Postoperative phlegmasia caerulea dolens: a case report and consideration of potential iatrogenic factors

While the haemorrhagic consequences of anti-coagulants are well and frequently described in the surgical literature, the paradoxical prothrombotic tendencies of these drugs tend to be under-recognised due, perhaps, to their clinical infrequency. However, when these effects pertain, their consequences can be devastating. Here, we present a postoperative oncology patient who suffered a massive recrudescence of his lower limb venous thrombosis immediately after discontinuation of his heparin infusion, despite seemingly being adequately anticoagulated by warfarin therapy (INR > 2.0). We intend this case to graphically illustrate the theoretical considerations that must govern the perioperative use of these drugs in high-risk patients

Selected static foot assessments do not predict medial longitudinal arch motion during running

Background: Static assessments of the foot are commonly advocated within the running community to classify the foot with a view to recommending the appropriate type of running shoe. The aim of this work was to determine whether selected static foot assessment could predict medial longitudinal arch (MLA) motion during running. Methods: Fifteen physically active males (27 ± 5 years, 1.77 ± 0.04m, 80 ± 10kg) participated in the study. Foot Posture Index (FPI-6), MLA angle and rearfoot angle were measured in a relaxed standing position. MLA motion was calculated using the position of retro-reflective markers tracked by a VICON motion analysis system, while participants ran barefoot on a treadmill at a self-selected pace (2.8 ± 0.5m.s-1). Bivariate linear regression was used to determine whether the static measures predicted MLA deformation and MLA angles at initial contact, midsupport and toe off. Results: All three foot classification measures were significant predictors of MLA angle at initial contact, midsupport and toe off (p < .05) explaining 41-90% of the variance. None of the static foot classification measures were significant predictors of MLA deformation during the stance phase of running. Conclusion: Selected static foot measures did not predict dynamic MLA deformation during running. Given that MLA deformation has theoretically been linked to running injuries, the clinical relevance of predicting MLA angle at discrete time points during the stance phase of running is questioned. These findings also question the validity of the selected static foot classification measures when looking to characterise the foot during running. This indicates that alternative means of assessing the foot to inform footwear selection are required

Structural sustainability appraisal in BIM

The provision of Application Programming Interface (API) in BIM-enable tools can contribute to facilitating BIM-related research. APIs are useful links for running plug-ins and external programmes but they are yet to be fully exploited in expanding the BIM scope. The modelling of n-Dimensional (nD) building performance measures can potentially benefit from BIM extension through API implementations. Sustainability is one such measure associated with buildings. For the structural engineer, recent design criteria have put great emphasis on the sustainability credentials as part of the traditional criteria of structural integrity, constructability and cost. This paper examines the utilization of API in BIM extension and presents a demonstration of an API application to embed sustainability issues into the appraisal process of structural conceptual design options in BIM. It concludes that API implementations are useful in expanding the BIM scope. Also, the approach including process modelling, algorithms and object-based instantiations demonstrated in the API implementation can be applicable to other nD building performance measures as may be relevant to the various professional platforms in the construction domain

Predictors of podiatry utilisation in Australia: the North West Adelaide Health Study

Background Foot problems are highly prevalent in the community; however no large population-based studies have examined the characteristics of those who do and do not access podiatry services in Australia. The aim of this study was to explore patterns of podiatry utilisation in a population-based sample of people aged 18 years and over living in the northwest region of Adelaide, South Australia.Methods The North West Adelaide Health Study is a representative longitudinal cohort study of 4,060 people randomly selected and recruited by telephone interview. The interview included questions regarding healthcare service utilisation in the past year. Data were also collected on education, income and major medical conditions.Results Overall, 9.5% of the total sample and 17.7% of those who reported foot pain had attended a podiatrist in the past year. Participants who had accessed podiatry treatment were more likely to be female, be aged over 45 years, be obese, and have major chronic medical conditions (osteoporosis, osteoarthritis, diabetes, cardiovascular disease and high blood pressure). Those who reported foot pain but had not accessed a podiatrist were more likely to be male and be aged 20 to 34 years.Conclusion Only a small proportion of people who report foot pain have accessed podiatry services in the past year. There is a need to further promote podiatry services to the general community, particularly to men and younger people.Hylton B Menz, Tiffany K Gill, Anne W Taylor and Catherine L Hil

Bicistronic Lentiviruses Containing a Viral 2A Cleavage Sequence Reliably Co-Express Two Proteins and Restore Vision to an Animal Model of LCA1

The disease processes underlying inherited retinal disease are complex and are not completely understood. Many of the corrective gene therapies designed to treat diseases linked to mutations in genes specifically expressed in photoreceptor cells restore function to these cells but fail to stop progression of the disease. There is growing consensus that effective treatments for these diseases will require delivery of multiple therapeutic proteins that will be selected to treat specific aspects of the disease process. The purpose of this study was to design a lentiviral transgene that reliably expresses all of the proteins it encodes and does so in a consistent manner among infected cells. We show, using both in vitro and in vivo analyses, that bicistronic lentiviral transgenes encoding two fluorescent proteins fused to a viral 2A-like cleavage peptide meet these expression criteria. To determine if this transgene design is suitable for therapeutic applications, we replaced one of the fluorescent protein genes with the gene encoding guanylate cyclase -1 (GC1) and delivered lentivirus carrying this transgene to the retinas of the GUCY1*B avian model of Leber congenital amaurosis – 1 (LCA1). GUCY1*B chickens carry a null mutation in the GC1 gene that disrupts photoreceptor function and causes blindness at hatching, a phenotype that closely matches that observed in humans with LCA1. We found that treatment of these animals with the 2A lentivector encoding GC1 restored vision to these animals as evidenced by the presence of optokinetic reflexes. We conclude that 2A-like peptides, with proper optimization, can be successfully incorporated into therapeutic vectors designed to deliver multiple proteins to neural retinal. These results highlight the potential of this vector design to serve as a platform for the development of combination therapies designed to enhance or prolong the benefits of corrective gene therapies

Hypoxia increases the metastatic ability of breast cancer cells via upregulation of CXCR4

<p>Abstract</p> <p>Background</p> <p>Chemokine SDF1α and its unique receptor CXCR4 have been implicated in organ-specific metastases of many cancers including breast cancer. Hypoxia is a common feature of solid tumors and is associated with their malignant phenotype. We hypothesized that hypoxia would upregulate CXCR4 expression and lead to increased chemotactic responsiveness to its specific ligand SDF1α.</p> <p>Methods</p> <p>Three breast cancer cell lines MDA-MB-231, MCF7 and 4T1 were subjected to 48 hrs of hypoxia or normoxia. Cell surface receptor expression was evaluated using flow cytometry. An extracellular matrix invasion assay and microporous migration assay was used to assess chemotactic response and metastatic ability.</p> <p>Results</p> <p>CXCR4 surface expression was significantly increased in the two human breast cancer cell lines, MDA-MB-231 and MCF7, following exposure to hypoxia. This upregulation of CXCR4 cell surface expression corresponded to a significant increase in migration and invasion in response to SDF1-α <it>in vitro</it>. The increase in metastatic potential of both the normoxic and the hypoxic treated breast cancer cell lines was attenuated by neutralization of CXCR4 with a CXCR4 neutralizing mAb, MAB172 or a CXCR4 antagonist, AMD3100, showing the relationship between CXCR4 overexpression and increased chemotactic responsiveness.</p> <p>Conclusions</p> <p>CXCR4 expression can be modulated by the tissue microenvironment such as hypoxia. Upregulation of CXCR4 is associated with increased migratory and invasive potential and this effect can be abrogated by CXCR4 inhibition. Chemokine receptor CXCR4 is a potential therapeutic target in the adjuvant treatment of breast cancer.</p

Transcriptional Responses of Cultured Rat Sympathetic Neurons during BMP-7-Induced Dendritic Growth

Dendrites are the primary site of synapse formation in the vertebrate nervous system; however, relatively little is known about the molecular mechanisms that regulate the initial formation of primary dendrites. Embryonic rat sympathetic neurons cultured under defined conditions extend a single functional axon, but fail to form dendrites. Addition of bone morphogenetic proteins (BMPs) triggers these neurons to extend multiple dendrites without altering axonal growth or cell survival. We used this culture system to examine differential gene expression patterns in naïve vs. BMP-treated sympathetic neurons in order to identify candidate genes involved in regulation of primary dendritogenesis.To determine the critical transcriptional window during BMP-induced dendritic growth, morphometric analysis of microtubule-associated protein (MAP-2)-immunopositive processes was used to quantify dendritic growth in cultures exposed to the transcription inhibitor actinomycin-D added at varying times after addition of BMP-7. BMP-7-induced dendritic growth was blocked when transcription was inhibited within the first 24 hr after adding exogenous BMP-7. Thus, total RNA was isolated from sympathetic neurons exposed to three different experimental conditions: (1) no BMP-7 treatment; (2) treatment with BMP-7 for 6 hr; and (3) treatment with BMP-7 for 24 hr. Affymetrix oligonucleotide microarrays were used to identify differential gene expression under these three culture conditions. BMP-7 significantly regulated 56 unique genes at 6 hr and 185 unique genes at 24 hr. Bioinformatic analyses implicate both established and novel genes and signaling pathways in primary dendritogenesis.This study provides a unique dataset that will be useful in generating testable hypotheses regarding transcriptional control of the initial stages of dendritic growth. Since BMPs selectively promote dendritic growth in central neurons as well, these findings may be generally applicable to dendritic growth in other neuronal cell types

Are clinical measures of foot posture and mobility associated with foot kinematics when walking?

Background: There is uncertainty as to which foot posture measures are the most valid in terms of predicting kinematics of the foot. The aim of this study was to investigate the associations of clinical measures of static foot posture and mobility with foot kinematics during barefoot walking. Method: Foot posture and mobility were measured in 97 healthy adults (46 males, 51 females; mean age 24.4 ± 6.2 years). Foot posture was assessed using the 6-item Foot Posture Index (FPI), Arch Index (AI), Normalised Navicular Height (NNHt) and Normalised Dorsal Arch Height (DAH). Foot mobility was evaluated using the Foot Mobility Magnitude (FMM) measure. Following this, a five-segment foot model was used to measure tri-planar motion of the rearfoot, midfoot, medial forefoot, lateral forefoot and hallux. Peak and range of motion variables during load acceptance and midstance/propulsion phases of gait were extracted for all relative segment to segment motion calculations. Hierarchical regression analyses were conducted, adjusting for potential confounding variables. Results: The degree of variance in peak and range of motion kinematic variables that was independently explained by foot posture measures was as follows: FPI 5 to 22 %, NNHt 6 to 20 %, AI 7 to 13 %, DAH 6 to 8 %, and FMM 8 %. The FPI was retained as a significant predictor across the most number of kinematic variables. However, the amount of variance explained by the FPI for individual kinematic variables did not exceed other measures. Overall, static foot posture measures were more strongly associated with kinematic variables than foot mobility measures and explained more variation in peak variables compared to range of motion variables. Conclusions: Foot posture measures can explain only a small amount of variation in foot kinematics. Static foot posture measures, and in particular the FPI, were more strongly associated with foot kinematics compared with foot mobility measures. These findings suggest that foot kinematics cannot be accurately inferred from clinical observations of foot posture alone