Larger stem to bone diameter ratio predicts lower cemented endoprosthesis failure.

BACKGROUND AND OBJECTIVES: With continued advances in treatment options, patients with endoprosthetic reconstruction are living longer and consequently relying upon their devices for a longer duration. Major causes of endoprosthesis failure include aseptic loosening and mechanical failure. In the setting of tumor resection, loss of bone stock and use of radiation therapy increase the risk for these complications. As such, considerations of remaining native bone and stem length and diameter may be increasingly important. We asked the following questions: (1) What was the overall rate of endoprosthesis failure at a minimum of 5-year follow-up? (2) Does resection length increase implant failure rates? (3) Does implant size and its ratio to cortical width of bone alter implant failure rates? METHODS: We retrospectively analyzed patient outcomes at a single institution between the years of 1999-2022 who underwent cemented endoprosthetic reconstruction at the hip or knee and identified 150 patients. Of these 150, 55 had a follow-up of greater than 5 years and were used for analysis. Radiographs of these patients at time of surgery were assessed and measured for resection length, bone diameter, stem diameter, and remaining bone length. Resection percentage, and stem to bone diameter ratios were then calculated and their relationship to endoprosthesis failure were analyzed. RESULTS: Patients in this cohort had a mean age of 55.8, and mean follow-up of 59.96 months. There were 78 distal femoral replacements (52%), 16 proximal femoral replacements (10.7%), and 56 proximal tibial replacements (37.3%). There were five patients who experienced aseptic loosening and six patients who experienced mechanical failure. Patients with implant failure had a smaller mean stem to bone diameter (36% vs. 44%; p = 0.002). A stem to bone diameter of 40% appeared to be a breaking point between success and failure in this series, with 90% of patients with implant failure having a stem: bone ratio less than 40%. Stem to bone ratio less than 40% increased risk for failure versus stems that were at least 40% the diameter of bone (6/19 [31.6%] vs. 0/36 [0%]; odds ratio 0.68; p < 0.001). Resection length did not appear to have an impact on the rates of aseptic loosening and mechanical failure in this series. CONCLUSIONS: Data from this series suggests a benefit to using stems with a larger diameter when implanting cemented endoprostheses at the hip or knee. Stems which were less than 40% the diameter of bone were substantially more likely to undergo implant failure.

Comparison of Treatment Options for Chronic Scapholunate Interosseous Ligament (SLIL): A Systematic Literature Review and Meta-Analysis.

Background: The scapholunate interosseous ligament (SLIL) is an important contributor to wrist stability and functionality. SLIL injury is debilitating and therefore many surgical techniques have been proposed, but the optimal treatment modality remains debated.This meta-analysis reviews the available literature comparing surgical techniques used in the treatment of chronic SLIL to determine the best approach. Methods: An electronic search of the literature was conducted to identify all randomized controlled trials and cohort studies published before January 2019 that evaluated clinical outcomes of capsulodesis reconstruction, the modified Brunelli technique, and the reduction and association of the scaphoid and lunate (RASL) procedure for treatment of chronic SLIL. A chi-square analysis was performed to identify possible differences between each technique for several outcome measures. Results: A total 20 studies encompassing 409 patients met inclusion criteria. Average age among patients was 36.7 years, and 68.2% of patients were male. Reductions in visual analog scale pain scale; Disabilities of Arm, Shoulder, and Hand (DASH) scores; and increases in grip strength and range of motion were observed for all techniques. Capsulodesis was superior to the modified Brunelli technique regarding preserved range of motion. Conclusions: No significant differences were observed among any of the techniques for pain, DASH score, and grip strength outcomes. Capsulodesis, modified Brunelli, and RASL surgical techniques for the treatment of chronic SLIL injuries may all be seen as reliable methods of treatment of chronic SLIL injuries. While future trials directly comparing these methods are needed, this study suggests there is no superiority of one technique over another.

Molecular Pathways for Muscle and Adipose Tissue Are Altered between Beef Steers Classed as Choice or Standard.

Targets for finished livestock are often determined by expected fat, either subcutaneous or intramuscular. These targets are used frequently to improve eating quality. Lower intramuscular fat, lack of product uniformity, and insufficient tenderness can negatively impact beef acceptability. This study aimed to investigate the differences in gene expression that alter metabolism and intercellular signaling in the muscle and adipose tissue in beef carcasses at different fat endpoints. In this study, longissimus thoracis muscle samples and adipose tissue were collected at harvest, and RNA was extracted and then sequenced using RNAseq. Differential expression was determined using edgeR, and p-values were adjusted using the Benjamini-Hochberg method. A corrected p-value of 0.005 and log2 (fold change) of >1 were the threshold to identify differential expression. Comparison between intermuscular and subcutaneous fat showed no differences in the genes activated in the two adipose tissue depots, suggesting that subcutaneous fat was an adequate sample. Carcass data allowed the classification of carcasses by USDA quality grades (marbling targets). In comparing muscle from Standard and Choice carcasses, 15 genes were downregulated, and 20 were upregulated. There were 49 downregulated and 113 upregulated genes comparing adipose tissue from Standard and Choice carcasses. These genes are related to the metabolism of fat and energy. This indicates that muscle transcript expression varies less than adipose. In addition, subcutaneous fat can be used to evaluate transcript changes in fat. However, it is unclear whether these fat tissues can be used as surrogates for marbling.

Developing the menstrual justice agenda: insights from a mixed method study in the mid-western region of Nepal.

This article develops the concept of "menstrual justice". The legal scholar Margaret E. Johnson has developed an expansive approach to menstrual justice incorporating rights, justice, and a framework for intersectional analysis, with a focus on the US. This framework provides a welcome alternative to the constrictive and medicalised approaches often taken towards menstruation. However, the framework is silent on several issues pertaining to menstruation in Global South contexts. This article therefore develops the concept of menstrual justice in order to extend its relevance beyond the Global North. It presents the findings of mixed-methods research conducted in April 2019 in the mid-western region of Nepal, particularly concerning the practice of chhaupadi, an extreme form of menstrual restriction. We conducted a quantitative survey of 400 adolescent girls and eight focus group discussions, four with adolescent girls and four with adult women. Our findings confirm that dignity in menstruation requires addressing pain management, security issues, and mental health, plus structural issues including economic disadvantage, environmental issues, criminal law, and education.

The recombinant Link module of human TSG-6 suppresses cartilage damage in models of osteoarthritis: A potential disease-modifying OA drug.

OBJECTIVE: To investigate the role of endogenous TSG-6 in human osteoarthritis (OA) and assess the disease-modifying potential of a TSG-6-based biological treatment in cell, explant and animal models of OA. DESIGN: Knee articular cartilages from OA patients were analyzed for TSG-6 protein and mRNA expression using immunohistochemistry and RNAscope, respectively. The inhibitory activities of TSG-6 and its isolated Link module (Link_TSG6) on cytokine-induced degradation of OA cartilage explants were compared. Human mesenchymal stem/stromal cell-derived chondrocyte pellet cultures were used to determine the effects of Link_TSG6 and full-length TSG-6 on IL-1α-, IL-1ß-, or TNF-stimulated ADAMTS4, ADAMTS5, and MMP13 mRNA expression. Link_TSG6 was administered i.a. to the rat ACLTpMMx model; cartilage damage and tactile allodynia were assessed. RESULTS: TSG-6 is predominantly associated with chondrocytes in regions of cartilage damage where high TSG-6 expression aligns with low MMP13, the major collagenase implicated in OA progression. Link_TSG6 is more potent than full-length TSG-6 at inhibiting cytokine-mediated matrix breakdown in human OA cartilage explants;>50% of donor cartilages, from 59 tested, were responsive to Link_TSG6 treatment. Link_TSG6 also displayed more potent effects in 3D pellet cultures, suppressing ADAMTS4, ADAMTS5, and MMP13 gene expression, which was consistent with reduced aggrecanase and collagenase activities in explant cultures. Link_TSG6 treatment reduced touch-evoked pain behavior and dose-dependently inhibited cartilage damage in a rodent model of surgically-induced OA. CONCLUSIONS: Link_TSG6 has enhanced chondroprotective activity compared to the full-length TSG-6 protein and shows potential as a disease modifying OA drug via its inhibition of aggrecanase and collagenase activity.

Fibrillin microfibril structure identifies long-range effects of inherited pathogenic mutations affecting a key regulatory latent TGFß-binding site.

Genetic mutations in fibrillin microfibrils cause serious inherited diseases, such as Marfan syndrome and Weill-Marchesani syndrome (WMS). These diseases typically show major dysregulation of tissue development and growth, particularly in skeletal long bones, but links between the mutations and the diseases are unknown. Here we describe a detailed structural analysis of native fibrillin microfibrils from mammalian tissue by cryogenic electron microscopy. The major bead region showed pseudo eightfold symmetry where the amino and carboxy termini reside. On the basis of this structure, we show that a WMS deletion mutation leads to the induction of a structural rearrangement that blocks interaction with latent TGFß-binding protein-1 at a remote site. Separate deletion of this binding site resulted in the assembly of shorter fibrillin microfibrils with structural alterations. The integrin αvß3-binding site was also mapped onto the microfibril structure. These results establish that in complex extracellular assemblies, such as fibrillin microfibrils, mutations may have long-range structural consequences leading to the disruption of growth factor signaling and the development of disease.

Fat Deposition and Fat Effects on Meat Quality-A Review.

Growth is frequently described as weight gain over time. Researchers have used this information in equations to predict carcass composition and estimate fat deposition. Diet, species, breed, and gender all influence fat deposition. Alterations in diets result in changes in fat deposition as well as the fatty acid profile of meat. Additionally, the amount and composition of the fat can affect lipid stability and flavor development upon cooking. Fat functions not only as a storage of energy and contributor of flavor compounds, but also participates in signaling that affects many aspects of the physiological functions of the animal. Transcription factors that are upregulated in response to excess energy to be stored are an important avenue of research to improve the understanding of fat deposition and thus, the efficiency of production. Additionally, further study of the inflammation associated with increased fat depots may lead to a better understanding of finishing animals, production efficiency, and overall health.

Resilient women scientists and the COVID-19 pandemic: an OWSD analysis.

Pandemics tend to have disruptive and uneven impacts on different population subgroups and across sectors. This paper investigates the impact of the COVID-19 pandemic on women scientists from the Global South to understand their resilience and adaptation strategies, utilising data from a survey of women in STEM fields, who are members of the Organization for Women in Science for the Developing World (OWSD). We employ a mixed-methods approach to examine the effects of the pandemic on the respondents' work and employment, home and family lives, and mental well-being. We find that the impact of the COVID-19 pandemic and the requirement to change practices in academia, indeed in all spheres of social and economic life, have provided a unique and most timely opportunity to observe, evaluate and revise what might be termed the current gender-limited environment for career progression for researchers in STEM subjects and instead create a gender-transformative environment that will have a profound effect on how scientific research is managed and undertaken in the world.

Latent TGFß complexes are transglutaminase cross-linked to fibrillin to facilitate TGFß activation.

TGFß superfamily members are potent growth factors in the extracellular matrix with essential roles in all aspects of cellular behaviour. Latent TGFß binding proteins (LTBPs) are co-expressed with TGFß, essential for correct folding and secretion of the growth factor, to form large latent complexes. These large latent complexes bind extracellular proteins such as fibrillin for sequestration of TGFß in the matrix, essential for normal tissue function, and dysregulated TGFß signalling is a hallmark of many fibrillinopathies. Transglutaminase-2 (TG2) cross-linking of LTBPs is known to play a role in TGFß activation but the underlying molecular mechanisms are not resolved. Here we show that fibrillin is a matrix substrate for TG2 and that TG2 cross-linked complexes can be formed between fibrillin and LTBP-1 and -3, and their latent TGFß complexes. The structure of the fibrillin-LTBP1 complex shows that the two elongated proteins interact in a perpendicular arrangement which would allow them to form distal interactions between the matrix and the cell surface. Formation of the cross-link with fibrillin does not change the interaction between latent TGFß and integrin αVß6 but does increase TGFß activation in cell-based assays. The activating effect may be due to direction of the latent complexes to the cell surface by fibrillin, as competition with heparan sulphate can ameliorate the activating effect. Together, these data support that TGFß activation can be enhanced by covalent tethering of LTBPs to the matrix via fibrillin.

Cemented-augmented fixation of metastatic humeral lesions without segmental bone loss results in reliable outcomes.

Background: Treatment of metastatic lesions to the humerus is dependent on patient's pain, lesion size and location, and post-operative functional goals. Surgical options include plate or nail fixation [open reduction internal fixation (ORIF)], or endoprosthetic replacement (EPR), with cement augmentation. The objective of this study was to perform a single institution retrospective analysis of outcomes by method of reconstruction, tumor volume, and pathologic diagnosis. Methods: The records of 229 consecutive patients treated surgically for appendicular metastatic disease from 2005-2018 at our musculoskeletal oncology center were retrospectively reviewed following institutional review board (IRB) approval. Indications for surgical treatment at the humerus included patients who presented with impending and displaced pathologic fractures. Results: Sixty patients (34 male, 26 female) with a mean age of 62.9±12.2 were identified who were treated surgically at the proximal (n=21), diaphyseal (n=29), or distal (n=10) humerus. Forty-nine (82%) patients presented with displaced pathologic fractures. The remaining eleven patients had a mean Mirels score of 9.5. There was no difference in overall complication rate between EPR or ORIF [4/36 (11%) versus 2/24 (8%); P=0.725]. Mean Musculoskeletal Tumor Society (MSTS) scores were 83% for both EPR and ORIF, with no differences in subgroup analyses at the proximal, diaphyseal, or distal humerus. Patients with cortical destruction on anterior posterior (AP) and lateral imaging were at increased risk for mechanical failure [2/6 (33%) versus 0/18 (0%), P=0.015]. Conclusions: In conclusion, when pathologic pattern permits, cement-augmented fixation allows for stabilization of pathologic bone, while minimizing risk of soft-tissue detachment, while EPR resulted in similar outcomes in patients with more extensive bone destruction. Increased tumor volume was associated with lower MSTS scores.

IVC filter placement in patients undergoing surgical treatment of bone or soft-tissue tumors.

BACKGROUND AND OBJECTIVES: Patients with cancer to bone or soft tissues undergoing orthopedic procedures may be unable to receive pharmacologic prophylaxis for venous thromboembolism (VTE). Inferior vena cava (IVC) filters may be an effective method to prevent fatal pulmonary embolism (PE) in these patients. METHODS: Retrospective chart review performed for patients surgically treated for malignant disease of bone or soft tissue who had IVC filter placement. Type of surgery, anatomic region, and development of wound complications requiring repeat surgery were analyzed. RESULTS: From 2007 to 2018, 286 patients received IVC filters. Ten (3.5%) patients suffered deep vein thrombus (DVT) postoperatively. There was no acute fatal PE. Two patients suffered PE at 2 and 99 days postoperatively. Risk of DVT was comparable following surgery with endoprosthesis versus open reduction and internal fixation (p = 0.056) and with soft tissue versus bone involvement (p = 0.620). Three filter-related complications occurred. Patients disease at the femur had the highest rate of DVT. CONCLUSIONS: Following treatment of malignant disease of bone or soft-tissues, two patients with IVC filter placement experienced nonfatal PE and three patients experienced filter-related complications. No patients in this series experienced a fatal PE.

Gene Expression and Carcass Traits Are Different between Different Quality Grade Groups in Red-Faced Hereford Steers.

Fat deposition is important to carcass value and some palatability characteristics. Carcasses with higher USDA quality grades produce more value for producers and processors in the US system and are more likely to have greater eating satisfaction. Using genomics to identify genes impacting marbling deposition provides insight into muscle biochemistry that may lead to ways to better predict fat deposition, especially marbling and thus quality grade. Hereford steers (16) were managed the same from birth through harvest after 270 days on feed. Samples were obtained for tenderness and transcriptome profiling. As expected, steaks from Choice carcasses had a lower shear force value than steaks from Select carcasses; however, steaks from Standard carcasses were not different from steaks from Choice carcasses. A significant number of differentially expressed (DE) genes was observed in the longissimus lumborum between Choice and Standard carcass RNA pools (1257 genes, p < 0.05), but not many DE genes were observed between Choice and Select RNA pools. Exploratory analysis of global muscle tissue transcriptome from Standard and Choice carcasses provided insight into muscle biochemistry, specifically the upregulation of extracellular matrix development and focal adhesion pathways and the downregulation of RNA processing and metabolism in Choice versus Standard. Additional research is needed to explore the function and timing of gene expression changes.

1H NMR based metabolic profiling distinguishes the differential impact of capture techniques on wild bighorn sheep.

Environmental metabolomics has the potential to facilitate the establishment of a new suite of tools for assessing the physiological status of important wildlife species. A first step in developing such tools is to evaluate the impacts of various capture techniques on metabolic profiles as capture is necessary to obtain the biological samples required for assays. This study employed 1H nuclear magnetic resonance (NMR)-based metabolite profiling of 562 blood serum samples from wild bighorn sheep to identify characteristic molecular serum makers of three capture techniques (dart, dropnet, and helicopter-based captures) to inform future sampling protocols for metabolomics studies, and to provide insights into the physiological impacts of capture. We found that different capture techniques induce distinct changes in amino acid serum profiles, the urea cycle, and glycolysis, and attribute the differences in metabolic patterns to differences in physical activity and stress caused by the different capture methods. These results suggest that when designing experiments involving the capture of wild animals, it may be prudent to employ a single capture technique to reduce confounding factors. Our results also supports administration of tranquilizers as soon as animals are restrained to mitigate short-term physiological and metabolic responses when using pursuit and physical restraint capture techniques.

Identification of Genomic Regions for Carcass Quality Traits within the American Simmental Association Carcass Merit Program.

USDA quality and yield grade are primary driving forces for carcass value in the United States. Carcass improvements can be achieved by making selection decisions based on the results of genetic evaluations in the form of expected progeny differences (EPD), real-time ultrasound imaging, and physical evaluation of candidate breeding animals. In an effort to advance their ability to accurately predict the breeding value of potential sires for carcass traits, the American Simmental Association launched the Carcass Merit Program as a means to collect progeny sire group carcass information. All records were extracted from the American Simmental Association database. Progeny data were organized by sire family and progeny performance phenotypes were constructed. Sire genotypes were filtered, and a multi-locus mixed linear model was used to perform an association analysis on the genotype data, while correcting for cryptic relatedness and pedigree structure. Three chromosomes were found to have genome-wide significance and this conservative approach identified putative QTL in those regions. Three hundred ninety-three novel regions were identified across all traits, as well as 290 novel positional candidate genes. Correlations between carcass characteristics and maternal traits were less unfavorable than those previously reported.

Management of Large Segmental Bone Defects at the Knee With Intramedullary Stabilized Antibiotic Spacers During Two-Stage Treatment of Endoprosthetic Joint Infection.

BACKGROUND: Following debridement of infected prostheses that require reconstruction with an endoprosthetic replacement (EPR), instability related to segmental residual bone defects present a challenge in management with 2-stage reimplantation. METHODS: We retrospectively reviewed all patients treated for revision total joint or endoprosthetic infection at the knee from 1998 to 2018. At our institution, patients with skeletal defects >6 cm following explant of prosthesis and debridement (stage 1) were managed with intramedullary nail-stabilized antibiotic spacers. Following stage 1, antimicrobial therapy included 6 weeks of intravenous antibiotics and a minimum of 6 weeks of oral antibiotics. Following resolution of inflammatory markers and negative tissue cultures, reimplantation (stage 2) of an EPR was performed. RESULTS: Twenty-one patients at a mean age of 54 ± 21 years were treated for prosthetic joint infection at the knee. Polymicrobial growth was detected in 38% of cases, followed by coagulase-negative staphylococci (24%) and Staphylococcus aureus (19%). Mean residual skeletal defect after stage 1 treatment was 20 cm. Prosthetic joint infection eradication was achieved in 18 (86%) patients, with a mean Musculoskeletal Tumor Society score of 77% and mean knee range of motion of 100°. Patients with polymicrobial infections had a greater number of surgeries prior to infection (P = .024), and were more likely to require additional debridement prior to EPR (odds ratio 12.0, P = .048). CONCLUSION: Management of large segmental skeletal defects at the knee following explant using intramedullary stabilized antibiotic spacers maintain stability and result in high rates of limb salvage with conversion to an endoprosthesis.

Differential haptoglobin responsiveness to a Mannheimia haemolytica challenge altered immunologic, physiologic, and behavior responses in beef steers.

Indicator traits associated with disease resiliency would be useful to improve the health and welfare of feedlot cattle. A post hoc analysis of data collected previously (Kayser et al., 2019a) was conducted to investigate differences in immunologic, physiologic, and behavioral responses of steers (N = 36, initial BW = 386 ± 24 kg) that had differential haptoglobin (HPT) responses to an experimentally induced challenge with Mannheimia haemolytica (MH). Rumen temperature, DMI, and feeding behavior data were collected continuously, and serial blood samples were collected following the MH challenge. Retrospectively, it was determined that 9 of the 18 MH-challenged steers mounted a minimal HPT response, despite having similar leukocyte and temperature responses to other MH-challenged steers with a greater HPT response. Our objective was to examine differences in behavioral and physiological responses between MH-challenged HPT responsive (RES; n = 9), MH-challenged HPT nonresponsive (NON; n = 9), and phosphate-buffered saline-inoculated controls (CON; n = 18). Additionally, 1H NMR analysis was conducted to determine whether the HPT-responsive phenotype affected serum metabolite profiles. The RES steers had lesser (P < 0.05) cortisol concentrations than NON and CON steers. The magnitude of the increases in neutrophil concentrations and rumen temperature, and the reduction in DMI following the MH challenge were greatest (P < 0.05) in RES steers. Univariate analysis of serum metabolites indicated differences between RES, NON, and CON steers following the MH challenge; however, multivariate analysis revealed no difference between HPT-responsive phenotypes. Prior to the MH challenge, RES steers had longer (P < 0.05) head down and bunk visit durations, slower eating rates (P < 0.01) and greater (P < 0.05) daily variances in bunk visit frequency and head down duration compared with NON steers, suggesting that feeding behavior patterns were associated with the HPT-responsive phenotype. During the 28-d postchallenge period, RES steers had decreased (P < 0.05) final BW, tended (P = 0.06) to have lesser DMI, and had greater (P < 0.05) daily variances in head down and bunk visit durations compared with NON steers, which may have been attributed to their greater acute-phase protein response to the MH challenge. These results indicate that the HPT-responsive phenotype affected feeding behavior patterns and may be associated with disease resiliency in beef cattle.

Do pediatric shoulder fractures benefit from surgery?

PURPOSE OF REVIEW: We aimed to review considerations, current treatment options, and complications in the management of pediatric proximal humerus fractures. RECENT FINDINGS: Recent literature has shown an increased incidence of operative management of proximal humerus fractures. With increased age, and increased deformity, studies report excellent outcomes after operative treatment. Still, patients under the age of 12 and with Neer grade I and II fractures are consistently treated nonoperatively. SUMMARY: Indications for operative management of proximal humerus fractures in skeletally immature patients have become increasingly widened. Current literature emphasizes the stratification of patients based on displacement, angulation, and shortening, with overall positive outcomes. Each case should be considered on individual bases, accounting for both radiographic parameters, developmental stages of patients, and potential complications. In the authors' opinion, adolescent patients with Neer Horowitz 3 and 4 fractures surgical management should be considered. In younger patients with nonoperative management, even with significant displacement, is the mainstay of treatment because of the tremendous remodeling potential of the proximal humerus in children. VIDEO ABSTRACT: http://links.lww.com/MOP/A56.

Transglutaminase-Mediated Cross-Linking of Tropoelastin to Fibrillin Stabilises the Elastin Precursor Prior to Elastic Fibre Assembly.

Elastic fibres are essential components of all mammalian elastic tissues such as blood vessels, lung and skin, and are critically important for the mechanical properties they endow. The main components of elastic fibres are elastin and fibrillin, where correct formation of elastic fibres requires a fibrillin microfibril scaffold for the deposition of elastin. It has been demonstrated previously that the interaction between fibrillin and tropoelastin, the elastin precursor, increases the rate of assembly of tropoelastin. Furthermore, tropoelastin and fibrillin can be cross-linked by transglutaminase-2, but the function of cross-linking on their elastic properties is yet to be elucidated. Here we show that transglutaminase cross-linking supports formation of a 1:1 stoichiometric fibrillin-tropoelastin complex. SAXS data show that the complex retains features of the individual proteins but is elongated supporting end-to-end assembly. Elastic network models were constructed to compare the dynamics of tropoelastin and fibrillin individually as well as in the cross-linked complex. Normal mode analysis was performed to determine the structures' most energetically favourable, biologically accessible motions which show that within the complex, tropoelastin is less mobile and this molecular stabilisation extends along the length of the tropoelastin molecule to regions remote from the cross-linking site. Together, these data suggest a long-range stabilising effect of cross-linking that occurs due to the covalent linkage of fibrillin to tropoelastin. This work provides insight into the interactions of tropoelastin and fibrillin and how cross-link formation stabilises the elastin precursor so it is primed for elastic fibre assembly.