Osteoarthritis affects the whole joint structure with progressive changes in cartilage, menisci, ligaments and subchondral bone, and synovial inflammation. Biomarkers are being developed to quantify ...joint remodelling and disease progression. This article was prepared following a working meeting of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis convened to discuss the value of biochemical markers of matrix metabolism in drug development in osteoarthritis. The best candidates are generally molecules or molecular fragments present in cartilage, bone or synovium and may be specific to one type of joint tissue or common to them all. Many currently investigated biomarkers are associated with collagen metabolism in cartilage or bone, or aggrecan metabolism in cartilage. Other biomarkers are related to non-collagenous proteins, inflammation and/or fibrosis. Biomarkers in osteoarthritis can be categorised using the burden of disease, investigative, prognostic, efficacy of intervention, diagnostic and safety classification. There are a number of promising candidates, notably urinary C-terminal telopeptide of collagen type II and serum cartilage oligomeric protein, although none is sufficiently discriminating to differentiate between individual patients and controls (diagnostic) or between patients with different disease severities (burden of disease), predict prognosis in individuals with or without osteoarthritis (prognostic) or perform so consistently that it could function as a surrogate outcome in clinical trials (efficacy of intervention). Future avenues for research include exploration of underlying mechanisms of disease and development of new biomarkers; technological development; the 'omics' (genomics, metabolomics, proteomics and lipidomics); design of aggregate scores combining a panel of biomarkers and/or imaging markers into single diagnostic algorithms; and investigation into the relationship between biomarkers and prognosis.
Synonymous codon replacement can change protein structure and function, indicating that protein structure depends on DNA sequence. During heterologous protein expression, low expression or formation ...of insoluble aggregates may be attributable to differences in synonymous codon usage between expression and natural hosts. This discordance may be particularly important during translation of the domain boundaries (link/end segments) that separate elements of higher ordered structure. Within such regions, ribosomal progression slows as the ribosome encounters clusters of infrequently used codons that preferentially encode a subset of amino acids. To replicate the modulation of such localized translation rates during heterologous expression, we used known relationships between codon usage frequencies and secondary protein structure to develop an algorithm ("codon harmonization") for identifying regions of slowly translated mRNA that are putatively associated with link/end segments. It then recommends synonymous replacement codons having usage frequencies in the heterologous expression host that are less than or equal to the usage frequencies of native codons in the native expression host. For protein regions other than these putative link/end segments, it recommends synonymous substitutions with codons having usage frequencies matched as nearly as possible to the native expression system. Previous application of this algorithm facilitated E. coli expression, manufacture and testing of two Plasmodium falciparum vaccine candidates. Here we describe the algorithm in detail and apply it to E. coli expression of three additional P. falciparum proteins. Expression of the "recoded" genes exceeded that of the native genes by 4- to 1,000-fold, representing levels suitable for vaccine manufacture. The proteins were soluble and reacted with a variety of functional conformation-specific mAbs suggesting that they were folded properly and had assumed native conformation. Codon harmonization may further provide a general strategy for improving the expression of soluble functional proteins during heterologous expression in hosts other than E. coli.
Wetlands constructed primarily for the treatment of wastewaters have been shown to have a role in enhancing biodiversity. However, while most biodiversity studies of constructed wetlands focus on the ...larger, more iconic animal groups, there is a paucity of information on the aerial phases of wetland invertebrate species associated with constructed wetlands. This study compares Sciomyzidae (Diptera) assemblages, established indicators of wetland dipteran communities, in Irish constructed and natural wetlands, in addition to determining the impacts of water quality and surrounding habitats on Sciomyzidae community structure. Natural wetlands had significantly greater species richness, abundances and diversity (measured as Shannon’s entropy) of sciomyzid flies than constructed wetlands. Nevertheless, although concentrations of nitrogen and phosphorus in waters were significantly greater in constructed wetlands, seven of the eight constructed wetlands examined hosted species of Sciomyzidae listed as scarce or threatened in Britain. In addition, sciomyzid species richness increased as areas of semi-natural habitat immediately surrounding constructed and natural wetlands increased. Composition of Sciomyzidae assembalges in both natural and constructed wetlands were analysed. The results of this study demonstrate that constructed wetlands can be important contributors to biodiversity particularly in the context of current losses of natural wetlands worldwide. The importance of habitats immediately surrounding constructed wetlands also highlights the need for relatively simple design recommendations (e.g. wet grassland creation or judicious planting of wetland trees) that could enhance the biodiversity of existing and future constructed wetlands.
Summary Vertebral fractures are a major adverse consequence of osteoporosis. In a large placebo-controlled trial in postmenopausal women with osteoporosis, strontium ranelate reduced vertebral ...fracture risk by 33% over 4 years, confirming the role of strontium ranelate as an effective long-term treatment in osteoporosis. Introduction Osteoporotic vertebral fractures are associated with increased mortality, morbidity, and loss of quality-of-life (QoL). Strontium ranelate (2 g/day) was shown to prevent bone loss, increase bone strength, and reduce vertebral and peripheral fractures. The preplanned aim of this study was to evaluate long-term efficacy and safety of strontium ranelate. Methods A total of 1,649 postmenopausal osteoporotic women were randomized to strontium ranelate or placebo for 4 years, followed by a 1-year treatment-switch period for half of the patients. Primary efficacy criterion was incidence of patients with new vertebral fractures over 4 years. Lumbar bone mineral density (BMD) and QoL were also evaluated. Results Over 4 years, risk of vertebral fracture was reduced by 33% with strontium ranelate (risk reduction = 0.67, p < 0.001). Among patients with two or more prevalent vertebral fractures, risk reduction was 36% (p < 0.001). QoL, assessed by the QUALIOST®, was significantly better (p = 0.025), and patients without back pain were greater (p = 0.005) with strontium ranelate than placebo over 4 years. Lumbar BMD increased over 5 years in patients who continued with strontium ranelate, while it decreased in patients who switched to placebo. Emergent adverse events were similar between groups. Conclusion In this 4- and 5-year study, strontium ranelate is an effective and safe treatment for long-term treatment of osteoporosis in postmenopausal women.
Individual preference for morning or evening activities (chronotype), affect, hardiness, and talent are associated with a variety of performance outcomes. This longitudinal study was designed to ...investigate the degree to which these variables are associated with academic, physical, and military performance. Self-reported measures of chronotype, affect, and hardiness were collected from 1149 cadets from the Class of 2016 upon entry to the United States Military Academy. Talent, a composite of academic, leadership, and physical fitness scores were drawn from cadet records. Academic, military, and physical performance measures were collected at graduation 4 years later. The results indicated that a morning orientation was associated with better physical and military performance. Higher talent scores, as well as lower levels of negative affect, were associated with better performance across all three performance measures. Hardiness was only associated with military performance. The findings suggest that a morning orientation and less negative affect may result in better performance overall within a challenging and structured military environment. Future studies of chronotype shifts may provide further insight into associated performance benefits.
The uptake of sodium selenite (Se(IV)) and sodium selenate (Se(VI)) from aqueous medium by
L. and the influence of different Se concentrations on its growth, morphological and ultrastructural ...characteristics were studied.
was grown at different concentrations (1, 3, 5 and 10 mg L
) of Se(IV) and Se(IV). The Se(IV) concentration in the plant tissue ranged between 77.7 (± 4.3) to 453 (± 0) mg kg
DW. The Se(VI) concentration in plant tissues ranged between 117 (± 11) to 417 (± 2) mg kg
DW. The highest bioconcentration factor for Se(VI) was 127 (± 7) at 3 mg/L, with a Se removal efficiency of 44%. For Se(IV), the highest bioconcentration factor was 77.7 (± 4.3) at 1 mg L
, which had a Se removal efficiency of 23%. Growth of
was suppressed at 10 mg L
Se in both forms. The addition of Se promoted the formation of starch granules in
which occupied a chloroplast area of 74% for Se(IV) and 77% for Se(VI). The efficient uptake of both Se forms by
indicates the potential application of this species for phytoremediation of Se laden wastewaters and its use as an alternative feedstock in biofuel production.
Introduction L’effet des antipsychotiques de seconde génération sur les concentrations plasmatiques d’adiponectine est mal connu. Cette étude ouverte prospective monocentrique compare les effets de ...l’olanzapine (OLA) et de la rispéridone (RIS) sur les taux d’adiponectine et divers paramètres métaboliques. Patients et Méthodes 113 patients schizophrènes (65% hommes, 32,3 années), naïfs de tout traitement par antipsychotiques, ont reçu soit de la RIS (n = 54 ; dose moyenne 4,35 mg/jour), soit de l’OLA (n = 59 ; dose moyenne 17,6 mg/ jour) et été suivis 12 semaines avec mesure du poids, des paramètres métaboliques à jeun (glucose, insuline, lipides) et des concentrations plasmatiques d’adiponectine. Résultats L’indice de masse corporelle (IMC : 23,7 vs 23,2 kg/m2 ), la prévalence du syndrome métabolique (SM selon le NCEP-ATPIII : 7,4 vs 8,0%), la glycémie à jeun (86,8 vs 86,9 mg/dl), l’insulinémie (11,4 vs 12,0 mIU/ml) et les taux d’adiponectine (10 154 vs 11 280 ng/ml) sont comparables à l’inclusion dans les groupes RIS et OLA, respectivement. La prise de poids est plus importante sous OLA que sous RIS (après 12 semaines : +7 kg vs +3,1 kg, p < 0,05). Des différences modérées, quoique non significatives, ont été observées dans la progression du SM (de 7,4% à 20,4% sous RIS vs de 8,5% à 33,9% sous OLA), l’augmentation de la glycémie (de 86,8 à 88,0 mg/dl sous RIS vs de 86,9 à 89,2 mg/dl sous OLA) et les variations de l’insulinémie (de 11,4 à 10,8 mIU/ml sous RIS vs de 12,0 à 14,0 mIU/ml sous OLA). Une interaction « traitement X temps » (p = 0,0002) est observée en ce qui concerne les taux d’adiponectine, avec une augmentation dans le groupe RIS (de 10 154 à 11 124 ng/ml) contrastant avec une diminution dans le groupe OLA (de 11 280 à 8 988 ng/ml). Cet effet est indépendant des modifications de l’IMC et de la présence/absence d’un SM. Discussion L’évolution différente des taux d’adiponectine suggère des effets spécifiques des deux antipsychotiques sur le tissu adipeux, ce qui pourrait contribuer au risque métabolique plus marqué en clinique de OLA par comparaison à RIS. Conclusion Lors de l’initiation d’un traitement par antipsychotiques de seconde génération chez des patients schizophrènes, l’olanzapine, contrairement à la rispéridone, diminue les taux d’adiponectine et ce, indépendamment des variations de l’IMC.
Lead and zinc mining was booming in the early 1900s in and near Joplin, Missouri; a town within the Tri-State Mining District, USA. After the ore became depleted, mining companies moved out, leaving ...a profoundly disturbed land. Presently, over 90% of the land has been remediated. We collected sediment samples along two creeks flowing through the historically contaminated area that have been identified as major contributors of metals to downstream reservoirs, Center Creek (14 samples) and Turkey Creek (30 samples). Sediment metal content was determined by aqua regia extraction, the potentially bioavailable fraction by 0.11 M acetic acid extraction, and toxicity by ΣPEC-QCd,Pb,Zn. Zinc and lead content in sediments were high in both creeks notwithstanding remediation actions; e.g., median concentrations of 521 mg/kg Pb and 5425 mg/kg Zn in Center Creek, corresponding to 19 and 52 times the background concentration. The metals’ distribution followed no discernible pattern downstream. The potentially bioavailable fraction varied between 0.36% (Pb, Center Creek) and 4.96% (Zn, Turkey Creek). High toxicity was found in 40% of the samples in Turkey Creek and 78.5% of the samples in Center Creek. While this level of toxicity would likely affect aquatic organisms, its limited mobility under alkaline conditions suggests a lesser threat to humans. On the other hand, this high toxicity will likely persist in sediments for at least a few decades, based on their high metal content and low mobility.
Sclerostin inhibits osteoblast differentiation and bone formation. If aberrant sclerostin action is involved in less efficient bone acquisition in men with idiopathic low bone mass, this might be ...reflected in higher serum sclerostin levels.
In 116 men with idiopathic osteoporosis (≤65 years old), 40 of their sons and healthy controls, areal bone parameters were measured using dual-energy X-ray absorptiometry, and volumetric and geometric bone parameters were measured using peripheral quantitative computed tomography. Serum analytes were measured using immunoassays and estradiol (E2) levels using liquid chromatography-tandem mass spectrometry.
Men with idiopathic low bone mass had lower levels of sclerostin than the controls (0.54±0.17 vs 0.66±0.23 ng/ml; P<0.001). In both groups, sclerostin levels were strongly associated with age; when adjusting for age, no associations with anthropometrics were observed (P>0.14). In multivariate analyses, sclerostin levels displayed a positive association with whole-body bone mineral content (BMC) and areal BMD (aBMD), as well as with trabecular and cortical volumetric bone mineral density (vBMD) at the tibia in the probands. No clear associations were observed in the control group, neither were sclerostin levels associated with BMC at the radius or lumbar spine (all P>0.11). Testosterone, but not E2, was inversely related to sclerostin levels in the probands. No difference in sclerostin levels was found in their sons when compared with their controls.
Lower rather than higher serum sclerostin levels in the probands with idiopathic low bone mass suggest that aberrant sclerostin secretion is not involved in the pathogenesis of low bone mass in these subjects.
The recognition of aquatic organisms plays a crucial role in the monitoring of the pollution and for the adoption of rapid preventive actions. A compact microscopic optical imaging system is proposed ...in order to acquire and treat the multibands fluorescence of several pigments in phytoplankton organisms. Two algorithms for automatic recognition of phytoplankton were proposed with a minimum number of calibration parameters. The first algorithm provides a morphological recognition based on “watershed” segmentation and Fourier descriptors, while the second one builds fluorescence pigment images by “k-means” partition of intensity ratios. The operation of these algorithms was illustrated by the study of two different organisms: a cyanobacteria (
Dolichospermum
sp.) and an alga (
Cladophora
sp.). The family and the genus of these organisms were then classified into a database which is independent of the size, the orientation and the position of the specimens in the images.
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