In Vivo Deformation and Strain Measurements in Human Bone Using Digital Volume Correlation (DVC) and 3T Clinical MRI

Strains within bone play an important role in the remodelling process and the mechanisms of fracture. The ability to assess these strains in vivo can provide clinically relevant information regarding bone health, injury risk, and can also be used to optimise treatments. In vivo bone strains have been investigated using multiple experimental techniques, but none have quantified 3D strains using non-invasive techniques. Digital volume correlation based on clinical MRI (DVC-MRI) is a non-invasive technique that has the potential to achieve this. However, before it can be implemented, uncertainties associated with the measurements must be quantified. Here, DVC-MRI was evaluated to assess its potential to measure in vivo strains in the talus. A zero-strain test (two repeated unloaded scans) was conducted using three MRI sequences, and three DVC approaches to quantify errors and to establish optimal settings. With optimal settings, strains could be measured with a precision of 200 με and accuracy of 480 με for a spatial resolution of 7.5 mm, and a precision of 133 με and accuracy of 251 με for a spatial resolution of 10 mm. These results demonstrate that this technique has the potential to measure relevant levels of in vivo bone strain and to be used for a range of clinical applications.     

Effect of rearing water temperature on protandrous sex inversion in cultured Asian Seabass (Lates calcarifer)

Asian Seabass, Lates calcarifer (Bloch, 1790), is a protandrous species cultured for Aquaculture. The cultured Asian Seabass in Australia exhibits precocious sex inversion before 2years of age. This phenomenon highly affects on maintaining a proper broodstock in a hatchery. The effect of temperature on sex inversion inducement in Asian Seabass was thus investigated at five different temperature regimes experienced in Australia. Asian Seabass (14months) grown in fresh water under natural temperature in a commercial farm in Queensland were transported to the research facility at James Cook University, Australia and held in fresh water at 28°C until acclimatized to the experimental conditions. Fish were acclimated to the experimental conditions (30ppt salinity) over the first and final week (22°C, 25°C, 28°C, 31°C and 34°C) of one month acclimatizing period. Fish were fed daily with a commercial pellet (50% protein, 18MJkg(-1)) to satiety. Blood, brain and gonad collected before transfer to the experimental temperature regime in the final week of acclimatization and at the end of the experiment were analysed. Plasma sex steroids level and aromatase activity of brain and gonad were also measured. There was an increase in plasma estradiol levels with increasing temperature from 25°C while no significant difference was observed among all treatment temperatures except at 25°C. However, fish held at 22°C showed higher estradiol level than at 25°C and 28°C. Significantly higher (p<0.05) plasma testosterone levels were detected in fish held at 31°C and 34°C while a reducing trend was observed towards lower temperature regimes. Fish held at 22°C had significantly lower plasma testosterone than all others as well those sampled at the beginning. The plasma 11-ketoTestosterone was at non-detectable levels in all experimental temperatures as shown at the beginning. The average aromatase activity in brain was highest at 28°C among all temperatures, but no significant differences (p>0.05) observed. The Average aromatase activity in gonad was highest at 31°C followed by at 34°C and 28°C. No or very low level of gonad aromatase activity recorded in fish sacrificed prior to treatment. The aromatase activity was greater in brain than in gonad suggesting that the aromatase produced in the brain yet to transfer to the gonad or brain is the first place to response for culture environmental temperature. It is concluded that plasma sex steroids levels and aromatase activity in Asian Seabass have positive response to increasing temperature in culture facilities.     

Combined cytoplasmic and membranous EGFR and p53 overexpression is a poor prognostic marker in early stage oral squamous cell carcinoma

J Oral Pathol Med (2012) 41 : 559–567 Objective: Our aim was to evaluate the expression of several molecules that regulate growth, the cell cycle and signalling pathways including EGFR, p53, p16 and p27 in oral squamous cell carcinomas (OSCC). We examined their utility as prognostic markers by relating to clinicopathological characteristics and the clinical outcome. Patients and methods: Using tissue microarray technology, we analysed 67 primary OSCC and examined immunohistochemical expression of EGFR, p53, p16 and p27. Multivariate analysis was conducted to examine their role in survival. Results: Many of the markers were highly expressed in these cancers. Membranous EGFR expression in 95.2%, both membrane and cytoplasm expression in 35%, p53 expression in 61.6%, p27 expression in 89.5% and p16 expression in 27.9% of cases. In the multivariate analysis, independent prognostic influence of a lower overall survival was determined only for advanced tumour stage (P < 0.001), p53 overexpression (P = 0.004), EGFR cytoplasm and membrane co‐expression location (P = 0.002) and p16 reduced expression (P = 0.002). When considering a subgroup of early stage tumours, p53 overexpression (P = 0.028) and combined membranous and cytoplasm EGFR co‐expression (P = 0.039) were indicators of a lower overall survival. For disease‐free survival, in addition to these three factors, the histological grade (P = 0.011) showed independent prognostic values. Conclusion: The independent value of EGFR subcellular location (cytoplasm and membrane) and p53 overexpression in overall survival even in early stages of OSCC suggests that these markers may serve as reliable biological markers to identify high‐risk subgroups and to guide therapy.     

Cenani–Lenz syndrome restricted to limb and kidney anomalies associated with a novel LRP4 missense mutation

Cenani–Lenz syndrome (CLS) is a rare autosomal recessive developmental disorder of the limbs. The disorder is characterized by complete syndactyly with metacarpal fusions and/or oligodactyly sometimes accompanied by radioulnar synostosis. The clinical expression is variable and kidney agenesis/hypoplasia, craniofacial dysmorphism and teeth abnormalities are frequent features as well as lower limb involvement. CLS was recently associated with mutations in the low-density lipoprotein receptor-related protein 4 (LRP4) gene and dysregulated canonical WNT signaling. We have identified a large consanguineous Pakistani pedigree with 9 members affected by CLS. The affected individuals present with a consistent expression of the syndrome restricted to the limbs and kidneys. Symptoms from the lower limb are mild or absent and there were no radioulnar synostosis or craniofacial involvement. Genetic analysis using autozygosity mapping and sequencing revealed homozygosity for a novel missense mutation c.2858T > C (p.L953P) in the LRP4 gene. The mutation is located in a region encoding the highly conserved low-density lipoprotein receptor repeat class B domain of LRP4. Our findings add to the genotype–phenotype correlations in CLS and support kidney anomalies as a frequent associated feature.     

Reduced loosening rate and loss of correction following posterior stabilization with or without PMMA augmentation of pedicle screws in vertebral fractures in the elderly

Background

Therapy of vertebral fractures in the elderly is a growing challenge for surgeons. Within the last two decades, the use of polymethylmethacrylate (PMMA) in the treatment of osteoporotic vertebral fractures has been widely established. Besides vertebroplasty and kyphoplasty, the augmentation of pedicle screws with PMMA found widespread use to strengthen the implant–bone interface. Several studies showed an enhanced pullout strength of augmented screws compared to standard pedicle screws in osteoporotic bone models. To validate the clinical relevance, we analyzed postoperative radiologic follow-up data in regard to secondary loss of correction and loosening of pedicle screws in elderly patients.

Materials and methods

In this retrospective comparative study, 24 patients admitted to our level I trauma center were analyzed concerning screw loosening and secondary loss of correction following vertebral fracture and posterior instrumentation. Loss of correction was determined by the bisegmental Cobb angle and kyphosis angle of the fractured vertebra. Follow-up computed tomography (CT) scans were used to analyze the prevalence of clear zones around the pedicle screws as a sign of loosening.

Results

In 15 patients (mean age 76 ± 9.3 years) with 117 PMMA-augmented pedicle screws, 4.3 % of screws showed signs of loosening, whereas in nine patients (mean age 75 ± 8.2 years) with 86 uncemented screws, the loosening rate was 62.8 %. Thus, PMMA-augmented pedicle screws showed a significantly lower loosening rate compared to regular pedicle screws. Loss of correction was minimal, despite poor bone quality. There was significantly less loss of correction in patients with augmented pedicle screws (1.1° ± 0.8°) as compared to patients without augmentation (5° ± 3.8°).

Conclusion

The reinforcement of pedicle screws using PMMA augmentation may be a viable option in the surgical treatment of spinal fractures in the elderly.