Receipt, 9 December 1871

https://egrove.olemiss.edu/aldrichdocs/1069/thumbnail.jp

Direct and indirect orthotic management of medial compartment osteoarthritis of the knee

Osteoarthritis (OA) is a painful condition and affects approximately 80% of individuals by the age of 55 [1], with knee OA occurring two times more frequently than OA of the hand or hip [2].The condition is more prevalent in the medial compartment and restricts the daily lives of individuals due to pain and a lack of functional independence. Patients with medial compartment osteoarthritis often have a varus alignment, with the mechanical axis and load bearing passing through this compartment with a greater adduction moment leading to greater pain and progression of osteoarthritis [3]. Surgery for the condition is possible although in some cases, particularly younger patients or those not yet requiring surgery, clinical management remains a challenge. Before surgery is considered, however, conservative management is advocated, though no one treatment has been shown to be most effective, and there are few quality biomechanical or clinical studies. Of the conservative approaches the principal orthotic treatments are valgus knee braces and laterally wedged foot inlays. Studies of knee valgus bracing have consistently demonstrated an associated decreased pain and improved function [4], and greater confidence [5]. A laterally wedged foot inlay has a thicker lateral border and applies a valgus moment to the heel. It is theorised that by changing the position of the ankle and subtalar joints during weight-bearing [6] the lateral wedges may apply a valgus moment across the knee as well as the rearfoot, with the assumed reduction on load in the medial knee compartment [7]. However, there has been no study to directly compare these orthotic treatments in the same study. The aim of this research is to investigate the efficacy of valgus knee braces and laterally wedged foot inlays in reducing the varus knee moment

The Role of Connexins in Wound Healing and Repair: Novel Therapeutic Approaches

Gap junctions are intercellular proteins responsible for mediating both electrical and biochemical coupling through the exchange of ions, second messengers and small metabolites. They consist of two connexons, with (one) connexon supplied by each cell. A connexon is a hexamer of connexins and currently more than 20 connexin isoforms have been described in the literature thus far. Connexins have a short half-life, and therefore gap junction remodeling constantly occurs with a high turnover rate. Post-translational modification, such as phosphorylation, can modify their channel activities. In this article, the roles of connexins in wound healing and repair are reviewed. Novel strategies for modulating the function or expression of connexins, such as the use of antisense technology, synthetic mimetic peptides and bioactive materials for the treatment of skin wounds, diabetic and pressure ulcers as well as cornea wounds, are considered.GT received a BBSRC Doctoral Training Award at the University of Cambridge and thanks The Croucher Foundation for supporting his clinical assistant professorship. YC is supported by the ESRC for her research at the University of Cambridge

Electrophysiological Mechanisms of Brugada Syndrome: Insights from Pre-clinical and Clinical Studies.

This is the final version of the article. It first appeared from Frontiers via https://doi.org/10.3389/fphys.2016.00467Brugada syndrome (BrS), is a primary electrical disorder predisposing affected individuals to sudden cardiac death via the development of ventricular tachycardia and fibrillation (VT/VF). Originally, BrS was linked to mutations in the SCN5A, which encodes for the cardiac Na+ channel. To date, variants in 19 genes have been implicated in this condition, with 11, 5, 3, and 1 genes affecting the Na+, K+, Ca2+, and funny currents, respectively. Diagnosis of BrS is based on ECG criteria of coved- or saddle-shaped ST segment elevation and/or T-wave inversion with or without drug challenge. Three hypotheses based on abnormal depolarization, abnormal repolarization, and current-load-mismatch have been put forward to explain the electrophysiological mechanisms responsible for BrS. Evidence from computational modeling, pre-clinical, and clinical studies illustrates that molecular abnormalities found in BrS lead to alterations in excitation wavelength (λ), which ultimately elevates arrhythmic risk. A major challenge for clinicians in managing this condition is the difficulty in predicting the subset of patients who will suffer from life-threatening VT/VF. Several repolarization risk markers have been used thus far, but these neglect the contributions of conduction abnormalities in the form of slowing and dispersion. Indices incorporating both repolarization and conduction and based on the concept of λ have recently been proposed. These may have better predictive values than the existing markers.GT received a BBSRC Doctoral CASE Studentship at the University of Cambridge and thanks the Croucher Foundation of Hong Kong for the support of his Clinical Assistant Professorship. YC is supported by the ESRC for her Ph.D. studies at the University of Cambridge. BY received funding from the Research Grant Council of Hong Kong for his research

Animal models of atherosclerosis.

Atherosclerosis is a significant cause of morbidity and mortality globally. Many animal models have been developed to study atherosclerosis, and permit experimental conditions, diet and environmental risk factors to be carefully controlled. Pathophysiological changes can be produced using genetic or pharmacological means to study the harmful consequences of different interventions. Experiments using such models have elucidated its molecular and pathophysiological mechanisms, and provided platforms for pharmacological development. Different models have their own advantages and disadvantages, and can be used to answer different research questions. In the present review article, different species of atherosclerosis models are outlined, with discussions on the practicality of their use for experimentation.GT was supported by a BBSRC Doctoral Training Award and thanks the Croucher Foundation of Hong Kong for the generous support of his clinical assistant professorship. YC is supported by the ESRC

Neighbourhood deprivation and access to early intervention and support for families of children with intellectual and developmental disabilities

Ensuring families of children with intellectual and/or developmental disabilities (e.g., developmental delay, intellectual disability, autism) can access early intervention and support is important. Current research indicates there are family‐level socioeconomic disparities of access to early intervention and support, however, there is limited evidence on the relationship between neighbourhood‐level socioeconomic deprivation and access to support. Therefore, the aim of this study was to examine the relationship between neighbourhood deprivation and families' access to and unmet need for early intervention and support. We collected cross‐sectional data using a survey of 673 parental caregivers of young children with suspected or diagnosed intellectual and/or developmental disabilities in the UK. Multiple regression models were fitted for three early intervention and support outcome variables: access to early intervention; access to services across education, health, social care, and other sectors; and unmet need for services. Each regression model included a neighbourhood deprivation variable based on the Index of Multiple Deprivation and five control variables: family‐level economic deprivation, country, caregivers' educational level, developmental disability diagnosis, and informal support sources. Neighbourhood deprivation was a significant independent predictor of access to services, but neighbourhood deprivation was not a significant predictor of access to early intervention or unmet need for services. Families living in the most deprived neighbourhoods accessed fewer services than other families. Socioeconomic disparities of access to early intervention and support, at both a neighbourhood and family level, exist for families of young children with suspected or diagnosed intellectual and/or developmental disabilities in the UK. Future research should focus on policy and other interventions aimed at addressing socioeconomic disparities at the neighbourhood and family level, to ensure equitable access to early intervention and support

Animal models of atherosclerosis.

Atherosclerosis is a significant cause of morbidity and mortality globally. Many animal models have been developed to study atherosclerosis, and permit experimental conditions, diet and environmental risk factors to be carefully controlled. Pathophysiological changes can be produced using genetic or pharmacological means to study the harmful consequences of different interventions. Experiments using such models have elucidated its molecular and pathophysiological mechanisms, and provided platforms for pharmacological development. Different models have their own advantages and disadvantages, and can be used to answer different research questions. In the present review article, different species of atherosclerosis models are outlined, with discussions on the practicality of their use for experimentation.GT was supported by a BBSRC Doctoral Training Award and thanks the Croucher Foundation of Hong Kong for the generous support of his clinical assistant professorship. YC is supported by the ESRC

Word processing as an act of collaboration: description of a media artwork

As described in an earlier contribution to the JMP (Photography as an act of collaboration - Vol 15, Issue 3), my research explores the possibilities and implications of treating the camera and the photographic process as an active collaborator in the creation of scenes, events and ‘moments’ that did not exist until brought into being by the act of photographing them. The media artwork described here is the result of an experiment to explore the possibility of establishing a similarly collaborative relationship with the ‘agency’ of word-processing software that I have endeavoured to establish with the medium of photography. Despite comprehensively stripping the original text of both sense and sequence, the resulting text not only retains an uncanny degree of consistency with both the style and meaning of the original, but also reveals insights which had been only latent within the original. The result would appear to reinforce the findings of my previous research in photographic practice: that, by giving up conscious, rational control over the means of expression, we can (sometimes) create the conditions necessary for a constructive and often illuminating dialogue with the deus ex machina

Functional polymorphism in ABCA1 influences age of symptom onset in coronary artery disease patients

ATP-binding-cassette-transporter-A1 (ABCA1) plays a pivotal role in intracellular cholesterol removal, exerting a protective effect against atherosclerosis. ABCA1 gene severe mutations underlie Tangier disease, a rare Mendelian disorder that can lead to premature coronary artery disease (CAD), with age of CAD onset being two decades earlier in mutant homozygotes and one decade earlier in heterozygotes than in mutation non-carriers. It is unknown whether common polymorphisms in ABCA1 could influence age of symptom onset of CAD in the general population. We examined common promoter and non-synonymous coding polymorphisms in relation to age of symptom onset in a group of CAD patients (n = 1164), and also carried out in vitro assays to test effects of the promoter variations on ABCA1 promoter transcriptional activity and effects of the coding variations on ABCA1 function in mediating cellular cholesterol efflux. Age of symptom onset was found to be associated with the promoter − 407G > C polymorphism, being 2.82 years higher in C allele homozygotes than in G allele homozygotes and intermediate in heterozygotes (61.54, 59.79 and 58.72 years, respectively; P = 0.002). In agreement, patients carrying ABCA1 haplotypes containing the −407C allele had higher age of symptom onset. Patients of the G/G or G/C genotype of the −407G > C polymorphism had significant coronary artery stenosis (>75%) at a younger age than those of the C/C genotype (P = 0.003). Reporter gene assays showed that ABCA1 haplotypes bearing the −407C allele had higher promoter activity than haplotypes with the −407G allele. Functional analyses of the coding polymorphisms showed an effect of the V825I substitution on ABCA1 function, with the 825I variant having higher activity in mediating cholesterol efflux than the wild-type (825V). A trend towards higher symptom onset age in 825I allele carriers was observed. The data indicate an influence of common ABCA1 functional polymorphisms on age of symptom onset in CAD patient