Cadaveric Tissue Research Articles

Determination of the Force Required to Produce Stab "Wounds" in Fruit Compared With Cadaveric Chest Tissue.

In laymen's terms, it can be difficult to communicate how much force is needed to create a stab wound into a person's chest. Previous work has determined the force to puncture the skin, rib cartilage, or bone but without putting the results in terms that are easy to understand.The purpose of this study was to determine the force needed to puncture 3 types of fruit using 3 different types of knives, namely, a steak knife, a butcher's knife, and a lock-blade knife, to help put these previous results in perspective.There was wide variation in the force required to insert a knife into different fruits, but no force for any knife at any location for all fruits exceeded 93.1 N. Results show that force needed to penetrate the skin and allow for an 8-cm blade penetration into the chest is similar to the force required to insert a steak knife for a 6-cm distance into a cantaloupe. In addition, the force needed to penetrate the cartilage is most similar to stabbing a watermelon to 6 cm with a butcher knife. However, the forces required to penetrate the bone are greater than those required to penetrate any fruit with any type of blade.

Immunohistochemical Study of C-cells morphology, distribution and localization in the thyroid gland: A pilot study in cadaveric tissue

Objective: Exact identification of C-cells in thyroid with defined morphological features, number of cells present in whole population, ratio of parafollicular to follicular cells and localization is a challenge with conventional analysis. A specific and sensitive calcitonin immunohistochemistry is necessary for the demonstration. Method: Tissue obtained from 30 cadaveric specimens at AIIMS Jodhpur were processed, sectioned and stained for immunohistochemical analysis using calcitonin. The results obtained were also compared with H&E staining for same section. Results: C-cells were found distributed in both lateral lobes, concentrated around a vertical axis in cranio-caudal direction. It was a randomized distribution with hardly any symmetry. A complete homogeneous distribution of C-cells all over the thyroid was never demonstrated. C-cells were usually concentrated in the middle thirds of the thyroid, and more in the right lobe. Upper third predominantly had more C-cells as compared to lower third of the gland. Incidentally, no C-cells were found in the isthmus in any thyroid at all. When observed for the localization, most of the C-cells were in the interfollicular position. Conclusion: The present study findings corroborate the use of IHC for C-cell analysis in thyroid gland. Calcitonin proved to be an important diagnostic marker in C-cell identification. Quantification was done reliably, proving calcitonin used in the procedure justified due to its high specificity and affinity.

Epidural electrical stimulation of the cervical spinal cord opposes opioid-induced respiratory depression.

Opioid overdose suppresses brainstem respiratory circuits, causes apnoea and may result in death. Epidural electrical stimulation (EES) at the cervical spinal cord facilitated motor activity in rodents and humans, and we hypothesized that EES of the cervical spinal cord could antagonize opioid-induced respiratory depression in humans. Eighteen patients requiring surgical access to the dorsal surface of the spinal cord between C2 and C7 received EES or sham stimulation for up to 90s at 5 or 30Hz during complete (OFF-State) or partial suppression (ON-State) of respiration induced by remifentanil. During the ON-State, 30Hz EES at C4 and 5Hz EES at C3/4 increased tidal volume and decreased the end-tidal carbon dioxide level compared to pre-stimulation control levels. EES of 5Hz at C5 and C7 increased respiratory frequency compared to pre-stimulation control levels. In the OFF-State, 30Hz cervical EES at C3/4 terminated apnoea and induced rhythmic breathing. In cadaveric tissue obtained from a brain bank, more neurons expressed both the neurokinin 1 receptor (NK1R) and somatostatin (SST) in the cervical spinal levels responsive to EES (C3/4, C6 and C7) compared to a region non-responsive to EES (C2). Thus, the capacity of cervical EES to oppose opioid depression of respiration may be mediated by NK1R+/SST+ neurons in the dorsal cervical spinal cord. This study provides proof of principle that cervical EES may provide a novel therapeutic approach to augment respiratory activity when the neural function of the central respiratory circuits is compromised by opioids or other pathological conditions. KEY POINTS: Epidural electrical stimulation (EES) using an implanted spinal cord stimulator (SCS) is an FDA-approved method to manage chronic pain. We tested the hypothesis that cervical EES facilitates respiration during administration of opioids in 18 human subjects who were treated with low-dose remifentanil that suppressed respiration (ON-State) or high-dose remifentanil that completely inhibited breathing (OFF-State) during the course of cervical surgery. Dorsal cervical EES of the spinal cord augmented the respiratory tidal volume or increased the respiratory frequency, and the response to EES varied as a function of the stimulation frequency (5 or 30Hz) and the cervical level stimulated (C2-C7). Short, continuous cervical EES restored a cyclic breathing pattern (eupnoea) in the OFF-State, suggesting that cervical EES reversed the opioid-induced respiratory depression. These findings add to our understanding of respiratory pattern modulation and suggest a novel mechanism to oppose the respiratory depression caused by opioids.

Practical Tips for Setting Up and Running OSCEs.

Objective structured clinical examinations (OSCEs) are used to assess students' skills on a variety of tasks using live animals, models, cadaver tissue, and simulated clients. OSCEs can be used to provide formative feedback, or they can be summative, impacting progression decisions. OSCEs can also drive student motivation to engage with clinical skill development and mastery in preparation for clinical placements and rotations. This teaching tip discusses top tips for running an OSCE for veterinary and veterinary nursing/technician students as written by an international group of authors experienced with running OSCEs at a diverse set of institutions. These tips include tasks to perform prior to the OSCE, on the day of the examination, and after the examination and provide a comprehensive review of the requirements that OSCEs place on faculty, staff, students, facilities, and animals. These tips are meant to assist those who are already running OSCEs and wish to reassess their existing OSCE processes or intend to increase the number of OSCEs used across the curriculum, and for those who are planning to start using OSCEs at their institution. Incorporating OSCEs into a curriculum involves a significant commitment of resources, and this teaching tip aims to assist those responsible for delivering these assessments with improving their implementation and delivery.

Comparative biocompatibility studies of Kirschner wire, allogeneic and canine xenogeneic cadaveric bone tissue implants in rat model

Pre-clinical safety or biocompatibility studies of newer biomaterials intended for clinical use are paramount in medical implant technology. The in vivo safety of rat (allogeneic) and dog (xenogeneic) cadaveric bone implants (CBI) in the present study were assessed through histological and haematological profiles. A total of 12 male Albino rats (average weight 120 g) divided into three groups (A, B & C) of four rats each was used. Rat (allogeneic) and dog (xenogeneic) cadaveric bone implants were surgically placed between the lateral and cranial vastus muscles (on the thigh) of the rats in groups B and C, respectively, while Kirschner wire/inert implants were used for group A and served as control. The rats were monitored for 30 days, and peripheral blood profiles, as well as tissue sections at intervals of 14 and 28 days, were harvested, studied and compared. Results showed that the overall performance of all groups of rats was good. There was marked cellular infiltration of myocytes in rats of groups B and C, and cartilage-like (hyaline) cells in group C at 14 and 28-days post-implantation, respectively. No significant alteration existed in the haemogram of all groups of rats except for the increased lymphocytes count observed in group B pre-implantation. In conclusion, canine CBI used in this study possess fairly excellent biocompatibility and osteoinductive potentials in the rat’s model. Therefore, having confirmed their relative in vivo safety and biocompatibility, further clinical trials involving the use of cadaveric bone tissues as good biomaterial for fabricating bone fixatives should be performed in higher animal models.

Determining the Optimal Soft Tissue Preservation Techniques for Surgical Skills Training

IntroductionCompetency Based Medical Education, overseen and implemented by the Royal College of Physicians and Surgeons of Canada, requires realistic simulation of specific tasks called Entrustable Professional Activities (EPAs). Mastery of these tasks is required to proceed in the surgical specialty. Due to the growing need for high fidelity training in postgraduate surgical education, there has been a shift from the use of hard‐fixed to soft‐fixed material for improved realism. Currently, there exists no standardized way of assessing the suitability of various fixation techniques for different EPAs.ObjectiveThe current study seeks to establish the most appropriate tissue fixation method for each EPA. Additionally, we aim to develop a standardized matrix to rate the effectiveness of soft‐fixation methods for the purposes of surgical training based on a number of factors such as the EPA, storage, longevity, biohazardous risk, cost, biomechanical properties, and realism.HypothesisWe hypothesize that different soft‐fixation methods possess varying suitabilities for each EPA, which could be deduced through the use of a testing matrix.MethodsEPAs will be performed on cadaveric tissues embalmed with various soft‐fixation solutions. In order to establish the solutions that will be used, initial tests will be conducted on porcine material. Each pork hock (the joint between the tibia/fibula and the metatarsals) will be embalmed with one of 8 soft‐fixation solutions. Surgical residents will perform an EPA on each embalmed tissue and record their observations. The residents will respond to statements about each of the embalming solutions using a 5‐point Likert scale. The results from this testing will be used to select the embalming solutions to be used when the study is conducted on human donors.ResultsTesting of porcine material to determine the most useful fixation technique is expected to be completed in February of 2022. Testing on cadaveric tissue is expected to be completed in July of 2022.ConclusionGaining an understanding of the suitability of various soft‐fixation methods allows for high fidelity surgical skills training and the maximization of the use of each donor.

Pituitary Lineage Differentiation from Human Induced Pluripotent Stem Cells in 2D and 3D Cultures.

Despite its small size, the pituitary gland plays a central role in the maintenance of normal homeostasis of most physiological systems through its regulation of the function of other endocrine glands. The complexity of the anterior pituitary gland, due to its composition of several different hormone-secreting cell types, begets a plethora of disorders and pathologies due primarily to hyposecretion or hypersecretion of hormones. The gonadotrophs, which make up less than 5% of the total number of cells in the anterior pituitary, serve to regulate gonad development and sexual reproduction in males and females. Despite the increased research on the development of models to study pituitary function within the last decade, a model specifically designed to study the gonadotrophs is still lacking. The development of organoid technology has facilitated research in the field of personalized medicine and physiological testing using patient-derived cells. The ability to produce pituitary organoids would allow researchers to construct an in vitro model of the human hypothalamic-pituitary-gonadal or hypothalamic-pituitary-adrenal axis to use in further fertility or endocrine research. The application of this technology in patients could revolutionize the treatment of infertility and a variety of neuroendocrine disorders. The impetus behind this study was to develop a pituitary-like organoid consisting only of gonadotrophs. Despite the lack of success in differentiating gonadotrophs, pituitary-like organoids were differentiated from human-induced pluripotent stem cells. In addition, two-dimensional and three-dimensional differentiated cultures were characterized and compared to human adult cadaveric pituitary tissue.

MP10-10 HEAD-TO-HEAD COMPARISON OF HYDROGEL MODELS TO CADAVERS FOR INFLATABLE PENILE PROSTHESIS (IPP) TRAINING

You have accessJournal of UrologyCME1 May 2022MP10-10 HEAD-TO-HEAD COMPARISON OF HYDROGEL MODELS TO CADAVERS FOR INFLATABLE PENILE PROSTHESIS (IPP) TRAINING Patrick Saba, Rachel Melnyk, Michael Witthaus, Christopher Wanderling, Tyler Holler, and Ahmed Ghazi Patrick SabaPatrick Saba More articles by this author , Rachel MelnykRachel Melnyk More articles by this author , Michael WitthausMichael Witthaus More articles by this author , Christopher WanderlingChristopher Wanderling More articles by this author , Tyler HollerTyler Holler More articles by this author , and Ahmed GhaziAhmed Ghazi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002532.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Cadavers have long been the standard for inflatable penile prosthetic (IPP) placement training. However limited availability, biohazard risk and specialized facilities hinders their widespread use. A previously validated high-fidelity, non-biohazardous, hydrogel procedural model for IPP placement was developed to address this need. We aim to evaluate if hydrogel models can adequately perform as an equivalent training tool for IPP placement to supplement standard cadaveric simulations. METHODS: 73 participants (12 experts, 13 fellows, 48 residents) performed guided IPP simulations on a cadaver followed by a hydrogel model (Figure 1). Surveys were completed to compare tissue properties, anatomical and procedural resemblance, and educational effectiveness between the two modalities on a 5-point Likert scale. RESULTS: 86% of participants agreed the hydrogel training model replicated relevant human anatomy. 86% agreed that the hydrogel tissues resembled the appearance of cadaveric tissues with participants also agreeing the dartos (92%), scrotum (90%), pubic bone (88%), skin (86%), and corpora (71%) resembled the texture/behavior of a cadaver. 96%, 94%, 93%, 89%, 89%, 86% agreed that the model replicated procedural steps in cadavers, regarding prosthesis measurement and placement, stay suture placement, tissue closure, corporal dilation, and skin/dartos incision respectively. 100% of experts and fellows agreed the model is useful for: improving technical skills, teaching the procedure, and assessing procedural ability vs 94%, 96%, and 88% of residents respectively. 75% of experts believed that the hydrogel model was equal if not better than cadavers at these respective categories. 83% of participants agreed the model was safer than cadavers and 75% agreed the model was equal if not better than cadavers as an educational tool. 82% (75%, 92%, 81% of experts, fellows, residents, respectively) stated they wish to include the models alongside current cadaver training with 1/4 of experts stating they preferred the models over cadavers. CONCLUSIONS: This procedural simulation allows the practice of each step of IPP placement with equivalent fidelity to standard cadaveric simulations. Its non-biohazardous nature provides a safe and effective educational equivalent for IPP surgical training. Source of Funding: Coloplast Research Grant © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e150 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Patrick Saba More articles by this author Rachel Melnyk More articles by this author Michael Witthaus More articles by this author Christopher Wanderling More articles by this author Tyler Holler More articles by this author Ahmed Ghazi More articles by this author Expand All Advertisement PDF DownloadLoading ...

Difficulties Performing Morphometric Assessment on the Costal Cartilage‐Rib Interface in Cadaveric Research

Costal cartilage is commonly used in a variety of reconstructive surgeries such as reconstruction of head and neck anatomy. However, there is disagreement among surgeons regarding the most appropriate costal cartilage from which to harvest (e.g., 5th cartilage versus 6th or 7th; left versus right side). Thus, assessment of costal cartilage morphometry is warranted. In an attempt to assess costal cartilage morphometry in a cadaveric sample, researchers encountered noteworthy inter‐examiner disagreement. This report details the difficulties encountered when attempting to perform morphometric assessment costal cartilage in a cadaveric sample. It is well‐established that the hyaline cartilage of the rib cage commonly undergoes calcific change with age; however, such changes were not appreciable in the cadaveric sample that was assessed. Predominantly, difficulties were encountered in the identification of the cartilage‐bone interface. The disagreement among examiners primarily stemmed from the nature of the costal cartilage and rib color. Some cadaveric specimens had a clear cartilage‐bone interface with evident gross color change between cartilage and bone tissues whereas other cadaveric specimens had relatively little color change between cartilage and bone. This research highlights the importance of cadaveric tissue color in research and underscores an important caveat: incongruent data may result if tissue color is not accounted for in cadaveric research.

Model Development of a Novel Robotic Surgery Training Exercise With Electrocautery

Robot-assisted surgery (RAS) has undergone rapid adoption in general surgery due to features such as three-dimensional visualization, wrist dexterity, improved precision of movement, and operator ergonomics. While many surgical trainees encounter RAS during their residency, robotic skills training programs and curricula vary across institutions and there is broad variation in graduating general surgeons’ robotic proficiency levels. Due to a need for a formalized process to achieve competence on the robotic platform, simulation-based training has become instrumental in closing this gap as it provides training in a low-stakes environment while allowing the trainee to improve their psychomotor and basic procedural skills.Several different models of simulation training exist including virtual reality, animal, cadaveric, and inanimate tissue platforms. Each form of training has its own merits and limitations. While virtual reality platforms have been well evaluated for face, content, and construct validity, their initial set-up costs can be as high as $125,000. Similarly, animal and cadaveric models are not only costly but also have ethical considerations that may preclude participation. There is an unmet need in developing high-fidelity, cost-effective simulations for basic videoscopic skills such as cautery use.We developed a cost-effective and high-fidelity inanimate tissue model that incorporates electrocautery. Using a double-layered bowel model secured to a moistened household sponge, this inanimate exercise simulates fundamental skills of robotic surgery such as tissue handling, camera control, suturing, and electrocautery.

Formalin-free soft embalming of human cadavers using N-vinyl-2-pyrrolidone: perspectives for cadaver surgical training and medical device development.

The traditional apprenticeship approach to surgical skill education for young surgeons has drastically changed to more systematic surgical training using cadavers. Cadavers fixed with formalin are not suitable for surgical training because of their associated health hazards and overhardening. Recently, we established a formalin-free soft preservation method for human cadavers using N-vinyl-2-pyrrolidone. Since 2012, 61 cadavers have been embalmed with pyrrolidone in our institution. Tissues of pyrrolidone-embalmed cadavers are soft and pliable, and their bodies can be preserved for as long as 37months without any signs of corruption. In this review, we introduce our recent attempts to apply pyrrolidone-embalmed cadavers in surgical and medical procedure training, including endotracheal intubation, motion physiology of the vocal folds, laparoscopic surgery, endoscopic skull base surgery, and development of novel medical devices. Future research perspectives on pyrrolidone embalming are discussed.

The Myopectineal Orifice: A Study of Thai Cadavers.

ObjectiveThis study aimed to determine the myopectineal orifice size measured in Thai human cadavers.Materials and MethodsA total of 30 human cadavers, comprising 55 groins, were assessed. Myopectineal orifices (MPOs) were measured in two dimensions: height from the lower border of the conjoined tendon to the upper border of the pectineal ligament and width from the lateral border of pubic tubercle to the medial border of the iliopsoas muscle.ResultsThe mean MPO size is 7.13 + 0.14 cm in width and 6.66 + 0.32 m in height. The mean width and height in male cadavers are 7.16 + 0.14 and 6.84 + 0.27 cm, respectively. The mean width and height in female cadavers are 7.09 + 0.12 and 6.45 + 0.24 cm, respectively. The mean MPO area is 37.26 ± 0.027 cm2, compared with the area of mesh graft 10 cm × 15 cm, 150 cm2. Although the shrinkage of cadaveric tissue and mesh size were adjusted, which were 39.56 ± 0.029 and 81 cm2, respectively, they were found to be sufficient for the mean MPO area. It was found that the mesh size was sufficient for the mean MPO area.ConclusionA mesh size of 10 cm × 15 cm is found to be the appropriate size to cover the MPO among Thais.

Standardized statement for the ethical use of human cadaveric tissues in anatomy research papers: Recommendations from Anatomical Journal Editors-in-Chief.

Human cadaveric donors are essential for research in the anatomical sciences. However, many research papers in the anatomical sciences often omit a statement regarding the ethical use of the donor cadavers or, as no current standardized versions exist, use language that is extremely varied. To rectify this issue, 22 editors-in-chief of anatomical journals, representing 17 different countries, developed standardized and simplified language that can be used by authors of studies that use human cadaveric tissues. The goal of these editor recommendations is to standardize the writing approach by which the ethical use of cadaveric donors is acknowledged in anatomical studies that use donor human cadavers. Such sections in anatomical papers will help elevate our discipline and promote standardized language use in others non anatomy journals and also other media outlets that use cadaveric tissues.

Efficacy of urea solution reperfusion to a formalin-embalmed cadaver for surgical skills training.

Formaldehyde has been traditionally used for embalming human cadavers for gross anatomy education and surgical skills training. However, exposure to formaldehyde negatively affects human health. This study aimed to assess the efficacy of reperfusing urea solution to a formalin-embalmed cadaver for surgical skills training and then investigate the cadaver's tissue elasticity alteration after being soaked into the urea solution. Twelve surgeons evaluated the similarity of tissue characteristics between the cadaver (embalmed by formalin solution and reperfused by urea solution) and a living human body. Furthermore, the tissue formaldehyde content and mechanical properties of the formalin-fixated femoral skin and artery specimens with or without soaking into urea solution were measured. Results showed that the tactile assessment, skin incision, vessel ligation and suture, and decollement were better and more useful in the cadaver reperfused by urea solution than in the cadaver merely fixated by formalin solution. In the urea-reperfused cadaver, the volatilized, or tissue formaldehyde levels declined. The stiffness and Young's modulus of the femoral skin and artery were also lower in the specimen than in the mere formalin-fixated specimen. In conclusion, reperfusion of urea solution to the formalin-fixated cadaver makes anatomical education and surgical skills training more efficient with fewer requirements for cadaver management.

The Effect of Needle Reuse on Piglet Skin Puncture Force.

The study investigated whether the repeat use of needles used to inject piglets with iron, influences the force required to puncture into piglet cadaver skin. Pig units (n = 31) were surveyed on needle reuse and injection practices, and these findings informed subsequent laboratory-based experiments on needle puncture force into piglet cadaver tissues. A 21 G 5/8” needle was reported as the most used needle type (67.7%), with 80.6% reporting needle reuse; 38.7% changed the needle between litters or earlier if damaged, 16.1% every three litters and 22.5% when it felt blunt or damaged, after each injection session or when changing the bottle of iron solution. There was a significant difference in puncture force between the 1st and 36th use (p < 0.05), and between the 1st and 100th use (p = 0.0015), but not between the 1st and 12th or 36th use (p > 0.999 and p = 0.8313, respectively). Scanning electron microscopy (SEM) imaging showed appreciable damage to the needle tip after 12 uses. The repeat use of needles in piglet cadavers increased the force of needle puncture compared to first-time use. When extrapolated to live animals, the use of blunt needles has the potential to cause pain and distress.

Learning, teaching, and training in microsurgery: A systematic review

Numerous microsurgical training techniques and materials have been developed to reduce animal use and training costs. This systematic review aimed to catalog the available microsurgery learning methods on non-living material in order to define an educational program. The PubMed database was searched for English and French articles related to the initial learning of microsurgery with inert, non-living, or digital material and containing the keywords “microsurgery”, “non-living”, “simulation” and “virtual reality”. Among the 488 articles found, 82 were included. This work reports the main microsurgery learning supports. They were classified according to the material used: inert material, cadaveric animal tissues, human cadaver model, virtual reality, and digital technologies. The educational program proposes here is a two-step program that uses non-living material (basic and deepening) before progressing to living models. This initial learning phase teaches basic microsurgical skills (precision, tremor management, and magnification). Then, frequent home training sessions help to maintain the acquired skills. Ethical, organizational, and economic constraints limit access to animal models. Therefore, inert models seem to be ideal support for initial microsurgical learning. The multiplicity of models described makes it possible to achieve progressive learning depending on which models are available.

Human cadaver model as a training tool for enzymatic burn debridement (Nexobrid®): A feasibility study

ObjectivesTo determine the feasibility of using human cadavers to demonstrate enzymatic burn debridement, as a training aid for clinical staff. Material and methodsA single, fresh-frozen human cadaver was used. Prior consent had been given. Burns were created by flame and scalding. Unburned control sites were also assessed. Nexobrid® enzymatic burn debridement paste was applied to all sites, in adherence to the local clinical protocol for treating burned patients. After removal of Nexobrid®, wounds were assessed to determine if the cadaveric tissue appeared similar to what would be expected in living burned patients and whether the technique could be viable for training of burn care staff. ResultsNexobrid® had a very similar effect upon burned cadaveric skin to what would have been expected in living burned skin. Burns of partial thickness burn depth and full thickness burn depth were debrided and could be clearly identified. ConclusionsFresh-frozen human cadaveric tissue is a valid means of provision of training in the technique of enzymatic burn debridement. This finding was unexpected and shows that our understanding of the mechanism of action of Nexobrid® is incomplete.

Ethical, Legal, and Policy Issues Surrounding Biospecimen Research Conducted or Supported in the USA.

Rapid and dramatic advances in molecular sequencing technology, as well as medical discoveries from genome-wide association and other precision medicine studies, have highlighted the longstanding ethical and legal challenges research biobanks consistently face. Whose authority is needed to conduct research with excised tissue, and how that authority may be exercised with respect and transparency, are central questions. This review article explores how scholars have addressed ethical and legal controversies such as the proper breadth and scope of consent for collection and future research use of biological specimens and data, the importance of disclosing individual research results and secondary findings, and collecting cadaver tissue from deceased persons. This article focuses on the legal and regulatory environment for conducting and/or supporting biospecimen research in the United States of America. It takes the position that proper biobank governance strategies, which ensure accountability and model respect toward biospecimen contributors, as well as transparency in communications between participants and researchers, reduce the likelihood of downstream legal disputes.

FEBio finite element model of a pediatric cervical spine.

The underlying biomechanical differences between the pediatric and adult cervical spine are incompletely understood. Computational spine modeling can address that knowledge gap. Using a computational method known as finite element modeling, the authors describe the creation and evaluation of a complete pediatric cervical spine model. Using a thin-slice CT scan of the cervical spine from a 5-year-old boy, a 3D model was created for finite element analysis. The material properties and boundary and loading conditions were created and model analysis performed using open-source software. Because the precise material properties of the pediatric cervical spine are not known, a published parametric approach of scaling adult properties by 50%, 25%, and 10% was used. Each scaled finite element model (FEM) underwent two types of simulations for pediatric cadaver testing (axial tension and cardinal ranges of motion [ROMs]) to assess axial stiffness, ROM, and facet joint force (FJF). The authors evaluated the axial stiffness and flexion-extension ROM predicted by the model using previously published experimental measurements obtained from pediatric cadaveric tissues. In the axial tension simulation, the model with 50% adult ligamentous and annulus material properties predicted an axial stiffness of 49 N/mm, which corresponded with previously published data from similarly aged cadavers (46.1 ± 9.6 N/mm). In the flexion-extension simulation, the same 50% model predicted an ROM that was within the range of the similarly aged cohort of cadavers. The subaxial FJFs predicted by the model in extension, lateral bending, and axial rotation were in the range of 1-4 N and, as expected, tended to increase as the ligament and disc material properties decreased. A pediatric cervical spine FEM was created that accurately predicts axial tension and flexion-extension ROM when ligamentous and annulus material properties are reduced to 50% of published adult properties. This model shows promise for use in surgical simulation procedures and as a normal comparison for disease-specific FEMs.

Evaluation of the expression of necroptosis pathway mediators and its association with tumor characteristics in functional and non-functional pituitary adenomas

BackgroundPituitary adenomas impose a burden of morbidity on patients and characterizing the molecular mechanisms underlying its pathogenesis received remarkable attention. Despite the appealing role of necroptosis as an alternative cell death pathway in cancer pathogenesis, its relevance to pituitary adenoma pathogenesis has yet to be determined that is perused in the current study.MethodsThe total number of 109 specimens including pituitary adenomas and cadaveric healthy pituitary tissues were enrolled in the current study. Tumor and healthy pituitary tissues were subjected to RNA extraction and gene analysis using Real-Time PCR. The expression levels of necroptosis markers (RIP1K, RIP3K and, MLKL) and their association with the patient’s demographic features were evaluated, also the protein level of MLKL was assessed using immunohistochemistry in tissues.ResultsBased on our data, the remarkable reduction in RIP3K and MLKL expression were detected in nonfunctional and GH-secreting pituitary tumors compared to pituitary normal tissues. Invasive tumors revealed lower expression of RIP3K and MLKL compared to non-invasive tumors, also the attenuated level of MLKL was associated with the tumor size in invasive NFPA. The simultaneous down-regulation of MLKL protein in pituitary adenoma tissues was observed which was in line with its gene expression. While, RIP1K over-expressed significantly in both types of pituitary tumors which showed no significant correlation with patient’s age, gender and tumor size in GHPPA and NFPA group. Notably, MLKL and RIP3K gene expression was significantly correlated in the GHPPA group.ConclusionsAccording to our data, the reduced expression of necroptosis mediators (RIP3K, MLKL) in pituitary adenoma reinforces the hypothesis that the necroptosis pathway can be effective in regulating the proliferation and growth of pituitary tumor cells and tumor recurrence.