human cervix proteome contains at least 4548 proteins and establish the types and relative abundance of cellular and soluble matrisome proteins found in the NP and PG human cervix. Further, we report the relative abundance of proteins involved with elastic fiber formation and ECM organization/degradation were significantly increased while proteins involved in RNA polymerase I/promoter opening, DNA methylation, senescence, immune system, and compliment activation were decreased in the PG compared to NP cervix. These findings establish an initial platform from which we can further comprehend how changes in the human cervix proteome results in normal and abnormal CR., (© 2022. Society for Reproductive Investigation.)

Tendon is a vital musculoskeletal tissue that is prone to degeneration. Proper tendon maintenance requires complex interactions between extracellular matrix components that remain poorly understood. Collagen VI and biglycan are two matrix molecules that localize pericellularly within tendon and are critical regulators of tissue properties. While evidence suggests that collagen VI and biglycan interact within the tendon matrix, the relationship between the two molecules and its impact on tendon function remains unknown. We sought to elucidate potential coordinate roles of collagen VI and biglycan within tendon by defining tendon properties in knockout models of collagen VI, biglycan, or both molecules. We first demonstrated co-expression and co-localization of collagen VI and biglycan within the healing tendon, providing further evidence of cooperation between the two molecules during nascent tendon matrix formation. Deficiency in collagen VI and/or biglycan led to significant reductions in collagen fibril size and tendon mechanical properties. However, collagen VI-null tendons displayed larger reductions in fibril size and mechanics than seen in biglycan-null tendons. Interestingly, knockout of both molecules resulted in similar properties to collagen VI knockout alone. These results indicate distinct and non-additive roles for collagen VI and biglycan within tendon. This work provides better understanding of regulatory interactions between two critical tendon matrix molecules., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Published by Elsevier B.V.)

Macroalgae supersede corals in the reefs worldwide, converting the coral-dominant systems into algal-dominant ones. Dissolved organic carbon (DOC) released by macroalgae play a prominent role in degrading the coral reefs by stimulating the bacterial growth and metabolism. However, the long-term remineralization of macroalgal DOC and their contribution to the carbon pool are least studied. In this study, we quantified the DOC released by five species of macroalgae that affected live corals through their physical contact and their subsequent remineralization for 100 days by coral mucus bacteria. Also, we analyzed the changes in bacterial community structure after 30 days of exposure to the macroalgal DOC. All the macroalgae released a significant amount of DOC ranging from 2.2 ± 0.17 to 8.1 ± 0.36 μmol C g -1 h -1 (mean ± SD). After 100 days, between 9.2 and 30.9% of the macroalgal DOC remained recalcitrant to bacterial remineralization. There was no apparent change in the dominant bacterial groups exposed to the DOC released by the green macroalgae Caulerpa racemosa and Halimeda sp. In comparison, the Proteobacteria group decreased with a prominent increase in the Firmicutes, Planctomycetes, and Bacteroidetes group in the samples exposed to DOC released by the brown macroalgae Turbinaria ornata, Sargassum tenerrimum, and Padina gymnospora. These inclusive data suggest that the DOC released by different species of macroalgae differed on their lability to microbial mineralization and highlight the comparable patterns in microbial responses to macroalgal exudates across different species., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Autologous protein solution (APS) has been used anecdotally for intralesional treatment of tendon and ligament injuries, however, its use in these injuries has never been studied in vivo . Our objective was to evaluate the effect of APS on tendon healing in an equine superficial digital flexor (SDF) tendonitis model. We hypothesized intralesional injection of APS would result in superior structural and biomechanical healing. SDF tendonitis was induced in both forelimbs of eight horses using collagenase injection. One forelimb was randomly assigned to receive an intralesional injection of APS, while the other was injected with saline. Ultrasonographic examinations were performed at weeks -1, 0, 2, 4, 8, and 12 following treatment. At 12 weeks, horses were euthanized and SDF samples harvested. Histologic evaluation, biomechanical testing, gene expression analysis, total glycosaminoglycan (GAG) and total DNA quantification were performed. Collagen type III ( COL3A1 ) expression was significantly higher ( p = 0.028) in saline treated tendon than in normal tendon. Otherwise, there were no significant differences in gene expression. There were no significant differences in histologic or ultrasonographic scores between groups. Mean total DNA content was significantly higher ( p = 0.024) in saline treated tendons than normal tendons, whereas total DNA content was not significantly different between APS treated tendon and normal tendon. Elastic modulus was higher in APS treated than saline treated tendon, but the difference was not significant. Reduced expression of COL3A1 in APS treated tendon may indicate superior healing. Increased total DNA content in saline treated tendon may indicate ongoing healing processes, vs. APS treated tendons which may be in the later stages of healing. Limitations include a relatively short study period and inconsistency in size and severity of induced lesions. Intralesional injection of APS resulted in some improvements in healing characteristics., Competing Interests: WK is the Director of Research and Development at Owl Manor, who's product was investigated in this study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gaesser, Underwood, Linardi, Even, Reef, Shetye, Mauck, King, Engiles and Ortved.)

Tendon plays a critical role in the joint movement by transmitting force from muscle to bone. This transmission of force is facilitated by its specialized structure, which consists of highly aligned extracellular matrix consisting predominantly of type I collagen. Tenocytes, fibroblast-like tendon cells residing between the parallel collagen fibers, regulate this specialized tendon matrix. Despite the importance of collagen structure and tenocyte function, the biological mechanisms regulating fibrillogenesis and tenocyte maturation are not well understood. Here we examine the function of Reticulocalbin 3 (Rcn3) in collagen fibrillogenesis and tenocyte maturation during postnatal tendon development using a genetic mouse model. Loss of Rcn3 in tendon caused decreased tendon thickness, abnormal tendon cell maturation, and decreased mechanical properties. Interestingly, Rcn3 deficient mice exhibited a smaller collagen fibril distribution and over-hydroxylation in C-telopeptide cross-linking lysine from α1(1) chain. Additionally, the proline 3-hydroxylation sites in type I collagen were also over-hydroxylated in Rcn3 deficient mice. Our data collectively suggest that Rcn3 is a pivotal regulator of collagen fibrillogenesis and tenocyte maturation during postnatal tendon development.

Objective: The aim was to identify the source of cells within the center of the abnormal fibrocartilage tissue of the degenerative intervertebral disc after injury., Design: Cross-breeding of mice with an inducible type II promoter collagen construct (Col2CreER) to Rosa26-TdTomato mice has been shown to result in Cre-recombinase activity and Tomato expression in inner annulus fibrosus cells after tamoxifen injection. To investigate the role of the inner annulus fibrosus in the intervertebral disc injury response, tail intervertebral discs of Col2CreER/tdTomato mice were punctured with a needle and examined 1-4 wks after injury. N-cadherin was examined by immunostaining., Results: After the injury, the fibrocartilage in the degenerative intervertebral disc consisted of residual diseased nucleus pulposus cells and encroaching inner annulus fibrosus cells. The residual nucleus pulposus cells had lost their epithelial cell-like morphology and instead became oval shaped, with reduced adhesion to neighboring nucleus pulposus cells. This change in cellular morphology coincided with a loss of N-cadherin, which contributes to maintenance of healthy nucleus pulposus cell morphology. As expected, injured tail intervertebral discs showed reduced compressive properties as determined by biomechanical assessments., Conclusions: The cellular composition of the degenerative intervertebral disc has been defined here, which is an important step in developing future treatments., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

We report seasonal and temporal variation of total organic carbon (TOC) in the eastern Arabian Sea (AS). In comparison to the deep, TOC in the top 100 m showed spatial variation with higher concentrations towards northern AS during North east monsoon (NEM) and South west monsoon (SWM). A comparison with the US-JGOFS data (1995) shows warmer temperatures, enhanced TOC and low chlorophyll in the recent years. High TOC is associated with Arabian Sea high saline waters (ASHSW), advected from the Arabian Gulf, might have resulted in an enhancement of TOC in the eastern AS. This excess TOC supports a high abundance of bacteria despite the low primary productivity. TOC oxidation accounted for 14.3% and 22.5% of oxygen consumption for waters with potential density between 24.5 and 27.3 kg/m 3 . This study attains great significance considering the missing links with respect to the role of transport processes in ocean deoxygenation under ongoing warming scenarios., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Ultrashort echo time (UTE) magnetic resonance imaging (MRI) measures proton signals in cortical bone from two distinct water pools, bound water, or water that is tightly bound to bone matrix, and pore water, or water that is freely moving in the pore spaces in bone. By isolating the signal contribution from the pore water pool, UTE biomarkers can directly quantify cortical bone porosity in vivo. The Porosity Index (PI) is one non-invasive, clinically viable UTE-derived technique that has shown strong associations in the tibia with μCT porosity and other UTE measures of bone water. However, the efficacy of the PI biomarker has never been examined in the proximal femur, which is the site of the most catastrophic osteoporotic fractures. Additionally, the loads experienced during a sideways fall are complex and the femoral neck is difficult to image with UTE, so the usefulness of the PI in the femur was unknown. Therefore, the aim of this study was to examine the relationships between the PI measure in the proximal cortical shaft of human cadaveric femora specimens compared to (1) QCT-derived bone mineral density (BMD) and (2) whole bone stiffness obtained from mechanical testing mimicking a sideways fall. Fifteen fresh, frozen whole cadaveric femora specimens (age 72.1 ± 15.0 years old, 10 male, 5 female) were scanned on a clinical 3-T MRI using a dual-echo UTE sequence. Specimens were then scanned on a clinical CT scanner to measure volumetric BMD (vBMD) and then non-destructively mechanically tested in a sideways fall configuration. The PI in the cortical shaft demonstrated strong correlations with bone stiffness (r = -0.82, P = 0.0014), CT-derived vBMD (r = -0.64, P = 0.0149), and with average cortical thickness (r = -0.60, P = 0.0180). Furthermore, a hierarchical regression showed that PI was a strong predictor of bone stiffness which was independent of the other parameters. The findings from this study validate the MRI-derived porosity index as a useful measure of whole-bone mechanical integrity and stiffness., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Anthropogenic activities release effluents containing nutrients and pathogenic bacteria that change the characteristics of coastal ecosystems. An important type of marine pollution which has occurred in 3 different states in India during 2019 is sea foam. Sea foam was found on Hole beach, Goa (Lat: 15.404° N, Long: 73.787° E), where nutrients (NO 3 - = 137 μM and organic nitrogen = 121 μM) from a garbage dumpyard are released directly via streams/gutters to coastal waters. This resulted in a bloom of the diatom Thalassiosira pseudonana, associated with high concentration of total organic carbon and fucoxanthin. Decay of this bloom along with strong agitation due to rocks and wave action resulted in sea foam. We isolated foam-associated bacteria and identified pathogenic bacteria including Enterobacter cancerogenus through 16S rRNA gene sequencing. Such foam-associated pathogenic bacteria, could be antibiotic resistant, and may have adverse effects on human health. This can also hamper the tourism industry of a small state like Goa that relies heavily on tourism.

Collagen XI is a fibril-forming collagen that regulates collagen fibrillogenesis. Collagen XI is normally associated with collagen II-containing tissues such as cartilage, but it also is expressed broadly during development in collagen I-containing tissues, including tendons. The goals of this study are to define the roles of collagen XI in regulation of tendon fibrillar structure and the relationship to function. A conditional Col11a1-null mouse model was created to permit the spatial and temporal manipulation of Col11a1 expression. We hypothesize that collagen XI functions to regulate fibril assembly, organization and, therefore, tendon function. Previous work using cho mice with ablated Col11a1 alleles supported roles for collagen XI in tendon fibril assembly. Homozygous cho/cho mice have a perinatal lethal phenotype that limited the studies. To circumvent this, a conditional Col11a1 flox/flox mouse model was created where exon 3 was flanked with loxP sites. Breeding with Scleraxis-Cre (Scx-Cre) mice yielded a tendon-specific Col11a1-null mouse line, Col11a1 Δten/Δten . Col11a1 flox/flox mice had no phenotype compared to wild type C57BL/6 mice and other control mice, e.g., Col11a1 flox/flox and Scx-Cre. Col11a1 flox/flox mice expressed Col11a1 mRNA at levels comparable to wild type and Scx-Cre mice. In contrast, in Col11a1 Δten/Δten mice, Col11a1 mRNA expression decreased to baseline in flexor digitorum longus tendons (FDL). Collagen XI protein expression was absent in Col11a1 Δten/Δten FDLs, and at ~50% in Col11a1 +/Δten compared to controls. Phenotypically, Col11a1 Δten/Δten mice had significantly decreased body weights (p < 0.001), grip strengths (p < 0.001), and with age developed gait impairment becoming hypomobile. In the absence of Col11a1, the tendon collagen fibrillar matrix was abnormal when analyzed using transmission electron microscopy. Reducing Col11a1 and, therefore collagen XI content, resulted in abnormal fibril structure, loss of normal fibril diameter control with a significant shift to small diameters and disrupted parallel alignment of fibrils. These alterations in matrix structure were observed in developing (day 4), maturing (day 30) and mature (day 60) mice. Altering the time of knockdown using inducible I-Col11a1 -/- mice indicated that the primary regulatory foci for collagen XI was in development. In mature Col11a1 Δten/Δten FDLs a significant decrease in the biomechanical properties was observed. The decrease in maximum stress and modulus suggest that fundamental differences in the material properties in the absence of Col11a1 expression underlie the mechanical deficiencies. These data demonstrate an essential role for collagen XI in regulation of tendon fibril assembly and organization occurring primarily during development., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Imaging of dextrocardia in humans requires an understanding of the orientation of the heart chambers and walls. There are many types of cardiac malpositioning, such as dextrocardia (with or without situs inversus), mesocardia, and levocardia. Myocardial perfusion scintigraphy of dextrocardia has been explained in case reports and imaging atlases; however, myocardial viability assessment using nuclear medicine imaging techniques is less documented in the literature. Methods: In 2 cases of dextrocardia with situs inversus and 1 case of mesocardia, myocardial viability was assessed using 99m Tc-sestamibi rest perfusion scintigraphy and 18 F-FDG PET. Cardiac SPECT images of dextrocardia with situs inversus were acquired using the feet-first supine position with a 180° arc from left anterior oblique to right posterior oblique, whereas a right-lateral-to-left-lateral arc was used for mesocardia. The processing and reconstruction were done by entering the dataset for the feet-first supine position and repeating after entering the dataset for the feet-first prone position. The 2 sets of reconstructed images were compared for orientation of walls and cardiac chambers. Results: The first processing, using the feet-first supine position, revealed an interchanged septum and lateral wall in reconstructed images of dextrocardia with situs inversus. This interchange was corrected by changing the position to prone during processing of the rest perfusion and PET raw data. The display of cardiac slices in various axes matched the conventional nomenclature for the septum and lateral wall, leading to easy interpretation. However, this change was not required in the mesocardia, for which the location of the heart chambers was not interchanged. Conclusion: Because the acquisition protocol for SPECT is a semicircular orbit, the various types of dextrocardia require careful selection of the arc, with the patient positioning kept feet-first supine. Processing and reconstruction of data by changing the patient position to prone was found to be most useful method of matching the septum and lateral wall orientation for interpretation of images., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)

Tendon injuries increase with age, yet the age-associated changes in tendon properties remain unexplained. Decorin and biglycan are two matrix proteoglycans that play complex roles in regulating tendon formation, maturation, and aging, most notably in extracellular matrix assembly and maintenance. However, the roles of decorin and biglycan have not been temporally isolated in a homeostatic aged context. The goal of this work was to temporally isolate and define the roles of decorin and biglycan in regulating aged murine patellar tendon mechanical properties. We hypothesized that decorin would have a larger influence than biglycan on aged tendon mechanical properties and that biglycan would have an additive role in this regulation. When decorin and biglycan were knocked down in aged tendons, minimal changes in gene expression were observed, implying that these models directly define the roles of decorin and biglycan in regulating tendon mechanical properties. Knockdown of decorin or biglycan led to minimal changes in quasi-static mechanical properties. However, decorin deficiency led to increases in stress relaxation and phase shift that were exacerbated when coupled with biglycan deficiency. This study highlights an important role for decorin, alone and in tandem with biglycan, in regulating aged tendon viscoelastic properties., (Copyright © 2020 by ASME.)

Pregnant women experience weight gain, gait changes, and biochemical fluctuations that impair joint function and alter the maternal skeleton. Hormonal changes increase pelvic ligament laxity in preparation for childbirth and affect peripheral joint laxity. Calcium demands also rise during pregnancy and lactation, resulting in reduced bone mineral density (BMD) and maternal bone loss. Altered tendon properties and bone loss during pregnancy and lactation may impact tendon insertion sites, such as rotator cuff tendons where insertion site ruptures are common. However, the effects of pregnancy and lactation at the tendon-to-bone interface have not been investigated. Therefore, the objective of this study was to evaluate supraspinatus tendon mechanical properties and insertion site microstructure during pregnancy, lactation, and postweaning recovery in female rats. We hypothesized that pregnancy and lactation would compromise supraspinatus tendon mechanical properties and subchondral bone microstructure. Female rats were divided into virgin, pregnancy, lactation, and recovery groups, and supraspinatus tendons were mechanically evaluated. Surprisingly, tendon mechanics was unaffected by pregnancy and lactation. However, tendon modulus decreased two-weeks postweaning. Additionally, tendons failed by bony avulsion at the insertion site, and the lactation group exhibited reduced failure properties corresponding to decreased subchondral bone mineralization. Lactation also resulted in dramatic bone loss at the epiphysis, but trabecular bone microarchitecture recovered postweaning. In conclusion, lactation following pregnancy impaired trabecular bone microstructure and subchondral bone mineralization, leading to reduced supraspinatus tendon-to-bone insertion site failure properties. These findings will contribute toward understanding the pathogenesis of tendon-to-bone disorders., (Copyright © 2020 by ASME.)

The study was conducted to define the biomechanical response of rat Achilles tendon after a single bout of exercise and a short or long duration of daily exercise. We hypothesized that a single bout or a short duration of exercise would cause a transient decrease in Achilles tendon mechanical properties and a long duration of daily exercise would improve these properties. One hundred and thirty-six Sprague-Dawley rats were divided into cage activity (CA) or exercise (EX) groups for a single bout, short-term, or long-term exercise. Animals in single bout EX groups were euthanized, 3, 12, 24, or 48 h upon completion of a single bout of exercise (10 m/min, 1 h) on a flat treadmill. Animals in short-term EX groups ran on a flat treadmill for 3 days, 1, or 2 weeks while animals in long-term EX groups ran for 8 weeks. Tendon quasi-static and viscoelastic response was evaluated for all Achilles tendons. A single bout of exercise increased tendon stiffness after 48 h of recovery. Short-term exercise up to 1 week decreased cross-sectional area, stiffness, modulus, and dynamic modulus of the Achilles tendon. In contrast, 8 weeks of daily exercise increased stiffness, modulus, and dynamic modulus of the tendon. This study highlights the response of Achilles tendons to single and sustained bouts of exercise. Adequate time intervals are important to allow for tendon adaptations when initiating a new training regimen and overall beneficial effects to the Achilles tendon., (Copyright © 2020 by ASME.)

Half of the women who sustain a hip fracture would not qualify for osteoporosis treatment based on current DXA-estimated bone mineral density criteria. Therefore, a better approach is needed to determine if an individual is at risk of hip fracture from a fall. The objective of this study was to determine the association between radiation-free MRI-derived bone strength and strain simulations compared to results from direct mechanical testing of cadaveric femora. Imaging was conducted on a 3-Tesla MRI scanner using two sequences: one balanced steady-state free precession sequence with 300 μm isotropic voxel size and one spoiled gradient echo with anisotropic voxel size of 234 × 234 × 1500 μm. Femora were dissected free of soft-tissue and 4350-ohm strain-gauges were securely applied to surfaces at the femoral shaft, inferior neck, greater trochanter, and superior neck. Cadavers were mechanically tested with a hydraulic universal test frame to simulate loading in a sideways fall orientation. Sideways fall forces were simulated on MRI-based finite element meshes and bone stiffness, failure force, and force for plastic deformation were computed. Simulated bone strength metrics from the 300 μm isotropic sequence showed strong agreement with experimentally obtained values of bone strength, with stiffness (r = 0.88, p = 0.0002), plastic deformation point (r = 0.89, p < 0.0001), and failure force (r = 0.92, p < 0.0001). The anisotropic sequence showed similar trends for stiffness, plastic deformation point, and failure force (r = 0.68, 0.70, 0.84; p = 0.02, 0.01, 0.0006, respectively). Surface strain-gauge measurements showed moderate to strong agreement with simulated magnitude strain values at the greater trochanter, superior neck, and inferior neck (r = -0.97, -0.86, 0.80; p ≤0.0001, 0.003, 0.03, respectively). The findings from this study support the use of MRI-based FE analysis of the hip to reliably predict the mechanical competence of the human femur in clinical settings., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Traditional tendon-to-bone repair where the tendon is reattached to bone via suture anchors often results in disorganized scar production rather than the formation of a zonal insertion. In contrast, ligament reconstructions where tendon grafts are passed through bone tunnels can yield zonal tendon-to-bone attachments between the graft and adjacent bone. Therefore, ligament reconstructions can be used to study mechanisms that regulate zonal tendon-to-bone repair in the adult. Anterior cruciate ligament (ACL) reconstructions are one of the most common reconstruction procedures and while we know that cells from outside the graft produce the attachments, we have not yet established specific cell populations that give rise to this tissue. To address this knowledge gap, we performed ACL reconstructions in lineage tracing mice where α-smooth muscle actin (αSMACreERT2) was used to label αSMA-expressing progenitors within the bone marrow that produced zonal attachments. Expression of αSMA was increased during early stages of the repair process such that the contribution of SMA-labeled cells to the tunnel integration was highest when tamoxifen was delivered in the first week post-surgery. The zonal attachments shared features with normal entheses, including tidemarks oriented perpendicularly to collagen fibers, Col1a1-expressing cells, alkaline phosphatase activity, and proteoglycan-rich staining. Finally, the integration strength increased with time, requiring 112% greater force to remove the graft from the tunnel at 28 days compared with 14 days post-surgery. Future studies will target these progenitor cells to define the pathways that regulate zonal tendon-to-bone repair in the adult. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:105-116, 2020., (© 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

The MRI-derived porosity index (PI) is a non-invasively obtained biomarker based on an ultrashort echo time sequence that images both bound and pore water protons in bone, corresponding to water bound to organic collagenous matrix and freely moving water, respectively. This measure is known to strongly correlate with the actual volumetric cortical bone porosity. However, it is unknown whether PI may also be able to directly quantify bone organic composition and/or mechanical properties. We investigated this in human cadaveric tibiae by comparing PI values to near infrared spectral imaging (NIRSI) compositional data and mechanical compression data. Data were obtained from a cohort of eighteen tibiae from male and female donors with a mean ± SD age of 70 ± 21 years. Biomechanical stiffness in compression and NIRSI-derived collagen and bound water content all had significant inverse correlations with PI ( r  = -0.79, -0.73, and -0.95 and p  = 0.002, 0.007, and <0.001, respectively). The MRI-derived bone PI alone was a moderate predictor of bone stiffness ( R 2  = 0.63, p  = 0.002), and multivariate analyses showed that neither cortical bone cross-sectional area nor NIRSI values improved bone stiffness prediction compared to PI alone. However, NIRSI-obtained collagen and water data together were a moderate predictor of bone stiffness (R 2  = 0.52, p  = 0.04). Our data validates the MRI-derived porosity index as a strong predictor of organic composition of bone and a moderate predictor of bone stiffness, and also provides preliminary evidence that NIRSI measures may be useful in future pre-clinical studies on bone pathology.

In this study we report silica rich anthropogenic spherules from the marine environment. We found spherical, dumbbell, teardrop and fused spherules in Zuari estuary (near the Dona paula jetty), south west coast of India. The spherules were composed of SiO 2 (69.8%), Na 2 O (13.2%), CaO (8.8%), MgO (3.8%), and traces of Al 2 O 3 , and FeO. Their high Na and Ca contents rules out the possibility of being an impact spherule or microtektite, or anthropogenic spherules coming from fly ash. Their elemental composition suggests that these are glass micro beads that have many applications including production of road and pavement marking materials, such as traffic paints. Considering that the glass micro beads are known to have high concentrations of Pb, As, and Sb that can leach into the marine environment, this study also raises questions regarding the impact of such spherules on marine biota, and highlights the need for further detailed study., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The relative importance of organic nitrogen (ON) and inorganic nitrogen (IN) as nitrogen sources for the phytoplankton communities were studied through a seasonal time series of nitrogen species in the eastern Arabian Sea. Seasonal data on nitrogen species showed that ON dominates the system throughout the year and account for >90% of the total nitrogen (TN) during north east monsoon (NEM). The average ON concentration in the study region was 11.5 μM during NEM as compared to 7.2 μM during south west monsoon (SWM). The contribution of picoplankton to the total phytoplankton pool (f pico ) increased from 19% during SWM to 36% in NEM. Along with cyanobacteria, the diatoms Thalassionema nitzchoides and Thalassiosira sp. and among the dinoflagellates Pronoctiluca sp. were found to proliferate in ON rich waters. We suggest atmospheric deposition, riverine-input, resuspension of bottom sediment and ground water intrusion as the possible sources of ON in the study region., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

A cadaveric study was performed to investigate the external mechanical forces required to fracture maxillary fourth premolar teeth in domestic dogs and describe a clinically relevant model of chewing forces placed on functionally important teeth in which fracture patterns are consistent with those defined by the American Veterinary Dental College (AVDC). Twenty-four maxillary fourth premolar teeth were harvested from dog cadavers. Samples consisted of teeth with surrounding alveolar bone potted in polycarbonate cylinders filled with acrylic. The cylinders were held by an aluminum device at an angle of 60° with respect to the ground. An axial compression test was performed, creating a force upon the occluso-palatal aspects of the main cusps of the crowns of the teeth. The highest compressive force prior to failure was considered the maximum force sustained by the teeth. Results showed the mean maximum force (± SD) sustained by the tested teeth at the point of fracture was 1,281 N (± 403 N) at a mean impact angle (± SD) of 59.7° (± 5.2°). The most common fracture type that occurred among all samples was a complicated crown fracture ( n = 12), followed by an uncomplicated crown fracture ( n = 6), complicated crown-root fracture ( n = 5), and uncomplicated crown-root fracture ( n = 1). There was no statistically significant correlation between dog breed, age, weight, impact angle, crown height or crown diameter, and the maximum force applied at the point of fracture. The only independent variable that remained significantly associated with maximum force was the crown height to diameter ratio ( p = 0.005), suggesting that a decreased ratio increases tooth fracture resistance. The methodology described herein has been successful in creating a pattern of fracture of maxillary fourth premolar teeth consistent with that defined by the AVDC under angled compression at forces within the maximum chewing capability of the average domestic dog.

Background: Lesions of the long head of the biceps tendon are often associated with massive rotator cuff tears (MRCTs), and biceps tenotomy is frequently performed for pain relief and functional reservation. However, the efficacy and safety of biceps tenotomy regarding the effects on the surrounding tissues in chronic MRCT are unclear., Hypothesis: Biceps tenotomy would result in improved mechanical and histological properties of the intact subscapularis tendon and improved in vivo shoulder function while not compromising glenoid cartilage properties., Study Design: Controlled laboratory study., Methods: Right supraspinatus and infraspinatus tendons were detached in 25 male Sprague-Dawley rats, followed by 4 weeks of cage activity to create a chronic MRCT condition. Animals were randomly divided into 2 groups and received either biceps tenotomy (n = 11) or sham surgery (n = 14) and were sacrificed 4 weeks thereafter. Forelimb gait and ground-reaction forces were recorded 1 day before the tendon detachment (baseline), 1 day before the surgical intervention (biceps tenotomy or sham), and 3, 7, 10, 14, 21, and 28 days after the intervention to assess in vivo shoulder joint function. The subscapularis tendon and glenoid cartilage were randomly allocated for mechanical testing or histologic assessment after the sacrifice., Results: Compared with sham surgery, biceps tenotomy partially restored the in vivo shoulder joint function, with several gait and ground-reaction force parameters returning closer to preinjury baseline values at 4 weeks. With biceps tenotomy, mechanical properties of the subscapularis tendons were improved, while mechanical properties and histological Mankin scores of the glenoid cartilage were not diminished when compared with the sham group., Conclusion: Biceps tenotomy in the presence of chronic MRCT partially preserves overall shoulder function and potentially restores subscapularis tendon health without causing detrimental effects to joint cartilage. This laboratory study adds to the growing literature regarding the protective effects of biceps tenotomy on the shoulder joint in a chronic MRCT model., Clinical Relevance: This study provides important basic science evidence supporting the use of biceps tenotomy in patients with massive rotator cuff tears.

Despite efforts to simulate the in vivo environment, post-mortem degradation and lack of blood perfusion complicate the use of ex vivo derived material models in computational studies of spinal cord injury. In order to quantify the mechanical changes that manifest ex vivo, the viscoelastic behavior of in vivo and ex vivo porcine spinal cord samples were compared. Stress-relaxation data from each condition were fit to a non-linear viscoelastic model using a novel characterization technique called the direct fit method. To validate the presented material models, the parameters obtained for each condition were used to predict the respective dynamic cyclic response. Both ex vivo and in vivo samples displayed non-linear viscoelastic behavior with a significant increase in relaxation with applied strain. However, at all three strain magnitudes compared, ex vivo samples experienced a higher stress and greater relaxation than in vivo samples. Significant differences between model parameters also showed distinct relaxation behaviors, especially in non-linear relaxation modulus components associated with the short-term response (0.1-1 s). The results of this study underscore the necessity of utilizing material models developed from in vivo experimental data for studies of spinal cord injury, where the time-dependent properties are critical. The ability of each material model to accurately predict the dynamic cyclic response validates the presented methodology and supports the use of the in vivo model in future high-resolution finite element modeling efforts., Statement of Significance: Neural tissues (such as the brain and spinal cord) display time-dependent, or viscoelastic, mechanical behavior making it difficult to model how they respond to various loading conditions, including injury. Methods that aim to characterize the behavior of the spinal cord almost exclusively use ex vivo cadaveric or animal samples, despite evidence that time after death affects the behavior compared to that in a living animal (in vivo response). Therefore, this study directly compared the mechanical response of ex vivo and in vivo samples to quantify these differences for the first time. This will allow researchers to draw more accurate conclusions about spinal cord injuries based on ex vivo data (which are easier to obtain) and emphasizes the importance of future in vivo experimental animal work., (Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

As the strongest of the meningeal tissues, the spinal dura mater plays an important role in the overall behavior of the spinal cord-meningeal complex (SCM). It follows that the accumulation of damage affects the dura mater's ability to protect the cord from excessive mechanical loads. Unfortunately, current computational investigations of spinal cord injury (SCI) etiology typically do not include postyield behavior. Therefore, a more detailed description of the material behavior of the spinal dura mater, including characterization of damage accumulation, is required to comprehensively study SCI. Continuum mechanics-based viscoelastic damage theories have been previously applied to other biological tissues; however, the current work is the first to report damage accumulation modeling in a tissue of the SCM complex. Longitudinal (i.e., cranial-to-caudal long-axis) samples of ovine cervical dura mater were tensioned-to-failure at one of three strain rates (quasi-static, 0.05/s, and 0.3/s). The resulting stress-strain data were fit to a hyperelastic continuum damage model to characterize the strain-rate-dependent subfailure and failure behavior. The results show that the damage behavior of the fibrous and matrix components of the dura mater are strain-rate dependent, with distinct behaviors when exposed to strain rates above that experienced during normal voluntary neck motion suggesting the possible existence of a protective mechanism., (Copyright © 2018 by ASME.)

The role of the cervicovaginal (CV) microbiome in regulating cervical function during pregnancy is poorly understood. Gardnerella vaginalis (G. vaginalis) is the most common bacteria associated with the diagnosis of bacterial vaginosis (BV). While BV has been associated with preterm birth (PTB), clinical trials targeting BV do not decrease PTB rates. It remains unknown if G. vaginalis is capable of triggering molecular, biomechanical and cellular events that could lead to PTB. The objective of this study was to determine if cervicovaginal colonization with G. vaginalis, in pregnant mice, induced cervical remodeling and modified cervical function. CD-1 timed-pregnant mice received a 5X108 CFU/mL intravaginal inoculation of G. vaginalis or control on embryonic day 12 (E12) and E13. On E15, the mice were sacrificed and cervicovaginal fluid (CVF), amniotic fluid (AF), cervix, uterus, placentas and fetal membranes (FM) were collected. Genomic DNA was isolated from the CVF, placenta, uterus and FM and QPCR was performed to confirm colonization. IL-6 was measured in the CVF and AF and soluble e-cadherin (seCAD) was assessed in the CVF by ELISA. RNA was extracted from the cervices to evaluate IL-10, IL-8, IL-1β, TNF-α, Tff-1, SPINK-5, HAS-1 and LOX expression via QPCR. Mucicarmine and trichrome staining was used to assess cervical mucin and collagen. Biomechanical properties of the cervix were studied using quasi-static tensile load-to-failure biomechanical tests. G. vaginalis successfully colonized the CV space. This colonization induced immune responses (increased IL-6 levels in CVF and AF, increased mRNA expression of cervical cytokines), altered the epithelial barrier (increased seCAD in the CVF), induced cervical remodeling (increased mucin production, altered collagen) and altered cervical biomechanical properties (a decrease in biomechanical modulus and an increase in maximum strain). The ability of G. vaginalis to induce these molecular, immune, cellular and biomechanical changes suggests that this bacterium may play a pathogenic role in premature cervical remodeling leading to PTB.

OBJECTIVE Because of limitations inherent to cadaver models of endotracheal intubation, the authors' group developed a finite element (FE) model of the human cervical spine and spinal cord. Their aims were to 1) compare FE model predictions of intervertebral motion during intubation with intervertebral motion measured in patients with intact cervical spines and in cadavers with spine injuries at C-2 and C3-4 and 2) estimate spinal cord strains during intubation under these conditions. METHODS The FE model was designed to replicate the properties of an intact (stable) spine in patients, C-2 injury (Type II odontoid fracture), and a severe C3-4 distractive-flexion injury from prior cadaver studies. The authors recorded the laryngoscope force values from 2 different laryngoscopes (Macintosh, high intubation force; Airtraq, low intubation force) used during the patient and cadaver intubation studies. FE-modeled motion was compared with experimentally measured motion, and corresponding cord strain values were calculated. RESULTS FE model predictions of intact intervertebral motions were comparable to motions measured in patients and in cadavers at occiput-C2. In intact subaxial segments, the FE model more closely predicted patient intervertebral motions than did cadavers. With C-2 injury, FE-predicted motions did not differ from cadaver measurements. With C3-4 injury, however, the FE model predicted greater motions than were measured in cadavers. FE model cord strains during intubation were greater for the Macintosh laryngoscope than the Airtraq laryngoscope but were comparable among the 3 conditions (intact, C-2 injury, and C3-4 injury). CONCLUSIONS The FE model is comparable to patients and cadaver models in estimating occiput-C2 motion during intubation in both intact and injured conditions. The FE model may be superior to cadavers in predicting motions of subaxial segments in intact and injured conditions.

The small leucine-rich proteoglycans (SLRPs), decorin and biglycan, are key regulators of collagen fibril and matrix assembly. The goal of this work was to elucidate the roles of decorin and biglycan in tendon homeostasis. Our central hypothesis is that decorin and biglycan expression in the mature tendon would be critical for the maintenance of the structural and mechanical properties of healthy tendons. Defining the function(s) of these SLRPs in tendon homeostasis requires that effects in the mature tendon be isolated from their influence on development. Thus, we generated an inducible knockout mouse model that permits genetic ablation of decorin and biglycan expression in the mature tendon, while maintaining normal expression during development. Decorin and biglycan expression were knocked out in the mature patellar tendon with the subsequent turnover of endogenous SLRPs deposited prior to induction. The acute absence of SLRP expression was associated with changes in fibril structure with a general shift to larger diameter fibrils in the compound knockout tendons, together with fibril diameter heterogeneity. In addition, tendon mechanical properties were altered. Compared to wild-type controls, acute ablation of both genes resulted in failure of the tendon at lower loads, decreased stiffness, a trend towards decreased dynamic modulus, as well as a significant increase in percent relaxation and tissue viscosity. Collagen fiber realignment was also increased with a delayed and slower in response to load in the absence of expression. These structural and functional changes in response to an acute loss of decorin and biglycan expression in the mature tendon demonstrate a significant role for these SLRPs in adult tendon homeostasis., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Classic Ehlers-Danlos syndrome (EDS) patients suffer from connective tissue hyperelasticity, joint instability, skin hyperextensibility, tissue fragility, and poor wound healing due to heterozygous mutations in COL5a1 or COL5a2 genes. This study investigated the roles of collagen V in establishing structure and function in uninjured patellar tendons as well as in the injury response using a Col5a1 +/- mouse, a model for classic EDS. These analyses were done comparing tendons from a classic EDS model (Col5a1 +/- ) with wild-type controls. Tendons were subjected to mechanical testing, histological, and fibril analysis before injury as well as 3 and 6 weeks after injury. We found that Col5a1 +/- tendons demonstrated diminished recovery of mechanical competency after injury as compared to normal wild-type tendons, which recovered their pre-injury values by 6 weeks post injury. Additionally, the Col5a1 +/- tendons demonstrated altered fibril morphology and diameter distributions compared to the wild-type tendons. This study indicates that collagen V plays an important role in regulating collagen fibrillogenesis and the associated recovery of mechanical integrity in tendons after injury. In addition, the dysregulation with decreased collagen V expression in EDS is associated with a diminished injury response. The results presented herein have the potential to direct future targeted therapeutics for classic EDS patients. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2707-2715, 2017., (© 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Aim: This study evaluated the antibacterial activity and dimensional stability of irreversible hydrocolloids mixed with different concentrations of chlorhexidine gluconate instead of water., Materials and Methods: Experimental specimens (45 specimens) were prepared and allocated into three groups of 15 each. Group I: Impression material mixed with distilled water served as control. Groups II and III were prepared with 0.12 and 0.2% chlorhexidine gluconate solution, respectively. Specimens in each group were subjected to tests for dimensional stability. For antimicrobial activity, 30 specimens were prepared and allocated into three groups of 10 each named as group I (control), group II (0.12% chlorhexidine gluconate), and group III (0.2% chlorhexidine gluconate) similar to specimens for dimensional stability. Statistical analysis was performed using a one-way analysis of variance (ANOVA) and Tukey test., Results: Zones of inhibition were observed around test specimens, but not around control specimens; there was a significant intergroup difference in the diameters of the inhibition zones. In the test for dimensional stability, no significant differences were detected among groups, and the accuracy was clinically acceptable., Conclusion: Irreversible hydrocolloid impression material mixed with chlorhexidine exhibits varying degrees of antibacterial activity without influencing the dimensional stability of set material., Clinical Significance: Many contagious diseases can be prevented by practical control of infection in the dental office. Chlorhexidine gluconate, as a mixing liquid, ensures disinfection of impression, and this method of disinfection is more convenient and avoids extra effort as in other disinfection techniques.

The cervix is a unique organ able to dramatically change its shape and function by serving as a physical barrier for the growing fetus and then undergoing dramatic dilation allowing for delivery of a term infant. As a result, the cervix endures changing mechanical forces from the growing fetus. There is an emerging concept that the cervix may change or remodel "early" in many cases of spontaneous preterm birth (sPTB). However, the mechanical role of the cervix in both normal and preterm birth remains unclear. Therefore, the primary objective of this study was to determine the mechanical and structural responses of murine cervical tissue throughout a normal gestational time course. In this study, both tissue structural and material properties were determined via a quasi-static tensile load-to-failure test, while simultaneously obtaining dynamic collagen fiber re-alignment via cross-polarization imaging. This study demonstrated that the majority of the mechanical properties evaluated decreased at midgestation and not just at term, while collagen fiber re-alignment occurred earlier in the loading curve for cervices at term. This suggests that although structural changes in the cervix occur throughout gestation, the differences in material properties function in combination with collagen fiber re-alignment as mechanical precursors to regulate term gestation. This work lays a foundation for investigating cervical biomechanics and the role of the cervix in preterm birth.

Context: The differential cortical function obtained by Tc-99m EC is comparable to that of Tc-99m DMSA. However, identification of scars on Tc-99m EC images needs to be studied., Aims: The aim of the study is to evaluate role of Tc-99m EC for detection of scarring and differential cortical function by comparing with Tc-99m DMSA., Settings and Design: Prospective observational study of recurrent UTI; minimum 6 weeks after acute episode; when urine examination is negative for pus cells., Materials and Methods: Forty-seven children with normal positioned kidneys underwent Tc-99m EC and DMSA scintigraphy. The DRF and cortical phase images of both studies in the same image matrix size were evaluated by two independent observers for scarring; Tc-99m DMSA was considered as the gold standard., Statistical Analysis Used: MS Excel 2007 and GraphPad Instat V3.1 and ROC analysis., Results: There was no significant difference in the detection of scarring using two studies with Cohen's kappa coefficient (κ) 0.932. The sensitivity and specificity of Tc-99m EC for detection of scarring was 98.75% and 99.15%, respectively. There was good agreement between the differential cortical function calculated using two studies., Conclusions: The summed Tc-99m EC images with an acceptable high image contrast allow detection of cortical scarring in patients with normal kidney positions. It is an excellent single-modality comprehensive investigational agent for renal parenchymal defects, function, and excretion evaluation with the added advantages of lower cost, convenience, and low radiation exposure to the child., Competing Interests: There are no conflicts of interest

Objective: Nerve root decompression to relieve pain and radiculopathy remains one of the main goals of fusion-promoting procedures in the subaxial cervical spine. The use of allograft facet spacers has been suggested as a potential alternative for performing foraminotomies to increase the space available for the cervical nerve roots while providing segmental stiffening. Therefore, the goal of this cadaveric biomechanical study was to determine the acute changes in kinetics and foraminal area after the insertion of cortical bone facet spacers into the subaxial cervical spine., Methods: Allograft spacers (2 mm in height) were placed bilaterally into cadaveric cervical spine specimens (C2-T1, age of donors 57.5 ± 9.5 years, n = 7) at 1 (C4-5) and 3 (C3-6) levels with and without laminectomies and posterior lateral mass screw fixation. Standard stereophotogrammetry under pure moment loading was used to assess spinal kinetics. In addition, the authors performed 3D principal component analysis of CT scans to determine changes in foraminal cross-sectional area (FCSA) available for the spinal nerve roots., Results: Generally, the introduction of 2-mm-height facet spacers to the cervical spine produced mild, statistically insignificant reductions in motion with particular exceptions at the levels of implantation. No significant adjacent-level motion effects in any bending plane were observed. The addition of the posterior instrumentation (PI) to the intact spines resulted in statistically significant reductions in motion at all cervical levels and bending planes. The same kinetic results were obtained when PI was added to spines that also had facet spacers at 3 levels and spines that had been destabilized by en bloc laminectomy. The addition of 2-mm facet spacers at C3-4, C4-5, and C5-6 did produce statistically significant increases in FCSA at those levels., Conclusions: The addition of allograft cervical facet spacers should be considered a potential option to accomplish indirect foraminal decompression as measured in this cadaveric biomechanical study. However, 2-mm spacers without supplemental instrumentation do not provide significantly increased spinal segmental stability.

OBJECT Low bone mineral density in patients undergoing lumbar spinal surgery with screws is an especially difficult challenge because poor bone quality can severely compromise the maximum achievable purchase of the screws. A relatively new technique, the cortical bone screw trajectory, utilizes a medialized trajectory in the caudocephalad direction to engage a greater amount of cortical bone within the pars interarticularis and pedicle. The objectives of this cadaveric biomechanical study were to 1) evaluate a cortical screw system and compare its mechanical performance to the traditional pedicle screw system; 2) determine differences in bone quality associated with the cortical screw trajectory versus the normal pedicle screw insertion technique; 3) determine the cortical wall breach rate with both the cortical and traditional screw trajectories; and 4) determine the performance of the traditional screw in the cortical screw trajectory. METHODS Fourteen fresh frozen human lumbar spine sections (L1-5) were used in this study (mean age 57 ± 19 years). The experimental plan involved drilling and tapping screw holes for 2 trajectories under navigation (a traditional pedicle screw and a cortical screw) in both high-and low-quality vertebrae, measuring the bone quality associated with these trajectories, placing screws in the trajectories, and evaluating the competence of the screw purchase via 2 mechanical tests (pullout and toggle). The 3 experimental variants were 1) traditional pedicle screws placed in the traditional pedicle screw trajectory, 2) traditional pedicle screws placed in the cortical screw trajectory, and 3) cortical screws placed in the cortical screw trajectory. RESULTS A statistically significant increase in bone quality was observed for the cortical trajectories with a cortical screw (42%; p < 0.001) and traditional pedicle screw (48%; p < 0.001) when compared to the traditional trajectory with a traditional pedicle screw within the high-quality bone group. These significant differences were also found in the lowquality bone cohort. All mechanical parameter comparisons (screw type and trajectory) between high-quality and lowquality samples were significant (p < 0.01), and these data were all linearly correlated (r ≥ 0.65) to bone mineral density. Not all mechanical parameters determined from pullout and toggle testing were statistically significant between the 3 screw/trajectory combinations. The incidence of cortical wall breach with the cortical or traditional pedicle screw trajectories was not significantly different. CONCLUSIONS The data demonstrated that the cortical trajectory provides denser bone that allows for utilization of smaller screws to obtain mechanical purchase that is equivalent to long pedicle screws placed in traditional pedicle screw trajectories for both normal- and low-quality bone. Overall, this biomechanical study in cadavers provides evidence that the cortical screw trajectory represents a good option to obtain fixation for the lumbar spine with low-quality bone.

The dura mater performs a major functional role in the stability and mechanical response of the spinal cord complex. Computational techniques investigating the etiology of spinal cord injury require an accurate mechanical description of the dura mater. Previous studies investigating the mechanical response of the dura mater have reported conflicting results regarding the anisotropic stiffness of the dura in the longitudinal and circumferential direction. The aim of this study was to investigate the biaxial response of the dura mater in order to establish the tissue level mechanical behavior under physiological loading scenarios. To this end, square sections of the dura were tested in a custom biaxial setup under a comprehensive uniaxial and biaxial loading protocol. The resultant data were fit via a transversely isotropic continuum model and an anisotropic continuum constitutive model. The transversely isotropic formulation failed to accurately predict the dura mater׳s uniaxial behavior. The anisotropic formulation accurately predicted the uniaxial response in both longitudinal and circumferential directions. Significantly higher stiffness (p<0.0001) was observed in the circumferential direction as compared to the longitudinal direction. Further, the longitudinal direction displayed a significantly lower degree of nonlinearity (p<0.045) and significantly higher degree of collagen fiber dispersion (p<0.032) as compared to the circumferential direction. Results indicate that the dura mater has differential mechanical response in the longitudinal and circumferential directions and future studies should utilize an anisotropic two fiber family continuum model to accurately describe dura mater mechanics., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Although quasi-static and quasi-linear viscoelastic properties of the spinal cord have been reported previously, there are no published studies that have investigated the fully (strain-dependent) nonlinear viscoelastic properties of the spinal cord. In this study, stress relaxation experiments and dynamic cycling were performed on six fresh porcine lumbar cord specimens to examine their viscoelastic mechanical properties. The stress relaxation data were fitted to a modified superposition formulation and a novel finite ramp time correction technique was applied. The parameters obtained from this fitting methodology were used to predict the average dynamic cyclic viscoelastic behavior of the porcine cord. The data indicate that the porcine spinal cord exhibited fully nonlinear viscoelastic behavior. The average weighted root mean squared error for a Heaviside ramp fit was 2.8 kPa, which was significantly greater (p<0.001) than that of the nonlinear (comprehensive viscoelastic characterization method) fit (0.365 kPa). Further, the nonlinear mechanical parameters obtained were able to accurately predict the dynamic behavior, thus exemplifying the reliability of the obtained nonlinear parameters. These parameters will be important for future studies investigating various damage mechanisms of the spinal cord and studies developing high-resolution finite elements models of the spine., (Copyright © 2013 Acta Materialia Inc. All rights reserved.)

Finite element (FE) models of articular joint structures do not typically implement the fully nonlinear viscoelastic behavior of the soft connective tissue components. Instead, contemporary whole joint FE models usually represent the transient soft tissue behavior with significantly simplified formulations that are computationally tractable. The resultant fidelity of these models is greatly compromised with respect to predictions under temporally varying static and dynamic loading regimes. In addition, models based upon experimentally derived nonlinear viscoelastic coefficients that do not account for the transient behavior during the loading event(s) may further reduce the model's predictive accuracy. The current study provides the derivation and validation of a novel, phenomenological nonlinear viscoelastic formulation (based on the single integral nonlinear superposition formulation) that can be directly inputted into FE algorithms. This formulation and an accompanying experimental characterization technique, which incorporates relaxation manifested during the loading period of stress relaxation experiments, is compared to a previously published characterization method and validated against an independent analytical model. The results demonstrated that the static and dynamic FE approximations are in good agreement with the analytical solution. Additionally, the predictive accuracy of these approximations was observed to be highly dependent upon the experimental characterization technique. It is expected that implementation of the novel, computationally tractable nonlinear viscoelastic formulation and associated experimental characterization technique presented in the current study will greatly improve the predictive accuracy of the individual connective tissue components for whole joint FE simulations subjected to static and dynamic loading regimes.

Computed tomography (CT) data can be employed with respect to determining mechanical properties and has been used to predict parameters such as elastic modulus, yield strength, and ultimate strength of intact bone. Micro-computed tomography (muCT) possesses the resolution capable of detecting apparent bone density in extremely local regions and can characterize the trabecular structure. It has been asserted that this micro-structure is susceptible to micro-buckling and bending, which has a controversial role in predicting the global mechanical properties of bone. The current study measured the mechanical properties of relatively high apparent density bone from the equine distal third metacarpal. The mechanical properties were correlated with trabecular morphology parameters and apparent densities of localized regions obtained with muCT. These data were used to test two hypotheses: (1) accounting for trabecular bending using trabecular morphology parameters would provide better global mechanical property predictions than using only apparent density, and (2) regions of low apparent density dominate the overall mechanical behavior and provide greater correlation to the measured mechanical properties than regions of high apparent density. The data indicated that accounting for trabecular bending with morphological parameters resulted in stronger correlations to mechanical properties than correlations that relied only on apparent density (r2= 0.91 versus r2= 0.81). Low apparent density regions were more strongly correlated with mechanical properties than high apparent density regions (r2= 0.85 versus r2= 0.77), demonstrating the importance of selecting appropriate regions when attempting to predict mechanical properties from CT data., (Copyright 2010 Elsevier Inc. All rights reserved.)

Objective: To evaluate the mechanical properties of canine carpal ligaments for use in a finite element model of the canine antebrachium., Sample Population: 26 forelimbs obtained from cadavers of 13 dogs euthanized for reasons unrelated to this study., Procedures: 6 ligaments (medial collateral, lateral collateral, palmar ulnocarpal, palmar radiocarpal, accessorometacarpal-V, and accessorometacarpal-IV) were evaluated. Quasistatic tensile tests were performed on all specimens (n = 8 specimens/ligament) by use of a servohydraulic materials testing system in conjunction with a 6-df load cell. Each specimen was preconditioned for 10 cycles by applying 2% strain by use of a Haversine waveform. Tension was subsequently applied to each specimen at a strain rate of 0.5%/s until ligament failure., Results: Significant differences in modulus of elasticity were detected among the ligaments. Elastic modulus did not differ significantly between the 2 accessorometacapal ligaments, between the 2 collateral ligaments, or between the 2 palmar carpal ligaments. Ligaments were classified into 3 groups (accessorometacarpal ligaments, intra-articular ligaments, and palmar carpal ligaments), and significant differences were detected among the 3 ligament groups. The accessorometacarpal ligaments had a relatively high elastic modulus, compared with results for the other ligaments. The medial and lateral collateral ligaments had the lowest elastic modulus of any of the ligaments tested., Conclusions and Clinical Relevance: These results indicated a strong function-elastic modulus relationship for the 6 ligaments tested. The mechanical properties described here will be of use in creating a finite element model of the canine antebrachium.