Virtopsy post-mortem multi-slice computed tomography (MSCT) and magnetic resonance imaging (MRI) demonstrating descending tonsillar herniation: comparison to clinical studies.

Descending cerebellar tonsillar herniation is a serious and common complication of intracranial mass lesions. We documented three cases of fatal blunt head injury using post-mortem multi-slice computed tomography (MSCT) and magnetic resonance imaging (MRI). The results showed massive bone and soft-tissue injuries of the head and signs of high intracranial pressure with herniation of the cerebellar tonsils. The diagnosis of tonsillar herniation by post-mortem radiological examination was performed prior to autopsy. This paper describes the detailed retrospective evaluation of the position of the cerebellar tonsils in post-mortem imaging in comparison to clinical studies.

Body Height Estimation from Femur Measurements in Postmortem Computed Tomography

After attending this presentation, attendees will: (1) understand how body height from computed tomography data can be estimated; and, (2) gain knowledge about the accuracy of estimated body height and limitations. The presentation will impact the forensic science community by providing knowledge and competence which will enable attendees to develop formulas for single bones to reconstruct body height using postmortem Computer Tomography (p-CT) data. The estimation of Body Height (BH) is an important component of the identification of corpses and skeletal remains. Stature can be estimated with relative accuracy via the measurement of long bones, such as the femora. Compared to time-consuming maceration procedures, p-CT allows fast and simple measurements of bones. This study undertook four objectives concerning the accuracy of BH estimation via p-CT: (1) accuracy between measurements on native bone and p-CT imaged bone (F1 according to Martin 1914); (2) intra-observer p-CT measurement precision; (3) accuracy between formula-based estimation of the BH and conventional body length measurement during autopsy; and, (4) accuracy of different estimation formulas available.1 In the first step, the accuracy of measurements in the CT compared to those obtained using an osteometric board was evaluated on the basis of eight defleshed femora. Then the femora of 83 female and 144 male corpses of a Swiss population for which p-CTs had been performed, were measured at the Institute of Forensic Medicine in Bern. After two months, 20 individuals were measured again in order to assess the intraobserver error. The mean age of the men was 53±17 years and that of the women was 61±20 years. Additionally, the body length of the corpses was measured conventionally. The mean body length was 176.6±7.2cm for men and 163.6±7.8cm for women. The images that were obtained using a six-slice CT were reconstructed with a slice thickness of 1.25mm. Analysis and measurements of CT images were performed on a multipurpose workstation. As a forensic standard procedure, stature was estimated by means of the regression equations by Penning & Riepert developed on a Southern German population and for comparison, also those referenced by Trotter & Gleser “American White.”2,3 All statistical tests were performed with a statistical software. No significant differences were found between the CT and osteometric board measurements. The double p-CT measurement of 20 individuals resulted in an absolute intra-observer difference of 0.4±0.3mm. For both sexes, the correlation between the body length and the estimated BH using the F1 measurements was highly significant. The correlation coefficient was slightly higher for women. The differences in accuracy of the different formulas were small. While the errors of BH estimation were generally ±4.5–5.0cm, the consideration of age led to an increase in accuracy of a few millimetres to about 1cm. BH estimations according to Penning & Riepert and Trotter & Gleser were slightly more accurate when age-at-death was taken into account.2,3 That way, stature estimations in the group of individuals older than 60 years were improved by about 2.4cm and 3.1cm.2,3 The error of estimation is therefore about a third of the common ±4.7cm error range. Femur measurements in p-CT allow very accurate BH estimations. Estimations according to Penning led to good results that (barely) come closer to the true value than the frequently used formulas by Trotter & Gleser “American White.”2,3 Therefore, the formulas by Penning & Riepert are also validated for this substantial recent Swiss population.

Experimental validation of a nonlinear μ FE model based on cohesive-frictional plasticity for trabecular bone

Trabecular bone is a porous mineralized tissue playing a major load bearing role in the human body. Prediction of age-related and disease-related fractures and the behavior of bone implant systems needs a thorough understanding of its structure-mechanical property relationships, which can be obtained using microcomputed tomography-based finite element modeling. In this study, a nonlinear model for trabecular bone as a cohesive-frictional material was implemented in a large-scale computational framework and validated by comparison of μFE simulations with experimental tests in uniaxial tension and compression. A good correspondence of stiffness and yield points between simulations and experiments was found for a wide range of bone volume fraction and degree of anisotropy in both tension and compression using a non-calibrated, average set of material parameters. These results demonstrate the ability of the model to capture the effects leading to failure of bone for three anatomical sites and several donors, which may be used to determine the apparent behavior of trabecular bone and its evolution with age, disease, and treatment in the future.

Novel MesoPorous BioGlass/silk scaffold containing adPDGF-B and adBMP7 for the repair of periodontal defects in beagle dogs

AIM The local delivery of growth factors via gene therapy has gained tremendous awareness in recent years due to their sustained growth factor delivery to target tissues. The aim of this study was to fabricate and investigate a scaffold able to release growth factors via gene therapy for the repair of periodontal tissues. MATERIALS AND METHODS Novel mesoporous bioglass (MBG)/silk fibrin scaffold combined with BMP7 and/or PDGF-B adenovirus was fabricated and tested in vitro for cell migration, proliferation and differentiation. Furthermore, acute-type buccal dehiscence periodontal defects (mesiodistal width × depth: 5 × 5 mm) were created on the buccal portion of the maxillary premolars in five normal male beagle dogs (12 months old, 15.0 ± 2.0 kg) and histologically examined for periodontal regeneration following implantation of the following five groups: (1) no scaffold, (2) MBG/silk scaffold alone, (3) scaffold + adPDGF-B, (4) scaffold + adBMP7, (5) scaffold + adPDGF-b + adBMP7. RESULTS In vitro findings demonstrated that adPDGF-B was able to rapidly recruit periodontal ligament (PDL) cells over sixfold more effectively than adBMP7, whereas adBMP7 was more able to induce osteoblast differentiation of PDL cells. In vivo findings demonstrate that scaffolds loaded with adPDGF-B were able to partially regenerate the periodontal ligament while adBMP7 scaffolds primarily improved new bone formation. The combination of both adPDGF-B and adBMP7 synergistically promoted periodontal regeneration by allowing up to two times greater regeneration of the periodontal ligament, alveolar bone and cementum when compared to each adenovirus used alone. CONCLUSIONS Although both PDGF-B and BMP7 are individually capable of promoting periodontal regeneration to some degree, their combination synergistically promotes wound healing in acute-type buccal dehiscence periodontal defects when delivered simultaneously. This study demonstrates the promise for successful delivery of low-cost, effective growth factor delivery via gene therapy for the treatment of periodontal defects.

Dual Role of Mesenchymal Stem Cells Allows for Microvascularized Bone Tissue-Like Environments in PEG Hydrogels.

In vitro engineered tissues which recapitulate functional and morphological properties of bone marrow and bone tissue will be desirable to study bone regeneration under fully controlled conditions. Among the key players in the initial phase of bone regeneration are mesenchymal stem cells (MSCs) and endothelial cells (ECs) that are in close contact in many tissues. Additionally, the generation of tissue constructs for in vivo transplantations has included the use of ECs since insufficient vascularization is one of the bottlenecks in (bone) tissue engineering. Here, 3D cocultures of human bone marrow derived MSCs (hBM-MSCs) and human umbilical vein endothelial cells (HUVECs) in synthetic biomimetic poly(ethylene glycol) (PEG)-based matrices are directed toward vascularized bone mimicking tissue constructs. In this environment, bone morphogenetic protein-2 (BMP-2) or fibroblast growth factor-2 (FGF-2) promotes the formation of vascular networks. However, while osteogenic differentiation is achieved with BMP-2, the treatment with FGF-2 suppressed osteogenic differentiation. Thus, this study shows that cocultures of hBM-MSCs and HUVECs in biological inert PEG matrices can be directed toward bone and bone marrow-like 3D tissue constructs.

Osteoblast Response to Commercially Available Ti-6Al-4V and Novel Porous Tantalum. In Vitro Biocompatibility Studies

The response of human osteoblasts to materials is crucial for evaluating biocompatibility of an implant material for bone defects. Previous work in our lab demonstrated that the response of human osteoblasts to orthopaedic and dental materials in vitro varies depending on the sex and age of the patient [1]. Osteoblasts from female patients older than 60 years old, adhered less and produced less matrix proteins and calcification than osteoblasts from younger female patients and all ages of male patients. Recently developed, porous tantalum demonstrates improved biomechanical properties for bone and good biocompatibility in in vivo human studies, however there are few, if any, in vitro biocompatibility studies on this material. In this project, we aimed to compare the phenotypic expression of human osteoblasts from young and old female patients to commercially available Ti-6Al-4V and porous tantalum in a well-developed in vitro system. 1. Zhang H, Lewis CG, Aronow MS, Gronowicz G. The effect of patient age on human osteoblasts’ response to Ti-6Al-4V implants in vitro. J. Orthop. Res. 2004;22(1):30-8.

A comparative analysis of Texas and Louisiana Oil-field NORM Waste Policy

NORM (Naturally Occurring Radioactive Material) Waste Policies for the nation's oil and gas producing states have been in existence since the 1980's, when Louisiana was the first state to develop a NORM regulatory program in 1989. Since that time, expectations for NORM Waste Policies have evolved, as Health, Safety, Environment, and Social responsibility (HSE & SR) grows increasingly important to the public. Therefore, the oil and gas industry's safety and environmental performance record will face challenges in the future, about its best practices for managing the co-production of NORM wastes. ^ Within the United States, NORM is not federally regulated. The U.S. EPA claims it regulates NORM under CERCLA (superfund) and the Clean Water Act. Though, there are no universally applicable regulations for radium-based NORM waste. Therefore, individual states have taken responsibility for developing NORM regulatory programs, because of the potential radiological risk it can pose to man (bone and lung cancer) and his environment. This has led to inconsistencies in NORM Waste Policies as well as a NORM management gap in both state and federal regulatory structures. ^ Fourteen different NORM regulations and guidelines were compared between Louisiana and Texas, the nation's top two petroleum producing states. Louisiana is the country's top crude oil producer when production from its Federal offshore waters are included, and fourth in crude oil production, behind Texas, Alaska, and California when Federal offshore areas are excluded. Louisiana produces more petroleum products than any state but Texas. For these reasons, a comparative analysis between Louisiana and Texas was undertaken to identify differences in their NORM regulations and guidelines for managing, handling and disposing NORM wastes. Moreover, this analysis was undertaken because Texas is the most explored and drilled worldwide and yet appears to lag behind its neighboring state in terms of its NORM Waste Policy and developing an industry standard for handling, managing and disposing NORM. As a result of this analysis, fourteen recommendations were identified.^

MUTATIONS IN STAT3 ASSOCIATED WITH HUMAN HYPER IgE SYNDROME ENHANCE NFκB AND MAPK-MEDIATED GENE EXPRESSION

Hyper IgE syndrome (HIES) is a multisystem disorder resulting in bone and immune system abnormalities. It is associated with mutations in STAT3, which disrupt protein domains responsible for transcriptional function. Patients with HIES display osteoporosis and enhanced inflammatory cytokine production similar to hematopoietic Stat3-deficient mice. Since osteoclast and inflammatory cytokine genes are NFκB targets, these observations indicate a possible deregulation of NFκB signaling in both mice and humans with STAT3-deficiency. Here, we sought to examine the role of STAT3 in the regulation of NFκB-mediated gene expression through analysis of three HIES STAT3 point mutations in both hematopoietic and non- hematopoietic cells. We found that IL-6-induced tyrosine phosphorylation of STAT3 was partially or completely abrogated by HIES mutations in the transactivation domain (V713L) or SH2 domain (V637M), respectively, in both hematopoietic and non- hematopoietic cells. By contrast, IL-6-induced tyrosine phosphorylation of an HIES mutant in the STAT3 DNA-binding domain (R382W) was intact. The R382W and V713L mutants significantly reduced IL-6-dependent STAT3 transcriptional activity in reporter gene assays. Moreover, the R382W and V637M mutants significantly diminished IL-6-responsive expression of the endogenous STAT3 target gene, Socs3, as assessed by quantitative real-time PCR (qPCR) in the RAW macrophage cell line. These observations indicate the HIES mutants dominantly suppress the transcriptional activity of wild type STAT3, albeit to varying degrees. All three HIES mutants enhanced LPS-induced expression of the NFκB target genes IL6 (IL-6), Cxcl10 (IP- 10), and Tnf (TNFα) in RAW cells, as indicated by qPCR. Furthermore, overexpression of wild type STAT3 in Stat3-deficient murine embryonic fibroblasts significantlyreduced LPS-stimulated expression of IL6, Cxcl10, and IL12p35. In addition, in aprimary murine osteoclast differentiation assay, a STAT3-specific SH2 domain inhibitor led to significantly increased levels of osteoclast-specific gene expression. These results suggest that STAT3 serves as a negative regulator of NFκB-mediated gene expression, and furthermore imply that STAT3 mutations associated with HIES contribute to the osteopenia and inflammation observed in HIES patients.

Cloning and molecular analysis of paraxis: A {\it trans\/}-acting factor required for somite maturation

During vertebrate embryogenesis, cells from the paraxial mesoderm coalesce in a rostral-to-caudal progression to form the somites. Subsequent compartmentalization of the somites yields the sclerotome, myotome and dermatome, which give rise to the axial skeleton, axial musculature, and dermis, respectively. Recently, we cloned a novel basic-Helix-Loop-Helix (bHLH) protein, called scleraxis, which is expressed in the sclerotome, in mesenchymal precursors of bone and cartilage, and in connective tissues. This dissertation focuses on the cloning, expression and functional analysis of a bHLH protein termed paraxis, which is nearly identical to scleraxis within the bHLH region but diverges in both its amino and carboxyl termini. During the process of mouse embryogenesis, paraxis transcripts are first detected at about day 7.5 post coitum within the primitive mesoderm lying posterior to the head and heart primordia. Subsequently, paraxis expression progresses caudally through the paraxial mesoderm, immediately preceding somite formation. Paraxis is expressed at high levels in newly formed somites before the first detectable expression of the myogenic bHLH genes, and as the somite becomes compartmentalized, paraxis becomes downregulated within the myotome.^ To determine the function of paraxis during mammalian embryogenesis, mice were generated with a null mutation in the paraxis locus. Paraxis null mice survived until birth, but exhibited severe foreshortening along the anteroposterior axis due to the absence of vertebrae caudal to the midthoracic region. The phenotype also included axial skeletal defects, particularly shortened bifurcated ribs which were detached from the vertebral column, fused vertebrae and extensive truncation and disorganization caudal to the hindlimbs. Mutant neonates also lacked normal levels of trunk muscle and exhibited defects in the dermis as well as the stratification of the epidermis. Analysis of paraxis -/- mutant embryos has revealed a failure of the somites to both properly epithelialize and compartmentalize, resulting in defects in somite-derived cell lineages. These results suggest that paraxis is an essential component of the genetic pathway regulating somitogenesis. ^

Miocene dissolution facies and microfacies at Northwest Atlantic Deep Sea Drilling Project Site 93-603

Depth fluctuations of the lysocline and calcite compensation depth (CCD) through time were investigated at Deep Sea Drilling Project Site 603, Leg 93. The CCD fell during the middle Miocene at the onset of the Western Boundary Undercurrent, correlated with seismic Horizon X. Subsequently deposited units show fluctuations of the dissolution curve. Major changes in dissolution facies correspond with lithologic boundaries.

Concentrations of PCBs, DDT and thyroid hormones in gray (Halichoerus grypus) and ringed (Phoca hispida) seals

The high levels of polychlorinated biphenyls (PCBs) and DDT in gray seal (Halichoerus grypus) and ringed seal (Phoca hispida botnica) in the Baltic Sea have been associated with pathological disruptions, including bone lesions and reproductive failures. The underlying environmental and toxicological mechanisms leading to these pathological changes are not yet fully understood. The present study investigated the relationship between the individual contaminant load and bone- and thyroid-related effects in adult gray seals (n = 30) and ringed seals (n = 46) in the highly contaminated Baltic Sea and in reference areas (Sable Island, Canada, and Svalbard, Norway). In the gray seals, multivariate and correlation analyses revealed a clear relationship between circulating 1,25-dihydroxyvitamin D3 (1,25(OH)2D), calcium, phosphate, and thyroid hormone (TH) levels and hepatic PCB and DDT load, which suggests contaminant-mediated disruption of the bone and thyroid homeostasis. Contaminants may depress 1,25(OH)2D levels or lead to hyperthyroidism, which may cause bone resorption. In the ringed seals, associations between circulating 1,25(OH)2D, THs, and hepatic contaminants were less prominent. These results suggest that bone lesions observed in the Baltic gray seals may be associated with contaminant-mediated vitamin D and thyroid disruption.

Abundance and chemical and mineral compositions of nodules from the Pacific Ocean

The monograph highlights extensive materials collected during expeditions of P.P. Shirshov Institute of Oceanology. We consider facial conditions of nodule formation, regularities of their distribution, stratigraphic position, petrography, mineral composition, textures, geochemistry of nodules and hosting sediments. Origin of iron-manganese nodules in the Pacific Ocean is considered as well.

Composition of bottom sediments and serpentinites from Core PS-846

A core of foraminiferal-coccolithic oozes filling a valley of the transform fault located at 29°40'S on the South Atlantic Ridge contains layers composed of angular fragments of igneous and metamorphic rocks. They include many serpentinites deriving from serpentinized ultrabasic rocks, probably exposed on the lower section of the southern slope of the fault valley. A mineral and chemical description of these serpentinites is given.

Biomaterials from beer manufacture waste for bone growth scaffolds

Agricultural wastes are a source of renewable raw materials (RRM), with structures that can be tailored for the use envisaged. Here, they have proved to be good replacement candidates for use as biomaterials for the growth of osteoblasts in bone replacement therapies. Their preparation is more cost effective than that of materials presently in use with the added bonus of converting a low-cost waste into a value-added product. Due to their origin these solids are ecomaterials. In this study, several techniques, including X-ray diffraction (XRD), chemical analysis, mercury intrusion porosimetry (MIP), scanning electron microscopy (SEM), and bioassays, were used to compare the biocompatibility and cell growth of scaffolds produced from beer bagasse, a waste material from beer production, with a control sample used in bone and dental regenerative processes.