Fragmenting densely mineralised acellular protrusions from articular calcified cartilage: a role in osteoarthritis?

Fragmenting densely mineralised acellular protrusions from articular calcified cartilage: a role in osteoarthritis? A. Boyde a, G.R. Davis a, D. Mills a, T. Zikmund a, V.L. Adams b, L.R. Ranganath b, N. Jeffery b, J.A. Gallagher b a Dental Physical Sciences, Oral Growth and Development, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK b Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK Objectives High density mineralised protrusions (HDMP) from the tidemark mineralising front into hyaline articular cartilage (HAC) were first discovered in Thoroughbred racehorse fetlock joints and later in Icelandic horse hock joints. If these fragment, they could make a significant contribution to joint destruction in osteoarthritis. We looked for them in human material. Methods Whole femoral heads removed at operation for joint replacement or from dissection room cadavers were studied by MRI DESS at 0.23mm resolution and 26 micron resolution high contrast x-ray microtomography (XMT), then sectioned and embedded in PMMA, and block faces polished and the blocks re-imaged with 6 micron resolution XMT. Tissue mineralisation density was imaged qualitatively by backscattered electron SEM (BSE SEM) at 20kV using uncoated samples at 50Pa chamber pressure to achieve charge neutralisation. HAC histology was studied by BSE SEM after staining block faces with ammonium triiodide solution. Block surfaces were sequentially repolished and restained. Results Figure: 3D rendering of 6 micron voxel resolution XMT data set showing HDMP complex projecting above subchondral bone plate. Human femoral head removed at arthroplasty. We found examples of HDMP in HAC in human hips. Their 3D shapes are complex and may show cutting blade forms. Their mineral content (a) exceeds that of articular calcified cartilage (ACC), otherwise the densest tissue in the joint and (b) is not uniform. The mineral phase morphology frequently shows the agglomeration of many fine particles into larger concretions. Cracks within them are frequent. Dense fragments may be found within damaged HAC. Conclusions HDMP arise via the extrusion of an uncharacterised matrix into clefts in HAC. Little evidence of their existence remains after tissue has been decalcified with usual histological protocols. Their formation may be an extension of a normal but poorly recognised crack self-healing mechanism found in bone and ACC. They are surrounded by HAC, are dense and brittle and show innumerable fault lines within them. We provide evidence that they break in vivo by being able to find matching fragments in HAC. We conclude that these hard and sharp particles contribute to the shredding destruction of HAC. The osteoarthritis research community should be aware of their existence so that the frequency and possible clinical significance can be assessed in the future. Larger HDMP can be detected with the best MRI imaging

Derrick's theorem beyond a potential

Scalar field theories with derivative interactions are known to possess solitonic excitations, but such solitons are generally unsatisfactory because the effective theory fails precisely where nonlinearities responsible for the solitons are important. A new class of theories possessing (internal) galilean invariance can in principle bypass this difficulty. Here, we show that these galileon theories do not possess stable solitonic solutions. As a by-product, we show that no stable solitons exist for a different class of derivatively coupled theories, describing for instance the infrared dynamics of superfluids, fluids, solids and some k-essence models.Comment: 4 page

Early MicroRNA expression profile as a prognostic biomarker for the development of pelvic inflammatory disease in a mouse model of chlamydial genital infection

It is not currently possible to predict the probability of whether a woman with a chlamydial genital infection will develop pelvic inflammatory disease (PID). To determine if specific biomarkers may be associated with distinct chlamydial pathotypes, we utilized two Chlamydia muridarum variants (C. muridarum Var001 [CmVar001] and CmVar004) that differ in their abilities to elicit upper genital tract pathology in a mouse model. CmVar004 has a lower growth rate in vitro and induces pathology in only 20% of C57BL/6 mouse oviducts versus 83.3% of oviducts in CmVar001-infected mice. To determine if chemokine and cytokine production within 24 h of infection is associated with the outcome of pathology, levels of 15 chemokines and cytokines were measured. CmVar004 infection induced significantly lower levels of CXCL1, CXCL2, tumor necrosis factor alpha (TNF-α), and CCL2 in comparison to CmVar001 infection with similar rRNA (rs16) levels for Chlamydiae. A combination of microRNA (miRNA) sequencing and quantitative real-time PCR (qRT-PCR) analysis of 134 inflammation-related miRNAs was performed 24 h postinfection to determine if the chemokine/cytokine responses would also be reflected in miRNA expression profiles. Interestingly, 12 miRNAs (miR-135a-5p, miR298-5p, miR142-3p, miR223-3p, miR299a-3p, miR147-3p, miR105, miR325-3p, miR132-3p, miR142-5p, miR155-5p, and miR-410-3p) were overexpressed during CmVar004 infection compared to CmVar001 infection, inversely correlating with the respective chemokine/cytokine responses. To our knowledge, this is the first report demonstrating that early biomarkers elicited in the host can differentiate between two pathological variants of chlamydiae and be predictive of upper tract disease. © 2014 Yeruva et al

Workshop to identify critical windows of exposure for children's health: cardiovascular and endocrine work group summary.

The work group on cardiovascular and endocrine effects was asked to review the current state of knowledge about children's windows of vulnerability to developmental toxicants and to recommend how that information may be used to improve risk assessment and public health. We considered differences between structural defects, where periods of vulnerability are rather well defined, and functional defects, where periods of vulnerability are quite elusive

Modular and predictable assembly of porous organic molecular crystals

Nanoporous molecular frameworks are important in applications such as separation, storage and catalysis. Empirical rules exist for their assembly but it is still challenging to place and segregate functionality in three-dimensional porous solids in a predictable way. Indeed, recent studies of mixed crystalline frameworks suggest a preference for the statistical distribution of functionalities throughout the pores rather than, for example, the functional group localization found in the reactive sites of enzymes. This is a potential limitation for 'one-pot' chemical syntheses of porous frameworks from simple starting materials. An alternative strategy is to prepare porous solids from synthetically preorganized molecular pores. In principle, functional organic pore modules could be covalently prefabricated and then assembled to produce materials with specific properties. However, this vision of mix-and-match assembly is far from being realized, not least because of the challenge in reliably predicting three-dimensional structures for molecular crystals, which lack the strong directional bonding found in networks. Here we show that highly porous crystalline solids can be produced by mixing different organic cage modules that self-assemble by means of chiral recognition. The structures of the resulting materials can be predicted computationally, allowing in silico materials design strategies. The constituent pore modules are synthesized in high yields on gram scales in a one-step reaction. Assembly of the porous co-crystals is as simple as combining the modules in solution and removing the solvent. In some cases, the chiral recognition between modules can be exploited to produce porous organic nanoparticles. We show that the method is valid for four different cage modules and can in principle be generalized in a computationally predictable manner based on a lock-and-key assembly between modules

The use of self-report questions to examine the prevalence of musculoskeletal problems: a test-retest study.

BACKGROUND: Case definition has long been an issue for comparability of results obtained for musculoskeletal pain prevalence, however the test-retest reliability of questions used to determine joint pain prevalence has not been examined. The objective of this study was to determine question reliability and the impact of question wording, ordering and the time between questions on responses. METHODS: A Computer Assisted Telephone Interviewing (CATI) survey was used to re-administer questions collected as part of a population-based longitudinal cohort study. On two different occasions questions were asked of the same sample of 203 community dwelling respondents (which were initially randomly selected) aged 18 years and over at two time points 14 to 27 days apart (average 15 days). Reliability of the questions was assessed using Cohen's kappa (κ) and intraclass correlation coefficient (ICC) and whether question wording and period effects existed was assessed using a crossover design. RESULTS: The self-reported prevalence of doctor diagnosed arthritis demonstrated excellent reliability (κ = 0.84 and κ = 0.79 for questionnaires 1 and 2 respectively). The reliability of questions relating to musculoskeletal pain and/or stiffness ranged from moderate to excellent for both types of questions, that is, those related to ever having joint pain on most days for at least a month (κ = 0.52 to κ = 0.95) and having pain and/or stiffness on most days for the last month (κ = 0.52 to κ = 0.90). However there was an effect of question wording on the results obtained for hand, foot and back pain and/or stiffness indicating that the area of pain may influence prevalence estimates. CONCLUSIONS: Joint pain and stiffness questions are reliable and can be used to determine prevalence. However, question wording and pain area may impact on estimates with issues such as pain perception and effect on activities playing a possible role in the recall of musculoskeletal pain

Investigating the Therapeutic Potential of a Probiotic in a Rat Model for Infection Following Fracture Fixation

Background: Staphylococcus aureus (S. aureus) is the most common pathogen responsible for osteomyelitis. Objectives: Our objective was to investigate the potential of a probiotic as a treatment for S. aureus-induced infection following fracture fixation in a rat model. Methods: Fifty male Sprague-Dawley rats were assigned to five groups (Control, S. aureus, S. aureus +ceftriaxone, S. aureus + once weekly probiotic, and S. aureus + twice weekly probiotic). Lactobacillus casei subsp. casei (ATCC: 39392) was selected from eight strains of probiotic bacteria with anti-staphylococcal activity. Infection was induced by inoculation with106 colony-forming units (CFU) of S. aureus in a closed femur fracture model stabilized with an intramedullary pin. Three weeks after the surgery, the development of infection and response to the therapy was documented using radiographs, microbiological and histopathological analysis. Results: No bacteria were recovered from rats in the Control group. The analysis of variance revealed a significant difference in the CFU/femur (P < 0.001) and CFU/pin (P = 0.001) across all five treatment groups. When the results were compared, the CFU/femur was significantly lower in the S. aureus + Probiotic twice weekly in comparison with S. aureus (P = 0.008) and the S. aureus + ceftriaxone (P = 0.012) groups. Repeated measure ANOVA to test the radiographic scores during the follow-up time between the intervention groups revealed no significant differences (P = 0.179). Conclusions: Parenteral administration of viable L. casei inhibits S. aureus-induced infection as shown by the bacteriologic analysis, but makes no difference to the radiological union rates. This could be the first step towards developing an effective, biologic adjunctive therapy for the management of osteomyelitis following fracture fixation

Letter processing and font information during reading: beyond distinctiveness, where vision meets design

Letter identification is a critical front end of the reading process. In general, conceptualizations of the identification process have emphasized arbitrary sets of distinctive features. However, a richer view of letter processing incorporates principles from the field of type design, including an emphasis on uniformities across letters within a font. The importance of uniformities is supported by a small body of research indicating that consistency of font increases letter identification efficiency. We review design concepts and the relevant literature, with the goal of stimulating further thinking about letter processing during reading

Escherichia coli induces apoptosis and proliferation of mammary cells

Mammary cell apoptosis and proliferation were assessed after injection of Escherichia coli into the left mammary quarters of six cows. Bacteriological analysis of foremilk samples revealed coliform infection in the injected quarters of four cows. Milk somatic cell counts increased in these quarters and peaked at 24 h after bacterial injection. Body temperature also increased, peaking at 12 h postinjection, The number of apoptotic cells was significantly higher in the mastitic tissue than in the uninfected control. Expression of Bax and interleukin-1 beta converting enzyme increased in the mastitic tissue at 24 h and 72 h postinfection, whereas Bcl-2 expression decreased at 24 h but did not differ significantly from the control at 72 h postinfection, Induction of matrix metalloproteinase-g, stromelysin-1 and urokinase-type plasminogen activator was also observed in the mastitic tissue. Moreover, cell proliferation increased in the infected tissue, These results demonstrate that Escherichia coli-induced mastitis promotes apoptosis and cell proliferation