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Background: There is a need for a new, less invasive surgical option for unicoronal synostosis (UCS). The aim of this study was to compare the resulting morphology and symmetry in patients with UCS following fronto-orbital distraction (FOD) or calvarial switch (CS)., Methods: 79 patients with isolated UCS operated between 2005 and 2021 were analyzed. Follow-up was until 3 years of age. Angles describing orbital dystopia (ODA) and the anterior cranial fossa deviation and cant (ACFD and ACFC, respectively) were measured. Key linear dimensions, cranial cavities, and indices were calculated., Results: 66 patients were included (14 in the FOD group and 52 in the CS group). The 3-year follow-up revealed significant improvement in all angles in both groups, with significant superiority in ODA correction following FOD (median improvement of 5.7 degrees as compared with 3.3 degrees after CS). Additionally, nasal and orbital volumes tended to be smaller, especially following CS; however, FOD resulted in a smaller absolute difference in orbital volume. Asymmetry in the orbital, nasal, and sphenoid regions also improved at the 3-year follow-up in both groups, although FOD resulted in complete normalization of the affected orbital shape and significantly improved overall asymmetry relative to that observed in the CS group., Conclusions: This study found that FOD achieves superior overall symmetry, as well as better shape correction of the cranium, as compared with CS, while also being less invasive. These findings suggest FOD as a safe and effective alternative to correct UCS and possibly the preferred surgical method., Competing Interests: Financial Disclosure Statement: This study was supported by the Gothenburg Medical Society (GLS-985874), grants from the Swedish State under the agreement between the government and the county councils, the ALF-agreement (ALFGBG-716621), Frimurare Barnhusdirektionen in Gothenburg (GLS-988921), the Swedish Society for Medical Research (TG-23-0459-H-01), the EJP RD ERN Research Mobility Fellowship call June 2022, and H.M. Queen Silvia’s Jubilee Fund, UCL Engineering Postgraduate Research Scholarship for Excellence (Dean's Prize) and China Scholarship Council (grant #202008060028), Marie Sklodowska-Curie Individual Fellowship (MSCA-IF-2020-no. 101025525), and EPSRC Open Fellowship (EP/W008092/1). The authors have no conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons. All rights reserved.)

Terrestrial animals not only need to walk and run but also lie prone to rest and then stand up. Sit-to-stand (STS) and sit-to-walk (STW) transitions are vital behaviours little studied in species other than humans so far, but likely impose biomechanical constraints on limb design because they involve near-maximal excursions of limb joints that should require large length changes and force production from muscles. By integrating data from experiments into musculoskeletal simulations, we analysed joint motions, ground reaction forces, and muscle dynamics during STS and STW in a large terrestrial, bipedal and cursorial bird: the emu (Dromaius novaehollandiae; body mass ∼30 kg). Simulation results suggest that in both STS and STW, emus operate near the functional limits (∼50% of shortening/lengthening) of some of their hindlimb muscles, particularly in distal muscles with limited capacity for length change and leverage. Both movements involved high muscle activations (>50%) and force generation of the major joint extensor muscles early in the transition. STW required larger net joint moments and non-sagittal motions than STS, entailing greater demands for muscle capacity. Whilst our study involves multiple assumptions, our findings lay the groundwork for future studies to understand, for example, how tendon contributions may reduce excessive muscle demands, especially in the distal hindlimb. As the first investigation into how an avian species stands up, this study provides a foundational framework for future comparative studies investigating organismal morphofunctional specialisations and evolution, offering potential robotics and animal welfare applications., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

X-ray Computed Tomography (CT) images are widely used in various fields of natural, physical, and biological sciences. 3D reconstruction of the images involves segmentation of the structures of interest. Manual segmentation has been widely used in the field of biological sciences for complex structures composed of several sub-parts and can be a time-consuming process. Many tools have been developed to automate the segmentation process, all with various limitations and advantages, however, multipart segmentation remains a largely manual process. The aim of this study was to develop an open-access and user-friendly tool for the automatic segmentation of calcified tissues, specifically focusing on craniofacial bones. Here we describe BounTI, a novel segmentation algorithm which preserves boundaries between separate segments through iterative thresholding. This study outlines the working principles behind this algorithm, investigates the effect of several input parameters on its outcome, and then tests its versatility on CT images of the craniofacial system from different species (e.g. a snake, a lizard, an amphibian, a mouse and a human skull) with various scan qualities. The case studies demonstrate that this algorithm can be effectively used to segment the craniofacial system of a range of species automatically. High-resolution microCT images resulted in more accurate boundary-preserved segmentation, nonetheless significantly lower-quality clinical images could still be segmented using the proposed algorithm. Methods for manual intervention are included in this tool when the scan quality is insufficient to achieve the desired segmentation results. While the focus here was on the craniofacial system, BounTI can be used to automatically segment any hard tissue. The tool presented here is available as an Avizo/Amira add-on, a stand-alone Windows executable, and a Python library. We believe this accessible and user-friendly segmentation tool can benefit the wider anatomical community., (© 2024 The Authors. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.)

Background: There is a standard methodology for measuring and evaluating the availability and affordability of selected medicines in the healthcare system, especially in low- and middle-income countries., Aim: To investigate availability, affordability and accessibility of medicines in the Islamic Republic of Iran in 2021 and compare the results with those from 2019., Methods: This descriptive cross-sectional study investigated the availability and affordability of 60 selected medicines in Islamic Republic of Iran. Availability and affordability were measured using the WHO/Health Action International methodology., Results: The availability rates for originator brands in the public, private and other sectors were 6.4%, 8.6% and 6.8%, respectively. In contrast, availability rates for lowest-priced and most-sold generics were 44.7% and 63.6% in the public sector, 45.4% and 66.4% in the private sector, and 39.6% and 58.6% in other sectors. Only 20.0% of originator brands in the Islamic Republic of Iran were affordable, while 96.6% of the lowest priced and 95.0% of the most sold generics were affordable., Conclusion: Most medicines in the Islamic Republic of Iran were affordable and the pharmaceutical supply chain was acceptable., (Copyright: © Authors 2024; Licensee: World Health Organization. EMHJ is an open access journal. All papers published in EMHJ are available under the Creative Commons Attribution Non-Commercial ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo).)

Osteoderms (ODs) are mineralized tissue embedded within the skin and are particularly common in reptiles. They are generally thought to form a protective layer between the soft tissues of the animal and potential external threats, although other functions have been proposed. The aim of this study was to characterize OD variation across the lizard body. Adults of three lizard species were chosen for this study. After whole body CT scanning of each lizard, single ODs were extracted from 10 different anatomical regions, CT scanned, and characterized using sectioning and nanoindentation. Morphological analysis and material characterization revealed considerable diversity in OD structure across the species investigated. The scincid Tiliqua gigas was the only studied species in which ODs had a similar external morphology across the head and body. Greater osteoderm diversity was found in the gerrhosaurid Broadleysaurus major and the scincid Tribolonotus novaeguineae. Dense capping tissue, like that reported for Heloderma, was found in only one of the three species examined, B. major. Osteoderm structure can be surprisingly complex and variable, both among related taxa, and across the body of individual animals. This raises many questions about OD function but also about the genetic and developmental factors controlling OD shape., (© 2024 The Authors. The Anatomical Record published by Wiley Periodicals LLC on behalf of American Association for Anatomy.)

Our fundamental understanding of the physico-mechanical forces that drive the size and shape changes of the cranium during ontogeny are limited. Biomechanical models based on finite element method present a huge opportunity to address this critical gap in our knowledge. Here, we describe a validated computational framework to predict normal craniofacial growth. Our results demonstrated that this approach is capable of predicting the growth of calvaria, face, and skull base. We highlighted the crucial role of skull base in antero-posterior growth of the face and also demonstrated the contribution of the maxillary expansion to the dorsoventral growth of the face and its interplay with the orbits. These findings highlight the importance of physical interactions of different components of the craniofacial system. The computational framework described here serves as a powerful tool to study fundamental questions in developmental biology and to advance treatment of conditions affecting the craniofacial system such as craniosynostosis., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Authors.)

The morphology and biomechanics of infant crania undergo significant changes between the pre- and post-weaning phases due to increasing loading of the masticatory system. The aims of this study were to characterize the changes in muscle forces, bite forces and the pattern of mechanical strain and stress arising from the aforementioned forces across crania in the first 48 months of life using imaging and finite element methods. A total of 51 head computed tomography scans of normal individuals were collected and analysed from a larger database of 217 individuals. The estimated mean muscle forces of temporalis, masseter and medial pterygoid increase from 30.9 to 87.0 N, 25.6 to 69.6 N and 23.1 to 58.9 N, respectively (0-48 months). Maximum bite force increases from 90.5 to 184.2 N (3-48 months). There is a change in the pattern of strain and stress from the calvaria to the face during postnatal development. Overall, this study highlights the changes in the mechanics of the craniofacial system during normal development. It further raises questions as to how and what level of changes in the mechanical forces during the development can alter the morphology of the craniofacial system.

Background: Multiple sclerosis (MS) is accompanied by many health-related issues. This study aimed to evaluate the anthropometric indices, nutrient intakes and health-related characteristics of MS patients as well as their possible correlations., Methods: This cross-sectional study was performed on 283 MS patients in Shiraz, Iran, during 2018-2019. Body mass index (BMI) and body composition were measured for each participant. A food frequency questionnaire was used to determine the patients' nutrient intakes. The level of fatigue, disability and quality of life of the individuals were assessed by the modified fatigue impact scale (MFIS), the expanded disability status scale and the multiple sclerosis quality of life-54 questionnaires, respectively., Results: The results revealed that 43.11% of the patients were overweight or obese, and their %body fat (%BF) was 35.65 ± 7.63. Besides, intakes of vitamins A, E, D, folic acid, calcium, zinc and magnesium were significantly lower than recommendations in both genders, and sodium intake was significantly higher than the tolerable upper intake level in females. A significant positive linear correlation was observed between MFIS and BMI ( r  = 0.12, P  = 0.045). Significant positive correlations were also found between psychosocial subscale of MFIS and both of %BF ( r  = 0.12, P  = 0.049) and visceral fat area ( r  = 0.14, P  = 0.02). Unexpectedly, the patients' quality of life showed significant negative correlations with fat free mass and skeletal muscle mass., Conclusion: Being overweight, having a high %BF and poor nutrient intakes are common among MS patients. Improving the patients' lifestyle and dietary intake is recommended to reduce fatigue and increase their life quality.

Background: Trigonocephaly occurs due to the premature fusion of the metopic suture, leading to a triangular forehead and hypotelorism. This condition often requires surgical correction for morphological and functional indications. Metopic ridges also originate from premature metopic closure but are only associated with mid-frontal bulging; their surgical correction is rarely required. Differential diagnosis between these two conditions can be challenging, especially in minor trigonocephaly., Methods: Two hundred seven scans of patients with trigonocephaly (90), metopic rigdes (27), and controls (90) were collected. Geometric morphometrics were used to quantify skull and orbital morphology as well as the interfrontal angle and the cephalic index. An innovative method was developed to automatically compute the frontal curvature along the metopic suture. Different machine-learning algorithms were tested to assess the predictive power of morphological data in terms of classification., Results: We showed that control patients, trigonocephaly and metopic rigdes have distinctive skull and orbital shapes. The 3D frontal curvature enabled a clear discrimination between groups (sensitivity and specificity > 92%). Furthermore, we reached an accuracy of 100% in group discrimination when combining 6 univariate measures., Conclusion: Two diagnostic tools were proposed and demonstrated to be successful in assisting differential diagnosis for patients with trigonocephaly or metopic ridges. Further clinical assessments are required to validate the practical clinical relevance of these tools., (© 2024. The Author(s).)

Premature fusion of craniofacial joints, i.e. sutures, is a major clinical condition. This condition affects children and often requires numerous invasive surgeries to correct. Minimally invasive external loading of the skull has shown some success in achieving therapeutic effects in a mouse model of this condition, promising a new non-invasive treatment approach. However, our fundamental understanding of the level of deformation that such loading has induced across the sutures, leading to the effects observed is severely limited, yet crucial for its scalability. We carried out a series of multiscale characterisations of the loading effects on normal and craniosynostotic mice, in a series of in vivo and ex vivo studies. This involved developing a custom loading setup as well as software for its control and a novel in situ CT strain estimation approach following the principles of digital volume correlation. Our findings highlight that this treatment may disrupt bone formation across the sutures through plastic deformation of the treated suture. The level of permanent deformations observed across the coronal suture after loading corresponded well with the apparent strain that was estimated. This work provides invaluable insight into the level of mechanical forces that may prevent early fusion of cranial joints during the minimally invasive treatment cycle and will help the clinical translation of the treatment approach to humans., (© 2023. The Author(s).)

This paper proposes novel compliant mechanisms for constructing hand prostheses based on soft robotics. Two models of prosthetic hands are developed in this work. Three mechanical evaluations are performed to determine the suitability of the two designs for carrying out activities of daily living (ADLs). The first test measures the grip force that the prosthesis can generate on objects. The second determines the energy required and dissipated from the prosthesis to operate. The third test identifies the maximum traction force that the prosthesis can support. The tests showed that the PrHand1 prosthesis has a maximum grip force of 23.38 ± 1.5 N, the required energy is 0.76 ± 0.13 J, and the dissipated energy is 0.21 ± 0.17 J. It supports a traction force of 173.31 ± 5.7 N. The PrHand2 prosthesis has a maximum grip force of 36.13 ± 2.3 N, the required energy is 1.28 ± 0.13 J, the dissipated energy is 0.96 ± 0.12 J, and it supports a traction force of 78.48 ± 0 N. In conclusion, the PrHand1 prosthesis has a better performance in terms of energy and tensile force supported. The difference between the energy and traction force results is related to two design features of the PrHand2: fully silicone-coated fingers and a unifying mechanism that requires more force on the tendons to close the prosthesis. The grip force of the PrHand2 prosthesis was more robust than the PrHand1 due to its silicone coating, which allowed for an improved grip., Competing Interests: The 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 © 2023 Ramos, de Arco, Cifuentes, Moazen, Wurdemann and Múnera.)

Osteoderms (ODs) are calcified organs formed directly within the skin of most major extant tetrapod lineages. Lizards possibly show the greatest diversity in ODs morphology and distribution. ODs are commonly hypothesized to function as a defensive armor. Here we tested the hypothesis that cranial osteoderms also contribute to the mechanics of the skull during biting. A series of in vivo experiments were carried out on three specimens of Tiliqua gigas. Animals were induced to bite a force plate while a single cranial OD was strain gauged. A finite element (FE) model of a related species, Tiliqua scincoides, was developed and used to estimate the level of strain across the same OD as instrumented in the in vivo experiments. FE results were compared to the in vivo data and the FE model was modified to test two hypothetical scenarios in which all ODs were (i) removed from, and (ii) fused to, the skull. In vivo data demonstrated that the ODs were carrying load during biting. The hypothetical FE models showed that when cranial ODs were fused to the skull, the overall strain across the skull arising from biting was reduced. Removing the ODs showed an opposite effect. In summary, our findings suggest that cranial ODs contribute to the mechanics of the skull, even when they are loosely attached., (© 2023 The Authors. The Anatomical Record published by Wiley Periodicals LLC on behalf of American Association for Anatomy.)

Background: Excessive inflammatory response is associated with several diseases. Recently, there has been an increasing trend for investigation of the acute or short-term effects of whey protein alone or in combination with carbohydrates on inflammatory status, especially in athletes. This systematic review aimed to clarify these effects., Materials and Methods: PubMed, Scopus, and Web of Science databases were searched from January 1990 to September 2021, without language restriction. Adult studies examining the effects of whey protein alone or together with carbohydrates on interleukin-6, tumor necrosis factor-α, and C-reactive protein levels with a maximum duration of 15 days and with at least one comparison group were included. The quality of studies was analyzed using the Cochrane risk of bias tool., Results: Twenty-five studies met the inclusion criteria. Significant reductions in inflammatory markers was observed in seven out of 25 studies (28%). However, one out of 25 studies (4%) reported a significant increase in inflammatory status. Among those studies comparing the effects of whey protein alone with non-protein or protein-containing groups, 18.18% (two out of 11) and 10% (one out of ten) of the trials revealed a significant decrease in the markers, respectively. Moreover, of those studies comparing whey protein plus carbohydrate with non-protein or protein-containing groups, 33.33% (two out of six) and 40% (two out of five) of them showed a significant reduction in the inflammatory response, respectively. The quality of the majority of studies (84%) was poor., Conclusion: It seems that whey protein alone or the combination of it with carbohydrates may not affect the inflammatory markers in the short run (PROSPERO registration number: CRD42021273915).[GMJ.2023;12:e2441]., Competing Interests: The authors declare that they have no competing interests., (Copyright© 2023, Galen Medical Journal.)

Introduction: The rise of soft robotics has driven the development of devices for assistance in activities of daily living (ADL). Likewise, different types of actuation have been developed for safer human interaction. Recently, textile-based pneumatic actuation has been introduced in hand exoskeletons for features such as biocompatibility, flexibility, and durability. These devices have demonstrated their potential use in assisting ADLs, such as the degrees of freedom assisted, the force exerted, or the inclusion of sensors. However, performing ADLs requires the use of different objects, so exoskeletons must provide the ability to grasp and maintain stable contact with a variety of objects to lead to the successful development of ADLs. Although textile-based exoskeletons have demonstrated significant advancements, the ability of these devices to maintain stable contact with a variety of objects commonly used in ADLs has yet to be fully evaluated., Materials and Methods: This paper presents the development and experimental validation in healthy users of a fabric-based soft hand exoskeleton through a grasping performance test using The Anthropomorphic Hand Assessment Protocol (AHAP), which assesses eight types of grasping with 24 objects of different shapes, sizes, textures, weights, and rigidities, and two standardized tests used in the rehabilitation processes of post- stroke patients., Results and Discussion: A total of 10 healthy users (45.50 ± 14.93 years old) participated in this study. The results indicate that the device can assist in developing ADLs by evaluating the eight types of grasps of the AHAP. A score of 95.76 ± 2.90% out of 100% was obtained for the Maintaining Score, indicating that the ExHand Exoskeleton can maintain stable contact with various daily living objects. In addition, the results of the user satisfaction questionnaire indicated a positive mean score of 4.27 ± 0.34 on a Likert scale ranging from 1 to 5., Competing Interests: The 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 © 2023 Maldonado-Mejía, Múnera, Diaz, Wurdemann, Moazen, Pontes, Vieira Segatto, Monteiro and Cifuentes.)

Knowledge of human craniofacial growth (increase in size) and development (change in shape) is important in the clinical treatment of a range of conditions that affects it. This study uses an extensive collection of clinical CT scans to investigate craniofacial growth and development over the first 48 months of life, detail how the cranium changes in form (size and shape) in each sex and how these changes are associated with the growth and development of various soft tissues such as the brain, eyes and tongue and the expansion of the nasal cavity. This is achieved through multivariate analyses of cranial form based on 3D landmarks and semi-landmarks and by analyses of linear dimensions, and cranial volumes. The results highlight accelerations and decelerations in cranial form changes throughout early childhood. They show that from 0 to 12 months, the cranium undergoes greater changes in form than from 12 to 48 months. However, in terms of the development of overall cranial shape, there is no significant sexual dimorphism in the age range considered in this study. In consequence a single model of human craniofacial growth and development is presented for future studies to examine the physio-mechanical interactions of the craniofacial growth., (© 2023. The Author(s).)

Nutritional interventions can be valuable for the prevention of postmenopausal osteoporosis. This study aimed to investigate the effects of kefir fortified with omega-3 and vitamin C on the bone and uterus parameters of ovariectomized rats. Seventy-seven female Sprague-Dawley rats were ovariectomized or sham-operated. The ovariectomized rats were assigned to six groups and received 1 ml/day of distilled water (OVX group), milk, kefir, kefir fortified with omega-3 fatty acids (kefir+ω3), kefir fortified with vitamin C (kefir+vit-C) or kefir fortified with omega-3 and vitamin C (kefir+ω3+vit-C) for 12 weeks. The sham group also received 1ml/day of distilled water. Subsequently, bone mineral content (BMC) and bone mineral density (BMD) of various bones were assessed. Femurs and uteri were harvested for bone ash analysis and histopathological examinations, respectively. Sera were analyzed for carboxy-terminal cross-linked telopeptide of type 1 collagen, procollagen type 1 amino-terminal propeptide, calcium, phosphorous, tumor necrosis factor-α (TNF-α) and total antioxidant capacity levels. Ovariectomy resulted in significant reduction in bone density (P<0.05). Kefir+ω3+vit-C significantly improved BMC of lumbar spine (0.699±0.027 g compared with 0.580±0.018 in the OVX group), and kefir, kefir+vit-C and kefir+ω3+vit-C significantly increased BMD of tibia (0.118±0.003 g/cm 2 , 0.119±0.001 and 0.120±0.004 compared with 0.102±0.005 in the OVX group). Moreover, ovariectomy markedly elevated TNF-α level, which was significantly reversed by kefir+ω3+vit-C. Significant atrophy of the uterus was observed following ovariectomy, although the uterus parameters did not change by any of the interventions. In conclusion, kefir fortified with omega-3 fatty acids and vitamin C may have protective effects against bone loss through suppressing inflammation.

The use of non-destructive approaches for digital acquisition (e.g. computerised tomography-CT) allows detailed qualitative and quantitative study of internal structures of skeletal material. Here, we present a new R-based software tool, Icex, applicable to the study of the sizes and shapes of skeletal cavities and fossae in 3D digital images. Traditional methods of volume extraction involve the manual labelling (i.e. segmentation) of the areas of interest on each section of the image stack. This is time-consuming, error-prone and challenging to apply to complex cavities. Icex facilitates rapid quantification of such structures. We describe and detail its application to the isolation and calculation of volumes of various cranial cavities. The R tool is used here to automatically extract the orbital volumes, the paranasal sinuses, the nasal cavity and the upper oral volumes, based on the coordinates of 18 cranial anatomical points used to define their limits, from 3D cranial surface meshes obtained by segmenting CT scans. Icex includes an algorithm (Icv) for the calculation of volumes by defining a 3D convex hull of the extracted cavity. We demonstrate the use of Icex on an ontogenetic sample (0-19 years) of modern humans and on the fossil hominin crania Kabwe (Broken Hill) 1, Gibraltar (Forbes' Quarry) and Guattari 1. We also test the tool on three species of non-human primates. In the modern human subsample, Icex allowed us to perform a preliminary analysis on the absolute and relative expansion of cranial sinuses and pneumatisations during growth. The performance of Icex, applied to diverse crania, shows the potential for an extensive evaluation of the developmental and/or evolutionary significance of hollow cranial structures. Furthermore, being open source, Icex is a fully customisable tool, easily applicable to other taxa and skeletal regions., (© 2023 The Authors. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.)

Purpose: The aim of this study was to investigate the biomechanics of endoscopically assisted strip craniectomy treatment for the management of sagittal craniosynostosis while undergoing three different durations of postoperative helmet therapy using a computational approach., Methods: A previously developed 3D model of a 4-month-old sagittal craniosynostosis patient was used. The strip craniectomy incisions were replicated across the segmented parietal bones. Areas across the calvarial were selected and constrained to represent the helmet placement after surgery. Skull growth was modelled and three variations of helmet therapy were investigated, where the timings of helmet removal alternated between 2, 5, and 8 months after surgery., Results: The predicted outcomes suggest that the prolonging of helmet placement has perhaps a beneficial impact on the postoperative long-term morphology of the skull. No considerable difference was found on the pattern of contact pressure at the interface of growing intracranial volume and the skull between the considered helmeting durations., Conclusion: Although the validation of these simulations could not be performed, these simulations showed that the duration of helmet therapy after endoscopically assisted strip craniectomy influenced the cephalic index at 36 months. Further studies require to validate these preliminary findings yet this study can lay the foundations for further studies to advance our fundamental understanding of mechanics of helmet therapy., (© 2022. The Author(s).)

Syndromic craniosynostosis (CS) patients exhibit early, bony fusion of calvarial sutures and cranial synchondroses, resulting in craniofacial dysmorphology. In this study, we chronologically evaluated skull morphology change after abnormal fusion of the sutures and synchondroses in mouse models of syndromic CS for further understanding of the disease. We found fusion of the inter-sphenoid synchondrosis (ISS) in Apert syndrome model mice (Fgfr2 S252W/+ ) around 3 weeks old as seen in Crouzon syndrome model mice (Fgfr2c C342Y/+ ). We then examined ontogenic trajectories of CS mouse models after 3 weeks of age using geometric morphometrics analyses. Antero-ventral growth of the face was affected in Fgfr2 S252W/+ and Fgfr2c C342Y/+ mice, while Saethre-Chotzen syndrome model mice (Twist1 +/- ) did not show the ISS fusion and exhibited a similar growth pattern to that of control littermates. Further analysis revealed that the coronal suture synostosis in the CS mouse models induces only the brachycephalic phenotype as a shared morphological feature. Although previous studies suggest that the fusion of the facial sutures during neonatal period is associated with midface hypoplasia, the present study suggests that the progressive postnatal fusion of the cranial synchondrosis also contributes to craniofacial dysmorphology in mouse models of syndromic CS. These morphological trajectories increase our understanding of the progression of syndromic CS skull growth., (© 2022 Anatomical Society.)

Stress shielding secondary to bone resorption is one of the main causes of aseptic loosening, which limits the lifespan of hip prostheses and exacerbates revision surgery rates. In order to minimise post-hip replacement stress variations, this investigation proposes a low-stiffness, porous Ti6Al4V hip prosthesis, developed through selective laser melting (SLM). The stress shielding effect and potential bone resorption properties of the porous hip implant were investigated through both in vitro quasi-physiological experimental assays, together with finite element analysis. A solid hip implant was incorporated in this investigation for contrast, as a control group. The stiffness and fatigue properties of both the solid and the porous hip implants were measured through compression tests. The safety factor of the porous hip stem under both static and dynamic loading patterns was obtained through simulation. The porous hip implant was inserted into Sawbone/PMMA cement and was loaded to 2,300 N (compression). The proposed porous hip implant demonstrated a more natural stress distribution, with reduced stress shielding (by 70%) and loss in bone mass (by 60%), when compared to a fully solid hip implant. Solid and porous hip stems had a stiffness of 2.76 kN/mm and 2.15 kN/mm respectively. Considering all daily activities, the porous hip stem had a factor of safety greater than 2. At the 2,300 N load, maximum von Mises stresses on the hip stem were observed as 112 MPa on the medial neck and 290 MPa on the distal restriction point, whereby such values remained below the endurance limit of 3D printed Ti6Al4V (375 MPa). Overall, through the strut thickness optimisation process for a Ti6Al4V porous hip stem, stress shielding and bone resorption can be reduced, therefore proposing a potential replacement for the generic solid implant., Competing Interests: The 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 © 2023 Naghavi, Tamaddon, Garcia-Souto, Moazen, Taylor, Hua and Liu.)

Background: Anthracyclines can improve survival in many types of malignancies, but dose-dependent and irreversible results following the use of anthracyclines have been associated with cardiomyopathy. This meta-analysis aimed to compare the effects of prophylactic agents for preventing cardiotoxicity induced following anticancer agents., Methods: In this meta-analysis, Scopus, Web of Science, and PubMed were surfed for articles published by December 30 th , 2020. The keywords were angiotensin-converting enzyme inhibitor (ACEI), enalapril, captopril, angiotensin receptor blocker, beta blocker, metoprolol, bisoprolol, isoprolol, statin, valsartan, losartan, eplerenone, idarubicin, nebivolol, dihydromyricetin, ampelopsin, spironolactone, dexrazoxane, antioxidants, cardiotoxicity, n-acetyl-tryptamine, cancer, neoplasms, chemotherapy, anthracyclines, doxorubicin, daunorubicin, epirubicin, idarubicin, ejection fraction or a combination of them in the titles or abstracts., Results: A total of 17 articles out of 728 studies examining 2,674 patients were included in this systematic review and meta-analysis. Ejection fraction (EF) values in the baseline, 6-month, and 12-month follow-up in the intervention group turned out to be 62.52 ± 2.48, 59.63 ± 4.85, and 59.42 ± 4.53, whereas in the control group appeared to be 62.81 ± 2.58, 57.69 ± 4.32, and 58.60 ± 4.58, respectively. Through comparison of the two groups, EF was found to increase in the intervention group by 0.40 after 6 months (Standardized mean difference (SMD): 0.40, 95% confidence interval (CI): 0.27, 0.54), thus proving higher than that of the control groups following the cardiac drugs., Conclusion: This meta-analysis showed that prophylactic treatment with cardio-protective drugs, including dexrazoxane, beta blocker, and ACEI drugs in patients undergoing chemotherapy with anthracycline, have a protective effect on LVEF and prevent EF drop., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Many species of lizards are partially enveloped by a dermal armour made of ossified units called osteoderms. Lizard osteoderms demonstrate considerable species-specific variation in morphology and histology. Although a physical/protective role (against predators, prey, conspecifics and impact loading during falls) is frequently advanced, empirical data on the biomechanics of lizard osteoderms are scarce, limiting our understanding of form-function relationships. Here, we report deformation recorded at the surface of temporal osteoderms during controlled external loading of preserved specimens of 11 lizard species (Tiliqua rugosa, Tiliqua scincoides, Corucia zebrata, Pseudopus apodus, Timon lepidus, Matobosaurus validus, Broadleysaurus major, Tribolonotus gracilis, Tribolonotus novaeguineae, Heloderma horridum and Heloderma suspectum). Based on the strain recorded in situ and from isolated osteoderms, the skin of the species investigated can be ranked along a marked stiffness gradient that mostly reflects the features of the osteoderms. Some species such as T. rugosa and the two Heloderma species had very stiff osteoderms and skin while others such as T. lepidus and P. apodus were at the other end of the spectrum. Histological sections of the osteoderms suggest that fused (versus compound) osteoderms with a thick layer of capping tissue are found in species with a stiff skin. In most cases, loading neighbouring osteoderms induced a large strain in the instrumented osteoderm, attesting that, in most species, lizard osteoderms are tightly interconnected. These data empirically confirm that the morphological diversity observed in lizard osteoderms is matched by variability in biomechanical properties., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2022. Published by The Company of Biologists Ltd.)

Intentional skull deformations have been practiced by every human population, from the prehistoric times until the XXth century. In Europe, they were specifically prevalent in the region of Toulouse, France. The soft-tissue modifications due to such practices are not well characterized in the literature due to the rarity of photographic data. Most studies on skull deformations are thus based on skeletal remains. Here we performed a controlled geometric morphometric assessment of 31 frontal pictures and 70 lateral pictures of individuals from Toulouse with intentional deformations extracted from two XIXth century historical French photographic archives. We also measured the forces exerted on the skull vault by the traditional deformation device from Toulouse using a 3D-printed skull and pressure sensors. We showed that individuals with Toulouse deformations have distinctive facial features, caused by moderate forces exerted on the skull vault. Our results exhibit and quantify for the first time the real face of intentional skull deformations, which are a ubiquitous and distinctive feature of the human species., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Additive manufacturing has been used to develop a variety of scaffold designs for clinical and industrial applications. Mechanical properties (i.e., compression, tension, bending, and torsion response) of these scaffolds are significantly important for load-bearing orthopaedic implants. In this study, we designed and additively manufactured porous metallic biomaterials based on two different types of triply periodic minimal surface structures (i.e., gyroid and diamond) that mimic the mechanical properties of bone, such as porosity, stiffness, and strength. Physical and mechanical properties, including compressive, tensile, bending, and torsional stiffness and strength of the developed scaffolds, were then characterised experimentally and numerically using finite element method. Sheet thickness was constant at 300 μm, and the unit cell size was varied to generate different pore sizes and porosities. Gyroid scaffolds had a pore size in the range of 600-1200 μm and a porosity in the range of 54-72%, respectively. Corresponding values for the diamond were 900-1500 μm and 56-70%. Both structure types were validated experimentally, and a wide range of mechanical properties (including stiffness and yield strength) were predicted using the finite element method. The stiffness and strength of both structures are comparable to that of cortical bone, hence reducing the risks of scaffold failure. The results demonstrate that the developed scaffolds mimic the physical and mechanical properties of cortical bone and can be suitable for bone replacement and orthopaedic implants. However, an optimal design should be chosen based on specific performance requirements.

Soft robotic approaches have been trialed for rehabilitation or assistive hand exoskeletons using silicone or textile actuators because they have more tolerance for alignment with biological joints than rigid exoskeletons. Textile actuators have not been previously evaluated, and this study compares the mechanical properties of textile and silicone actuators used in hand exoskeletons. The physical dimensions, the air pressure required to achieve a full bending motion, and the forces generated at the tip of the actuator were measured and compared. The results showed that the construction method of the silicone actuators is slower than the textile actuators, but it generates better dimensional accuracy. However, the air pressure required for the actuators to generate a full bending motion is significantly lower for textile actuators, and the blocking force generated at that pressure is 35% higher in the textile actuators. There are significant differences across all variables compared, indicating that actuators constructed using pleated textile techniques have greater potential for the construction of an exoskeleton for hand rehabilitation or assistance., Competing Interests: The 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 © 2022 Ramos, Múnera, Moazen, Wurdemann and Cifuentes.)

Additively manufactured Ti scaffolds have been used for bone replacement and orthopaedic applications. In these applications, both morphological and mechanical properties are important for their in vivo performance. Additively manufactured Ti6Al4V triply periodic minimal surface (TPMS) scaffolds with diamond and gyroid structures are known to have high stiffness and high osseointegration properties, respectively. However, morphological deviations between the as-designed and as-built types of these scaffolds have not been studied before. In this study, the morphological and mechanical properties of diamond and gyroid scaffolds at macro and microscales were examined. The results demonstrated that the mean printed strut thickness was greater than the designed target value. For diamond scaffolds, the deviation increased from 7.5 μm (2.5% excess) for vertical struts to 105.4 μm (35.1% excess) for horizontal struts. For the gyroid design, the corresponding deviations were larger, ranging from 12.6 μm (4.2% excess) to 198.6 μm (66.2% excess). The mean printed pore size was less than the designed target value. For diamonds, the deviation of the mean pore size from the designed value increased from 33.1 μm (-3.0% excess) for vertical struts to 92.8 μm (-8.4% excess) for horizontal struts. The corresponding deviation for gyroids was larger, ranging from 23.8 μm (-3.0% excess) to 168.7 μm (-21.1% excess). Compressive Young's modulus of the bulk sample, gyroid and diamond scaffolds was calculated to be 35.8 GPa, 6.81 GPa and 7.59 GPa, respectively, via the global compression method. The corresponding yield strength of the samples was measured to be 1012, 108 and 134 MPa. Average microhardness and Young's modulus from α and β phases of Ti6Al4V from scaffold struts were calculated to be 4.1 GPa and 131 GPa, respectively. The extracted morphology and mechanical properties in this study could help understand the deviation between the as-design and as-built matrices, which could help develop a design compensation strategy before the fabrication of the scaffolds.

Vertebrate skin is a remarkable organ that supports and protects the body. It consists of two layers, the epidermis and the underlying dermis. In some tetrapods, the dermis includes mineralised organs known as osteoderms (OD). Lizards, with over 7,000 species, show the greatest diversity in OD morphology and distribution, yet we barely understand what drives this diversity. This multiscale analysis of five species of lizards, whose lineages diverged ∼100-150 million years ago, compared the micro- and macrostructure, material properties, and bending rigidity of their ODs, and examined the underlying bones of the skull roof and jaw (including teeth when possible). Unsurprisingly, OD shape, taken alone, impacts bending rigidity, with the ODs of Corucia zebrata being most flexible and those of Timon lepidus being most rigid. Macroscopic variation is also reflected in microstructural diversity, with differences in tissue composition and arrangement. However, the properties of the core bony tissues, in both ODs and cranial bones, were found to be similar across taxa, although the hard, capping tissue on the ODs of Heloderma and Pseudopus had material properties similar to those of tooth enamel. The results offer evidence on the functional adaptations of cranial ODs, but questions remain regarding the factors driving their diversity. STATEMENT OF SIGNIFICANCE: Understanding nature has always been a significant source of inspiration for various areas of the physical and biological sciences. Here we unravelled a novel biomineralization, i.e. calcified tissue, OD, forming within the skin of lizards which show significant diversity across the group. A range of techniques were used to provide an insight into these exceptionally diverse natural structures, in an integrated, whole system fashion. Our results offer some suggestions into the functional and biomechanical adaptations of OD and their hierarchical structure. This knowledge can provide a potential source of inspiration for biomimetic and bioinspired designs, applicable to the manufacturing of light-weight, damage-tolerant and multifunctional materials for areas such as tissue engineering., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Polyether-ether-ketone (PEEK) is widely used in producing prosthesis and have gained great attention for repair of large bone defect in recent years with the development of additive manufacturing. This is due to its excellent biocompatibility, good heat and chemical stability and similar mechanical properties which mimics natural bone. In this study, three replicates of rectilinear scaffolds were designed for compression, tension, three-point bending and torsion test with unit cell size of 0.8 mm, a pore size of 0.4 mm, strut thickness of 0.4 mm and nominal porosity of 50%. Stress-strain graphs were developed from experimental and finite element analysis models. Experimental Young's modulus and yield strength of the scaffolds were measured from the slop of the stress-strain graph to be 395 and 19.50 MPa respectively for compression, 427 and 6.96 MPa respectively for tension, 257 and 25.30 MPa respectively for three-point bending and 231 and 12.83 MPa respectively for torsion test. The finite element model was found to be in good agreement with the experimental results. Ductile fracture of the struct subjected to tensile strain was the main failure mode of the PEEK scaffold, which stems from the low crystallinity of additive manufacturing PEEK. The mechanical properties of porous PEEK are close to those of cancellous bone and thus are expected to be used in additive manufacturing PEEK bone implants in the future, but the lower yield strength poses a design challenge.

Children with syndromic forms of craniosynostosis undergo a plethora of surgical interventions to resolve the clinical features caused by the premature fusion of cranial sutures. While surgical correction is reliable, the need for repeated rounds of invasive treatment puts a heavy burden on the child and their family. This study explores a non-surgical alternative using mechanical loading of the cranial joints to prevent or delay craniofacial phenotypes associated with Crouzon syndrome. We treated Crouzon syndrome mice before the onset of craniosynostosis by cyclical mechanical loading of cranial joints using a custom designed set-up. Cranial loading applied to the frontal bone partially restores normal skull morphology, significantly reducing the typical brachycephalic appearance. This is underpinned by the delayed closure of the coronal suture and of the intersphenoidal synchondrosis. This study provides a novel treatment alternative for syndromic craniosynostosis which has the potential to be an important step towards replacing, reducing or refining the surgical treatment of all craniosynostosis patients., (© 2022. The Author(s).)

Axis I disorders are one of the major health burdens worldwide. Evidence suggests that Mediterranean diet has key biological factors associated with reducing the progression of these disorders. This systematic review aimed to clarify the relationship between Mediterranean diet and Axis I disorders. PubMed and Scopus databases were searched from January 2016 up to June 2021. Those observational studies in English language that assessed the relationship between Mediterranean diet and Axis I disorders (such as depression, anxiety, eating disorders, schizophrenia, etc.) were included in this review. The Newcastle-Ottawa Scale was used to evaluate the quality of studies. Thirty-six studies (15 cohorts, 19 cross-sectional, and 2 case-control) met the inclusion criteria. The results revealed that more than two-thirds of the studies (25 studies, 69.44%) had significant protective relationship between receiving Mediterranean diet and reducing the symptoms or incidence of Axis I disorders. Most studies were performed on depression (29 studies measured depression at least as one of the Axis I disorders), of which 72.41% reported an inverse relationship. There were also 9 studies on anxiety (studies that measured anxiety at least as one of the Axis I disorders), that 77.77% of them observed protective association. Moreover, majority of the studies (25 studies, 69.44%) had high quality, of which 76% found an inverse relationship. In conclusion, it seems that the Mediterranean diet can reduce the symptoms or the occurrence of Axis I disorders (especially depression and anxiety). However, more extensive review studies, particularly with interventional designs, are necessary to prove the result., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

The neonate skull consists of several bony plates, connected by fibrous soft tissue called sutures. Premature fusion of sutures is a medical condition known as craniosynostosis. Sagittal synostosis, caused by premature fusion of the sagittal suture, is the most common form of this condition. The optimum management of this condition is an ongoing debate in the craniofacial community while aspects of the biomechanics and mechanobiology are not well understood. Here, we describe a computational framework that enables us to predict and compare the calvarial growth following different reconstruction techniques for the management of sagittal synostosis. Our results demonstrate how different reconstruction techniques interact with the increasing intracranial volume. The framework proposed here can be used to inform optimum management of different forms of craniosynostosis, minimising the risk of functional consequences and secondary surgery., Competing Interests: The 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 © 2022 Cross, Khonsari, Patermoster, Arnaud, Larysz, Kölby, Johnson, Ventikos and Moazen.)

The aim of this study was to carry out a retrospective multicentre study comparing the morphological outcome of 8 techniques used for the management of sagittal synostosis versus a large cohort of control patients. Computed tomographic (CT) images were obtained from children CT-scanned for non-craniosynostosis related events (n = 241) and SS patients at preoperative and postoperative follow-up stages (n = 101). No significant difference in morphological outcomes was observed between the techniques considered in this study. However, the majority of techniques showed a tendency for relapse. Further, the more invasive procedures at older ages seem to lead to larger intracranial volume compared to less invasive techniques at younger ages. This study can be a first step towards future multicentre studies, comparing surgical results and offering a possibility for objective benchmarking of outcomes between methods and centres., Competing Interests: Declaration of competing interest 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., (Copyright © 2021 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Osteoderms are mineralised structures consisting mainly of calcium phosphate and collagen. They form directly within the skin, with or without physical contact with the skeleton. Osteoderms, in some form, may be primitive for tetrapods as a whole, and are found in representatives of most major living lineages including turtles, crocodilians, lizards, armadillos, and some frogs, as well as extinct taxa ranging from early tetrapods to dinosaurs. However, their distribution in time and space raises questions about their evolution and homology in individual groups. Among lizards and their relatives, osteoderms may be completely absent; present only on the head or dorsum; or present all over the body in one of several arrangements, including non-overlapping mineralised clusters, a continuous covering of overlapping plates, or as spicular mineralisations that thicken with age. This diversity makes lizards an excellent focal group in which to study osteoderm structure, function, development and evolution. In the past, the focus of researchers was primarily on the histological structure and/or the gross anatomy of individual osteoderms in a limited sample of taxa. Those studies demonstrated that lizard osteoderms are sometimes two-layered structures, with a vitreous, avascular layer just below the epidermis and a deeper internal layer with abundant collagen within the deep dermis. However, there is considerable variation on this model, in terms of the arrangement of collagen fibres, presence of extra tissues, and/or a cancellous bone core bordered by cortices. Moreover, there is a lack of consensus on the contribution, if any, of osteoblasts in osteoderm development, despite research describing patterns of resorption and replacement that would suggest both osteoclast and osteoblast involvement. Key to this is information on development, but our understanding of the genetic and skeletogenic processes involved in osteoderm development and patterning remains minimal. The most common proposition for the presence of osteoderms is that they provide a protective armour. However, the large morphological and distributional diversity in lizard osteoderms raises the possibility that they may have other roles such as biomechanical reinforcement in response to ecological or functional constraints. If lizard osteoderms are primarily for defence, whether against predators or conspecifics, then this 'bony armour' might be predicted to have different structural and/or mechanical properties compared to other hard tissues (generally intended for support and locomotion). The cellular and biomineralisation mechanisms by which osteoderms are formed could also be different from those of other hard tissues, as reflected in their material composition and nanostructure. Material properties, especially the combination of malleability and resistance to impact, are of interest to the biomimetics and bioinspired material communities in the development of protective clothing and body armour. Currently, the literature on osteoderms is patchy and is distributed across a wide range of journals. Herein we present a synthesis of current knowledge on lizard osteoderm evolution and distribution, micro- and macrostructure, development, and function, with a view to stimulating further work., (© 2021 The Authors. Biological Reviews published by John Wiley & Sons Ltd on behalf of Cambridge Philosophical Society.)

Introduction: Our understanding of the impact of the stem fixation method in total hip arthroplasty (THA) on the subsequent management of periprosthetic femoral fractures (PFF) is still limited. This study aimed to investigate and quantify the effect of the stem fixation method, i.e., cemented vs. uncemented THA, on the management of Vancouver Type B1 periprosthetic femoral fractures with the same plate., Methods: Eight laboratory models of synthetic femora were divided into two groups and implanted with either a cemented or uncemented hip prosthesis. The overall stiffness and strain distribution were measured under an anatomical one-legged stance. All eight specimens underwent an osteotomy to simulate Vancouver type B1 PFF's. Fractures were then fixed using the same extramedullary plate and screws. The same measurements and fracture movement were taken under the same loading conditions., Results: Highlighted that the uncemented THA and PFF fixation constructs had a lower overall stiffness. Subsequently, the mechanical strain on the fracture plate for the uncemented construct was higher compared to the cemented constructs., Conclusion: PFF fixation of a Vancouver type B1 fracture using a plate may have a higher risk of failure in uncemented THAs., (© The Authors, published by EDP Sciences, 2022.)

Background: Early failure of uncemented femoral stems associated with incorrect sizing is a known postoperative complication. Surgeons are often faced with the question of whether an uncemented stem of adequate stability or a larger-sized stem should be implanted, especially when the proximal femoral cancellous bone is adequate. The biomechanical effect of sub-optimal stem sizing in the femur remains unclear. This study investigated the mechanical behaviour of two sequential sized uncemented stems of the same type., Methods: Six laboratory models of synthetic non-osteoporotic femora were randomly divided into two groups and implanted with either a nominal or oversized uncemented hydroxyapatite-coated nonporous titanium collarless stem. Stiffness, uniaxial strain, and pattern of strain distribution were measured under an anatomical one-legged stance., Results: Oversized stems demonstrated a higher overall stiffness compared to nominal; however, this was not statistically significant. The nominal stem showed a higher strain in the neck and the proximal medial diaphyseal region. The oversized stem showed higher strains in the distal region around the implant tip., Conclusion: Opting to use a larger stem may potentially increase primary stability, thus allowing safer early mobility. However, higher stiffness may lead to stress shielding, bone loss, and thigh pain in the long term. In addition, strains in the diaphysis and the tip of the stem may predispose to periprosthetic fractures, especially in osteoporotic bones, making this a relatable aspect for users and biomechanical loading. Given the wide range of complex factors that need to be considered when choosing stem size in uncemented THA surgery, this study's results should be interpreted cautiously., (© The Authors, published by EDP Sciences, 2022.)

Current approaches for bladder reconstruction surgery are associated with many morbidities. Tissue engineering is considered an ideal approach to create constructs capable of restoring the function of the bladder wall. However, many constructs to date have failed to create a sufficient improvement in bladder capacity due to insufficient neobladder compliance. This review evaluates the biomechanical properties of the bladder wall and how the current reconstructive materials aim to meet this need. To date, limited data from mechanical testing and tissue anisotropy make it challenging to reach a consensus on the native properties of the bladder wall. Many of the materials whose mechanical properties have been quantified do not fall within the range of mechanical properties measured for native bladder wall tissue. Many promising new materials have yet to be mechanically quantified, which makes it difficult to ascertain their likely effectiveness. The impact of scaffold structures and the long-term effect of implanting these materials on their inherent mechanical properties are areas yet to be widely investigated that could provide important insight into the likely longevity of the neobladder construct. In conclusion, there are many opportunities for further investigation into novel materials for bladder reconstruction. Currently, the field would benefit from a consensus on the target values of key mechanical parameters for bladder wall scaffolds.

Sagittal synostosis is the most occurring form of craniosynostosis, resulting in calvarial deformation and possible long-term neurocognitive deficits. Several surgical techniques have been developed to correct these issues. Debates as to the most optimal approach are still ongoing. Finite element method is a computational tool that's shown to assist with the management of craniosynostosis. The aim of this study was to compare and predict the outcomes of three reconstruction methods for sagittal craniosynostosis. Here, a generic finite element model was developed based on a patient at 4 months of age and was virtually reconstructed under all three different techniques. Calvarial growth was simulated to predict the skull morphology and the impact of different reconstruction techniques on the brain growth up to 60 months of age. Predicted morphology was then compared with in vivo and literature data. Our results show a promising resemblance to morphological outcomes at follow up. Morphological characteristics between considered techniques were also captured in our predictions. Pressure outcomes across the brain highlight the potential impact that different techniques have on growth. This study lays the foundation for further investigation into additional reconstructive techniques for sagittal synostosis with the long-term vision of optimizing the management of craniosynostosis., (© 2021. The Author(s).)

Osteoderms (OD) are mineralised dermal structures consisting mainly of calcium phosphate and collagen. The sheer diversity of OD morphologies and their distribution within the skin of lizards makes these reptiles an ideal group in which to study ODs. Nonetheless, our understanding of the structure, development, and function of lizard ODs remains limited. The specific aims of this study were: (1) to carry out a detailed morphological characterisation of ODs in three lizard species; (2) to design and manufacture biomimetic sheets of ODs corresponding to the OD arrangement in each species; and (3) to evaluate the impact resistance of the manufactured biomimetic sheets under a drop weight test. Skin samples of the anguimorphs H. suspectum and O. ventralis , and the skink C. zebrata were obtained from frozen lab specimens. Following a series of imaging and image characterisations, 3D biomimetic models of the ODs were developed. 3D models were then printed using additive manufacturing techniques and subjected to drop weight impact tests. The results suggest that a 3D printed compound of overlapping ODs as observed in Corucia can potentially offers a higher energy absorption by comparison with the overlapping ODs of Ophisaurus and the non-overlapping ODs of Heloderma. Compound overlapping ODs need to be further tested and explored as a biomimetic concept to increase the shock absorption capabilities of devices and structures., (Creative Commons Attribution license.)

Craniosynostosis is the premature fusion of one or more sutures across the calvaria, resulting in morphological and health complications that require invasive corrective surgery. Finite element (FE) method is a powerful tool that can aid with preoperative planning and post-operative predictions of craniosynostosis outcomes. However, input factors can influence the prediction of skull growth and the pressure on the growing brain using this approach. Therefore, the aim of this study was to carry out a series of sensitivity studies to understand the effect of various input parameters on predicting the skull morphology of a sagittal synostosis patient post-operatively. Preoperative CT images of a 4-month old patient were used to develop a 3D model of the skull, in which calvarial bones, sutures, cerebrospinal fluid (CSF), and brain were segmented. Calvarial reconstructive surgery was virtually modeled and two intracranial content scenarios labeled "CSF present" and "CSF absent," were then developed. FE method was used to predict the calvarial morphology up to 76 months of age with intracranial volume-bone contact parameters being established across the models. Sensitivity tests with regards to the choice of material properties, methods of simulating bone formation and the rate of bone formation across the sutures were undertaken. Results were compared to the in vivo data from the same patient. Sensitivity tests to the choice of various material properties highlighted that the defined elastic modulus for the craniotomies appears to have the greatest influence on the predicted overall skull morphology. The bone formation modeling approach across the sutures/craniotomies had a considerable impact on the level of contact pressure across the brain with minimum impact on the overall predicated morphology of the skull. Including the effect of CSF (based on the approach adopted here) displayed only a slight reduction in brain pressure outcomes. The sensitivity tests performed in this study set the foundation for future comparative studies using FE method to compare outcomes of different reconstruction techniques for the management of craniosynostosis., Competing Interests: The 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 Cross, Khonsari, Galiay, Patermoster, Johnson, Ventikos and Moazen.)

Objectives: To: (1) design an artifact-free 3D-printed MR-safe temporary transfer device, (2) engineer bone-pins from carbon fiber reinforced polyether ether ketone (CFR-PEEK), (3) evaluate the imaging artifacts of CFR-PEEK, and (4) confirm the osteointegration potential of CFR-PEEK, thus enhancing 3D-planning of bony advancements in hemifacial microsomia using sequential magnetic resonance imaging (MRI)., Study Design: Engineered CRF-PEEK bone pins and a 3D printed ex-fix device were implanted into a sheep head and imaged with MRI and computed tomography . The osseointegration and bony compatibility potential of CFR-PEEK was assessed with scanning electron microscopy images of MC3T3 preosteoblast cells on the surface of the material., Results: The CFR-PEEK pins resulted in a signal void equivalent to the dimension of the pin, with no adjacent areas of MR-signal loss or computed tomography artifact. MCT3 cells adhered and proliferated on the surface of the discs by forming a monolayer of cells, confirming compatibility and osseointegration potential., Conclusion: A 3D printed transfer device could be utilized temporarily during MRI to permit artifact-free 3D planning. CFR-PEEK pins eliminate imaging artifact permitting sequential MRI examination. In combination, this has the potential to enhance distraction osteogenesis, by permitting accurate three-dimensional planning without ionizing radiation., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 by Mutaz B. Habal, MD.)

Aim: We have encountered four cases with Taylor spatial frames (TSF) (Smith & Nephew, Memphis, TN, USA) with breakage at the half-ring junction of the distal ring. This study examines the strain produced on different locations of the distal ring during loading and the effects on the strain of altering the frame construct., Materials and Methods: We mounted two ring TSF constructs on tibia saw bone models. The proximal ring was the same in all constructs and consisted of a 2/3 180 mm ring attached with three wires. Construct 1 is reproducing the configuration of cases where failure was seen. The distal 155 mm ring is attached with three half pins. The half-ring junction is located in the midline. Construct 2 has a different half pin placement and an additional wire on the distal ring. Constructs 3 and 4 have the same half pin configuration to construct 1 but the distal ring is rotated 60° internally and externally, respectively. Strain gauges were attached to different locations and measurements recorded during loading. Statistical analysis was performed., Results: Highest strain values were recorded at the half-ring junction of constructs 1 and 2 (>600 microstrains (με) in tension). Rotating the ring 60° internally significantly reduces the strain at the half-ring junction (<300 με) whilst external rotation by 60° further reduces the strain (<180 με). Ring strain is higher in areas close to half pin attachments., Conclusion: The highest strain is in the half-ring junction as the half rings are subjected to different loading modes. The thickness of the half-ring is halved and the second moment of area reduced further increasing breakage risk. Placing this junction close to the half pin-frame interface, as dictated by the anatomical safe zone further increases the strain. Rotating the distal ring 60° significantly reduces the strain at the half-ring junction., Clinical Significance: Ring breakage is a rare but significant complication. This is the first study to address this potential mode of TSF failure. Insights and technical tips from this study can help reduce this., How to Cite This Article: Iliadis AD, Bebja R, Wang K, et al. Reducing the Risk of Ring Breakage in Taylor Spatial Frames: The Effect of Frame Configuration on Strain at the Half-ring Junction. Strategies Trauma Limb Reconstr 2020;15(3):146-150., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2020; Jaypee Brothers Medical Publishers (P) Ltd.)

Peripheral arterial disease and critical limb ischemia are common symptoms of cardiovascular disease. Vascular surgery is used to create a bypass around occluded blood vessels to improve blood flow to ischemic muscle, thus avoiding the need for amputation. Attempts to vascularize tissues by therapeutic angiogenesis using delivery of exogenous angiogenic agents are underwhelming. A material-based approach that provides an endogenous stimulus capable of promoting angiogenesis and increased tissue perfusion would provide a paradigm shift in treatment options available. It is reported here that microporous biodegradable films produced using thermally induced phase separation provide a localized biophysical stimulus of proangiogenic genes in vivo that is associated with increased blood vessel density and restoration of blood flow to ischemic tissue. These findings show, for the first time, that acellular, nonfunctionalized biodegradable biomaterials can provide an innovative, material-based approach for therapeutic angiogenesis to enhance tissue reperfusion in vivo., (© 2020 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We describe the histological appearance of the osteoderms (ODs) of Heloderma suspectum and Varanus komodoensis using multiple staining and microscopy techniques to yield information about their morphology and development. Histological analysis showed that the ODs of H. suspectum are composed of three main tissue types, a superficial layer, herein identified as osteodermine, capping a base composed of Sharpey-fibre bone and lamellar bone rich in secondary osteons (Haversian bone tissue). In contrast, ODs in V. komodoensis are composed of a core of woven bone surrounded by parallel-fibred bone without a capping tissue. Thus, in these two species, ODs differ both in terms of their structural composition and in details of their skeletogenesis. The histology of the mineralised tissues observed in these two reptile taxa provides insights into the mechanism of formation of lizard ODs and presents a direct comparison of the histological properties between the ODs of the two species. These data allow greater understanding of the comparative histological appearance of the dermal bones of lizards and highlight their structural diversity., (© 2020 The Authors. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.)

Osteoderms are hard tissues embedded in the dermis of vertebrates and have been suggested to be formed from several different mineralized regions. However, their nano architecture and micro mechanical properties had not been fully characterized. Here, using electron microscopy, µ-CT, atomic force microscopy and finite element simulation, an in-depth characterization of osteoderms from the lizard Heloderma suspectum, is presented. Results show that osteoderms are made of three different mineralized regions: a dense apex, a fibre-enforced region comprising the majority of the osteoderm, and a bone-like region surrounding the vasculature. The dense apex is stiff, the fibre-enforced region is flexible and the mechanical properties of the bone-like region fall somewhere between the other two regions. Our finite element analyses suggest that when combined into the osteoderm structure, the distinct tissue regions are able to shield the body of the animal by bearing the external forces. These findings reveal the structure-function relationship of the Heloderma suspectum osteoderm in unprecedented detail. STATEMENT OF SIGNIFICANCE: The structures of bone and teeth have been thoroughly investigated. They provide a basis not only for understanding the mechanical properties and functions of these hard tissues, but also for the de novo design of composite materials. Osteoderms, however, are hard tissues that must possess mechanical properties distinct from teeth and bone to function as a protective armour. Here we provide a detailed analysis of the nanostructure of vertebrate osteoderms from Heloderma suspectum, and show that their mechanical properties are determined by their multiscale hierarchical tissue. We believe this study contributes to advance the current knowledge of the structure-function relationship of the hierarchical structures in the Heloderma suspectum osteoderm. This knowledge might in turn provide a source of inspiration for the design of bioinspired and biomimetic materials., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2020. Published by Elsevier Ltd.)

Background and Aim: Partial hand amputations are common in developing countries and have a negative impact on patients and their families' quality of life. The uniqueness of each partial hand amputation, coupled with the relatively high costs of prostheses, makes it challenging to provide suitable prosthetic solutions in developing countries. Current solutions often have long lead times and require a high level of expertise to produce. The aim of this study was to design and develop an affordable patient-specific partial hand prosthesis for developing countries., Technique: The prosthesis was designed for a patient with transmetacarpal amputation (i.e. three amputated fingers and partial palm). The final design was passive, controlled by the contralateral hand, and utilized the advanced flexibility properties of thermoplastic polyurethane in a glove-like design that costs approximately 20 USD to fabricate. Quantitative and qualitative tests were conducted to assess performance of the device after the patient used the final design. A qualitative assessment was performed to gather the patient's feedback following a series of tests of grasp taxonomy. A quantitative assessment was performed through a grasp and lift test to measure the prosthesis' maximum load capacity., Discussion: This study showed that the prosthesis enhanced the patient's manual handling capabilities, mainly in the form of grasp stability. The prosthesis was light weight and could be donned and doffed by the patient independently. Limitations include the need to use the contralateral hand to achieve grasping and low grasp strength., Clinical Relevance: Persons with partial hand amputation in developing countries lack access to affordable functional prostheses, hindering their ability to participate in the community. 3D-printed prostheses can provide a low-cost solution that is adaptable to different amputation configurations.

The Intraosseous Transcutaneous Amputation Prosthesis (ITAP) offers transfemoral amputees an ambulatory method potentially reducing soft tissue complications seen with socket and stump devices. This study validated a finite element (in silico) model based on an ITAP design and investigated implant stem stiffness influence on periprosthetic femoral bone strain. Results showed good agreement in the validation of the in silico model against the in vitro results using uniaxial strain gauges and Digital Image Correlation (DIC). Using Strain Energy Density (SED) thresholds as the stimulus for adaptive bone remodelling, the validated model illustrated that: (a) bone apposition increased and resorption decreased with increasing implant stem flexibility in early stance; (b) bone apposition decreased (mean change = - 9.8%) and resorption increased (mean change = 20.3%) from distal to proximal in most stem stiffness models in early stance. By engineering the flow of force through the implant/bone (e.g. by changing material properties) these results demonstrate how periprosthetic bone remodelling, thus aseptic loosening, can be managed. This paper finds that future implant designs should be optimised for bone strain under a variety of relevant loading conditions using finite element models to maximise the chances of clinical success.

Early fusion of the sagittal suture is a clinical condition called, sagittal craniosynostosis. Calvarial reconstruction is the most common treatment option for this condition with a range of techniques being developed by different groups. Computer simulations have a huge potential to predict the calvarial growth and optimise the management of this condition. However, these models need to be validated. The aim of this study was to develop a validated patient-specific finite element model of a sagittal craniosynostosis. Here, the finite element method was used to predict the calvarial morphology of a patient based on its preoperative morphology and the planned surgical techniques. A series of sensitivity tests and hypothetical models were carried out and developed to understand the effect of various input parameters on the result. Sensitivity tests highlighted that the models are sensitive to the choice of input parameter. The hypothetical models highlighted the potential of the approach in testing different reconstruction techniques. The patient-specific model highlighted that a comparable pattern of calvarial morphology to the follow up CT data could be obtained. This study forms the foundation for further studies to use the approach described here to optimise the management of sagittal craniosynostosis.

Increasingly, the rat femoral fracture model is being used for preclinical investigations of fracture healing, however, the effect of gap size and its influence on mechanobiology is not well understood. We aimed to evaluate the influence of osteotomy gap on osteotomy healing between the previously published extremes of guaranteed union (0.5 mm) and non-union (3 mm) using this model. A femoral osteotomy in 12-14 week old female Wistar rats was stabilised with a micro fixator (titanium blocks, carbon fiber bars) with an osteotomy gap of 1.0 mm (n = 5), 1.5 mm (n = 7), 2.0 mm (n = 6). After five weeks, the left femur was retrieved. The osteotomy gap was scanned using X-ray microtomography and then histologically evaluated. The radiographic union rate (complete mineralised bone bridging across the osteotomy) was three times higher for the 1.0 mm than the 2.0 mm gap. The 1.0 mm gap had the largest callus (0.069μm 3 ) and bone volume (0.035μm 3 ). Callus and bone volume were approximately 50% smaller within the 2.0 mm gap. Using cadaveric rat femurs stabilised with the external fixator, day 0 mechanical assessment of construct stiffness was calculated on materials testing machine displacement vs load output. The construct stiffness for the 1.0, 1.5 and 2.0 mm gaps was 32.6 ± 5.4, 32.5 ± 2.4, and 32.4 ± 8.3 N/mm (p = 0.779). Interfragmentary strain (IFS) was calculated using the change in osteotomy gap displacement as measured using microstrain miniature differential reluctance transducer spanning the osteotomy gap. Increasing the gap size significantly reduced the IFS (p = 0.013). The mean 'day 0' IFS for the 1.0, 1.5 and 2.0 mm gaps were 11.2 ± 1.3, 8.4 ± 1.5 and 6.1 ± 1.2% respectively. A 1.5 mm gap resulted in a delayed fracture healing by 5 weeks and may represent a useful test environment for fracture healing therapy. Increasing gap size did not affect construct stiffness, but did reduce the 'day 0' IFS, with a doubling of non-union and halving of bone volume measured between 1.0 and 2.0 mm gaps., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Acne vulgaris is a dermatological disorder that is related to inflammation and oxidative stress. Recent studies have also suggested diet as a potential reason for acne. Considering the inconsistency of the few previous reports, the present study aimed to determine the levels of vitamin D, adiponectin, oxidative stress, lipid profile and nutrient intakes in females with acne., Materials and Methods: Forty females with acne vulgaris and 40 age-matched healthy females were included in this study in Shiraz, Iran. Data on their sociodemographic status, acne history, and anthropometric indices were collected. Blood samples were taken to determine the levels of 25-hydroxyvitamin D, adiponectin, malondialdehyde, total antioxidant capacity, and lipid profile. Three 24-hour dietary recalls were also obtained from each of the individuals to evaluate nutrient intakes. Data were analyzed using the Chi-square test, Independent-samples t-test or Mann-Whitney U-test, and Logistic Regression., Results: Patients with acne had a significantly higher family history of acne compared to controls (P=0.006). Serum level of malondialdehyde was significantly higher in cases (P=0.01), while high-density lipoprotein cholesterol was significantly lower (P=0.02). Moreover, significantly lower fiber intake was observed in cases compared with controls (P=0.007). In the multivariate analysis, a family history of acne and increased malondialdehyde levels were risk factors for acne, whereas a higher fiber intake was protective., Conclusion: Family history of acne, oxidative stress, dyslipidemia, and lower dietary fiber intakes may play a role in acne pathogenesis. An early assessment of these parameters may be useful for planning treatment procedures., (Copyright© 2019, Galen Medical Journal.)