The clinical potential of antiangiogenic fragments of extracellular matrix proteins

Neovasculature development is a crucial step in the natural history of a cancer. While much emphasis has been placed on proangiogenic growth factors such as VEGF, it is clear that endogenous angiogenesis inhibitors also have critical roles in the regulation of this process. Recent research has identified several cryptic fragments of extracellular matrix/vascular basement membrane proteins that have potent antiangiogenic properties in vivo. It has become apparent that many of these fragments signal via interactions with endothelial integrins, although multiple downstream effector pathways have been implicated and endostatin, the first non-collagenous domain of collagen XVIII, influences an intricate signalling network. The activity of these molecules in animal models suggests that they may have significant clinical activity; however, results of phase I/II trials with endostatin were disappointing. Many possible reasons can be found for the failure of these studies. Weaknesses in trial design, endostatin administration regimen and patient selection are identifiable, and importantly the lack of a clearly defined antiangiogenic mechanism for endostatin hindered assessment of biologically effective dose. Additionally, in vivo immunological and proteolytic function-neutralising mechanisms may have negated endostatin's actions. Lessons learned from these studies will aid the future clinical development of other antiangiogenic extracellular matrix protein fragments

One year soy protein supplementation has positive effects on bone formation markers but not bone density in postmenopausal women

BACKGROUND: Although soy protein and its isoflavones have been reported to reduce the risk of osteoporosis in peri- and post-menopausal women, most of these studies are of short duration (i.e. six months). The objective of this study was to examine if one year consumption of soy-containing foods (providing 25 g protein and 60 mg isoflavones) exerts beneficial effects on bone in postmenopausal women. METHODS: Eighty-seven eligible postmenopausal women were randomly assigned to consume soy or control foods daily for one year. Bone mineral density (BMD) and bone mineral content (BMC) of the whole body, lumbar (L1-L4), and total hip were measured using dual energy x-ray absorptiometry at baseline and after one year. Blood and urine markers of bone metabolism were also assessed. RESULTS AND DISCUSSION: Sixty-two subjects completed the one-year long study. Whole body and lumbar BMD and BMC were significantly decreased in both the soy and control groups. However, there were no significant changes in total hip BMD and BMC irrespective of treatment. Both treatments positively affected markers of bone formation as indicated by increased serum bone-specific alkaline phosphatase (BSAP) activity, insulin-like growth factor-I (IGF-I), and osteocalcin (BSAP: 27.8 and 25.8%, IGF-I: 12.8 and 26.3%, osteocalcin: 95.2 and 103.4% for control and soy groups, respectively). Neither of the protein supplements had any effect on urinary deoxypyridinoline excretion, a marker of bone resorption. CONCLUSION: Our findings suggest that although one year supplementation of 25 g protein per se positively modulated markers of bone formation, this amount of protein was unable to prevent lumbar and whole body bone loss in postmenopausal women

Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries

Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in approximate to 131 K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P <1.0 x 10(-5)). In Stage 2, these SNVs were tested for independent external replication in individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10(-8)). For African ancestry samples, we detected 18 potentially novel BP loci (P< 5.0 x 10(-8)) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2 have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension

A Look Back in Time: Sir Robert Jones, ‘Father of Modern Orthopaedics’

This paper describes the life of Sir Robert Jones, from his humble beginnings as an apprentice of Thomas Smith, to his many contributions to the orthopaedic specialty. Robert Jones’ passion and interest in the subject led to its advancement from a specialty that dealt mainly with crippling diseases in children, to that of treating and rehabilitating disabled adults. He revolutionized the practice by integrating the use of plain radiography, and by developing many new surgical and procedural techniques. He largely improved the specialty by publishing many textbooks and papers, and trained many orthopaedic surgeons from within England and internationally. The purpose of this paper seeks to provide a platform for readers to learn about the man behind the Jones fracture and bandage. It will help readers understand how one man’s passion for orthopaedics helped transform it into a specialty in its own rights

Validity and reliability of an adapted questionnaire measuring acceptance of traditional Chinese medicine among cancer patients

Acceptance of traditional chinese medicine (TCM) treatment is important in cancer patients to improve treatment efficacy, reduce side effects and prolong prognosis and survival rate. However, such studies and validated instruments that assess the acceptance of TCM treatment in Malaysia are limited. This study aimed to evaluate the validity and reliability of the acceptance of the TCM treatment questionnaire based on applying the Theory of Planned Behaviour. The validation study was conducted in two phases. The first phase included content validation, adaptation and face validity using the Survey Validation Rubric for Expert Panel (VREP). The second phase included construct reliability by using Cronbach alpha. The first phase validation of the questionnaire met expectations from the experts’ panel with a score of 3.33. In phase two, 78 patients were included in the analysis. All constructs achieved a Cronbach Alpha &amp;gt;0.8, showing good reliability of the questionnaire. This study demonstrated good validity and reliability of the major constructs in the acceptance of the TCM questionnaire. Our results showed that the acceptance of the TCM questionnaire was a reliable instrument that could be applied to evaluate the acceptance of TCM treatment among cancer patients

Field evaluation of a glass-fiber soil reinforcement system

A soil reinforcement system using the combination of glass-fiber-reinforced polymer (GFRP) pipe and pressure grouting has been developed by a Korean company. The system is being adopted as slope stabilization measures in Hong Kong. Individual GFRP pipes were designed and installed as soil nails with the exception that two-stage pressure grouting was applied instead of gravity grouting. A full-scale field evaluation on constructability and in situ performance of the system was performed in Hong Kong. The performance of the constructed nails was evaluated by pullout tests. The construction procedure, site adaptations of the Korean product made in Hong Kong, field test procedure, and performance of the constructed soil nails are reported in this paper. © 2007 ASCE.link_to_subscribed_fulltex

Time-dependent strength degradation of granite

Understanding the time-dependent strength degradation and associated creep behavior is essential to the safety evaluation of a radioactive waste disposal system in rock. In this study, a series of constant loading tests under different confining pressures and temperatures with acoustic emission monitoring have been performed to study evolution of dilatancy (damage) and strength degradation. Source location analysis and moment tensor analysis were carried out to reproduce the progressive damage process during constant load helping to understand the failure mechanism from a microscopic point of view. In this paper, we report on the findings of the experimental results. © 2009 Elsevier Ltd. All rights reserved.link_to_subscribed_fulltex