The role of influenza neuraminidase transmembrane domain on budding and virus morphology

Influenza A virus neuraminidase (NA), a type II transmembrane glycoprotein plays a role in the cleavage of sialic acids and facilitating the release of mature virions from the surface of infected cells. NA has also previously been shown to play a role in virion formation during influenza A virus budding, although the exact mechanisms by which NA contributes to influenza virion formation and morphology is currently unknown. Previous research has shown that mutations within the transmembrane domain (TMD) of NA can result in alteration in virion morphology, particularly in the production of filament like influenza virions. In this research project we examined if the TMD does indeed play a role in influenza virus budding and morphology. We utilised both full and partial mutations of the TMD of NA from A/WSN/33, a primarily spherical lab adapted influenza strain, with the TMD of a primarily filamentous strain A/California/09. To evaluate the effects of TMD on the morphology of a primarily spherical strain with that of filamentous strain. This study used a transfection based virus like particle (VLP) system to examine the effects of TMD alterations on morphology, utilising various biochemical and microscopy methods. Our findings show that as previously indicated mutations within the TMD do result in alterations to virion morphology, as well as showing that despite previous theories both NA and NA’s TMD may play a more active role in in budding and morphology than previously though

Revisiting the pathogenesis of podagra: why does gout target the foot?

This invited paper provides a summary of a keynote lecture delivered at the 2011 Australasian Podiatry Conference. Gout is the most prevalent inflammatory arthropathy. It displays a striking predilection to affect the first metatarsophalangeal joint as well as joints within the mid-foot and ankle. A number of factors are known to reduce urate solubility and enhance nucleation of monosodium urate crystals including decreased temperature, lower pH and physical shock, all of which may be particularly relevant to crystal deposition in the foot. An association has also been proposed between monosodium urate crystal deposition and osteoarthritis, which also targets the first metatarsophalangeal joint. Cadaveric, clinical and radiographic studies indicate that monosodium urate crystals more readily deposit in osteoarthritic cartilage. Transient intra-articular hyperuricaemia and precipitation of monosodium urate crystals is thought to follow overnight resolution of synovial effusion within the osteoarthritic first metatarsophalangeal joint. The proclivity of gout for the first metatarsophalangeal joint is likely to be multi-factorial in origin, arising from the unique combination of the susceptibility of the joint to osteoarthritis and other determinants of urate solubility and crystal nucleation such as temperature and minor physical trauma which are particularly relevant to the foot

Why does gout target the foot? The pathogenesis of podagra

This invited paper provides a summary of a keynote lecture delivered at the 2011 Australasian Podiatry Conference. Gout is the most prevalent inflammatory arthropathy. It displays a striking predilection to affect the first metatarsophalangeal joint as well as joints within the mid-foot and ankle. A number of factors are known to reduce urate solubility and enhance nucleation of monosodium urate crystals including decreased temperature, lower pH and physical shock, all of which may be particularly relevant to crystal deposition in the foot. An association has also been proposed between monosodium urate crystal deposition and osteoarthritis, which also targets the first metatarsophalangeal joint. Cadaveric, clinical and radiographic studies indicate that monosodium urate crystals more readily deposit in osteoarthritic cartilage. Transient intra-articular hyperuricaemia and precipitation of monosodium urate crystals is thought to follow overnight resolution of synovial effusion within the osteoarthritic first metatarsophalangeal joint. The proclivity of gout for the first metatarsophalangeal joint is likely to be multi-factorial in origin, arising from the unique combination of the susceptibility of the joint to osteoarthritis and other determinants of urate solubility and crystal nucleation such as temperature and minor physical trauma which are particularly relevant to the foot

Merrimack College: Genesis and Growth, 1947-1972

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Structural characteristics associated with radiographic severity of first metatarsophalangeal joint osteoarthritis

ObjectiveTo determine whether foot structure varies according to the presence and radiographic severity of first metatarsophalangeal joint osteoarthritis (first MTPJ OA).MethodsWeight-bearing dorso-plantar and lateral radiographs were obtained for the symptomatic foot of 185 participants (105 females, aged 22 to 85 years) with clinically diagnosed first MTPJ OA. A validated atlas was used to classify participants as having radiographic first MTPJ OA and to stratified into three categories of severity (none/mild, moderate, severe). Bone length, width and angular measures of the forefoot and medial arch were performed on radiographs, and differences between categories were compared using univariate general linear models, adjusting for confounders.ResultsOne hundred and fifty participants were categorised as having radiographic first MTPJ OA, and participants were further stratified into none/mild (n = 35), moderate (n = 69) or severe (n = 81) OA categories. Participants with radiographically defined first MTPJ OA displayed a greater hallux abductus interphalangeal angle. Increasing radiographic severity of first MTPJ OA was associated with a larger hallux abductus interphalangeal angle, wider first metatarsal and proximal phalanx and smaller intermetatarsal angle. No differences in medial arch measurements were observed between the categories.ConclusionFirst ray alignment and morphology differ according to the presence and severity of first MTPJ OA. Prospective studies are required to determine whether the observed differences are a cause or consequence of OA

GPs' attitudes, beliefs and behaviours regarding exercise for chronic knee pain: a questionnaire survey

OBJECTIVES:The aim of this study was to investigate general practitioners' (GPs) attitudes, beliefs and behaviours regarding the use of exercise for patients with chronic knee pain (CKP) attributable to osteoarthritis.SETTING: Primary care GPs in the UK.PARTICIPANTS: 5000 GPs, randomly selected from Binley's database, were mailed a cross-sectional questionnaire survey.OUTCOME MEASURES: GPs' attitudes and beliefs were investigated using attitude statements, and reported behaviours were identified using vignette-based questions. GPs were invited to report barriers experienced when initiating exercise with patients with CKP RESULTS: 835 (17%) GPs responded. Overall, GPs were positive about general exercise for CKP. 729 (87%) reported using exercise, of which, 538 (74%) reported that they would use both general and local (lower limb) exercises. However, only 92 (11% of all responding) GPs reported initiating exercise in ways aligning with best-evidence recommendations. 815 (98%) GPs reported barriers in using exercise for patients with CKP, most commonly, insufficient time in consultations (n=419; 51%) and insufficient expertise (n=337; 41%). CONCLUSIONS: While GPs' attitudes and beliefs regarding exercise for CKP were generally positive, initiation of exercise was often poorly aligned with current recommendations, and barriers and uncertainties were reported. GPs' use of exercise may be improved by addressing the key barriers of time and expertise, by developing a pragmatic approach that supports GPs to initiate individualised exercise, and/or by other professionals taking on this role

Effectiveness of Foot Orthoses Versus Rocker-Sole Footwear for First Metatarsophalangeal Joint Osteoarthritis: Randomized Trial

Objective To compare the effectiveness of prefabricated foot orthoses to rocker-sole footwear in reducing foot pain in people with first metatarsophalangeal joint osteoarthritis (1(st) MTPJ OA). Design Participants (n=102) with 1(st) MTPJ OA were randomly allocated to receive individualized, prefabricated foot orthoses or rocker-sole footwear. The primary outcome measure was the pain subscale on the Foot Health Status Questionnaire (FHSQ) at 12 weeks. Secondary outcome measures included the function, footwear and general foot health subscales of the FHSQ, the Foot Function Index, severity of pain and stiffness at the 1(st) MTPJ, perception of global improvement, general health status, use of rescue medication and co-interventions to relieve pain, physical activity and the frequency of self-reported adverse events. Results The FHSQ pain subscale scores improved in both groups, but no statistically significant difference between the groups was observed (adjusted mean difference 2.05 points, 95%CI -3.61 to 7.71, p=0.477). However, the footwear group exhibited lower adherence (mean [SD] total hours worn 287 [193] versus 448 [234], p<0.001), were less likely to report global improvement in symptoms (39 versus 62%, relative risk [RR] 0.63, 95% confidence interval [CI] 0.41 to 0.99, p=0.043), and were more likely to experience adverse events (39 versus 16%, RR 2.47, 95%CI 1.12 to 5.44, p=0.024) compared to the orthoses group. Conclusion Prefabricated foot orthoses and rocker-sole footwear are similarly effective at reducing foot pain in people with 1(st) MTPJ OA. However, prefabricated foot orthoses may be the intervention of choice due to greater adherence and fewer associated adverse events. This article is protected by copyright. All rights reserved

Effects of Shoe-Stiffening Inserts on Lower Limb Kinematics in Individuals with First Metatarsophalangeal Joint Osteoarthritis.

OBJECTIVE: To examine the effects of shoe-stiffening inserts on lower limb kinematics in individuals with first metatarsophalangeal (MTP) joint osteoarthritis (OA). METHODS: Forty-eight individuals with radiographically confirmed first MTP joint OA (24 males and 24 females; mean age 57.8 years, standard deviation 10.5) were randomized to receive either shoe-stiffening inserts or sham inserts, and underwent gait analysis during level walking using a 10-camera infrared Vicon motion analysis system. Sagittal plane kinematics of the first MTP, ankle, knee, and hip joints were compared between the shoe only (control) and insert conditions in both groups (within-groups) and between both insert conditions (between-groups). RESULTS: Compared to the shoe only condition, the sham insert reduced knee flexion and total excursion, and the shoe-stiffening insert reduced first MTP joint maximum dorsiflexion and ankle joint maximum plantarflexion, and increased maximum knee flexion and total excursion. Between-group comparisons indicated that the shoe-stiffening inserts significantly decreased first MTP joint maximum dorsiflexion, ankle joint maximum plantarflexion and total excursion, and increased knee joint maximum flexion and total excursion compared to the sham inserts. CONCLUSION: Carbon fibre shoe-stiffening inserts significantly alter sagittal plane lower limb joint kinematics during walking, particularly first MTP joint maximum dorsiflexion. These findings provide insights into the mechanisms that may be responsible for their clinical effectiveness in the treatment of first MTP joint OA, and potentially explain changes in symptoms in other lower limb joints