The mechanical properties of fresh versus fresh/frozen and preserved (Thiel and Formalin) long head of biceps tendons : a cadaveric investigation

Human cadaveric specimens commonly serve as mechanical models and as biological tissue donors in basic biomechanical research. Although these models are used to explain both in vitro and in vivo behavior, the question still remains whether the specimens employed reflect the normal in vivo situation. The mechanical properties of fresh-frozen or preserved cadavers may differ, and whether they can be used to reliably investigate pathology could be debated. The purpose of this study was to therefore examine the mechanical properties of cadaveric long biceps tendons, comparing fresh (n = 7) with fresh-frozen (n = 8), formalin embalmed (n = 15), and Thiel-preserved (n = 6) specimens using a Universal Testing Machine. The modulus of elasticity and the ultimate tensile strength to failure was recorded. Tensile failure occurred at an average of 12 N/mm2 in the fresh group, increasing to 40.1 N/mm2 in the fresh-frozen group, 50.3 N/mm2 in the formalin group, and 52 N/mm2 in the Thiel group. The modulus of elasticity/stiffness of the tendon increased from fresh (25.6 MPa), to fresh-frozen (55.3 MPa), to Thiel (82.5 MPa), with the stiffest being formalin (510.6 MPa). Thiel-preserved and formalin-embalmed long head of biceps tendons and fresh-frozen tendons have a similar load to failure. Either the Thiel or formalin preserved tendon could therefore be considered as alternatives for load to failure studies. However, the Young’s modulus of embalmed tendons were significantly stiffer than fresh or fresh frozen specimens, and these methods might be less suitable alternatives when viscoelastic properties are being investigated.http://www.elsevier.com/locate/aanat2019-06-04hj2018AnatomyOrthopaedic Surger

Les effets de la vente en ligne sur les inégalités territoriales d'accès au commerce. Vers un nivellement des disparités urbain-périurbain ?

L’accessibilité géographique des populations aux biens est différenciée selon les espaces. Les populations des centres-villes peuvent accéder à pieds, à proximité de leur domicile à des magasins offrant un large choix de biens, alors que les populations périurbaines doivent parcourir plusieurs kilomètres en voiture pour accéder au premier magasin de proximité. Depuis les années 1990, le commerce à destination des particuliers (business-to-consumer) connaît de fortes évolutions, avec le développement d‘Internet et de la vente en ligne. Cette « électronisation » offre la possibilité d’une séparation croissante des fonctions du commerce, notamment la vente en elle-même et la logistique de distribution . Ainsi, la livraison à domicile et celle dans des relais-livraison se sont affirmées comme des modes de distribution alternatifs aux magasins, bouleversant les cadres de l’analyse de l’accessibilité des populations aux commerces, notamment dans les espaces périurbains. L’accessibilité est entendue ici comme l’ensemble des contraintes spatiales, temporelles et modales pesant sur les déplacements nécessaires pour accéder à un bien.Les principales formes de distribution de la vente en ligne, les livraisons à domicile et en relais-livraison, proposent une redéfinition de l’accessibilité à un large éventail de biens matériels, en offrant ces biens à domicile et/ou dans des commerces de proximité plutôt que, pour certains biens, dans un magasin du centre-ville. Les disparités d’accessibilités aux commerces, parfois fortes selon le type de bien recherché, marquées par un gradient urbain-périurbain et par une hétérogénéité des territoires périurbains, devraient s’en trouver significativement nivelées par une multiplication attendue des points de distribution, notamment dans des territoires qui n’en disposaient pas. Cependant cela nécessite, d’une part, que les habitants des territoires concernés adoptent largement le commerce électronique et tirent parti des options de livraison. D’autre part, le développement de la vente en ligne entraîne une transformation de l’offre commerciale existante par la concurrence qu’elle opère. Certaines localisations commerciales existantes s’en trouvent fragilisées ou remises en cause, tout autant que l’accessibilité et les pratiques d’achat des populations résidant dans ces territoires.Les trois parties du rapport fournissent des réponses et des éclairages différenciés sur ces interrogations, plus précisément sur celle formulée en titre. La première partie sera focalisée sur l'accès aux produits alimentaires et de consommation courante via l'analyse des zones de dessertes des cybermarchés. La seconde partie s'intéressera à un acteur émergent du e-commerce: les points relais. Enfin la dernière partie essaiera de saisir plus finement les usages et pratiques des ménages en termes de ventes en ligne

Religion and Popular Music

The interactions between popular music and religion are manyfold and highly complex. Popular music as an important part of popular culture is a means of communication. Music can transmit not only emotions and a sense of community but also religious knowledge, knowledge that leaves diverse traces in different times and places. In the end, whether we extract religious meaning from popular music and what that meaning is depend on our background and on our capacity to contextualise symbols, motives and narratives – and also on the media used to convey these references. By analysing Florence + The Machines song “Big God” and its music video we will address some of the questions that arise while working in the field of popular music and religion

Differential Inhibition of Human Atherosclerotic Plaque-Induced Platelet Activation by Dimeric GPVI-Fc and Anti-GPVI Antibodies: Functional and Imaging Studies.

BACKGROUND: Glycoprotein VI (GPVI) is the essential platelet collagen receptor in atherothrombosis, but its inhibition causes only a mild bleeding tendency. Thus, targeting this receptor has selective antithrombotic potential. OBJECTIVES: This study sought to compare compounds interfering with platelet GPVI-atherosclerotic plaque interaction to improve current antiatherothrombotic therapy. METHODS: Human atherosclerotic plaque-induced platelet aggregation was measured in anticoagulated blood under static and arterial flow conditions (550/s, 1,100/s, and 1,500/s). Inhibition by dimeric GPVI fragment crystallizable region of IgG (Fc) masking GPVI binding sites on collagen was compared with that of 3 anti-GPVI antibodies: BLO8-1, a human domain antibody; 5C4, a fragment antigen-binding (Fab fragment) of monoclonal rat immunoglobulin G; and m-Fab-F, a human recombinant sFab against GPVI dimers. RESULTS: GPVI-Fc reduced plaque-triggered platelet aggregation in static blood by 51%, BLO8-1 by 88%, and 5C4 by 93%. Under arterial flow conditions, BLO8-1 and 5C4 almost completely inhibited platelet aggregation while preserving platelet adhesion on plaque. Inhibition by GPVI-Fc, even at high concentrations, was less marked but increased with shear rate. Advanced optical imaging revealed rapid persistent GPVI-Fc binding to collagen under low and high shear flow, upstream and downstream of plaque fragments. At low shear particularly, platelets adhered in plaque flow niches to GPVI-Fc-free segments of collagen fibers and recruited other platelets onto aggregates via ADP and TxA2 release. CONCLUSIONS: Anti-GPVI antibodies inhibit atherosclerotic plaque-induced platelet aggregation under static and flow conditions more effectively than GPVI-Fc. However, potent platelet inhibition by GPVI-Fc at a higher shear rate (1,500/s) suggests localized antithrombotic efficacy at denuded or fissured stenotic high-risk lesions without systemic bleeding. The compound-specific differences have relevance for clinical trials targeting GPVI-collagen interaction combined with established antiplatelet therapies in patients with spontaneous plaque rupture or intervention-associated plaque injury.The study was supported by grants from advanceCOR GmbH (JJ), the August-Lenz foundation, the Deutsche Forschungsgemeinschaft SFB1123/Z01 (MB), and the British Heart Foundation (SMJ and RWF; grants RG/09/003/27122 and PG/10/011/28199). Two-photon laser scanning microscopy experiments have been supported by the Deutsche Forschungsgemeinschaft (INST 409/97-1) and the LMU.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.jacc.2015.03.57

Abatacept modulates CD80 and CD86 expression and memory formation in human B-cells

Background: Cytotoxic T lymphocyte antigen-4 (CTLA-4) limits T-cell activation and is expressed on T-regulatory cells. Human CTLA-4 deficiency results in severe immune dysregulation. Abatacept (CTLA-4 Ig) is approved for the treatment of rheumatoid arthritis (RA) and its mechanism of action is attributed to effects on T-cells. It is known that CTLA-4 modulates the expression of its ligands CD80 and CD86 on antigen presenting cells (APC) by transendocytosis. As B-cells express CD80/CD86 and function as APC, we hypothesize that B-cells are a direct target of abatacept. Objectives: To investigate direct effects of abatacept on human B-lymphocytes in vitro and in RA patients. Methods: The effect of abatacept on healthy donor B-cells’ phenotype, activation and CD80/CD86 expression was studied in vitro. Nine abatacept-treated RA patients were studied. Seven of these were followed up to 24 months, and two up to 12 months only and treatment response, immunoglobulins, ACPA, RF concentrations, B-cell phenotype and ACPA-specific switched memory B-cell frequency were assessed. Results: B-cell development was unaffected by abatacept. Abatacept treatment resulted in a dose-dependent decrease of CD80/CD86 expression on B-cells in vitro, which was due to dynamin-dependent internalization. RA patients treated with abatacept showed a progressive decrease in plasmablasts and serum IgG. While ACPA-titers only moderately declined, the frequency of ACPA-specific switched memory B-cells significantly decreased. Conclusions: Abatacept directly targets B-cells by reducing CD80/CD86 expression. Impairment of antigen presentation and T-cell activation may result in altered B-cell selection, providing a new therapeutic mechanism and a base for abatacept use in B-cell mediated autoimmunity.Fil: Lorenzetti, Raquel. Albert Ludwigs University of Freiburg; AlemaniaFil: Janowska, Iga. Albert Ludwigs University of Freiburg; AlemaniaFil: Smulski, Cristian Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; ArgentinaFil: Frede, Natalie. Albert Ludwigs University of Freiburg; AlemaniaFil: Henneberger, Nadine. Albert Ludwigs University of Freiburg; AlemaniaFil: Walter, Lea. Albert Ludwigs University of Freiburg; AlemaniaFil: Schleyer, Marei-Theresa. Albert Ludwigs University of Freiburg; AlemaniaFil: Hüppe, Janika M.. Albert Ludwigs University of Freiburg; AlemaniaFil: Staniek, Julian. Albert Ludwigs University of Freiburg; AlemaniaFil: Salzer, Ulrich. Albert Ludwigs University of Freiburg; AlemaniaFil: Venhoff, Ana. Albert Ludwigs University of Freiburg; AlemaniaFil: Troilo, Arianna. Albert Ludwigs University of Freiburg; AlemaniaFil: Voll, Reinhard Edmund. Albert Ludwigs University of Freiburg; AlemaniaFil: Venhoff, Nils. Albert Ludwigs University of Freiburg; AlemaniaFil: Thiel, Jens. Albert Ludwigs University of Freiburg; AlemaniaFil: Rizzi, Marta. Albert Ludwigs University of Freiburg; Alemani

Chassis organism from Corynebacterium glutamicum – a top-down approach to identify and delete irrelevant gene clusters

Unthan S, Baumgart M, Radek A, et al. Chassis organism from Corynebacterium glutamicum – a top-down approach to identify and delete irrelevant gene clusters. Biotechnology Journal. 2015;10(2):290-301

Guidance Statement On BRCA1/2 Tumor Testing in Ovarian Cancer Patients

International audienceThe approval, in 2015, of the first poly (adenosine diphosphate-ribose) polymerase inhibitor (PARPi; olaparib, Lynparza) for platinum-sensitive relapsed high-grade ovarian cancer with either germline or somatic BRCA1/2 deleterious mutations is changing the way that BRCA1/2 testing services are offered to patients with ovarian cancer. Ovarian cancer patients are now being referred for BRCA1/2 genetic testing for treatment decisions, in addition to familial risk estimation, and irrespective of a family history of breast or ovarian cancer. Furthermore, testing of tumor samples to identify the estimated 3%-9% of patients with somatic BRCA1/2 mutations who, in addition to germline carriers, could benefit from PARPi therapy is also now being considered. This new testing paradigm poses some challenges, in particular the technical and analytical difficulties of analyzing chemically challenged DNA derived from formalin-fixed, paraffin-embedded specimens. The current manuscript reviews some of these challenges and technical recommendations to consider when undertaking BRCA1/2 testing in tumor tissue samples to detect both germline and somatic BRCA1/2 mutations. Also provided are considerations for incorporating genetic analysis of ovarian tumor samples into the patient pathway and ethical requirements

JAK inhibitors differentially modulate B cell activation, maturation and function: A comparative analysis of five JAK inhibitors in an in-vitro B cell differentiation model and in patients with rheumatoid arthritis

BackgroundJanus kinase (JAK) inhibitors have been approved for the treatment of several immune-mediated diseases (IMIDs) including rheumatoid arthritis (RA) and psoriatic arthritis and are in clinical trials for numerous other IMIDs. However, detailed studies investigating the effects of different JAK inhibitors on B cells are missing. Within this study, we therefore aimed to characterize the effect of JAK inhibition on the B cell compartment.MethodsTo this end, we investigated the B cell compartment under JAK inhibition and compared the specific effects of the different JAK inhibitors tofacitinib (pan-JAK), baricitinib (JAK1/2), ruxolitinib (JAK1/2), upadacitinib (JAK1/2) as well as filgotinib (selective JAK1) on in-vitro B cell activation, proliferation, and class switch recombination and involved pathways.ResultsWhile B cell phenotyping of RA patients showed an increase in marginal zone (MZ) B cells under JAK inhibition, comparison with healthy donors revealed that the relative frequency of MZ B cells was still lower compared to healthy controls. In an in-vitro model of T-cell-independent B cell activation we observed that JAK1/2 and selective JAK1 inhibitor treatment led to a dose-dependent decrease of total B cell numbers. We detected an altered B cell differentiation with a significant increase in MZ-like B cells and an increase in plasmablast differentiation in the first days of culture, most pronounced with the pan-JAK inhibitor tofacitinib, although there was no increase in immunoglobulin secretion in-vitro. Notably, we further observed a profound reduction of switched memory B cell formation, especially with JAK1/2 inhibition. JAK inhibitor treatment led to a dose-dependent reduction of STAT3 expression and phosphorylation as well as STAT3 target gene expression and modulated the secretion of pro- and anti-inflammatory cytokines by B cells.ConclusionJAK inhibition has a major effect on B cell activation and differentiation, with differential outcomes between JAK inhibitors hinting towards distinct and unique effects on B cell homeostasis

The detection and prevention of adverse drug events in nursing home and home care patients: Study protocol of a quasi-experimental study

Aim: To estimate the cost-effectiveness of an intervention facilitating the early detection of adverse drug events through the means of health professional training and the application of a digital screening tool. Design: Multi-centred non-randomized controlled trial from August 2018 to March 2020 including 65 nursing homes or home care providers. Methods: We aim to estimate the effect of the intervention on the rate of adverse drug events as primary outcome through a quasi-experimental empirical study design. As secondary outcomes, we use hospital admissions and falls. All outcomes will be measured on patient-month level. Once the causal effect of the intervention is estimated, cost-effectiveness will be calculated. For cost-effectiveness, we include all patient costs observed by the German statutory health insurance. Results: The results of this study will inform about the cost-effectiveness of the optimized drug supply intervention and provide evidence for potential reimbursement within the German statutory health insurance system.TU Berlin, Open-Access-Mittel – 202

Burden of disease and impact on quality of life in chronic back pain – a comparative cross-sectional study of 150 axial spondyloarthritis and 150 orthopedic back pain patients

ObjectiveChronic back pain (CBP) constitutes one of the most common complaints in primary care and a leading cause of disability worldwide. CBP may be of mechanical or inflammatory character and may lead to functional impairment and reduced quality of life. In this study, we aimed to assess and compare burden of disease, functional capacity, quality of life and depressive symptoms in axial spondyloarthritis (axSpA) patients with orthopedic chronic back pain patients (OBP). We further aimed to identify factors associated with quality of life.MethodsCross-sectional survey of a cohort of 300 CBP patients including 150 patients from a University Hospital Orthopedic Back Pain Outpatient Clinic with OBP and 150 patients with confirmed axSpA from a University Hospital Rheumatology Outpatient Clinic. Questionnaire-based assessment of pain character (Inflammatory Back Pain, MAIL-Scale), functional status (FFbH, BASFI), quality of life (WHOQOL-Bref) and depressive symptoms (Phq9) and retrospective medical chart analysis.ResultsBoth, OBP and axSpA patients reported on average intermediate pain levels of mostly mixed pain character. Both groups demonstrated a reduced health-related quality of life and the presence of depressive symptoms. However, axSpA patients reported a significantly better subjective quality of life, more satisfaction with their health status and better functional capacity compared to OBP patients (all p < 0.001). In a multivariate regression model, depressive symptoms, mechanical back pain, pain level and age were negative predictors of subjective quality of life, whereas functional capacity was a positive predictor.ConclusionChronic back pain was associated with a high morbidity and reduced quality of life regardless of pain character. We identified multiple factors associated with reduced quality of life. Awareness and addressing of these factors may help to overcome unmet needs and improve quality of life for these patients