Identification and molecular characterisation of Lausanne Institutional Biobank participants with familial hypercholesterolaemia - a proof-of-concept study.

We aimed to identify familial hypercholesterolaemia mutation carriers among participants to the Lausanne Institutional Biobank (BIL). Our experimental workflow was designed as a proof-of-concept demonstration of the resources and services provided by our integrated institutional clinical research support platform. Familial hypercholesterolaemia was used as a model of a relatively common yet often underdiagnosed and inadequately treated Mendelian disease. Clinical and laboratory information was extracted from electronic hospital records. Patients were selected using elevated plasma cholesterol levels (total cholesterol ≥7.5 mM or low-density lipoprotein cholesterol ≥5 mM), premature coronary artery disease status and age (18-60 yr) as main inclusion criteria. LDLR, APOB and PCSK9 were analysed by high-throughput DNA sequencing. The most relevant mutations were confirmed by Sanger sequencing. Of 23 737 patients contacted by the BIL, 17 760 individuals consented to participate and 13 094 wished to be recontacted if there were findings requiring clinical action. Plasma cholesterol records were available for 5111 participants, of whom 94 were selected for genetic screening. Twenty-five of the tested patients presented with premature coronary artery disease while 69 had no such diagnosis. Seven heterozygous carriers of eight rare coding missense variants were identified. Three mutations were pathogenic (APOB p.R3527Q) or likely pathogenic (LDLR p.C27W, LDLR p.P526S) for hypercholesterolaemia, while the others were either benign or of unknown significance. One patient was a double heterozygote for variants APOB p.R3527Q and LDLR p.P526S. This work illustrates how clinical and translational research can benefit from a dedicated platform integrating both a hospital-based biobank and a data support team

Thoracic and Lumbar Vertebral Bone Mineral Density Changes in a Natural Occurring Dog Model of Diffuse Idiopathic Skeletal Hyperostosis

Ankylosing spinal disorders can be associated with alterations in vertebral bone mineral density (BMD). There is however controversy about vertebral BMD in patients wuse idiopathic skeletal hyperostosis (DISH). DISH in Boxer dogs has been considered a natural occurring disease model for DISH in people. The purpose of this study was to compare vertebral BMD between Boxers with and without DISH. Fifty-nine Boxers with (n=30) or without (n=29) DISH that underwent computed tomography were included. Vertebral BMD was calculated for each thoracic and lumbar vertebra by using an earlier reported and validated protocol. For each vertebral body, a region of interest was drawn on the axial computed tomographic images at three separate locations: immediately inferior to the superior end plate, in the middle of the vertebral body, and superior to the inferior end plate. Values from the three axial slices were averaged to give a mean Hounsfield Unit value for each vertebral body. Univariate statistical analysis was performed to identify factors to be included in a multivariate model. The multivariate model including all dogs demonstrated that vertebral DISH status (Coefficient 24.63; 95% CI 16.07 to 33.19; p <0.001), lumbar vertebrae (Coefficient -17.25; 95% CI -23.42 to -11.09; p < 0.01), and to a lesser extent higher age (Coefficient -0.56; 95% CI -1.07 to -0.05; p = 0.03) were significant predictors for vertebral BMD. When the multivariate model was repeated using only dogs with DISH, vertebral DISH status (Coefficient 20.67; 95% CI, 10.98 to 30.37; p < 0.001) and lumbar anatomical region (Coefficient -38.24; 95% CI, -47.75 to -28.73; p < 0.001) were again predictors for vertebral BMD but age was not. The results of this study indicate that DISH can be associated with decreased vertebral BMD. Further studies are necessary to evaluate the clinical importance and pathophysiology of this finding

Primary osteosarcoma of the urinary bladder following cyclophosphamide therapy for systemic lupus erythematosus: a case report

<p>Abstract</p> <p>Introduction</p> <p>The association of systemic lupus erythematosus with malignancies is an uncommon occurrence. We present the case of an osteosarcoma of the urinary bladder developing in a patient with a prolonged history of active systemic lupus erythematosus. This is a previously unreported association. Primary osteosarcoma is an extremely rare disease in the urinary bladder.</p> <p>Case presentation</p> <p>A 24-year-old Caucasian woman with a 13-year history of systemic lupus erythematosus, who had been treated with high dose immunosuppressive agents, presented with pain and hematuria. A deeply invasive high-grade tumor was detected in the urinary bladder and the patient underwent radical surgery. A diagnosis of osteosarcoma was made based on the characteristic histology.</p> <p>Conclusion</p> <p>Predisposing factors for primary sarcomas in the urinary bladder are mostly unknown; however, in our case, long-term administration of immunosuppressive agents, as well as long standing systemic lupus erythematosus, may both be of significance.</p

The relation between bone mineral density, bone turnover markers, and vitamin D status in ankylosing spondylitis patients with active disease: a cross-sectional analysis

Osteoporosis is a well recognized complication of ankylosing spondylitis (AS). This study indicates that increased bone turnover, inflammation, and low vitamin D levels are important in the pathophysiology of AS-related osteoporosis, and that bone turnover markers (BTM) are valuable markers to detect bone loss in AS. The aim of this study was to elucidate the pathophysiology of AS-related osteoporosis by investigating the relation between bone mineral density (BMD), BTM, vitamin D, and clinical assessments of disease activity and physical function, as well as to identify parameters that are related to low BMD (osteopenia or osteoporosis) in AS patients with active disease. One hundred twenty-eight consecutive Dutch AS outpatients were included in this cross-sectional study. Bath AS Disease Activity Index (BASDAI), erythrocyte sedimentation rate (ESR), C-reactive protein, ASAS-endorsed disease activity score (ASDAS), Bath AS Functional Index (BASFI), bone formation markers procollagen type 1 N-terminal peptide (PINP) and osteocalcin (OC), bone resorption marker serum C-telopeptides of type I collagen (sCTX), 25-hydroxyvitamin D (25OHvitD), lumbar spine and hip BMD, and vertebral fractures were assessed. Z-scores of BTM were calculated using matched 10-year cohorts of a Dutch reference group to correct for the normal influence that age and gender have on bone turnover. sCTX Z-score, OC Z-score, BASDAI, age, and gender were independently related to low BMD. In addition, PINP Z-score, ESR, 25OHvitD, age, and gender were independently related to sCTX and/or OC Z-score. This study indicates that increased bone turnover, inflammation, and low vitamin D levels are important in the pathophysiology of AS-related osteoporosis. Furthermore, sCTX and OC Z-scores seem to be valuable markers to detect bone loss in AS patients in daily clinical practice where BMD of the lumbar spine, measured by DXA, may be overestimated due to osteoproliferation in patients with advanced AS

Neither participation nor revolution: the strategy of the Moroccan Jamiat al-Adl wal-Ihsan

Scholars and students of Islamist movements are divided over the issue of Islamists' commitment to democracy and a number of studies have attempted to discover the true nature of Islamist parties. This paper rejects this approach and argues that the behaviour of Islamist parties can be better understood through an analysis of the constraints and opportunities that their surrounding environment provides. Specifically, the paper aims at explaining the choice of the Moroccan Jamiat al-Adl wal-Ihsan neither to participate in institutional politics nor to undertake violent actions to transform the regime. This is done through an examination of its relations with the other political actors. The paper argues that Jamiat al-Adl wal-Ihsan's behaviour is as much the product of rational thinking as it is of ideology and provides evidence to support this claim. Such findings are important not only in the Moroccan context, but contribute to a growing literature claiming that Islamist movements should be treated as rational political actors operating under 'environmental' constraints and opportunities

Annealing study and thermal investigation on bismuth sulfide thin films prepared by chemical bath deposition in basic medium

This is a post-peer-review, pre-copyedit version of an article published in Applied Physics A 124.2 (2018): 166. The final authenticated version is available online at: http://doi.org/10.1007/s00339-018-1584-7Bismuth sulfide thin films were prepared by chemical bath deposition using thiourea as sulfide ion source in basic medium. First, the effects of both the deposition parameters on films growth as well as the annealing effect under argon and sulfur atmosphere on as-deposited thin films were studied. The parameters were found to be influential using the Doehlert matrix experimental design methodology. Ranges for a maximum surface mass of films (3 mg cm-2) were determined. A well crystallized major phase of bismuth sulfide with stoichiometric composition was achieved at 190°C for 3 hours. The prepared thin films were characterized using Grazing Incidence X-ray diffraction (GIXRD), Scanning Electron Microscopy (SEM) and Energy Dispersive X-ray analysis (EDX). Second, the band gap energy value was found to be 1.5 eV. Finally, the thermal properties have been studied for the first time by means of the electropyroelectric (EPE) technique. Indeed, the thermal conductivity varied in the range of 1.20 - 0.60 W m-1 K-1 while the thermal diffusivity values increased in terms of the annealing effect ranging from 1.8 to 3.5 10-7 m2s-1This work was financially supported by the Tunisian Ministry of Higher Education and Scientific Research and by the WINCOST (ENE2016-80788-C5-2-R) project funded by the Spanish Ministry of Economy and Competitivenes

Genetic diversity and taxonomic aspects of wild carrot in France

If in France, genetic resources of cultivated carrot are well studied and preserved, the wild compartment of the species remains unknown and underutilized, while there are many populations of wild carrot on the French territory. Several collecting missions were undertaken from 2009 to 2013 to identify and collect populations, particularly in coastal areas, in continental France and Corsica. More than a hundred populations were collected, with a good distribution throughout the territory, and eleven taxa were identified. The status of these taxa is variable, with some very common and others underrepresented or specific to a given area. Morphological and molecular studies are developed in order to improve the knowledge of taxonomy and diversity. The study conducted with microsatellite markers showed a high genetic diversity at the intra-and inter-populations levels. The overall results show that the Mediterranean coast and Corsica exhibit a particularly high diversity. The work confirms the specific interest of some populations and the taxonomic separation into 2 subgroups carota and gummifer in Daucus carota L. This study will allow developing a strategy for management of genetic resources and their valorisation in breeding

Baseline new bone formation does not predict bone loss in ankylosing spondylitis as assessed by quantitative computed tomography (QCT) - 10-year follow-up

<p>Abstract</p> <p>Background</p> <p>To evaluate the relationship between bone loss and new bone formation in ankylosing spondylitis (AS) using 10-year X-ray, dual-energy x-ray absorptiometry (DXA) and quantitative computed tomography (QCT) follow-up.</p> <p>Methods</p> <p>Fifteen AS patients free from medical conditions and drugs affecting bone metabolism underwent X-ray, DXA and QCT in 1999 and 2009.</p> <p>Results</p> <p>In spine QCT a statistically significant (p = 0,001) decrease of trabecular bone mineral content (BMC) was observed (change ± SD: 18.0 ± 7.3 mg/cm³). In contrast, spine DXA revealed a significant increase of bone mineral density (change ± SD: -0.15 ± 0.14 g/cm²). The mean BMC, both at baseline and follow-up was significantly lower (p = 0.02 and p = 0.005, respectively) in advanced radiological group as compared to early radiological group. However, in multiple regression model after adjustment for baseline BMC, the baseline radiological scoring did not influence the progression of bone loss as assessed with QCT (p = 0.22, p for BMC*X-ray syndesmophyte scoring interaction = 0.65, p for ANOVA-based X-ray syndesmophyte scoring*time interaction = 0.39). Baseline BMC was the only significant determinant of 10-year BMC change, to date the longest QCT follow-up data in AS.</p> <p>Conclusions</p> <p>In AS patients who were not using antiosteoporotic therapy spine trabecular bone density evaluated by QCT decreased over 10-year follow-up and was not related to baseline radiological severity of spine involvement.</p