Sustained release and osteogenic potential of heparan sulfate-doped fibrin glue scaffolds within a rat cranial model

This paper explores the potential therapeutic role of the naturally occurring sugar heparan sulfate (HS) for the augmentation of bone repair. Scaffolds comprising fibrin glue loaded with 5 lg of embryonically derived HS were assessed, firstly as a release-reservoir, and secondly as a scaffold to stimulate bone regeneration in a critical size rat cranial defect. We show HS-loaded scaffolds have a uniform distribution of HS, which was readily released with a typical burst phase, quickly followed by a prolonged delivery lasting several days. Importantly, the released HS contributed to improved wound healing over a 3-month period as determined by microcomputed tomography (lCT) scanning, histology, histomorphometry, and PCR for osteogenic markers. In all cases, only minimal healing was observed after 1 and 3 months in the absence of HS. In contrast, marked healing was observed by 3 months following HS treatment, with nearly full closure of the defect site. PCR analysis showed significant increases in the gene expression of the osteogenic markers Runx2, alkaline phosphatase, and osteopontin in the heparin sulfate group compared with controls. These results further emphasize the important role HS plays in augmenting wound healing, and its successful delivery in a hydrogel provides a novel alternative to autologous bone graft and growth factorbased therapies.

Effects of scaffold architecture on cranial bone healing

Scaffolds for bone tissue engineering should be designed to optimize cell migration, enhance new bone formation and give mechanical support. In the present study, we used polycaprolactone-tricalciumphosphate (PCL/TCP) scaffolds with two different fibre lay down patterns which were coated with hydroxyapatite and gelatine as an approach for optimizing bone regeneration in a critical sized calvarial defect. After 12 weeks bone regeneration was quantified using microCT analysis, biomechanical testing and histological evaluation. Notably, the experimental groups containing coated scaffolds showed lower bone formation and lower biomechanical properties within the defect compared to the uncoated scaffolds. Surprisingly, the different lay down pattern of the fibres resulted in different bone formation and biomechanical properties; namely 0/60/120° scaffolds revealed lower bone formation and biomechanical properties compared to the 0/90° scaffolds in all the experimental groups. The different architecture of the scaffold fibres may have an effect on nutrition supply as well as the attachment of the newly formed matrix to the scaffold. Therefore, future bone regeneration strategies utilising scaffolds should consider scaffold architecture as an important factor during the scaffold optimisation stages in order to move closer to a clinical application.

Evaluation of BMP-2 gene-activated muscle grafts for cranial defect repair

Large, osseous, segmental defects heal poorly. Muscle has a propensity to form bone when exposed to an osteogenic stimulus such as that provided by transfer and expression of cDNA encoding bone morphogenetic protein-2 (BMP-2). The present study evaluated the ability of genetically modified, autologous muscle to heal large cranial defects in rats. Autologous grafts (8 mm � 2 mm) were punched from the biceps femoris muscle and transduced intraoperatively with recombinant adenovirus vector containing human BMP-2 or green fluorescent protein cDNA. While the muscle biopsies were incubating with the vector, a central parietal 8 mm defect was surgically created in the calvarium of the same animal. The gene-activated muscle graft was then implanted into the cranial defect. After 8 weeks, crania were examined radiographically, histologically, and by micro-computed tomography and dual energy X-ray absorptiometry. Although none of the defects were completely healed in this time, muscle grafts expressing BMP-2 deposited more than twice as much new bone as controls. Histology confirmed the anatomical integrity of the newly formed bone, which was comparable in thickness and mineral density to the original cranial bone. This study confirms the in vivo osteogenic properties of genetically modified muscle and suggests novel strategies for healing bone. � 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1095–1102, 2012

Three-dimensional reconstruction of an ancient Egyptian mummy

A complete series of cross-sectional computed tomography (CT) scans were obtained of a mummy of an Egyptian priestess, Tjenmutengebtiu, (Jeni), who lived in the twenty-second Dynasty (c. 945-715 BC). The purpose of this joint British Museum and St. Thomas’ Hospital project was effectively to ‘unwrap’ a mummy using cross-sectional X-rays. Jeni is encased in a beautifully decorated anthropomorphic cartonnage coffin. The head and neck were scanned with 2mm slices, the teeth with 1mm slices and the rest of the body with 4 mm slices, a 512 x 512 matrix was used. The 2D CT images, and 3D surface reconstruction’s, demonstrate many features of the embalming techniques and funerary customs of the XXII Dynasty. The presence of cloth protruding from the nasal cavities into the otherwise empty cranial cavity indicates that the brain was extracted via the nose. The remains of the heart can be seen as well as four organ packs corresponding to the mummified and repackaged lungs, intestines, stomach and liver. Each of the organ packs encloses a wax figurine representing one of the four sons of Horus. The teeth are in very good condition with little signs of wear, which, considering the gritty diet of the Egyptians, indicates that Jeni must have been very young when she died. A young age of death is also suggested by analysis of the shape of the molar teeth. The body is generally in very good condition demonstrating the consummate skill of the twenty-second Dynasty embalmers.

Resorbable composite scaffolds for craniofacial bone tissue engineering

Aim: Bone loss associated with trauma, osteo-degenerative diseases and tumors has tremendous socioeconomic impact related to personal and occupation disability and health care costs. In the present climate of increasing life expectancy with an ensuing increase in bone-related injuries, orthopaedic surgery is undergoing a paradigm shift from bone-grafting to bone engineering, where a scaffold is implanted to provide adequate load bearing and enhance tissue regeneration. We aim to develop composite scaffolds for bone tissue engineering applications to replace the current gold standard of autografting. ---------- Methods: Medical grade polycaprolactone-tricalcium phosphate (mPCL/TCP) scaffolds (80/20 wt%) were custom made using fused deposition modelling to produce 1x1.5x2 cm sized implants for critical-sized pig cranial implantations, empty defects were used as a control. Autologous bone marrow stromal cells (BMSCs) were extracted and precultured for 2 weeks, dispersed within fibrin glue and injected during scaffold implantation. After 2 years, microcomputed tomography and histology were used to assess bone regenerative capabilities of cell versus cell-free scaffolds. ---------- Results: Extensive bone regeneration was evident throughout the entire scaffold. Clear osteocytes embedded within mineralised matrix and active osteoblasts present around scaffold struts were observed. Cell groups performed better than cell-free scaffolds. ---------- Conclusions: Bone regeneration within defects which cannot heal unassisted can be achieved using mPCL/TCP scaffolds. This is improved by the inclusion of autogenous BMSCs. Further work will include the inclusion of growth factors including BMP-2, VEGF and PDGF to provide multifunctional scaffolds, where the three-dimensional (3D) template itself acts as a biomimetic, programmable and multi-drug delivery device.

Investigation of stereotactic radiotherapy dose using dosimetry film and Monte Carlo simulations

This study uses dosimetry film measurements and Monte Carlo simulations to investigate the accuracy of type-a (pencil-beam) dose calculations for predicting the radiation doses delivered during stereotactic radiotherapy treatments of the brain. It is shown that when evaluating doses in a water phantom, the type-a algorithm provides dose predictions which are accurate to within clinically relevant criteria, gamma(3%,3mm), but these predictions are nonetheless subtly different from the results of evaluating doses from the same fields using radiochromic film and Monte Carlo simulations. An analysis of a clinical meningioma treatment suggests that when predicting stereotactic radiotherapy doses to the brain, the inaccuracies of the type-a algorithm can be exacerbated by inadequate evaluation of the effects of nearby bone or air, resulting in dose differences of up to 10% for individual fields. The results of this study indicate the possible advantage of using Monte Carlo calculations, as well as measurements with high-spatial resolution media, to verify type-a predictions of dose delivered in cranial treatments.

Evaluation of coronary angiographic projections to balance the clinical yield with the radiation risk

Objective: Radiation safety principles dictate that imaging procedures should minimise the radiation risks involved, without compromising diagnostic performance. This study aims to define a core set of views that maximises clinical information yield for minimum radiation risk. Angiographers would supplement these views as clinically indicated. Methods: An algorithm was developed to combine published data detailing the quality of information derived for the major coronary artery segments through the use of a common set of views in angiography with data relating to the dose–area product and scatter radiation associated with these views. Results: The optimum view set for the left coronary system comprised four views: left anterior oblique (LAO) with cranial (Cr) tilt, shallow right anterior oblique (AP-RAO) with caudal (Ca) tilt, RAO with Ca tilt and AP-RAO with Cr tilt. For the right coronary system three views were identified: LAO with Cr tilt, RAO and AP-RAO with Cr tilt. An alternative left coronary view set including a left lateral achieved minimally superior efficiency (,5%), but with an ,8% higher radiation dose to the patient and 40% higher cardiologist dose. Conclusion: This algorithm identifies a core set of angiographic views that optimises the information yield and minimises radiation risk. This basic data set would be supplemented by additional clinically determined views selected by the angiographer for each case. The decision to use additional views for diagnostic angiography and interventions would be assisted by referencing a table of relative radiation doses for the views being considered.

Taxonomy and redescription of the Yellow-footed Antechinus, Antechinus flavipes (Waterhouse) (Marsupialia: Dasyuridae)

We provide a taxonomic redescription of the ubiquitous and variable dasyurid marsupial Yellow-footed Antechinus, Antechinus flavipes (Waterhouse), which comprises three currently recognized subspecies whose combined geographic distribution spans almost the length and breadth of Australia. A. flavipes leucogaster Gray is confined to south-west Western Australia; A. flavipes flavipes is distributed in south-eastern Australia across four states—South Australia, Victoria, New South Wales and Queensland; A. flavipes rubeculus Van Dyck is confined to the wet tropics of Queensland. A. flavipes is readily distinguished from all extant congeners based on external morphology by the following combination of features: a grey head; orange-yellow toned flanks/rump, feet and tail base; pale eye-rings and a darkened tail tip. A. flavipes skulls are stout, being broad at the level of the rear upper molars, have small palatal vacuities and small entoconid cusps on the lower molars. However, notable differences among subspecies of A. flavipesprevent any obvious collection of skull characters being diagnostic for species-level discrimination among congeners. A. flavipes rubeculus is the largest of the three subspecies of Yellow-footed Antechinus and most similar in skull morphology to A. leo, A. bellus and A. godmani—all four species are geographically limited to tropical Australia. A. f. rubeculus is notably larger in many characters than its conspecifics: A. f. flavipes, the next largest, and A. f. leucogaster, the smallest of the group. A. f. flavipes and A. f. leucogaster diverge significantly at only a few skull characters, and both subspecies have cranial morphological affinities with the recently discovered A. mysticus, most notably A. f. leucogaster. Phylogenies generated from mt- and nDNA data strongly support Antechinus flavipes as monophyletic with respect to other members of the genus; within A. flavipes, each of the three recognized subspecies form distinctive monophyletic clades.

Burn healing is dependent on burn site : a quantitative analysis from a porcine burn model

This retrospective review examines healing in different sites on a porcine burn model; 24 pairs of burns on 18 pigs from other animal trials were selected for analysis. Each pair of burns was located on the either the cranial or the caudal part of the thoracic ribs region, on the same side of the animal. The burns were 40-50 cm(2) in size and of uniform deep-dermal partial thickness. Caudal burns healed significantly better than cranial burns, demonstrated by earlier closure of wounds, less scar formation and better cosmesis. To our knowledge, this is the first detailed study reporting that burn healing is affected by location on a porcine burn model. We recommend that similar symmetrical burns should be used for future comparative assessments of burn healing.

Predicting the likelihood of QA failure using treatment plan accuracy metrics

This study used automated data processing techniques to calculate a set of novel treatment plan accuracy metrics, and investigate their usefulness as predictors of quality assurance (QA) success and failure. 151 beams from 23 prostate and cranial IMRT treatment plans were used in this study. These plans had been evaluated before treatment using measurements with a diode array system. The TADA software suite was adapted to allow automatic batch calculation of several proposed plan accuracy metrics, including mean field area, small-aperture, off-axis and closed-leaf factors. All of these results were compared the gamma pass rates from the QA measurements and correlations were investigated. The mean field area factor provided a threshold field size (5 cm2, equivalent to a 2.2 x 2.2 cm2 square field), below which all beams failed the QA tests. The small aperture score provided a useful predictor of plan failure, when averaged over all beams, despite being weakly correlated with gamma pass rates for individual beams. By contrast, the closed leaf and off-axis factors provided information about the geometric arrangement of the beam segments but were not useful for distinguishing between plans that passed and failed QA. This study has provided some simple tests for plan accuracy, which may help minimise time spent on QA assessments of treatments that are unlikely to pass.

Temporal Characterization of Ossification of the Crania in Australian Subadults: New standards for Age Estimation using Computed Tomography

After attending this presentation, attendees will gain awareness of the ontogeny of cranial maturation, specifically: (1) the fusion timings of primary ossification centers in the basicranium; and (2) the temporal pattern of closure of the anterior fontanelle, to develop new population-specific age standards for medicolegal death investigation of Australian subadults. This presentation will impact the forensic science community by demonstrating the potential of a contemporary forensic subadult Computed Tomography (CT) database of cranial scans and population data, to recalibrate existing standards for age estimation and quantify growth and development of Australian children. This research welcomes a study design applicable to all countries faced with paucity in skeletal repositories. Accurate assessment of age-at-death of skeletal remains represents a key element in forensic anthropology methodology. In Australian casework, age standards derived from American reference samples are applied in light of scarcity in documented Australian skeletal collections. Currently practitioners rely on antiquated standards, such as the Scheuer and Black1 compilation for age estimation, despite implications of secular trends and population variation. Skeletal maturation standards are population specific and should not be extrapolated from one population to another, while secular changes in skeletal dimensions and accelerated maturation underscore the importance of establishing modern standards to estimate age in modern subadults. Despite CT imaging becoming the gold standard for skeletal analysis in Australia, practitioners caution the application of forensic age standards derived from macroscopic inspection to a CT medium, suggesting a need for revised methodologies. Multi-slice CT scans of subadult crania and cervical vertebrae 1 and 2 were acquired from 350 Australian individuals (males: n=193, females: n=157) aged birth to 12 years. The CT database, projected at 920 individuals upon completion (January 2014), comprises thin-slice DICOM data (resolution: 0.5/0.3mm) of patients scanned since 2010 at major Brisbane Childrens Hospitals. DICOM datasets were subject to manual segmentation, followed by the construction of multi-planar and volume rendering cranial models, for subsequent scoring. The union of primary ossification centers of the occipital bone were scored as open, partially closed or completely closed; while the fontanelles, and vertebrae were scored in accordance with two stages. Transition analysis was applied to elucidate age at transition between union states for each center, and robust age parameters established using Bayesian statistics. In comparison to reported literature, closure of the fontanelles and contiguous sutures in Australian infants occur earlier than reported, with the anterior fontanelle transitioning from open to closed at 16.7±1.1 months. The metopic suture is closed prior to 10 weeks post-partum and completely obliterated by 6 months of age, independent of sex. Utilizing reverse engineering capabilities, an alternate method for infant age estimation based on quantification of fontanelle area and non-linear regression with variance component modeling will be presented. Closure models indicate that the greatest rate of change in anterior fontanelle area occurs prior to 5 months of age. This study complements the work of Scheuer and Black1, providing more specific age intervals for union and temporal maturity of each primary ossification center of the occipital bone. For example, dominant fusion of the sutura intra-occipitalis posterior occurs before 9 months of age, followed by persistence of a hyaline cartilage tongue posterior to the foramen magnum until 2.5 years; with obliteration at 2.9±0.1 years. Recalibrated age parameters for the atlas and axis are presented, with the anterior arch of the atlas appearing at 2.9 months in females and 6.3 months in males; while dentoneural, dentocentral and neurocentral junctions of the axis transitioned from non-union to union at 2.1±0.1 years in females and 3.7±0.1 years in males. These results are an exemplar of significant sexual dimorphism in maturation (p<0.05), with girls exhibiting union earlier than boys, justifying the need for segregated sex standards for age estimation. Studies such as this are imperative for providing updated standards for Australian forensic and pediatric practice and provide an insight into skeletal development of this population. During this presentation, the utility of novel regression models for age estimation of infants will be discussed, with emphasis on three-dimensional modeling capabilities of complex structures such as fontanelles, for the development of new age estimation methods.

Sensorineural hearing loss after treatment for head and neck cancer : a review of the literature

Background Definitive cisplatin-based is increasingly delivered as the treatment of choice for patients with head and neck cancer. Sensorineural hearing loss is a significant long term side effect of cisplatin-based chemoradiation and is associated with potential major quality of life issues for patients. Purpose The purpose of this manuscript was to review the mechanism behind sensorineural hearing loss in patients treated with cisplatin-based chemoradiation, including incidence, the contributions of radiotherapy and cisplatin to sensorineural hearing loss and the impact of the toxicity on patient quality of life. Methods Database searches were conducted through PubMed (National Centre for Biotechnology Information) and OvidSP Medline via the Queensland University of Technology Library website. General article searches were conducted through the online search engine Google Scholar. Articles were excluded if the full-text was unavailable, they were not in English or if they were published prior to 1990. Keywords included hearing loss, ototoxicity, cancer, quality of life, cisplatin and radiotherapy. Results/Discussion The total number of journal articles accessed was 290. Due to exclusion criteria, 129 articles were deemed appropriated for review. Findings indicated that sensorineural hearing loss is a significant, long term complication for patients treated with cisplatin-based chemoradiation. Current literature recognises the ototoxic effects of cisplatin and cranial irradiation as separate entities, however the impact of combined modality therapy on sensorineural hearing loss is seldom reported. Multiple risk factors for hearing loss are described, however there are contradictory opinions on incidence and severity and the exact radiation dose threshold responsible for inducing hearing loss in patients receiving combined modality therapy. Sensorineural hearing loss creates a subset of complexities for patients with head and neck cancer and that these patients face significant quality of life impairment. Conclusion The literature review identified that sensorineural hearing loss is a major quality of life issue for patients treated with cisplatin-based chemoradiation for head and neck cancer. Further investigation evaluating the contribution of cisplatin-based chemoradiation to sensorineural hearing loss and the subsequent effect on patient quality of life is warranted.

Parameterization and reliability of single-leg balance test assessed with inertial sensors in stroke survivors: a cross-sectional study

Background and purpose There are no published studies on the parameterisation and reliability of the single-leg stance (SLS) test with inertial sensors in stroke patients. Purpose: to analyse the reliability (intra-observer/inter-observer) and sensitivity of inertial sensors used for the SLS test in stroke patients. Secondary objective: to compare the records of the two inertial sensors (trunk and lumbar) to detect any significant differences in the kinematic data obtained in the SLS test. Methods Design: cross-sectional study. While performing the SLS test, two inertial sensors were placed at lumbar (L5-S1) and trunk regions (T7–T8). Setting: Laboratory of Biomechanics (Health Science Faculty - University of Málaga). Participants: Four chronic stroke survivors (over 65 yrs old). Measurement: displacement and velocity, Rotation (X-axis), Flexion/Extension (Y-axis), Inclination (Z-axis); Resultant displacement and velocity (V): RV=(Vx2+Vy2+Vz2)−−−−−−−−−−−−−−−−−√ Along with SLS kinematic variables, descriptive analyses, differences between sensors locations and intra-observer and inter-observer reliability were also calculated. Results Differences between the sensors were significant only for left inclination velocity (p = 0.036) and extension displacement in the non-affected leg with eyes open (p = 0.038). Intra-observer reliability of the trunk sensor ranged from 0.889-0.921 for the displacement and 0.849-0.892 for velocity. Intra-observer reliability of the lumbar sensor was between 0.896-0.949 for the displacement and 0.873-0.894 for velocity. Inter-observer reliability of the trunk sensor was between 0.878-0.917 for the displacement and 0.847-0.884 for velocity. Inter-observer reliability of the lumbar sensor ranged from 0.870-0.940 for the displacement and 0.863-0.884 for velocity. Conclusion There were no significant differences between the kinematic records made by an inertial sensor during the development of the SLS testing between two inertial sensors placed in the lumbar and thoracic regions. In addition, inertial sensors. Have the potential to be reliable, valid and sensitive instruments for kinematic measurements during SLS testing but further research is needed.

Relationship between Barthel index with physical tests in adults with intellectual disabilities

We usually find low levels of fitness condition affect other aspects of living for people with ID like dependency in carrying out activivities of daily living. Therefore we find high levels of dependency in activities of daily living due to poor fitness condition. The aim of the study is to explore the criterion validity of the Barthel index with a physical fitness test. An observational cross-sectional study was conducted. Data from the Barthel index and a physical fitness test were measured in 122 adults with intellectual disability. The data were analysed to find out the relationship between four categories of the physical fitness test and the Barthel index. It needs to be stressed that the correlations between the Barthel index and leg, abdominal and arm strength can confirm that these physical test are predictive of the Barthel index. The correlations between the balance variables as functional reach and single-leg stance with eyes open shown relationships with Barthel Index. We found important correlations between the physical fitness test and the Barthel index, so we can affirm that some physical fitness features are predictor variables of the Barthel index.

Improving adherence physical activity with a smartphone application based on adults with intellectual disabilities (APPCOID)

Background People with intellectual disabilities (ID) have lower levels of physical activity and quality of life and they have a lot of barriers to face when taking part in physical activity. Other problems are the poor adherence to physical activity such people have so this study is designed to improve adherence to physical activity for people with intellectual disabilities with the assistance of an application for smartphones. The aim of the study will be to improve physical activity and physical condition after multimodal intervention and to analyse the promotion of adherence to physical activity through a multimodal intervention and an app intervention (mHealth) in people with ID. Methods A two-stage study will be conducted. In stage 1 a multimodal intervention will take place will be done with physical activity and educational advice over eight weeks, two days a week. Data will be measured after and before the intervention. In stage 2 a randomized controlled trial will be conducted. In the intervention group we will install an application to a smartphone; this application will be a reminder to do a physical activity and they have to select whether they have or haven’t done a physical activity every day. This application will be installed for 18 weeks. Data will be measured after and before the application is installed in two groups. We will measure results 10 weeks later when the two groups don’t have the reminder. The principal outcome used to measure the adherence to physical activity will be the International Physical Activity Questionnaire; secondary outcomes will be a fun-fitness test and self-report survey about quality of life, self-efficacy and social support. Samples will be randomized by sealed envelope in two groups, with approximately 20 subjects in each group. It’s important to know that the therapist will be blinded and won’t know the subjects of each group. Discussion Offering people with ID a multimodal intervention and tool to increase the adherence to a physical activity may increase the levels of physical activity and quality of life. Such a scheme, if beneficial, could be implemented successfully within public health sense. Trial registration ClinicalTrials.gov Identifier: NCT01915381.