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Sieberts S.K.,Sage Bionetworks | Zhu F.,University of Michigan | Garcia-Garcia J.,University Pompeu Fabra | Stahl E.,Mount Sinai School of Medicine | And 124 more authors.
Nature Communications | Year: 2016

Rheumatoid arthritis (RA) affects millions world-wide. While anti-TNF treatment is widely used to reduce disease progression, treatment fails in 1/4one-third of patients. No biomarker currently exists that identifies non-responders before treatment. A rigorous community-based assessment of the utility of SNP data for predicting anti-TNF treatment efficacy in RA patients was performed in the context of a DREAM Challenge (http://www.synapse.org/RA-Challenge). An open challenge framework enabled the comparative evaluation of predictions developed by 73 research groups using the most comprehensive available data and covering a wide range of state-of-the-art modelling methodologies. Despite a significant genetic heritability estimate of treatment non-response trait (h 2 =0.18, P value=0.02), no significant genetic contribution to prediction accuracy is observed. Results formally confirm the expectations of the rheumatology community that SNP information does not significantly improve predictive performance relative to standard clinical traits, thereby justifying a refocusing of future efforts on collection of other data. © The Author(s) 2016.


Elfakir A.,Biometrics and Epidemiology Unit | Ezzedine K.,University of Paris 13 | Ezzedine K.,Bordeaux University Hospital Center | Latreille J.,Biometrics and Epidemiology Unit | And 10 more authors.
Journal of Investigative Dermatology | Year: 2010

The objective of this study was to assess the association between melanocortin-1 receptor (MC1R) variants and the severity of facial skin photoaging. The study population comprised 530 middle-aged French women. A trained dermatologist graded the severity of facial skin photoaging from photographs using a global scale. Logistic regressions were performed to assess the influence of MC1R polymorphisms on severe photoaging with adjustment for possible confounders (demographic and phenotypic data and sun exposure intensity). Among the fifteen MC1R variants identified, the nine most common were V60L, V92M, R151C, R160W, R163Q, R142H, D294H, D84E, and I155T. One hundred and eighty-five individuals (35%) were WT homozygotes, 261 (49%) had one common variant, 78 (15%) had two common variants, and six (1%) had at least one rare variant. After adjustment for possible confounders, the presence of two common variants was already a risk factor for severe photoaging (AOR (95% confidence interval): 2.33 (1.17-4.63)). This risk reached 5.61 (1.43-21.96) when two major diminished-function variants were present. Surprisingly, the minor variant, V92M, was associated with increased risk of photoaging (2.57 (1.23-5.35)). Our results suggest that genetic variations of MC1R are important determinants for severe photoaging. © 2010 The Society for Investigative Dermatology.


News Article | November 4, 2016
Site: www.eurekalert.org

The comfort and wellbeing of the animals is an important consideration when dairy cows are kept in barns. The freedom afforded by loose housing systems such as freestall cubicle barns promotes the natural behaviour and health of the animals. The widespread switch from tie-stall housing to loose housing has seen a change in the type of claw lesions, but the frequency of claw disorders has been on the rise. Wood chips and sawdust instead of straw International studies have identified the compost bedded barn as the beneficial for claw health. Compost bedded barns use wood chips or sawdust as bedding instead of straw. The wood residue binds the excrement and daily aerating incorporates the manure and starts the composting process. This makes an even concrete floor important in the roaming area. Slatted flooring, in which manure and urine fall into a separate area beneath the floor, should only be installed in the feed alley. Fresh bedding should also be added daily following aeration. A team of researchers from Vetmeduni Vienna, led by Johann Burgstaller from the Clinical Unit of Ruminant Medicine, has for the first time compared the frequency of claw disorders and lameness in compost bedded barns and the more common freestall cubicle barns in Austria. The researchers investigated the frequency and severity of claw lesions in five compost bedded barns and five freestall barns. "Lesions of low severity were categorized as grade 1, severe lesions as grade 3. The results for the individual lesions were weighted and subsequently added together to calculate an index value for the claw health per barn," Burgstaller explains. "A high value indicates poor claw health; a low value indicates good claw health. This value, however, is also influenced by factors such as frequency of care, feeding and genetics." Compost bedding reduces the number of cases of claw lesions The compost bedded barns exhibited about one half the number claw disorders, such as foot rot or white line disease, as the freestall barns. Both the frequency and severity were lower. Lesions of grades 2 and 3 were seen only rarely. The compost bedding thus has a proven beneficial effect on claw health. Lameness, on the other hand, occurred at nearly the same frequency in both barn types. At about 18 percent, however, the average of the freestall and compost bedded barns was below the international and previous Austrian level of 25 percent. Even if modern barn types give dairy cows more freedom to roam, the animals must still stand in manure and urine for longer periods of time. The excrement increases the floor humidity and has negative consequences for claw health. The result are claw lesions, such as foot rot or white line disease. "Floor humidity softens the skin between the claws, which makes it susceptible to bacterial infections. The reduced horn quality can lead to lesions and, in serious cases, sole haemorrhages," Burgstaller explains. White line disease occurs when floor humidity attacks the sensitive junction between the sole and the wall of the claw. Sudden or rotating movements create pressure on the affected junction and the sole slowly separates from the wall. This type of claw disorder is one of the main causes of lameness. Compost bedded barns that are aerated and refilled daily can counter claw damage over the long term. This requires more work and effort on the part of the farmers. But after one year of composting, they can use the bedding as fertilizer. According to Burgstaller, the situation for dairy cows living in freestall barns can also be improved with more frequent re-bedding to keep the area dry. The main difference between the compost bedded barn and the freestall barn is that the former has just one large area for roaming. "There are no cubicles. This is more in keeping with the pronounced social behaviour of cattle," Burgstaller explains. A dairy herd is organized hierarchically. If a cow is forced to leave its place for an animal of a higher rank, it can get up quickly and move out of the way without any obstacles. The stable and nonslip surface also allows weaker animals to get up or lie down safely, which is an enormous advantage in cases of milk fever. Service: The article "Claw health and prevalence of lameness in cows from compost bedded and cubicle freestall dairy barns in Austria" by J. Burgstaller, J. Raith, S. Kuchling, V. Mandl, A. Hund and J. Kofler was published in The Veterinary Journal. http://www. About the University of Veterinary Medicine, Vienna The University of Veterinary Medicine, Vienna in Austria is one of the leading academic and research institutions in the field of Veterinary Sciences in Europe. About 1,300 employees and 2,300 students work on the campus in the north of Vienna which also houses five university clinics and various research sites. Outside of Vienna the university operates Teaching and Research Farms. http://www.


O'Reilly D.,Royal Center for Defence Medicine | O'Reilly D.,University of Birmingham | Lordan J.,University of Birmingham | Streets C.,University of Bristol | And 3 more authors.
Journal of the Royal Army Medical Corps | Year: 2016

The closure of the Medical Treatment facility in Camp BASTION and the return to contingency operations presents a new challenge in training and maintaining the skills of military surgeons. Multivisceral organ retrieval presents a unique opportunity to practice some of the more unusual techniques required in military surgery in the National Health Service. This article details the experience that organ retrieval offers and matches this to the needs of military surgeons. National Organ Retrieval Service teams need skilled surgeons, and a mutually beneficial partnership is in prospect. © 2016, BMJ Publishing Group. All rights reserved.


Vella S.,Laboratory of Angiogenesis | Pomella S.,Instituto Dermopatico Dellimmacolata | Leoncini P.P.,Laboratory of Angiogenesis | Colletti M.,Laboratory of Angiogenesis | And 10 more authors.
Clinical Epigenetics | Year: 2015

Background: Rhabdomyosarcoma (RMS) is a pediatric soft tissue sarcoma arising from myogenic precursors that have lost their capability to differentiate into skeletal muscle. The polycomb-group protein EZH2 is a Lys27 histone H3 methyltransferase that regulates the balance between cell proliferation and differentiation by epigenetically silencing muscle-specific genes. EZH2 is often over-expressed in several human cancers acting as an oncogene. We previously reported that EZH2 inhibition induces cell cycle arrest followed by myogenic differentiation of RMS cells of the embryonal subtype (eRMS). MiR-101 is a microRNA involved in a negative feedback circuit with EZH2 in different normal and tumor tissues. To that, miR-101 can behave as a tumor suppressor in several cancers by repressing EZH2 expression. We, therefore, evaluated whether miR-101 is de-regulated in eRMS and investigated its interplaying with EZH2 as well as its role in the in vitro tumorigenic potential of these tumor cells. Results: Herein, we report that miR-101 is down-regulated in eRMS patients and in tumor cell lines compared to their controls showing an inverse pattern of expression with EZH2. We also show that miR-101 is up-regulated in eRMS cells following both genetic and pharmacological inhibition of EZH2. In turn, miR-101 forced expression reduces EZH2 levels as well as restrains the migratory potential of eRMS cells and impairs their clonogenic and anchorage-independent growth capabilities. Finally, EZH2 recruitment to regulatory region of miR-101-2 gene decreases in EZH2-silenced eRMS cells. This phenomenon is associated to reduced H3K27me3 levels at the same regulatory locus, indicating that EZH2 directly targets miR-101 for repression in eRMS cells. Conclusions: Altogether, our data show that, in human eRMS, miR-101 is involved in a negative feedback loop with EZH2, whose targeting has been previously shown to halt eRMS tumorigenicity. They also demonstrate that the re-induction of miR-101 hampers the tumor features of eRMS cells. In this scenario, epigenetic dysregulations confirm their crucial role in the pathogenesis of this soft tissue sarcoma. © 2015, Vella et al.


Aaben C.,Karolinska Institutet | Hammarqvist F.,Karolinska Institutet | Mabesa T.,Inkosi Albert Luthuli Central Hospital | Hardcastle T.,Clinical Unit | Hardcastle T.,University of KwaZulu - Natal
South African Journal of Clinical Nutrition | Year: 2015

Objectives: The aim of the study was to compare the incidence of complications in patients receiving enteral and parenteral nutrition (PN), and review how the early initiation of enteral feeding and early achievement of caloric goal would affect the incidence of complications. Design: The design was a retrospective audit of an ethics-approved prospective trauma registry and electronic medical record. Setting: The setting was a level one trauma centre intensive care unit. Subjects: One thousand and two consecutively treated patients were selected from 1 096 in the database. Outcome measures: Demographic data, nutrition, route of administration, time of initiation and complications in the form of sepsis, pneumonia and feed intolerance, were determined. Results: Patients receiving total PN (TPN) during their length of stay had a hazard ratio of 9.11 for the development of sepsis, compared to patients who were solely fed via the enteral route (p-value <0.001). The patients who reached their nutritional goal late showed a hazard ratio of 2.67 for the development of sepsis, compared to patients who reached the goal early (p-value < 0.001). Patients with late initiation of feeding also had a greater risk of developing sepsis, with a hazard ratio of 2.41, compared to patients with early initiation (p-value < 0.001). Patients achieving the nutritional goal late had a 17.9% increased risk of developing pneumonia (p-value < 0.001). Conclusion: This study confirms previous findings that the use of TPN is a strong predictor of the development of sepsis, compared to enteral nutrition. Causality linkage should be made with caution owing to the study design. © SAJCN.


PubMed | Autonomous University of Barcelona, Instituto Dermopatico dellImmacolata, Laboratory of Angiogenesis, University of Bologna and 2 more.
Type: | Journal: Clinical epigenetics | Year: 2015

Rhabdomyosarcoma (RMS) is a pediatric soft tissue sarcoma arising from myogenic precursors that have lost their capability to differentiate into skeletal muscle. The polycomb-group protein EZH2 is a Lys27 histone H3 methyltransferase that regulates the balance between cell proliferation and differentiation by epigenetically silencing muscle-specific genes. EZH2 is often over-expressed in several human cancers acting as an oncogene. We previously reported that EZH2 inhibition induces cell cycle arrest followed by myogenic differentiation of RMS cells of the embryonal subtype (eRMS). MiR-101 is a microRNA involved in a negative feedback circuit with EZH2 in different normal and tumor tissues. To that, miR-101 can behave as a tumor suppressor in several cancers by repressing EZH2 expression. We, therefore, evaluated whether miR-101 is de-regulated in eRMS and investigated its interplaying with EZH2 as well as its role in the in vitro tumorigenic potential of these tumor cells.Herein, we report that miR-101 is down-regulated in eRMS patients and in tumor cell lines compared to their controls showing an inverse pattern of expression with EZH2. We also show that miR-101 is up-regulated in eRMS cells following both genetic and pharmacological inhibition of EZH2. In turn, miR-101 forced expression reduces EZH2 levels as well as restrains the migratory potential of eRMS cells and impairs their clonogenic and anchorage-independent growth capabilities. Finally, EZH2 recruitment to regulatory region of miR-101-2 gene decreases in EZH2-silenced eRMS cells. This phenomenon is associated to reduced H3K27me3 levels at the same regulatory locus, indicating that EZH2 directly targets miR-101 for repression in eRMS cells.Altogether, our data show that, in human eRMS, miR-101 is involved in a negative feedback loop with EZH2, whose targeting has been previously shown to halt eRMS tumorigenicity. They also demonstrate that the re-induction of miR-101 hampers the tumor features of eRMS cells. In this scenario, epigenetic dysregulations confirm their crucial role in the pathogenesis of this soft tissue sarcoma.


News Article | November 21, 2016
Site: www.businesswire.com

CONSHOHOCKEN, Pa.--(BUSINESS WIRE)--BioKinetic Europe Deploys ALPHADAS; Automates Phase I Clinical Unit in Belfast

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