Type Of Ossification Research Articles

Thecal and Epithecal Ossifications of the Turtle Shell: Ontogenetic And Phylogenetic Aspects.

The problem of the origin of the bony shell in turtles has a two-century history and still has not lost its relevance. First, this concerns the issues of the homology, the sources of formation and the ratio of bones of different nature, that is, thecal and epithecal, in particular. This article analyzes various views on the nature of the shell elements, and proposes their typification, based on modern data on developmental biology. It is proposed that the defining characteristic of the types of shell ossifications is not the level of their anlage in the dermis (thecality or epithecality), but, first of all, the primary sources of their formation: (1) neural crest (nuchal and plastral plates); (2) vertebral and rib periosteum (neural and costal plates); and (3) dermal mesenchyme (peripheral, suprapygal and pygal plates, as well as epithecal elements). In addition, there is complete correspondence between these types of ossifications and the sequence of their appearance in the turtle ontogenesis. The data show fundamental coincidence of the modifications of the ontogenetic development and evolutionary formation of the shell ossifications and are in agreement with a stepwise model for the origin of the turtle body plan. Particular attention is paid to the origin of the epithecal elements of the turtle shell, which correspond to the additional or supernumerary ossifications and seem to have wider distribution among turtles, than previously thought.

Identification of Risk Factors for Primary Osteoporosis: The Role of Cervical Ligament Ossification.

BACKGROUND Long-term clinical practice has suggested a possible association between ossification of cervical ligament (OCL) and primary osteoporosis (POP). However, there is a lack of relevant research data. This study aimed to clarify the potential relationship between OCL and POP, and propose new strategies for preventing the onset of POP. MATERIAL AND METHODS The study involved 107 patients. The patients' diagnosis included OCL (ossification of the posterior longitudinal ligament, ossification of the ligamentum flavum, and ossification of the nuchal ligament) and POP. Bone mineral density (BMD), types of OCL, types of ossification of posterior longitudinal ligament, age, sex, serum calcium, serum phosphorus, alkaline phosphatase, type I collagen amino-terminal extension peptide, type I collagen degradation products, osteocalcin N-terminal molecular fragments, 25-hydroxyvitamin D, and history of taking steroid drugs were collected. SPSS24.0 and GraphPad Prism 8 were used to obtain the risk factors for POP. RESULTS One-way analysis of variance found that OCL, ossification of posterior longitudinal ligament, alkaline phosphatase, and osteocalcin N-terminal molecular fragments had statistical significance on BMD of the femoral neck (P<0.05). The independent sample t test showed that patient sex had statistical significant effect on BMD (femoral neck) (P=0.036). Incorporating the above factors into multiple linear regression analysis, it was found that OCL, alkaline phosphatase, and osteocalcin N-terminal molecular fragments were risk factors affecting BMD of femoral neck (P<0.05). CONCLUSIONS OCL, osteocalcin N-terminal molecular fragments, and alkaline phosphatase are risk factors for POP.

Posterior Thoracic Antidisplacement and Fusion Surgery for a Special Type of Ossification of the Posterior Longitudinal Ligament in the Thoracic Spine: Indications and Preliminary Clinical Results of 2-Year Follow-Up

To describe a novel technique, posterior thoracic antidisplacement and fusion (PTAF), for a special type of ossification of the posterior longitudinal ligament in the thoracic spine (T-OPLL), and to evaluate its safety and efficacy. From July to December 2020, 5 consecutive patients with beak-type T-OPLL located at the thoracic vertebral body level underwent PTAF surgery. Their demographic data, radiological parameters, perioperative complications, and surgery-related findings were recorded and analyzed. The surgical outcomes were assessed using a modified Japanese Orthopedic Association scale, and the recovery rate was calculated using the Hirabayashi's method. All patients were followed up for at least two years. The mean thickness of OPLL was 9.4±1.0mm, and the OPLL spinal canal occupying ratio was 67.7%±8.5%. Postoperatively, the mean antidisplacement distance of OPLL was 8.1±1.8mm, and the average shortened distance of the spinal column was 6.0±1.13mm. The mean operation time and blood loss were 158.2±26.3minutes and 460±89.4mL, respectively. Perioperative complications were cerebrospinal fluid leakage and instrument failure, 2 cases each. The mean modified Japanese Orthopedic Association score was increased from 3.6±2.9 before surgery to 9.4±3.0 at the last follow-up, and the average recovery rate was 84.2±30.5%. The preliminary clinical outcomes indicate that PTAF is a safe and effective method for the treatment of beak-type T-OPLL, which has its apex located at the vertebral body level and has a high spinal canal occupation ratio.

Rankl genetic deficiency and functional blockade undermine skeletal stem and progenitor cell differentiation

BackgroundSkeletal Stem Cells (SSCs) are required for skeletal development, homeostasis, and repair. The perspective of their wide application in regenerative medicine approaches has supported research in this field, even though so far results in the clinic have not reached expectations, possibly due also to partial knowledge of intrinsic, potentially actionable SSC regulatory factors. Among them, the pleiotropic cytokine RANKL, with essential roles also in bone biology, is a candidate deserving deep investigation.MethodsTo dissect the role of the RANKL cytokine in SSC biology, we performed ex vivo characterization of SSCs and downstream progenitors (SSPCs) in mice lacking Rankl (Rankl−/−) by means of cytofluorimetric sorting and analysis of SSC populations from different skeletal compartments, gene expression analysis, and in vitro osteogenic differentiation. In addition, we assessed the effect of the pharmacological treatment with the anti-RANKL blocking antibody Denosumab (approved for therapy in patients with pathological bone loss) on the osteogenic potential of bone marrow-derived stromal cells from human healthy subjects (hBMSCs).ResultsWe found that, regardless of the ossification type of bone, osteochondral SSCs had a higher frequency and impaired differentiation along the osteochondrogenic lineage in Rankl−/− mice as compared to wild-type. Rankl−/− mice also had increased frequency of committed osteochondrogenic and adipogenic progenitor cells deriving from perivascular SSCs. These changes were not due to the peculiar bone phenotype of increased density caused by lack of osteoclast resorption (defined osteopetrosis); indeed, they were not found in another osteopetrotic mouse model, i.e., the oc/oc mouse, and were therefore not due to osteopetrosis per se. In addition, Rankl−/− SSCs and primary osteoblasts showed reduced mineralization capacity. Of note, hBMSCs treated in vitro with Denosumab had reduced osteogenic capacity compared to control cultures.ConclusionsWe provide for the first time the characterization of SSPCs from mouse models of severe recessive osteopetrosis. We demonstrate that Rankl genetic deficiency in murine SSCs and functional blockade in hBMSCs reduce their osteogenic potential. Therefore, we propose that RANKL is an important regulatory factor of SSC features with translational relevance.

Quality of life and clinical outcomes in severely involved cerebral palsy patients and spastic hips undergoing Castle surgery: a cross-sectional study.

As progressive hip dislocation causes pain in children with spastic cerebral palsy (CP) and spasticity needs surgical correction, we aimed to describe clinical and radiographic outcomes in CP patients with painful hip deformity treated with the Castle salvage procedure. We included all patients operated in the same hospital between 1989 and 2017 with painful spastic hips and femoral head deformity making joint reconstruction unfeasible. We collected clinical and functional data from medical records and evaluated radiographies to classify cases for femoral head shape and migration, type of deformity, spinal deformity, and heterotopic ossification. We investigated quality of life oneyear after surgery. We analyzed 41 patients (70 hips) with complete medical records. All had severe function compromise GMFCS V (Gross Motor Function Classification System) and heterotopic ossifications, all but one had scoliosis, and most had undergone other surgeries before Castle procedure. Patients were followed up for 77.1months (mean) after surgery. The mean initial migration index was 73%. Seven patients had complications, being three patients minor (two femur and one tibial fracture) and four majors (patients requiring surgical revision). Quality of life was considered improved by most of the carers (35 children; 85.3%) as level 4/5 according to CPCHILD instrument. No child was able to stand or walk, but moving in and out of bed, of vehicles, and to a chair, remaining seated, or visiting public places was "very easy." We considered most patients (37 patients-90%, 66 hips-94%) as having satisfactory outcomes because they had no or minor complications, absence of pain, free mobility of the lower limbs and were able to sit in a wheelchair.

Enzymatic activity of bone markers on Lithobates catesbeianus (Shaw, 1802) growth during the ossification process.

In order to better understand the ossification processes in anurans our study was carried out on tadpoles and adults of Lithobates catesbeianus. In this sense, we characterized the kinetic properties of alkaline phosphatase with p-nitrophenylphosphatase (pNPP) and pyrophosphate (PPi) and evaluated the activities of tartrate-resistant acid phosphatase and acid phosphatase. The enzyme extracts were obtained from tadpoles and adult femurs, which were divided into epiphysis and diaphysis. After homogenization, the samples were submitted to differential centrifugation to obtain cell membranes and, further, to phospholipase C (PIPLC) treatment, to remove membrane-bound proteins anchored by phosphatidylinositol. The average of specific activity for pNPP hydrolysis (at pH 10.5) by alkaline phosphatase released by phosphatidylinositol-specific phospholipase C (PIPLC) from Bacillus cereus among different bone regions at different animal ages was 1,142.57 U.mg-1, while for PPi hydrolysis (at pH 8.0), it was 1,433.82 U.mg-1. Among the compounds tested for enzymatic activity, the one that influenced the most was EDTA, with approximately 67% of inhibition for pNPPase activity and 77% for PPase activity. In the case of kinetic parameters, the enzyme showed a "Michaelian" behavior for pNPP and PPi hydrolysis. The Km value was around 0.6mM for pNPPase activity and ranged from 0.01 to 0.11mM for PPase activity, indicating that the enzyme has a higher affinity for this substrate. The study of pNPP and PPi hydrolysis by the enzyme revealed that the optimum pH of actuation for pNPP was 10.5, while for PPi, which is considered the true substrate of alkaline phosphatase, was 8.0, close to the physiological value. The results show that regardless of the ossification type that occurs, the same enzyme or isoenzymes act on the different bone regions and different life stages of anurans. The similarity of the results of studies with other vertebrates shows that anurans can be considered excellent animal models for the study of biological calcification.

The Quality of Life of the Patients with Thoracic Ossification of the Ligamentum Flavum after Surgery Using EQ-5D-5L.

There is a lack of studies on the quality of life (QoL) after posterior laminectomy in patients with thoracic ossification of the ligamentum flavum (TOLF), and risk factors associated with poor prognosis remain controversial. Therefore, the present study was conducted to illustrate the QoL for TOLF patients after surgery and determine its relationship with their demographic, surgery-related, clinical characteristics and imaging data. One hundred and eighteen patients diagnosed with thoracic myelopathy because of TOLF were enrolled in this retrospective study. They all underwent posterior decompressive laminectomy from August 2010 to January 2022. The QoL was evaluated based on the EQ-5D-5L. Collecting gender, age, number of operations, compressed segments, Frankel grade, complications, body mass index (BMI), symptoms and duration, modified Japanese Orthopaedic Association (mJOA) score (preoperative), follow-up time and type of ossification, increased signal on Sagittal T2-weighted Images (ISST2I), occupancy rate and analyzing by Mann-Whitney U-test, Kruskal-Wallis test, the χ2 -test, and logistic regression tests. Average follow-up 70.8 months (18-149), the mean age was 59.74 ± 9.81 years and the mean score for the QoL based on the EQ-5D-5 L and visual analogue scale (VAS) score were 0.71 ± 0.28 and 78.88 ± 10.21 at the final follow-up. Moderate and severe problems were found in the pain/discomfort in 22.0% of the patients. These mobility and usual activities numbers were slightly higher (24.6% and 30.4%, respectively). The mean scores for QoL and VAS were significantly higher in patients with mild and moderate neurological impairment, normal BMI, <60 years of age, no dural tears, symptom relief at hospital discharge, unilateral and bilateral ossification on axial CT scan, ≤ 50% spinal canal occupancy on CT and MRI, and none or fuzzy on ISST2I. QoL after posterior laminectomy in TOLF patients is generally satisfactory compared to preoperative levels. Preoperative mJOA score, Age, comorbid diabetes, the major symptom is activity limitation, BMI, ISST2I, Intraoperative dural tears and spinal canal occupancy rate correlate significantly with the corresponding dimensions and are predictive. Age, spinal canal occupancy rate, ISST2I, preoperative mJOA score, BMI are significantly associated with and have predictive value for overall postoperative QoL.

Association between serum interleukin-17 levels and ectopic bone formation in OPLL patients with DISH.

To investigate the relationship between the severity and morphology of heterotopic ossification in the spinal ligaments including sacroiliac (SI) joints, and serum interleukin-17 (IL-17) levels in patients with ossification of the posterior longitudinal ligament (OPLL) with or without diffuse idiopathic skeletal hyperostosis (DISH), as well as a non-OPLL group. A total of 103 patients with OPLL [DISH (-), n = 50; DISH (+), n = 53] and 53 age- and gender-matched controls were included. The serum levels of IL-17 were analysed, and the severity of ectopic ossification and the morphology of ectopic bone formation were evaluated. The SI joint morphological variations were categorized into four types. No significant differences were found in serum IL-17 levels between the OPLL and control groups. However, the DISH (+) group showed higher IL-17 levels than the DISH (-) group, especially in female patients (P = 0.003). Additionally, IL-17 levels were positively correlated with the number of flat vertebral units, this being one of the characteristic DISH ossification types (R2 = 0.199, P = 0.012). IL-17 levels in the type showing bridging osteophyte and bone fusion were significantly higher in the DISH (+) group than in the DISH (-) group. The morphological characteristics of paravertebral bone formation in the entire spine, including the SI joint, are likely associated with serum IL-17 levels in OPLL. These findings provide pathological and serological evidence of local inflammation contributing to paravertebral ossification of OPLL patients.

The biomechanical effect of different types of ossification of the ligamentum flavum on the spinal cord during cervical dynamic activities

Ossification of the ligamentum flavum (OLF) is thought to be an influential etiology of myelopathy, as thickened ligamentum flavum causes the stenosis of the vertebral canal, which could subsequently compress the spinal cord. Unfortunately, there was little information available on the effects of cervical OLF on spinal cord compression, such as the relationship between the progression of cervical OLF and nervous system symptoms during dynamic cervical spine activities. In this research, a finite element model of C1-C7 including the spinal cord featured by dynamic fluid-structure interaction was reconstructed and utilized to analyze how different types of cervical OLF affect principal strain and stress distribution in spinal cord during spinal activities towards six directions. For patients with cervical OLF, cervical extension induces higher stress within the spinal cord among all directions. From the perspective of biomechanics, extension leads to stress concentration in the lateral corticospinal tracts or the posterior of gray matter. Low energy damage to the spinal cord would be caused by the high and fluctuating stresses during cervical movements to the affected side for patients with unilateral OLF at lower grades.

Effect of Different Types of Ossification of the Posterior Longitudinal Ligament on the Dynamic Biomechanical Response of the Spinal Cord: A Finite Element Analysis.

Ossification of the posterior longitudinal ligament (OPLL) has been identified as an important cause of cervical myelopathy. However, the biomechanical mechanism between the OPLL type and the clinical characteristics of myelopathy remains unclear. The aim of this study was to evaluate the effect of different types of OPLL on the dynamic biomechanical response of the spinal cord. A three-dimensional finite element model of the fluid-structure interaction of the cervical spine with spinal cord was established and validated. The spinal cord stress and strain, cervical range of motion (ROM) in different types of OPLL models were predicted during dynamic flexion and extension activity. Different types of OPLL models showed varying degrees of increase in stress and strain under the process of flexion and extension, and there was a surge toward the end of extension. Larger spinal cord stress was observed in segmental OPLL. For continuous and mixed types of OPLL, the adjacent segments of OPLL showed a dramatic increase in ROM, while the ROM of affected segments was limited. As a dynamic factor, flexion and extension of the cervical spine play an amplifying role in OPLL-related myelopathy, while appropriate spine motion is safe and permitted. Segmental OPLL patients are more concerned about the spinal cord injury induced by large stress, and patients with continuous OPLL should be noted to progressive injuries of adjacent level.

Come together over me: Cells that form the dermatocranium and chondrocranium in mice.

Most bone develops either by intramembranous ossification where bone forms within a soft connective tissue, or by endochondral ossification by way of a cartilage anlagen or model. Bones of the skull can form endochondrally or intramembranously or represent a combination of the two types of ossification. Contrary to the classical definition of intramembranous ossification, we have previously described a tight temporo-spatial relationship between cranial cartilages and dermal bone formation and proposed a mechanistic relationship between chondrocranial cartilage and dermal bone. Here, we further investigate this relationship through an analysis of how cells organize to form cranial cartilages and dermal bone. Using Wnt1-Cre2 and Mesp1-Cre transgenic mice, we determine the derivation of cells that comprise cranial cartilages from either cranial neural crest (CNC) or paraxial mesoderm (PM). We confirm a previously determined CNC-PM boundary that runs through the hypophyseal fenestra in the cartilaginous braincase floor and identify four additional CNC-PM boundaries in the chondrocranial lateral wall, including a boundary that runs along the basal and apical ends of the hypochiasmatic cartilage. Based on the knowledge that as osteoblasts differentiate from CNC- and PM-derived mesenchyme, the differentiating cells express the transcription factor genes RUNX2 and osterix (OSX), we created a new transgenic mouse line called R2Tom. R2Tom mice carry a tdTomato reporter gene joined with an evolutionarily well-conserved enhancer sequence of RUNX2. R2Tom mice crossed with Osx-GFP mice yield R2Tom;Osx-GFP double transgenic mice in which various stages of osteoblasts and their precursors are detected with different fluorescent reporters. We use the R2Tom;Osx-GFP mice, new data on the cell derivation of cranial cartilages, histology, immunohistochemistry, and detailed morphological observations combined with data from other investigators to summarize the differentiation of cranial mesenchyme as it forms condensations that become chondrocranial cartilages and associated dermal bones of the lateral cranial wall. These data advance our previous findings of a tendency of cranial cartilage and dermal bone development to vary jointly in a coordinated manner, promoting a role for cranial cartilages in intramembranous bone formation.

Acetabular Rim Ossification Variants Are Found in Almost 20% of Patients Presenting With Hip Pain

To determine the prevalence of 4 different types of acetabular rim ossifications, including partial labral ossification or punctate calcification, true os acetabuli, acetabular rim stress fracture, and complete labral ossification, and to determine whether different types of periacetabular ossifications are linked to demographic or radiological factors. We retrospectively reviewed the medial records of patients presenting for hip-related complaints at 2 sports medicine practices from September 2007 to December 2009. An anteroposterior radiograph of both hips and a lateral radiograph of each hip was obtained for all patients and reviewed for findings of cam and pincer femoroacetabular impingement, degenerative changes (Tönnis grade), and periacetabular calcifications for both hips. These parameters were also evaluated with respect to symptoms, sex, and age. Four hundred ninety-one consecutive patients (982 hips) presented to 2 orthopaedic surgeons at 2 centers for "hip"-related complaints. There were 223 males and 268 females (age 39 ± 14 years). The overall prevalence of periacetabular calcifications in hips was 17.6%, with 56.6% of calcifications in the symptomatic hip and 43.4% in the contralateral hip. Four basic patterns of calcification were identified: punctuate calcifications within the labrum (8.0% hips), large rounded calcifications (os acetabuli) (4.2% hip), large fragments with a vertical line of the superior-lateral acetabular rim, consistent with healed or non-healed stress fracture (2.0% hips), and complete ossification of the labrum (3.4% hips). Overall, male sex (P= .002), increased lateral center-edge angle (P= .046), and higher Tönnis grade (P < .001) statistically predicted the presence of periacetabular ossification. Punctate calcifications were more prevalent in males (P= .002). Higher Tönnis grade (P=.029) and increased alpha angle (P= .046) were more prevalent with os acetabuli. Younger age (P= .001), male sex (P= .048), increased alpha angle (P= .012), and increased lateral center-edge angle (P < .001) were more prevalent in acetabular rim fractures. No factors were statistically significant at predicting the presence of an ossified labrum. Periacetabular calcifications are not uncommon. Four particular patterns of calcification are identified: punctate labral calcifications (8%), larger rounded calcifications (i.e., os acetabuli) (4.2%), acetabular rim stress fractures (2%), and complete ossification of the labrum (3.4%) for a combined prevalence of 17.6% in patients presenting to an orthopaedic surgeon with "hip"-related complaints. Nearly half were in the asymptomatic hip. Male sex had a higher prevalence of periacetabular calcifications. An increased lateral center edge angle and higher Tönnis grade also had a higher prevalence of periacetabular calcifications. Younger male patients are more likely to have acetabular rim stress fractures. Patients with an increased alpha angle have a higher prevalence of os acetabuli and rim stress fractures. This study aims to identify, quantify, and categorize periacetabular calcifications about the hip. Their clinical relationships and relevance have been discussed, but no study has distinctly categorized the various types and their prevalence. This study provides a framework for identification and categorization.

Nasal capsule ossification: A histological study using human foetuses to find an association between the foetus and adult morphologies of the nasal wall.

Recent molecular biology studies have revealed the process of nasal capsule determination. We aimed to create a fate map showing the association between the adult and embryonic components of the nasal wall and nasal capsule derivatives. We examined paraffin-embedded histological sections between 15 mid-term (9-16 weeks) and 12 near-term (27-40 weeks) foetuses. Until 15 weeks, membranous ossification occurred 'along' the capsular cartilage, contributing to the formation of the vomer, maxilla and bony nasal septum as well as the nasal, frontal and lacrimal bones. After 15 weeks, a wide lateral part of the capsule became thin and fragmented, and degenerative cartilage was observed near the lacrimal bone, in the three conchae, and at the inferolateral end of the capsule sandwiched between the maxilla and palatine bone. The disappearing cartilages appeared to be replaced by nearby membranous bones. This type of membranous ossification did not appear to use the capsular cartilage as a 'mould', although the perichondrium may have a role in inducing ossification. Calcified cartilage indicated endochondral ossification in the inferior concha until 15 weeks and, later, at the bases of three conchae and around the future sphenoid sinus (i.e. the concha sphenoidalis). The capsular cartilage extended antero-superiorly over the frontal bone and inserted into the nasal bone. At 40 weeks, the capsular cartilage remained in the cribriform plate and at the inferolateral end along the palatine bone. Consequently, less guidance from the nasal capsule seemed to provide great individual variation in the shape of the wide anterolateral wall of the nasal cavity.

Usefulness of K-line in predicting prognosis of laminoplasty for cervical spondylotic myelopathy

BackgroundK-line is widely recognized as a useful index for evaluating cervical alignment and the size of the cervical ossification at the posterior longitudinal ligament (OPLL). The purpose of this study was to investigate whether the K-line could be a useful clinical tool for predicting the prognosis of laminoplasty (LP) for cervical spondylotic myelopathy (CSM).MethodsAdult CSM patients scheduled for cervical LP were recruited for this study. C2-7 angle, local kyphosis angle, and K-line was evaluated by T2-weighted sagittal magnetic resonance imaging (MRI). Clinical findings were evaluated by the JOA score and the recovery rate. Clinical and radiological findings were evaluated preoperation and final follow-up. Patients were grouped into K-line ( +) and K-line (-). Patients with Kline (-) were further divided into two sub-groups: disc type (anterior cord compression due to disc protrusion with kyphosis) and osseous type (due to osseous structure such as osteophyte).ResultsSixty-eight patients were included in the analysis. The recovery rate of K-line (-) group (n = 11,19.4%) was significantly worse than that of K-line ( +) group (n = 57, 50.6%, p<0.05). Among 11 K-line (-) patients, 7 were disc type and 4 were osseous type. Over the period of follow-up, the disc type K-line (-) patients changed to K-line ( +) and showed significantly better recovery rate (27.6%) compared to the osseous type K-line (-) group (5.0%, p < 0.05).ConclusionThe present of this study indicate that K-line may have a predictive value for clinical outcome in patients undergoing LP for CSM. K-line (-) of osseous type was worse than k-line (-) of disc type.

The Correlation between Mechanobiology and Fracture Healing; Osteosynthesis, Biomaterial Optimization and TRIZ Design Principles to Develop Ameliorative Implants for Reconstruction of Median Osteochondrotomy of the Sternum.

The application of stainless-steel wire is still the "standard of care" and is believed to be the "gold standard" after trans-sternal thoracotomy. To overcome postoperative instability and surgical wound infection there had been the development of a variety of circumferential, Hemi-circular, and surface on-lay implant designs to enhance bone healing of the sternum particularly in compromised patients. This fundamental descriptive theoretical research study probes into biology and effects of mechanical environment on fracture healing in general and various types of ossifications that may occur during healing of the sternum. Following surgical anatomy of the sternum, the biology of fracture (osteotomy) healing, an update on the conventional and newer biomaterials, and role of 3D printing in custom additive manufacturing of the surgical implants have been discussed in detail. There is discussion on design principles and structural optimization in-line with patient-specific and patient-appropriate osteosynthesis. In support, the Teorija Rezhenija Izobretatelskikh Zadatch engineering principles have been applied to improve implant design in the face of the current strategies to relieve some of the recalcitrant deficiencies underlying the mechanics of the most favored implant for the reconstruction of the sternum. Several scientific domains of the engineering design principles and fracture healing processes have been connected leading to four newly conceptualized prototype designs for the reconstruction of the sternum. In conclusion, despite increased knowledge of the fracture healing process there are limited means to mitigate the adverse mechanical environment experienced by the healing sternum. There are uncertainties how to transfer the well-known facts of tissue strain during healing from the experimental platform to the operating table at the time of fracture fixation and reconstruction of the sternum for its optimal healing.

An insight into cancer palaeobiology: does the Mesozoic neoplasm support tissue organization field theory of tumorigenesis?

BackgroundNeoplasms are common across the animal kingdom and seem to be a feature plesiomorphic for metazoans, related with an increase in somatic complexity. The fossil record of cancer complements our knowledge of the origin of neoplasms and vulnerability of various vertebrate taxa. Here, we document the first undoubted record of primary malignant bone tumour in a Mesozoic non-amniote. The diagnosed osteosarcoma developed in the vertebral intercentrum of a temnospondyl amphibian, Metoposaurus krasiejowensis from the Krasiejów locality, southern Poland.ResultsA wide array of data collected from gross anatomy, histology, and microstructure of the affected intercentrum reveals the tumour growth dynamics and pathophysiological aspects of the neoplasm formation on the histological level. The pathological process almost exclusively pertains to the periosteal part of the bone composed from a highly vascularised tissue with lamellar matrix. The unorganised arrangement of osteocyte lacunae observed in the tissue is characteristic for bone tissue types connected with static osteogenesis, and not for lamellar bone. The neoplastic bone mimics on the structural level the fast growing fibrolamellar bone, but on the histological level develops through a novel ossification type. The physiological process of bone remodelling inside the endochondral domain continued uninterrupted across the pathology of the periosteal part.ConclusionsBased on the results, we discuss our case study’s consistence with the Tissue Organization Field Theory of tumorigenesis, which locates the causes of neoplastic transformations in disorders of tissue architecture.

Re-Assessment of the Plant Protection Product PROMAN – with the Active Ingredient Metobromuron [Edition 2

Proman is a broad spectrum selective herbicide for potatoes grown outdoors, containing the active substance metobromuron. VKM’s Panel on Plant Protection Products has previously discussed questions concerning Proman raised by The Norwegian Food Safety Authority, and stated its opinion in a report of 21. January 2015 (http://www.vkm.no/dav/3c64afe035.pdf). &#x0D; Following this report, The Norwegian Food Safety Authority turned down the application to register Proman as a plant protection product in Norway. The applicant filed a complaint on this decision, and the VKM Panel has been asked to reassess its previous opinion in light of the information given by the applicant in the complaint. &#x0D; The VKM Panel has discussed the arguments put forward in the complaint. The arguments did not change the Panel’s main conclusions in the original assessment. Some changes in the wording of the conclusions were however done, in order to put more emphasis on areas of uncertainty. &#x0D; These are the standing conclusions of VKM’s Panel on Plant Protection Products:&#x0D; &#x0D; On the relevance of the carcinogenic effects observed in the rat carcinogenicity study; fibrosarcomas in females and pheochromocytomas and Leydig cell tumours in males: &#x0D; It is the opinion of VKM’s Panel for Plant Protection Products that the relevance of the observed incidences of mammary gland tumours and Leydig cell tumours in the rat carcinogenicity study is strengthened by the fact that the increases in tumours associated with exposure to metobromuron are observed in hormone responsive tissues. The panel concludes that the carcinogenic effects observed in the rat carcinogenicity study could be relevant for tumour induction in humans. &#x0D; Higher incidences of still dumbbell-shaped centres of thoracic vertebrae and nonossification of the 13th rib observed in the rat developmental toxicity study and whether these are considered to be malformations: &#x0D; VKM’s Panel on Plant Protection Products has discussed the classification of the different types of incomplete ossifications and concluded that incomplete ossification of sternebrae and non-ossification of the 13th rib in rats should by itself be considered to be variations, and not adverse developmental effects. On the other hand, the Panel agrees with ECHA that the “thoracic vertebral centres still dumbbell-shaped” should be considered as malformations, due to limited data and understanding of the mechanism underlying the observed slow reversal of these anomalies. Furthermore, it is the view of the Panel that the different types of retarded ossification induced by the exposure should be considered as a whole when assessing for developmental effects. &#x0D; Establishment of the NOAEL for the developmental toxicity study in rats and the reference value (ARfD): &#x0D; VKM’s Panel on Plant Protection Products supports the proposal of an ADI value of 0.008 mg/kg bw/day based on a NOAEL of 0.8 mg/kg bw/day from the 2-year study in mouse, and AOEL of 0.016 mg/kg bw/day based on the NOAEL of 1.6 mg/kg bw/day from the 1-year feeding study in dog. The panel suggests an alternative ARfD value of 0.03 mg/kg bw based on a LOAEL of 10 mg/kg bw /day for the observations of incomplete ossification in the rat developmental study. &#x0D; The anti-androgenic potential of metobromuron: &#x0D; The rat carcinogenicity study indicates that metobromuron may interact with the endocrine system. The data from the Hershberger in vivo rat study, the in vitro studies, as well as the comparison with demonstrated effects and mechanisms for flutamide and linuron is suggestive of an anti-androgenic effect. Thus, it is the opinion of the VKM Panel on Plant Protection Products that an anti-androgenic effect of metobromuron cannot be excluded.

The influence of ossification morphology on surgery outcomes in patients with thoracic ossification of ligamentum flavum (TOLF)

BackgroundTo determine whether there is a correlation between the type of ossification and radiological parameters, modified thoracic JOA scores, and complications in patients with thoracic ossification of ligamentum flavum treated by posterior thoracic surgery.MethodsThis retrospective cohort study included 48 patients with thoracic myelopathy caused by single-level thoracic ossification of ligamentum flavum who underwent thoracic posterior approach surgery in our Hospital o between December 2013 to December 2018. Patients were divided into unilateral, bilateral, and bridged groups in axial position, and beak and round groups in sagittal position. The differences were analyzed according to the ossification morphology.ResultsIn axial myelopathy, there was no significant difference in preop and postop JOA scores and RR among the three groups in axial position (P = 0.884). In sagittal view, there was no significant difference in preoperative JOA score between the two groups (P = 0.710), while the postop JOA score and the recovery rate in the beak group were significantly lower than that of the round group (P = 0.010, P = 0.034). Two-way ANOVA showed that sagittal morphology had a significant effect on postop JOA score (P = 0.028), but axial morphology don’t (P = 0.431); there was no interaction between them (P = 0.444). For the recovery rate, sagittal morphology also had a significant effect (P = 0.043), but axial ossification don’t (P = 0.998); there was no interaction between them (P = 0.479).ConclusionSagittal morphology had a significant adverse effect on postop JOA score and surgical outcome, while axial morphology had no effect on surgical outcome, and there was no interaction between sagittal morphology and axial morphology.

Analysis of intervertebral disc degeneration in patients with ossification of the posterior longitudinal ligament.

As degenerative disease with nerve compression, little is known about the relationship between cervical ossification of the posterior longitudinal ligament (OPLL) and intervertebral disc degeneration (IVDD). This study investigates the effect of ossification of ligaments on IVDD in patients with cervical OPLL. We focus on the ossification-related segment in patients diagnosed with OPLL, which is characterized by ossification that crosses intervertebral space or occurs concurrently in the upper and lower vertebrae. A total of 92 ossification-related segments from 40 patients were involved in the study. X-ray, computed tomography (CT), and magnetic resonance imaging (MRI) were used to evaluate the ossification thickness, disc height, cervical range of motion (ROM) of the segment, Kang's grade, and disc signal loss. We conducted correlation analysis and subgroup comparisons to analyze the type of ossification, ossification thickness, disc height, disc signal loss, ROM and Kang's grade. The specific ossification thickness was negatively correlated with the disc signal loss (P<0.05). Specific ossification thickness and specific disc height were positively correlated (P<0.05). Segments were divided into the nude group (ossification not crossing the intervertebral space) and the covered group (ossification crossing the intervertebral space). The nude group presented smaller ossification thickness and disc height, and a higher grade of disc signal loss and ROM (P<0.05). The formation of OPLL may be interrelated with the alleviation of IVDD at the same segment. Furthermore, IVDD is not only related to the limited ROM caused by ossification, but also the size and shape of the ossified mass. A negative correlation exists between the ossification thickness and the severity of IVDD in OPLL patients. Ossification that crosses the interverbal space is associated with lower ROM, a thicker ossified mass, and better disc signal. For patients with nude ossification-related segments, a fusion surgery to restore intervertebral stabilization deserves serious consideration.

РАЗВИТИЕ И РОСТ КОСТЕЙ ЧЕРЕПА В ПРЕ- И РАННЕМ ПОСТНАТАЛЬНОМ ПЕРИОДАХ ОНТОГЕНЕЗА

The lecture contains the background about the development of the human during embryonic and early postembryonic periods of ontogenesis. The main part of the lecture is concerned with the basic data about the sources of primordias forming of the skull: sclerotomes of the mesoderm’s somites and nerve crest cells that migrate into the regions of the skull primordia; about differentiation processes in skull: intramembranous ossification as the example of the parietal bone development, endochondral ossification as the example of basic and lateral parts of the occipital bone development and the main stages of both types of ossification and cells taking part in bone forming. The information about the rebuilding of the human skull during early postembryonic period and about humoral factors regulating resorption and forming bone tissue for maintain homeostasis of mineral substances in the organism is provided.